bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022‒09‒25
255 papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.
  2. 'Mito-Bomb': a novel mitochondria-targeting nanosystem for ferroptosis-boosted sonodynamic antitumor therapy.
  3. Peroxide mediated oxygen delivery in cancer therapy.
  4. The Potential of Curcumin-Capped Nanoparticle Synthesis in Cancer Therapy: A Green Synthesis Approach.
  5. Interplays of glucose metabolism and KRAS mutation in pancreatic ductal adenocarcinoma.
  6. Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage.
  7. Combined HASPIN and mTOR inhibition is synergistic against KRAS-driven carcinomas.
  8. Recent Strategies to Address Hypoxic Tumor Environments in Photodynamic Therapy.
  9. Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery ofPeganum harmalasmoke extract to breast cancer cells.
  10. Multifaceted Elevation of ROS Generation for Effective Cancer Suppression.
  11. Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways.
  12. Chemosensitivity enhanced by autophagy inhibition based on a polycationic nano-drug carrier.
  13. Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges.
  14. Targeted chitosan nanoparticles embedded into graphene oxide functionalized with caffeic acid as a potential drug delivery system: New insight into cancer therapy.
  15. Hybrid Membrane-Derived Nanoparticles for Isoliquiritin Enhanced Glioma Therapy.
  16. Role of Medicinal plant-derived Nutraceuticals as a potential target for the treatment of breast cancer.
  17. A Review of the Pharmacological Potential of Spatholobus suberectus Dunn on Cancer.
  18. Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor.
  19. Two-in-One Nanoparticle Formulation to Deliver a Tyrosine Kinase Inhibitor and microRNA for Targeting Metabolic Reprogramming and Mitochondrial Dysfunction in Gastric Cancer.
  20. Targeted co-delivery of a photosensitizer and an antisense oligonucleotide based on an activatable hyaluronic acid nanosystem with endogenous oxygen generation for enhanced photodynamic therapy of hypoxic tumors.
  21. Importance of Rose Bengal Loaded with Nanoparticles for Anti-Cancer Photodynamic Therapy.
  22. Embelin and Its Derivatives: Design, Synthesis, and Potential Delivery Systems for Cancer Therapy.
  23. A selenium-substituted heptamethine cyanine photosensitizer for near-infrared photodynamic therapy.
  24. Erythrocyte-Derived Nanoparticles with Folate Functionalization for Near Infrared Pulsed Laser-Mediated Photo-Chemotherapy of Tumors.
  25. Pulmonary drug delivery applications of natural polysaccharide polymer derived nano/micro-carrier systems: A review.
  26. Metabolic changes during prostate cancer development and progression.
  27. Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism.
  28. Redox-Responsive Drug Delivery Systems: A Chemical Perspective.
  29. Assessing the therapeutic response of tumors to hypoxia-targeted prodrugs with an in silico approach.
  30. Dietary EVOO Polyphenols and Gut Microbiota Interaction: Are There Any Sex/Gender Influences?
  31. Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy.
  32. Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters.
  33. Crosstalk between Hypoxia and Extracellular Matrix in the Tumor Microenvironment in Breast Cancer.
  34. A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug.
  35. Advantages of combined photodynamic therapy in the treatment of oncological diseases.
  36. Recent advances in redox-responsive nanoparticles for combined cancer therapy.
  37. Bioactive Iridium Nanoclusters with Glutathione Depletion Ability for Enhanced Sonodynamic-Triggered Ferroptosis-like Cancer Cell Death.
  38. Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer.
  39. iRGD-grafted N-trimethyl chitosan-coated protein nanotubes enhanced the anticancer efficacy of curcumin and melittin.
  40. Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.
  41. Date Palm as Source of Nutraceuticals for Health Promotion: a Review.
  42. Curcumin's prevention of inflammation-driven early gastric cancer and its molecular mechanism.
  43. A convergent fabrication of pH and redox dual-responsive hybrids of mesoporous silica nanoparticles for the treatment of breast cancer.
  44. Emerging indocyanine green-integrated nanocarriers for multimodal cancer therapy: a review.
  45. Green Tea Catechins: Nature's Way of Preventing and Treating Cancer.
  46. Nanocarriers as a Delivery Platform for Anticancer Treatment: Biological Limits and Perspectives in B-Cell Malignancies.
  47. Enzymatic Nanosphere-to-Nanofiber Transition and Autophagy Inducer Release Promote Tumor Chemotherapy.
  48. A Multifunctional Cascade Bioreactor Based on a Layered Double Oxides Composite Hydrogel for Synergetic Tumor Chemodynamic/Starvation/Photothermal Therapy.
  49. Evodiamine as an anticancer agent: a comprehensive review on its therapeutic application, pharmacokinetic, toxicity, and metabolism in various cancers.
  50. Effects of Ketogenic Diet on Muscle Metabolism in Health and Disease.
  51. Harnessing Lipid Polymer Hybrid Nanoparticles for Enhanced Oral Bioavailability of Thymoquinone: In Vitro and In Vivo Assessments.
  52. Food Applications and Potential Health Benefits of Hawthorn.
  53. Combination Therapy Using Polyphenols: An Efficient Way to Improve Antitumoral Activity and Reduce Resistance.
  54. A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy.
  55. Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing.
  56. Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.
  57. Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.
  58. Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome.
  59. Effects of polymer carriers on the occurrence and development of autophagy in drug delivery.
  60. Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer.
  61. Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy.
  62. Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis.
  63. Marine Bioactive Compounds Derived from Macroalgae as New Potential Players in Drug Delivery Systems: A Review.
  64. An effective in vivo mitochondria-targeting nanocarrier combined with a π-extended porphyrin-type photosensitizer.
  65. Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts.
  66. Radioiodination, nasal nanoformulation and preliminary evaluation of isovanillin: A new potential brain cancer-targeting agent.
  67. A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders.
  68. Ultrasound-Induced Drug Release from Stimuli-Responsive Hydrogels.
  69. A review on health benefits of phenolics derived from dietary spices.
  70. MicroRNAs, Key Regulators in Glioma Progression as Potential Therapeutic Targets for Chinese Medicine.
  71. Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects.
  72. Recent advances in pomegranate peel extract mediated nanoparticles for clinical and biomedical applications.
  73. Development of surface modified bilosomes for the oral delivery of quercetin: optimization, characterization in-vitro antioxidant, antimicrobial, and cytotoxicity study.
  74. Novel pH-sensitive nanoparticles based on prodrug strategy to delivery All-Trans Retinoic Acid for breast cancer.
  75. The Potential Role of Apigenin in Cancer Prevention and Treatment.
  76. Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies.
  77. Essential Oil-Loaded Nanofibers for Pharmaceutical and Biomedical Applications: A Systematic Mini-Review.
  78. Alpha-fetoprotein mediated targeting of polymeric nanoparticles to treat solid tumors.
  79. Preparation of Fluorescently Labeled Chitosan-Quercetin Drug-Loaded Nanoparticles with Excellent Antibacterial Properties.
  80. Targeting autophagy in atherosclerosis: Advances and therapeutic potential of natural bioactive compounds from herbal medicines and natural products.
  81. Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020.
  82. Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.
  83. Inhaled antibiotic-loaded polymeric nanoparticles for the management of lower respiratory tract infections.
  84. Chemical constituents and pharmacological activities of medicinal plants from Rosa genus.
  85. Preparation, physicochemical, and retinal anti-angiogenic evaluation of poloxamer hydrogel containing dexamethasone/avastin-loaded chitosan-N-acetyl-L-cysteine nanoparticles.
  86. Triterpenoid Saponins from Washnut (Sapindus mukorossi Gaertn.)-A Source of Natural Surfactants and Other Active Components.
  87. Effective Sonosensitizer Delivery by Redox Sensitive Nanoparticles for Prostate Cancer Sonodynamic Therapy via Amplifying Oxidative Stress and Peroxidation.
  88. The impact of diet upon mitochondrial physiology (Review).
  89. Polymeric Micelles for Breast Cancer Therapy: Recent Updates, Clinical Translation and Regulatory Considerations.
  90. Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy.
  91. Targeting immunometabolism by active ingredients derived from traditional Chinese medicines for treatment of rheumatoid arthritis.
  92. Senotherapies: A novel strategy for synergistic anti-tumor therapy.
  93. Methanol Extract of Clavularia inflata Exerts Apoptosis and DNA Damage to Oral Cancer Cells.
  94. Insights into stimuli-responsive diselenide bonds utilized in drug delivery systems for cancer therapy.
  95. Therapeutic nanodendrites: current applications and prospects.
  96. Nanoscale Delivery Systems of Lutein: An Updated Review from a Pharmaceutical Perspective.
  97. Brassica Genus Seeds: A Review on Phytochemical Screening and Pharmacological Properties.
  98. Recent advances in nanoparticle-based drug delivery systems for rheumatoid arthritis treatment.
  99. Unveiling major ethnopharmacological aspects of genus Diospyros in context to its chemical diversity: A comprehensive overview.
  100. Self-Emulsifying Drug Delivery System Enhances Tissue Distribution of Cinnamaldehyde by Altering the Properties of the Mucus Layer.
  101. Key Health Benefits of Korean Ueong Dry Root Extract Combined Silver Nanoparticles.
  102. Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.
  103. A Comprehensive Review with Updated Future Perspectives on the Ethnomedicinal and Pharmacological Aspects of Moringa oleifera.
  104. Mitotane Nanocarriers for the Treatment of Adrenocortical Carcinoma: Evaluation of Albumin-Stabilized Nanoparticles and Liposomes in a Preclinical In Vitro Study with 3D Spheroids.
  105. Dual targeted zeolitic imidazolate framework nanoparticles for treating metastatic breast cancer and inhibiting bone destruction.
  106. Bioactive Compounds, Health Benefits and Food Applications of Grape.
  107. A Photoactivated Sorafenib-Ruthenium(II) Prodrug for Resistant Hepatocellular Carcinoma Therapy through Ferroptosis and Purine Metabolism Disruption.
  108. A Review on Annona muricata and Its Anticancer Activity.
  109. Targeting lipid metabolism reprogramming of immunocytes in response to the tumor microenvironment stressor: A potential approach for tumor therapy.
  110. Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations.
  111. The Importance of Antioxidant Biomaterials in Human Health and Technological Innovation: A Review.
  112. Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen).
  113. Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.
  114. Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine.
  115. Graphene-based phenformin carriers for cancer cell treatment: a comparative study between oxidized and pegylated pristine graphene in human cells and zebrafish.
  116. Biopolymeric Prodrug Systems as Potential Antineoplastic Therapy.
  117. Nano-Formulation Based Intravesical Drug Delivery Systems: An Overview of Versatile Approaches to Improve Urinary Bladder Diseases.
  118. Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review.
  119. Neuroendocrine Tumors: A Comprehensive Review on Nutritional Approaches.
  120. Applications of nanomaterials for gastrointestinal tumors: A review.
  121. Preparation, Characterization and Pharmacokinetics of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles.
  122. Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route.
  123. Nanocarrier System: State-of-the-Art in Oral Delivery of Astaxanthin.
  124. Nutraceutical Properties of Medicago sativa L., Agave spp., Zea mays L. and Avena sativa L.: A Review of Metabolites and Mechanisms.
  125. Mucus-Penetrating Silk Fibroin-Based Nanotherapeutics for Efficient Treatment of Ulcerative Colitis.
  126. Injectable Hydrogel-Based Combination Cancer Immunotherapy for Overcoming Localized Therapeutic Efficacy.
  127. Microalgae as a potential therapeutic drug candidate for neurodegenerative diseases.
  128. The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles.
  129. Curcumin against gastrointestinal cancer: A review of the pharmacological mechanisms underlying its antitumor activity.
  130. The antitumor properties of atractylenolides: Molecular mechanisms and signaling pathways.
  131. Preparation of Black pepper (Piper nigrum L.) essential oil nanoparticles and its antitumor activity on triple negative breast cancer in vitro.
  132. Developing a Versatile Multiscale Therapeutic Platform for Osteosarcoma Synergistic Photothermo-Chemotherapy with Effective Osteogenicity and Antibacterial Capability.
  133. Nanozyme hydrogel for enhanced alkyl radical generation and potent antitumor therapy.
  134. Photodynamic Therapy for Bladder Cancers, A Focused Review.
  135. The Impact of Dietary Consumption of Palm Oil and Olive Oil on Lipid Profile and Hepatocyte Injury in Hypercholesterolemic Rats.
  136. Immunogenic Cell Death Role in Urothelial Cancer Therapy.
  137. Formulation, In Vitro Characterization and Antibacterial Activity of Chitosan-Decorated Cream Containing Bacitracin for Topical Delivery.
  138. Supercritical Fluids and Nanoparticles in Cancer Therapy.
  139. Preparation, Characterization, and Biological Evaluation of a Hydrophilic Peptide Loaded on PEG-PLGA Nanoparticles.
  140. Current progress of nanomedicine for prostate cancer diagnosis and treatment.
  141. Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles.
  142. Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of "same treatment for different diseases" in traditional Chinese medicine.
  143. Myricetin alleviates the formaldehyde-enhanced Warburg effect in tumor cells through inhibition of HIF-1α.
  144. Coumarins as Fungal Metabolites with Potential Medicinal Properties.
  145. Peptide Shuttles for Blood-Brain Barrier Drug Delivery.
  146. Surface-Coated Cerium Nanoparticles to Improve Chemotherapeutic Delivery to Tumor Cells.
  147. Revisiting the outstanding questions in cancer nanomedicine with a future outlook.
  148. Flavonoids and their therapeutic applications in skin diseases.
  149. Advances in Nanofabrication Technology for Nutraceuticals: New Insights and Future Trends.
  150. Medicinal Plants from Latin America with Wound Healing Activity: Ethnomedicine, Phytochemistry, Preclinical and Clinical Studies-A Review.
  151. Ferroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.
  152. Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis.
  153. Chemical and Antimicrobial Characterization of Mentha piperita L. and Rosmarinus officinalis L. Essential Oils and In Vitro Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.
  154. Exploring the role of nanomedicines for the therapeutic approach of central nervous system dysfunction: At a glance.
  155. Antioxidant and neuroprotective actions of resveratrol in cerebrovascular diseases.
  156. KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.
  157. [Arthrospira platensis: antioxidant, hypoglycemic and hypolipidemic effects in vitro and in vivo (brief review)].
  158. Bioactive Compounds from Marine Sponges and Algae: Effects on Cancer Cell Metabolome and Chemical Structures.
  159. Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention.
  160. Ultrasound-Responsive Nanocarriers for Breast Cancer Chemotherapy.
  161. Recent Advances of Chitosan Formulations in Biomedical Applications.
  162. Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy.
  163. 6-Methoxydihydrosanguinarine induces apoptosis and autophagy in breast cancer MCF-7 cells by accumulating ROS to suppress the PI3K/AKT/mTOR signaling pathway.
  164. Fast-Fed Variability: Insights into Drug Delivery, Molecular Manifestations, and Regulatory Aspects.
  165. Low concentrations of Ambrosia maritima L. phenolic extract protect endothelial cells from oxidative cell death induced by H2O2 and sera from Crohn's disease patients.
  166. Induction of apoptosis and suppression of Ras gene expression in MCF human breast cancer cells.
  167. Total Bioactive Contents, Metabolic Profiling, Docking Studies, Antioxidant & Enzyme inhibition Activities of Convolvulus arvensis L. and Multivariate Analysis to Unravel a Potential herb as Natural Resource for Pharmaceutical Industry.
  168. Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy.
  169. [Cancer Neuroscience].
  170. Chitosan Based MicroRNA Nanocarriers.
  171. Ultrasound-mediated blood-brain barrier opening: an effective drug delivery system for theranostics of brain diseases.
  172. lncRNAs: Key Regulators of Signaling Pathways in Tumor Glycolysis.
  173. Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy.
  174. Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities.
  175. Combined Ramipril and Black Seed Oil Dosage Forms Using Bioactive Self-Nanoemulsifying Drug Delivery Systems (BIO-SNEDDSs).
  176. Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug-A Review.
  177. Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics.
  178. Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation.
  179. Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway.
  180. Rare earth nanoparticles for sprayed and intravenous NIR II imaging and photodynamic therapy of tongue cancer.
  181. Structuring and De-Structuring of Nanovectors from Algal Lipids: Simulated Digestion, Preliminary Antioxidant Capacity and In Vitro Tests.
  182. Recent Advances in Oral Peptide or Protein-Based Drug Liposomes.
  183. Protection against Paraquat-Induced Oxidative Stress by Curcuma longa Extract-Loaded Polymeric Nanoparticles in Zebrafish Embryos.
  184. The emerging role of KRAS G12C inhibitors in the treatment of locally advanced or metastatic colorectal cancer.
  185. Enhanced permeability and retention effect-focused tumor-targeted nanomedicines: latest trends, obstacles and future perspective.
  186. Synergistic antioxidant effects of natural compounds on H2O2-induced cytotoxicity of human monocytes.
  187. The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation.
  188. Fucoidan from Marine Macroalgae: Biological Actions and Applications in Regenerative Medicine, Drug Delivery Systems and Food Industry.
  189. Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
  190. The Case for Moxibustion for Painful Syndromes: History, principles and rationale.
  191. Calcium alginate/silk fibroin peptide/Bletilla striata polysaccharide blended microspheres loaded with tannic acid for rapid wound healing.
  192. Importance of temperature on immuno-metabolic regulation and cancer progression.
  193. Relationship Between the In Vitro Efficacy, Pharmacokinetics and In Vivo Efficacy of Curcumin.
  194. Anticancer Secondary Metabolites: From Ethnopharmacology and Identification in Native Complexes to Biotechnological Studies in Species of Genus Astragalus L. and Gloriosa L.
  195. Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.
  196. Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin.
  197. Aegle marmelos (L.) Correa: An Underutilized Fruit with High Nutraceutical Values: A Review.
  198. Recent progress in single-atom nanozymes research.
  199. Modulating Microbiota as a New Strategy for Breast Cancer Prevention and Treatment.
  200. Healing Potential of Propolis in Skin Wounds Evidenced by Clinical Studies.
  201. Use of Ferulic Acid in the Management of Diabetes Mellitus and Its Complications.
  202. Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment.
  203. Sweet Potato Is Not Simply an Abundant Food Crop: A Comprehensive Review of Its Phytochemical Constituents, Biological Activities, and the Effects of Processing.
  204. Recent advances in phase change material based nanoplatforms for cancer therapy.
  205. Protective effects of curcumin on ischemia/reperfusion injury.
  206. Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.
  207. A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation.
  208. Complementary and alternative therapies in skin cancer: A literature review of biologically active compounds.
  209. Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.
  210. Dual acting acid-cleavable self-assembling prodrug from hyaluronic acid and ciprofloxacin: A potential system for simultaneously targeting bacterial infections and cancer.
  211. Study of the Antioxidant Properties of Filipendula ulmaria and Alnus glutinosa.
  212. A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy.
  213. Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer.
  214. Metabokines in the regulation of systemic energy metabolism.
  215. Puffball spores improve wound healing in a diabetic rat model.
  216. Dietary Choice Reshapes Metabolism in Drosophila by Affecting Consumption of Macronutrients.
  217. Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species.
  218. Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.
  219. Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms.
  220. Exercise as cancer treatment: A clinical oncology framework for exercise oncology research.
  221. Nanotechnology for Pediatric Retinoblastoma Therapy.
  222. Multi-Target Mechanisms of Phytochemicals in Alzheimer's Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation.
  223. Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines.
  224. The Application of Ultrasound in Honey: Antioxidant Activity, Inhibitory Effect on α-amylase and α-glucosidase, and In Vitro Digestibility Assessment.
  225. Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases.
  226. Antimicrobial cryogel dressings towards effective wound healing.
  227. Health Benefits and Side Effects of Short-Chain Fatty Acids.
  228. Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids.
  229. Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells.
  230. Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives.
  231. Anti- and Pro-Oxidant Properties of Essential Oils against Antimicrobial Resistance.
  232. Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance.
  233. Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies.
  234. TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.
  235. A novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer.
  236. "Targeting Design" of Nanoparticles in Tumor Therapy.
  237. Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis.
  238. Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis.
  239. Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers.
  240. Mucoadhesive Polymers and Their Applications in Drug Delivery Systems for the Treatment of Bladder Cancer.
  241. Hybrid-Based Wound Dressings: Combination of Synthetic and Biopolymers.
  242. Significance of Capping Agents of Colloidal Nanoparticles from the Perspective of Drug and Gene Delivery, Bioimaging, and Biosensing: An Insight.
  243. A Review of Non-Invasive Drug Delivery through Respiratory Routes.
  244. Synergetic Thermal Therapy for Cancer: State-of-the-Art and the Future.
  245. Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease.
  246. Amino acid metabolism in skeletal cells.
  247. Study protocol to determine the effects of highly absorbable oral curcumin on the indicators of cognitive functioning: a double-blind randomised controlled trial.
  248. Advanced Drug Delivery Micro- and Nanosystems for Cardiovascular Diseases.
  249. Grifola frondosa Extract Containing Bioactive Components Blocks Skin Fibroblastic Inflammation and Cytotoxicity Caused by Endocrine Disrupting Chemical, Bisphenol A.
  250. Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.
  251. Extracellular Vesicles: A Novel Tool in Nanomedicine and Cancer Treatment.
  252. A review on role of metformin as a potential drug for epilepsy treatment and modulation of epileptogenesis.
  253. Phytochemical Characterization, Anti-Oxidant, Anti-Enzymatic and Cytotoxic Effects of Artemisia verlotiorum Lamotte Extracts: A New Source of Bioactive Agents.
  254. Polymer-Based Hydrogels Enriched with Essential Oils: A Promising Approach for the Treatment of Infected Wounds.
  255. Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights.
  1. Nutrients. 2022 Sep 17. pii: 3851. [Epub ahead of print]14(18):
    Ketogenic Diet in the Treatment of Gliomas and Glioblastomas.
    Simone Dal Bello, Francesca Valdemarin, Deborah Martinuzzi, Francesca Filippi, Gian Luigi Gigli, Mariarosaria Valente.
      In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer.
    Keywords:  Warburg effect; cancer; glioblastoma; glioma; ketogenic diet; ketones; ketosis; tumor
    DOI:  https://doi.org/10.3390/nu14183851
  2. Drug Deliv. 2022 Dec;29(1): 3111-3122
    'Mito-Bomb': a novel mitochondria-targeting nanosystem for ferroptosis-boosted sonodynamic antitumor therapy.
    Jianxin Wang, Zhiyu Zhao, Yan Liu, Xinyu Cao, Fuxin Li, Haitao Ran, Yang Cao, Changjun Wu.
      Mitochondria play an important role in regulating tumor cell death and metabolism so that they can be potential therapeutic targets. Sonodynamic therapy (SDT) represents an attractive antitumor method that induces apoptosis by producing highly toxic reactive oxygen species (ROS). Mitochondria-targeting SDT can cause oxidative damage and improve the efficiency of tumor therapy. However, due to the nonselective distribution of nanosystems and the anti-apoptotic mechanism of cancer cells, the therapeutic effect of SDT is not ideal. Therefore, we proposed a novel mitochondria-targeting nanosystem ('Mito-Bomb') for ferroptosis-boosted SDT. Sonosensitizer IR780 and ferroptosis activator RSL-3 were both encapsulated in biocompatible poly(lactic-co-glycolic acid) (PLGA) nanoparticles to form 'Mito-Bomb' (named IRP NPs). IR780 in this nanosystem was used to mediate mitochondria-targeting SDT. RSL-3 inhibited the activity of GPX4 in the antioxidant system to induce ferroptosis of tumor cells, which could rewire tumor metabolism and make tumor cells extremely sensitive to SDT-induced apoptosis. Notably, we also found that RSL-3 can inhibit hypoxia inducible factor-1α (HIF-1α) and induce ROS production to improve the efficacy of SDT to synergistically antitumor. RSL-3 was applied as a 'One-Stone-Three-Birds' agent for cooperatively enhanced SDT against triple-negative breast cancer. This study presented the first example of RSL-3 boosting mitochondria-targeting SDT as a ferroptosis activator. The 'Mito-Bomb' biocompatible nanosystem was expected to become an innovative tumor treatment method and clinical transformation.
    Keywords:  GPX4; RSL-3; Sonodynamic therapy; ferroptosis; reactive oxygen species
    DOI:  https://doi.org/10.1080/10717544.2022.2126027
  3. Colloids Surf B Biointerfaces. 2022 Sep 09. pii: S0927-7765(22)00515-X. [Epub ahead of print]219 112832
    Peroxide mediated oxygen delivery in cancer therapy.
    Sajedeh Khorshidi, Sogol Younesi, Akbar Karkhaneh.
      Hypoxia is a serious obstacle in cancer treatment. The aberrant vascular network as well as the abnormal extracellular matrix arrangement results in formation of a hypoxic regions in tumors which show high resistance to the curing. Hypoxia makes the cancer treatment challengeable via two mechanisms; first and foremost, hypoxia changes the cell metabolism and leads the cells towards an aggressive and metastatic phenotype and second, hypoxia decreases the efficiency of the various cancer treatment modalities. Most of the cancer treatment methods including chemotherapy, radiotherapy, photodynamic therapy, sonodynamic therapy and immunotherapy are negatively affected by the oxygen deprivation. Therefore, the regional oxygenation is requisite to alleviate the negative impacts of the hypoxia on tumor cells and tumor therapy modalities. A great deal of effort has been put forth to resolve the problem of hypoxia in tumors. Peroxides have gained tremendous attention as oxygen generating components in cancer therapy. The concurrent loading of the peroxides and cancer treatment components into a single delivery system can bring about a multipurpose delivery system and substantially encourage the success of the cancer amelioration. In this review, we have tried to after the description of a relation between hypoxia and cancer treatment modalities, discuss the role of peroxides in tumor hyperoxygenation and cancer therapy success. Thereafter, we have summarized a number of vehicles for the delivery of the peroxide alone or in combination with other therapeutic components for cancer treatment.
    Keywords:  Cancer; Hypoxia; Oxygen delivery; Peroxide
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112832
  4. Nanomaterials (Basel). 2022 Sep 15. pii: 3201. [Epub ahead of print]12(18):
    The Potential of Curcumin-Capped Nanoparticle Synthesis in Cancer Therapy: A Green Synthesis Approach.
    Jeaneen Venkatas, Aliscia Daniels, Moganavelli Singh.
      Cancer nanotherapeutics is an important field of research which utilizes nanomaterials as an approach to cancer therapy. Nano-mediated therapeutic delivery systems overcome the adverse side effects of traditional cancer treatment methods. Nanoparticles (NPs) are considered excellent tumor-targeting vehicles due to their compact and variable size, large surface area, ability to load several genes and drugs, and mediation of increased therapeutic payload uptake. Despite the rapid development of nanotechnology, there is growing concern regarding the possible long-term side effects of NPs on the environment and human health. Green chemistry using plant materials, such as curcumin, is a sustainable alternative to conventional reduction methods and confers dual reducing and capping properties. Curcumin is a bioactive compound isolated from the rhizome of the Curcuma longa plant, which exhibits various medicinal properties. Curcumin-capped NPs exhibit increased solubility, bioavailability, therapeutic indices, and antitumor properties. This review highlights the potential and antitumor properties of economical, simple, and eco-friendly curcumin-synthesized and capped NPs for the localized delivery of therapeutic genes and drugs to the cancer tumor microenvironment with fewer adverse side effects.
    Keywords:  cancer; curcumin; delivery systems; green chemistry; nanoparticles
    DOI:  https://doi.org/10.3390/nano12183201
  5. Cell Death Dis. 2022 Sep 24. 13(9): 817
    Interplays of glucose metabolism and KRAS mutation in pancreatic ductal adenocarcinoma.
    Yu-Huei Liu, Chun-Mei Hu, Yuan-Sheng Hsu, Wen-Hwa Lee.
      Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide. The primary reasons for this are the lack of early detection methods and targeted therapy. Emerging evidence highlights the metabolic addiction of cancer cells as a potential target to combat PDAC. Oncogenic mutations of KRAS are the most common triggers that drive glucose uptake and utilization via metabolic reprogramming to support PDAC growth. Conversely, high glucose levels in the pancreatic microenvironment trigger genome instability and de novo mutations, including KRASG12D, in pancreatic cells through metabolic reprogramming. Here, we review convergent and diverse metabolic networks related to oncogenic KRAS mutations between PDAC initiation and progression, emphasizing the interplay among oncogenic mutations, glucose metabolic reprogramming, and the tumor microenvironment. Recognizing cancer-related glucose metabolism will provide a better strategy to prevent and treat the high risk PDAC population.
    DOI:  https://doi.org/10.1038/s41419-022-05259-w
  6. Cancers (Basel). 2022 Sep 14. pii: 4462. [Epub ahead of print]14(18):
    Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage.
    Luca Menilli, Celeste Milani, Elena Reddi, Francesca Moret.
      The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient's adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models.
    Keywords:  biomimetic nanoparticles; chemotherapy; nanoparticles; photodynamic therapy; photosensitizers; synergistic combination; targeted tumor therapy; tumor microenvironment responsive drugs; upconverting nanoparticles
    DOI:  https://doi.org/10.3390/cancers14184462
  7. Transl Oncol. 2022 Sep 14. pii: S1936-5233(22)00199-1. [Epub ahead of print]26 101540
    Combined HASPIN and mTOR inhibition is synergistic against KRAS-driven carcinomas.
    Chenyue Xu, Qiongmei Gao, Zhengming Wu, Weijuan Lou, Xiaoyan Li, Menghui Wang, Nianhong Wang, Qingquan Li.
      BACKGROUND: Oncogenic mutations in the KRAS gene are very common in human cancers, resulting in cells with well-characterized selective advantages. For more than three decades, the development of effective therapeutics to inhibit KRAS-driven tumorigenesis has proved a formidable challenge and KRAS was considered 'undruggable'. Therefore, multi-targeted therapy may provide a reasonable strategy for the effective treatment of KRAS-driven cancers. Here, we assess the efficacy and mechanistic rationale for combining HASPIN and mTOR inhibition as a potential therapy for cancers carrying KRAS mutations.METHODS: We investigated the synergistic effect of a combination of mTOR and HASPIN inhibitors on cell viability, cell cycle, cell apoptosis, DNA damage, and mitotic catastrophe using a panel of human KRAS-mutant and wild-type tumor cell lines. Subsequently, the human transplant models were used to test the therapeutic efficacy and pharmacodynamic effects of the dual therapy.
    RESULTS: We demonstrated that the combination of mTOR and HASPIN inhibitors induced potent synergistic cytotoxic effects in KRAS-mutant cell lines and delayed the growth of human tumor xenograft. Mechanistically, we showed that inhibiting of mTOR potentiates HASPIN inhibition by preventing the phosphorylation of H3 histones, exacerbating mitotic catastrophe and DNA damage in tumor cell lines with KRAS mutations, and this effect is due in part to a reduction in VRK1.
    CONCLUSIONS: These findings indicate that increased DNA damage and mitotic catastrophe are the basis for the effective synergistic effect observed with mTOR and HASPIN inhibition, and support the clinical evaluation of this dual therapy in patients with KRAS-mutant tumors.
    Keywords:  Cancer; HASPIN; KRAS; VRK1; mTOR
    DOI:  https://doi.org/10.1016/j.tranon.2022.101540
  8. Pharmaceutics. 2022 Aug 24. pii: 1763. [Epub ahead of print]14(9):
    Recent Strategies to Address Hypoxic Tumor Environments in Photodynamic Therapy.
    Yuyin Du, Jianhua Han, Feiyang Jin, Yongzhong Du.
      Photodynamic therapy (PDT) has become a promising method of cancer treatment due to its unique properties, such as noninvasiveness and low toxicity. The efficacy of PDT is, however, significantly reduced by the hypoxia tumor environments, because PDT involves the generation of reactive oxygen species (ROS), which requires the great consumption of oxygen. Moreover, the consumption of oxygen caused by PDT would further exacerbate the hypoxia condition, which leads to angiogenesis, invasion of tumors to other parts, and metastasis. Therefore, many research studies have been conducted to design nanoplatforms that can alleviate tumor hypoxia and enhance PDT. Herein, the recent progress on strategies for overcoming tumor hypoxia is reviewed, including the direct transport of oxygen to the tumor site by O2 carriers, the in situ generation of oxygen by decomposition of oxygen-containing compounds, reduced O2 consumption, as well as the regulation of tumor microenvironments. Limitations and future perspectives of these technologies to improve PDT are also discussed.
    Keywords:  hypoxia; oxygen; oxygen supply; photodynamic therapy
    DOI:  https://doi.org/10.3390/pharmaceutics14091763
  9. Nanotechnology. 2022 Sep 19. 33(49):
    Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery ofPeganum harmalasmoke extract to breast cancer cells.
    Masoud Homayouni Tabrizi.
      In this study, PLGA-NPs coated with folic acid-chitosan (PCF-NPs) loaded withPeganum harmalasmoke extract (PSE) were synthesized (PSE-PCF-NPs), and their anti-cancer effects were evaluated. PSE-PCF-NPs were synthesized by the nanoprecipitation method and then characterized by DLS, SEM, and FTIR methods. HPLC and UV-vis spectroscopy were used to evaluate the PSE's folic acid (FA) binding and encapsulation. PSE-PCF-NPs-mediated cell viability and apoptosis were investigated by MTT, qPCR, flow cytometry, AO/PI, and DAPI staining. Anti-oxidant properties of PSE-PCF-NPs were evaluated by ABTS, DPPH, FRAP, and ROS. Angiogenic effects of PSE-PCF-NPs were assessed by CAM assay. The PSE-PCF-NPs (276.16 nm, PDI: 0.25, zeta-potential: +32.31 mV, FB: 67.6% and %EE: 89%) demonstrated selective toxicity on MCF-7 cells (IC50: 75.65μg ml-1). The occurrence of apoptosis in MCF-7 cells was confirmed by up-regulation of P53, Cas-3, and Cas-9 genes, increased SubG1 phase cells, and the results of fluorescent staining. Scavenging free radicals, reducing iron ions, increasing intracellular ROS, and decreasing SOD gene confirmed the anti- and pro-oxidant effects of PSE-PCF-NPs outside and inside MCF-7 cells. Reduction of angiogenic factors in CAM assay showed the anti-angiogenic effects of PSE-PCF-NPs. PSE-PCF-NPs, due to their anti-cancer properties, can be considered a therapeutic agent in cancer studies.
    Keywords:  PLGA nanoparticles; antioxidant; breast cancer cells; chitosan; folic acid; peganum harmala smoke extract
    DOI:  https://doi.org/10.1088/1361-6528/ac8e0a
  10. Nanomaterials (Basel). 2022 Sep 11. pii: 3150. [Epub ahead of print]12(18):
    Multifaceted Elevation of ROS Generation for Effective Cancer Suppression.
    Huizhe Wang, Mengyuan Cui, Yanqi Xu, Tianguang Liu, Yueqing Gu, Peng Wang, Hui Tang.
      The in situ lactate oxidase (LOx) catalysis is highly efficient in reducing oxygen to H2O2 due to the abundant lactate substrate in the hypoxia tumor microenvironment. Dynamic therapy, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and enzyme dynamic therapy (EDT), could generate reactive oxygen species (ROS) including ·OH and 1O2 through the disproportionate or cascade biocatalytic reaction of H2O2 in the tumor region. Here, we demonstrate a ROS-based tumor therapy by integrating LOx and the antiglycolytic drug Mito-LND into Fe3O4/g-C3N4 nanoparticles coated with CaCO3 (denoted as FGLMC). The LOx can catalyze endogenous lactate to produce H2O2, which decomposes cascades into ·OH and 1O2 through Fenton reaction-induced CDT and photo-triggered PDT. Meanwhile, the released Mito-LND contributes to metabolic therapy by cutting off the source of lactate and increasing ROS generation in mitochondria for further improvement in CDT and PDT. The results showed that the FGLMC nanoplatform can multifacetedly elevate ROS generation and cause fatal damage to cancer cells, leading to effective cancer suppression. This multidirectional ROS regulation strategy has therapeutic potential for different types of tumors.
    Keywords:  CDT; PDT; ROS; cancer; lactate oxidase
    DOI:  https://doi.org/10.3390/nano12183150
  11. Molecules. 2022 Sep 10. pii: 5889. [Epub ahead of print]27(18):
    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways.
    Saleh A Almatroodi, Mohammed A Alsahli, Arshad Husain Rahmani.
      Cancer is the most commonly diagnosed type of disease and a major cause of death worldwide. Despite advancement in various treatment modules, there has been little improvement in survival rates and side effects associated with this disease. Medicinal plants or their bioactive compounds have been extensively studied for their anticancer potential. Novel drugs based on natural products are urgently needed to manage cancer through attenuation of different cell signaling pathways. In this regard, berberine is a bioactive alkaloid that is found in variety of plants, and an inverse association has been revealed between its consumption and cancer. Berberine exhibits an anticancer role through scavenging free radicals, induction of apoptosis, cell cycle arrest, inhibition of angiogenesis, inflammation, PI3K/AKT/mammalian target of rapamycin (mTOR), Wnt/β-catenin, and the MAPK/ERK signaling pathway. In addition, synergistic effects of berberine with anticancer drugs or natural compounds have been proven in several cancers. This review outlines the anticancer effects and mechanisms of action of berberine in different cancers through modulation of various cell signaling pathways. Moreover, the recent developments in the drug delivery systems and synergistic effect of berberine are explained.
    Keywords:  berberine; bioavailability; cancer; cell signaling pathways; synergistic effects
    DOI:  https://doi.org/10.3390/molecules27185889
  12. Nanoscale Adv. 2021 Mar 23. 3(6): 1656-1673
    Chemosensitivity enhanced by autophagy inhibition based on a polycationic nano-drug carrier.
    Na Li, Shangcong Han, Baohua Ma, Xia Huang, Lisa Xu, Jie Cao, Yong Sun.
      In recent years, with the increasing understanding of the role of autophagy in tumorigenesis and development, a steady stream of studies have demonstrated that both excessive induction and inhibition of autophagy could effectively improve the therapeutic efficacy against tumors during cytotoxic or molecularly targeted drug therapy. Among them, autophagy inhibition mediated by nanomaterials has become an appealing notion in nanomedicine therapeutics, since it can be exploited as an effective adjuvant in chemotherapy or as a potential anti-tumor agent. Herein, we constructed a pH-sensitive nanoplatform loaded with epirubicin (EPI) (mPEG-b-P(DPA-b-DMAEMA)/EPI), enabling effective autophagy inhibition in the process of tumor-targeting therapy and further sensitized the tumors to EPI. It was found that polycationic nanomicelles (PEDD-Ms) displayed specific localization in lysosomes after entering tumor cells and caused the impairment of lysosomal degradation capacity through lysosomal alkalization in a dose-dependent manner. HepG2 cells treated with PEDD-Ms displayed a large-scale accumulation of autophagosomes and LC3 (an autophagosome marker protein), and the degradation of the autophagy substrate p62 was also blocked, which indicated that these functional nanomicelles could significantly inhibit autophagy. Meanwhile, the typical morphological characteristics of autophagosomes were directly visualized by TEM. In vivo results also showed that the tumor-targeted and autophagy inhibition-associated nanoplatform therapy could effectively improve the therapeutic efficiency of EPI, which may be partially attributed to the fact that autophagy inhibition could enhance the sensitivity of tumor cells to EPI. Overall, we revealed the effect of polycationic nanomicelles on autophagic processes in tumor cells and explored their possible molecular mechanism, also considering the synergistic outcome between autophagy mediated by nanomaterials and chemotherapeutic drugs to improve the therapeutic effect on tumors.
    DOI:  https://doi.org/10.1039/d0na00990c
  13. Drug Deliv. 2022 Dec;29(1): 3052-3070
    Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges.
    Ruirui Zhang, Hao Zhang, Houyin Shi, Dan Zhang, Zhuo Zhang, Hao Liu.
      Dihydromyricetin (DHM) is an important natural flavonoid that has attracted much attention because of its various functions such as protecting the cardiovascular system and liver, treating cancer and neurodegenerative diseases, and anti-inflammation effect, etc. Despite its great development potential in pharmacy, DHM has some problems in pharmaceutical applications such as low solubility, permeability, and stability. To settle these issues, extensive research has been carried out on its physicochemical properties and dosage forms to produce all kinds of DHM preparations in the past ten years. In addition, the combined use of DHM with other drugs is a promising strategy to expand the application of DHM. However, although invention patents for DHM preparations have been issued in several countries, the current transformation of DHM research results into market products is insufficient. To date, there is still a lack of deep research into the pharmacokinetics, pharmacodynamics, toxicology, and action mechanism of DHM preparations. Besides, preparations for combined therapy of DHM with other drugs are scarcely reported, which necessitates the development of dosage forms for this application. Apart from medicine, the development of DHM in the food industry is also of great potential. Due to its multiple effects and excellent safety, DHM preparations can be developed for functional drinks and foods. Through this review, we hope to draw more attention to the development potential of DHM and the above challenges and provide valuable references for the research and development of other natural products with a similar structure-activity relationship to this drug.
    Keywords:  Dihydromyricetin; dosage forms; drug delivery; natural product; pharmaceutics
    DOI:  https://doi.org/10.1080/10717544.2022.2125601
  14. Int J Biol Macromol. 2022 Sep 14. pii: S0141-8130(22)02001-3. [Epub ahead of print]
    Targeted chitosan nanoparticles embedded into graphene oxide functionalized with caffeic acid as a potential drug delivery system: New insight into cancer therapy.
    Bushra Tousian, Mohammad Hadi Ghasemi, Ali Reza Khosravi.
      As a novel drug delivery technology, chitosan (CHI) nanoparticles are encapsulated in graphene oxide (GO) with caffeic acid (CA). The nanocarrier technique combines targeted drug delivery with molecular imaging to provide new cancer insights. Attachment of CA, an anticancer agent for controlled drug release, to functionalized graphene oxide (GON) utilizing 3-aminopropyltriethoxysilane (APTES) was followed by encapsulation of GO with folic acid (FA) attached CHI to produce this novel system. FT-IR was used to characterize and confirm the chemical production process. BET analysis was used to validate multi-holes and nanometric dimensions (1-100 nm) and assess their drug administration use. Release and loading tests showed a pH dependence and implied CA hydrogen-bonding in GON. CA encapsulation and loading percentages are 86 % and 67 %, respectively. The acidic environment (pH 5.3) of tumor cells may produce a larger release of CA, and the release rate of CA maintains a constant trend, indicating the drug is released for more than a week (because the release rate has not reached zero). The proposed method provides a potential candidate for a novel drug delivery system in cancer therapy. The resulting nanohybrid system is a new way to combine biodegradable materials, that can be used in biomedical applications.
    Keywords:  Caffeic acid; Chitosan; Drug delivery; Graphene oxide; Surface functionalization
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.084
  15. Pharmaceuticals (Basel). 2022 Aug 26. pii: 1059. [Epub ahead of print]15(9):
    Hybrid Membrane-Derived Nanoparticles for Isoliquiritin Enhanced Glioma Therapy.
    Wenwan Shi, Xia Cao, Qi Liu, Qin Zhu, Kai Liu, Tianwen Deng, Qingtong Yu, Wenwen Deng, Jiangnan Yu, Qilong Wang, Ximing Xu.
      Due to the obstruction and heterogeneity of the blood-brain barrier, the clinical treatment of glioma has been extremely difficult. Isoliquiritigenin (ISL) exhibits antitumor effects, but its low solubility and bioavailability limit its application potential. Herein, we established a nanoscale hybrid membrane-derived system composed of erythrocytes and tumor cells. By encapsulating ISL in hybrid membrane nanoparticles, ISL is expected to be enhanced for the targeting and long-circulation in gliomas therapy. We fused erythrocytes with human glioma cells U251 and extracted the fusion membrane via hypotension, termed as hybrid membrane (HM). HM-camouflaged ISL nanoparticles (ISL@HM NPs) were prepared and featured with FT-IR, SEM, TEM, and DLS particle analysis. As the results concluded, the ISL active pharmaceutical ingredients (APIs) were successfully encapsulated with HM membranes, and the NPs loading efficiency was 38.9 ± 2.99% under maximum entrapment efficiency. By comparing the IC50 of free ISL and NPs, we verified that the solubility and antitumor effect of NPs was markedly enhanced. We also investigated the mechanism of the antitumor effect of ISL@HM NPs, which revealed a marked inhibition of tumor cell proliferation and promotion of senescence and apoptosis of tumor cells of the formulation. In addition, the FSC and WB results examined the effects of different concentrations of ISL@HM NPs on tumor cell disruption and apoptotic protein expression. Finally, it can be concluded that hybridized membrane-derived nanoparticles could prominently increase the solubility of insoluble materials (as ISL), and also enhance its targeting and antitumor effect.
    Keywords:  antitumor; mechanism; nanoparticle; red blood cell membrane
    DOI:  https://doi.org/10.3390/ph15091059
  16. J Food Biochem. 2022 Sep 19. e14387
    Role of Medicinal plant-derived Nutraceuticals as a potential target for the treatment of breast cancer.
    Khalid Saad Alharbi, Waleed Hassan Almalki, Hafiz A Makeen, Mohammed Albratty, Abdulkarim M Meraya, Rupak Nagraik, Avinash Sharma, Deepak Kumar, Dinesh Kumar Chellappan, Sachin Kumar Singh, Kamal Dua, Gaurav Gupta.
      Breast cancer (BC) is one of the most challenging cancers to treat, accounting for many cancer-related deaths. Over some years, chemotherapy, hormone treatment, radiation, and surgeries have been used to treat cancer. Unfortunately, these treatment options are unsuccessful due to crucial adverse reactions and multidrug tolerance/resistance. Although it is clear that substances in the nutraceuticals category have a lot of anti-cancer activity, using a supplementary therapy strategy, in this case, could be very beneficial. Nutraceuticals are therapeutic agents, which are nutrients that have drug-like characteristics and can be used to treat diseases. Plant nutraceuticals categorized into polyphenols, terpenoids, vitamins, alkaloids, and flavonoids are part of health food products, that have great potential for combating BC. Nutraceuticals can reduce BC's severity, limit malignant cell growth, and modify cancer-related mechanisms. Nutraceuticals acting by attenuating Hedgehog, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Notch, and Wnt/β-catenin signaling are the main pathways in controlling the self-renewal of breast cancer stem cells (BCSCs). This article reviews some important nutraceuticals and their modes of action, which can be very powerful versus BC. PRACTICAL APPLICATIONS: Nutraceuticals' importance to the control and diagnosis of breast cancer is undeniable and cannot be overlooked. Natural dietary compounds have a wide range of uses and have been used in traditional medicine. In addition, these natural chemicals can enhance the effectiveness of other traditional medicines. They may also be used as a treatment process independently because of their capacity to affect several cancer pathways. This study highlights a variety of natural chemicals, and their mechanisms of action, routes, synergistic effects, and future potentials are all examined.
    Keywords:  Hedgehog; Nutraceuticals; Wnt/β-catenin; breast cancer; polyphenols
    DOI:  https://doi.org/10.1111/jfbc.14387
  17. Cells. 2022 Sep 15. pii: 2885. [Epub ahead of print]11(18):
    A Review of the Pharmacological Potential of Spatholobus suberectus Dunn on Cancer.
    Feng Zhang, Kumar Ganesan, Qingqing Liu, Jianping Chen.
      Spatholobus suberectus Dunn (SSD) has been extensively employed in Traditional Chinese Medicine to treat several ailments. SSD and its active compounds are effective therapeutic agents for treating a variety of diseases with negligible side effects. Therefore, we aimed to investigate its phytochemistry, pharmacology, and potential therapeutic effects exclusively in cancer prevention and treatment. Phytochemical and pharmacological information was collected and arranged in a rational order. SSD has been frequently attributed to having antioxidant, anti-diabetic, anti-inflammatory, hematopoietic, neuroprotective, antimicrobial, and anticancer properties. Evidence has indicated that the bioactive constituents in SSD have attracted increasing scientific attention due to their preventive role in cancers. Further, the present review provides the current information on the health implications of SSD, thus allowing for future clinical trials to explore its restorative benefits. All data of in vitro and animal investigations of SSD, as well as its effect on human health, were obtained from an electronic search and library database. The diverse pharmacological potential of SSD provides an opportunity for preclinical drug discovery, and this comprehensive review strongly indicates that SSD is an excellent anti-tumorigenic agent that modulates or prevents breast cancer.
    Keywords:  Spatholobus suberectus Dunn; cancer prevention; mechanism; pharmacological activity; phytochemistry
    DOI:  https://doi.org/10.3390/cells11182885
  18. J Control Release. 2022 Sep 16. pii: S0168-3659(22)00612-5. [Epub ahead of print]
    Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor.
    Haoyu Guo, Lutong Wang, Wei Wu, Mingke Guo, Lingkai Yang, Zhenhao Zhang, Li Cao, Feifei Pu, Xin Huang, Zengwu Shao.
      Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.
    Keywords:  Cell membrane-coated nanotechnology; Hypoxic tumor; Synergistic photodynamic-chemotherapy; Targeted delivery system
    DOI:  https://doi.org/10.1016/j.jconrel.2022.09.020
  19. Pharmaceutics. 2022 Aug 23. pii: 1759. [Epub ahead of print]14(9):
    Two-in-One Nanoparticle Formulation to Deliver a Tyrosine Kinase Inhibitor and microRNA for Targeting Metabolic Reprogramming and Mitochondrial Dysfunction in Gastric Cancer.
    Yu-Li Lo, Tse-Yuan Wang, Chun-Jung Chen, Yih-Hsin Chang, Anya Maan-Yuh Lin.
      Dysregulational EGFR, KRAS, and mTOR pathways cause metabolic reprogramming, leading to progression of gastric cancer. Afatinib (Afa) is a broad-spectrum tyrosine kinase inhibitor that reduces cancer growth by blocking the EGFR family. MicroRNA 125 (miR-125) reportedly diminishes EGFRs, glycolysis, and anti-apoptosis. Here, a one-shot formulation of miR-125 and Afa was presented for the first time. The formulation comprised solid lipid nanoparticles modified with mitochondrial targeting peptide and EGFR-directed ligand to suppress pan-ErbB-facilitated epithelial-mesenchymal transition and mTOR-mediated metabolism discoordination of glycolysis-glutaminolysis-lipids. Results showed that this cotreatment modulated numerous critical proteins, such as EGFR/HER2/HER3, Kras/ERK/Vimentin, and mTOR/HIF1-α/HK2/LDHA pathways of gastric adenocarcinoma AGS cells. The combinatorial therapy suppressed glutaminolysis, glycolysis, mitochondrial oxidative phosphorylation, and fatty acid synthesis. The cotreatment also notably decreased the levels of lactate, acetyl-CoA, and ATP. The active involvement of mitophagy supported the direction of promoting the apoptosis of AGS cells, which subsequently caused the breakdown of tumor-cell homeostasis and death. In vivo findings in AGS-bearing mice confirmed the superiority of the anti-tumor efficacy and safety of this combination nanomedicine over other formulations. This one-shot formulation disturbed the metabolic reprogramming; alleviated the "Warburg effect" of tumors; interrupted the supply of fatty acid, cholesterol, and triglyceride; and exacerbated the energy depletion in the tumor microenvironment, thereby inhibiting tumor proliferation and aggressiveness. Collectively, the results showed that the two-in-one nanoparticle formulation of miR-125 and Afa was a breakthrough in simplifying drug preparation and administration, as well as effectively inhibiting tumor progression through the versatile targeting of pan-ErbB- and mTOR-mediated mitochondrial dysfunction and dysregulated metabolism.
    Keywords:  microRNA; mitochondrial dysfunction; mitochondrial targeting; nanoparticle; tumor metabolism reprogramming; tyrosine kinase inhibitor
    DOI:  https://doi.org/10.3390/pharmaceutics14091759
  20. Acta Biomater. 2022 Sep 14. pii: S1742-7061(22)00588-8. [Epub ahead of print]
    Targeted co-delivery of a photosensitizer and an antisense oligonucleotide based on an activatable hyaluronic acid nanosystem with endogenous oxygen generation for enhanced photodynamic therapy of hypoxic tumors.
    Yanni Wu, Lei Ding, Cheng Zheng, Hongsheng Li, Ming Wu, Yupeng Sun, Xiaolong Liu, Xiaolong Zhang, Yongyi Zeng.
      Photodynamic therapy (PDT) is a promising cancer treatment modality with advantages of minimal invasiveness, repeatable therapy, and mild systemic toxicity. However, the limited bioavailability of photosensitizer (PS), tumor hypoxia, and the presence of antiapoptotic proteins in cancer cells, has hampered the efficiency of PDT. To address these limitations, herein, we developed a hyaluronic acid (HA) based nanosystem (HA-Ce6-Hemin@DNA-Protamine NPs, HCH@DP) loaded with chlorin e6 (Ce6, as PS), hemin (as mimetic catalase) and antisense oligonucleotide (ASO) of B-cell lymphoma 2 (Bcl-2) anti-apoptosis protein via a simple electrostatic self-assembly method for enhanced PDT of hypoxic solid tumors. The HCH@DP can target deliver the PS and ASO to tumor cells via cancer cell overexpressed HA receptors (i.e., CD44 or RHAMM). The Ce6 was released from HA-ss-Ce6 (HSC conjugates) after the reaction of cleavable disulfide bond with glutathione (GSH), which recovered the fluorescence and phototoxicity of Ce6 upon laser irradiation. Meanwhile, the catalase-mimicking hemin (degradation of HA-eda-hemin by hyaluronidase) decomposed the tumor overdressed endogenous H2O2 to oxygen, which relieved tumor hypoxia and further overcome hypoxia-associated resistance of PDT. Furthermore, the inhibition of Bcl-2 expression by Bcl-2 ASO also greatly improved the cellular sensitivity to PDT. Both in vitro and in vivo results showed the tumor cell targeting ability, hypoxia relief and significantly enhanced antitumor PDT efficacy of HCH@DP for hypoxic tumor cells upon laser irradiation. Thus, by improving the target delivery of PS and ASO, relieving tumor hypoxia, and down-regulation of anti-apoptotic proteins, this HCH@DP nanosystem achieved enhanced PDT efficiency against hypoxic tumors. In general, our work provided a promising strategy to increase the utilization of key components (PS and oxygen) of PDT and the cell sensitivity to PDT by targeting co-delivery PS and oligonucleotides to tumor cells via a biocompatible HA based carrier, thereby achieving efficiently PDT treatment of hypoxic solid tumors with potential translation possibility. STATEMENT OF SIGNIFICANCE: The efficiency of PDT against solid tumor is severely restricted by the limited bioavailability of photosensitizer, tumor hypoxia, and the presence of antiapoptotic proteins in cancer cells. Herein, we have developed an activatable hyaluronic acid (HA) based nanosystem (HA-Ce6-Hemin@DNA-Protamine NPs, HCH@DP) via a simple electrostatic self-assembly method for PDT treatment of hypoxic solid tumors. The HCH@DP enabled to target co-delivery of photosensitizer and antisense oligonucleotide to tumor cells, overcoming tumor hypoxia through in situ oxygen production and improving cellular sensitivity by efficiently reducing anti-apoptosis effect of cancer cells for synergistically enhancing PDT efficiency. This work suggests a promising strategy to develop small molecule drug and oligonucleotides co-delivery nanoplatforms for efficiently PDT treatment of hypoxic solid tumor.
    Keywords:  antisense oligonucleotide; hyaluronic acid; hypoxia; synergistic PDT; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.actbio.2022.09.025
  21. Pharmaceuticals (Basel). 2022 Aug 31. pii: 1093. [Epub ahead of print]15(9):
    Importance of Rose Bengal Loaded with Nanoparticles for Anti-Cancer Photodynamic Therapy.
    Batoul Dhaini, Laurène Wagner, Morgane Moinard, Joël Daouk, Philippe Arnoux, Hervé Schohn, Perrine Schneller, Samir Acherar, Tayssir Hamieh, Céline Frochot.
      Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT.
    Keywords:  X-rays; cancer; nanomedicine; nanoparticle; photodynamic therapy; rose bengal; singlet oxygen
    DOI:  https://doi.org/10.3390/ph15091093
  22. Pharmaceuticals (Basel). 2022 Sep 09. pii: 1131. [Epub ahead of print]15(9):
    Embelin and Its Derivatives: Design, Synthesis, and Potential Delivery Systems for Cancer Therapy.
    Michael Danquah.
      Embelin is a naturally occurring benzoquinone that inhibits the growth of cancer cells, making it a potent anticancer drug. However, the low water solubility of embelin restricts its clinical applicability. This review provides a concise summary and in-depth analysis of the published literature on the design and synthesis of embelin derivatives possessing increased aqueous solubility and superior therapeutic efficacy. In addition, the potential of drug delivery systems to improve the anticancer capabilities of embelin and its derivatives is discussed.
    Keywords:  XIAP; XIAP inhibitor; anticancer; cancer therapy; drug delivery; embelin; embelin derivatives
    DOI:  https://doi.org/10.3390/ph15091131
  23. Chembiochem. 2022 Sep 23.
    A selenium-substituted heptamethine cyanine photosensitizer for near-infrared photodynamic therapy.
    Jinghan Sun, Erting Feng, Yutong Shao, Fangyuan Lv, Yingnan Wu, Jiarui Tian, Han Sun, Fengling Song.
      Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (Φ Δ ) are not ideal. Herein, we developed a NIR photosensitizer with a long-lived excited triplet state (t = 4.3 ms) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (Φ Δ = 0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we firmly believe that it will have a promising future in biomedical and clinical applications.
    Keywords:  NIR excitation; cyanine dyes; heavy atom effect; photodynamic therapy; selenium
    DOI:  https://doi.org/10.1002/cbic.202200421
  24. Int J Mol Sci. 2022 Sep 07. pii: 10295. [Epub ahead of print]23(18):
    Erythrocyte-Derived Nanoparticles with Folate Functionalization for Near Infrared Pulsed Laser-Mediated Photo-Chemotherapy of Tumors.
    Jenny T Mac, Raviraj Vankayala, Chi-Hua Lee, Bahman Anvari.
      Despite its common side effects and varying degrees of therapeutic success, chemotherapy remains the gold standard method for treatment of cancer. Towards developing a new therapeutic approach, we have engineered nanoparticles derived from erythrocytes that contain indocyanine green as a photo-activated agent that enables near infrared photothermal heating, and doxorubicin hydrochloride (DOX) as a chemotherapeutic drug. We hypothesize that milliseconds pulsed laser irradiation results in rapid heating and photo-triggered release of DOX, providing a dual photo-chemo therapeutic mechanism for tumor destruction. Additionally, the surface of the nanoparticles is functionalized with folate to target the folate receptor-α on tumor cells to further enhance the therapeutic efficacy. Using non-contract infrared radiometry and absorption spectroscopy, we have characterized the photothermal response and photostability of the nanoparticles to pulsed laser irradiation. Our in vitro studies show that these nanoparticles can mediate photo-chemo killing of SKOV3 ovarian cancer cells when activated by pulsed laser irradiation. We further demonstrate that this dual photo-chemo therapeutic approach is effective in reducing the volume of tumor implants in mice and elicits an apoptotic response. This treatment modality presents a promising approach in destruction of small tumor nodules.
    Keywords:  biomimetics; cancer; drug delivery; laser therapy; nanotechnology; photothermal therapy; red blood cells
    DOI:  https://doi.org/10.3390/ijms231810295
  25. Int J Biol Macromol. 2022 Sep 16. pii: S0141-8130(22)02048-7. [Epub ahead of print]220 1464-1479
    Pulmonary drug delivery applications of natural polysaccharide polymer derived nano/micro-carrier systems: A review.
    Akshad Balde, Se-Kwon Kim, Soottawat Benjakul, Rasool Abdul Nazeer.
      Respiratory distress syndrome and pneumothorax are the foremost causes of death as a result of the changing lifestyle and increasing air pollution. Numerous approaches have been studied for the pulmonary delivery of drugs, proteins as well as peptides using meso/nanoparticles, nanocrystals, and liposomes. These nano/microcarrier systems (NMCs) loaded with drug provide better systemic as well as local action. Furthermore, natural polysaccharide-based polymers such as chitosan (CS), alginate (AG), hyaluronic acid, dextran, and cellulose are highly used for the preparation of nanoparticles and delivery of the drug into the pulmonary tract due to their advantageous properties such as low toxicity, high hydrophobicity, supplementary mucociliary clearance, mucoadhesivity, and biological efficacy. These properties ease the delivery of drugs onto the targeted site. Herein, recent advances in the natural polymer-derived NMCs have been reviewed for their transport and mechanism of action into the bronchiolar region as well as the respiratory region. Various physicochemical properties such as surface charge, size of nanocarrier system, surface modifications, and toxicological effects of these nanocarriers in vitro and in vivo are elucidated as well. Furthermore, challenges faced for the preparation of a model NMCs for pulmonary drug delivery are also discoursed.
    Keywords:  Drug delivery; Nanomedicine; Pulmonary distress; Toxicity evaluation
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.116
  26. J Cancer Res Clin Oncol. 2022 Sep 23.
    Metabolic changes during prostate cancer development and progression.
    Alicia-Marie K Beier, Martin Puhr, Matthias B Stope, Christian Thomas, Holger H H Erb.
      Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour's bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic and biochemical changes in 1927. In prostate cancer (PCa) epithelial cells, the tumour metabolism also changes during development and progress. These alterations are partly driven by the androgen receptor, the key regulator in PCa development, progress, and survival. In contrast to other epithelial cells of different entities, glycolytic metabolism in prostate cells sustains physiological citrate secretion in the normal prostatic epithelium. In the early stages of PCa, citrate is utilised to power oxidative phosphorylation and fuel lipogenesis, enabling tumour growth and progression. In advanced and incurable castration-resistant PCa, a metabolic shift towards choline, amino acid, and glycolytic metabolism fueling tumour growth and progression has been described. Therefore, even if the metabolic changes are not fully understood, the altered metabolism during tumour progression may provide opportunities for novel therapeutic strategies, especially in advanced PCa stages. This review focuses on the main differences in PCa's metabolism during tumourigenesis and progression highlighting glutamine's role in PCa.
    Keywords:  CRPC; Glutamine; Metabolic reprogramming
    DOI:  https://doi.org/10.1007/s00432-022-04371-w
  27. Cell Death Dis. 2022 Sep 21. 13(9): 808
    Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism.
    Pengyun Li, Qiaohong Lin, Shiyang Sun, Ning Yang, Yu Xia, Shengjie Cao, Wenjuan Zhang, Qian Li, Haoxin Guo, Maoxiang Zhu, Yilong Wang, Zhibing Zheng, Song Li.
      Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that displays highly aggressive with poor prognosis. Owing to the limited targets and drugs for TNBC clinical therapy, it is necessary to investigate the factors regulating cancer progression and develop novel therapies for cancer treatment. Ferroptosis, a nonapoptotic form of programmed cell death characterized by accumulation of iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating potential combinational therapeutic strategies for cancer treatment. In this study, by drug combination screen of lipid metabolism compounds with ferroptosis inducers in decreasing TNBC cell viability, we found potent synergy of the CB1 antagonist rimonabant with erastin/(1 S, 3 R)-RSL3 (RSL3) in inhibiting TNBC cell growth both in vitro and in vivo via promoting the levels of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and cytosolic reactive oxygen species (ROS) production, enhancing intracellular glutathione (GSH) depletion and inducing G1 cell cycle arrest. We identified that inhibition of CB1 promoted the effect of erastin/RSL3 on inducing ferroptosis and enhanced their inhibitory effect on tumor growth. Using RNA-Seq, fatty acid analyses and functional assays, we found that CB1 regulated stearoyl-CoA desaturase 1 (SCD1)- and fatty acyl desaturase 2 (FADS2)-dependent fatty acid metabolism via phosphatidylinositol 3 kinase (PI3K)-AKT and mitogen-activated protein kinase (MAPK) signaling pathways to modulate ferroptosis sensitivity in TNBC cells. These data demonstrate that dual targeting of CB1 and ferroptosis could be a promising therapeutic strategy for TNBC.
    DOI:  https://doi.org/10.1038/s41419-022-05242-5
  28. Nanomaterials (Basel). 2022 Sep 14. pii: 3183. [Epub ahead of print]12(18):
    Redox-Responsive Drug Delivery Systems: A Chemical Perspective.
    Heba F Abed, Waad H Abuwatfa, Ghaleb A Husseini.
      With the widespread global impact of cancer on humans and the extensive side effects associated with current cancer treatments, a novel, effective, and safe treatment is needed. Redox-responsive drug delivery systems (DDSs) have emerged as a potential cancer treatment with minimal side effects and enhanced site-specific targeted delivery. This paper explores the physiological and biochemical nature of tumors that allow for redox-responsive drug delivery systems and reviews recent advances in the chemical composition and design of such systems. The five main redox-responsive chemical entities that are the focus of this paper are disulfide bonds, diselenide bonds, succinimide-thioether linkages, tetrasulfide bonds, and platin conjugates. Moreover, as disulfide bonds are the most commonly used entities, the review explored disulfide-containing liposomes, polymeric micelles, and nanogels. While various systems have been devised, further research is needed to advance redox-responsive drug delivery systems for cancer treatment clinical applications.
    Keywords:  bonds; drug delivery systems; linkers; redox-responsive; reducing
    DOI:  https://doi.org/10.3390/nano12183183
  29. Math Biosci Eng. 2022 Aug 01. 19(11): 10941-10962
    Assessing the therapeutic response of tumors to hypoxia-targeted prodrugs with an in silico approach.
    Defne Yilmaz, Mert Tuzer, Mehmet Burcin Unlu.
      Tumor hypoxia is commonly recognized as a condition stimulating the progress of the aggressive phenotype of tumor cells. Hypoxic tumor cells inhibit the delivery of cytotoxic drugs, causing hypoxic areas to receive insufficient amounts of anticancer agents, which results in adverse treatment responses. Being such an obstruction to conventional therapies for cancer, hypoxia might be considered a target to facilitate the efficacy of treatments in the resistive environment of tumor sites. In this regard, benefiting from prodrugs that selectively target hypoxic regions remains an effective approach. Additionally, combining hypoxia-activated prodrugs (HAPs) with conventional chemotherapeutic drugs has been used as a promising strategy to eradicate hypoxic cells. However, determining the appropriate sequencing and scheduling of the combination therapy is also of great importance in obtaining favorable results in anticancer therapy. Here, benefiting from a modeling approach, we study the efficacy of HAPs in combination with chemotherapeutic drugs on tumor growth and the treatment response. Different treatment schedules have been investigated to see the importance of determining the optimal schedule in combination therapy. The effectiveness of HAPs in varying hypoxic conditions has also been explored in the study. The model provides qualitative conclusions about the treatment response, as the maximal benefit is obtained from combination therapy with greater cell death for highly hypoxic tumors. It has also been observed that the antitumor effects of HAPs show a hypoxia-dependent profile.
    Keywords:   cancer ; chemotherapy ; hypoxia ; hypoxia-activated prodrugs ; mathematical modeling ; multiscale model ; treatment response
    DOI:  https://doi.org/10.3934/mbe.2022511
  30. Antioxidants (Basel). 2022 Sep 02. pii: 1744. [Epub ahead of print]11(9):
    Dietary EVOO Polyphenols and Gut Microbiota Interaction: Are There Any Sex/Gender Influences?
    Massimo D'Archivio, Carmela Santangelo, Annalisa Silenzi, Beatrice Scazzocchio, Rosaria Varì, Roberta Masella.
      Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with beneficial health effects and a reduced risk of developing chronic degenerative disorders. The beneficial effects of EVOO can be attributed to its unique composition in monounsaturated fats and phenolic compounds that provide important antioxidant, anti-inflammatory, and immune-modulating activities. On the other hand, it is well known that the gut microbiota has several important roles in normal human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors, among which dietary components play a relevant role. In the last few years, the two-way interaction between polyphenols, including those in EVOO, and the gut microbiota, i.e., the modulation of the microbiota by polyphenols and that of polyphenol metabolism and bioavailability by the microbiota, has attracted growing attention, being potentially relevant to explain the final effects of polyphenols, as well as of the microbiota profile. Furthermore, sex and gender can affect dietary habits, polyphenol intake, and nutrient metabolism. Lastly, it has been recently suggested that differences in gut microbiota composition could be involved in the unequal incidence of metabolic diseases observed between women and men, due to sex-dependent effects on shaping gut microbiota profiles according to diet. This review summarizes the most recent studies on the relationship between EVOO polyphenols and the gut microbiota, taking into account possible influences of sex and gender in modulating such an interaction.
    Keywords:  diet; extra virgin olive oil; gender; gut microbiota; polyphenols; sex
    DOI:  https://doi.org/10.3390/antiox11091744
  31. Pharmaceutics. 2022 Aug 27. pii: 1802. [Epub ahead of print]14(9):
    Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy.
    Zhaoming Ma, Xuzhu Gao, Faisal Raza, Hajra Zafar, Guanhong Huang, Yunyun Yang, Feng Shi, Deqiang Wang, Xia He.
      Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a GSH-sensitive material, ATRA-SS-HA, was developed and self-assembled with curcumin, a natural polyphenol antitumor drug, into nanomicelles Cur@ATRA-SS-HA. The micelles had a suitable particle size, excellent drug loading, encapsulation rate, stability, biocompatibility, and stable release behaviour. In the tumor microenvironment, GSH induced disulfide bond rupture in Cur@ATRA-SS-HA and promoted the release of curcumin, improving tumor targeting. Following GSH-induced release, the curcumin IC50 value was significantly lower than that of free curcumin and better than that of 5-FU. In vivo pharmacokinetic experiments showed that the drug-loaded nanomicelles exhibited better metabolic behaviour than free drugs, which greatly increased the blood concentration of curcumin and increased the half-life of the drug. The design of the nanomicelle provides a novel clinical treatment for oesophageal cancer.
    Keywords:  GSH responsive; curcumin; nanomicelles; oesophageal cancer
    DOI:  https://doi.org/10.3390/pharmaceutics14091802
  32. Polymers (Basel). 2022 Sep 08. pii: 3758. [Epub ahead of print]14(18):
    Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters.
    Ismail A Walbi, Mohammad Zaki Ahmad, Javed Ahmad, Mohammed S Algahtani, Amer S Alali, Samar A Alsudir, Alhassan H Aodah, Hassan A Albarqi.
      Curcumin (CUR) has impressive pharmacologic properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activity. However, the pharmaceutical application of CUR is limited due to its poor aqueous solubility and low bioavailability. The development of novel formulations has attracted considerable attention to the idea of applying nanobiotechnology to improve the therapeutic efficacy of these challenging compounds. In this study, CUR-loaded lecithin-chitosan nanoparticles (CUR/LCSNPs) were developed and optimized by the concentration of chitosan, lecithin, and stirring speed by a 3-factorial Box-Behnken statistical design, resulting in an optimal concentration of chitosan (A) and lecithin (B) with a 1200 rpm stirring speed (C), with applied constraints of minimal average particle size (Y1), optimal zeta potential (Y2), and maximum entrapment efficiency (%EE) (Y3). The mean particle size of the checkpoint formulation ranged from 136.44 ± 1.74 nm to 267.94 ± 3.72, with a zeta potential of 18.5 ± 1.39 mV to 36.8 ± 3.24 mV and %EE of 69.84 ± 1.51% to 78.50 ± 2.11%. The mean particle size, zeta potential, %EE, and % cumulative drug release from the optimized formulation were 138.43 ± 2.09 nm, +18.98 ± 0.72 mV, 77.39 ± 1.70%, and 86.18 ± 1.5%, respectively. In vitro drug release followed the Korsmeyer-Peppas model with Fickian diffusion (n < 0.45). The optimized technique has proven successful, resulting in a nanoformulation that can be used for the high loading and controlled release of lipophilic drugs.
    Keywords:  3-factorial Box-Behnken statistical design; chitosan; curcumin; lecithin; nanoparticles; stirring speed
    DOI:  https://doi.org/10.3390/polym14183758
  33. Genes (Basel). 2022 Sep 03. pii: 1585. [Epub ahead of print]13(9):
    Crosstalk between Hypoxia and Extracellular Matrix in the Tumor Microenvironment in Breast Cancer.
    Yasmin Dekker, Sylvia E Le Dévédec, Erik H J Danen, Qiuyu Liu.
      Even though breast cancer is the most diagnosed cancer among women, treatments are not always successful in preventing its progression. Recent studies suggest that hypoxia and the extracellular matrix (ECM) are important in altering cell metabolism and tumor metastasis. Therefore, the aim of this review is to study the crosstalk between hypoxia and the ECM and to assess their impact on breast cancer progression. The findings indicate that hypoxic signaling engages multiple mechanisms that directly contribute to ECM remodeling, ultimately increasing breast cancer aggressiveness. Second, hypoxia and the ECM cooperate to alter different aspects of cell metabolism. They mutually enhance aerobic glycolysis through upregulation of glucose transport, glycolytic enzymes, and by regulating intracellular pH. Both alter lipid and amino acid metabolism by stimulating lipid and amino acid uptake and synthesis, thereby providing the tumor with additional energy for growth and metastasis. Third, YAP/TAZ signaling is not merely regulated by the tumor microenvironment and cell metabolism, but it also regulates it primarily through its target c-Myc. Taken together, this review provides a better understanding of the crosstalk between hypoxia and the ECM in breast cancer. Additionally, it points to a role for the YAP/TAZ mechanotransduction pathway as an important link between hypoxia and the ECM in the tumor microenvironment, driving breast cancer progression.
    Keywords:  YAP/TAZ; breast cancer; cell metabolism; extracellular matrix; hypoxia; mechanotransduction; tumor microenvironment
    DOI:  https://doi.org/10.3390/genes13091585
  34. Eur J Med Chem. 2022 Sep 09. pii: S0223-5234(22)00651-1. [Epub ahead of print]243 114749
    A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug.
    De-Chao Yang, Xiao-Zhen Yang, Cheng-Miao Luo, Lin-Feng Wen, Jian-Yong Liu, Zhonghui Lin.
      Herein, we fabricate a multifunctional molecular prodrug BAC where the chemotherapeutical agent camptothecin (CPT) is linked with a boron dipyrromethene (BODIPY)-based photosensitizer by an azobenzene chain which is sensitive to over-expressed azoreductase in hypoxic tumor cells. This prodrug was further loaded into biodegradable monomethoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) to improve its solubility and tumor accumulation. The formed BAC nanoparticles (BAC NPs) can destroy aerobic tumor cells with relatively short distance from blood vessels by photodynamic therapy (PDT) under illumination. The PDT action inevitably leads to consumption of O2, and subsequently acute hypoxia which can induce cleavage of azobenzene linkage to boost release of CPT killing the other hypoxic interior tumor cells survived from PDT. Both in vitro and in vivo studies have verified that BAC NPs possess remarkable antitumor activity by a synergistic action of PDT and chemotherapy.
    Keywords:  BODIPY; Hypoxia-activated; Photodynamic therapy; Prodrug; Synergetic therapy
    DOI:  https://doi.org/10.1016/j.ejmech.2022.114749
  35. Biophys Rev. 2022 Aug;14(4): 941-963
    Advantages of combined photodynamic therapy in the treatment of oncological diseases.
    Mikhail Grin, Nikita Suvorov, Petr Ostroverkhov, Viktor Pogorilyy, Nikita Kirin, Alexander Popov, Anna Sazonova, Elena Filonenko.
      When conducting combined therapy of malignant neoplasms, treatment methods with various mechanisms of antitumor effects are used, while an additive or even synergistic effect can be realized. Combination treatment regimens are aimed at increasing the efficiency and, above all, at the complete eradication of the tumor, which can be achieved either by suppressing the survival mechanisms in PDT-resistant tumor cells or by pre-attenuation of tumor cells so that they become more susceptible to subsequent PDT. Photodynamic therapy is an approved medical technology for the treatment of various malignant neoplasms, and several precancerous and non-cancer diseases. To date, numerous data have been published on the combined use of PDT with traditional and innovative methods of treatment. This review considers research in this area in recent years.
    Keywords:  Combined cancer therapy; Nanoparticle drug delivery; Photodynamic therapy; Photosensitizer
    DOI:  https://doi.org/10.1007/s12551-022-00962-6
  36. Nanoscale Adv. 2022 Aug 23. 4(17): 3504-3516
    Recent advances in redox-responsive nanoparticles for combined cancer therapy.
    Yanjun Yang, Wen Sun.
      The combination of multiple therapeutic modalities has attracted increasing attention as it can achieve better therapeutic effects through different treatment mechanisms. However, traditional small molecule agents are non-specific to the tumor tissue, which leads to off-target toxic effects for healthy tissues. To solve this problem, a number of stimuli-responsive nanoscale drug-delivery systems have been developed. Among these stimuli, a high concentration of reactive oxygen species (ROS) and glutathione (GSH) are characteristic of the tumor microenvironment (TME), which can distinguish it from normal tissue. In this review, we summarize the redox-responsive nanoparticles (NPs) reported in the past three years classified by different functional groups, including GSH-responsive disulfide, ditelluride, and multivalent metal ions, ROS-responsive thioketal, arylboronic ester, aminoacrylate, and bilirubin as well as GSH/ROS dual-responsive diselenide and dicarbonyl thioethers. The prospects and challenges of redox-responsive NPs are also discussed.
    DOI:  https://doi.org/10.1039/d2na00222a
  37. Adv Mater. 2022 Sep 22. e2206286
    Bioactive Iridium Nanoclusters with Glutathione Depletion Ability for Enhanced Sonodynamic-Triggered Ferroptosis-like Cancer Cell Death.
    Tongtong Nie, Weijuan Zou, Zheying Meng, Longchen Wang, Tao Ying, Xiaojun Cai, Jianrong Wu, Yuanyi Zheng, Bing Hu.
      Ferroptosis is a regulated form of necrotic cell death that involves the accumulation of lipid peroxide (LPO) species in an iron- and reactive oxygen species (ROS)-dependent manner. Previous investigations reported that ferroptosis-based cancer therapy could overcome the limitations of traditional therapeutics targeting the apoptosis pathway. However, it is still challenging to enhance the antitumor efficacy of ferroptosis due to intrinsic cellular regulation. In this study, ferroptosis-inducing agent, i.e., chlorine e6 (Ce6)-conjugated human serum albumin-iridium oxide (HSA-Ce6-IrO2 , HCIr) nanoclusters were developed to achieve sonodynamic therapy (SDT)-triggered ferroptosis-like cancer cells death. The sonosensitizing role of both Ce6 and IrO2 within the HCIr nanoclusters exhibited highly efficient 1 O2 generation capacity upon ultrasound stimulation, which promoted the accumulation of LPO and subsequently induced ferroptosis. Meanwhile, the HCIr could deplete glutathione (GSH) by accelerating Ir (IV)-Ir (III) transition, which further suppressed the activity of glutathione peroxidase 4 (GPX4) to enhance the ferroptosis efficacy. Through in vitro and in vivo experiments, we demonstrated that HCIr possessed tremendous capacity to reduce the intracellular GSH content, which enhanced SDT-triggered ferroptosis-like cancer cell death. We developed iridium nanoclusters-based ferroptosis-inducing agent providing a promising strategy for inducing ferroptosis-like cancer cell death. This article is protected by copyright. All rights reserved.
    Keywords:  Ferroptosis; GSH depletion; iridium oxide; nanocluster; sonodynamic therapy
    DOI:  https://doi.org/10.1002/adma.202206286
  38. Front Oncol. 2022 ;12 971479
    Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer.
    Yinjie Wu, Xuewei Zhang, Ziyi Wang, Wanzhen Zheng, Huimin Cao, Wenjing Shen.
      Ovarian cancer is an aggressive tumor that remains to be the most lethal gynecological malignancy in women. Metabolic adaptation is an emerging hallmark of tumors. It is important to exploit metabolic vulnerabilities of tumors as promising strategies to develop more effective anti-tumor regimens. Tumor cells reprogram the metabolic pathways to meet the bioenergetic, biosynthetic, and mitigate oxidative stress required for tumor cell proliferation and survival. Oxidative phosphorylation has been found to be altered in ovarian cancer, and oxidative phosphorylation is proposed as a therapeutic target for management of ovarian cancer. Herein, we initially introduced the overview of oxidative phosphorylation in cancer. Furthermore, we discussed the role of oxidative phosphorylation and chemotherapeutic resistance of ovarian cancer. The role of oxidative phosphorylation in other components of tumor microenvironment of ovarian cancer has also been discussed.
    Keywords:  metabolic reprograming; mitochondria; ovarian cancer; oxidative phoshorylation; resistance
    DOI:  https://doi.org/10.3389/fonc.2022.971479
  39. Int J Biol Macromol. 2022 Sep 20. pii: S0141-8130(22)02102-X. [Epub ahead of print]
    iRGD-grafted N-trimethyl chitosan-coated protein nanotubes enhanced the anticancer efficacy of curcumin and melittin.
    Guohua Hou, Yuan Li, Qimeng Wang, Huijuan Zhang, Shuang Liang, Bin Liu, Wenbiao Shi.
      Curcumin (Cur) and Melittin (Mel) are two natural extracts that have been shown anti-tumor effects. However, their applications are limited due to poor oral bioavailability and the lack of tumor-targeting property. Here, we developed a novel nanocomposite that enabled the co-delivery of Cur and Mel, which consists of α-lactalbumin protein nanotubes (NTs), positively charged N,N,N-trimethyl chitosan (TMC), and a tumor-targeting cyclic peptide iRGD. The results showed that NTs/Cur-TMC-Mel-iRGD incorporated the advantages of each component, for instance, effective compounds loading by NTs, improved cellular uptake by TMC, prolonged accumulation in tumors by iRGD as well as synergistic anti-tumor effects of Cur and Mel. In the tumor-bearing mice, NTs/Cur-TMC-Mel-iRGD treatment remarkably induced cancer cell apoptosis while inhibiting cell proliferation, leading to suppressed tumor growth. Besides, no obvious adverse effects were observed in the blood physiology and tissue histology. Overall, our study provided an effective strategy for co-delivering Cur and Mel, which has a potential for translational clinical research aiming to treat solid tumors.
    Keywords:  Chitosan; Co-delivery; Curcumin; Melittin; Nanocomposite; Tumor targeting
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.171
  40. Front Oncol. 2022 ;12 978603
    Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.
    Yi-Chao Wang, Jing-Yan Tian, Ying-Ying Han, Yun-Fei Liu, Si-Yao Chen, Feng-Jun Guo.
      Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.
    Keywords:  RNA therapeutics; chemotherapeutics; drug delivery; dual-mode imaging; microbubble; ultrasound
    DOI:  https://doi.org/10.3389/fonc.2022.978603
  41. Curr Nutr Rep. 2022 Sep 20.
    Date Palm as Source of Nutraceuticals for Health Promotion: a Review.
    Sahar Y Al-Okbi.
      PURPOSE OF REVIEW: Chronic diseases are problematic to health professional specially when using drugs throughout the course of life with un-tolerated side effects. Returning to nature through using nutraceuticals might have both protective and therapeutic effects. Date palm was claimed to be a good source of such nutraceuticals or functional food ingredients. The purpose of the present review was to spot light on the different phytochemicals, phytonutrients, and remedial effects of date palm (Phoenix dactylifera L.) in a goal to be utilized in form of nutraceuticals. The possible mechanisms of action of the remedial effects were among the aim of the study.RECENT FINDINGS: A protein hydrolyzate prepared from date seed could prevent DNA mutation and susceptibility to cancer. In addition to cancer prevention, date palm fruit improved the treatment outcome of cancer pediatric patients and possesses anti-angiogenic activity as one of the important anticancer mechanisms of action. On the other hand, date seed extracts was recently reported to protect from ulcerative colitis. It seems that all the aforementioned remedial effect might be ascribed to immunoregulatory effect of date palm. These findings proposed that date palm is beneficial for health. Date palm fruit is a rich source of vitamins, minerals, dietary fibers, energy, and easily digestible and absorbable sugars that instantaneously replenish and revitalize the body specially after fasting condition. Mineral contents in date fruits include potassium, phosphorus, magnesium, and calcium. Diverse health claims were reported to belong to various parts of the tree including the edible part of fruits, the seeds, the leaves, spathe (an envelope-like structure that encloses male and female date palm flowers), and pollen grains due to the presence of different bioactive constituents. The main phytochemicals and phytonutrients reported in date palms are phenolic compounds, carotenoids, sterols, anthocyanins, and others. In folk medicine, date palm fruits are used for enhancing immunity and treating gastrointestinal tract disorders, edema, bronchitis, wound, cancer, as well as infectious diseases. However, the exact health benefits and remedial effects of date palm were not fully and deeply investigated. The present review focused on the bioactive constituents and the reported health benefits of date palm and proposed mechanism of action.
    Keywords:  Bioactive ingredients; Date palm; Health benefits; Nutrients
    DOI:  https://doi.org/10.1007/s13668-022-00437-w
  42. Chin Herb Med. 2022 Apr;14(2): 244-253
    Curcumin's prevention of inflammation-driven early gastric cancer and its molecular mechanism.
    Wensen Zhang, Na Cui, Jin Ye, Bingyou Yang, Yanping Sun, Haixue Kuang.
      Worldwide, gastric cancer is the second leading cause of cancer deaths and the fifth most common malignant tumor. Gastric cancer is believed to be caused by a variety of factors, such as genetics, epigenetics, and environmental influences. Among the pathogenic factors, inflammation has been considered as one of the main risk factors for gastric cancer. There are currently limited ways to prevent gastric cancer. Although the combined application of aspirin and non-steroidal anti-inflammatory drugs can reduce the risk, it has great side effects and can easily cause gastric perforation or gastric bleeding. Therefore, an alternative plan is urgently needed. Curcumin is the yellow pigment in the rhizome of the plant turmeric. Current studies have found that curcumin has a protective effect on gastric mucosal damage caused by non-steroidal anti-inflammatory drugs, gastric mucosal damage in rats, and gastric mucosal damage caused by stress bleeding and Helicobacter pylori infection. Curcumin shows significant anti-inflammatory and anti-cancer activities by regulating DNA methylation, histone modification, nuclear factor erythrocyte 2 related factor 2 and other related signal pathways. In this article, the latest evidence of curcumin for epigenetic changes in gastric cancer and its potential contribution to gastric cancer were discussed.
    Keywords:  curcumin; epigenetics; gastric cancer; inflammation; prevention
    DOI:  https://doi.org/10.1016/j.chmed.2021.11.003
  43. J Biomater Sci Polym Ed. 2022 Sep 22. 1-15
    A convergent fabrication of pH and redox dual-responsive hybrids of mesoporous silica nanoparticles for the treatment of breast cancer.
    Limin Zhu, Shuangyan Wang.
      Mesoporous silica nanoparticle (MSN), sodium hyaluronate (SH), silk fibroin (SS), and oxidized sodium carboxymethyl cellulose (O-CMC) hybrids were used to develop an intelligent drug delivery platform that may be employed for pH and redox-responsive bi-drug administration. The first drug, cytarabine (Cyt), was loaded with amino-functionalized mesoporous silica (MSN-NH2) encased by the hydrogel of cystamine (Cys) and SH cross-linked by amide bonds. Hydrophobic doxorubicin (DOX) was co-loaded with Cyt/MSN-NH2/SA in the hydrogel of SS and O-CMC in the Cyt- loaded hydrogel. Dual-responsive drug delivery may be achieved by encapsulating SS and O-CMC in a hydrogel, including Cyt/MSN-NH2/SA/DOX/SS/O-CMC, which has acyl hydrazone bonds (-HC = N) and disulfide bond (-S-S-) exchange reaction with glutathione (GSH). Compared to hydrogels encapsulating only one drug (Cyt or DOX), cell survival analysis revealed that the newly fabricated hydrogels have significantly greater chemotherapeutic efficacy. The cell proliferation of the fabricated nanoparticles was examined in MCF-7 and MDA-MB-231 cells, which indicates that the nanoparticles effectively kill the cancer cells without affecting non-cancerous cells. Further, we effectively investigated the morphological changes, and various biochemical staining methods examined nuclear fragmentation/condensation. Furthermore, the biosafety of the nanoparticles was investigated by the in vivo animal model, which reveals that they remarkably enhanced the safety profile in various organs. These outcomes demonstrated that this nanoparticle platform was a promising beneficial agent for improving breast cancer treatment.
    Keywords:  Apoptosis; Breast cancer; Doxorubicin; Mesoporous nanoparticles; Systemic toxicity
    DOI:  https://doi.org/10.1080/09205063.2022.2112303
  44. Nanoscale Adv. 2021 Jun 15. 3(12): 3332-3352
    Emerging indocyanine green-integrated nanocarriers for multimodal cancer therapy: a review.
    Karunanidhi Gowsalya, Vellingiri Yasothamani, Raju Vivek.
      Nanotechnology is a branch of science dealing with the development of new types of nanomaterials by several methods. In the biomedical field, nanotechnology is widely used in the form of nanotherapeutics. Therefore, the current biomedical research pays much attention to nanotechnology for the development of efficient cancer treatment. Indocyanine green (ICG) is a near-infrared tricarbocyanine dye approved by the Food and Drug Administration (FDA) for human clinical use. ICG is a biologically safe photosensitizer and it can kill tumor cells by producing singlet oxygen species and photothermal heat upon NIR irradiation. ICG has some limitations such as easy aggregation, rapid aqueous degradation, and a short half-life. To address these limitations, ICG is further formulated with nanoparticles. Therefore, ICG is integrated with organic nanomaterials (polymers, micelles, liposomes, dendrimers and protein), inorganic nanomaterials (magnetic, gold, mesoporous, calcium, and LDH based), and hybrid nanomaterials. The combination of ICG with nanomaterials provides highly efficient therapeutic effects. Nowadays, ICG is used for various biomedical applications, especially in cancer therapeutics. In this review, we mainly focus on ICG-based combined cancer nanotherapeutics for advanced cancer treatment.
    DOI:  https://doi.org/10.1039/d1na00059d
  45. Int J Mol Sci. 2022 Sep 14. pii: 10713. [Epub ahead of print]23(18):
    Green Tea Catechins: Nature's Way of Preventing and Treating Cancer.
    Mohd Farhan.
      Green tea's (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a substantial impact on the antioxidant activity of catechins. Unfermented green tea is the finest source of these chemicals. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers. Literature evidence, based on epidemiological and laboratory studies, indicates that green tea catechins have certain properties that can serve as the basis for their consideration as lead molecules in the synthesis of novel anticancer drugs and for further exploration of their role as pharmacologically active natural adjuvants to standard chemotherapeutics. The various sections of the article will focus on how catechins affect the survival, proliferation, invasion, angiogenesis, and metastasis of tumors by modulating cellular pathways.
    Keywords:  EGCG; anticancer; cancer prevention; cancer therapy; green tea catechins
    DOI:  https://doi.org/10.3390/ijms231810713
  46. Pharmaceutics. 2022 Sep 17. pii: 1965. [Epub ahead of print]14(9):
    Nanocarriers as a Delivery Platform for Anticancer Treatment: Biological Limits and Perspectives in B-Cell Malignancies.
    Sara Bozzer, Michele Dal Bo, Maria Cristina Grimaldi, Giuseppe Toffoli, Paolo Macor.
      Nanoparticle-based therapies have been proposed in oncology research using various delivery methods to increase selectivity toward tumor tissues. Enhanced drug delivery through nanoparticle-based therapies could improve anti-tumor efficacy and also prevent drug resistance. However, there are still problems to overcome, such as the main biological interactions of nanocarriers. Among the various nanostructures for drug delivery, drug delivery based on polymeric nanoparticles has numerous advantages for controlling the release of biological factors, such as the ability to add a selective targeting mechanism, controlled release, protection of administered drugs, and prolonging the circulation time in the body. In addition, the functionalization of nanoparticles helps to achieve the best possible outcome. One of the most promising applications for nanoparticle-based drug delivery is in the field of onco-hematology, where there are many already approved targeted therapies, such as immunotherapies with monoclonal antibodies targeting specific tumor-associated antigens; however, several patients have experienced relapsed or refractory disease. This review describes the major nanocarriers proposed as new treatments for hematologic cancer, describing the main biological interactions of these nanocarriers and the related limitations of their use as drug delivery strategies.
    Keywords:  cancer; delivery; nanocarriers; polymeric NPs
    DOI:  https://doi.org/10.3390/pharmaceutics14091965
  47. Adv Healthc Mater. 2022 Sep 23. e2201916
    Enzymatic Nanosphere-to-Nanofiber Transition and Autophagy Inducer Release Promote Tumor Chemotherapy.
    Xiaotong Cheng, Tiantian Xia, Wenjun Zhan, Hai-Dong Xu, Jiaoming Jiang, Xiaoyang Liu, Xianbao Sun, Fu-Gen Wu, Gaolin Liang.
      Chemotherapy remains an effective and predominant cancer treatment for the past decades, but is hampered by its low response rate and severe systemic toxicity. Combination chemotherapies have been proposed to address these issues, yet their therapeutic outcomes are still far from satisfactory. Thus, it is urgent to develop novel strategies to promote tumor chemosensitivity while reduce toxic side effects of chemotherapeutics. Herein, employing a rationally designed peptide conjugate Nap-Phe-Phe-Lys(SA-AZD8055)-Tyr(H2 PO3 )-OH (Nap-AZD-Yp), we  propose a novel approach of simultaneous intracellular nanofiber formation and autophagy inducer release for selectively sensitizing tumor to chemotherapy. Upon sequential catalyses of alkaline phosphatase and esterase, Nap-AZD-Yp undergoes nanosphere-to-nanofiber transition accompanied by autophagy inducer AZD8055 release in cancer cells. Cell experiments show enhanced endocytosis of anticancer drug doxorubicin and inhibition of cell migration due to the intracellular nanofiber formation. The released AZD8055 further activates excessive autophagy of cancer cells, sensitizing them to chemotherapy. Animal experiment results suggest Nap-AZD-Yp can significantly enhance the therapeutic effects of doxorubicin on tumors while mitigate its toxic adverse effects on normal tissues. We  anticipate that our  "smart" concept in this work could  be widely employed to develop novel combinational therapies for the treatment of cancers and other diseases in near future. This article is protected by copyright. All rights reserved.
    Keywords:  autophagy; cancer; morphology transformation; self-assembly; tandem enzyme-responsive
    DOI:  https://doi.org/10.1002/adhm.202201916
  48. Acta Biomater. 2022 Sep 14. pii: S1742-7061(22)00587-6. [Epub ahead of print]
    A Multifunctional Cascade Bioreactor Based on a Layered Double Oxides Composite Hydrogel for Synergetic Tumor Chemodynamic/Starvation/Photothermal Therapy.
    Ru Xu, Dongdong Zhang, Ji Tan, Naijian Ge, Dan Liu, Junyu Liu, Liping Ouyang, Hongqin Zhu, Yuqin Qiao, Jiajun Qiu, Shijie Zhu, Xuanyong Liu.
      The field of nanomedicine-catalyzed tumor therapy has achieved a lot of progress; however, overcoming the limitations of the tumor microenvironment (TME) to achieve the desired therapeutic effect remains a major challenge. In this study, a nanocomposite hydrogel (GH@LDO) platform combining the nanozyme CoMnFe-layered double oxides (CoMnFe-LDO) and natural enzyme glucose oxidase (GOX) was engineered to remodel the TME to enhance tumor catalytic therapy. The CoMnFe-LDO is a nanozyme that can convert endogenous H2O2 into reactive oxygen species (ROS) and O2 to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Meanwhile, GOX can catalyze the conversion of glucose and O2 to gluconic acid and H2O2, which not only represses the ATP production of tumor cells to achieve starvation therapy (ST), but also decreases the pH value of TME and supplies extra H2O2 to enhance the CDT effect. Furthermore, this well-designed CoMnFe-LDO possessed a high photothermal conversion efficiency (66.63%), which could promote the generation of ROS to enhance the CDT effect and achieve photothermal therapy (PTT) under near-infrared light irradiation. The GH@LDO hydrogel cascade reaction overcomes the limitation of the TME and achieves satisfactory CDT/ST/PTT synergetic effects in vitro and in vivo. This work provides a new strategy for remodeling the TME using nanomedicine to achieve precise tumor cascaded catalytic therapy. STATEMENT OF SIGNIFICANCE: At present, the focus of tumor therapy has begun to shift from monotherapy to combination therapy for improving the overall therapeutic effect. In this study, we synthesized a CoMnFe-layered double oxide (CoMnFe-LDO) nanozyme composed of multiple transition metal oxides, which demonstrated improved peroxidase and oxidase activities as well as favorable photothermal conversion capability. The CoMnFe-LDO nanozyme was compounded with an injectable GH hydrogel crosslinked by glucose oxidase (GOX) and peroxidase (HRP). This nanocomposite hydrogel overcame the limitations of weak acidity, H2O2, and O2 levels in the tumor microenvironment (TME) and achieved synergetic chemodynamic therapy (CDT), starvation therapy (ST), and photothermal therapy (PTT) effects based on the cascaded catalytic actions of CoMnFe-LDO and GOX to H2O2 and glucose.
    Keywords:  cascade reaction; layered double oxides; tumor catalytic therapy; tumor microenvironment remodeling
    DOI:  https://doi.org/10.1016/j.actbio.2022.09.024
  49. Cell Biol Toxicol. 2022 Sep 23.
    Evodiamine as an anticancer agent: a comprehensive review on its therapeutic application, pharmacokinetic, toxicity, and metabolism in various cancers.
    Munmun Panda, Surya Kant Tripathi, Gokhan Zengin, Bijesh K Biswal.
      Evodiamine is a major alkaloid component found in the fruit of Evodia rutaecarpa. It shows the anti-proliferative potential against a wide range of cancers by suppressing cell growth, invasion, and metastasis and inducing apoptosis both in vitro and in vivo. Evodiamine shows its anticancer potential by modulating aberrant signaling pathways. Additionally, the review focuses on several therapeutic implications of evodiamine, such as epigenetic modification, cancer stem cells, and epithelial to mesenchymal transition. Moreover, combinatory drug therapeutics along with evodiamine enhances the anticancer efficacy of chemotherapeutic drugs in various cancers by overcoming the chemo resistance and radio resistance shown by cancer cells. It has been widely used in preclinical trials in animal models, exhibiting very negligible side effects against normal cells and effective against cancer cells. The pharmacokinetic and pharmacodynamics-based collaborations of evodiamine are also included. Due to its poor bioavailability, synthetic analogs of evodiamine and its nano capsule have been formulated to enhance its bioavailability and reduce toxicity. In addition, this review summarizes the ongoing research on the mechanisms behind the antitumor potential of evodiamine, which proposes an exciting future for such interests in cancer biology.
    Keywords:  Cancer; Combinatory therapy; Drug resistance; Evodiamine; Pharmacokinetics
    DOI:  https://doi.org/10.1007/s10565-022-09772-8
  50. Nutrients. 2022 Sep 16. pii: 3842. [Epub ahead of print]14(18):
    Effects of Ketogenic Diet on Muscle Metabolism in Health and Disease.
    Elmira I Yakupova, Alexey D Bocharnikov, Egor Y Plotnikov.
      Dietary intervention is widely used as a therapeutic approach ranging from the treatment of neurological disorders to attempts to extend lifespan. The most important effect of various diets is a change in energy metabolism. Since muscles constitute 40% of total body mass and are one of the major sites of glucose and energy uptake, various diets primarily affect their metabolism, causing both positive and negative changes in physiology and signaling pathways. In this review, we discuss changes in the energy metabolism of muscles under conditions of the low-carbohydrate, high-fat diet/ketogenic diet (KD), fasting, or administration of exogenous ketone bodies, which are all promising approaches to the treatment of various diseases. KD's main influence on the muscle is expressed through energy metabolism changes, particularly decreased carbohydrate and increased fat oxidation. This affects mitochondrial quantity, oxidative metabolism, antioxidant capacity, and activity of enzymes. The benefits of KD for muscles stay controversial, which could be explained by its different effects on various fiber types, including on muscle fiber-type ratio. The impacts of KD or of its mimetics are largely beneficial but could sometimes induce adverse effects such as cardiac fibrosis.
    Keywords:  fasting; heart; ketogenic diet; ketone bodies; muscle; muscle metabolism
    DOI:  https://doi.org/10.3390/nu14183842
  51. Polymers (Basel). 2022 Sep 06. pii: 3705. [Epub ahead of print]14(18):
    Harnessing Lipid Polymer Hybrid Nanoparticles for Enhanced Oral Bioavailability of Thymoquinone: In Vitro and In Vivo Assessments.
    Syed Sarim Imam, Sadaf Jamal Gilani, May Nasser Bin Jumah, Md Rizwanullah, Ameeduzzafar Zafar, Mohammed Muqtader Ahmed, Sultan Alshehri.
      The clinical application of phytochemicals such as thymoquinone (THQ) is restricted due to their limited aqueous solubility and oral bioavailability. Developing mucoadhesive nanocarriers to deliver these natural compounds might provide new hope to enhance their oral bioavailability. Herein, this investigation aimed to develop THQ-loaded lipid-polymer hybrid nanoparticles (THQ-LPHNPs) based on natural polymer chitosan. THQ-LPHNPs were fabricated by the nanoprecipitation technique and optimized by the 3-factor 3-level Box-Behnken design. The optimized LPHNPs represented excellent properties for ideal THQ delivery for oral administration. The optimized THQ-LPHNPs revealed the particles size (PS), polydispersity index (PDI), entrapment efficiency (%EE), and zeta potential (ZP) of &lt;200 nm, &lt;0.25, &gt;85%, and &gt;25 mV, respectively. THQ-LPHNPs represented excellent stability in the gastrointestinal milieu and storage stability in different environmental conditions. THQ-LPHNPs represented almost similar release profiles in both gastric as well as intestinal media with the initial fast release for 4 h and after that a sustained release up to 48 h. Further, the optimized THQ-LPHNPs represent excellent mucin binding efficiency (&gt;70%). Cytotoxicity study revealed much better anti-breast cancer activity of THQ-LPHNPs compared with free THQ against MDA-MB-231 and MCF-7 breast cancer cells. Moreover, ex vivo experiments revealed more than three times higher permeation from the intestine after THQ-LPHNPs administration compared to the conventional THQ suspension. Furthermore, the THQ-LPHNPs showed 4.74-fold enhanced bioavailability after oral administration in comparison with the conventional THQ suspension. Therefore, from the above outcomes, mucoadhesive LPHNPs might be suitable nano-scale carriers for enhanced oral bioavailability and therapeutic efficacy of highly lipophilic phytochemicals such as THQ.
    Keywords:  breast cancer; cytotoxicity; lipid-polymer hybrid nanoparticles; oral bioavailability; thymoquinone
    DOI:  https://doi.org/10.3390/polym14183705
  52. Foods. 2022 Sep 15. pii: 2861. [Epub ahead of print]11(18):
    Food Applications and Potential Health Benefits of Hawthorn.
    Juan Zhang, Xiaoyun Chai, Fenglan Zhao, Guige Hou, Qingguo Meng.
      Hawthorn (Crataegus) is a plant of the Rosaceae family and is widely grown throughout the world as one of the medicinal and edible plants, known as the "nutritious fruit" due to its richness in bioactive substances. Preparations derived from it are used in the formulation of dietary supplements, functional foods, and pharmaceutical products. Rich in amino acids, minerals, pectin, vitamin C, chlorogenic acid, epicatechol, and choline, hawthorn has a high therapeutic and health value. Many studies have shown that hawthorn has antioxidant, anti-inflammatory, anticancer, anti-cardiovascular disease, and digestive enhancing properties. This is related to its bioactive components such as polyphenols (chlorogenic acid, proanthocyanidin B2, epicatechin), flavonoids (proanthocyanidins, mucoxanthin, quercetin, rutin), and pentacyclic triterpenoids (ursolic acid, hawthornic acid, oleanolic acid), which are also its main chemical constituents. This paper briefly reviews the chemical composition, nutritional value, food applications, and the important biological and pharmacological activities of hawthorn. This will contribute to the development of functional foods or nutraceuticals from hawthorn.
    Keywords:  anti-cardiovascular disease; antioxidant; beverage; bread; flavonoids; meat; nutrition; phenolic acid
    DOI:  https://doi.org/10.3390/foods11182861
  53. Int J Mol Sci. 2022 Sep 06. pii: 10244. [Epub ahead of print]23(18):
    Combination Therapy Using Polyphenols: An Efficient Way to Improve Antitumoral Activity and Reduce Resistance.
    Alina Florentina Vladu, Denisa Ficai, Alexandra Gabriela Ene, Anton Ficai.
      Polyphenols represent a structural class of mainly natural organic chemicals that contain multiple phenol structural units. The beneficial properties of polyphenols have been extensively studied for their antitumor, anti-inflammatory, and antibacterial effects, but nowadays, their medical applications are starting to be extended to many other applications due to their prebiotic role and their impact on the microbiota. This review focused on the use of polyphenols in cancer treatment. Their antineoplastic effects have been demonstrated in various studies when they were tested on numerous cancer lines and some in in vivo models. A431 and SCC13 human skin cancer cell lines treated with EGCG presented a reduced cell viability and enhanced cell death due to the inactivation of β-catenin signaling. Additionally, resveratrol showed a great potential against breast cancer mainly due to its ability to exert both anti-estrogenic and estrogenic effects (based on the concentration) and because it has a high affinity for estrogen receptors ERα and Erβ. Polyphenols can be combined with different classical cytostatic agents to enhance their therapeutic effects on cancer cells and to also protect healthy cells from the aggressiveness of antitumor drugs due to their anti-inflammatory properties. For instance, curcumin has been reported to reduce the gastrointestinal toxicity associated with chemotherapy. In the case of 5-FU-induced, it reduced the gastrointestinal toxicity by increasing the intestinal permeability and inhibiting mucosal damage. Co-administration of EGCG and doxorubicin induced the death of liver cancer cells. EGCG has the ability to inhibit autophagic activity and stop hepatoma Hep3B cell proliferation This symbiotic approach is well-known in medical practice including in multiple chemotherapy.
    Keywords:  antioxidants; cancer therapy; carcinogenesis; oxidative stress; reactive oxygen species; synergistic effect
    DOI:  https://doi.org/10.3390/ijms231810244
  54. Biomater Sci. 2022 Sep 21.
    A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy.
    Peng-Yu Wu, Zhi-Chun Shen, Jia-Li Jiang, Bing-Chen Zhang, Wen-Zhong Zhang, Jun-Jie Zou, Juan-Fang Lin, Chao Li, Jing-Wei Shao.
      Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.
    DOI:  https://doi.org/10.1039/d2bm00803c
  55. Pharmaceutics. 2022 Sep 19. pii: 1971. [Epub ahead of print]14(9):
    Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing.
    Anis Rehman, Muhammad Iqbal, Barkat A Khan, Muhammad Khalid Khan, Bader Huwaimel, Sameer Alshehri, Ali H Alamri, Rami M Alzhrani, Deena M Bukhary, Awaji Y Safhi, Khaled M Hosny.
      Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p &lt; 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.
    Keywords:  eucalyptol; nanoemulgel; sustainability of natural resources; topical delivery; wound healing; zeta potential
    DOI:  https://doi.org/10.3390/pharmaceutics14091971
  56. Biomolecules. 2022 Sep 16. pii: 1306. [Epub ahead of print]12(9):
    Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.
    Qiongyu Hao, Yanyuan Wu, Jaydutt V Vadgama, Piwen Wang.
      Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds' chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
    Keywords:  chemotherapy; mechanisms studies; natural products; prostate cancer
    DOI:  https://doi.org/10.3390/biom12091306
  57. Chin Herb Med. 2021 Jul;13(3): 313-331
    Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.
    Ying Huai, Wen-Juan Zhang, Wei Wang, Kai Dang, Shan-Feng Jiang, Dan-Ming Li, Meng Li, Qiang Hao, Zhi-Ping Miao, Yu Li, Ai-Rong Qian.
      Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment.Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis.
    Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis.
    Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.
    Keywords:  asperosaponin VI; betulinic acid; calycosin; drug discovery; hederagenin; luteolin; osteoporosis; systems pharmacology; traditional Chinese medicine
    DOI:  https://doi.org/10.1016/j.chmed.2021.06.001
  58. Food Funct. 2022 Sep 22.
    Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome.
    Shaohui Wang, Qinyun Du, Xianli Meng, Yi Zhang.
      Metabolic syndrome (MS) is the term for a combination of hypertension, dyslipidemia, insulin resistance, and central obesity as factors leading to cardiovascular and metabolic disease. Epidemiological investigation has shown that polyphenol intake is negatively correlated with the incidence of MS. Natural polyphenols are widely found in cocoa beans, tea, vegetables, fruits, and some Chinese herbal medicines; they are a class of plant compounds containing a variety of phenolic structural units, which are potent antioxidants and anti-inflammatory agents in plants. Polyphenols are composed of flavonoids (such as flavanols, anthocyanidins, anthocyanins, isoflavones, etc.) and non-flavonoids (such as phenolic acids, stilbenes, and lignans). Modern pharmacological studies have proved that polyphenols can reduce blood pressure, improve lipid metabolism, lower blood glucose, and reduce body weight, thereby preventing and improving MS. Due to the unique characteristics and potential development and application value of polyphenols, this review summarizes some natural polyphenols that could treat MS, including their chemical properties, plant sources, and pharmacological action against MS, to provide a basis for the further study of polyphenols in MS.
    DOI:  https://doi.org/10.1039/d2fo01552h
  59. Nanoscale Adv. 2022 Sep 13. 4(18): 3676-3688
    Effects of polymer carriers on the occurrence and development of autophagy in drug delivery.
    Changduo Wang, Yang Li, Yu Tian, Wenyuan Ma, Yong Sun.
      Autophagy is an evolutionarily conserved catabolic process that can degrade cytoplasmic materials and recycle energy to maintain metabolite homeostasis in cells. Autophagy is closely related to various physiological or pathological processes. Macromolecular materials are widely used in drug delivery systems and disease treatments due to their intrinsic effects, such as altered pharmacokinetics and biodistribution. Interaction of autophagic flux or the signal pathway with macromolecules may cause autophagy inhibition or autophagy cell death. This review covers autophagy regulation pathways and macromolecular materials (including functional micelles, biodegradable and pH-sensitive polymers, biomacromolecules, dendrimers, coordination polymers, and hybrid nanoparticles) mediated autophagy modulation.
    DOI:  https://doi.org/10.1039/d2na00355d
  60. Int J Mol Sci. 2022 Sep 09. pii: 10479. [Epub ahead of print]23(18):
    Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer.
    Nada Oršolić, Maja Jazvinšćak Jembrek.
      In recent years, interest in natural products such as alternative sources of pharmaceuticals for numerous chronic diseases, including tumors, has been renewed. Propolis, a natural product collected by honeybees, and polyphenolic/flavonoid propolis-related components modulate all steps of the cancer progression process. Anticancer activity of propolis and its compounds relies on various mechanisms: cell-cycle arrest and attenuation of cancer cells proliferation, reduction in the number of cancer stem cells, induction of apoptosis, modulation of oncogene signaling pathways, inhibition of matrix metalloproteinases, prevention of metastasis, anti-angiogenesis, anti-inflammatory effects accompanied by the modulation of the tumor microenvironment (by modifying macrophage activation and polarization), epigenetic regulation, antiviral and bactericidal activities, modulation of gut microbiota, and attenuation of chemotherapy-induced deleterious side effects. Ingredients from propolis also "sensitize" cancer cells to chemotherapeutic agents, likely by blocking the activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In this review, we summarize the current knowledge related to the the effects of flavonoids and other polyphenolic compounds from propolis on tumor growth and metastasizing ability, and discuss possible molecular and cellular mechanisms involved in the modulation of inflammatory pathways and cellular processes that affect survival, proliferation, invasion, angiogenesis, and metastasis of the tumor.
    Keywords:  cancer; cancer therapy; chemoprevention; epigenetic and genetic mechanisms; molecular targets; polyphenolic/flavonoid compounds; propolis
    DOI:  https://doi.org/10.3390/ijms231810479
  61. Front Bioeng Biotechnol. 2022 ;10 994655
    Nanocarriers for intracellular co-delivery of proteins and small-molecule drugs for cancer therapy.
    Zhihong Cheng, Yongshuang Li, Duoyi Zhao, Wei Zhao, Meng Wu, Weilin Zhang, Yan Cui, Peng Zhang, Zhiyu Zhang.
      In the past few decades, the combination of proteins and small-molecule drugs has made tremendous progress in cancer treatment, but it is still not satisfactory. Because there are great differences in molecular weight, water solubility, stability, pharmacokinetics, biodistribution, and the ways of release and action between macromolecular proteins and small-molecule drugs. To improve the efficacy and safety of tumor treatment, people are committed to developing protein and drug co-delivery systems. Currently, intracellular co-delivery systems have been developed that integrate proteins and small-molecule drugs into one nanocarrier via various loading strategies. These systems significantly improve the blood stability, half-life, and biodistribution of proteins and small-molecule drugs, thus increasing their concentration in tumors. Furthermore, proteins and small-molecule drugs within these systems can be specifically targeted to tumor cells, and are released to perform functions after entering tumor cells simultaneously, resulting in improved effectiveness and safety of tumor treatment. This review summarizes the latest progress in protein and small-molecule drug intracellular co-delivery systems, with emphasis on the composition of nanocarriers, as well as on the loading methods of proteins and small-molecule drugs that play a role in cells into the systems, which have not been summarized by others so far.
    Keywords:  cancer therapy; intracellular co-delivery; nanocarriers; proteins; small-molecule drugs
    DOI:  https://doi.org/10.3389/fbioe.2022.994655
  62. Molecules. 2022 Sep 14. pii: 5973. [Epub ahead of print]27(18):
    Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis.
    Shixin Zhang, Miaomiao Zhang, Xiangyu Li, Ge Li, Bo Yang, Xinyue Lu, Yang Gao, Fengying Sun.
      A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients' quality of life. Given the complexity of RA's biology, no single treatment can totally block the disease's progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.
    Keywords:  co-delivery system; combination therapy; drug delivery; nanoparticles; phototherapy; rheumatoid arthritis (RA)
    DOI:  https://doi.org/10.3390/molecules27185973
  63. Pharmaceutics. 2022 Aug 25. pii: 1781. [Epub ahead of print]14(9):
    Marine Bioactive Compounds Derived from Macroalgae as New Potential Players in Drug Delivery Systems: A Review.
    Bogdan-Stefan Negreanu-Pirjol, Ticuta Negreanu-Pirjol, Dan Razvan Popoviciu, Ruxandra-Elena Anton, Ana-Maria Prelipcean.
      The marine algal ecosystem is characterized by a rich ecological biodiversity and can be considered as an unexploited resource for the discovery and isolation of novel bioactive compounds. In recent years, marine macroalgae have begun to be explored for their valuable composition in bioactive compounds and opportunity to obtain different nutraceuticals. In comparison with their terrestrial counterparts, Black Sea macroalgae are potentially good sources of bioactive compounds with specific and unique biological activities, insufficiently used. Macroalgae present in different marine environments contain several biologically active metabolites, including polysaccharides, oligosaccharides, polyunsaturated fatty acids, sterols, proteins polyphenols, carotenoids, vitamins, and minerals. As a result, they have received huge interest given their promising potentialities in supporting antitumoral, antimicrobial, anti-inflammatory, immunomodulatory, antiangiogenic, antidiabetic, and neuroprotective properties. An additional advantage of ulvans, fucoidans and carrageenans is the biocompatibility and limited or no toxicity. This therapeutic potential is a great natural treasure to be exploited for the development of novel drug delivery systems in both preventive and therapeutic approaches. This overview aims to provide an insight into current knowledge focused on specific bioactive compounds, which represent each class of macroalgae e.g., ulvans, fucoidans and carrageenans, respectively, as valuable potential players in the development of innovative drug delivery systems.
    Keywords:  bioactive compounds; carrageenans; drug delivery; fucoidans; marine macroalgae; ulvans
    DOI:  https://doi.org/10.3390/pharmaceutics14091781
  64. Nanoscale Adv. 2021 Oct 12. 3(20): 5919-5927
    An effective in vivo mitochondria-targeting nanocarrier combined with a π-extended porphyrin-type photosensitizer.
    Satrialdi, Yuta Takano, Eri Hirata, Natsumi Ushijima, Hideyoshi Harashima, Yuma Yamada.
      A photochemical reaction mediated by light-activated molecules (photosensitizers) in photodynamic therapy (PDT) causes molecular oxygen to be converted into highly reactive oxygen species (ROS) that are beneficial for cancer therapy. As the active oxygen consumer and the primary regulator of apoptosis, mitochondria are known as an important target for optimizing PDT outcomes. However, most of the clinically used photosensitizers exhibited a poor tumor accumulation profile as well as lack of mitochondria targeting ability. Therefore, by applying a nanocarrier platform, mitochondria-specific delivery of photosensitizers can be materialized. The present research develops an effective mitochondria-targeting liposome-based nanocarrier system (MITO-Porter) encapsulating a π-extended porphyrin-type photosensitizer (rTPA), which results in a significant in vivo antitumor activity. A single PDT treatment of the rTPA-MITO-Porter resulted in a dramatic tumor inhibition against both human and murine tumors that had been xenografted in a mouse model. Furthermore, depolarization of the mitochondrial membrane was observed, implying the damage of the mitochondrial membrane due to the photochemical reaction that occurred specifically in the mitochondria of tumor cells. The findings presented herein serve to verify the significance of the mitochondria-targeted nanocarrier system for advancing the in vivo PDT effectivity in cancer therapy regardless of tumor type.
    DOI:  https://doi.org/10.1039/d1na00427a
  65. Molecules. 2022 Sep 16. pii: 6057. [Epub ahead of print]27(18):
    Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts.
    Dongping Li, Yaroslav Ilnytskyy, Esmaeel Ghasemi Gojani, Olga Kovalchuk, Igor Kovalchuk.
      Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes. In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold. We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation. A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA. Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.
    Keywords:  Cannabis sativa; anti-cancer property; anti-inflammatory property; delta-9-tetrahydrocannabinol; flower extracts
    DOI:  https://doi.org/10.3390/molecules27186057
  66. Appl Radiat Isot. 2022 Sep 17. pii: S0969-8043(22)00349-9. [Epub ahead of print]189 110464
    Radioiodination, nasal nanoformulation and preliminary evaluation of isovanillin: A new potential brain cancer-targeting agent.
    O A El-Kawy, H A Shweeta, K M Attallah.
      Brain cancer is a challenging disease to treat using conventional approaches. The present investigation aimed to develop a radiopharmaceutical targeting brain cancer based on natural isovanillin. Different parameters were optimized, resulting in high radiolabeling efficiency (97.3 ± 1.2%) and good stability (<48 h). The tracer was formulated for intranasal delivery in a chitosan nanoparticles system with a mean particle size of 141 ± 2 nm, a polydispersity index of 0.23 ± 0.02, and a zeta potential of -17.4 ± 0.3 mV to enhance nasal uptake and surmount the blood-brain barrier. The system was characterized and assessed in-vitro for suitability and specificity and evaluated in-vivo in normal and tumorized mice. The biodistribution profile in brain tumor showed 20.5 ± 0.4 %ID/g localization and cancer cell targeting within 60 min. Improvement in brain tumor uptake resulted from both the nanoformulation and nasal administration of iodoisovanillin. Overall, the reported results encourage the potential use of the nanoformulated labeled compound as an anticancer agent.
    Keywords:  Brain cancer; Chitosan; Iodine-131; Isovanillin; Labeling; Nanoparticles; Nasal; Preclinical evaluation
    DOI:  https://doi.org/10.1016/j.apradiso.2022.110464
  67. Gels. 2022 Sep 06. pii: 563. [Epub ahead of print]8(9):
    A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders.
    Leshasha T Mashabela, Mahlako M Maboa, Ntombi F Miya, Taiwo O Ajayi, Rumbidzai S Chasara, Marnus Milne, Shoeshoe Mokhele, Patrick H Demana, Bwalya A Witika, Xavier Siwe-Noundou, Madan S Poka.
      Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.
    Keywords:  central nervous system; cross-linked gels; injectable cross-linked gels; non-injectable cross-linked gels; spatial drug delivery
    DOI:  https://doi.org/10.3390/gels8090563
  68. Gels. 2022 Sep 01. pii: 554. [Epub ahead of print]8(9):
    Ultrasound-Induced Drug Release from Stimuli-Responsive Hydrogels.
    Tyus J Yeingst, Julien H Arrizabalaga, Daniel J Hayes.
      Stimuli-responsive hydrogel drug delivery systems are designed to release a payload when prompted by an external stimulus. These platforms have become prominent in the field of drug delivery due to their ability to provide spatial and temporal control for drug release. Among the different external triggers that have been used, ultrasound possesses several advantages: it is non-invasive, has deep tissue penetration, and can safely transmit acoustic energy to a localized area. This review summarizes the current state of understanding about ultrasound-responsive hydrogels used for drug delivery. The mechanisms of inducing payload release and activation using ultrasound are examined, along with the latest innovative formulations and hydrogel design strategies. We also report on the most recent applications leveraging ultrasound activation for both cancer treatment and tissue engineering. Finally, the future perspectives offered by ultrasound-sensitive hydrogels are discussed.
    Keywords:  Tissue engineering; cancer therapy; controlled drug release; drug delivery; hydrogels; polymers; smart hydrogels; stimuli-responsive; thermoresponsive materials; ultrasound
    DOI:  https://doi.org/10.3390/gels8090554
  69. Curr Res Food Sci. 2022 ;5 1508-1523
    A review on health benefits of phenolics derived from dietary spices.
    Neetu Singh, Surender Singh Yadav.
      Spices are an affluentpool of polyphenolcompounds that possessgigantic medicinal peculiarities such as remedying microbial infections, oxidative stress, inflammation, diabetes, cancers, neurodegenerative disorders, cardiac disorders, etc. On that account, thepresent review illustrates the therapeutic potential, mechanism of action, and different procedures for conscious extraction of polyphenols. The various ethnopharmacological properties; reasons for their diverse pharmacological actions and the mechanism of action of spices-derived phenolics have also been discussed. The findings of this review may be utilized by the food and pharmaceutical industries for developing suitable alternatives to synthetic antioxidants and can be developed into effective food supplements. Further in-depth scientific studies are needed to find out their actual and exact relevance as natural health boosters. Moreover, clinical and toxicological studies are also required for harnessing the full therapeutic potential of polyphenols derived from dietary spices.
    Keywords:  Inflammation; Oxidative stress; Pharmacology; Polyphenols; Secondary metabolites; Spices
    DOI:  https://doi.org/10.1016/j.crfs.2022.09.009
  70. Am J Chin Med. 2022 Sep 17. 1-27
    MicroRNAs, Key Regulators in Glioma Progression as Potential Therapeutic Targets for Chinese Medicine.
    Huali Fan, Xiaofang Xie, Xi Kuang, Junrong Du, Fu Peng.
      Gliomas are tumors of the primary central nervous system associated with poor prognosis and high mortality. The 5-year survival rate of patients with gliomas received surgery combined with chemotherapy or radiotherapy does not exceed 5%. Although temozolomide is commonly used in the treatment of gliomas, the development of resistance limits its use. MicroRNAs are non-coding RNAs involved in numerous processes of glioma cells, such as proliferation, migration and apoptosis. MicroRNAs regulate cell cycle, PI3K/AKT signal pathway, and target apoptosis-related genes (e.g., BCL6), angiogenesis-related genes (e.g., VEGF) and other related genes to suppress gliomas. Evidence illustrates that microRNAs can regulate the sensitivity of gliomas to temozolomide, cisplatin, and carmustine, thereby enhancing the efficacy of these agents. Moreover, traditional Chinese medicine (e.g., tanshinone IIA, xanthohumol, and curcumin) exert antiglioma effects by regulating the expression of microRNAs, and then microRNAs inhibit gliomas through influencing the process of tumors by targeting certain genes. In this paper, the mechanisms through which microRNAs regulate the sensitivity of gliomas to therapeutic drugs are described, and traditional Chinese medicine that can suppress gliomas through microRNAs are discussed. This review aims to provide new insights into the traditional Chinese medicine treatment of gliomas.
    Keywords:  Chinese Medicine; Drug Resistance; Gliomas; Isoliquiritigenin; Resveratrol; Shikonin; TCM Compouds; Therapeutic Targets; Tumor Progression; miRNAs
    DOI:  https://doi.org/10.1142/S0192415X22500768
  71. Life Sci. 2022 Sep 20. pii: S0024-3205(22)00684-1. [Epub ahead of print] 120984
    Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects.
    Mehrdad Hashemi, Sepideh Mirzaei, Maryamsadat Barati, Elahe Sadat Hejazi, Amirabbas Kakavand, Maliheh Entezari, Shokooh Salimimoghadam, Alireza Kalbasi, Mohsen Rashidi, Afshin Taheriazam, Gautam Sethi.
      Urological cancers include bladder, prostate and renal cancers that can cause death in males and females. Patients with urological cancers are mainly diagnosed at an advanced disease stage when they also develop resistance to therapy or poor response. The use of natural products in the treatment of urological cancers has shown a significant increase. Curcumin has been widely used in cancer treatment due to its ability to trigger cell death and suppress metastasis. The beneficial effects of curcumin in the treatment of urological cancers is the focus of current review. Curcumin can induce apoptosis in the three types of urological cancers limiting their proliferative potential. Furthermore, curcumin can suppress invasion of urological cancers through EMT inhibition. Notably, curcumin decreases the expression of MMPs, therefore interfering with urological cancer metastasis. When used in combination with chemotherapy agents, curcumin displays synergistic effects in suppressing cancer progression. It can also be used as a chemosensitizer. Based on pre-clinical studies, curcumin administration is beneficial in the treatment of urological cancers and future clinical applications might be considered upon solving problems related to the poor bioavailability of the compound. To improve the bioavailability of curcumin and increase its therapeutic index in urological cancer suppression, nanostructures have been developed to favor targeted delivery.
    Keywords:  Cancer treatment; Curcumin; Drug resistance; Natural products; Urological tumors
    DOI:  https://doi.org/10.1016/j.lfs.2022.120984
  72. Biotechnol Genet Eng Rev. 2022 Sep 18. 1-29
    Recent advances in pomegranate peel extract mediated nanoparticles for clinical and biomedical applications.
    Prakash Monika, M N Chandraprabha, R Hari Krishna, Maanya Vittal, C Likhitha, N Pooja, Vishal Chaudhary, Manjunatha C.
      Manufacturing new materials at the nanoscale level is a field that is rapidly expanding with widespread application in advanced science and MMT is effectively used for the technology. Nanoparticles (NP), the building blocks of nanotechnology, exhibit improved properties than the larger counterparts and can be prepared from a variety of metals, including silver, copper, gold, zinc, and others. Phytonanotechnology is gaining major attention as various clinical researches have focused on the excellent properties (physicochemical and biological) of nanoscale phytochemicals and its applications in biological systems. In recent developments, pomegranate (Punica granatum L.) has gained major attention due to the phenolic compounds like apigenin, caffeic acid, chlorogenic acid, cyanidin, ellagic acid, gallic acid, granatin A, granatin B, pelargonidin, punicalagin, punicalin and quercetin found in its peel. Pomegranate Peel Extract (PPE) that aid the synthesis of PPE mediated nanoparticles (PPE-MNPs) like PPE-MAuNPs, PPE-MAgNPs, PPE-MZnONPs, PPE-MCuNPs, PPE-MPtNPs and PPE-MFeNPs has yielded plethora of beneficial properties in both plants and humans. In the current review, we discuss in detail the recent advances in synthesis and characterization of various nanoparticles from PPE. Moreover, the multitude biological properties of PPE-MNPs make up the long list of clinical uses. In addition, we discuss the pharmacokinetics, current advantages, and limitations of PPE-MNPs which can further help in development of more efficient therapeutics. Despite some of the challenges, PPE-MNPs hold a lot of potential for drug delivery and are always a better choice. The convergence of science and engineering has created new hopes, in which phytomedicines will have more efficacy, bioavailability, and less toxicity.
    Keywords:  biological properties; nanoparticles; phytonanotechnology; pomegranate peel extract
    DOI:  https://doi.org/10.1080/02648725.2022.2122299
  73. Drug Deliv. 2022 Dec;29(1): 3035-3050
    Development of surface modified bilosomes for the oral delivery of quercetin: optimization, characterization in-vitro antioxidant, antimicrobial, and cytotoxicity study.
    Nabil K Alruwaili, Ameeduzzafar Zafar, Omar Awad Alsaidan, Mohd Yasir, Ehab M Mostafa, Sultan F Alnomasy, Alenazy Rawaf, Ali Alquraini, Fadhel A Alomar.
      Quercetin (QT) is a flavonoid that exhibits anti-oxidant and chemo-preventive activity. This research work aimed to develop surface-modified bilosomes (BS) of QT. The BS was prepared by the solvent evaporation method and optimized by the Box-Behnken design. The optimized QT-BS (QT-BS3opt) displayed vesicle size (143.51 nm), PDI (0.256), zeta potential (-15.4 mV), and entrapment efficiency (89.52%). Further, the optimized QT-BS formulation was coated with chitosan (CS). The XRD diffractogram of CS-QT-BS3opt1 did not exhibit extensive peaks of QT, revealing that QT is properly encapsulated in the polymer matrix. The QT-BS3opt and CS-QT-BS3opt1 exhibited sustained-release (86.62 ± 3.23% and 69.32 ± 2.57%, respectively) up to 24 h with the Korsmeyer-Peppas kinetic model (R2 =0.9089). CS-QT-BS3opt1 exhibited significantly (P < .05) high flux, i.e. 4.20-fold more than pure QT dispersion and 1.27-fold higher than QT-BS3opt. CS-QT-BS3opt1 showed significantly greater bio-adhesion (76.43 ± 2.42%) than QT-BS3opt (20.82 ± 1.45%). The antioxidant activity showed that QT from CS-QT-BS3opt1 has more remarkable (P < .05) antioxidant activity at each concentration than pure QT. The CS-QT-BS3opt1 exhibited 1.61-fold higher cytotoxicity against MFC7 and 1.44-fold higher cytotoxicity against MDA-MB-231 than pure QT. The CS-QT-BS3opt1 displayed a significantly greater antimicrobial potential against E. coli than against S. aureus. From all these findings, it could be concluded that surface-modified QT-BS might be an effective approach for increasing the efficacy of QT in the treatment of certain ailments.
    Keywords:  Quercetin; antioxidant; bilosomes; breast cancer; chitosan
    DOI:  https://doi.org/10.1080/10717544.2022.2122634
  74. Colloids Surf B Biointerfaces. 2022 Sep 14. pii: S0927-7765(22)00521-5. [Epub ahead of print]219 112838
    Novel pH-sensitive nanoparticles based on prodrug strategy to delivery All-Trans Retinoic Acid for breast cancer.
    Weinan Li, HeXin Gong, Yuhan Fu, Jialin Sun, Yanhong Wang.
      Developing chemotherapy with nanoparticle-based prodrugs provides promising strategies for improving the safety and delivery of anti-cancer drugs therapeutics and effective cancer treatment. Herein, we developed a pH-sensitive prodrug delivery system (All-Trans-Retinoic Acid (ATRA) grafted poly (β-amino esters) (PBAE) copolymers, ATRA-g-PBAE) for delivery of ATRA with some physicochemical and biological properties. The in vitro release of ATRA-g-PBAE prodrug nanoparticles (PNPs) was sustained-release and pH-sensitive. The cytotoxicity and uptake of different preparations in vitro were evaluated on MCF-7 cells at pH 7.4 and 5.5. The carrier PBAE had no cytotoxicity, and ATRA-g-PBAE PNPs could significantly inhibit cell growth at pH 5.5. MCF-7 cells treated with Cy5.5 grafted PBAE (Cy5.5-PBAE) showed stronger fluorescence signals at pH 5.5. Meanwhile, ATRA-g-PBAE PNPs entered the cell via a clathrin-mediated endocytic pathway. Subsequently, PBAE protonation facilitated the escape of PNPs from the lysosome and released the drug. ATRA-g-PBAE seems promising as a novel pH-sensitive prodrug to overcome the limitations of ATRA for breast cancer therapy.
    Keywords:  All-Trans-Retinoic Acid; Breast cancer; Pin1; Prodrug nanoparticles
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112838
  75. Molecules. 2022 Sep 16. pii: 6051. [Epub ahead of print]27(18):
    The Potential Role of Apigenin in Cancer Prevention and Treatment.
    Arshad Husain Rahmani, Mohammed A Alsahli, Ahmad Almatroudi, Mashael Abdullah Almogbel, Amjad Ali Khan, Shehwaz Anwar, Saleh A Almatroodi.
      Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista.
    Keywords:  apigenin; bioavailability; cancer; cell signalling pathways; synergistic effects
    DOI:  https://doi.org/10.3390/molecules27186051
  76. Nutrients. 2022 Sep 13. pii: 3773. [Epub ahead of print]14(18):
    Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies.
    Theodora Nikou, Maria Eleni Sakavitsi, Evangelos Kalampokis, Maria Halabalaki.
      Consumption of olive products has been established as a health-promoting dietary pattern due to their high content in compounds with eminent pharmacological properties and well-described bioactivities. However, their metabolism has not yet been fully described. The present critical review aimed to gather all scientific data of the past two decades regarding the absorption and metabolism of the foremost olive compounds, specifically of the phenylalcohols hydroxytyrosol (HTyr) and tyrosol (Tyr) and the secoiridoids oleacein (Olea), oleocanthal (Oleo) and oleuropein (Oleu). A meticulous record of the in vitro assays and in vivo (animals and humans) studies of the characteristic olive compounds was cited, and a critical discussion on their bioavailability and metabolism was performed taking into account data from their gut microbial metabolism. The existing critical review summarizes the existing knowledge regarding the bioavailability and metabolism of olive-characteristic phenylalchohols and secoiridoids and spotlights the lack of data for specific chemical groups and compounds. Critical observations and conclusions were derived from correlating structure with bioavailability data, while results from in vitro, animal and human studies were compared and discussed, giving significant insight to the future design of research approaches for the total bioavailability and metabolism exploration thereof.
    Keywords:  ADMET properties; human studies; hydroxytyrosol; in vitro assays; in vivo; metabolism; oleacein; oleocanthal; oleuropein; tyrosol
    DOI:  https://doi.org/10.3390/nu14183773
  77. Pharmaceutics. 2022 Aug 26. pii: 1799. [Epub ahead of print]14(9):
    Essential Oil-Loaded Nanofibers for Pharmaceutical and Biomedical Applications: A Systematic Mini-Review.
    Ioannis Partheniadis, Georgios Stathakis, Dimitra Tsalavouti, Jyrki Heinämäki, Ioannis Nikolakakis.
      Essential oils (EOs) have been widely exploited for their biological properties (mainly as antimicrobials) in the food industry. Encapsulation of EOs has opened the way to the utilization of EOs in the pharmaceutical and biomedical fields. Electrospinning (ES) has proved a convenient and versatile method for the encapsulation of EOs into multifunctional nanofibers. Within the last five years (2017-2022), many research articles have been published reporting the use of ES for the fabrication of essential oil-loaded nanofibers (EONFs). The objective of the present mini-review article is to elucidate the potential of EONFs in the pharmaceutical and biomedical fields and to highlight their advantages over traditional polymeric films. An overview of the conventional ES and coaxial ES technologies for the preparation of EONFs is also included. Even though EONFs are promising systems for the delivery of EOs, gaps in the literature can be recognized (e.g., stability studies) emphasizing that more research work is needed in this field to fully unravel the potential of EONFs.
    Keywords:  antimicrobial; coaxial; electrospinning; emulsion; long-term stability; topical delivery; wound healing
    DOI:  https://doi.org/10.3390/pharmaceutics14091799
  78. Nanomedicine (Lond). 2022 Sep 22.
    Alpha-fetoprotein mediated targeting of polymeric nanoparticles to treat solid tumors.
    Mariya B Sokol, Nikita G Yabbarov, Mariia R Mollaeva, Margarita V Chirkina, Murad D Mollaev, Artur I Zabolotsky, Sergey L Kuznetsov, Elena D Nikolskaya.
      Background: Serious side effects caused by paclitaxel formulation, containing toxic solubilizer Cremophor® EL, and its nonspecific accumulation greatly limit clinical paclitaxel application. Aim: To design paclitaxel-loaded copolymer of lactic and glycolic acids nanoparticles decorated with alpha-fetoprotein third domain (rAFP3d-NP) to increase paclitaxel safety profile. Methods: rAFP3d-NP was obtained via carbodiimide technique. Results: The particles were characterized with high paclitaxel loading content of 5% and size of 280 nm. rAFP3d-NP revealed biphasic profile with 67% release of paclitaxel during 220 h. Increased area under the curveinf and mean residence time values after rAFP3d-NP administration confirmed prolonged blood circulation compared with paclitaxel. rAFP3d-NP demonstrated significant tumor growth inhibition at 4T1 and SKOV-3 models. Conclusion: rAFP3d-NP is a promising delivery system for paclitaxel and can be applied similarly for delivery of other hydrophobic drugs.
    Keywords:  PLGA; alpha-fetoprotein; antitumor efficacy; nanoparticles; paclitaxel; pharmacokinetics
    DOI:  https://doi.org/10.2217/nnm-2022-0097
  79. J Funct Biomater. 2022 Sep 04. pii: 141. [Epub ahead of print]13(3):
    Preparation of Fluorescently Labeled Chitosan-Quercetin Drug-Loaded Nanoparticles with Excellent Antibacterial Properties.
    Jingxin Zhou, Na Li, Ping Liu, Zhiwei Liu, Lili Gao, Tifeng Jiao.
      In recent years, quercetin plays an increasingly important role in the medical field. However, the absorption and effect of quercetin as a drug in vivo are limited due to its extremely poor solubility in water. In addition, chitosan nanoparticles can deliver poorly soluble drugs as drug delivery carriers. Herein, chitosan nanoparticles were prepared by oxidative degradation and ionic cross-linking technology to study the drug loading properties of quercetin. On the other hand, the application of chitosan for fluorescent materials can improve the biocompatibility of fluorescent materials and increase the adsorption of fluorescent materials. Fluorescently labeled chitosan nanoparticles, especially chitosan microsphere fluorescent probes prepared using the abundant amino groups on chitosan chains to react with fluorescein isothiocyanate (FTIC), have been widely used as fluorescent probes in biomarkers and medical diagnostics. Therefore, chitosan-quercetin (CS-QT) drug-loaded nanoparticles are labeled with FITC, and the drug-loaded rate, encapsulation efficiency, and antioxidant properties were investigated. The drug-loaded rate of the sample reaches 8.39%, the encapsulation rate reaches 83.65%, and exhibits good antioxidant capacity. The fluorescence aperture of the obtained sample was consistent with the inhibition zone, which could realize the visualization of the antibacterial performance of the sample. The fluorescent-labeled nano-system exhibit superior antibacterial properties, which provide a strategy for observing the release and function of drugs.
    Keywords:  chitosan; fluorescein isothiocyanate; fluorescence labeling; nanoparticle
    DOI:  https://doi.org/10.3390/jfb13030141
  80. Biomed Pharmacother. 2022 Sep 19. pii: S0753-3322(22)01101-5. [Epub ahead of print]155 113712
    Targeting autophagy in atherosclerosis: Advances and therapeutic potential of natural bioactive compounds from herbal medicines and natural products.
    Sijian Wang, Ruolan Yuan, Miao Liu, Yiwen Zhang, Bona Jia, Jingya Ruan, Jiayan Shen, Yi Zhang, Mengyang Liu, Tao Wang.
      Atherosclerosis (AS) is the most common causes of cardiovascular disease characterized by the formation of atherosclerotic plaques in the arterial wall, and it has become a dominant public health problem that seriously threaten people worldwide. Autophagy is a cellular self-catabolism process, which is critical to protect cellular homeostasis against harmful conditions. Emerging evidence suggest that dysregulated autophagy is involved in the development of AS. Therefore, pharmacological interventions have been developed to inhibit the AS via autophagy induction. Among various AS treating methods, herbal medicines and natural products have been applied as effective complementary and alternative medicines to ameliorate AS and its associated cardiovascular disease. Recently, mounting evidence revealed that natural bioactive compounds from herbs and natural products could induce autophagy to suppress the occurrence and development of AS, by promoting cholesterol efflux, reducing plaque inflammation, and inhibiting apoptosis or senescence. In the present review, we highlight recent findings regarding possible effects and molecular mechanism of natural compounds in autophagy-targeted mitigation of atherosclerosis, aiming to provide new potential therapeutic strategies for the atherosclerosis treatment preclinically and clinically.
    Keywords:  Atherosclerosis; Autophagy; Herbal medicines; Natural bioactive compounds
    DOI:  https://doi.org/10.1016/j.biopha.2022.113712
  81. Chin Herb Med. 2022 Apr;14(2): 171-186
    Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020.
    Xiaojie Gu, Dacheng Hao, Peigen Xiao.
      Traditional Chinese medicines (TCMs) have continued to be a treasure trove. The study of chemodiversity and versatility of bioactivities has always been an important content of pharmacophylogeny. There is amazing progress in the discovery and research of natural components with novel structures and significant bioactivities in 2020. In this paper we review 271 valuable natural products, including terpenoids, steroids, flavonoids, phenylpropanoids, phenolics, nitrogen containing compounds and essential oil, etc., isolated and identified from TCMs published in journals of Chinese Traditional and Herbal Drugs (Zhong Cao Yao) and Chinese Herbal Medicines (CHMs), and focus on their structures, source organisms, and relevant bioactivities, paying special attention to structural characteristics of novel compounds and newly revealed pharmacological properties of known compounds. It is worth noting that natural products with antitumor activity still constitute the primary object of research. Among the reported compounds, two new triterpenoids, i.e., ursolic acid 3-O-β-cis-caffeate and mollugoside E, display remarkable cytotoxicity against PC-9 and HL-60 cell lines, respectively. Three known phenolic compounds, i.e., pyoluteorin, 4-hydroxy-3-methoxy cinnamaldehyde and 3,7-dimethoxy-5-hydroxy-1,4-phenanthrenequinone, exhibit significant cytotoxicity against multiple cell lines. Numerous studies on the free radical scavenging activity of reported compounds are currently underway. In vitro, three known phenolic compounds, i.e., 3,4-O-dicaffeoylquinic acid methyl ester, 3,4,5-O-tricaffeoylquinic acid methyl ester and arbutin, had more considerable antioxidant activities than vitamin C. The anti-inflammatory, anti-diabetic, hypolipidemic, neuroprotective and antimicrobial activities of isolated compounds are also encouraging. The structural characteristics and bioactivities of TCM compounds highlighted here reflect the enormous progress of CHM research in 2020 and will play a positive role in the future drug discovery and development. According to pharmacophylogeny, the phylogenetic distribution of compounds with different natures and flavors can be explored, with view to better mining TCM resources.
    Keywords:  chemical constituents; medicinal plants; natural products; pharmacological activities; traditional Chinese medicine
    DOI:  https://doi.org/10.1016/j.chmed.2022.03.004
  82. Front Pharmacol. 2022 ;13 942996
    Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.
    Shan Wang, Hui-Feng Hao, Yan-Na Jiao, Jia-Lei Fu, Zheng-Wang Guo, Yang Guo, Yuan Yuan, Ping-Ping Li, Shu-Yan Han.
      Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.
    Keywords:  choline kinase α; dandelion extract; glycerophospholipid metabolism; multi-omics; triple-negative breast cancer
    DOI:  https://doi.org/10.3389/fphar.2022.942996
  83. Nanoscale Adv. 2021 Jul 13. 3(14): 4005-4018
    Inhaled antibiotic-loaded polymeric nanoparticles for the management of lower respiratory tract infections.
    Mohammad Zaidur Rahman Sabuj, Nazrul Islam.
      Lower respiratory tract infections (LRTIs) are one of the leading causes of deaths in the world. Currently available treatment for this disease is with high doses of antibiotics which need to be administered frequently. Instead, pulmonary delivery of drugs has been considered as one of the most efficient routes of drug delivery to the targeted areas as it provides rapid onset of action, direct deposition of drugs into the lungs, and better therapeutic effects at low doses and is self-administrable by the patients. Thus, there is a need for scientists to design more convenient pulmonary drug delivery systems towards the innovation of a novel treatment system for LRTIs. Drug-encapsulating polymer nanoparticles have been investigated for lung delivery which could significantly reduce the limitations of the currently available treatment system for LRTIs. However, the selection of an appropriate polymer carrier for the drugs is a critical issue for the successful formulations of inhalable nanoparticles. In this review, the current understanding of LRTIs, management systems for this disease and their limitations, pulmonary drug delivery systems and the challenges of drug delivery through the pulmonary route are discussed. Drug-encapsulating polymer nanoparticles for lung delivery, antibiotics used in pulmonary delivery and drug encapsulation techniques have also been reviewed. A strong emphasis is placed on the impact of drug delivery into the infected lungs.
    DOI:  https://doi.org/10.1039/d1na00205h
  84. Chin Herb Med. 2022 Apr;14(2): 187-209
    Chemical constituents and pharmacological activities of medicinal plants from Rosa genus.
    Yansheng Wang, Yanmin Zhao, Xinnan Liu, Jingyang Li, Jingze Zhang, Dailin Liu.
      The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.
    Keywords:  Rosa; medicine and food homology; pharmacological effect; phytochemistry; safety
    DOI:  https://doi.org/10.1016/j.chmed.2022.01.005
  85. Int J Biol Macromol. 2022 Sep 15. pii: S0141-8130(22)02032-3. [Epub ahead of print]
    Preparation, physicochemical, and retinal anti-angiogenic evaluation of poloxamer hydrogel containing dexamethasone/avastin-loaded chitosan-N-acetyl-L-cysteine nanoparticles.
    Sayed Latif Taheri, Mahboubeh Rezazadeh, Farshid Hassanzadeh, Vajihe Akbari, Alireza Dehghani, Ardeshir Talebi, Sayed Abolfazl Mostafavi.
      This study was meant to describe a Poloxamer hydrogel combining Chitosan-N-acetyl-L-cysteine (CNAC) nanoparticles to increase loading and sustained intravitreal administration of Avastin macromolecule. To increase the drug's efficacy and reduce the interfacial fluid pressure in a formulation, dexamethasone was used. To do so, CNAC was synthesized. Then, Avastin- loaded CNAC nanoparticles were prepared and optimized. The resulting hydrogel's sol-gel transition time and viscosity were determined using poloxamer and hydroxypropylmethylcellulose (HPMC). In vitro and in vivo investigations of Avastin-loaded CNAC nanoparticles and hydrogel comprising dexamethasone/Avastin-loaded CNAC nanoparticles were determined. In vitro, the drug release profile of optimized hydrogel containing Avastin-loaded CNAC nanoparticles was sustained and controlled over 256 h. The obtained results point to poloxamer/HPMC (18 %/0.5 %) as the best formulations for this hydrogel to develop a sol-gel transition. About 97 % of dexamethasone was released from the hydrogel within 18 h. In vivo results indicated that the optimized formulation compared with free Avastin could improve Diabetic retinopathy (DR). Consequently, we infer that this new drug delivery method may enhance Avastin intravitreal administration, lowering the frequency, danger, and expense of heavy intravitreal injections and resulting in improved treatment of posterior eye segment neovascularization and concomitant vitreoretinal disorders.
    Keywords:  Avastin; Chitosan-N-acetyl-L-cysteine; Dexamethasone; Hydrogel; Poloxamer; Retinopathy
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.101
  86. Plants (Basel). 2022 Sep 09. pii: 2355. [Epub ahead of print]11(18):
    Triterpenoid Saponins from Washnut (Sapindus mukorossi Gaertn.)-A Source of Natural Surfactants and Other Active Components.
    Mateusz Sochacki, Otmar Vogt.
      Sapindus mukorossi Gaertn., also called the washnut, is a tropical tree of the Sapindaceae family. The plant owes its name to its cleaning and washing properties used by the local population as a natural detergent. The most important ingredients of the plant are triterpenoid saponins contained in many parts of the plant, inducing fruits, galls, or roots. The tree also contains other valuable, biologically active compounds that are obtained by extraction methods. Raw or purified extract and isolated saponins are valuable plant products that can be used in the food, pharmaceutical, cosmetic, and chemical industries. This review includes the most important biological and surfactant properties of extracts and isolated saponins obtained from various parts of the plant.
    Keywords:  Sapindus mukorossi; bioactive compounds; natural surfactants; triterpenoid saponins; washnut
    DOI:  https://doi.org/10.3390/plants11182355
  87. Adv Healthc Mater. 2022 Sep 20. e2201472
    Effective Sonosensitizer Delivery by Redox Sensitive Nanoparticles for Prostate Cancer Sonodynamic Therapy via Amplifying Oxidative Stress and Peroxidation.
    Tongyu Tong, Hanqi Lei, Shiqiang Zhang, Donggen Jiang, Yupeng Guan, Chengyuan Xing, Huikun Chen, Xiangwei Yang, Yang Kang, Jun Pang.
      Sonodynamic therapy (SDT), a novel noninvasive therapeutic modality, provides many noteworthy benefits by generating reactive oxygen species (ROS). However, water-insoluble sonosensitizer delivery strategies have continuously underperformed because of unavoidable toxicity and a short circulation time. In this study, we designed and synthesized L-cystine derivative-based biocompatible nanoparticles (NPs) that can be used in SDT and induce limited cytotoxicity. After ultrasonic (US) irradiation, these sonosensitizer-loaded NPs showed highly efficient sonodynamic performance that led to cytotoxic ROS production. The ability to stop and start ROS generation induced by US irradiation enabled accurate temporal and spatial control. In vivo and in vitro experiments were systematically performed to investigate the effects of this system on tumors, and the results indicated remarkable tumor suppression via markedly high persistent oxidative stress that induced peroxidation and endoplasmic reticulum stress. Thus, this novel temporally and spatially controllable ROS generation platform offers a safe and effective theranostic strategy for prostate cancer treatment. This article is protected by copyright. All rights reserved.
    Keywords:  drug delivery; oxidative stress; prostate cancer; sonodynamic therapy
    DOI:  https://doi.org/10.1002/adhm.202201472
  88. Int J Mol Med. 2022 Nov;pii: 135. [Epub ahead of print]50(5):
    The impact of diet upon mitochondrial physiology (Review).
    Ioannis D Kyriazis, Eleni Vassi, Maria Alvanou, Christos Angelakis, Zoi Skaperda, Fotios Tekos, Venkata Naga Srikanth Garikipati, Demetrios A Spandidos, Demetrios Kouretas.
      Mitochondria are considered the 'powerhouses' of cells, generating the essential energy in the form of adenosine triphosphate that they need for their energy demands. Nevertheless, their function is easily adaptable as regards the energy demands and the availability of chemical substrates. This allows cells to buffer sudden changes and reassure cellular metabolism, growth or survival. Currently, humans have different dietary habits, which provide several stimuli to the cell. According to the energy substrate availability due to the diet quality and diet temporality, mitochondrial physiology is greatly affected. The present review article aimed to collect all the available information that has been published to date concerning the impact of five different popular diets (high‑fat diet, ketogenic diet, fasting, caloric restriction diet and the Mediterranean diet) on specific mitochondrial physiological aspects, such as function, biogenesis, mitophagy and mitochondrial fission/fusion.
    Keywords:  biogenesis; caloric restriction; dynamics; fasting; high‑fat diet; ketogenic; mitochondria; mitophagy; physiology
    DOI:  https://doi.org/10.3892/ijmm.2022.5191
  89. Pharmaceutics. 2022 Sep 03. pii: 1860. [Epub ahead of print]14(9):
    Polymeric Micelles for Breast Cancer Therapy: Recent Updates, Clinical Translation and Regulatory Considerations.
    Vijayabhaskarreddy Junnuthula, Praveen Kolimi, Dinesh Nyavanandi, Sunitha Sampathi, Lalitkumar K Vora, Sathish Dyawanapelly.
      With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future.
    Keywords:  bioavailability; breast cancer; clinical translation; drug delivery; polymeric micelles; regulatory affairs
    DOI:  https://doi.org/10.3390/pharmaceutics14091860
  90. Pharmaceutics. 2022 Aug 24. pii: 1765. [Epub ahead of print]14(9):
    Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy.
    Bo Yu, Yiping Shen, Xuejie Zhang, Lijuan Ding, Zheng Meng, Xiaotong Wang, Meihua Han, Yifei Guo, Xiangtao Wang.
      Owing to its pH-sensitive property and chelating Cu2+ effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50 value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.
    Keywords:  chelating Cu2+ effect; doxorubicin; pH sensitive; poly(methacrylate citric acid)
    DOI:  https://doi.org/10.3390/pharmaceutics14091765
  91. Chin Herb Med. 2021 Oct;13(4): 451-460
    Targeting immunometabolism by active ingredients derived from traditional Chinese medicines for treatment of rheumatoid arthritis.
    Yu-Fei He, Chu-Tian Mai, Hu-Dan Pan, Liang Liu, Hua Zhou, Ying Xie.
      Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.
    Keywords:  immune cells; immunometabolism; natural compounds; rheumatoid arthritis; traditional Chinese medicines
    DOI:  https://doi.org/10.1016/j.chmed.2021.09.005
  92. Drug Discov Today. 2022 Sep 14. pii: S1359-6446(22)00358-0. [Epub ahead of print] 103365
    Senotherapies: A novel strategy for synergistic anti-tumor therapy.
    Xuxin Qi, Li Jiang, Ji Cao.
      Cellular senescence was initially considered an effective antitumor mechanism, and senescence-induced therapy has previously been regarded as an efficient treatment. However, increasing studies have discovered that persistent senescent cells (SNCs) might have unanticipated negative repercussions for antitumor treatment. The long-term build-up of SNCs exacerbates toxic side effects, treatment resistance, and poor prognosis, and tumor cells that undergo senescence escape can acquire stemness to repopulate the tumor, leading to cancer recurrence. Thus, senotherapies that eliminate SNCs could be used as a new strategy for synergistic antitumor therapy. In this review, we summarize the adverse effects of SNCs in tumor development and the mechanisms by which senescent tumor cells escape senescence, discuss the relationship between senescence and polyploidy, and highlight the potential of senotherapies as an emerging adjuvant antitumor treatment strategy. Such a strategy is expected to provide new approaches for antitumor drug development from the perspective of cellular senescence.
    Keywords:  Antitumor therapy; Cellular senescence; Polyploid; Senescence escape; Senotherapy
    DOI:  https://doi.org/10.1016/j.drudis.2022.103365
  93. Antioxidants (Basel). 2022 Sep 08. pii: 1777. [Epub ahead of print]11(9):
    Methanol Extract of Clavularia inflata Exerts Apoptosis and DNA Damage to Oral Cancer Cells.
    Yin-Yin Hsu, Ya-Ting Chuang, Ching-Yu Yen, Ming-Ya Cheng, Ching-Yeu Chen, Yuan-Bin Cheng, Hsueh-Wei Chang.
      Antiproliferation effects of Clavularia-derived natural products against cancer cells have been reported on, but most studies have focused on identifying bioactive compounds, lacking a detailed investigation of the molecular mechanism. Crude extracts generally exhibit multiple targeting potentials for anticancer effects, but they have rarely been assessed for methanol extracts of Clavularia inflata (MECI). This investigation aims to evaluate the antiproliferation of MECI and to examine several potential mechanisms between oral cancer and normal cells. A 24 h MTS assay demonstrated that MECI decreased cell viability in several oral cancer cell lines more than in normal cells. N-acetylcysteine (NAC), an oxidative stress inhibitor, recovered these antiproliferation effects. Higher oxidative stress was stimulated by MECI in oral cancer cells than in normal cells, as proven by examining reactive oxygen species and mitochondrial superoxide. This preferential induction of oxidative stress was partly explained by downregulating more cellular antioxidants, such as glutathione, in oral cancer cells than in normal cells. Consequently, the MECI-generated high oxidative stress in oral cancer cells was preferred to trigger more subG1 population, apoptosis expression (annexin V and caspase activation), and DNA damage, reverted by NAC. In conclusion, MECI is a potent marine natural product showing preferential antiproliferation against oral cancer cells.
    Keywords:  antiproliferation; marine natural product; oral cancer; oxidative stress; soft corals
    DOI:  https://doi.org/10.3390/antiox11091777
  94. Biomed Pharmacother. 2022 Sep 16. pii: S0753-3322(22)01096-4. [Epub ahead of print]155 113707
    Insights into stimuli-responsive diselenide bonds utilized in drug delivery systems for cancer therapy.
    Zhenfeng Shi, Jifang Liu, Lei Tian, Jingyi Li, Yue Gao, Yue Xing, Wenjing Yan, Chenyu Hua, Xiaolin Xie, Chang Liu, Chengyuan Liang.
      Due to the complexity and particularity of cancer cell microenvironments, redox responsive drug delivery systems (DDSs) for cancer therapy have been extensively explored. Compared with widely reported cancer treatment systems based on disulfide bonds, diselenide bonds have better redox properties and greater anticancer efficiency. In this review, the significance and application of diselenide bonds in DDSs are summarized, and the stimulation sensitivity of diselenide bonds is comprehensively reported. The potential and prospects for the application of diselenide bonds in next-generation anticancer drug treatment systems are extensively discussed.
    Keywords:  Anticancer drugs; Diselenide bonds; Drug delivery systems (DDSs); Reactive oxygen species (ROS); Redox responsiveness; Reduced glutathione (GSH)
    DOI:  https://doi.org/10.1016/j.biopha.2022.113707
  95. Nanoscale Adv. 2020 Nov 11. 2(11): 5152-5165
    Therapeutic nanodendrites: current applications and prospects.
    Adewale O Oladipo, Thabo T I Nkambule, Bhekie B Mamba, Titus A M Msagati.
      Multidisciplinary efforts in the field of nanomedicine for cancer therapy to provide solutions to common limitations of traditional drug administration such as poor bioaccumulation, hydrophobicity, and nonspecific biodistribution and targeting have registered very promising progress thus far. Currently, a new class of metal nanostructures possessing a unique dendritic-shaped morphology has been designed for improved therapeutic efficiency. Branched metal nanoparticles or metal nanodendrites are credited to present promising characteristics for biomedical applications owing to their unique physicochemical, optical, and electronic properties. Nanodendrites can enhance the loading efficiency of bioactive molecules due to their three-dimensional (3D) high surface area and can selectively deliver their cargo to tumor cells using their stimuli-responsive properties. With the ability to accumulate sufficiently within cells, nanodendrites can overcome the detection and clearance by glycoproteins. Moreover, active targeting ligands such as antibodies and proteins can as well be attached to these therapeutic nanodendrites to enhance specific tumor targeting, thereby presenting a multifunctional nanoplatform with tunable strategies. This mini-review focuses on recent developments in the understanding of metallic nanodendrite synthesis, formation mechanism, and their therapeutic capabilities for next-generation cancer therapy. Finally, the challenges and future opportunities of these fascinating materials to facilitate extensive research endeavors towards the design and application were discussed.
    DOI:  https://doi.org/10.1039/d0na00672f
  96. Pharmaceutics. 2022 Sep 02. pii: 1852. [Epub ahead of print]14(9):
    Nanoscale Delivery Systems of Lutein: An Updated Review from a Pharmaceutical Perspective.
    Aslihan Hilal Algan, Ayca Gungor-Ak, Aysegul Karatas.
      Carotenoids are natural lipid-soluble pigments that produce yellow to red colors in plants as well as providing bright coloration in vegetables and fruits. Lutein belongs to the xanthophyll subgroup of the carotenoid family, which plays an essential role in photosynthesis and photoprotection in nature. In the human body, lutein, together with its isomer zeaxanthin and its metabolite meso-zeaxanthin, accumulates in the macula of the eye retina, which is responsible for central, high-resolution, and color vision. As a bioactive phytochemical, lutein has essential physiological functions, providing photoprotection against damaging blue light, along with the neutralization of oxidants and the preservation of the structural and functional integrity of cellular membranes. As a potent antioxidant and anti-inflammatory agent, lutein unfortunately has a low bioavailability because of its lipophilicity and a low stability as a result of its conjugated double bonds. In order to enhance lutein stability and bioavailability and achieve its controlled delivery to a target, nanoscale delivery systems, which have great potential for the delivery of bioactive compounds, are starting to be employed. The current review highlights the advantages and innovations associated with incorporating lutein within promising nanoscale delivery systems, such as liposomes, nanoemulsions, polymer nanoparticles, and polymer-lipid hybrid nanoparticles, as well as their unique physiochemical properties.
    Keywords:  anti-inflammatory effect; antioxidant; degenerative diseases; drug delivery systems; lutein; nanoencapsulation; xanthophylls
    DOI:  https://doi.org/10.3390/pharmaceutics14091852
  97. Molecules. 2022 Sep 15. pii: 6008. [Epub ahead of print]27(18):
    Brassica Genus Seeds: A Review on Phytochemical Screening and Pharmacological Properties.
    Jawaher Ayadi, Mohamed Debouba, Rami Rahmani, Jalloul Bouajila.
      Traditionally, Brassica species are widely used in traditional medicine, human food, and animal feed. Recently, special attention has been dedicated to Brassica seeds as source of health-promoting phytochemicals. This review provides a summary of recent research on the Brassica seed phytochemistry, bioactivity, dietary importance, and toxicity by screening the major online scientific database sources and papers published in recent decades by Elsevier, Springer, and John Wiley. The search was conducted covering the period from January 1964 to July 2022. Phytochemically, polyphenols, glucosinolates, and their degradation products were the predominant secondary metabolites in seeds. Different extracts and their purified constituents from seeds of Brassica species have been found to possess a wide range of biological properties including antioxidant, anticancer, antimicrobial, anti-inflammatory, antidiabetic, and neuroprotective activities. These valuable functional properties of Brassica seeds are related to their richness in active compounds responsible for the prevention and treatment of various chronic diseases such as obesity, diabetes, cancer, and COVID-19. Currently, the potential properties of Brassica seeds and their components are the main focus of research, but their toxicity and health risks must also be accounted for.
    Keywords:  Brassica plants; COVID-19; bioactive phytochemicals; cancer; diabetes; nutrients; oilseeds; pharmacological activities; seeds; toxicity
    DOI:  https://doi.org/10.3390/molecules27186008
  98. Nanoscale Adv. 2022 Aug 23. 4(17): 3479-3494
    Recent advances in nanoparticle-based drug delivery systems for rheumatoid arthritis treatment.
    Simran Nasra, Dhiraj Bhatia, Ashutosh Kumar.
      Nanotechnology has increasingly emerged as a promising tool for exploring new approaches, from treating complex conditions to early detection of the onset of multiple disease states. Tailored designer nanoparticles can now more comprehensively interact with their cellular targets and various pathogens due to a similar size range and tunable surface properties. The basic goal of drug delivery is to employ pharmaceuticals only where they are needed, with as few adverse effects and off-target consequences as possible. Rheumatoid arthritis (RA) is a chronic inflammatory illness that leads to progressive loss of bone and cartilage, resulting in acute impairment, decreased life expectancy, and increased death rates. Recent advancements in treatment have significantly slowed the progression of the disease and improved the lives of many RA sufferers. Some patients, on the other hand, attain or maintain illness remission without needing to continue immunosuppressive therapy. Furthermore, a large percentage of patients do not respond to current treatments or acquire tolerance to them. As a result, novel medication options for RA therapy are still needed. Nanocarriers, unlike standard medications, are fabricated to transport drugs directly to the location of joint inflammation, evading systemic and negative effects. As a result, researchers are reconsidering medicines that were previously thought to be too hazardous for systemic delivery. This article gives an overview of contemporary nanotechnology-based tactics for treating rheumatoid arthritis, as well as how the nanotherapeutic regimen could be enhanced in the future.
    DOI:  https://doi.org/10.1039/d2na00229a
  99. J Food Biochem. 2022 Sep 22. e14413
    Unveiling major ethnopharmacological aspects of genus Diospyros in context to its chemical diversity: A comprehensive overview.
    Nada Fareed, Dina M El-Kersh, Fadia S Youssef, Rola M Labib.
      Diospyros species (DS), "Ebenaceae," were known for their therapeutic uses in folk medicine since days of yore. Thereafter, scientific evidence related their health benefits to a myriad of chemical classes, for instance, naphthoquinones, flavonoids, tannins, coumarins, norbergenin derivatives, sterols, secoiridoids, sesquiterpenes, diterpenoids, triterpenoids, volatile organic compounds (VOCs), and carotenoids. The available literature showed that more than 200 compounds were isolated and identified via spectroscopic techniques. Many pharmacological activities of DS have been previously described, such as antioxidant, neuroprotective, antibacterial, antiviral, antiprotozoal, antifungal, antiinflammatory, analgesic, antipyretic and cosmeceutical, investigated, and confirmed through versatile in vitro and in vivo assays. Previous studies proved that genus Diospyros is a rich reservoir of valuable bioactive compounds. However, further comparative studies among its different species are recommended for more precise natural source-based drug discovery and clinical application. Accordingly, this review is to recall the chemical abundance and diversity among different members of genus Diospyros and their ethnopharmacological and pharmacological uses. PRACTICAL APPLICATIONS: Practically, providing sufficient background on both secondary metabolites divergence and pharmacological properties of genus Diospyros has many fruitful aspects. As demonstrated below, extracts and many isolated compounds have significant curative properties, which can lead to the discovery of pharmaceutically relevant alternative substitutes to conventional medicine. Consequently, molecular docking on various receptors can be applied. On the grounds, Naoxinqing tablets, a standardized herbal product containing D. kaki leaves extract, have been patented and recorded in Chinese Pharmacopeia as an approved Traditional Chinese Medicine (TCM) for the treatment of cerebro- and cardiovascular diseases, although the underlying mechanism remains under advisement. Moreover, the antimicrobial applications of DS are of considerable concern; since the widespread use of antibiotics resulted in different forms of bacterial resistance, hence, limiting and compromising effective treatment. In addition, as a result of contemporary rampant memory disorders, neuroprotective activities of different extracts of DS became of great emphasis.
    Keywords:   Diospyros ; Ebenaceae; bioactive compounds; ethnopharmacology; phytochemical diversity
    DOI:  https://doi.org/10.1111/jfbc.14413
  100. AAPS PharmSciTech. 2022 Sep 21. 23(7): 261
    Self-Emulsifying Drug Delivery System Enhances Tissue Distribution of Cinnamaldehyde by Altering the Properties of the Mucus Layer.
    Liu Liu, Wenxuan Cao, Mengqiu Xia, Chunling Tian, Wenqing Wu, Ye Cai, Xiaoqin Chu.
      Oral delivery is considered the preferred route of administration due to its convenience and favorable compliance. However, this delivery often faces difficulties, such as poor solubility, limited absorption, and undesirable stability, especially for some volatile oils. The aim of this study was to develop self-emulsifying drug delivery systems (SEDDS) containing cinnamaldehyde (CA) to overcome these shortcomings. The CA-SEDDS were spherical and smooth with an average size of 14.96 ± 0.18 nm. Differential scanning calorimetry (DSC) and attenuated total reflection by Fourier transform infrared (ATR-FTIR) showed that CA has been successfully loaded into SEDDS. The accumulative release of CA-SEDDS (73.39%) was approximately 2.14-fold that of free CA when using simulated intestinal fluid as the release medium. A scanning electron microscope was used to observe the mucus network structure. Rheological tests found that CA-SEDDS can appropriately enhance the viscosity of the mucus system. We found from tissue distribution studies that CA was more widely distributed in various tissues in the CA-SEDDS group compared to the free CA group. The cinnamaldehyde and cinnamon acid also accumulated more in various tissues in the CA-SEDDS group than in the free CA group, especially in the kidney. These findings hinted that SEDDS exhibited lower irritation, good release, and penetration, which demonstrated great potential for utilizing CA. Our research supports the rational implications of SEDDS in delivering similar volatile substances by improving the solubility, mucus penetration, and stability, resulting in excellent clinical efficacy.
    Keywords:  cinnamaldehyde; mucus layer; rheology; self-emulsifying drug delivery system; tissue distribution
    DOI:  https://doi.org/10.1208/s12249-022-02416-4
  101. Int J Nanomedicine. 2022 ;17 4261-4275
    Key Health Benefits of Korean Ueong Dry Root Extract Combined Silver Nanoparticles.
    Gitishree Das, Han-Seung Shin, Jayanta Kumar Patra.
      Introduction: Nowadays, in nanotechnology and material science, biosynthesis of the metal nanoparticle is a promising approach.Methods: In the current research, the extract of the Korean Ueong dry root (BdkR), which belongs to the Asteraceae family, was used as a reducing and capping agent, for the green synthesis of the BdkR-Ag nanoparticles in a cost-effective and highly efficient manner. In this study for the reaction measures, UV-Vis spectroscopy was applied. SEM, EDX, FTIR, XRD, mean size distribution, and zeta potential were used for the characterization of the green synthesized BdkR-AgNPs. In the beginning, the primary phytochemical screening of BdkR extract was estimated and the cytotoxicity, antidiabetic, antioxidant, and antibacterial activities of the green synthesized BdkR-AgNPs were evaluated.
    Results: According to the results, the BdkR extract is rich in various phytochemicals and the generated AgNPs were crystalline in nature. The surface plasmon resonance value of the BdkR-AgNPs was 444 nm confirming the synthesis of AgNPs. The BdkR-AgNPs displayed four clear diffraction peaks at 2 theta angles (38.22); (46.15); (64.88); (76.83), respectively, which are equivalent to (111), (200), (220) and (311). The obtained nanoparticles have a zeta potential of -17.0 mV. Furthermore, the generated BdkR-AgNPs exhibited considerable antidiabetic effect in terms of the inhibition of α-glucosidase with a maximum inhibition value of 95.41% at 5.0 µg/mL and more than 86% inhibition at 2.5 µg/mL and the estimated IC50 value was found to be 0.653 µg/mL. Further, it also displayed a significant cytotoxicity activity against the HepG2 cancer cell lines at 10 µg/mL and 100 µg/mL concentrations with 86% and 88% of inhibition, respectively. Besides this, the synthesized AgNPs also displayed promising antioxidant activities in terms of the DPPH (IC50 value - 56.26 µg/mL), ABTS (IC50 value - 171.43 µg/mL) and reducing power (IC0.5 value - 227.42 µg/mL).
    Discussion: The multipotential effects of the synthesized BdkR-AgNPs might be attributed to the presence of the bioactive compounds in the BdkR extract that acted as the capping and reducing agent in the synthesis process. The green synthesized BdkR-AgNPs exhibited promising bioactive potential for their future applications in the food and biomedical field.
    Keywords:  antidiabetic; antioxidant; cytotoxicity; green synthesis; silver nanoparticle
    DOI:  https://doi.org/10.2147/IJN.S357343
  102. Int J Mol Sci. 2022 Sep 10. pii: 10502. [Epub ahead of print]23(18):
    Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.
    Hye-Jin Park.
      Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushrooms and the underlying molecular mechanisms. We provide information regarding the current clinical status and possible modes of molecular actions of various mushrooms and mushroom-derived compounds. This review will help researchers and clinicians in designing evidence-based preclinical and clinical studies to test the anticancer potential of mushrooms and their active compounds in different types of cancers.
    Keywords:  cancer; multidrug resistance (MDR); mushroom-derived compounds; mushrooms; signaling pathways
    DOI:  https://doi.org/10.3390/ijms231810502
  103. Molecules. 2022 Sep 06. pii: 5765. [Epub ahead of print]27(18):
    A Comprehensive Review with Updated Future Perspectives on the Ethnomedicinal and Pharmacological Aspects of Moringa oleifera.
    Ummi Kalthum Azlan, Ahmed Mediani, Emelda Rosseleena Rohani, Xiaohui Tong, Rongchun Han, Norazlan Mohmad Misnan, Faidruz Azura Jam, Hamidun Bunawan, Murni Nazira Sarian, Hamizah Shahirah Hamezah.
      Moringa oleifera is an ancient remedy plant, known as the miraculous plant due to its many prominent uses and significant health benefits. It is a nutrient-rich plant, with exceptional bioactive compounds, such as polyphenols that possess several medicinal properties. Many significant studies have been carried out to evaluate the ethnomedicinal and pharmacological properties of M. oleifera in various applications. Therefore, this comprehensive review compiles and summarizes important findings from recent studies on the potential properties of different parts of M. oleifera. The pharmacological properties of M. oleifera have been studied for various potential biological properties, such as cardio-protective, anti-oxidative, antiviral, antibacterial, anti-diabetic and anti-carcinogenic effects. Therefore, the potential of this plant is even more anticipated. This review also highlights the safety and toxicity effects of M. oleifera treatment at various doses, including in vitro, in vivo and clinical trials from human studies.
    Keywords:  M. oleifera; antioxidant activity; bioactive compounds; nutritional composition; pharmacological properties; polyphenols
    DOI:  https://doi.org/10.3390/molecules27185765
  104. Pharmaceutics. 2022 Sep 07. pii: 1891. [Epub ahead of print]14(9):
    Mitotane Nanocarriers for the Treatment of Adrenocortical Carcinoma: Evaluation of Albumin-Stabilized Nanoparticles and Liposomes in a Preclinical In Vitro Study with 3D Spheroids.
    Carolin Langer, Monika Köll-Weber, Martin Holzer, Constanze Hantel, Regine Süss.
      Adrenocortical carcinoma (ACC) is a heterogeneous malignancy related to poor prognosis and limited treatment options. The orphan drug mitotane (MT) is still a cornerstone in ACC therapy, however, its application is characterized by low aqueous solubility, poor bioavailability, and unfavorable pharmacokinetics, often resulting in below-target plasma concentrations or toxic side effects. Throughout the last decades, nanoparticulate formulations have become attractive carriers to improve anticancer therapy. In this study, injectable MT liposomes (DOPC-MT) and albumin-stabilized MT nanoparticles (BSA-MT) were investigated in depth with respect to their physicochemical properties, and their colloidal and therapeutical stability upon storage. Furthermore, in vitro cytotoxicity was evaluated using the ACC model cell line NCI-H295R for preparing multicellular tumor spheroids, and was compared to non-malignant human dermal fibroblasts. Our results clearly demonstrate that BSA-MT, unlike DOPC-MT, represents a stable and storable MT formulation with a high drug concentration in an aqueous medium. Dual centrifugation was established as a reproducible method for nanoparticle preparation. Although an efficient cytotoxic effect on ACC tumor spheroids was demonstrated, concomitant low toxicity to fibroblasts suggests that higher drug concentrations may be tolerated in vivo. Consequently, BSA-MT is a novel and promising therapeutical approach to address key challenges in MT treatment.
    Keywords:  3D spheroids; adrenocortical carcinoma; albumin nanoparticles; cancer therapy; dual centrifugation; liposomes; mitotane
    DOI:  https://doi.org/10.3390/pharmaceutics14091891
  105. Colloids Surf B Biointerfaces. 2022 Sep 05. pii: S0927-7765(22)00509-4. [Epub ahead of print]219 112826
    Dual targeted zeolitic imidazolate framework nanoparticles for treating metastatic breast cancer and inhibiting bone destruction.
    Yaping Shen, Yonggang Lv.
      Tumor bone metastasis is still difficult to cure despite the development of various treatment strategies. Drug delivery systems can improve the poor biological distribution of anticancer drugs in tumors. But only a very small number of nanoparticles can cross the physiological barrier to reach the tumor. In addition, the progression of bone metastasis is influenced by tumor cells, osteoclasts and bone matrix. To address these problems, a bone and tumor dual targeted nanocarrier was developed by utilizing NF-κB inhibitor loaded into zeolitic imidazolate framework-8 (ZIF-8) (CZ), which was then coated with hyaluronic acid/alendronate (HA/ALN). The CZ prepared by two-step method had high loading capacity, and the loading efficiency of Cur was to be 47.55 ± 4.03%. HA/ALN functionalization avoided explosive release of reagents and improved the stability of nanoparticles. The dual targeted ZIF-8 nanoparticle (CZ@HA/ALN) had a pH-triggered drug release performance, which effectively inhibited breast cancer cells growth and osteoclastogenesis in vitro. Uptake experiments showed that the conjugation of ALN with HA did not affect targeting ability of HA. Moreover, HA/ALN functionalized nanoparticles were more aggregated at bone metastasis sites than HA functionalized nanoparticles. CZ@HA/ALN could block the PD-1 immune check point, leading to Raw 264.7 cells differentiation into anti-tumor macrophage rather than osteoclast. The antitumor experiments in vivo exhibited that the dual targeted ZIF-8 nanoparticle effectively inhibited bone resorption and tumor progress, thereby improving the bone microenvironment. Therefore, this single but versatile nanoparticle provided a promising therapeutic scheme for bone metastasis treatment.
    Keywords:  Alendronate; Bone metastase; Bone targeting; Hyaluronic acid; Osteoclast; Zeolitic imidazolate framework
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112826
  106. Foods. 2022 Sep 07. pii: 2755. [Epub ahead of print]11(18):
    Bioactive Compounds, Health Benefits and Food Applications of Grape.
    Dan-Dan Zhou, Jiahui Li, Ruo-Gu Xiong, Adila Saimaiti, Si-Yu Huang, Si-Xia Wu, Zhi-Jun Yang, Ao Shang, Cai-Ning Zhao, Ren-You Gan, Hua-Bin Li.
      Grape (Vitis vinifera L.) is one of the most popular fruits worldwide. It contains various bioactive compounds, such as proanthocyanidins, anthocyanins, flavonols, phenolic acids and stilbenes, the contents of which could vary considerably in grape skin, pulp and seed. Many studies have revealed that grape possesses a variety of health benefits, such as antioxidant, anti-inflammatory, gut-microbiota-modulating, anticancer and cardioprotective effects. Grape is eaten as fresh fruit and is also used as raw material to produce various products, such as wine, grape juice and raisins. Moreover, the byproducts of grape, such as grape pomace and grape seed, have many applications in the food industry. In this paper, the bioactive compounds in grape are briefly summarized based on literature published in recent years. In addition, the health benefits of grape and its bioactive components are discussed, with special attention paid to the underlying mechanisms. Furthermore, the applications of grape in the food industry are elucidated, especially the applications of grape pomace and grape seed. This paper can contribute to understanding the health benefits and mechanisms of grape and its bioactive compounds, as well as the promotion of the use of grape in the food industry.
    Keywords:  antioxidant; application; bioactive compounds; grape; grape seed; health benefits
    DOI:  https://doi.org/10.3390/foods11182755
  107. J Med Chem. 2022 Sep 22.
    A Photoactivated Sorafenib-Ruthenium(II) Prodrug for Resistant Hepatocellular Carcinoma Therapy through Ferroptosis and Purine Metabolism Disruption.
    Yidan Lai, Nong Lu, Shuangling Luo, Haobing Wang, Pingyu Zhang.
      The curative effect of sorafenib in hepatocellular carcinoma (HCC) is limited and sorafenib resistance remains a major obstacle for HCC. To overcome this obstacle, a new photoactive sorafenib-Ru(II) complex Ru-Sora has been designed. Upon irradiation (λ = 465 nm), Ru-Sora rapidly releases sorafenib and generates reactive oxygen species, which can oxidize intracellular substances such as GSH. Cellular experiments show that irradiated Ru-Sora is highly cytotoxic toward Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared to sorafenib, Ru-Sora has a significant photoactivated chemotherapeutic effect against Hep-G2-SR cancer cells and 3D Hep-G2 multicellular tumor spheroids. Furthermore, Ru-Sora inducing apoptosis and ferroptosis is proved by GSH depletion, GPX4 downregulation, and lipid peroxide accumulation. Metabolomics results suggest that Ru-Sora exerts photocytotoxicity by disrupting the purine metabolism, which is expected to inhibit tumor development. This study provides a promising strategy for enhancing chemotherapy and combating drug-resistant HCC disease.
    DOI:  https://doi.org/10.1021/acs.jmedchem.2c00880
  108. Cancers (Basel). 2022 Sep 19. pii: 4539. [Epub ahead of print]14(18):
    A Review on Annona muricata and Its Anticancer Activity.
    Suganya Ilango, Dipak Kumar Sahoo, Biswaranjan Paital, Kavibharathi Kathirvel, Jerrina Issac Gabriel, Kalyani Subramaniam, Priyanka Jayachandran, Rajendra Kumar Dash, Akshaya Kumar Hati, Tapas Ranjan Behera, Pragnyashree Mishra, Ramalingam Nirmaladevi.
      The ongoing rise in the number of cancer cases raises concerns regarding the efficacy of the various treatment methods that are currently available. Consequently, patients are looking for alternatives to traditional cancer treatments such as surgery, chemotherapy, and radiotherapy as a replacement. Medicinal plants are universally acknowledged as the cornerstone of preventative medicine and therapeutic practices. Annona muricata is a member of the family Annonaceae and is familiar for its medicinal properties. A. muricata has been identified to have promising compounds that could potentially be utilized for the treatment of cancer. The most prevalent phytochemical components identified and isolated from this plant are alkaloids, phenols, and acetogenins. This review focuses on the role of A. muricata extract against various types of cancer, modulation of cellular proliferation and necrosis, and bioactive metabolites responsible for various pharmacological activities along with their ethnomedicinal uses. Additionally, this review highlights the molecular mechanism of the role of A. muricata extract in downregulating anti-apoptotic and several genes involved in the pro-cancer metabolic pathways and decreasing the expression of proteins involved in cell invasion and metastasis while upregulating proapoptotic genes and genes involved in the destruction of cancer cells. Therefore, the active phytochemicals identified in A. muricata have the potential to be employed as a promising anti-cancer agent.
    Keywords:  Annona muricata; anticancer activity; bioactive metabolites; ethnomedicinal; pharmacological activities
    DOI:  https://doi.org/10.3390/cancers14184539
  109. Front Immunol. 2022 ;13 937406
    Targeting lipid metabolism reprogramming of immunocytes in response to the tumor microenvironment stressor: A potential approach for tumor therapy.
    Ming Zhang, Tingju Wei, Xiaodan Zhang, Danfeng Guo.
      The tumor microenvironment (TME) has become a major research focus in recent years. The TME differs from the normal extracellular environment in parameters such as nutrient supply, pH value, oxygen content, and metabolite abundance. Such changes may promote the initiation, growth, invasion, and metastasis of tumor cells, in addition to causing the malfunction of tumor-infiltrating immunocytes. As the neoplasm develops and nutrients become scarce, tumor cells transform their metabolic patterns by reprogramming glucose, lipid, and amino acid metabolism in response to various environmental stressors. Research on carcinoma metabolism reprogramming suggests that like tumor cells, immunocytes also switch their metabolic pathways, named "immunometabolism", a phenomenon that has drawn increasing attention in the academic community. In this review, we focus on the recent progress in the study of lipid metabolism reprogramming in immunocytes within the TME and highlight the potential target molecules, pathways, and genes implicated. In addition, we discuss hypoxia, one of the vital altered components of the TME that partially contribute to the initiation of abnormal lipid metabolism in immune cells. Finally, we present the current immunotherapies that orchestrate a potent antitumor immune response by mediating the lipid metabolism of immunocytes, highlight the lipid metabolism reprogramming capacity of various immunocytes in the TME, and propose promising new strategies for use in cancer therapy.
    Keywords:  immunocyte; immunometabolism; immunotherapy; lipid metabolism reprogramming; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2022.937406
  110. Front Pharmacol. 2022 ;13 902551
    Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations.
    Çiğdem Yücel, Gökçe Şeker Karatoprak, Özlem Bahadır Açıkara, Esra Küpeli Akkol, Timur Hakan Barak, Eduardo Sobarzo-Sánchez, Michael Aschner, Samira Shirooie.
      Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined.
    Keywords:  Zingiber officinale; cytokine; ginger; gingerol; immunomodulatory
    DOI:  https://doi.org/10.3389/fphar.2022.902551
  111. Antioxidants (Basel). 2022 Aug 24. pii: 1644. [Epub ahead of print]11(9):
    The Importance of Antioxidant Biomaterials in Human Health and Technological Innovation: A Review.
    Alessandra Cristina Pedro, Oscar Giordani Paniz, Isabela de Andrade Arruda Fernandes, Débora Gonçalves Bortolini, Fernanda Thaís Vieira Rubio, Charles Windson Isidoro Haminiuk, Giselle Maria Maciel, Washington Luiz Esteves Magalhães.
      Biomaterials come from natural sources such as animals, plants, fungi, algae, and bacteria, composed mainly of protein, lipid, and carbohydrate molecules. The great diversity of biomaterials makes these compounds promising for developing new products for technological applications. In this sense, antioxidant biomaterials have been developed to exert biological and active functions in the human body and industrial formulations. Furthermore, antioxidant biomaterials come from natural sources, whose components can inhibit reactive oxygen species (ROS). Thus, these materials incorporated with antioxidants, mainly from plant sources, have important effects, such as anti-inflammatory, wound healing, antitumor, and anti-aging, in addition to increasing the shelf-life of products. Aiming at the importance of antioxidant biomaterials in different technological segments as biodegradable, economic, and promising sources, this review presents the main available biomaterials, antioxidant sources, and assigned biological activities. In addition, potential applications in the biomedical and industrial fields are described with a focus on innovative publications found in the literature in the last five years.
    Keywords:  antioxidant biomaterials; biological properties; technological applications
    DOI:  https://doi.org/10.3390/antiox11091644
  112. Chin Herb Med. 2021 Jan;13(1): 78-89
    Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen).
    Ruo-Ning Wang, Hua-Cong Zhao, Jian-Yu Huang, Hong-Lan Wang, Jun-Song Li, Yin Lu, Liu-Qing Di.
      Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.
    Keywords:  Salvia miltiorrhiza Bunge; Salviae Miltiorrhizae Radix et Rhizoma; active ingredients; challenges and strategies; drug delivery systems; traditional Chinese medicines
    DOI:  https://doi.org/10.1016/j.chmed.2020.08.001
  113. Nutrients. 2022 Sep 16. pii: 3828. [Epub ahead of print]14(18):
    Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.
    Dvya Delilaa Clarence, Keshav Raj Paudel, Bikash Manandhar, Sachin Kumar Singh, Hari Prasad Devkota, Jithendra Panneerselvam, Vivek Gupta, Nitin Chitranshi, Nitin Verma, Sonia Saad, Gaurav Gupta, Philip Michael Hansbro, Brian Gregory Oliver, Thiagarajan Madheswaran, Kamal Dua, Dinesh Kumar Chellappan.
      Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.
    Keywords:  functional foods; inflammation; nanoparticles; pulmonary; respiratory diseases
    DOI:  https://doi.org/10.3390/nu14183828
  114. Pharmaceutics. 2022 Aug 23. pii: 1760. [Epub ahead of print]14(9):
    Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine.
    Han Wu, Ming-Da Wang, Jia-Qi Zhu, Zhen-Li Li, Wan-Yin Wang, Li-Hui Gu, Feng Shen, Tian Yang.
      Primary liver cancer is the seventh-most-common cancer worldwide and the fourth-leading cause of cancer mortality. In the current era of precision medicine, the diagnosis and management of liver cancer are full of challenges and prospects. Mesoporous nanoparticles are often designed as specific carriers of drugs and imaging agents because of their special morphology and physical and chemical properties. In recent years, the design of the elemental composition and morphology of mesoporous nanoparticles have greatly improved their drug-loading efficiency, biocompatibility and biodegradability. Especially in the field of primary liver cancer, mesoporous nanoparticles have been modified as highly tumor-specific imaging contrast agents and targeting therapeutic medicine. Various generations of complexes and structures have been determined for the complicated clinical management requirements. In this review, we summarize these advanced mesoporous designs in the different diagnostic and therapeutic fields of liver cancer and discuss the relevant advantages and disadvantages of transforming applications. By comparing the material properties, drug-delivery characteristics and application methods of different kinds of mesoporous materials in liver cancer, we try to help determine the most suitable drug carriers and information media for future clinical trials. We hope to improve the fabrication of biomedical mesoporous nanoparticles and provide direct evidence for specific cancer management.
    Keywords:  liver cancer; mesoporous nanoparticles; nanotechnology; precise medicine; tumor diagnosis
    DOI:  https://doi.org/10.3390/pharmaceutics14091760
  115. Nanoscale Adv. 2022 Mar 15. 4(6): 1668-1680
    Graphene-based phenformin carriers for cancer cell treatment: a comparative study between oxidized and pegylated pristine graphene in human cells and zebrafish.
    Abdelnour Alhourani, Jan-Lukas Førde, Mojdeh Nasrollahzadeh, Lutz Andreas Eichacker, Lars Herfindal, Hanne Røland Hagland.
      Graphene is an attractive choice for the development of an effective drug carrier in cancer treatment due to its high adsorption area and pH-responsive drug affinity. In combination with the highly potent metabolic drug phenformin, increased doses could be efficiently delivered to cancer cells. This study compares the use of graphene oxide (GO) and polyethylene glycol stabilized (PEGylated) pristine graphene nanosheets (PGNSs) for drug delivery applications with phenformin. The cytotoxicity and mitotoxicity of the graphene-based systems were assessed in human cells and zebrafish larvae. Targeted drug release from GO and PGNSs was evaluated at different pH levels known to arise in proliferating tumor microenvironments. PGNSs were less cytotoxic and mitotoxic than GO, and showed an increased release of phenformin at lower pH in cells, compared to GO. In addition, the systemic phenformin effect was mitigated in zebrafish larvae when bound to GO and PGNSs compared to free phenformin, as measured by flavin metabolic lifetime imaging. These results pave the way for improved phenformin-based cancer therapy using graphene nano-sheets, where PGNSs were superior to GO.
    DOI:  https://doi.org/10.1039/d1na00778e
  116. Pharmaceutics. 2022 Aug 25. pii: 1773. [Epub ahead of print]14(9):
    Biopolymeric Prodrug Systems as Potential Antineoplastic Therapy.
    Adriana Aurelia Chis, Anca Maria Arseniu, Claudiu Morgovan, Carmen Maximiliana Dobrea, Adina Frum, Anca Maria Juncan, Anca Butuca, Steliana Ghibu, Felicia Gabriela Gligor, Luca Liviu Rus.
      Nowadays, cancer represents a major public health issue, a substantial economic issue, and a burden for society. Limited by numerous disadvantages, conventional chemotherapy is being replaced by new strategies targeting tumor cells. In this context, therapies based on biopolymer prodrug systems represent a promising alternative for improving the pharmacokinetic and pharmacologic properties of drugs and reducing their toxicity. The polymer-directed enzyme prodrug therapy is based on tumor cell targeting and release of the drug using polymer-drug and polymer-enzyme conjugates. In addition, current trends are oriented towards natural sources. They are biocompatible, biodegradable, and represent a valuable and renewable source. Therefore, numerous antitumor molecules have been conjugated with natural polymers. The present manuscript highlights the latest research focused on polymer-drug conjugates containing natural polymers such as chitosan, hyaluronic acid, dextran, pullulan, silk fibroin, heparin, and polysaccharides from Auricularia auricula.
    Keywords:  Auricularia auricula polysaccharides; PDEPT; antineoplastic therapy; biopolymer; chitosan; dextran; heparin; hyaluronic acid; prodrug systems; pullulan; silk fibroin
    DOI:  https://doi.org/10.3390/pharmaceutics14091773
  117. Pharmaceutics. 2022 Sep 08. pii: 1909. [Epub ahead of print]14(9):
    Nano-Formulation Based Intravesical Drug Delivery Systems: An Overview of Versatile Approaches to Improve Urinary Bladder Diseases.
    Muhammad Sarfraz, Shaista Qamar, Masood Ur Rehman, Muhammad Azam Tahir, Muhammad Ijaz, Anam Ahsan, Mulazim Hussain Asim, Imran Nazir.
      Intravesical drug delivery is a direct drug delivery approach for the treatment of various bladder diseases. The human urinary bladder has distinctive anatomy, making it an effective barrier against any toxic agent seeking entry into the bloodstream. This screening function of the bladder derives from the structure of the urothelium, which acts as a semi-permeable barrier. However, various diseases related to the urinary bladder, such as hyperactive bladder syndrome, interstitial cystitis, cancer, urinary obstructions, or urinary tract infections, can alter the bladder's natural function. Consequently, the intravesical route of drug delivery can effectively treat such diseases as it offers site-specific drug action with minimum side effects. Intravesical drug delivery is the direct instillation of medicinal drugs into the urinary bladder via a urethral catheter. However, there are some limitations to this method of drug delivery, including the risk of washout of the therapeutic agents with frequent urination. Moreover, due to the limited permeability of the urinary bladder walls, the therapeutic agents are diluted before the process of permeation, and consequently, their efficiency is compromised. Therefore, various types of nanomaterial-based delivery systems are being employed in intravesical drug delivery to enhance the drug penetration and retention at the targeted site. This review article covers the various nanomaterials used for intravesical drug delivery and future aspects of these nanomaterials for intravesical drug delivery.
    Keywords:  dendrimers; intravesical delivery; liposomes; nanomaterial; targeted delivery
    DOI:  https://doi.org/10.3390/pharmaceutics14091909
  118. Nutrients. 2022 Sep 15. pii: 3805. [Epub ahead of print]14(18):
    Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review.
    Anna Mazur, Katarzyna Koziorowska, Klaudia Dynarowicz, David Aebisher, Dorota Bartusik-Aebisher.
      Photodynamic therapy is an unconventional yet increasingly common method of treating dermatological diseases and cancer that is implemented more often in adults than in children. Current clinical uses include treatment of actinic keratosis, superficial basal cell carcinomas, and acne. Despite its high efficiency, photodynamic therapy support supplements have recently been reported in the literature, including calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, and vitamin D3 cholecalciferol. In clinical trials, photodynamic therapy enhanced with vitamin D or D3 supplementation has been reported for treatment of squamous cell skin cancers, actinic keratosis, and psoriasis. Experimental research on the effect of photodynamic therapy with vitamin D or D3 has also been carried out in breast cancer cell lines and in animal models. The aim of this review is to evaluate the usefulness and effectiveness of vitamin D and D3 as supports for photodynamic therapy. For this purpose, the Pubmed and Scopus literature databases were searched. The search keyword was: "vitamin D in photodynamic therapy". In the analyzed articles (1979-2022), the authors found experimental evidence of a positive effect of vitamin D and D3 when used in conjunction with photodynamic therapy. An average of 6-30% (in one case, up to 10 times) increased response to photodynamic therapy was reported in combination with vitamin D and D3 as compared to photodynamic therapy alone. Implementing vitamin D and D3 as a supplement to photodynamic therapy is promising and may lead to further clinical trials and new clinical methodologies.
    Keywords:  calcitriol; cancer treatment; photodynamic therapy; topical application
    DOI:  https://doi.org/10.3390/nu14183805
  119. Cancers (Basel). 2022 Sep 10. pii: 4402. [Epub ahead of print]14(18):
    Neuroendocrine Tumors: A Comprehensive Review on Nutritional Approaches.
    NIKE
      Neuroendocrine neoplasms are a heterogeneous group of neoplasms with increasing incidence, high prevalence, and survival worldwide. About 90% of cases are well differentiated forms, the so-called neuroendocrine tumors (NETs), with slow proliferation rates and prolonged survival but frequent development of liver metastases and endocrine syndromes. Both the tumor itself and systemic therapy may have an impact on patient nutrition. Malnutrition has a negative impact on outcome in patients with NETs, as well as obesity. In addition, obesity and metabolic syndrome have been shown to be risk factors for both the development and prognosis of NET. Therefore, dietary assessment based on body composition and lifestyle modifications should be an integral part of the treatment of NET patients. Nutrition plans, properly formulated by a dietician, are an integral part of the multidisciplinary treatment team for patients with NETs because they allow an improvement in quality of life, providing a tailored approach based on nutritional needs and nutritional manageable signs and/or symptoms related to pharmacological treatment. The aim of this review is to condense the latest evidence on the role of the most used dietary models, the Mediterranean diet, the ketogenic diet, and intermittent fasting, in the context of NETs, while considering the clinical and molecular mechanisms by which these dietary models act.
    Keywords:  Mediterranean diet; cancer; diet; fasting; ketogenic diet; neuroendocrine neoplasms; neuroendocrine tumors
    DOI:  https://doi.org/10.3390/cancers14184402
  120. Front Med Technol. 2022 ;4 997123
    Applications of nanomaterials for gastrointestinal tumors: A review.
    Rahul Kanaoujiya, Dipiti Porwal, Shekhar Srivastava.
      Nanotechnology is the emerging and advance field of research for the diagnosis and treatment of various diseases. With the development of nanotechnology, different nanoparticles are used in the treatment of cancer due to their unique optical properties, excellent biocompatibility, surface effects, and small size effects. Nanoparticles are the particles which have the particular size from 1 to 100 nm. These nanoparticles are zero dimension, one dimension, two dimension and three dimension etc. In present scenario a variety of research is focused on the tailored synthesis of nanoparticles for medicinal applications that can be used for cancer treatment based on the morphology, composition, interaction with target cell. The gastrointestinal (GI) tumors are found one of the deadest cancer types with highest reoccurrence rates. The diagnosis and treatment of gastrointestinal cancer is very challenging due to its deep location and complicated surgery. Nanotechnology provides fast diagnosis and immediate treatment for the gastrointestinal disease. A variety of nanomaterials are used for the diagnosis and treatment of GI disease. Nanoparticles target directly to the tumor cell as diagnostic and therapeutic tools facilitating the identification and removal of tumor cells. A number of nanoparticles are developed for the uses are quantum dots (QDs), carbon nanotubes (CNTs), metallic nanoparticles (MNPs), Dendrimers etc. This review article gives an overview of the most promising nanomaterials used for the diagnosis and treatment of GI diseases. This review attempts to incorporate numerous uses for the most current nanomaterials, which have great potential for treating gastrointestinal diseases.
    Keywords:  carbon nanotubes; dendrimers; gastric cancer; gastrointestinal; iron oxide nanoparticles; nanoshells; nanotechnology; quantum dots
    DOI:  https://doi.org/10.3389/fmedt.2022.997123
  121. Pharmaceutics. 2022 Sep 13. pii: 1929. [Epub ahead of print]14(9):
    Preparation, Characterization and Pharmacokinetics of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles.
    Wei Xu, Zhaoyou Deng, Yifei Xiang, Dujuan Zhu, Dandan Yi, Yihao Mo, Yu Liu, Lanqian Qin, Ling Huang, Bingjie Wan, Liqin Wu, Xin Feng, Jiakang He.
      The clinical use of nonsteroidal anti-inflammatory drugs is limited by their poor water solubility, unstable absorption, and low bioavailability. Solid lipid nanoparticles (SLNs) exhibit high biocompatibility and the ability to improve the bioavailability of drugs with low water solubility. Therefore, in this study, a tolfenamic acid solid lipid nanoparticle (TA-SLN) suspension was prepared by a hot melt-emulsification ultrasonication method to improve the sustained release and bioavailability of TA. The encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), and zeta potential of the TA-SLN suspension were 82.50 ± 0.63%, 25.13 ± 0.28%, 492 ± 6.51 nm, 0.309 ± 0.02 and -21.7 ± 0.51 mV, respectively. The TA-SLN suspension was characterized by dynamic light scattering (DLS), fluorescence microscopy (FM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The TA-SLN suspension showed improved sustained drug release in vitro compared with the commercially available TA injection. After intramuscular administration to pigs (4 mg/kg), the TA-SLN suspension displayed increases in the pharmacokinetic parameters Tmax, T1/2, and MRT0-∞ by 4.39-, 3.78-, and 3.78-fold, respectively, compared with TA injection, and showed a relative bioavailability of 185.33%. Thus, this prepared solid lipid nanosuspension is a promising new formulation.
    Keywords:  bioavailability; solid lipid nanoparticles; suspension; sustained release; tolfenamic acid
    DOI:  https://doi.org/10.3390/pharmaceutics14091929
  122. Pharm Dev Technol. 2022 Sep 21. 1-11
    Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route.
    Hezhong Ouyang, Jinquan Hu, XingYing Qiu, Shaochang Wu, Fudong Guo, Youguo Tan.
      This study aims to develop, characterize, and examine olanzapine-loaded solid lipid nanocarriers (OLAN-SLNs) for effective brain delivery. OLAN has poor water solubility and low penetration through blood-brain barrier (BBB). Herein, OLAN-SLNs were fabricated using high-pressure homogenization (HPH) method followed by their investigation for particle properties. Moreover, in vitro release and in vivo pharmacokinetics profiles of OLAN-SLNs were compared with pure drug. Anti-psychotic activity was performed in LPS-induced psychosis mice model. Furthermore, expressions of the COX-2 and NF-κB were measured trailed by histopathological examination. The optimized formulation demonstrated nanoparticle size (149.1 nm) with rounded morphology, negative zeta potential (-28.9 mV), lower PDI (0.334), and excellent entrapment efficiency (95%). OLAN-SLNs significantly retarded the drug release and showed sustained release pattern as compared to OLAN suspension. Significantly enhanced bioavailability (ninefold) was demonstrated in OLAN-SLNs when compared with OLAN suspension. Behavioral tests showed significantly less immobility and more struggling time in OLAN-SLNs treated mice group. Additionally, reduced expression of COX-2 and -NF κB in brain was found. Altogether, it can be concluded that SLNs have the potential to deliver active pharmaceutical ingredients to brain, most importantly to enhance their bioavailability and antipsychotic effect, as indicated for OLAN in this study.
    Keywords:  LPS-induced psychosis; Olanzapine; anti-depressant activity; anti-psychotic activity; brain delivery; solid lipid nanocarriers
    DOI:  https://doi.org/10.1080/10837450.2022.2124521
  123. Antioxidants (Basel). 2022 Aug 27. pii: 1676. [Epub ahead of print]11(9):
    Nanocarrier System: State-of-the-Art in Oral Delivery of Astaxanthin.
    Nur Rafiqah Abdol Wahab, Meor Mohd Redzuan Meor Mohd Affandi, Sharida Fakurazi, Ekram Alias, Haniza Hassan.
      Astaxanthin (3,3'-dihydroxy-4,4'-diketo-β-β carotene), which belongs to the xanthophyll class, has shown potential biological activity in in vitro and in vivo models including as a potent antioxidant, anti-lipid peroxidation and cardiovascular disease prevention agent. It is mainly extracted from an alga, Haematococcus pluvialis. As a highly lipid-soluble carotenoid, astaxanthin has been shown to have poor oral bioavailability, which limits its clinical applications. Recently, there have been several suggestions and the development of various types of nano-formulation, loaded with astaxanthin to enhance their bioavailability. The employment of nanoemulsions, liposomes, solid lipid nanoparticles, chitosan-based and PLGA-based nanoparticles as delivery vehicles of astaxanthin for nutritional supplementation purposes has proven a higher oral bioavailability of astaxanthin. In this review, we highlight the pharmacological properties, pharmacokinetics profiles and current developments of the nano-formulations of astaxanthin for its oral delivery that are believed to be beneficial for future applications. The limitations and future recommendations are also discussed in this review.
    Keywords:  antioxidants; astaxanthin; bioavailability; carotenoids; nanoparticles; oral delivery; reactive oxygen species
    DOI:  https://doi.org/10.3390/antiox11091676
  124. Metabolites. 2022 Aug 28. pii: 806. [Epub ahead of print]12(9):
    Nutraceutical Properties of Medicago sativa L., Agave spp., Zea mays L. and Avena sativa L.: A Review of Metabolites and Mechanisms.
    Tannia A Quiñones-Muñoz, Socorro J Villanueva-Rodríguez, Juan G Torruco-Uco.
      Plants are the main sources of bioactive compounds (nutraceuticals) that function under different mechanisms of action for the benefit of human health. Mexico ranks fifth in the world in biodiversity, offering opportunities for healthy food. An important variety of crops are produced in the state of Hidalgo, e.g., based on the 2021 production, alfalfa, oats, maguey, and corn. The present review presents the latest findings of these crops, regarding the benefits they provide to health (bioactivity, nutraceuticals), and presents the compounds and mechanisms identified by which the benefit is provided. The knowledge compiled here is for the benefit of the recovery of the crops, the recognition of their bioactivities, in search of identifying the best routes of action for prevention, treatment and possible cure of chronic degenerative diseases (thereby promoting crop valorization). Exhaustive bibliographic research was carried out by means of engines and scientific databases. Articles published between 2001 and 2022 that included specific keywords (Scopus, EMBASE, EBSCO, PubMed, Science Direct, Web of Science, Google Scholar). Outstanding activities have been identified for the compounds in the crops, such as antiinflammatory, anticholesterolemic, antihypertensive, antidiabetic, anticancer, antimicrobial, antioxidant, and chelating. The compounds that provide these properties are total phenols, phenolic acids, tannins, anthocyanins, carotenoids, iso-flavones, phytosterols, saponins, fructans, glycosides, glucans, avenanthramides, and polysaccharides.
    Keywords:  antioxidant compound; bioactive extracts; bioactivities; crops; functional food
    DOI:  https://doi.org/10.3390/metabo12090806
  125. Biomolecules. 2022 Sep 08. pii: 1263. [Epub ahead of print]12(9):
    Mucus-Penetrating Silk Fibroin-Based Nanotherapeutics for Efficient Treatment of Ulcerative Colitis.
    Dengchao Xie, Xin Zhou, Bo Xiao, Lian Duan, Zhenhua Zhu.
      Oral nanoparticles have been considered a prospective drug delivery carrier against ulcerative colitis (UC). To enhance the mucus-penetrating capacity and aqueous solubility, and strengthen the anti-inflammatory effect of resveratrol (RSV), we fabricated RSV-loaded silk fibroin-based nanoparticles with the functionalization of Pluronic F127 (PF-127). The obtained PF-127-functionalized RSV-loaded NPs had an average particle size around 170 nm, a narrow size distribution (polydispersity index &lt; 0.2), and negative zeta potential (-20.5 mV). Our results indicated that the introduction of PF-127 strengthened the mucus-penetrating property of NPs. In vitro studies suggested that NPs with PF-127 enhanced the suppression of the secretion of proinflammatory cytokine TNF-α and reactive oxygen species (ROS) from RAW 264.7 macrophages under lipopolysaccharide stimulation in comparison with other counterparts. According to the evaluation of macro symptoms and main inflammatory cytokines, we further report preferable therapeutic outcomes achieved by PF-127 functionalized-NP-treated dextran sulphate sodium (DSS) groups in the colitis model compared with blank silk fibroin NPs and RSV-loaded NPs without the functionalization of PF-127. Taken together, this work suggests that the fabricated PF-127 NPs via the oral route are promising and useful RSV-loaded nanocarriers for UC treatment.
    Keywords:  nanoparticles; resveratrol; silk fibroin; ulcerative colitis
    DOI:  https://doi.org/10.3390/biom12091263
  126. Pharmaceutics. 2022 Sep 08. pii: 1908. [Epub ahead of print]14(9):
    Injectable Hydrogel-Based Combination Cancer Immunotherapy for Overcoming Localized Therapeutic Efficacy.
    Jeongrae Kim, Yongwhan Choi, Dong-Hwee Kim, Hong Yeol Yoon, Kwangmeyung Kim.
      Various immunotherapeutic agents that can elicit antitumor immune responses have recently been developed with the potential for improved efficacy in treating cancer. However, insufficient delivery efficiency at the tumor site, along with severe side effects after systemic administration of these anticancer agents, have hindered their therapeutic application in cancer immunotherapy. Hydrogels that can be directly injected into tumor sites have been developed to help modulate or elicit antitumor responses. Based on the biocompatibility, degradability, and controllable mechanochemical properties of these injectable hydrogels, various types of immunotherapeutic agents, such as hydrophobic anticancer drugs, cytokines, antigens, and adjuvants, have been easily and effectively encapsulated, resulting in the successful elicitation of antitumor immune responses and the retention of long-term immunotherapeutic efficacy following administration. This review summarizes recent advances in combination immunotherapy involving injectable hydrogel-based chemoimmunotherapy, photoimmunotherapy, and radioimmunotherapy. Finally, we briefly discuss the current limitations and future perspectives on injectable hydrogels for the effective combination immunotherapy of tumors.
    Keywords:  cancer immunotherapy; drug delivery; injectable hydrogel
    DOI:  https://doi.org/10.3390/pharmaceutics14091908
  127. J Biotechnol. 2022 Sep 16. pii: S0168-1656(22)00218-8. [Epub ahead of print]
    Microalgae as a potential therapeutic drug candidate for neurodegenerative diseases.
    R P Parameswari, Thangavelu Lakshmi.
      Microalgae are highly photosynthetic unicellular organism that have increased demand in the recent days owing to the presence of valuable cellular metabolites. They are ubiquitous in terrestrial and aquatic habitats, rich in species diversity and are capable of generating significant biomass by efficiently using CO2, light and other nutrients like nitrogen, phosphate etc., The microalgal biomass has upsurged in economic potential and is used as both food and feed in many countries across the world, accounting for more than 75% of annual microalgal biomass production in the past decades. The microalgal cells are sustainable resource that synthesize various secondary metabolites such as carotenoids, polysaccharides, polyphenols, essential amino acids, sterols, and polyunsaturated fatty acids (PUFA). Microalgae and its derived compounds possess significant pharmacological and biological effects such as antioxidant, anti-inflammatory, anti-cancer, immunomodulatory and anti-obesity. Because of their potential health promoting properties, the utilization of microalgae and its derived substances in food, pharmaceutical and cosmetic industries has skyrocketed in recent years. In this context, the current review discusses about the benefits of microalgae and its bioactive compounds against several neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS).
    Keywords:  Microalgae; anti-inflammatory; antioxidant; bioactive compounds; neuroprotection
    DOI:  https://doi.org/10.1016/j.jbiotec.2022.09.009
  128. AAPS PharmSciTech. 2022 Sep 22. 23(7): 262
    The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles.
    Wasfy M Obeidat, Shadi F Gharaibeh, Abdolelah Jaradat.
      Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.
    Keywords:  chitosan; entrapment efficiency; mean particle diameter; solubility; zeta potential
    DOI:  https://doi.org/10.1208/s12249-022-02420-8
  129. Front Pharmacol. 2022 ;13 990475
    Curcumin against gastrointestinal cancer: A review of the pharmacological mechanisms underlying its antitumor activity.
    Yuanyuan Fan, Xiqin Zhang, Yuxin Tong, Suning Chen, Jingjing Liang.
      Gastrointestinal cancer (GIC) poses a serious threat to human health globally. Curcumin (CUR), a hydrophobic polyphenol extracted from the rhizome of Curcuma longa, has shown reliable anticancer function and low toxicity, thereby offering broad research prospects. Numerous studies have demonstrated the pharmacological mechanisms underlying the effectiveness of CUR against GIC, including the induction of apoptosis and autophagy, arrest of the cell cycle, inhibition of the epithelial-mesenchymal transition (EMT) processes, inhibition of cell invasion and migration, regulation of multiple signaling pathways, sensitization to chemotherapy and reversal of resistance to such treatments, and regulation of the tumor survival environment. It has been confirmed that CUR exerts its antitumor effects on GIC through these mechanisms in vitro and in vivo. Moreover, treatment with CUR is safe and tolerable. Newly discovered types of regulated cell death (RCD), such as pyroptosis, necroptosis, and ferroptosis, may provide a new direction for research on the efficacy of CUR against GIC. In this review, we discuss the recently found pharmacological mechanisms underlying the effects of CUR against GIC (gastric and colorectal cancers). The objective is to provide a reference for further research on treatments against GIC.
    Keywords:  colorectal cancer; curcumin; gastric cancer; gastrointestinal cancer; pharmacological mechanism
    DOI:  https://doi.org/10.3389/fphar.2022.990475
  130. Biomed Pharmacother. 2022 Sep 16. pii: S0753-3322(22)01088-5. [Epub ahead of print]155 113699
    The antitumor properties of atractylenolides: Molecular mechanisms and signaling pathways.
    Yu Jiang, Kaibo Guo, Peipei Wang, Ying Zhu, Jiaqi Huang, Shanming Ruan.
      Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts.
    Keywords:  Anticancer phytochemical; Atractylenolides; Chinese herbal medicine
    DOI:  https://doi.org/10.1016/j.biopha.2022.113699
  131. J Food Biochem. 2022 Sep 19. e14406
    Preparation of Black pepper (Piper nigrum L.) essential oil nanoparticles and its antitumor activity on triple negative breast cancer in vitro.
    Mengying Zhang, Beibei Qiu, Mengjia Sun, Yunfei Wang, Meijiao Wei, Yanling Gong, Meixing Yan.
      The active compounds isolated from Black pepper have anticancer effects, but the bioactivity of Black pepper essential oil (BP-EO) is rarely studied. BP-EO has poor stability and a suitable dose form should be prepared for in vivo delivery. Triple negative breast cancer (TNBC) has attracted more and more attention due to its high mitotic index, high metastasis rate and poor prognosis. In this study, the composition of BP-EO was analyzed by gas chromatography-mass spectrometry (GC-MS), and nanoparticles (NPs) loaded with BP-EO were prepared by nanoprecipitation method using Eudragit L100 as a carrier. We investigated the preparation, characterization, stability and in vitro release of nanoparticles. MTT assay, cell wound healing, Transwell invasion assay and Western blot were used to study the anti-tumor effect and mechanism of MDA-MB-231 cells. The GC-MS analysis identified a total of 33 compounds among which alkenes account for 63.55%. The prepared BP-EO NPs exhibited nanoscale morphology, good stability and pH-responsive and sustained release character which is suitable for in vivo delivery. BP-EO NPs significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells. Furthermore, BP-EO NPs significantly inhibited the expressions of Wnt and β-catenin and significantly activated the expression of GSK-3β in MDA-MB-231 cells. Therefore, BP-EO NPs prepared in this study provide a new effective strategy for the treatment of TNBC. PRACTICAL APPLICATIONS: Black pepper is rich in essential oil and has excellent antioxidant and antibacterial activities. However, the anti-tumor activity of BP-EO has not been studied. In this study, we found that BP-EO has excellent anticancer activity. To achieve effective encapsulation of black pepper essential oil and an excellent anti-triple negative breast cancer activity, nanoparticles loaded with BP-EO were prepared using Eudragit L100 as the carrier by the nanoprecipitation method. The in vitro study revealed that BP-EO NPs inhibited proliferation, migration and invasion of MDA-MB-231 cells via inhibiting the Wnt/β-Catenin signaling pathway. This study provides new ideas and innovations for the treatment of invasive triple negative breast cancer in the future. At the same time, we will further reveal the application potential, pharmacokinetic characteristics and precise mechanism of BP-EO NPs in vivo in subsequent studies.
    Keywords:   Black pepper ; essential oil; nanoparticles; triple negative breast cancer
    DOI:  https://doi.org/10.1111/jfbc.14406
  132. ACS Appl Mater Interfaces. 2022 Sep 20.
    Developing a Versatile Multiscale Therapeutic Platform for Osteosarcoma Synergistic Photothermo-Chemotherapy with Effective Osteogenicity and Antibacterial Capability.
    Yunlong Ma, Lan Jiang, Jie Hu, Enjun Zhu, Nan Zhang.
      Osteosarcoma is a devastating malignant neoplasm that seriously threatens human health. After an osteosarcoma resection, the simultaneous treatment of tumor recurrence, postoperative infection, and large bone loss remains a formidable challenge clinically. Herein, a versatile multiscale therapeutic platform (Fs-BP-DOX@PDA) is engineered based on NiTi alloys with versatile properties for near-infrared (NIR)-mediated osteosarcoma synergistic photothermo-chemotherapy, bone regeneration, and bacterial elimination. First, an intriguing method for fabricating groovelike micro-nanostructures (Fs-NiTi) through femtosecond laser direct writing to enhance osseointegration with strong contact guidance is proposed. Then, black phosphorus (BP) nanosheets as gratifying photothermal conversion agents, osteogenetic agents, and a drug delivery platform are decorated on Fs-NiTi to construct multiscale hierarchical structures (Fs-BP). Finally, the polydopamine (PDA) modification is utilized to enhance the photothermal performance, biocompatibility, and chemical stability of doxorubicin (DOX)-loaded Fs-BP and endow NIR/pH-dual-responsive DOX release properties. Fs-BP-DOX@PDA effectively induces tumor cell (Saos-2 and MDA-MB-231) death in vitro, completely eradicates osteosarcoma in mice, and observably promotes bone-regeneration bioactivity. Furthermore, it possesses prominent antibacterial efficiencies toward Staphylococcus aureus (99.2%) and Pseudomonas aeruginosa (99.6%). Overall, this work presents a smart comprehensive fabrication methodology to construct a versatile multiscale therapeutic platform for multimodal osteosarcoma treatment and biomedical tissue engineering.
    Keywords:  bacterial elimination; bone-tissue engineering; femtosecond laser direct writing; osteosarcoma multimodal therapy; versatile multiscale therapeutic platform
    DOI:  https://doi.org/10.1021/acsami.2c10772
  133. Nanoscale Adv. 2022 Sep 13. 4(18): 3950-3956
    Nanozyme hydrogel for enhanced alkyl radical generation and potent antitumor therapy.
    Shipeng Ning, Zeming Liu, Mingzhu Chen, Daoming Zhu, Qinqin Huang.
      Alkyl radicals (R˙), which do not rely on oxygen generation for causing cellular stress, have been applied in tumor treatment, but a large amount of glutathione (GSH) in the tumor cells reacts with alkyl radicals, thereby reducing their antitumor effect. In this study, an enhanced alkyl radical generation system responsive to near-infrared light was designed. The alkyl radical trigger 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) and nanozyme pyrite (FeS2) were encapsulated in agarose hydrogel to prepare the AIPH-FeS2-hydrogel (AFH) system. FeS2 can be used as a photothermal agent to convert near-infrared light energy into heat energy, leading to the dissolution of the hydrogel. AIPH is simultaneously induced to produce alkyl radicals. FeS2 can also be used as an oxidative stress amplifier to reduce intracellular GSH content, thereby boosting the therapeutic effect of alkyl radicals. Eventually, the oxygen-independent free radicals generated by the AFH system under near-infrared laser irradiation and photothermal treatment can kill cancer cells through the synergistic oxidation/photothermal effect. The AFH system developed herein provides new insights into enhancing the therapeutic effect of alkyl radicals.
    DOI:  https://doi.org/10.1039/d2na00395c
  134. Photochem Photobiol. 2022 Sep 22.
    Photodynamic Therapy for Bladder Cancers, A Focused Review.
    Kazi Md Mahabubur Rahman, Prabhanjan Giram, Barbara A Foster, Youngjae You.
      Bladder cancer is first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers, and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle-invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non-muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but wasn't successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet-oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an in vivo setting without causing collateral damage to bladder function.
    Keywords:  Photodynamic therapy; bladder cancer; formulations; photodynamic diagnosis; photosensitizer
    DOI:  https://doi.org/10.1111/php.13726
  135. Pharmaceuticals (Basel). 2022 Sep 04. pii: 1103. [Epub ahead of print]15(9):
    The Impact of Dietary Consumption of Palm Oil and Olive Oil on Lipid Profile and Hepatocyte Injury in Hypercholesterolemic Rats.
    Tarfa Albrahim, Maram H M Alotaibi, Norah M M Altamimi, Atheer M A Albariqi, Lamees A O Alqarni, Sara N A Alassaf, Hisham S Aloudah, Mohammed Alahmed, Ahmad T Almnaizel, Maha R Aldraihem, Mona Alonazi.
      A metabolic disease called hypercholesterolemia is connected to both oxidative damage and inflammation. The goal of the current investigation was to determine if olive oil and palm oil could prevent hypercholesterolemia-induced oxidative stress in the liver of rats fed a high-cholesterol diet (HCD). The experimental mice were given HCD for three months while also receiving 0.5 mL/kg of either palm or olive oil. Serum triglycerides, total cholesterol, LDL cholesterol, vLDL cholesterol, and the atherogenic index all significantly increased in HCD-fed rats, while HDL cholesterol significantly dropped. Additionally, HCD caused a notable rise in proinflammatory cytokines and serum transaminases in liver tissue. Additionally, HCD significantly increased the production of nitric oxide and lipid peroxidation in the liver while decreasing antioxidant enzymes. Treatment with palm and olive oils dramatically reduced the levels of pro-inflammatory cytokines and lipid peroxidation, improved antioxidant defenses, and considerably improved liver function indicators. Additionally, the examined oils dramatically decreased the expression of fatty acid synthase (FAS) in the liver of rats receiving HCD. In conclusion, HCD-fed rats exhibit significant antihyperlipidemic and cholesterol-lowering benefits from palm and olive oils. The improved antioxidant defenses, lower inflammation and lipid peroxidation, and altered hepatic FAS mRNA expression were the main mechanisms by which palm and olive oils produced their advantageous effects.
    Keywords:  FAS; hypercholesterolemia; inflammation; olive oil; oxidative stress; palm oil
    DOI:  https://doi.org/10.3390/ph15091103
  136. Curr Oncol. 2022 Sep 18. 29(9): 6700-6713
    Immunogenic Cell Death Role in Urothelial Cancer Therapy.
    Reza Yadollahvandmiandoab, Mehrsa Jalalizadeh, Keini Buosi, Herney Andrés Garcia-Perdomo, Leonardo Oliveira Reis.
      PURPOSE: Bladder cancer is the 13th most common cause of cancer death with the highest lifetime cost for treatment of all cancers. This scoping review clarifies the available evidence on the role of a novel therapeutic approach called immunogenic cell death (ICD) in urothelial cancer of the bladder.METHODS: In accordance with the recommendations of the Joanna Briggs Institute, we searched MEDLINE (Ovid), EMBASE, CENTRAL databases, and supplemented with manual searches through the conferences, Google scholar, and clinicaltrials.gov for published studies up to April 2022. We included literature that studied molecular mechanisms of ICD and the role of certain danger-associated molecular patterns (DAMPs) in generating ICD, safety and efficacy of different ICD inducers, and their contributions in combination with other urothelial cancer treatments.
    RESULTS: Oncolytic viruses, radiotherapy, certain chemo/chemo radiation therapy combinations, photodynamic therapy, and novel agents were studied as ICD-inducing treatment modalities in the included studies. ICD was observed in vitro (murine or human urothelial carcinoma) in ten studies, eight studies were performed on mouse models (orthotopic or subcutaneous), and five clinical trials assessed patient response to ICD inducing agents. The most common studied DAMPs were Calreticulin, HMGB1, ATP, and Heat Shock Proteins (HSP) 70 and 90, which were either expressed on the cancer cells or released.
    CONCLUSION: ICD inducers were able to generate lasting antitumor immune responses with memory formation in animal studies (vaccination effect). In clinical trials these agents generally had low side effects, except for one trial, and could be used alone or in combination with other cancer treatment strategies in urothelial cancer patients.
    Keywords:  bladder cancer; immune checkpoint inhibitors; immunogenic cell death; immunotherapy; scoping review
    DOI:  https://doi.org/10.3390/curroncol29090526
  137. Antibiotics (Basel). 2022 Aug 25. pii: 1151. [Epub ahead of print]11(9):
    Formulation, In Vitro Characterization and Antibacterial Activity of Chitosan-Decorated Cream Containing Bacitracin for Topical Delivery.
    Rumana Zaib Khattak, Asif Nawaz, Maha Abdallah Alnuwaiser, Muhammad Shahid Latif, Sheikh Abdur Rashid, Asghar Ali Khan, Soha A Alamoudi.
      (1) Background: Bacitracin is a broad spectrum antibiotic that is used against various microorganisms. Chitosan is a natural polymer that has been widely investigated as an antimicrobial agent for preventing and treating infections owing to its intrinsic antimicrobial properties, as well as its ability to effectively deliver extrinsic antimicrobial compounds to infected areas. Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of administered compounds/drugs. The topical use of chitosan-decorated bacitracin-loaded cream improves the permeation of the drug across the skin and enhances the drug bioavailability by prolonging the residence time of the drug when applied topically, as well as producing synergistic effects and reducing the side effects of the drug. Topical chitosan-decorated cream can be a promising approach to administer the drug more efficiently and enhance the efficacy of treatment in wound healing and antibacterial activity. (2) Methods: This study was conducted to prepare, assess and investigate the synergistic antibacterial activity of a chitosan-coated bacitracin cream. The results were compared to the antibacterial activity of simple bacitracin-loaded cream. The prepared cream was evaluated for various in vitro characteristics such as rheology, pH, viscosity, drug content and antibacterial activity studies. (3) Result: The formulations were found to be stable regarding color, liquefaction and phase separation at all accelerated conditions. It was observed that with time, substantial variations in the pH of the preparations were found. The introduction of chitosan results in controlled release of the drug from the formulations. The antibacterial activity of the formulated creams was assessed with the disc diffusion method against Staphylococcus aureus(ATCC),Escherichiacoli (STCC),Pseudomonas aeruginosa(ATCC) and Bacillus cereus(ATCC). The strains, E. coli, S. aureus, P. aeruginosa and B. cereus were susceptible to 50 µg chitosan-decorated bacitracin cream, showing inhibition zones of 10 ± 0.6, 34 ± 1.5, 31 ± 0.76 and 21 ± 2.02 mm, respectively. The zones of inhibition for simple bacitracin-loaded cream were significantly smaller than chitosan-decorated cream, at 2 ± 0.2, 28 ± 0.92, 15 ± 0.5 and 11 ± 1.25 mm (ANOVA; p &lt; 0.05), respectively. (4) Conclusion: It was observed that the zones of inhibition of simple bacitracin-loaded cream were significantly smaller than those of chitosan-decorated bacitracin-loaded cream. Chitosan synergistically improves the antimicrobial activity of bacitracin. Hence, the developed formulation was effective and should be considered as a suitable candidate for topical management of skin infections and wound healing.
    Keywords:  antibacterial activity; bacitracin; chitosan; cream; in vitro evaluation
    DOI:  https://doi.org/10.3390/antibiotics11091151
  138. Micromachines (Basel). 2022 Sep 01. pii: 1449. [Epub ahead of print]13(9):
    Supercritical Fluids and Nanoparticles in Cancer Therapy.
    Iolanda De Marco.
      Nanoparticles are widely used in the pharmaceutical industry due to their high surface-to-volume ratio. Among the many techniques used to obtain nanoparticles, those based on supercritical fluids ensure reduced dimensions, narrow particle size distributions, and a very low or zero solvent residue in the powders. This review focuses on using supercritical carbon dioxide-based processes to obtain the nanoparticles of compounds used for the treatment or prevention of cancer. The scientific literature papers have been classified into two groups: nanoparticles consisting of a single active principle ingredient (API) and carrier/API nanopowders. Various supercritical carbon dioxide (scCO2) based techniques for obtaining the nanoparticles were considered, along with the operating conditions and advantages and disadvantages of each process.
    Keywords:  anticancer effect; carrier-free nanoparticles; coprecipitated nanoparticles; in vitro and in vivo studies; supercritical carbon dioxide
    DOI:  https://doi.org/10.3390/mi13091449
  139. Pharmaceutics. 2022 Aug 29. pii: 1821. [Epub ahead of print]14(9):
    Preparation, Characterization, and Biological Evaluation of a Hydrophilic Peptide Loaded on PEG-PLGA Nanoparticles.
    Lisa Marinelli, Michele Ciulla, Jeffrey A S Ritsema, Cornelus F van Nostrum, Ivana Cacciatore, Marilisa Pia Dimmito, Ferdinando Palmerio, Giustino Orlando, Iole Robuffo, Rossella Grande, Valentina Puca, Antonio Di Stefano.
      The encapsulation of peptides and proteins in nanosystems has been extensively investigated for masking unfavorable biopharmaceutical properties, including short half-life and poor permeation through biological membranes. Therefore, the aim of this work was to encapsulate a small antimicrobial hydrophilic peptide (H-Ser-Pro-Trp-Thr-NH2, FS10) in PEG-PLGA (polyethylene glycol-poly lactic acid-co-glycolic acid) nanoparticles (Nps) and thereby overcome the common limitations of hydrophilic drugs, which because they facilitate water absorption suffer from rapid degradation. FS10 is structurally related to the well-known RNAIII inhibiting peptide (RIP) and inhibits S. aureus biofilm formation. Various parameters, including different method (double emulsion and nanoprecipitation), pH of the aqueous phase and polymeric composition, were investigated to load FS10 into PEG-PLGA nanoparticles. The combination of different strategies resulted in an encapsulation efficiency of around 25% for both the double emulsion and the nanoprecipitation method. It was found that the most influential parameters were the pH-which tailors the peptides charge-and the polymeric composition. FS10-PEG-PLGA nanoparticles, obtained under optimized parameters, showed size lower than 180 nm with zeta potential values ranging from -11 to -21 mV. In vitro release studies showed that the Nps had an initial burst release of 48-63%, followed by a continuous drug release up to 21 h, probably caused by the porous character of the Nps. Furthermore, transmission electron microscopy (TEM) analysis revealed particles with a spherical morphology and size of around 100 nm. Antimicrobial assay showed that the minimum inhibitory concentration (MIC) of the FS10-loaded Nps, against S. aureus strains, was lower (&gt;128 µg/mL) than that of the free FS10 (&gt;256 µg/mL). The main goal of this work was to develop polymeric drug delivery systems aiming at protecting the peptide from a fast degradation, thus improving its accumulation in the target site and increasing the drug-bacterial membrane interactions.
    Keywords:  PEG-PLGA; RNAIII inhibiting peptide; S. aureus biofilm; double emulsion; nanoprecipitation; polymeric nanoparticles; quorum sensing inhibitors
    DOI:  https://doi.org/10.3390/pharmaceutics14091821
  140. Biomed Pharmacother. 2022 Sep 20. pii: S0753-3322(22)01103-9. [Epub ahead of print]155 113714
    Current progress of nanomedicine for prostate cancer diagnosis and treatment.
    Jiang Zhao, Chi Zhang, Weihao Wang, Chen Li, Xupeng Mu, Kebang Hu.
      Prostate cancer (PCa) is the most common new cancer case and the second most fatal malignancy in men. Surgery, endocrine therapy, radiotherapy and chemotherapy are the main clinical treatment options for PCa. However, most prostate cancers can develop into castration-resistant prostate cancer (CRPC), and due to the invasiveness of prostate cancer cells, they become resistant to different treatments and activate tumor-promoting signaling pathways, thereby inducing chemoresistance, radioresistance, ADT resistance, and immune resistance. Nanotechnology, which can combine treatment with diagnostic imaging tools, is emerging as a promising treatment modality in prostate cancer therapy. Nanoparticles can not only promote their accumulation at the pathological site through passive targeting techniques for enhanced permeability and retention (EPR), but also provide additional advantages for active targeting using different ligands. This property results in a reduced drug dose to achieve the desired effect, a longer duration of action within the tumor and fewer side effects on healthy tissues. In addition, nanotechnology can create good synergy with radiotherapy, chemotherapy, thermotherapy, photodynamic therapy and gene therapy to enhance their therapeutic effects with greater scope, and reduce the resistance of prostate cancer. In this article, we intend to review and discuss the latest technologies regarding the use of nanomaterials as therapeutic and diagnostic tools for prostate cancer.
    Keywords:  Drug delivery systems; Nanotechnology; Prostate cancer; Theranostics
    DOI:  https://doi.org/10.1016/j.biopha.2022.113714
  141. Pharmaceutics. 2022 Sep 06. pii: 1886. [Epub ahead of print]14(9):
    Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles.
    Sakshi V Khairnar, Pritha Pagare, Aditya Thakre, Aswathy Rajeevan Nambiar, Vijayabhaskarreddy Junnuthula, Manju Cheripelil Abraham, Praveen Kolimi, Dinesh Nyavanandi, Sathish Dyawanapelly.
      Solid lipid nanoparticles (SLNs) are an alternate carrier system to liposomes, polymeric nanoparticles, and inorganic carriers. SLNs have attracted increasing attention in recent years for delivering drugs, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics. These nanocarriers have attracted industrial attention due to their ease of preparation, physicochemical stability, and scalability. These characteristics make SLNs attractive for manufacture on a large scale. Currently, several products with SLNs are in clinical trials, and there is a high possibility that SLN carriers will quickly increase their presence in the market. A large-scale manufacturing unit is required for commercial applications to prepare enough formulations for clinical studies. Furthermore, continuous processing is becoming more popular in the pharmaceutical sector to reduce product batch-to-batch differences. This review paper discusses some conventional methods and the rationale for large-scale production. It further covers recent progress in scale-up methods for the synthesis of SLNs, including high-pressure homogenization (HPH), hot melt extrusion coupled with HPH, microchannels, nanoprecipitation using static mixers, and microemulsion-based methods. These scale-up technologies enable the possibility of commercialization of SLNs. Furthermore, ongoing studies indicate that these technologies will eventually reach the pharmaceutical market.
    Keywords:  drug delivery; high-pressure homogenization; nanomedicines; scale-up; solid lipid nanoparticles
    DOI:  https://doi.org/10.3390/pharmaceutics14091886
  142. Chin Herb Med. 2021 Apr;13(2): 189-201
    Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of "same treatment for different diseases" in traditional Chinese medicine.
    Ru-Pu He, Zheng Jin, Ru-Yun Ma, Fang-di Hu, Jian-Ye Dai.
      Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine (TCM) theory. Codonopsis Radix (Codonopsis pilosula, Dangshen in Chinese) with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases", based on its common mechanism in the treatment of gastric diseases including gastric ulcer, gastritis and gastric cancer via network pharmacology research.Methods: Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer, gastritis and gastric cancer. The active components and their target proteins of Dangshen were integrated from TCMSP, BATMAN-TCM databases. The targets of gastric ulcer, gastritis and gastric cancer were collected through GeneCards, PubMed, TDD and DisGeNET Database. Through screening, the key components and the key targets of Dangshen in treating gastric ulcer, gastritis and gastric cancer were obtained. After KEGG pathway analysis and GO analysis, the important pathways and biological processes were analyzed.
    Results: Through data and literature mining, the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions. It was shown that Dangshen mainly acted on gastric ulcer, gastritis and gastric cancer through the overall regulation of the PI3K-AKT signaling pathway. With the development of the disease, it will gradually increase the control of inflammation through TNF, NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage. For tumorigenesis, it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells. In addition, Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer, gastritis and gastric cancer.
    Conclusion: Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer, gastritis and gastric cancer through multiple targets in multiple pathways, especially PI3K-AKT pathway and HIF-1 pathway. It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.
    Keywords:  Codonopsis Radix; gastric cancer; gastric ulcer; gastritis; network pharmacology; same treatment for different diseases; spleen-fortifying effect
    DOI:  https://doi.org/10.1016/j.chmed.2020.12.005
  143. Toxicol Appl Pharmacol. 2022 Sep 16. pii: S0041-008X(22)00391-X. [Epub ahead of print]454 116246
    Myricetin alleviates the formaldehyde-enhanced Warburg effect in tumor cells through inhibition of HIF-1α.
    Linyi Li, Huijuan Ma, Dan Li, Qi Shu, Tingqian Wang, Xiaodong Song, Huan Xu.
      Myricetin is a flavonoid widely-distributed in foods with many beneficial health effects, which has been marketed in health products. Formaldehyde is an environmental carcinogen which can enhance the Warburg effect through the induction of human hypoxia-inducible factor 1 subunit alpha (HIF-1α), the primary regulator of cellular glycolysis. HIF-1α was verified as an important target in lung and ovarian tumors, which was also identified as a receptor for myricetin via molecular docking. The reinforced HIF-1α signaling, the Warburg effect and T cell suppression induced by 50 μM formaldehyde in both A549 and Caov-3 cells were dose-dependently attenuated by myricetin from 20 to 100 μM, and the attenuative effects were diminished by the stabilization of HIF-1α with deferoxamine. Exposure to 2.0 mg/m3 formaldehyde also stimulated tumor growth and elevated HIF-1α expression in tumor tissues of A549 xenograft mice, which were also alleviated by oral administration of 100 mg/kg myricetin. These results demonstrated that myricetin alleviated formaldehyde-enhanced Warburg effect in tumor cells through HIF-1α inhibition, which could be further developed as a therapeutic or complementary agent for formaldehyde-induced carcinogenesis.
    Keywords:  Formaldehyde; Glycolysis; HIF-1α; Myricetin; Tumor microenvironment; Warburg effect
    DOI:  https://doi.org/10.1016/j.taap.2022.116246
  144. Antibiotics (Basel). 2022 Aug 26. pii: 1156. [Epub ahead of print]11(9):
    Coumarins as Fungal Metabolites with Potential Medicinal Properties.
    Olga M Tsivileva, Oleg V Koftin, Nina V Evseeva.
      Coumarins are a structurally varied set of 2H-chromen-2-one compounds categorized also as members of the benzopyrone group of secondary metabolites. Coumarin derivatives attract interest owing to their wide practical application and the unique reactivity of fused benzene and pyrone ring systems in molecular structure. Coumarins have their own specific fingerprints as antiviral, antimicrobial, antioxidant, anti-inflammatory, antiadipogenic, cytotoxic, apoptosis, antitumor, antitubercular, and cytotoxicity agents. Natural products have played an essential role in filling the pharmaceutical pipeline for thousands of years. Biological effects of natural coumarins have laid the basis of low-toxic and highly effective drugs. Presently, more than 1300 coumarins have been identified in plants, bacteria, and fungi. Fungi as cultivated microbes have provided many of the nature-inspired syntheses of chemically diverse drugs. Endophytic fungi bioactivities attract interest, with applications in fields as diverse as cancer and neuronal injury or degeneration, microbial and parasitic infections, and others. Fungal mycelia produce several classes of bioactive molecules, including a wide group of coumarins. Of promise are further studies of conditions and products of the natural and synthetic coumarins' biotransformation by the fungal cultures, aimed at solving the urgent problem of searching for materials for biomedical engineering. The present review evaluates the fungal coumarins, their structure-related peculiarities, and their future therapeutic potential. Special emphasis has been placed on the coumarins successfully bioprospected from fungi, whereas an industry demand for the same coumarins earlier found in plants has faced hurdles. Considerable attention has also been paid to some aspects of the molecular mechanisms underlying the coumarins' biological activity. The compounds are selected and grouped according to their cytotoxic, anticancer, antibacterial, antifungal, and miscellaneous effects.
    Keywords:  anticancer activity; antimicrobials; biosynthesis; coumarins; endophytes; fungal biotechnology; fungi; natural compounds; pathogenic bacteria; secondary metabolites
    DOI:  https://doi.org/10.3390/antibiotics11091156
  145. Pharmaceutics. 2022 Sep 05. pii: 1874. [Epub ahead of print]14(9):
    Peptide Shuttles for Blood-Brain Barrier Drug Delivery.
    Macarena Sánchez-Navarro, Ernest Giralt.
      The blood-brain barrier (BBB) limits the delivery of therapeutics to the brain but also represents the main gate for nutrient entrance. Targeting the natural transport mechanisms of the BBB offers an attractive route for brain drug delivery. Peptide shuttles are able to use these mechanisms to increase the transport of compounds that cannot cross the BBB unaided. As peptides are a group of biomolecules with unique physicochemical and structural properties, the field of peptide shuttles has substantially evolved in the last few years. In this review, we analyze the main classifications of BBB-peptide shuttles and the leading sources used to discover them.
    Keywords:  BBB–peptide shuttle; blood–brain barrier; brain delivery
    DOI:  https://doi.org/10.3390/pharmaceutics14091874
  146. ACS Omega. 2022 Sep 13. 7(36): 31651-31657
    Surface-Coated Cerium Nanoparticles to Improve Chemotherapeutic Delivery to Tumor Cells.
    Nilkamal Pramanik, Tamasa De, Preeti Sharma, Alakesh Alakesh, Sameer Kumar Jagirdar, Annapoorni Rangarajan, Siddharth Jhunjhunwala.
      The antioxidant property of cerium oxide nanoparticles has increased their demand as a nanocarrier to improve the delivery and therapeutic efficacy of anticancer drugs. Here, we report the synthesis of alginate-coated ceria nanoformulations (ceria NPs) and characterization using FTIR spectroscopy, Raman microscopy, and X-ray diffraction. The synthesized ceria NPs show negligible inherent in vitro toxicity when tested on a MDA-MB-231 breast cancer cell line at higher particle concentrations. Upon loading these particles with doxorubicin (Dox) and paclitaxel (PTX) drugs, we observe a potential synergistic cytotoxic effect mediated by the drug and the ceria NPs, resulting in the better killing capacity as well as suppression of cell migration against the MDA-MB-231 cell line. Further, to verify the immune-escaping capacity before targeting cancer cells, we coated the drug-loaded ceria NPs with the membrane of MDA-MB-231 cells using an extrusion method. The resultant delivery system exhibited in vitro preferential uptake by the MDA-MB-231 cell line and showed reduced uptake by the murine macrophage cell line (RAW 264.7), assigning its potential application as non-immunogenic personalized therapy in targeting and killing of cancer cells.
    DOI:  https://doi.org/10.1021/acsomega.2c00062
  147. Nanoscale Adv. 2022 Feb 01. 4(3): 634-653
    Revisiting the outstanding questions in cancer nanomedicine with a future outlook.
    M S Sudheesh, K Pavithran, Sabitha M.
      The field of cancer nanomedicine has been fueled by the expectation of mitigating the inefficiencies and life-threatening side effects of conventional chemotherapy. Nanomedicine proposes to utilize the unique nanoscale properties of nanoparticles to address the most pressing questions in cancer treatment and diagnosis. The approval of nano-based products in the 1990s inspired scientific explorations in this direction. However, despite significant progress in the understanding of nanoscale properties, there are only very few success stories in terms of substantial increase in clinical efficacy and overall patient survival. All existing paradigms such as the concept of enhanced permeability and retention (EPR), the stealth effect and immunocompatibility of nanomedicine have been questioned in recent times. In this review we critically examine impediments posed by biological factors to the clinical success of nanomedicine. We put forth current observations on critical outstanding questions in nanomedicine. We also provide the promising side of cancer nanomedicine as we move forward in nanomedicine research. This would provide a future direction for research in nanomedicine and inspire ongoing investigations.
    DOI:  https://doi.org/10.1039/d1na00810b
  148. Arch Dermatol Res. 2022 Sep 21.
    Flavonoids and their therapeutic applications in skin diseases.
    Emily Z Ma, Amor Khachemoune.
      Flavonoids are a class of plant polyphenols found in a variety of fruits, vegetables, teas, and flowers. These compounds are present in many common dietary sources, such as green tea, wine, pomegranates, and turmeric, and possess a broad spectrum of biological activity due to their unique chemical structure. Flavonoids exhibit antioxidant, anti-inflammatory, antiviral, and anticarcinogenic properties that have been widely studied as potential therapeutics for diseases ranging from Alzheimer's disease to liver disease. There is currently significant research into therapeutic benefits of flavonoids in various skin conditions as these compounds have been shown to absorb ultraviolet radiation and modulate cancer and inflammation signaling pathways. This review discusses the current research in the application of flavonoids in skin diseases (e.g., prevention of premature photoaging, prevention and treatment of skin cancer, and promotion of skin wound healing) and their proposed mechanisms to provide a basis for future basic and translational research of flavonoids as potential drugs in the prevention and treatment of skin disorders.
    Keywords:  Anti-inflammation; Antioxidant; Chemoprotection; Flavonoids; Photoprotection; Wound healing
    DOI:  https://doi.org/10.1007/s00403-022-02395-3
  149. Bioengineering (Basel). 2022 Sep 16. pii: 478. [Epub ahead of print]9(9):
    Advances in Nanofabrication Technology for Nutraceuticals: New Insights and Future Trends.
    Rachitha Puttasiddaiah, Rohitha Lakshminarayana, Nandini Lalithadripura Somashekar, Vijai Kumar Gupta, Baskaran Stephen Inbaraj, Zeba Usmani, Vinay Basavegowda Raghavendra, Kandi Sridhar, Minaxi Sharma.
      Bioactive components such as polyphenolics, flavonoids, bioactive peptides, pigments, and essential fatty acids were known to ward off some deadliest diseases. Nutraceuticals are those beneficial compounds that may be food or part of food that has come up with medical or health benefits. Nanoencapsulation and nanofabricated delivery systems are an imminent approach in the field of food sciences. The sustainable fabrication of nutraceuticals and biocompatible active components indisputably enhances the food grade and promotes good health. Nanofabricated delivery systems include carbohydrates-based, lipids (solid and liquid), and proteins-based delivery systems. Solid nano-delivery systems include lipid nanoparticles. Liquid nano-delivery systems include nanoliposomes and nanoemulsions. Physicochemical properties of nanoparticles such as size, charge, hydrophobicity, and targeting molecules affect the absorption, distribution, metabolism, and excretion of nano delivery systems. Advance research in toxicity studies is necessary to ensure the safety of the nanofabricated delivery systems, as the safety of nano delivery systems for use in food applications is unknown. Therefore, improved nanotechnology could play a pivotal role in developing functional foods, a contemporary concept assuring the consumers to provide programmed, high-priced, and high-quality research toward nanofabricated delivery systems.
    Keywords:  liposomes; nano-emulsions; nano-formulation; nanofabricated delivery system; nutraceuticals; prebiotics
    DOI:  https://doi.org/10.3390/bioengineering9090478
  150. Pharmaceuticals (Basel). 2022 Aug 31. pii: 1095. [Epub ahead of print]15(9):
    Medicinal Plants from Latin America with Wound Healing Activity: Ethnomedicine, Phytochemistry, Preclinical and Clinical Studies-A Review.
    Anuar Salazar-Gómez, Angel Josabad Alonso-Castro.
      Latin America is a multicultural region with ancient traditional medicine. There is extensive knowledge of the use of medicinal plants for wound healing in this region. Nevertheless, many of these medicinal plants lack pharmacological, toxicological, and chemical studies. This review focuses on the ethnomedicinal, phytochemical, and pharmacological (preclinical and clinical) studies of medicinal plants with wound healing activity, from Latin America. An electronic database search was conducted by consulting scientific articles and books. A total of 305 plant species with wound healing activity were recorded, based on traditional medicine. Most medicinal plants used in wound healing in Latin America are topically administered; their methods of preparation are mainly by water infusion from aerial parts. Only thirty-five percent of medicinal plants used in traditional medicine for wound healing have been experimentally validated for their pharmacological effects, and the wound healing activity of five medicinal plants has been studied in clinical trials. In all, 25 compounds (mostly terpenes and flavonoids) have been isolated from medicinal plants with wound healing activity; therefore, extensive work is necessary for a multidisciplinary approach to evaluate the wound healing effects of medicinal plants in Latin America. The mechanism of action of medicinal plants, their toxicological actions on the skin, and their bioactive compounds, have yet to be investigated. This review on the ethnomedicinal, phytochemical, and pharmacological studies, of medicinal plants from Latin America with wound healing activity, offers promising data for further studies, as well as providing new insights into their possible role in wound care.
    Keywords:  complementary medicine; medicinal plant; wound healing
    DOI:  https://doi.org/10.3390/ph15091095
  151. Chem Sci. 2022 Aug 31. 13(34): 9921-9926
    Ferroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.
    Yidan Lai, Nong Lu, Ai Ouyang, Qianling Zhang, Pingyu Zhang.
      Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)-cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (1O2) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. In vivo studies further demonstrate that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT in vivo. This is the first example of platinum(ii) complexes for sonodynamic therapy. This work extends the biological applications of metal complexes from PDT to SDT.
    DOI:  https://doi.org/10.1039/d2sc02597c
  152. J Nanobiotechnology. 2022 Sep 19. 20(1): 419
    Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis.
    Zengxin Jiang, Hao Wang, Zeng Zhang, Jianfeng Pan, Hengfeng Yuan.
      Targeting cartilage is a promising strategy for the treatment of osteoarthritis, and various delivery vehicles were developed to assist the therapeutic agents into cartilage. However, the underlying biomechanisms and potential bioactivities remain oversimplified. Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β. Then a functional reactive oxygen species (ROS) responsive nanocarrier, mesoporous silica nanoparticles (MSN) modified with methoxy polyethylene glycol-thioketal, was constructed. In vitro biomolecular results showed that compared with OL alone, MSN-OL could significantly activate Nrf2/HO-1 signaling pathway, which exhibited better ROS-scavenging proficiency and greater anti-apoptotic ability to protect mitochondrial membrane potential of chondrocytes. Further bioinformatics analysis revealed that MSN-OL suppressed clusters of genes associated with extracellular matrix organization, cell apoptosis and cellular response to oxidative stress. Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.
    Keywords:  Cartilage; Mesoporous silica nanoparticles; Nrf2; Reactive oxygen species; Thioketal
    DOI:  https://doi.org/10.1186/s12951-022-01629-w
  153. Molecules. 2022 Sep 19. pii: 6106. [Epub ahead of print]27(18):
    Chemical and Antimicrobial Characterization of Mentha piperita L. and Rosmarinus officinalis L. Essential Oils and In Vitro Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.
    Alina Dolghi, Dorina Coricovac, Stefania Dinu, Iulia Pinzaru, Cristina Adriana Dehelean, Cristina Grosu, Doina Chioran, Petru Eugen Merghes, Cristian Andrei Sarau.
      Colorectal cancer is one of the most frequently diagnosed forms of cancer, and the therapeutic solutions are frequently aggressive requiring improvements. Essential oils (EOs) are secondary metabolites of aromatic plants with important pharmacological properties that proved to be beneficial in multiple pathologies including cancer. Mentha piperita L. (M_EO) and Rosmarinus officinalis L. (R_EO) essential oils are well-known for their biological effects (antimicrobial, antioxidant, anti-inflammatory and cytotoxic in different cancer cells), but their potential as complementary treatment in colorectal cancer is underexplored. The aim of the present study was to investigate the M_EO and R_EO in terms of chemical composition, antioxidant, antimicrobial, and cytotoxic effects in a colorectal cancer cell line-HCT 116. The gas-chromatographic analysis revealed menthone and menthol, and eucalyptol, α-pinene and L-camphor as major compounds in M_EO and R_EO respectively. M_EO exhibited potent antimicrobial activity, moderate antioxidant activity and a low cytotoxic effect in HCT 116 cells. R_EO presented a significant cytotoxicity in colorectal cancer cells and a low antimicrobial effect. The cytotoxic effect on non-cancerous cell line HaCaT was not significant for both essential oils. These results may provide an experimental basis for further research concerning the potential use of M_EO and R_EO for anticancer treatment.
    Keywords:  Mentha piperita L. essential oil; Rosmarinus officinalis L. essential oil; antimicrobial potential; colorectal cancer; cytotoxicity
    DOI:  https://doi.org/10.3390/molecules27186106
  154. Front Cell Dev Biol. 2022 ;10 989471
    Exploring the role of nanomedicines for the therapeutic approach of central nervous system dysfunction: At a glance.
    Md Mominur Rhaman, Md Rezaul Islam, Shopnil Akash, Mobasharah Mim, Md Noor Alam, Eugenie Nepovimova, Martin Valis, Kamil Kuca, Rohit Sharma.
      In recent decades, research scientists, molecular biologists, and pharmacologists have placed a strong emphasis on cutting-edge nanostructured materials technologies to increase medicine delivery to the central nervous system (CNS). The application of nanoscience for the treatment of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), brain cancer, and hemorrhage has the potential to transform care. Multiple studies have indicated that nanomaterials can be used to successfully treat CNS disorders in the case of neurodegeneration. Nanomedicine development for the cure of degenerative and inflammatory diseases of the nervous system is critical. Nanoparticles may act as a drug transporter that can precisely target sick brain sub-regions, boosting therapy success. It is important to develop strategies that can penetrate the blood-brain barrier (BBB) and improve the effectiveness of medications. One of the probable tactics is the use of different nanoscale materials. These nano-based pharmaceuticals offer low toxicity, tailored delivery, high stability, and drug loading capacity. They may also increase therapeutic effectiveness. A few examples of the many different kinds and forms of nanomaterials that have been widely employed to treat neurological diseases include quantum dots, dendrimers, metallic nanoparticles, polymeric nanoparticles, carbon nanotubes, liposomes, and micelles. These unique qualities, including sensitivity, selectivity, and ability to traverse the BBB when employed in nano-sized particles, make these nanoparticles useful for imaging studies and treatment of NDs. Multifunctional nanoparticles carrying pharmacological medications serve two purposes: they improve medication distribution while also enabling cell dynamics imaging and pharmacokinetic study. However, because of the potential for wide-ranging clinical implications, safety concerns persist, limiting any potential for translation. The evidence for using nanotechnology to create drug delivery systems that could pass across the BBB and deliver therapeutic chemicals to CNS was examined in this study.
    Keywords:  blood-brain barrier; drug delivery; nanomedicine and nanocarrier; nanotechnology; neurodegenerative diseases
    DOI:  https://doi.org/10.3389/fcell.2022.989471
  155. Front Pharmacol. 2022 ;13 948889
    Antioxidant and neuroprotective actions of resveratrol in cerebrovascular diseases.
    Qing Wang, Qi Yu, Min Wu.
      Cerebralvascular diseases are the most common high-mortality diseases worldwide. Despite its global prevalence, effective treatments and therapies need to be explored. Given that oxidative stress is an important risk factor involved with cerebral vascular diseases, natural antioxidants and its derivatives can be served as a promising therapeutic strategy. Resveratrol (3, 5, 4'-trihydroxystilbene) is a natural polyphenolic antioxidant found in grape skins, red wine, and berries. As a phytoalexin to protect against oxidative stress, resveratrol has therapeutic value in cerebrovascular diseases mainly by inhibiting excessive reactive oxygen species production, elevating antioxidant enzyme activity, and other antioxidant molecular mechanisms. This review aims to collect novel kinds of literature regarding the protective activities of resveratrol on cerebrovascular diseases, addressing the potential mechanisms underlying the antioxidative activities and mitochondrial protection of resveratrol. We also provide new insights into the chemistry, sources, and bioavailability of resveratrol.
    Keywords:  anti-oxidant; neuroprotection; resveratrol; stroke; vascular dementia
    DOI:  https://doi.org/10.3389/fphar.2022.948889
  156. Oncologist. 2022 Sep 17. pii: oyac179. [Epub ahead of print]
    KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.
    Adam C Diehl, Lindsay M Hannan, David B Zhen, Andrew L Coveler, Gentry King, Stacey A Cohen, William P Harris, Veena Shankaran, Kit M Wong, Steven Green, Natasha Ng, Venu G Pillarisetty, Jonathan G Sham, James O Park, Deepti Reddi, Eric Q Konnick, Colin C Pritchard, Kelsey Baker, Mary Redman, E Gabriela Chiorean.
      BACKGROUND: KRAS variant alleles may have differential biological properties which impact prognosis and therapeutic options in pancreatic ductal adenocarcinomas (PDA).MATERIALS AND METHODS: We retrospectively identified patients with advanced PDA who received first-line therapy and underwent blood and/or tumor genomic sequencing at the University of Washington between 2013 and 2020. We examined the incidence of KRAS mutation variants with and without co-occurring PI3K or other genomic alterations and evaluated the association of these mutations with clinicopathological characteristics and survival using a Cox proportional hazards model.
    RESULTS: One hundred twenty-six patients had genomic sequencing data; KRAS mutations were identified in 111 PDA and included the following variants: G12D (43)/G12V (35)/G12R (23)/other (10). PI3K pathway mutations (26% vs. 8%) and homologous recombination DNA repair (HRR) defects (35% vs. 12.5%) were more common among KRAS G12R vs. non-G12R mutated cancers. Patients with KRAS G12R vs. non-G12R cancers had significantly longer overall survival (OS) (HR 0.55) and progression-free survival (PFS) (HR 0.58), adjusted for HRR pathway co-mutations among other covariates. Within the KRAS G12R group, co-occurring PI3K pathway mutations were associated with numerically shorter OS (HR 1.58), while no effect was observed on PFS.
    CONCLUSIONS: Patients with PDA harboring KRAS G12R vs. non-G12R mutations have longer survival, but this advantage was offset by co-occurring PI3K alterations. The KRAS/PI3K genomic profile could inform therapeutic vulnerabilities in patients with PDA.
    Keywords:  KRAS; PI3K; pancreatic cancer
    DOI:  https://doi.org/10.1093/oncolo/oyac179
  157. Vopr Pitan. 2022 ;91(4): 19-25
    [Arthrospira platensis: antioxidant, hypoglycemic and hypolipidemic effects in vitro and in vivo (brief review)].
    V K Mazo, N A Biryulina, Yu S Sidorova.
      The cyanobacterium Arthrospira platensis biomass is a promising food source of biologically active substances with pharmacological activity. The aim of this research was a brief review and analysis of experimental in vitro and in vivo studies of the antioxidant, hypoglycemic and hypolipidemic properties of A. platensis biomass, phycocyanins, and their chromophore - phycocyanobilin. Material and methods. For the main search of the literature, the PubMed Internet resource was used, the key component of which is the Medline article database, covering about 75% of the world's medical publications. In addition, Scopus and Web of Science databases were used. Search depth - 20 years. Search keywords: Arthrospira platensis, phycobiliprotein, C-phycocyanin, allophycocyanin, hypoglycemic effect, hypolipidemic effect, antioxidant activity, in vitro and in vivo studies. Results. A brief description of the composition of the cyanobacterium Arthrospira platensis biomass, methods of its cultivation, phycocyanins extraction methods is presented. The results of experimental studies indicate the presence of pronounced antioxidant properties of A. platensis biomass, mainly due to phycocyanins in its composition. The hypoglycemic and hypolipidemic effects of A. platensis biomass and extracted phycocyanins intake have been established in vivo when modeling carbohydrate and/or lipid metabolism disorders. The results of in vitro and in vivo studies indicate the presence of pronounced antioxidant properties of phycocyanins. Hypoglycemic effects are shown in particular in experiments on rats with hyperlipidemia and alloxan diabetes fed a diet enriched with A. platensis biomass and on KKAy mice, treated with C-phycocyanin extract. Conclusion. The analysis of the results of in vitro and in vivo studies of the antioxidant, hypoglycemic and hypolipidemic properties of A. platensis biomass and extracts with a high content of phycocyanins, presented in a brief review, suggests that their use in the diet of people with impaired carbohydrate and lipid metabolism is promising. Accordingly, from the standpoint of evidence-based medicine, clinical studies on the use of spirulina biomass and/or its extracts with a high content of phycocyanins as part of specialized foods intended for the prevention and/or dietary correction of carbohydrate and lipid metabolism disorders should be preceded by additional experimental physical-chemical, physiological and biochemical research.
    Keywords:  Arthrospira platensis; C-phycocyanin; allophycocyanin; antioxidants; hypoglycemic; hypolipidemic; phycobillyprotein
    DOI:  https://doi.org/10.33029/0042-8833-2022-91-4-19-25
  158. Int J Mol Sci. 2022 Sep 14. pii: 10680. [Epub ahead of print]23(18):
    Bioactive Compounds from Marine Sponges and Algae: Effects on Cancer Cell Metabolome and Chemical Structures.
    Roberta Esposito, Serena Federico, Francesca Glaviano, Emanuele Somma, Valerio Zupo, Maria Costantini.
      Metabolomics represent the set of small organic molecules generally called metabolites, which are located within cells, tissues or organisms. This new "omic" technology, together with other similar technologies (genomics, transcriptomics and proteomics) is becoming a widely used tool in cancer research, aiming at the understanding of global biology systems in their physiologic or altered conditions. Cancer is among the most alarming human diseases and it causes a considerable number of deaths each year. Cancer research is one of the most important fields in life sciences. In fact, several scientific advances have been made in recent years, aiming to illuminate the metabolism of cancer cells, which is different from that of healthy cells, as suggested by Otto Warburg in the 1950s. Studies on sponges and algae revealed that these organisms are the main sources of the marine bioactive compounds involved in drug discovery for cancer treatment and prevention. In this review, we analyzed these two promising groups of marine organisms to focus on new metabolomics approaches for the study of metabolic changes in cancer cell lines treated with chemical extracts from sponges and algae, and for the classification of the chemical structures of bioactive compounds that may potentially prove useful for specific biotechnological applications.
    Keywords:  algae; cancer; marine eukaryotes; metabolism; sponges
    DOI:  https://doi.org/10.3390/ijms231810680
  159. Pharmaceutics. 2022 Aug 25. pii: 1775. [Epub ahead of print]14(9):
    Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention.
    Haseeb Ahsan, Salman Ul Islam, Muhammad Bilal Ahmed, Young Sup Lee.
      Cancer is a complex and multistage disease that affects various intracellular pathways, leading to rapid cell proliferation, angiogenesis, cell motility, and migration, supported by antiapoptotic mechanisms. Chemoprevention is a new strategy to counteract cancer; to either prevent its incidence or suppress its progression. In this strategy, chemopreventive agents target molecules involved in multiple pathways of cancer initiation and progression. Nrf2, STAT3, and Src are promising molecular candidates that could be targeted for chemoprevention. Nrf2 is involved in the expression of antioxidant and phase II metabolizing enzymes, which have direct antiproliferative action as well as indirect activities of reducing oxidative stress and eliminating carcinogens. Similarly, its cross-talk with NF-κB has great anti-inflammatory potential, which can be utilized in inflammation-induced/associated cancers. STAT3, on the other hand, is involved in multiple pathways of cancer initiation and progression. Activation, phosphorylation, dimerization, and nuclear translocation are associated with tumor cell proliferation and angiogenesis. Src, being the first oncogene to be discovered, is important due to its convergence with many upstream stimuli, its cross-talk with other potential molecular targets, such as STAT3, and its ability to modify the cell cytoskeleton, making it important in cancer invasion and metastasis. Therefore, the development of natural/synthetic molecules and/or design of a regimen that can reduce oxidative stress and inflammation in the tumor microenvironment and stop multiple cellular targets in cancer to stop its initiation or retard its progression can form newer chemopreventive agents.
    Keywords:  NF κB; Nrf2; STAT3; Src; chemoprevention; inflammation
    DOI:  https://doi.org/10.3390/pharmaceutics14091775
  160. Micromachines (Basel). 2022 Sep 11. pii: 1508. [Epub ahead of print]13(9):
    Ultrasound-Responsive Nanocarriers for Breast Cancer Chemotherapy.
    Gelan Ayana, Jaemyung Ryu, Se-Woon Choe.
      Breast cancer is the most common type of cancer and it is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite chemotherapy's ample use, it has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target. In this paper, we review recent developments in ultrasound-guided nanocarriers for breast cancer chemotherapy, discuss the relevant challenges, and provide insights into future directions.
    Keywords:  breast cancer; chemotherapy; micro-/nano-bubbles; nanocarriers; ultrasound
    DOI:  https://doi.org/10.3390/mi13091508
  161. Int J Mol Sci. 2022 Sep 19. pii: 10975. [Epub ahead of print]23(18):
    Recent Advances of Chitosan Formulations in Biomedical Applications.
    Mohammed A S Abourehab, Sheersha Pramanik, Mohamed A Abdelgawad, Bassam M Abualsoud, Ammar Kadi, Mohammad Javed Ansari, A Deepak.
      Chitosan, a naturally abundant cationic polymer, is chemically composed of cellulose-based biopolymers derived by deacetylating chitin. It offers several attractive characteristics such as renewability, hydrophilicity, biodegradability, biocompatibility, non-toxicity, and a broad spectrum of antimicrobial activity towards gram-positive and gram-negative bacteria as well as fungi, etc., because of which it is receiving immense attention as a biopolymer for a plethora of applications including drug delivery, protective coating materials, food packaging films, wastewater treatment, and so on. Additionally, its structure carries reactive functional groups that enable several reactions and electrochemical interactions at the biomolecular level and improves the chitosan's physicochemical properties and functionality. This review article highlights the extensive research about the properties, extraction techniques, and recent developments of chitosan-based composites for drug, gene, protein, and vaccine delivery applications. Its versatile applications in tissue engineering and wound healing are also discussed. Finally, the challenges and future perspectives for chitosan in biomedical applications are elucidated.
    Keywords:  biomedical applications; chitosan; drug delivery; natural polymer; tissue engineering; wound healing
    DOI:  https://doi.org/10.3390/ijms231810975
  162. Oxid Med Cell Longev. 2022 ;2022 8006642
    Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy.
    Mingying Liu, Yu Zhang, Xuewei Ma, Bo Zhang, Yinghui Huang, Jinghong Zhao, Shaobo Wang, Yan Li, Yingguo Zhu, Jiachuan Xiong, Ting He, Yue Wang, Wenhao Han, Ke Yang, Xianjin Bi, Yong Liu, Hao Zhang.
      Atherosclerosis is the key pathogenesis of cardiovascular diseases; oxidative stress, which is induced by the generated excess reactive oxygen species (ROS), has been a crucial mechanism underlying this pathology. Nanoparticles (NPs) represent a novel strategy for the development of potential therapies against atherosclerosis, and multifunctional NPs possessing antioxidative capacities hold promise for amelioration of vascular injury caused by ROS and for evading off-target effects; materials that are currently used for NP synthesis often serve as vehicles that do not possess intrinsic biological activities; however, they may affect the surrounding healthy environment due to decomposition of products. Herein, we used nontoxic fucoidan, a sulfated polysaccharide derived from a marine organism, to develop chitosan-fucoidan nanoparticles (CFNs). Then, by binding to P-selectin, an inflammatory adhesion exhibited molecule expression on the endothelial cells and activated platelets, blocking leukocyte recruitment and rolling on platelets and endothelium. CFNs exhibit antioxidant and anti-inflammatory properties. Nevertheless, by now, the application of CFNs for the target delivery regarding therapeutics specific to atherosclerotic plaques is not well investigated. The produced CFNs were physicochemically characterized using transmission electron microscopy (TEM), together with Fourier transform infrared spectroscopy (FTIR). Evaluations of the in vitro antioxidant as well as anti-inflammatory activities exhibited by CFNs were based on the measurement of their ROS scavenging abilities and investigating inflammatory mediator levels. The in vivo pharmacokinetics and binding efficiency of the CFNs to atherosclerotic plaques were also evaluated. The therapeutic effects indicated that CFNs effectively suppressed local oxidative stress and inflammation by targeting P-selectin in atheromatous plaques and thereby preventing the progression of atherosclerosis.
    DOI:  https://doi.org/10.1155/2022/8006642
  163. Phytother Res. 2022 Sep 18.
    6-Methoxydihydrosanguinarine induces apoptosis and autophagy in breast cancer MCF-7 cells by accumulating ROS to suppress the PI3K/AKT/mTOR signaling pathway.
    Lei Zhang, Xinyue Zhang, Delu Che, Lizhong Zeng, Yu Zhang, Kai Nan, Xinxin Zhang, Hui Zhang, Zengjun Guo.
      6-Methoxydihydrosanguinarine (6-MDS) is a natural benzophenanthridine alkaloid extracted from Hylomecon japonica (Thunb.) Prantl. It is the first time to explore the effect and mechanism of 6-MDS in breast cancer. Network pharmacology, molecular docking, and molecular dynamics simulation technology were adopted to identify the potential targets and pathways of 6-MDS in breast cancer. Besides, cell proliferation, apoptosis, and western blotting assays were conducted to investigate the effect of 6-MDS on MCF-7 cells. Network pharmacology, molecular docking, and molecular dynamics simulation results confirmed the effect of 6-MDS on resisting breast cancer via the PI3K/AKT/mTOR signaling pathway. In addition, the functional experiments results demonstrated that 6-MDS inhibited proliferation and induced apoptosis and autophagy. The autophagy inhibitor chloroquine and the silence of Atg5 augmented the effect of 6-MDS on promoting apoptosis. Furthermore, 6-MDS suppressed the PI3K/AKT/mTOR signaling pathway, and the PI3K inhibitor LY294002 enhanced these changes and promoted the 6-MDS pro-apoptotic and autophagy effects. 6-MDS triggered the generation of reactive oxygen species. The pretreatment with antioxidant N-acetyl-L-cysteine reversed the changes induced by 6-MDS, including increases in apoptosis and autophagy and inhibition of the PI3K/AKT/mTOR pathway. In conclusion, 6-MDS induces the apoptosis and autophagy of MCF-7 cells by ROS accumulation to suppress the PI3K/AKT/mTOR signaling pathway.
    Keywords:  6-Methoxydihydrosanguinarine; PI3K/AKT/mTOR; apoptosis; autophagy; breast cancer
    DOI:  https://doi.org/10.1002/ptr.7601
  164. Pharmaceutics. 2022 Aug 27. pii: 1807. [Epub ahead of print]14(9):
    Fast-Fed Variability: Insights into Drug Delivery, Molecular Manifestations, and Regulatory Aspects.
    Nagarjun Rangaraj, Sunitha Sampathi, Vijayabhaskarreddy Junnuthula, Praveen Kolimi, Preethi Mandati, Sagar Narala, Dinesh Nyavanandi, Sathish Dyawanapelly.
      Among various drug administration routes, oral drug delivery is preferred and is considered patient-friendly; hence, most of the marketed drugs are available as conventional tablets or capsules. In such cases, the administration of drugs with or without food has tremendous importance on the bioavailability of the drugs. The presence of food may increase (positive effect) or decrease (negative effect) the bioavailability of the drug. Such a positive or negative effect is undesirable since it makes dosage estimation difficult in several diseases. This may lead to an increased propensity for adverse effects of drugs when a positive food effect is perceived. However, a negative food effect may lead to therapeutic insufficiency for patients suffering from life-threatening disorders. This review emphasizes the causes of food effects, formulation strategies to overcome the fast-fed variability, and the regulatory aspects of drugs with food effects, which may open new avenues for researchers to design products that may help to eliminate fast-fed variability.
    Keywords:  bioavailability; fast-fed variability; food effect; formulation; pH dependent; pharmacokinetics
    DOI:  https://doi.org/10.3390/pharmaceutics14091807
  165. J Ethnopharmacol. 2022 Sep 14. pii: S0378-8741(22)00761-9. [Epub ahead of print]300 115722
    Low concentrations of Ambrosia maritima L. phenolic extract protect endothelial cells from oxidative cell death induced by H2O2 and sera from Crohn's disease patients.
    Iman Ramli, Anna Maria Posadino, Sakina Zerizer, Ylenia Spissu, Antonio Barberis, Hanane Djeghim, Emanuela Azara, Chawki Bensouici, Zahia Kabouche, Khellaf Rebbas, Guy D'hallewin, Leonardo Antonio Sechi, Gianfranco Pintus.
      ETHNOPHARMACOLOGICAL RELEVANCE: A rising resort to herbal therapies in Crohn's disease (CD) alternative treatments has been recently observed due to their remarkable natural efficiency. In this context, the weed plant Ambrosia maritima L., traditionally known as Hachich el Aouinet in Algeria and as Damsissa in Egypt and Sudan, is widely used in North African folk medicine to treat infections, inflammatory diseases, gastrointestinal and urinary tract disturbances, rheumatic pain, respiratory problems, diabetes, hypertension and cancer.AIM OF THE STUDY: To assess an Ambrosia maritima L. phenolic extract for its phenolic profile composition, its potential antioxidant activity in vitro, and its cytoprotective effect on cultured primary human endothelial cells (ECs) stressed with H2O2 and sera from CD patients.
    MATERIALS AND METHODS: Phenolic compound extraction was performed with a low-temperature method. Extract chemical profile was attained by HPLC-DAD/ESI-MS. The extract in vitro antioxidant activity was assessed using several methods including cupric ion reducing power, DPPH radical scavenging assay, O-Phenanthroline free radical reducing activity, ABTS cation radical decolourisation assay, Galvinoxyl free radicals scavenging assay. Intracellular reactive oxygen species levels were evaluated in human endothelial cells by H2DCFDA, while cell viability was assessed by MTT.
    RESULTS: The phenolic compounds extraction showed a yield of 17.66% with three di-caffeoylquinic acid isomers detected for the first time in Ambrosia maritima L. Using different analytical methods, a significant in vitro antioxidant activity was reported for the Ambrosia maritima L. extract, with an IC50 value of 14.33 ± 3.86 μg/mL for the Galvinoxyl antioxidant activity method. Challenged with ECs the Ambrosia maritima L. extract showed a biphasic dose-dependent effect on H2O2-treated cells, cytoprotective and antioxidant at low doses, and cytotoxic and prooxidant at high doses, respectively. Viability and ROS levels data also demonstrated a prooxidant and cytotoxic effect of CD sera on cultured ECs. Interestingly, 10 μg/mL of Ambrosia maritima L. extract was able to counteract both CD sera-induced oxidative stress and ECs death.
    CONCLUSION: Our data indicated Ambrosia maritima L. as a source of bioactive phenolics potentially employable as a natural alternative for CD treatment.
    Keywords:  Ambrosia maritima L.; Antioxidant activity; Cell death; Crohn's disease; Oxidative stress; Phenols
    DOI:  https://doi.org/10.1016/j.jep.2022.115722
  166. J Cancer Res Ther. 2022 Jul-Sep;18(4):18(4): 1052-1060
    Induction of apoptosis and suppression of Ras gene expression in MCF human breast cancer cells.
    Sadegh Saremi, Maryam Kolahi, Mohammad Reza Tabandeh, Mahmoud Hashemitabar.
      Breast cancer is the leading invasive cancer in women globally. This study aimed at evaluating the anti-apoptotic activity of p-Coumaric acid (PCA) on MCF-7 breast cancer cell line. Experiments were conducted in which the MCF-7 cell line was treated with PCA. which showed decreased cell viability, increased lactate dehydrogenase activity, and caspase-3 activation. The results were evaluated with real-time polymerase chain reaction which revealed that PCA reduced the amount of H-Ras and K-Ras transcript in MCF-7 breast cancer cells. In the presence of PCA there was a significant increase in the levels of mRNA gene Bax and late apoptotic cells which was dose dependent. It also retarded the relative expression of antiapoptotic gene, Bcl2 in treated cells. The results suggest that PCA exhibits anti-cancer properties against MCF-7 cells. PCA inhibited the growth of MCF7 cell. The optimum concentration of PCA was 75-150 mM. PCA can inhibit the growth of MCF-7 cells by reducing Ras expression and inducing cell apoptosis. Our results suggest that PCA could prove valuable in the search for possible inhibitors of Ras oncogene functionality and gain further support for its potential utilization in the treatment of patients with breast cancer. PCA is safe and could complement current treatments employed for the disease.
    Keywords:  Apoptosis; Caspase; H-Ras oncogenes; N-Ras oncogenes; p-Coumaric acid
    DOI:  https://doi.org/10.4103/jcrt.JCRT_624_20
  167. Chem Biodivers. 2022 Sep 23.
    Total Bioactive Contents, Metabolic Profiling, Docking Studies, Antioxidant & Enzyme inhibition Activities of Convolvulus arvensis L. and Multivariate Analysis to Unravel a Potential herb as Natural Resource for Pharmaceutical Industry.
    Muhammad Imran Tousif, Mamona Nazir, Muhammad Saleem, Saba Touseef, Reaz Uddin, Gokhan Zengin, Mohamad Fawzi Mahomoodally, Zaheer Abbas.
      Convolvulus arvensis L. is an evergreen herb growing in various regions of Pakistan. Despite of several medicinal properties associated to this herb, it was not investigated scientifically for its bioactive compounds and detailed pharmaceutical properties. Therefore, its methanolic extract was divided into hexane (CA-H), chloroform (CA-C), ethyl acetate (CA-E) and butanol (CA-B) soluble fractions. CA-H and CA-C were found rich in phenolics (30.73±0.63 and 20.15±0.59 mg GAE/g of the extract respectively), and the same fractions exhibited significant antioxidant activities (DPPH: 5.23±0.11 & 12.34±0.17 mg TE/g extract, respectively; ABTS: 36.82±0.04 & 56.74±0.61 mg TE/g extract, respectively). Also in CUPRAC activity assay, CA-H and CA-C exhibited highest activities as 87.30±0.46 and 56.74±0.61 mg TE/g extract, respectively, while CA-C was most active in FRAP activity assay with value of 40.21± 2.19 mg TE/g extract. Total antioxidant capacity (1.23±0.033 mmol TE/ g extract) was also found higher for CA-C, while CA-H activity was also comparable, however, CA-H showed higher metal chelating activity (22.74±0.001 mg EDTAE/g extract) than that of CA-C (17.55± 0.22 mg EDTAE/g extract). These activities clearly revealed a direct relation between antioxidant potential and phenolic contents of CA-H and CA-C. In AChE and BChE inhibitory assay, CA-H and CA-E showed better inhibition (AChE: 8.24±0.77 & 4.46±0.007 mg GALAE/g extract; BChE: 5.40±0.02 & 1.92±0.24 mg GALAE/g extract) as compared to other fractions, whereas, against tyrosinase, CA-B was most active (37.35±0.53 mg KAE/g extract). CA-H and CA-C also showed higher inhibitory potential (0.98±0.08 & 0.58±0.01 mmol ACAE/g extract) against a-Amylase; while against a-Glucosidase, CA-E was the most active fraction. UHPLC-MS analysis of the methanolic extract of C. arvensis disclosed the presence of 62 compounds as sterols, triterpenes, flavonoids, fatty acids, alkaloids and coumarins.. Docking analyses confirmed these findings, as identified compounds had high binding free energy and inhibition constants with the enzymes studied. It was finally concluded that C. arvensis is a potential industrial crop, which can be a component of nutraceuticals and functional foods, if evaluated for its toxicity.
    Keywords:  Convolvulus arvensis L; antioxidant activities; enzyme inhibition activities; multivariate analysis; phytochemical investigation
    DOI:  https://doi.org/10.1002/cbdv.202200521
  168. Biomater Res. 2022 Sep 22. 26(1): 47
    Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy.
    Xianghui Li, Haoran Wang, Zhiyan Li, Dandan Li, Xiaofeng Lu, Shichao Ai, Yuxiang Dong, Song Liu, Jinhui Wu, Wenxian Guan.
      BACKGROUND: Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge.METHODS: Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core.
    RESULTS: Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo.
    CONCLUSIONS: This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.
    Keywords:  Artificial red blood cells; Mitochondrial respiratory inhibition; Organelle targeted therapy; PDT; Synergistic oxygen modulation; Tumor hypoxia
    DOI:  https://doi.org/10.1186/s40824-022-00296-0
  169. Nervenarzt. 2022 Sep 21.
    [Cancer Neuroscience].
    Varun Venkataramani, Frank Winkler.
      The nervous system integrates and processes information to act as master regulator of various vital, biological processes. However, increasing data suggest that the nervous system is also a key player in the initiation of cancer and cancer progression. Following the tenet that oncology follows ontogeny, it has been shown that brain tumors follow neural developmental processes. Incurable gliomas form neurite-like membrane tubes called tumor microtubes and are controlled by neurodevelopmental pathways. Tumor microtubes are used for invasion, proliferation and interconnection with other tumor cells, forming a tumor network that is therapeutically resistant. Additionally, neurons can activate tumor cells via glutamatergic synapses to drive tumor invasion and growth. The most recent knowledge of brain cancer neuroscience presented here with a focus on brain tumours has already led to new approaches for antitumour treatment.
    Keywords:  Antitumor treatment; Brain tumors; Nervous system; Treatment resistance; Tumor network
    DOI:  https://doi.org/10.1007/s00115-022-01380-5
  170. Pharmaceuticals (Basel). 2022 Aug 23. pii: 1036. [Epub ahead of print]15(9):
    Chitosan Based MicroRNA Nanocarriers.
    Hussein H Genedy, Thierry Delair, Alexandra Montembault.
      Vectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can be very promising candidates to overcome these challenges. One of the most suitable polymers for this purpose is chitosan. Chitosan (CS), a biodegradable biocompatible natural polysaccharide, has always been of interest for drug and gene delivery. Being cationic, chitosan can easily form particles with anionic polymers to encapsulate microRNA or even complex readily forming polyplexes. However, fine tuning of chitosan characteristics is necessary for a successful formulation. In this review, we cover all chitosan miRNA formulations investigated in the last 10 years, to the best of our knowledge, so that we can distinguish their differences in terms of materials, formulation processes, and intended applications. The factors that make some optimized systems superior to their predecessors are also discussed to reach the highest potential of chitosan microRNA nanocarriers.
    Keywords:  Chitosan; microRNA; nanoparticle; polymer; polyplex; polysaccharide
    DOI:  https://doi.org/10.3390/ph15091036
  171. Adv Drug Deliv Rev. 2022 Sep 15. pii: S0169-409X(22)00429-X. [Epub ahead of print] 114539
    Ultrasound-mediated blood-brain barrier opening: an effective drug delivery system for theranostics of brain diseases.
    Jieqiong Wang, Zhenzhou Li, Min Pan, Muhammad Fiaz, Yongsheng Hao, Yiran Yan, Litao Sun, Fei Yan.
      Blood-brain barrier (BBB) remains a significant obstacle to drug therapy for brain diseases. Focused ultrasound (FUS) combined with microbubbles (MBs) can locally and transiently open the BBB, providing a potential strategy for drug delivery across the BBB into the brain. Nowadays, taking advantage of this technology, many therapeutic agents, such as antibodies, growth factors, and nanomedicine formulations, are intensively investigated across the BBB into specific brain regions for the treatment of various brain diseases. Several preliminary clinical trials also have demonstrated its safety and good tolerance in patients. This review gives an overview of the basic mechanisms, ultrasound contrast agents, evaluation or monitoring methods, and medical applications of FUS-mediated BBB opening in glioblastoma, Alzheimer's disease, and Parkinson's disease.
    Keywords:  Blood-brain barrier; Cavitation; Drug delivery; Focused ultrasound; Theranostics; Ultrasound contrast agents
    DOI:  https://doi.org/10.1016/j.addr.2022.114539
  172. Dis Markers. 2022 ;2022 2267963
    lncRNAs: Key Regulators of Signaling Pathways in Tumor Glycolysis.
    Li Wen, Chang Tan, Shuai Ma, Xinzhi Li.
      In response to overstimulation of growth factor signaling, tumor cells can reprogram their metabolism to preferentially utilize and metabolize glucose to lactate even in the presence of abundant oxygen, which is termed the "Warburg effect" or aerobic glycolysis. Long noncoding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides and do not encode proteins. Accumulating evidence suggests that lncRNAs can affect aerobic glycolysis through multiple mechanisms, including the regulation of glycolytic transporters and key rate-limiting enzymes. In addition, maladjusted signaling pathways are critical for glycolysis. Therefore, this article mainly reviews the lncRNAs involved in the regulation of tumor glycolysis key signal pathways in recent years and provides an in-depth understanding of the role of differentially expressed lncRNAs in the key signal pathways of glucose metabolism, which may help to provide new therapeutic targets and new diagnostic and prognostic markers for human cancer.
    DOI:  https://doi.org/10.1155/2022/2267963
  173. Int J Nanomedicine. 2022 ;17 4163-4193
    Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy.
    Wenhao Liao, Yuchen Li, Jing Wang, Maoyuan Zhao, Nianzhi Chen, Qiao Zheng, Lina Wan, Yu Mou, Jianyuan Tang, Zhilei Wang.
      Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.
    Keywords:  cancer; cancer stem cells; nanoformulations; natural products; targeted therapy
    DOI:  https://doi.org/10.2147/IJN.S380697
  174. Molecules. 2022 Sep 17. pii: 6070. [Epub ahead of print]27(18):
    Promising Nanocarriers to Enhance Solubility and Bioavailability of Cannabidiol for a Plethora of Therapeutic Opportunities.
    Lucia Grifoni, Giulia Vanti, Rosa Donato, Cristiana Sacco, Anna Rita Bilia.
      In recent years, the interest in cannabidiol (CBD) has increased because of the lack of psychoactive properties. However, CBD has low solubility and bioavailability, variable pharmacokinetics profiles, poor stability, and a pronounced presystemic metabolism. CBD nanoformulations include nanosuspensions, polymeric micelles and nanoparticles, hybrid nanoparticles jelled in cross-linked chitosan, and numerous nanosized lipid formulations, including nanostructured lipid carriers, vesicles, SNEEDS, nanoemulsions, and microemulsions. Nanoformulations have resulted in high CBD solubility, encapsulation efficiency, and stability, and sustained CBD release. Some studies assessed the increased Cmax and AUC and decreased Tmax. A rational evaluation of the studies reported in this review evidences how some of them are very preliminary and should be completed before performing clinical trials. Almost all the developed nanoparticles have simple architectures, are well-known and safe nanocarriers, or are even simple nanosuspensions. In addition, the conventional routes of administration are generally investigated. As a consequence, many of these studies are almost ready for forthcoming clinical translations. Some of the developed nanosystems are very promising for a plethora of therapeutic opportunities because of the versatility in terms of the release, the crossing of physiological barriers, and the number of possible routes of administration.
    Keywords:  bioavailability; cannabidiol; efficacy; nanocarriers; solubility
    DOI:  https://doi.org/10.3390/molecules27186070
  175. Pharmaceuticals (Basel). 2022 Sep 08. pii: 1120. [Epub ahead of print]15(9):
    Combined Ramipril and Black Seed Oil Dosage Forms Using Bioactive Self-Nanoemulsifying Drug Delivery Systems (BIO-SNEDDSs).
    Ahmad Abdul-Wahhab Shahba, Abdelrahman Y Sherif, Ehab M Elzayat, Mohsin Kazi.
      Purpose: Ramipril (RMP)-an angiotensin-converting enzyme (ACE) inhibitor-and thymoquinone (THQ) suffer from poor oral bioavailability. Developing a combined liquid SNEDDS that comprises RMP and black seed oil (as a natural source of THQ) could lead to several formulations and therapeutic benefits. Methods: The present study involved comprehensive optimization of RMP/THQ liquid SNEDDS using self-emulsification assessment, equilibrium solubility studies, droplet size analysis, and experimentally designed phase diagrams. In addition, the optimized RMP/THQ SNEDDS was evaluated against pure RMP, pure THQ, and the combined pure RMP + RMP-free SNEDDS (capsule-in-capsule) dosage form via in vitro dissolution studies. Results: The phase diagram study revealed that black seed oil (BSO) showed enhanced self-emulsification efficiency with the cosolvent (Transcutol P) and hydrogenated castor oil. The phase diagram studies also revealed that the optimized formulation BSO/TCP/HCO-30 (32.25/27.75/40 % w/w) showed high apparent solubility of RMP (25.5 mg/g), good THQ content (2.7 mg/g), and nanometric (51 nm) droplet size. The in-vitro dissolution studies revealed that the optimized drug-loaded SNEDDS showed good release of RMP and THQ (up to 86% and 89%, respectively). Similarly, the isolation between RMP and SNEDDS (pure RMP + RMP-free SNEDDS) using capsule-in-capsule technology showed &gt;84% RMP release and &gt;82% THQ release. Conclusions: The combined pure RMP + RMP-free SNEDDS (containing black seed oil) could be a potential dosage form combining the solubilization benefits of SNEDDSs, enhancing the release of RMP/THQ along with enhancing RMP stability through its isolation from lipid-based excipients during storage.
    Keywords:  BIO-SNEDDS; black seed oil; combined delivery systems; hypertension; ramipril
    DOI:  https://doi.org/10.3390/ph15091120
  176. Molecules. 2022 Sep 16. pii: 6032. [Epub ahead of print]27(18):
    Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug-A Review.
    Jun-O Jin, Dhananjay Yadav, Kajal Madhwani, Nidhi Puranik, Vishal Chavda, Minseok Song.
      Marine natural products are a discerning arena to search for the future generation of medications to treat a spectrum of ailments. Meanwhile, cancer is becoming more ubiquitous over the world, and the likelihood of dying from it is rising. Surgery, radiation, and chemotherapy are the mainstays of cancer treatment worldwide, but their extensive side effects limit their curative effect. The quest for low-toxicity marine drugs to prevent and treat cancer is one of the current research priorities of researchers. Fucoidan, an algal sulfated polysaccharide, is a potent therapeutic lead candidate against cancer, signifying that far more research is needed. Fucoidan is a versatile, nontoxic marine-origin heteropolysaccharide that has received much attention due to its beneficial biological properties and safety. Fucoidan has been demonstrated to exhibit a variety of conventional bioactivities, such as antiviral, antioxidant, and immune-modulatory characteristics, and anticancer activity against a wide range of malignancies has also recently been discovered. Fucoidan inhibits tumorigenesis by prompting cell cycle arrest and apoptosis, blocking metastasis and angiogenesis, and modulating physiological signaling molecules. This review compiles the molecular and cellular aspects, immunomodulatory and anticancer actions of fucoidan as a natural marine anticancer agent. Specific fucoidan and membranaceous polysaccharides from Ecklonia cava, Laminaria japonica, Fucus vesiculosus, Astragalus, Ascophyllum nodosum, Codium fragile serving as potential anticancer marine drugs are discussed in this review.
    Keywords:  adjuvant; cancer; fucoidan; marine algae; marine drugs; prebiotics; seaweeds; sulfated polysaccharide
    DOI:  https://doi.org/10.3390/molecules27186032
  177. Biomedicines. 2022 Aug 23. pii: 2055. [Epub ahead of print]10(9):
    Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics.
    Dixit V Bhalani, Bhingaradiya Nutan, Avinash Kumar, Arvind K Singh Chandel.
      The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry's screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.
    Keywords:  BCS classification; bioavailability; crystal engineering; dissolution; drug conjugates; encapsulation; low water solubility; micelles; micronization; nanoparticles; solid dispersion; solid lipid nanoparticles; solubility
    DOI:  https://doi.org/10.3390/biomedicines10092055
  178. Pharmaceuticals (Basel). 2022 Sep 05. pii: 1106. [Epub ahead of print]15(9):
    Novel Bile Salt Stabilized Vesicles-Mediated Effective Topical Delivery of Diclofenac Sodium: A New Therapeutic Approach for Pain and Inflammation.
    Tamer M Mahmoud, Mohamed M Nafady, Hanan O Farouk, Dina M Mahmoud, Yasmin M Ahmed, Randa Mohammed Zaki, Doaa S Hamad.
      The oral delivery of diclofenac sodium (DNa), a non-steroidal analgesic, anti-inflammatory drug, is associated with various gastrointestinal side effects. The aim of the research was to appraise the potential of transdermal delivery of DNa using bilosomes as a vesicular carrier (BSVC) in inflamed paw edema. DNa-BSVCs were elaborated using a thin-film hydration technique and optimized using a 31.22 multilevel categoric design with Design Expert® software 10 software (Stat-Ease, Inc., Minneapolis, MI, USA). The effect of formulation variables on the physicochemical properties of BSVC, as well as the optimal formulation selection, was investigated. The BSVCs were evaluated for various parameters including entrapment efficiency (EE%), vesicle size (VS), zeta potential (ZP) and permeation studies. The optimized BSVC was characterized for in vitro release, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and incorporated into hydrogel base. The optimized DNa-BSVC gel effectiveness was assessed in vivo using carrageenan-induced paw edema animal model via cyclooxygenase 2 (COX-2), interleukin 6 (IL-6), Hemooxygenase 1 (HO-1) and nuclear factor-erythroid factor2-related factor 2 (Nfr-2) that potentiate anti-inflammatory and anti-oxidant activity coupled with histopathological investigation. The resulting vesicles presented VS from 120.4 ± 0.65 to 780.4 ± 0.99 nm, EE% from 61.7 ± 3.44 to 93.2 ± 2.21%, ZP from -23.8 ± 2.65 to -82.1 ± 12.63 mV and permeation from 582.9 ± 32.14 to 1350.2 ± 45.41 µg/cm2. The optimized BSVCs were nano-scaled spherical vesicles with non-overlapped bands of their constituents in the FTIR. Optimized formulation has superior skin permeability ex vivo approximately 2.5 times greater than DNa solution. Furthermore, histological investigation discovered that the formed BSVC had no skin irritating properties. It was found that DNa-BSVC gel suppressed changes in oxidative inflammatory mediators (COX-2), IL-6 and consequently enhanced Nrf2 and HO-1 levels. Moreover, reduction of percent of paw edema by about three-folds confirmed histopathological alterations. The results revealed that the optimized DNa-BSVC could be a promising transdermal drug delivery system to boost anti-inflammatory efficacy of DNa by enhancing the skin permeation of DNa and suppressing the inflammation of rat paw edema.
    Keywords:  NSAIDs; bilosomes; permeation study; rat paw edema; the nuclear factor erythroid 2–related factor 2; transdermal drug delivery
    DOI:  https://doi.org/10.3390/ph15091106
  179. J Cancer. 2022 ;13(11): 3234-3243
    Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway.
    Kezhong Tang, Qing Chen, Yanmo Liu, Lantian Wang, Wenjie Lu.
      Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups in vivo. Moreover, the combination treatment greatly induced ferroptosis in HCC cells through inhibiting Nrf2 expression. Based on our findings, the combination treatment suppressed proliferation of HCC cells through ferroptosis induction, by p62-Keap1-Nrf2/HO1 signaling way.
    Keywords:  Hepatocellular carcinoma (HCC); NF-E2-related factor 2 (Nrf2); ferroptosis; metformin; sorafenib
    DOI:  https://doi.org/10.7150/jca.76618
  180. Nanoscale Adv. 2022 May 03. 4(9): 2224-2232
    Rare earth nanoparticles for sprayed and intravenous NIR II imaging and photodynamic therapy of tongue cancer.
    Lingling Cai, Zhan Wang, Bi Lin, Kaikai Liu, Yanxing Wang, Ying Yuan, Xiaofeng Tao, Ruichan Lv.
      In this research, rare earth nanoparticles coupled with dihydroartemisinin (DHA) and a targeted antibody (RENP-DHA-Cap) for sprayed NIR II imaging and photodynamic therapy (PDT) of tongue cancer were designed. Genetic algorithms combined with combinatorial chemistry were proposed and successfully achieved in a single optimized luminescent phosphor with enhanced NIR II and high upconversion luminescence (UCL) under a NIR laser of wavelength 980 nm or/and 808 nm. In particular, T1 magnetic resonance imaging (MRI) signals can be adjusted with the Gd ion concentration. In combination with the targeted antibody of capmatinib (Cap), precise NIR II imaging for in situ tongue cancer by a simple spray method can be achieved. Most importantly, NIR II imaging and PDT treatment can be realized with RENP-DHA-capmatinib injected intravenously. This orthogonal theranostic mode with precise diagnosis under 808 nm and targeted effective treatment under 980 nm may promote tongue cancer theranostics.
    DOI:  https://doi.org/10.1039/d2na00197g
  181. Pharmaceutics. 2022 Sep 01. pii: 1847. [Epub ahead of print]14(9):
    Structuring and De-Structuring of Nanovectors from Algal Lipids: Simulated Digestion, Preliminary Antioxidant Capacity and In Vitro Tests.
    Ilaria Clemente, Stefania Lamponi, Gabriella Tamasi, Liliana Rodolfi, Claudio Rossi, Sandra Ristori.
      Biocompatible nanocarriers can be obtained by lipid extraction from natural sources such as algal biomasses, which accumulate different lipid classes depending on the employed culture media. Lipid aggregates can be distinguished according to supramolecular architecture into lamellar and nonlamellar structures. This distinction is mainly influenced by the lipid class and molecular packing parameter, which determine the possible values of interfacial curvature and thus the supramolecular symmetries that can be obtained. The nanosystems prepared from bio-sources are able to self-assemble into different compartmentalized structures due to their complex composition. They also present the advantage of increased carrier-target biocompatibility and are suitable to encapsulate and vehiculate poorly water-soluble compounds, e.g., natural antioxidants. Their functional properties stem from the interplay of several parameters. Following previous work, here the functionality of two series of structurally distinct lipid nanocarriers, namely liposomes and cubosomes deriving from algal biomasses with different lipid composition, is characterized. In the view of their possible use as pharmaceutical or nutraceutical formulations, both types of nanovectors were loaded with three well-known antioxidants, i.e., curcumin, α-tocopherol and piperine, and their carrier efficacy was compared considering their different structures. Firstly, carrier stability in biorelevant conditions was assessed by simulating a gastrointestinal tract model. Then, by using an integrated chemical and pharmacological approach, the functionality in terms of encapsulation efficiency, cargo bioaccessibility and kinetics of antioxidant capacity by UV-Visible spectroscopy was evaluated. Subsequently, in vitro cytotoxicity and viability tests after administration to model cell lines were performed. As a consequence of this investigation, it is possible to conclude that nanovectors from algal lipids, i.e., cubosomes and liposomes, can be efficient delivery agents for lipophilic antioxidants, being able to preserve and enhance their activity toward different targets while promoting sustained release.
    Keywords:  algal biomass; antioxidant capacity; curcumin; in vitro tests; lipid nanocarriers; simulated digestion
    DOI:  https://doi.org/10.3390/pharmaceutics14091847
  182. Pharmaceuticals (Basel). 2022 Aug 28. pii: 1072. [Epub ahead of print]15(9):
    Recent Advances in Oral Peptide or Protein-Based Drug Liposomes.
    Jian Cui, Zhiwei Wen, Wei Zhang, Wei Wu.
      The high physiology and low toxicity of therapeutic peptides and proteins have made them a hot spot for drug development in recent years. However, their poor oral bioavailability and unstable metabolism make their clinical application difficult. The bilayer membrane of liposomes provides protection for the drug within the compartment, and their high biocompatibility makes the drug more easily absorbed by the body. However, phospholipids-which form the membranes-are subjected to various digestive enzymes and mucosal adhesion in the digestive tract and disintegrate before absorption. Improvements in the composition of liposomes or modifying their surface can enhance the stability of the liposomes in the gastrointestinal tract. This article reviews the basic strategies for liposome preparation and surface modification that promote the oral administration of therapeutic polypeptides.
    Keywords:  drug delivery system; liposomes; oral administration; oral bioavailability; polypeptide and protein drugs
    DOI:  https://doi.org/10.3390/ph15091072
  183. Polymers (Basel). 2022 Sep 09. pii: 3773. [Epub ahead of print]14(18):
    Protection against Paraquat-Induced Oxidative Stress by Curcuma longa Extract-Loaded Polymeric Nanoparticles in Zebrafish Embryos.
    Ana Teixeira, Marisa P Sárria, Inês Pinto, Begoña Espiña, Andreia C Gomes, Alberto C P Dias.
      The link between oxidative stress and environmental factors plays an important role in chronic degenerative diseases; therefore, exogenous antioxidants could be an effective alternative to combat disease progression and/or most significant symptoms. Curcuma longa L. (CL), commonly known as turmeric, is mostly composed of curcumin, a multivalent molecule described as having antioxidant, anti-inflammatory and neuroprotective properties. Poor chemical stability and low oral bioavailability and, consequently, poor absorption, rapid metabolism, and limited tissue distribution are major restrictions to its applicability. The advent of nanotechnology, by combining nanosacale with multi-functionality and bioavailability improvement, offers an opportunity to overcome these limitations. Therefore, in this work, poly-Ɛ-caprolactone (PCL) nanoparticles were developed to incorporate the methanolic extract of CL, and their bioactivity was assessed in comparison to free or encapsulated curcumin. Their toxicity was evaluated using zebrafish embryos by applying the Fish Embryo Acute Toxicity test, following recommended OECD guidelines. The protective effect against paraquat-induced oxidative damage of CL extract, free or encapsulated in PCL nanoparticles, was evaluated. This herbicide is known to cause oxidative damage and greatly affect neuromotor functions. The overall results indicate that CL-loaded PCL nanoparticles have an interesting protective capacity against paraquat-induced damage, particularly in neuromuscular development that goes well beyond that of CL extract itself and other known antioxidants.
    Keywords:  PCL nanoparticles; curcumin; neuroprotection; oxidative stress; paraquat; zebrafish embryogenesis
    DOI:  https://doi.org/10.3390/polym14183773
  184. Clin Adv Hematol Oncol. 2022 Aug;20(8): 503-505
    The emerging role of KRAS G12C inhibitors in the treatment of locally advanced or metastatic colorectal cancer.
    Kristen Ciombor.
      
  185. Nanomedicine (Lond). 2022 Sep 22.
    Enhanced permeability and retention effect-focused tumor-targeted nanomedicines: latest trends, obstacles and future perspective.
    Saurabh Shekhar, Mahima Chauhan, Sonali, Bhavna Yadav, Rohit Dutt, Liandong Hu, Madaswamy S Muthu, Rahul Pratap Singh.
      
    Keywords:  cancer nanomedicines; cancer/oncology; controlled drug release; enhanced permeability and retention effect; factors affecting EPR effect; nanoparticle toxicity; targeted cancer therapy
    DOI:  https://doi.org/10.2217/nnm-2022-0065
  186. Front Pharmacol. 2022 ;13 830323
    Synergistic antioxidant effects of natural compounds on H2O2-induced cytotoxicity of human monocytes.
    Reda Ben Mrid, Najat Bouchmaa, Wessal Ouedrhiri, Abdelhamid Ennoury, Zakia ZouaouI, Imad Kabach, Mohamed Nhiri, Rachid El Fatimy.
      Natural compounds are endowed with a broad spectrum of biological activities, including protection against Toxins. Most of them are known for their antioxidant and radical scavenging activities. However, the synergistic combination of these natural molecules is not well studied. Therefore, the present study aims first to investigate the effect of four potent natural molecules [rosmarinic acid (Ros-A), ellagic acid (Ella-A), curcumin (Cur), and syringic acid (Syr-A)] on H2O2 -induced cell cytotoxicity and oxidative stress on the human monocytes (THP-1) and then to evaluate their combined action effect. Optimal combinations of these molecules were predicted using an augmented mixture design approach. In the first, as preliminary antioxidant activities screening, two in vitro assays were adopted to assess the single radicals scavenging activity of these natural compounds, DPPH• and ABTS• + tests. Based on the results obtained, the multitude of optimal formulas proposed by the mixture design study led to choosing four potent compositions (comp) in addition to ellagic acid, proposed as the most efficient when applied alone. The different molecules and mixtures were used to assess their cytoprotective effect on THP-1 cells in the presence and absence of H2O2. The most potent Comp-4, as well as the molecules forming this mixture, were exploited in a second experiment, aiming to understand the effect on oxidative stress via antioxidant enzyme activities analysis in the H2O2-induced oxidative stress in the THP-1 cell line. Interestingly, the natural molecules used for THP-1 cells treatment exhibited a significant increase in the antioxidant defense and glyoxalase system as well as suppression of ROS generation evaluated as MDA content. These results indicate that the natural compounds tested here, especially the synergistic effect of Cur and Ros-A (Comp-4), could serve as cytoprotective and immunostimulant agents against H2O2-induced cytotoxicity THP-1 cells, which makes them interesting for further investigations on the molecular mechanisms in preclinical animal models.
    Keywords:  H2O2-induced cytotoxicity; ROS protection; antioxidants; monocytes; synergistic interaction
    DOI:  https://doi.org/10.3389/fphar.2022.830323
  187. Antioxidants (Basel). 2022 Aug 27. pii: 1668. [Epub ahead of print]11(9):
    The Role Played by Ferroptosis in Osteoarthritis: Evidence Based on Iron Dyshomeostasis and Lipid Peroxidation.
    Shaoyun Zhang, Jiawen Xu, Haibo Si, Yuangang Wu, Shengliang Zhou, Bin Shen.
      Ferroptosis, a recently discovered regulated cell death modality, is characterised by iron-dependent accumulation of lipid hydroperoxides, which can reach lethal levels but can be specifically reversed by ferroptosis inhibitors. Osteoarthritis (OA), the most common degenerative joint disease, is characterised by a complex pathogenesis involving mechanical overload, increased inflammatory mediator levels, metabolic alterations, and cell senescence and death. Since iron accumulation and oxidative stress are the universal pathological features of OA, the role played by ferroptosis in OA has been extensively explored. Increasing evidence has shown that iron dyshomeostasis and lipid peroxidation are closely associated with OA pathogenesis. Therefore, in this review, we summarize recent evidence by focusing on ferroptotic mechanisms and the role played by ferroptosis in OA pathogenesis from the perspectives of clinical findings, animal models, and cell research. By summarizing recent research advances that characterize the relationship between ferroptosis and OA, we highlight avenues for further research and potential therapeutic targets.
    Keywords:  ferroptosis; iron dyshomeostasis; lipid peroxidation; osteoarthritis
    DOI:  https://doi.org/10.3390/antiox11091668
  188. Bioengineering (Basel). 2022 Sep 14. pii: 472. [Epub ahead of print]9(9):
    Fucoidan from Marine Macroalgae: Biological Actions and Applications in Regenerative Medicine, Drug Delivery Systems and Food Industry.
    Grace Sathyanesan Anisha, Savitha Padmakumari, Anil Kumar Patel, Ashok Pandey, Reeta Rani Singhania.
      The marine macroalgae produce a collection of bioactive polysaccharides, of which the sulfated heteropolysaccharide fucoidan produced by brown algae of the class Phaeophyceae has received worldwide attention because of its particular biological actions that confer nutritional and health benefits to humans and animals. The biological actions of fucoidan are determined by their structure and chemical composition, which are largely influenced by the geographical location, harvest season, extraction process, etc. This review discusses the structure, chemical composition and physicochemical properties of fucoidan. The biological action of fucoidan and its applications for human health, tissue engineering, regenerative medicine and drug delivery are also addressed. The industrial scenario and prospects of research depicted would give an insight into developing fucoidan as a commercially viable and sustainable bioactive material in the nutritional and pharmacological sectors.
    Keywords:  anticancer; antimicrobial; antioxidant; antiviral; food packaging; fucoidan; regenerative medicine
    DOI:  https://doi.org/10.3390/bioengineering9090472
  189. Antioxidants (Basel). 2022 Aug 29. pii: 1696. [Epub ahead of print]11(9):
    Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
    Alessandro Allegra, Alessandro Tonacci, Laura Giordano, Caterina Musolino, Sebastiano Gangemi.
      Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease.
    Keywords:  acute lymphoblastic leukemia; acute myeloid leukemia; mitochondria; oxidative stress; reactive oxygen species
    DOI:  https://doi.org/10.3390/antiox11091696
  190. Curr Res Compliment Altern Med. 2022 ;pii: 153. [Epub ahead of print]6(1):
    The Case for Moxibustion for Painful Syndromes: History, principles and rationale.
    Nigel C Dawes, Joyce K Anastasi.
      Traditional Chinese Medicine (TCM) has evolved over thousands of years. TCM practitioners use various approaches (such as acupuncture and tai chi) as well as herbal products to address health problems. Though lesser known in the west, the practice of Moxibustion is an integral part of Traditional East Asian Medicine. Moxibustion is an important non-invasive treatment that has shown to be beneficial in treating painful syndromes including neuropathy. It has been suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-kB and by activating Nrf2. These anti-inflammatory and protective mechanisms could be key to exploring the use of moxibustion in treating other etiologies of neuropathy including HIV. There is ample scope for future study in this area and consideration of the history, development and practical applications of moxibustion therapy may be of help in this regard. This article seeks to explore the background, principles, and application of moxibustion in the clinical setting with particular emphasis on its potential for symptom management in the treatment of neuropathy and pain.
    DOI:  https://doi.org/10.29011/2577-2201.100053
  191. Int J Biol Macromol. 2022 Sep 16. pii: S0141-8130(22)02054-2. [Epub ahead of print]220 1329-1344
    Calcium alginate/silk fibroin peptide/Bletilla striata polysaccharide blended microspheres loaded with tannic acid for rapid wound healing.
    Nan Wang, Xiaoyong Tian, Baijie Cheng, Shanyi Guang, Hongyao Xu.
      Biodegradable natural polymers are receiving increasing attention as potential candidates for wound dressing. In the present study, composite microspheres (mCSB) based on calcium alginate (CA), silk fibroin peptide (SP), and Bletilla striata polysaccharide (BSP) were prepared by the reverse emulsion method. The excellent swelling properties of microspheres enable them to rapidly promote thrombosis. Microspheres can increase the platelet aggregation index to 1.5 and the aggregation rate of red blood cells to as high as 80 %. Furthermore, tannic acid (TA)-loaded microspheres demonstrate a slow-release effect on TA; this allows the microspheres to exhibit good long-lasting antibacterial properties. Due to the synergistic effects of SP and TA, the cell senescence was delayed, with a 126.69 % survival rate of fibroblasts after 3 days of incubation. In addition, TA led to a rapid reduction in inflammation levels, with a wound closure rate of >92.80 % within 7 days. The multifunctional TA-loaded mCSB has great application potential for rapid wound healing and the treatment of wound hemostasis.
    Keywords:  Multifunctional microsphere dressing; Slow-release; Tannic acid
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.123
  192. FEBS J. 2022 Sep 24.
    Importance of temperature on immuno-metabolic regulation and cancer progression.
    Haiping Wang, Melis Ülgen, Mirko Trajkovski.
      Cancer immunotherapies emerge as promising strategies for restricting tumor growth. The tumor microenvironment (TME) has a major impact on the anti-tumor immune response and on the efficacy of the immunotherapies. Environmental factors play critical roles in affecting overall energy metabolism and can also impact the TME. Recent studies have linked changes in the ambient temperature with particular immunometabolic reprogramming and anti-cancer immune response in laboratory animals. Here, we describe the energetic balance of the organism during change in temperature, and link this to the immune alterations that could be of relevance for cancer, as well as for other human diseases. We highlight the contribution of the gut microbiota in modifying this interaction. We describe the overall metabolic response and underlying mechanisms of tumorigenesis in mouse models at varying ambient temperatures and shed light on their potential importance in developing therapeutics against cancer.
    Keywords:  Temperature; cancer immunometabolism; energy balance; fat metabolism; gut microbiota
    DOI:  https://doi.org/10.1111/febs.16632
  193. Biochem Pharmacol. 2022 Sep 18. pii: S0006-2952(22)00345-8. [Epub ahead of print] 115251
    Relationship Between the In Vitro Efficacy, Pharmacokinetics and In Vivo Efficacy of Curcumin.
    Gordon T Bolger, Kresimir Pucaj, Yvonne O Minta, Peter Sordillo.
      Considerable interest continues to be focused on the development of curcumin either as an effective stand-alone therapeutic or as an adjunct therapy to established therapies. Curcumin (1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5- dione; also called diferuloylmethane) is a polyphenolic phytochemical extracted from the root of curcuma longa, commonly called turmeric. Despite evidence from in vitro (cell culture) and preclinical studies in animals, clinical studies have not provided strong evidence for a therapeutic effect of curcumin. The relevance of curcumin as a drug has been questioned based on its classification as a compound with pan assay interference and invalid metabolic panaceas properties bringing into question the relevance of the therapeutic targets identified for curcumin. To some extent this is due to the lack of a complete understanding of the link between the in vitro (cell culture activity), pharmacokinetics and in vivo activity of curcumin. In this review and using NF-κB as a cellular target for curcumin, we have investigated the relationship between the potency of curcumin as an inhibitor of NF-κB in cell culture, the pharmacokinetics of curcumin and curcumin's anticancer and anti-inflammatory effects in preclinical models of cancer and inflammation. Plausible explanations and rationale are provided to link these activities together and suggest that both curcumin and its more soluble Phase II metabolite curcumin glucuronide may play a key role in the treatment effects of curcumin in vivo mediated at NF-κB.
    Keywords:  Cell culture; Curcumin; Nuclear factor κ-B; Oral and Intraperitoneal dosing; Pharmacokinetics; Preclinical disease models
    DOI:  https://doi.org/10.1016/j.bcp.2022.115251
  194. Curr Issues Mol Biol. 2022 Aug 26. 44(9): 3884-3904
    Anticancer Secondary Metabolites: From Ethnopharmacology and Identification in Native Complexes to Biotechnological Studies in Species of Genus Astragalus L. and Gloriosa L.
    Iliana Ionkova, Aleksandar Shkondrov, Yancho Zarev, Ekaterina Kozuharova, Ilina Krasteva.
      Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. This work aims to present the chemical diversity of antitumor bioactive compounds and biotechnological approaches as alternative production and sustainable plant biodiversity conservation. Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) are selected as research objects within this review because they are known for their anticancer activity, because they represent two of the largest families respectively in dicots and monocots, and also because many of the medicinally important plants are rare and endangered. We summarized the ethnobotanical data concerning their anticancer application, highlighted the diversity of their secondary metabolites possessing anticancer properties such as saponins, flavonoids, and alkaloids, and revealed the potential of the in vitro cultures as an alternative way of their production. Since the natural supply is limited, it is important to explore the possibility of employing plant cell or organ in vitro cultures for the biotechnological production of these compounds as an alternative.
    Keywords:  Agrobacterium rhizogenes; Astragalus; Gloriosa; alkaloids; conservation; ethnobotany; flavonoids; in vitro production; plant anticancer compounds; saponins
    DOI:  https://doi.org/10.3390/cimb44090267
  195. Oxid Med Cell Longev. 2022 ;2022 1422929
    Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.
    Madumani Amararathna, David W Hoskin, H P Vasantha Rupasinghe.
      Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues and entrapment of anthocyanins increases their stability, bioavailability, and therapeutic efficacy. The objective of the present study was to develop a direct delivery system of anthocyanins into pulmonary tissues via encapsulated nanocarriers. A cyanidin-3-O-glucoside (C3G)-rich anthocyanin extract was prepared from well-ripened haskap (Lonicera caerulea L.) berries (HB) and encapsulated in three different polymeric nanocarrier systems: polyethylene glycol-poly(lactide-co-glycolide), maltodextrin, and carboxymethyl chitosan (CMC). The anthocyanin encapsulation efficiency was significantly higher in CMC (10%) than in the other two polymers. The cytotoxicity and cytoprotective effect of HB anthocyanin-encapsulated CMC (HB-CMC, 4 μg of C3G equivalent anthocyanin in 2 mg/mL nanoparticle) and anthocyanin-free CMC (E-CMC, 2 mg/mL) were tested for cytotoxicity using human normal lung epithelial BEAS-2B cells. The CMC nanoparticles were not cytotoxic for BEAS-2B cells. The HB-CMC nanoparticles reduced carcinogen-induced oxidative stress in BEAS-2B cells and restored the expression of superoxide dismutase and glutathione peroxidase enzymes. The HB-CMC nanoparticles also reduced carcinogen-induced DNA single-strand breaks and alkaline-labile sites but not the double-strand breaks. The E-CMC, HB-CMC (28 μg C3G equivalent/mouse/day for six days), or the same dose of free HB anthocyanin was administered to A/JCr mice through a nose-only passive inhalation device. C3G and its metabolites, cyanidin, peonidin-3-O-glucoside, and cyanidin-3-O-glucuronide, were detected by UPLC/ESI/Q-TOF-MS in the lungs of mice after one hour of exposure. Therefore, the CMC could be a promising noncytotoxic candidate to encapsulate HB anthocyanin. Direct delivery of anthocyanin to lung tissues enhances tissue retention, slows phase 2 metabolism, and improves therapeutic efficacy.
    DOI:  https://doi.org/10.1155/2022/1422929
  196. Int J Nanomedicine. 2022 ;17 4227-4259
    Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin.
    Yukun Chen, Zhenzhi Wang, Xiaofan Wang, Mingliang Su, Fan Xu, Lian Yang, Lijun Jia, Zhanxia Zhang.
      10-Hydroxycamptothecin (HCPT) is a natural plant alkaloid from Camptotheca that shows potent antitumor activity by targeting intracellular topoisomerase I. However, factors such as instability of the lactone ring and insolubility in water have limited the clinical application of this drug. In recent years, unprecedented advances in biomedical nanotechnology have facilitated the development of nano drug delivery systems. It has been found that nanomedicine can significantly improve the stability and water solubility of HCPT. NanoMedicines with different diagnostic and therapeutic functions have been developed to significantly improve the anticancer effect of HCPT. In this paper, we collected reports on HCPT nanomedicines against tumors in the past decade. Based on current research advances, we dissected the current status and limitations of HCPT nanomedicines development and looked forward to future research directions.
    Keywords:  10-hydroxycamptothecin; antitumor; nano-drug delivery systems; nanomedicine
    DOI:  https://doi.org/10.2147/IJN.S377149
  197. Int J Mol Sci. 2022 Sep 17. pii: 10889. [Epub ahead of print]23(18):
    Aegle marmelos (L.) Correa: An Underutilized Fruit with High Nutraceutical Values: A Review.
    Niharika Sharma, Radha, Manoj Kumar, Baohong Zhang, Neeraj Kumari, Daljeet Singh, Deepak Chandran, Tanmay Sarkar, Sangram Dhumal, Vijay Sheri, Abhijit Dey, Sureshkumar Rajalingam, Sabareeshwari Viswanathan, Pran Mohankumar, Marthandan Vishvanathan, Sangeetha Kizhakkumkara Sathyaseelan, Jose M Lorenzo.
      Aegle marmelos (L.) Correa (Bael) fruit, a member of the Rutaceae family, is a major cultivated fruit plant in tropical and subtropical regions in countries of southeast Asia. Bael fruit has been a major topic for studies in recent years mainly due to its high nutritional (carbohydrates, proteins, minerals, and vitamins) value and presence of various phytochemicals, which attributed to its high medicinal value. These phytochemicals include various compounds, e.g., alkaloids, flavonoids, and phenolic acids (protocatechuic acid, gallic, and ellagic acid). The fruit extract of bael has been also an important study area for its pharmacological activities, including antidiarrheal, antioxidant, antidiabetic, hepatoprotective, radioprotective, anticancer, antiulcer properties. The current review mainly highlighted the nutritional and pharmacological activities of bael fruit. The nutritional profile and phytochemical profile were discussed in the review, along with their concentration in the fruit. Moreover, the experiments carried out in vivo and in vitro of bael fruit extracts with respect to their pharmacological activities were also discussed in the article. The recent literature based on nutritional and pharmacological values of bael fruit showed its high potential as a food and pharmaceutical product. Despite having high nutritional and pharmacological value, research related to molecular mechanisms of bael fruit is still limited, and clinical trials are needed to ensure its safety as a product in the food and pharma industries.
    Keywords:  Aegle marmelos (Bael); industrial applications; nutrition; pharmacological properties; phytochemical
    DOI:  https://doi.org/10.3390/ijms231810889
  198. Nano Res. 2022 Sep 12. 1-12
    Recent progress in single-atom nanozymes research.
    Bing Jiang, Zhanjun Guo, Minmin Liang.
      Single-atom nanozyme (SAzyme) is the hot topic of the current nanozyme research. Its intrinsic properties, such as high activity, stability, and low cost, present great substitutes to natural enzymes. Moreover, its fundamental characteristics, i.e., maximized atom utilizations and well-defined geometric and electronic structures, lead to higher catalytic activities and specificity than traditional nanozymes. SAzymes have been applied in many biomedical areas, such as anti-tumor therapy, biosensing, antibiosis, and anti-oxidation therapy. Here, we will discuss a series of representative examples of SAzymes categorized by their biomedical applications in this review. In the end, we will address the future opportunities and challenges SAzymes facing in their designs and applications.
    Keywords:  biomedical applications; enzyme-like activity; natural enzymes; single-atom nanozymes
    DOI:  https://doi.org/10.1007/s12274-022-4856-7
  199. Microorganisms. 2022 Aug 27. pii: 1727. [Epub ahead of print]10(9):
    Modulating Microbiota as a New Strategy for Breast Cancer Prevention and Treatment.
    Huixin Wu, Sebanti Ganguly, Trygve O Tollefsbol.
      Breast cancer (BC) is the most common cancer in women in the United States. There has been an increasing incidence and decreasing mortality rate of BC cases over the past several decades. Many risk factors are associated with BC, such as diet, aging, personal and family history, obesity, and some environmental factors. Recent studies have shown that healthy individuals and BC patients have different microbiota composition, indicating that microbiome is a new risk factor for BC. Gut and breast microbiota alterations are associated with BC prognosis. This review will evaluate altered microbiota populations in gut, breast tissue, and milk of BC patients, as well as mechanisms of interactions between microbiota modulation and BC. Probiotics and prebiotics are commercially available dietary supplements to alleviate side-effects of cancer therapies. They also shape the population of human gut microbiome. This review evaluates novel means of modulating microbiota by nutritional treatment with probiotics and prebiotics as emerging and promising strategies for prevention and treatment of BC. The mechanistic role of probiotic and prebiotics partially depend on alterations in estrogen metabolism, systematic immune regulation, and epigenetics regulation.
    Keywords:  breast cancer; breast microbiota; epigenetics; gut microbiota; prebiotics; probiotics
    DOI:  https://doi.org/10.3390/microorganisms10091727
  200. Pharmaceuticals (Basel). 2022 Sep 14. pii: 1143. [Epub ahead of print]15(9):
    Healing Potential of Propolis in Skin Wounds Evidenced by Clinical Studies.
    Cristiano da Rosa, Ian Lucas Bueno, Ana Clara Martins Quaresma, Giovanna Barbarini Longato.
      Propolis has been used since ancient times for the treatment of skin diseases and, currently, its pharmacological potential for healing and repairing various types of wounds is widely cited in the literature. The healing properties of propolis are mainly attributed to its composition which is rich in phenolic compounds, and propolis has aroused the interest of the pharmaceutical industry as a low-cost product as compared with other treatments and medications; however, most of the published data refer to its effects in vitro and in vivo and, so far, few clinical studies have been carried out proving its therapeutic efficacy. In this article, we aimed to review clinical trail data published in Portuguese, Spanish, and English, in Scielo, PubMed, Google Scholar, Medline, and Lilacs between 1990 and 2021 on the clinical use of propolis for skin ulcers. The potential of propolis as an alternative healing treatment for skin wounds such as diabetic, venous, and surgical wounds, as well as wounds caused by burns, etc., is mainly due to its evidenced properties such as antimicrobial, anti-inflammatory, analgesic, and angiogenesis promoter effects. However, there is a need to standardize the type of administration and the concentration of propolis for each type of wound. Furthermore, further clinical studies are essential to add information about propolis safety and for obtaining the best possible therapeutic benefits from its use.
    Keywords:  clinical studies; propolis; skin ulcers
    DOI:  https://doi.org/10.3390/ph15091143
  201. Molecules. 2022 Sep 15. pii: 6010. [Epub ahead of print]27(18):
    Use of Ferulic Acid in the Management of Diabetes Mellitus and Its Complications.
    Xu Li, Jingxian Wu, Fanxing Xu, Chun Chu, Xiang Li, Xinyi Shi, Wen Zheng, Zhenzhong Wang, Ying Jia, Wei Xiao.
      Diabetes mellitus, a metabolic disease mainly characterized by hyperglycemia, is becoming a serious social health problem worldwide with growing prevalence. Many natural compounds have been found to be effective in the prevention and treatment of diabetes, with negligible toxic effects. Ferulic acid (FA), a phenolic compound commonly found in medicinal herbs and the daily diet, was proved to have several pharmacological effects such as antihyperglycemic, antihyperlipidemic and antioxidant actions, which are beneficial to the management of diabetes and its complications. Data from PubMed, EM-BASE, Web of Science and CNKI were searched with the keywords ferulic acid and diabetes mellitus. Finally, 28 articles were identified after literature screening, and the research progress of FA for the management of DM and its complications was summarized in the review, in order to provide references for further research and medical applications of FA.
    Keywords:  diabetes mellitus; diabetic complications; ferulic acid
    DOI:  https://doi.org/10.3390/molecules27186010
  202. Pharmaceuticals (Basel). 2022 Aug 30. pii: 1083. [Epub ahead of print]15(9):
    Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment.
    Randa Mohammed Zaki, Mohammed F Aldawsari, Manal A Alossaimi, Shaikah F Alzaid, Vidya Devanathadesikan Seshadri, Alanood S Almurshedi, Basmah Nasser Aldosari, Rehab Mohammad Yusif, Ossama M Sayed.
      A liposphere system for intranasal delivery of quetiapine fumarate (QTF) was created to assess the potential for enhanced drug delivery. We investigated the effects of particle size, entrapment effectiveness, poly dispersibility index, and pluronic incorporation percentage on these variables. The optimal formula was examined using a TEM, and investigations into DSC, XRD, and FTIR were made. Optimized liposphere formulation in vitro dissolution investigation with a mean diameter of 294.4 ± 18.2 nm revealed about 80% drug release in 6 h. The intranasal injection of QTF-loaded lipospheres showed a shorter Tmax compared to that of intranasal and oral suspension, per the findings of an in vivo tissue distribution investigation in Wistar mice. Lipospheres were able to achieve higher drug transport efficiency (DTE %) and direct nose-to-brain drug transfer (DTP %). A potentially effective method for delivering QTF to specific brain regions is the liposphere system.
    Keywords:  DTE%; brain targeting; intranasal; lipospheres; quetiapine fumarate
    DOI:  https://doi.org/10.3390/ph15091083
  203. Antioxidants (Basel). 2022 Aug 25. pii: 1648. [Epub ahead of print]11(9):
    Sweet Potato Is Not Simply an Abundant Food Crop: A Comprehensive Review of Its Phytochemical Constituents, Biological Activities, and the Effects of Processing.
    Emily P Laveriano-Santos, Anallely López-Yerena, Carolina Jaime-Rodríguez, Johana González-Coria, Rosa M Lamuela-Raventós, Anna Vallverdú-Queralt, Joan Romanyà, Maria Pérez.
      Nowadays, sweet potato (Ipomoea batata L.; Lam.) is considered a very interesting nutritive food because it is rich in complex carbohydrates, but as a tubercle, contains high amounts of health-promoting secondary metabolites. The aim of this review is to summarize the most recently published information on this root vegetable, focusing on its bioactive phytochemical constituents, potential effects on health, and the impact of processing technologies. Sweet potato is considered an excellent source of dietary carotenoids, and polysaccharides, whose health benefits include antioxidant, anti-inflammatory and hepatoprotective activity, cardiovascular protection, anticancer properties and improvement in neurological and memory capacity, metabolic disorders, and intestinal barrier function. Moreover, the purple sweet potato, due to its high anthocyanin content, represents a unique food option for consumers, as well as a potential source of functional ingredients for healthy food products. In this context, the effects of commercial processing and domestic cooking techniques on sweet potato bioactive compounds require further study to understand how to minimize their loss.
    Keywords:  Ipomoea batata L. roots; bioactive compounds; biological functions; carotenes; cooking; healthy food; polyphenols
    DOI:  https://doi.org/10.3390/antiox11091648
  204. Nanoscale Adv. 2021 Jan 07. 3(1): 106-122
    Recent advances in phase change material based nanoplatforms for cancer therapy.
    Changyu Cao, Nan Yang, Hanming Dai, Han Huang, Xuejiao Song, Qi Zhang, Xiaochen Dong.
      Cancer has become a severe threat to human life due to its high mortality and metastatic rate. Effective inhibition and killing of cancer cells using chemotherapeutic drugs have been a promising means in clinical cancer therapy. However, the low selectivity, drug-resistance, uncontrollability and serious side effects of chemotherapy significantly limit its further development. There is an urgent need for new treatment strategies to compensate for deficiencies inherent in chemotherapy alone. A growing body of research shows that combined treatment strategies have the potential to overcome this dilemma by achieving significantly enhanced synergistic effects and reduced side effects. Emerging phase change materials (PCMs) create an ideal nanoplatform for cancer combination therapy due to their universal loading properties, stable and temperature-responsive phase transition capability, and excellent natural biocompatibility/biodegradability. The release of therapeutic agents can be precisely controlled through external, non-intrusive stimuli (such as NIR light and ultrasound), avoiding systemic toxicity associated with conventional chemotherapy. Herein, the construction methods and design principles of PCM-based nanoplatforms serving as strict gatekeeper and smart payload delivery systems are discussed in detail. Moreover, the advantages and disadvantages of these nanoplatforms are provided. A suitable discussion and perspective of the remaining challenges and future opportunities for PCM-based nanoplatforms in cancer treatment are also given in conclusion.
    DOI:  https://doi.org/10.1039/d0na00622j
  205. Phytother Res. 2022 Sep 19.
    Protective effects of curcumin on ischemia/reperfusion injury.
    Malihe Mohamadian, Negin Parsamanesh, Hossein Chiti, Thozhukat Sathyapalan, Amirhossein Sahebkar.
      Ischemia/reperfusion (I/R) injury is a term used to describe phenomena connected to the dysfunction of various tissue damage due to reperfusion after ischemic injury. While I/R may result in systemic inflammatory response syndrome or multiple organ dysfunction syndrome, there is still a long way to improve therapeutic outcomes. A number of cellular metabolic and ultrastructural alterations occur by prolonged ischemia. Ischemia increases the expression of proinflammatory gene products and bioactive substances within the endothelium, such as cytokines, leukocytes, and adhesion molecules, even as suppressing the expression of other "protective" gene products and substances, such as thrombomodulin and constitutive nitric oxide synthase (e.g., prostacyclin, nitric oxide [NO]). Curcumin is the primary phenolic pigment derived from turmeric, the powdered rhizome of Curcuma longa. Numerous studies have shown that curcumin has strong antiinflammatory and antioxidant characteristics. It also prevents lipid peroxidation and scavenges free radicals like superoxide anion, singlet oxygen, NO, and hydroxyl. In our study, we highlight the mechanisms of protective effects of curcumin against I/R injury in various organs.
    Keywords:  curcumin; gastrointestinal system; heart; ischemia-reperfusion injury; kidney; nervous system; reproductive organs
    DOI:  https://doi.org/10.1002/ptr.7620
  206. Polymers (Basel). 2022 Sep 09. pii: 3770. [Epub ahead of print]14(18):
    Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.
    Iqra Mubeen, Muhammad Zaman, Muhammad Farooq, Asim Mehmood, Fahad Khan Azeez, Wajiha Rehman, Sohail Akhtar, Mueen Ahmad Chaudhry, Muhammad Hammad Butt, Qurat-Ul-Ain Shamim, Sherjeel Adnan, Muhammad Rizwan Khan, Atta-Ur-Rehman.
      The objective of this work was to formulate co-loaded bilayer tablets containing ezetimibe (EZB) and atorvastatin (ATC). ATC loaded in the immediate-release (IR) layer is an HMG CoA reductase inhibitor, while EZB, added in the sustained-release (SR) layer, is a lipid-lowering agent. This study was conducted to evaluate the effects of polymer on the formulation and characterization of bilayer tablets, as well as the therapeutic impact of the concurrent use of both drugs having a sequential release pattern. To obtain the optimized results, four different formulations with variable compositions were developed and evaluated for different parameters. The drug release studies were carried out using a type II dissolution apparatus, using phosphate buffer solution (PBS) of 1.2 pH for IR of EZB for an initial 2 h, followed by 24 h studies for ATC in PBS 6.8 pH. The IR layer showed rapid drug release (96%) in 2 h, while 80% of the ATC was released in 24 h from the SR layer. Locally obtained, 6-week-old female albino rats were selected for in vivo studies. Both preventive and curative models were applied to check the effects of the drug combination on the lipid profile, atherosclerosis and physiology of different organs. Studies have shown that the administration of both drugs with different release patterns has a better therapeutic effect (p &lt; 0.05), both in preventing and in curing hyperlipidemia. Conclusively, through the sequential release of ATC and EZB, a better therapeutic response could be obtained.
    Keywords:  HPMC K-100; atorvastatin; bilayer tablets; ezetimibe
    DOI:  https://doi.org/10.3390/polym14183770
  207. Drug Deliv Transl Res. 2022 Sep 21.
    A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation.
    Prakash Khadka, Jack Dummer, Philip C Hill, Rajesh Katare, Shyamal C Das.
      Inhaled drug delivery is a promising approach to achieving high lung drug concentrations to facilitate efficient treatment of tuberculosis (TB) and to reduce the overall duration of treatment. Rifampicin is a good candidate for delivery via the pulmonary route. There have been no clinical studies yet at relevant inhaled doses despite the numerous studies investigating its formulation and preclinical properties for pulmonary delivery. This review discusses the clinical implications of pulmonary drug delivery in TB treatment, the drug delivery systems reported for pulmonary delivery of rifampicin, animal models, and the animal studies on inhaled rifampicin formulations, and the research gaps hindering the transition from preclinical development to clinical investigation. A review of reports in the literature suggested there have been minimal attempts to test inhaled formulations of rifampicin in laboratory animals at relevant high doses and there is a lack of appropriate studies in animal models. Published studies have reported testing only low doses (≤ 20 mg/kg) of rifampicin, and none of the studies has investigated the safety of inhaled rifampicin after repeated administration. Preclinical evaluations of inhaled anti-TB drugs, such as rifampicin, should include high-dose formulations in preclinical models, determined based on allometric conversions, for relevant high-dose anti-TB therapy in humans.
    Keywords:  Animal models; Inhalation; Preclinical development; Rifampicin; Tuberculosis
    DOI:  https://doi.org/10.1007/s13346-022-01238-y
  208. Dermatol Ther. 2022 Sep 20. e15842
    Complementary and alternative therapies in skin cancer: A literature review of biologically active compounds.
    Leonel Hidalgo, Cristóbal Saldías-Fuentes, Karina Carrasco, K S Allan C Halpern, Jun J Mao, Cristian Navarrete-Dechent.
      INTRODUCTION: Complementary and alternative medicine or therapies (CAM) are frequently used by skin cancers patients. Patient's self-administration of CAM in melanoma can reach up to 40-50%. CAMs such as botanical agents, phytochemicals, herbal formulas ("black salve") and cannabinoids, among others, have been described in skin cancer patients.OBJECTIVE: To acknowledge the different CAM for skin cancers through the current evidence, focusing on biologically active CAM rather than mind-body approaches.
    METHODS: We searched MEDLINE database for articles published through July 2022, regardless of study design.
    RESULTS: Of all CAMs, phytochemicals have the best in vitro evidence supporting efficacy against skin cancer including melanoma; however, to date, none have proved efficacy on human patients. Of the phytochemicals, Curcumin is the most widely studied. Several findings support Curcumin efficacy in vitro through various molecular pathways, although most studies are in the preliminary phase. In addition, the use of alternative therapies is not exempt of risks physicians should be aware of their adverse effects, interactions with standard treatments, and possible complications arising from CAM usage.
    CONCLUSION: There is emerging evidence for CAM use in skin cancer, but no human clinical trials support the effectiveness of any CAM in the treatment of skin cancer to date. Nevertheless, patients worldwide frequently use CAM, and physicians should educate themselves on currently available CAMs. This article is protected by copyright. All rights reserved.
    Keywords:  complementary and alternative medicine; complementary therapy; melanoma; non-melanoma skin cancer; skin cancer
    DOI:  https://doi.org/10.1111/dth.15842
  209. Neoplasma. 2022 Sep 22. pii: 220414N410. [Epub ahead of print]
    Resveratrol reduces lactate production and modifies the ovarian cancer immune microenvironment.
    Jing Chen, Shu-Ting Huang, Jian-Guo Chen, Jian-Hui He, Wu-Mei Lin, Zhi-Hong Huang, Hai-Yan Ye, Shan-Yang He.
      Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.
    DOI:  https://doi.org/10.4149/neo_2022_220414N410
  210. Int J Biol Macromol. 2022 Sep 20. pii: S0141-8130(22)02105-5. [Epub ahead of print]
    Dual acting acid-cleavable self-assembling prodrug from hyaluronic acid and ciprofloxacin: A potential system for simultaneously targeting bacterial infections and cancer.
    Usri H Ibrahim, Nikita Devnarain, Mahir Mohammed, Calvin A Omolo, Mohammed A Gafar, Mohammed Salih, Amit Pant, Letitia Shunmugam, Chunderika Mocktar, Rene Khan, Jung Kwon Oh, Thirumala Govender.
      The incidence and of bacterial infections, and resulting mortality, among cancer patients is growing dramatically, worldwide. Several therapeutics have been reported to have dual anticancer and antibacterial activity. However, there is still an urgent need to develop new drug delivery strategies to improve their clinical efficacy. Therefore, this study aimed to develop a novel acid cleavable prodrug (HA-Cip) from ciprofloxacin and hyaluronic acid to simultaneously enhance the anticancer and antibacterial properties of Cip as a superior drug delivery system. HA-Cip was synthesised and characterised (FT-IR, HR-MS, and H1 NMR). HA-Cip generated stable micelles with an average particle size, poly dispersion index (PDI) and zeta potential (ZP) of 237.89 ± 25.74 nm, 0.265 ± 0.013, and -17.82 ± 1.53 mV, respectively. HA-Cip showed ≥80 % cell viability against human embryonic kidney 293 cells (non-cancerous cells), ˂0.3 % haemolysis; and a faster pH-responsive ciprofloxacin release at pH 6.0. HA-Cip showed a 5.4-fold improvement in ciprofloxacin in vitro anticancer activity against hepatocellular cancer (HepG2) cells; and enhanced in vitro antibacterial activity against Escherichia coli and Klebsiella pneumoniae at pH 6.0. Our findings show HA-Cip as a promising prodrug for targeted delivery of ciprofloxacin to efficiently treat bacterial infections associated, and/or co-existing, with cancer.
    Keywords:  Antibacterial; Anticancer; Ciprofloxacin; Hyaluronic acid; Micelles; Prodrug; Self-assembly; pH-responsive
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.09.173
  211. Plants (Basel). 2022 Sep 16. pii: 2415. [Epub ahead of print]11(18):
    Study of the Antioxidant Properties of Filipendula ulmaria and Alnus glutinosa.
    Stanislav Sukhikh, Svetlana Ivanova, Liubov Skrypnik, Alina Bakhtiyarova, Viktoria Larina, Olesia Krol, Alexander Prosekov, Andrey Frolov, Maria Povydysh, Olga Babich.
      The demographic situation of the last few decades is characterized by the increased numbers of elderly and senile people, i.e., by the aging of the population. In humans, ageing is closely associated with the enhanced production of reactive oxygen species (ROS), development of systemic inflammation and related vascular atherosclerotic alterations and metabolic disorders, like obesity, diabetes mellitus and neurodegenerative diseases. As these age-related alterations are directly associated with up-regulation of ROS production and development of chronic oxidative stress, their onset can be essentially delayed by continuous daily consumption of dietary antioxidants-natural products of plant origin. Such antioxidants (in the form of plant extracts, biologically active complexes or individual compounds) can be supplemented to functional foods, i.e., dietary supplementations for daily diet aiming prolongation of active life and delay of the senescence onset. Thereby, use of widely spread medicinal plants might essentially improve cost efficiency of this strategy and availability of antioxidant-rich functional foods. Therefore, here we addressed, to the best of our knowledge for the first time, the antioxidant activity of the extracts prepared from the aerial parts of Filipendula ulmaria and Alnus glutinosa growing in the Kaliningrad region of Russia, and assessed the contents of the biologically active substances underlying these properties. It was found that the extract prepared with the leaves of Filipendula ulmaria and female catkins of Alnus glutinosa demonstrated high antioxidant activity, although the former plant was featured with a higher antioxidant potential. The highest antioxidant activity detected in the methanol extracts of Alnus glutinosa reached 1094.02 ± 14.53 µmol TE/g, radical scavenging of activity was 584.45 ± 35.3 µmol TE/g, reducing capacity at interaction with iron complex-471.63 ± 7.06 µmol TE/g. For the methanol extracts of Filipendula ulmaria the antioxidant activity reached 759.78 ± 19.08 µmol TE/g, antioxidant activity for free radical removal was 451.08 ± 24.45 µmol TE/g and antioxidant activity for restorative ability with iron complex was 332.28 ± 10.93 µmol TE/g. These values are consistent with the total yields of the extracts and their content of ellagic acid. The ethyl acetate extracts of the both plants showed just minimal antioxidant activity. Thus, the considered extracts have an essential potential. This creates good prospects for the further use of herbal extracts of Filipendula ulmaria and Alnus glutinosa as a source of natural antioxidants.
    Keywords:  Alnus glutinosa; Filipendula ulmaria; aging; antioxidant activity; free radicals; reactive oxygen species
    DOI:  https://doi.org/10.3390/plants11182415
  212. Children (Basel). 2022 Sep 10. pii: 1372. [Epub ahead of print]9(9):
    A Review of the Multi-Systemic Complications of a Ketogenic Diet in Children and Infants with Epilepsy.
    Kyra Newmaster, Zahra Zhu, Elizabeth Bolt, Ryan J Chang, Christopher Day, Asmaa Mhanna, Sita Paudel, Osman Farooq, Arun Swaminathan, Prakrati Acharya, Wisit Cheungpasitporn, Siddharth Gupta, Debopam Samanta, Naeem Mahfooz, Gayatra Mainali, Paul R Carney, Sunil Naik.
      Ketogenic diets (KDs) are highly effective in the treatment of epilepsy. However, numerous complications have been reported. During the initiation phase of the diet, common side effects include vomiting, hypoglycemia, metabolic acidosis and refusal of the diet. While on the diet, the side effects involve the following systems: gastrointestinal, hepatic, cardiovascular, renal, dermatological, hematologic and bone. Many of the common side effects can be tackled easily with careful monitoring including blood counts, liver enzymes, renal function tests, urinalysis, vitamin levels, mineral levels, lipid profiles, and serum carnitine levels. Some rare and serious side effects reported in the literature include pancreatitis, protein-losing enteropathy, prolonged QT interval, cardiomyopathy and changes in the basal ganglia. These serious complications may need more advanced work-up and immediate cessation of the diet. With appropriate monitoring and close follow-up to minimize adverse effects, KDs can be effective for patients with intractable epilepsy.
    Keywords:  children; epilepsy; ketogenic diet; modified atkins diet; nutrition; pediatrics; seizures
    DOI:  https://doi.org/10.3390/children9091372
  213. Exp Mol Med. 2022 Sep 18.
    Targeted inhibition of tumor-derived exosomes as a novel therapeutic option for cancer.
    Ye Li, Zhuo-Kun Chen, Xu Duan, He-Jing Zhang, Bo-Lin Xiao, Kui-Ming Wang, Gang Chen.
      Mounting evidence indicates that tumor-derived exosomes (TDEs) play critical roles in tumor development and progression by regulating components in the tumor microenvironment (TME) in an autocrine or paracrine manner. Moreover, due to their delivery of critical molecules that react to chemotherapy and immunotherapy, TDEs also contribute to tumor drug resistance and impede the effective response of antitumor immunotherapy, thereby leading to poor clinical outcomes. There is a pressing need for the inhibition or removal of TDEs to facilitate the treatment and prognosis of cancer patients. Here, in the present review, we systematically overviewed the current strategies for TDE inhibition and clearance, providing novel insights for future tumor interventions in translational medicine. Moreover, existing challenges and potential prospects for TDE-targeted cancer therapy are also discussed to bridge the gaps between progress and promising applications.
    DOI:  https://doi.org/10.1038/s12276-022-00856-3
  214. Curr Opin Pharmacol. 2022 Sep 19. pii: S1471-4892(22)00113-8. [Epub ahead of print]67 102286
    Metabokines in the regulation of systemic energy metabolism.
    Amanda Dv MacCannell, Lee D Roberts.
      Metabolism consists of life-sustaining chemical reactions involving metabolites. Historically, metabolites were defined as the intermediates or end products of metabolism and considered to be passive participants changed by metabolic processes. However, recent research has redefined how we view metabolism. There is emerging evidence of metabolites which function to mediate cellular signalling and interorgan crosstalk, regulating local metabolism and systemic physiology. These bioactive metabolite signals have been termed metabokines. Metabokines regulate diverse energy metabolism pathways across multiple tissues, including fatty acid β-oxidation, mitochondrial oxidative phosphorylation, lipolysis, glycolysis and gluconeogenesis. There is increasing impetus to uncover novel metabokine signalling axes to better understand how these may be perturbed in metabolic diseases and determine their utility as therapeutic targets.
    DOI:  https://doi.org/10.1016/j.coph.2022.102286
  215. Front Endocrinol (Lausanne). 2022 ;13 942549
    Puffball spores improve wound healing in a diabetic rat model.
    Tangtang He, Pengfei Sun, Bo Liu, Shiwei Wan, Penghua Fang, Jun Chen, Guicheng Huang, Wen Min.
      Persistent chronic oxidative stress is a primary pathogenic characteristics of diabetic foot ulcers. Puffball spores are a traditional Chinese medicine used to treat diabetic foot ulcers infections and bedsores. However, their effects against diabetic wounds and the mechanism underlying these effects remain largely unknown. The present study explored the effectiveness of puffball spores in diabetic wound treatment and the mechanisms underlying their effects. Sprague-Dawley rats with streptozotocin (STZ)-induced diabetes were treated with puffball spores to ascertain whether they accelerated wound healing.Real-time quantitative PCR, western blotting, hematoxylin-eosin and Masson's trichrome staining, immunohistochemistry analysis, and immunofluorescence assays were performed. As indicated by wound and serum histology and biochemical analyses, the puffball spores accelerated wound healing by activating Akt/Nrf2 signaling and promoting the expression of its downstream antioxidant genes, markedly stimulating antioxidant activity and enhanceing angiogenesis and collagen deposition. Our findings showed that puffball spores could accelerate diabetic wound healing, enhance antioxidant ability, promote the expression of vascular markers, and suppress inflammation, thus providing a theoretical basis for the treatment of diabetic and refractory wounds.
    Keywords:  Puffball spores; angiogenesis; diabetic wound ulcer; oxidative stress; wound healing
    DOI:  https://doi.org/10.3389/fendo.2022.942549
  216. Biomolecules. 2022 Aug 30. pii: 1201. [Epub ahead of print]12(9):
    Dietary Choice Reshapes Metabolism in Drosophila by Affecting Consumption of Macronutrients.
    Olha Strilbytska, Uliana Semaniuk, Volodymyr Bubalo, Kenneth B Storey, Oleh Lushchak.
      The precise regulation of metabolism and feeding behavior is important for preventing the development of metabolic diseases. Here we examine the effects on Drosophila metabolism of dietary choice. These changes are predicted to be dependent on both the quantity and quality of the chosen diet. Using a geometric framework for both no-choice and two-choice conditions, we found that feeding decisions led to higher glucose and trehalose levels but lower triglycerides pools. The feeding regimens had similar strategies for macronutrient balancing, and both maximized hemolymph glucose and glycogen content under low protein intake. In addition, the flies showed significant differences in the way they regulated trehalose and triglyceride levels in response to carbohydrate and protein consumption between choice and no-choice nutrition. Under choice conditions, trehalose and triglyceride levels were maximized at the lowest protein and carbohydrate consumption. Thus, we suggest that these changes in carbohydrate and lipid metabolism are caused by differences in the macronutrients consumed by flies. Food choice elicits rapid metabolic changes to maintain energy homeostasis. These results contribute to our understanding of how metabolism is regulated by the revealed nutrient variation in response to food decisions.
    Keywords:  Drosophila; food choice; macronutrients; metabolism
    DOI:  https://doi.org/10.3390/biom12091201
  217. Front Oncol. 2022 ;12 998346
    Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species.
    Mohd Farhan, Asim Rizvi, Ferasat Ali, Aamir Ahmad, Mohammad Aatif, Arshi Malik, Mir Waqas Alam, Ghazala Muteeb, Saheem Ahmad, Awal Noor, Farhan Asif Siddiqui.
      Anthocyanidins are the most abundant polyphenols in pomegranate juice. This class of molecules includes Delphinidin (Del), Cyanidin (Cya), and Pelargonidin (Pel). Using prostate, breast and pancreatic cancer cell lines PC3, MDA-MB-231, BxPC-3 and MiaPaCa-2, we show that anthocyanidins inhibit cell proliferation (measured by MTT assay) and induce apoptosis like cell death (measured by DNA/Histone ELISA). Copper chelator neocuproine and reactive oxygen species scavengers (thiourea for hydroxyl radical and superoxide dismutase for superoxide anion) significantly inhibit this reaction thus demonstrating that intracellular copper reacts with anthocyanidins in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitizes normal breast epithelial cells (MCF-10A) to Del-mediated growth inhibition as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters Ctr1 and ATP7A in MCF-10A cells, which is attenuated by the addition of Del in the medium. We propose that the copper mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of anthocyanidins.
    Keywords:  DNA damage; anthocyanidin; cell death; copper; prooxidant; reactive oxygen species
    DOI:  https://doi.org/10.3389/fonc.2022.998346
  218. Chem Sci. 2022 Aug 24. 13(33): 9525-9530
    Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.
    Jie Sun, Ning Cheng, Kai Yin, Rongchen Wang, Tianli Zhu, Jinzhu Gao, Xuemei Dong, Chengjun Dong, Xianfeng Gu, Chunchang Zhao.
      Photothermal agents (PTAs) with minimized side effects are critical for transforming cancer photothermal therapy (PTT) into clinical applications. However, most currently available PTAs lack true selective activation to reduce side effects because of heavy spectral overlap between photothermal agents and their corresponding products. This study reports the construction of activatable PTAs with target-initiated large spectral separation for highly effective reduction of side effects. Such designed probes involve two H2O2-activatable PTAs, aza-BOD-B1 (single activatable site) and aza-BOD-B2 (multiple activatable site). After interacting with H2O2, aza-BOD-B1 only displays a mild absorption redshift (60 nm) from 750 nm to 810 nm with serious spectral overlap, resulting in a mild photothermal effect on normal tissues upon 808 nm light irradiation. In contrast, aza-BOD-B2 displays a large absorption spectral separation (150 nm) from 660 nm to 810 nm, achieving true selective activation to minimize side effects during PTT of cancer. Besides, in vitro and in vivo investigations demonstrated that aza-BOD-B2 can specifically induce photothermal ablation of cancer cells and tumors while leaving normal sites undamaged, whereas aza-BOD-B1 exhibits undesirable side effects on normal cells. Our study provides a practical solution to the problem of undesired side effects of phototherapy, an advance in precision medicine.
    DOI:  https://doi.org/10.1039/d2sc02467e
  219. Biomed Res Int. 2022 ;2022 7659765
    Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms.
    Ali Salimi, Nejat Kheiripour, Ali Fathi Jouzdani, Hassan Ghasemi, Sara Soleimani Asl, Abolfazl Ghafouri-Khosrowshahi, Akram Ranjbar.
      Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin.Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity.
    Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.
    DOI:  https://doi.org/10.1155/2022/7659765
  220. Front Oncol. 2022 ;12 957135
    Exercise as cancer treatment: A clinical oncology framework for exercise oncology research.
    Kerry S Courneya, Christopher M Booth.
      Exercise has been proposed as a possible cancer treatment; however, there are an infinite number of clinical oncology settings involving diverse cancer types and treatment protocols in which exercise could be tested as a cancer treatment. The primary purpose of this paper is to propose a conceptual framework to organize and guide research on exercise as a cancer treatment across distinct clinical oncology settings. A secondary purpose is to provide an overview of existing exercise research using the proposed framework. The Exercise as Cancer Treatment (EXACT) framework proposes nine distinct clinical oncology scenarios based on tumor/disease status and treatment status at the time of the proposed exercise treatment. In terms of tumor/disease status, the primary tumor has either been surgically removed (primary goal to treat micrometastases), not surgically removed (primary goal to treat the primary tumor), or metastatic disease is present (primary goal to treat metastatic disease). In terms of treatment status, the extant disease has either not been treated yet (treatment naïve), is currently being treated (active treatment), or has previously been treated. These two key clinical oncology variables-tumor/disease status and treatment status-result in nine distinct clinical oncology scenarios in which exercise could be tested as a new cancer treatment: (a) treatment naïve micrometastases, (b) actively treated micrometastases, (c) previously treated micrometastases, (d) treatment naïve primary tumors, (e) actively treated primary tumors, (f) previously treated primary tumors, (g) treatment naïve metastatic disease, (h) actively treated metastatic disease, and (i) previously treated metastatic disease. To date, most preclinical animal studies have examined the effects of exercise on treatment naïve and actively treated primary tumors. Conversely, most observational human studies have examined the associations between exercise and cancer recurrence/survival in patients actively treated or previously treated for micrometastases. Few clinical trials have been conducted in any of these scenarios. For exercise to be integrated into clinical oncology practice as a cancer treatment, it will need to demonstrate benefit in a specific clinical setting. The EXACT framework provides a simple taxonomy for systematically evaluating exercise as a potential cancer treatment across a diverse range of cancer types and treatment protocols.
    Keywords:  cancer therapy; exercise; physical activity; survival; tumor growth
    DOI:  https://doi.org/10.3389/fonc.2022.957135
  221. Pharmaceuticals (Basel). 2022 Aug 31. pii: 1087. [Epub ahead of print]15(9):
    Nanotechnology for Pediatric Retinoblastoma Therapy.
    Eleonora Russo, Andrea Spallarossa, Bruno Tasso, Carla Villa, Chiara Brullo.
      Retinoblastoma is a rare, sometimes hereditary, pediatric cancer. In high-income countries this disease has a survival rate approaching 100%, while in low- and middle-income countries the prognosis is fatal for about 80% of cases. Depending on the stage of the disease, different therapeutic protocols are applied. In more advanced forms of the disease, surgical removal of the entire globe and its intraocular contents (enucleation) is, unfortunately, necessary, whereas in other cases, conventional chemotherapy is normally used. To overcome the side-effects and reduced efficacy of traditional chemotherapic drugs, nanodelivery systems that ensure a sustained drug release and manage to reach the target site have more recently been developed. This review takes into account the current use and advances of nanomedicine in the treatment of retinoblastoma and discusses nanoparticulate formulations that contain conventional drugs and natural products. In addition, future developments in retinoblastoma treatment are discussed.
    Keywords:  cancer; conventional chemotherapy; nanomedicine; nanoparticle; pediatric rare disease; retinoblastoma
    DOI:  https://doi.org/10.3390/ph15091087
  222. J Pers Med. 2022 Sep 15. pii: 1515. [Epub ahead of print]12(9):
    Multi-Target Mechanisms of Phytochemicals in Alzheimer's Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation.
    Javad Sharifi-Rad, Simona Rapposelli, Simona Sestito, Jesús Herrera-Bravo, Alejandra Arancibia-Diaz, Luis A Salazar, Balakyz Yeskaliyeva, Ahmet Beyatli, Gerardo Leyva-Gómez, Carlos González-Contreras, Eda Sönmez Gürer, Miquel Martorell, Daniela Calina.
      Alzheimer's disease (AD) is a neurodegenerative disease characterized by a tangle-shaped accumulation of beta-amyloid peptide fragments and Tau protein in brain neurons. The pathophysiological mechanism involves the presence of Aβ-amyloid peptide, Tau protein, oxidative stress, and an exacerbated neuro-inflammatory response. This review aims to offer an updated compendium of the most recent and promising advances in AD treatment through the administration of phytochemicals. The literature survey was carried out by electronic search in the following specialized databases PubMed/Medline, Embase, TRIP database, Google Scholar, Wiley, and Web of Science regarding published works that included molecular mechanisms and signaling pathways targeted by phytochemicals in various experimental models of Alzheimer's disease in vitro and in vivo. The results of the studies showed that the use of phytochemicals against AD has gained relevance due to their antioxidant, anti-neuroinflammatory, anti-amyloid, and anti-hyperphosphorylation properties of Tau protein. Some bioactive compounds from plants have been shown to have the ability to prevent and stop the progression of Alzheimer's.
    Keywords:  Alzheimer’s disease; molecular mechanisms; neuroinflammation; neuroprotective effects; oxidative damage; phytochemicals; protein aggregation
    DOI:  https://doi.org/10.3390/jpm12091515
  223. Pharmaceuticals (Basel). 2022 Aug 29. pii: 1075. [Epub ahead of print]15(9):
    Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple-Negative Breast Cancer Cell Lines.
    Fu Hou Wong, Vijayaraj Kumar Palanirajan, Edmond Siah Chye Ng, Chung Keat Tan, Eugenie Sin Sing Tan, Farahnaz Amini.
      Monotherapy for triple-negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real-time cell analyzer assay), (ii.) cell migration (CIM-Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA-MB-468 and BT-20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT-20 was 91.6 and 10 µM, respectively, and in MDA-MB-468, it was 1 mM and 10 µM. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT-20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA-MB-468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA-MB-468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC.
    Keywords:  TNBC; anticancer effect; breast cancer; calcitriol; combined therapy; talazoparib; triple−negative breast cancer
    DOI:  https://doi.org/10.3390/ph15091075
  224. Molecules. 2022 Sep 08. pii: 5825. [Epub ahead of print]27(18):
    The Application of Ultrasound in Honey: Antioxidant Activity, Inhibitory Effect on α-amylase and α-glucosidase, and In Vitro Digestibility Assessment.
    Armando Peláez-Acero, Diana Belem Garrido-Islas, Rafael Germán Campos-Montiel, Lucio González-Montiel, Gabriela Medina-Pérez, Lorena Luna-Rodríguez, Uriel González-Lemus, Antonio de Jesús Cenobio-Galindo.
      In the present study, the effects of ultrasound (10, 20, and 30 min) on the bioactive compounds, antioxidant capacity, enzymatic inhibition, and in vitro digestion of six honey extracts from the Oaxaca state, Mexico, were analyzed. Significant differences were found in each honey extract with respect to the ultrasonic treatment applied (p &lt; 0.05). In the honey extract P-A1 treated with 20 min of ultrasound, the phenols reached a maximum concentration of 29.91 ± 1.56 mg EQ/100 g, and the flavonoids of 1.92 ± 0.01 mg EQ/100 g; in addition, an inhibition of α-amylase of 37.14 ± 0.09% was noted. There were also differences in the phases of intestinal and gastric digestion, presenting a decrease in phenols (3.92 ± 0.042 mg EQ/100 g), flavonoids (0.61 ± 0.17 mg EAG/100 mg), antioxidant capacity (8.89 ± 0.56 mg EAG/100 mg), and amylase inhibition (9.59 ± 1.38%). The results obtained from this study indicate that, in some honeys, the processing method could increase the concentration of bioactive compounds, the antioxidant capacity, and the enzymatic inhibition; however, when subjected to in vitro digestion, the properties of honey are modified. The results obtained could aid in the development of these compounds for use in traditional medicine as a natural source of bioactive compounds.
    Keywords:  botanical origin; enzyme inhibition; flavonoids; phenols; ultrasound
    DOI:  https://doi.org/10.3390/molecules27185825
  225. J Funct Biomater. 2022 Aug 24. pii: 125. [Epub ahead of print]13(3):
    Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases.
    Nicolò Montegiove, Eleonora Calzoni, Carla Emiliani, Alessio Cesaretti.
      Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood-brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases.
    Keywords:  biopolymers; blood–brain barrier; drug delivery systems; glioblastoma; lysosomal storage diseases; nanoparticles; neurodegenerative disorders; nose-to-brain administration
    DOI:  https://doi.org/10.3390/jfb13030125
  226. Prog Biomater. 2022 Sep 19.
    Antimicrobial cryogel dressings towards effective wound healing.
    Basak Akin, Mehmet Murat Ozmen.
      Cryogels are macroporous hydrogels that have been widely utilized in a variety of biomedical applications including wound dressings. Cryogels reveal superior mechanical and swelling properties as well as large and interconnected porosity. As traditional hydrogel wound dressings generally show undesirable mechanical and swelling characteristics, cryogels, due to their toughness and superfast swelling, offer an outstanding platform to address the growing number of various types of wounds. Moreover, recently, cryogel wound dressings loaded with an antimicrobial agent emerged as a feasible option to reduce infection, and thus improve the wound healing process. However, a comprehensive review of antimicrobial cryogels as a wound dressing is still lacking in the literature. In this review, we summarize the progress of cryogels in the area of wound dressings and provide an overview of the various polymers, namely, natural and synthetic which have been employed in cryogel wound dressing preparation. Furthermore, the most prominent antimicrobial agents incorporated in cryogel wound dressings are provided. Finally, the future directions of cryogel wound dressings for wound healing are also discussed.
    Keywords:  Antimicrobial; Biomaterial; Cryogel; Macroporous; Wound dressing
    DOI:  https://doi.org/10.1007/s40204-022-00202-w
  227. Foods. 2022 Sep 15. pii: 2863. [Epub ahead of print]11(18):
    Health Benefits and Side Effects of Short-Chain Fatty Acids.
    Ruo-Gu Xiong, Dan-Dan Zhou, Si-Xia Wu, Si-Yu Huang, Adila Saimaiti, Zhi-Jun Yang, Ao Shang, Cai-Ning Zhao, Ren-You Gan, Hua-Bin Li.
      The gut microbiota and their metabolites could play an important role in health and diseases of human beings. Short-chain fatty acids (SCFAs) are mainly produced by gut microbiome fermentation of dietary fiber and could also be produced by bacteria of the skin and vagina. Acetate, propionate, and butyrate are three major SCFAs, and their bioactivities have been widely studied. The SCFAs have many health benefits, such as anti-inflammatory, immunoregulatory, anti-obesity, anti-diabetes, anticancer, cardiovascular protective, hepatoprotective, and neuroprotective activities. This paper summarizes health benefits and side effects of SCFAs with a special attention paid to the mechanisms of action. This paper provides better support for people eating dietary fiber as well as ways for dietary fiber to be developed into functional food to prevent diseases.
    Keywords:  SCFAs; cancer; cardiovascular disease; diabetes mellitus; inflammation; obesity
    DOI:  https://doi.org/10.3390/foods11182863
  228. Pharmaceuticals (Basel). 2022 Aug 28. pii: 1071. [Epub ahead of print]15(9):
    Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids.
    Ankit Kumar Singh, Adarsh Kumar, Harshwardhan Singh, Pankaj Sonawane, Harshali Paliwal, Suresh Thareja, Prateek Pathak, Maria Grishina, Mariusz Jaremko, Abdul-Hamid Emwas, Jagat Pal Yadav, Amita Verma, Habibullah Khalilullah, Pradeep Kumar.
      Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011-2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.
    Keywords:  anticancer agents; cell lines; in vitro; molecular hybridization; pharmacophore
    DOI:  https://doi.org/10.3390/ph15091071
  229. Life (Basel). 2022 Sep 02. pii: 1369. [Epub ahead of print]12(9):
    Self-Nanoemulsifying Drug Delivery System of 2-Methoxyestradiol Exhibits Enhanced Anti-Proliferative and Pro-Apoptotic Activities in MCF-7 Breast Cancer Cells.
    Salwa D Al-Qahtani, Hawazen H Bin-Melaih, Eman M Atiya, Usama A Fahmy, Lenah S Binmahfouz, Thikryat Neamatallah, Fahad A Al-Abbasi, Ashraf B Abdel-Naim.
      (1) Background: 2-Methoxyestradiol (2ME) is a metabolite of estrogens and possesses promising anti-proliferative and cytotoxic activities. However, it suffers unfavorable pharmacokinetic characteristics such as absorption after oral administration. The aim of this study was to prepare an optimized 2ME self-nanoemulsifying drug delivery system (2ME-SNEDDS) and evaluate its cytotoxicity and pro-apoptotic activities in MCF-7 breast cancer cells. (2) Methods: For optimization of the 2ME-SNEDDS, a three-component system was used in the D-optimal mixture experimental study. MCF-7 cells were incubated with the 2ME-SNEDDS and subjected to an assessment of growth inhibition, cell cycle progression, annexin V staining, caspase-3 concentration, Bax, Bcl-2, and cyclin D1 mRNA expression, and reactive oxygen species (ROS) generation. (3) Results: The optimized formula had a globule size of 94.97 ± 4.35 nm. Zeta potential was found to be -3.4 ± 1.2 mV with a polydispersity index (PDI) of 0.34. In addition, 96.3  ± 4.3% of 2ME was released from the 2ME-SNEDDS within 24 h using the activated analysis bag technique. Moreover, the prepared 2ME-SNEDDS exhibited a significant enhancement of the anti-proliferative activity against MCF-7 cells in comparison to raw 2ME. This was associated with cyclin D1 expression down-regulation and the accumulation of cells in the G0/G1 and G2/M phases. The pro-apoptotic activities of the 2ME-SNEDDS were confirmed by annexin V staining, which indicated enhanced early and late cell death. This accompanied modulation of the mRNA expression of Bax and Bcl-2 in favor of apoptosis. The 2ME-SNEDDS significantly enhanced cleaved caspase-3 concentration in comparison to raw 2ME. In addition, the 2ME-SNEDDS significantly increased the generation of ROS in MCF-7 cells. (4) Conclusions: The 2ME-SNEDDS exhibits enhanced cytotoxicity and pro-apoptotic activity in MCF-7 cells. This is mediated by, at least partially, ROS generation.
    Keywords:  2-methoxyestradiol; apoptosis; breast cancer cells; cytotoxicity; self-nanoemulsifying drug delivery system
    DOI:  https://doi.org/10.3390/life12091369
  230. J Biochem Mol Toxicol. 2022 Sep 19. e23206
    Betulinic acid: A natural promising anticancer drug, current situation, and future perspectives.
    Maniyamma Aswathy, Ajesh Vijayan, Uzini D Daimary, Sosmitha Girisa, Kokkuvayil V Radhakrishnan, Ajaikumar B Kunnumakkara.
      Natural products serve as the single most productive source for the discovery of drugs and pharmaceutical leads. Among the various chemicals derived from microbes, plants, and animals, phytochemicals have emerged as potential candidates for the development of anticancer drugs due to their structural diversities, complexities, and pleiotropic effects. Herein, we discuss betulinic acid (BA), a ubiquitously distributed lupane structured pentacyclic triterpenoid, scrutinized as a promising natural agent for the prevention, suppression, and management of various human malignancies. Ease of availability, common occurrences, cell-specific cytotoxicity, and astonishing selectivity are the important factors that contribute to the development of BA as an anticancer agent. The current review delineates the mechanistic framework of BA-mediated cancer suppression through the modulation of multiple signaling pathways and also summarizes the key outcomes of BA in preclinical investigations.
    Keywords:  anticancer; apoptosis; betulin; betulinic acid; cytotoxicity; hydrosolubility; pharmacokinetics
    DOI:  https://doi.org/10.1002/jbt.23206
  231. Antioxidants (Basel). 2022 Sep 15. pii: 1819. [Epub ahead of print]11(9):
    Anti- and Pro-Oxidant Properties of Essential Oils against Antimicrobial Resistance.
    Amanda Shen-Yee Kong, Sathiya Maran, Polly Soo-Xi Yap, Swee-Hua Erin Lim, Shun-Kai Yang, Wan-Hee Cheng, Yong-Hui Tan, Kok-Song Lai.
      The rapid evolution of antimicrobial resistance (AMR) has remained a major public health issue, reducing the efficacy of antibiotics and increasing the difficulty of treating infections. The discovery of novel antimicrobial agents is urgently needed to overcome the challenges created by AMR. Natural products such as plant extracts and essential oils (EOs) have been viewed as potential candidates to combat AMR due to their complex chemistry that carries inherent pro-oxidant and antioxidant properties. EOs and their constituents that hold pro-oxidant properties can induce oxidative stress by producing reactive oxygen species (ROS), leading to biological damage in target cells. In contrast, the antioxidant properties scavenge free radicals through offsetting ROS. Both pro-oxidant and antioxidant activities in EOs represent a promising strategy to tackle AMR. Thus, this review aimed to discuss how pro-oxidants and antioxidants in EOs may contribute to the mitigation of AMR and provided a detailed description of the challenges and limitations of utilizing them as a means to combat AMR.
    Keywords:  ROS; antimicrobial resistance; antioxidant; essential oil; pro-oxidant
    DOI:  https://doi.org/10.3390/antiox11091819
  232. Pharmaceutics. 2022 Aug 30. pii: 1823. [Epub ahead of print]14(9):
    Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance.
    Shadreen Fairuz, Rajesh Sreedharan Nair, Nashiru Billa.
      Amphotericin B is an effective polyene antifungal considered as a "gold standard" in the management of fungal infections. Currently, it is administered mainly by IV due to poor aqueous solubility, which precludes its delivery orally. Paradoxically, IV administration is akin to side effects that have not been fully eliminated even with more recent IV formulations. Thus, the need for alternative formulations/route of administration for amphotericin B remains crucial. The oral route offers the possibility of delivering amphotericin B systemically and with diminished side effects; however, enterocyte permeation remains a constraint. Cellular phagocytosis of submicron particles can be used to courier encapsulated drugs. In this regard, nanoparticulate delivery systems have received much attention in the past decade. This review examines the trajectory of orally delivered amphotericin B and discusses key physical factors of nanoformulations that impact bioavailability. The review also explores obstacles that remain and gives a window into the possibility of realizing an oral nanoformulation of amphotericin B in the near future.
    Keywords:  amphotericin B; bioavailability; clinical; nanoparticle; oral
    DOI:  https://doi.org/10.3390/pharmaceutics14091823
  233. Pharmaceutics. 2022 Aug 25. pii: 1771. [Epub ahead of print]14(9):
    Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies.
    Abdulsalam Alhalmi, Saima Amin, Zafar Khan, Sarwar Beg, Omkulthom Al Kamaly, Asmaa Saleh, Kanchan Kohli.
      This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization-sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance.
    Keywords:  acute toxicity study; breast cancer; central composite design; combination; nanostructured lipid carriers; naringin; raloxifene
    DOI:  https://doi.org/10.3390/pharmaceutics14091771
  234. J Hematol Oncol. 2022 Sep 17. 15(1): 135
    TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.
    Xueke Shi, Jin Yang, Shuzhi Deng, Hongdan Xu, Deyang Wu, Qingxiang Zeng, Shimeng Wang, Tao Hu, Fanglong Wu, Hongmei Zhou.
      Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an "engine" of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an "endocrine" cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.
    Keywords:  Cancer cell; Host metabolism; Stromal cell; TGF-β signaling; Tumor metabolic microenvironment
    DOI:  https://doi.org/10.1186/s13045-022-01349-6
  235. Drug Deliv. 2022 Dec;29(1): 3123-3133
    A novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer.
    Xiaoming Cui, Fang Zhang, Yanyan Zhao, Pan Li, Ting Wang, Zhilu Xu, Jingjing Zhang, Weifen Zhang.
      Chemotherapy is the first choice for the treatment of cancer but it is still limited by insufficient kill efficiency and drug resistance. These problems urgently need to be overcome in a way that minimizes damage to the body. In this study, we designed the nanocomposite microparticles (NMPs) modified by cetuximab (Cet) and loaded anti-tumor agents- quercetin (QUE) and paclitaxel (PTX)- for eliciting specific drugs homing and enhancing the killing efficiency of chemotherapy drugs (P/Q@CNMPs). Physicochemical characteristics results presented that P/Q@CNMPs have a suitable aerodynamic diameter and uniform morphology that could meet the requirements of particles deposition in the lung. And it also had the characteristics of sustained-release and pH-responsive which could release the agents in the right place and has a continuous effect. In vitro and in vivo analysis results presented that P/Q@CNMPs have the accuracy targeting ability and killing effect on non-small cell lung cancer (NSCLC) which express positive epidermal growth factor receptor (EGFR) on the membrane. Furthermore, this system also has low toxicity and good biocompatibility. These results demonstrated that P/Q@CNMPs could be a potential intelligent targeting strategy used for chemo-resistant NSCLC therapies.
    Keywords:  NSCLC; active targeting; anti-tumor; nanocomposite microspheres; orthotopic
    DOI:  https://doi.org/10.1080/10717544.2022.2120567
  236. Pharmaceutics. 2022 Sep 11. pii: 1919. [Epub ahead of print]14(9):
    "Targeting Design" of Nanoparticles in Tumor Therapy.
    Tingting Yang, Jingming Zhai, Dong Hu, Ruyue Yang, Guidan Wang, Yuanpei Li, Gaofeng Liang.
      Tumor-targeted therapy based on nanoparticles is a popular research direction in the biomedical field. After decades of research and development, both the passive targeting ability of the inherent properties of NPs and the active targeting based on ligand receptor interaction have gained deeper understanding. Unfortunately, most targeted delivery strategies are still in the preclinical trial stage, so it is necessary to further study the biological fate of particles in vivo and the interaction mechanism with tumors. This article reviews different targeted delivery strategies based on NPs, and focuses on the physical and chemical properties of NPs (size, morphology, surface and intrinsic properties), ligands (binding number/force, activity and species) and receptors (endocytosis, distribution and recycling) and other factors that affect particle targeting. The limitations and solutions of these factors are further discussed, and a variety of new targeting schemes are introduced, hoping to provide guidance for future targeting design and achieve the purpose of rapid transformation of targeted particles into clinical application.
    Keywords:  application; cancer therapy; drug delivery; nanoparticles; targeted transportation
    DOI:  https://doi.org/10.3390/pharmaceutics14091919
  237. Int J Nanomedicine. 2022 ;17 4195-4210
    Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis.
    Zi Chao Wu, Xin Yu Liu, Jia Yan Liu, Jing Shu Piao, Ming Guan Piao.
      Aim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver.Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro.
    Results: BA-GC-NPs with diameters <200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice.
    Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.
    Keywords:  betulinic acid; chitosan; lactobionic acid; liver fibrosis; nanoparticles
    DOI:  https://doi.org/10.2147/IJN.S373430
  238. Antioxidants (Basel). 2022 Aug 30. pii: 1722. [Epub ahead of print]11(9):
    Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis.
    Yi Ting Lee, Mohd Heikal Mohd Yunus, Azizah Ugusman, Muhammad Dain Yazid.
      Osteoarthritis (OA) is the most common type of arthritis and chronic joint disease, affecting more than 240 million people worldwide. Although there are numerous advances in using drugs in treating OA, the use of natural compounds has aroused much interest among researchers due to their safety margin. Recent discovery shows that natural compounds play an extensive role in the oxidative stress signaling pathway in treating OA. Thus, this review summarizes the commonly used natural compounds for treating OA focusing on the oxidative stress signaling pathway and its downstream mediators. Selected databases-such as Scopus, Web of Science, Nature, and PubMed-were used to search for potentially relevant articles. The search is limited to the last 15 years and the search was completed using the Boolean operator's guideline using the keywords of natural product AND oxidative stress AND osteoarthritis OR natural extract AND ROS AND degenerative arthritis OR natural plant AND free radicals AND degenerative joint disease. In total, 37 articles were selected for further review. Different downstream mechanisms of oxidative stress involved in the usage of natural compounds for OA treatment and anabolic and catabolic effects of natural compounds that exhibit chondroprotective effects have been discussed with the evidence of in vitro and in vivo trials in this review.
    Keywords:  ROS; anabolic/catabolic effects; antioxidants; natural compounds; osteoarthritis; oxidative stress
    DOI:  https://doi.org/10.3390/antiox11091722
  239. Cancers (Basel). 2022 Sep 15. pii: 4474. [Epub ahead of print]14(18):
    Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers.
    Alberto Juan, María Del Mar Noblejas-López, Iván Bravo, María Arenas-Moreira, Cristina Blasco-Navarro, Pilar Clemente-Casares, Agustín Lara-Sánchez, Atanasio Pandiella, Carlos Alonso-Moreno, Alberto Ocaña.
      BRCA1/2 protein-deficient or mutated cancers comprise a group of aggressive malignancies. Although PARPis have shown considerably efficacy in their treatment, the widespread use of these agents in clinical practice is restricted by various factors, including the development of acquired resistance due to the presence of compensatory pathways. BETis can completely disrupt the HR pathway by repressing the expression of BRCA1 and could be aimed at generation combination regimes to overcome PARPi resistance and enhance PARPi efficacy. Due to the poor pharmacokinetic profile and short half-life, the first-in-class BETi JQ1 was loaded into newly developed nanocarrier formulations to improve the effectivity of olaparib for the treatment of BRCAness cancers. First, polylactide polymeric nanoparticles were generated by double emulsion. Moreover, liposomes were prepared by ethanol injection and evaporation solvent method. JQ1-loaded drug delivery systems display optimal hydrodynamic radii between 60 and 120 nm, with a very low polydispersity index (PdI), and encapsulation efficiencies of 92 and 16% for lipid- and polymeric-based formulations, respectively. Formulations show high stability and sustained release. We confirmed that all assayed JQ1 formulations improved antiproliferative activity compared to the free JQ1 in models of ovarian and breast cancers. In addition, synergistic interaction between JQ1 and JQ1-loaded nanocarriers and olaparib evidenced the ability of encapsulated JQ1 to enhance antitumoral activity of PARPis.
    Keywords:  JQ1; breast cancer; combination regimes; liposomes; nanomedicine; olaparib; ovarian cancer; polymeric nanoparticles
    DOI:  https://doi.org/10.3390/cancers14184474
  240. Gels. 2022 Sep 15. pii: 587. [Epub ahead of print]8(9):
    Mucoadhesive Polymers and Their Applications in Drug Delivery Systems for the Treatment of Bladder Cancer.
    Caroline S A de Lima, Justine P R O Varca, Victória M Alves, Kamila M Nogueira, Cassia P C Cruz, M Isabel Rial-Hermida, Sławomir S Kadłubowski, Gustavo H C Varca, Ademar B Lugão.
      Bladder cancer (BC) is the tenth most common type of cancer worldwide, affecting up to four times more men than women. Depending on the stage of the tumor, different therapy protocols are applied. Non-muscle-invasive cancer englobes around 70% of the cases and is usually treated using the transurethral resection of bladder tumor (TURBIT) followed by the instillation of chemotherapy or immunotherapy. However, due to bladder anatomy and physiology, current intravesical therapies present limitations concerning permeation and time of residence. Furthermore, they require several frequent catheter insertions with a reduced interval between doses, which is highly demotivating for the patient. This scenario has encouraged several pieces of research focusing on the development of drug delivery systems (DDS) to improve drug time residence, permeation capacity, and target release. In this review, the current situation of BC is described concerning the disease and available treatments, followed by a report on the main DDS developed in the past few years, focusing on those based on mucoadhesive polymers as a strategy. A brief review of methods to evaluate mucoadhesion properties is also presented; lastly, different polymers suitable for this application are discussed.
    Keywords:  bladder tumor; drug release; intravesical therapy; mucoadhesion; polymeric hydrogels
    DOI:  https://doi.org/10.3390/gels8090587
  241. Polymers (Basel). 2022 Sep 12. pii: 3806. [Epub ahead of print]14(18):
    Hybrid-Based Wound Dressings: Combination of Synthetic and Biopolymers.
    Blessing Atim Aderibigbe.
      Most commercialized wound dressings are polymer-based. Synthetic and natural polymers have been utilized widely for the development of wound dressings. However, the use of natural polymers is limited by their poor mechanical properties, resulting in their combination with synthetic polymers and other materials to enhance their mechanical properties. Natural polymers are mostly affordable, biocompatible, and biodegradable with promising antimicrobial activity. They have been further tailored into unique hybrid wound dressings when combined with synthetic polymers and selected biomaterials. Some important features required in an ideal wound dressing include the capability to prevent bacteria invasion, reduce odor, absorb exudates, be comfortable, facilitate easy application and removal as well as frequent changing, prevent further skin tear and irritation when applied or removed, and provide a moist environment and soothing effect, be permeable to gases, etc. The efficacy of polymers in the design of wound dressings cannot be overemphasized. This review article reports the efficacy of wound dressings prepared from a combination of synthetic and natural polymers.
    Keywords:  biomaterials; hybrid wound dressings; natural polymers; skin regeneration; synthetic polymers; wound dressings; wound healing; wounds
    DOI:  https://doi.org/10.3390/polym14183806
  242. Int J Mol Sci. 2022 Sep 10. pii: 10521. [Epub ahead of print]23(18):
    Significance of Capping Agents of Colloidal Nanoparticles from the Perspective of Drug and Gene Delivery, Bioimaging, and Biosensing: An Insight.
    Rabia Javed, Anila Sajjad, Sania Naz, Humna Sajjad, Qiang Ao.
      The over-growth and coagulation of nanoparticles is prevented using capping agents by the production of stearic effect that plays a pivotal role in stabilizing the interface. This strategy of coating the nanoparticles' surface with capping agents is an emerging trend in assembling multipurpose nanoparticles that is beneficial for improving their physicochemical and biological behavior. The enhancement of reactivity and negligible toxicity is the outcome. In this review article, an attempt has been made to introduce the significance of different capping agents in the preparation of nanoparticles. Most importantly, we have highlighted the recent progress, existing roadblocks, and upcoming opportunities of using surface modified nanoparticles in nanomedicine from the drug and gene delivery, bioimaging, and biosensing perspectives.
    Keywords:  biosensing; capping agents; diagnostics; drug delivery; nanoparticles; therapeutics
    DOI:  https://doi.org/10.3390/ijms231810521
  243. Pharmaceutics. 2022 Sep 19. pii: 1974. [Epub ahead of print]14(9):
    A Review of Non-Invasive Drug Delivery through Respiratory Routes.
    Yong-Bo Zhang, Dong Xu, Lu Bai, Yan-Ming Zhou, Han Zhang, Yuan-Lu Cui.
      With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.
    Keywords:  COVID-19; nanoparticles; nasal drug delivery; pulmonary drug delivery; scientometric analysis
    DOI:  https://doi.org/10.3390/pharmaceutics14091974
  244. Bioengineering (Basel). 2022 Sep 15. pii: 474. [Epub ahead of print]9(9):
    Synergetic Thermal Therapy for Cancer: State-of-the-Art and the Future.
    Qizheng Dai, Bo Cao, Shiqing Zhao, Aili Zhang.
      As a safe and minimal-invasive modality, thermal therapy has become an effective treatment in cancer treatment. Other than killing the tumor cells or destroying the tumor entirely, the thermal modality results in profound molecular, cellular and biological effects on both the targeted tissue, surrounding environments, and even the whole body, which has triggered the combination of the thermal therapy with other traditional therapies as chemotherapy and radiation therapy or new therapies like immunotherapy, gene therapy, etc. The combined treatments have shown encouraging therapeutic effects both in research and clinic. In this review, we have summarized the outcomes of the existing synergistic therapies, the underlying mechanisms that lead to these improvements, and the latest research in the past five years. Limitations and future directions of synergistic thermal therapy are also discussed.
    Keywords:  cancer; combination; physical therapy; thermal therapy
    DOI:  https://doi.org/10.3390/bioengineering9090474
  245. Front Neurosci. 2022 ;16 962922
    Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer's disease.
    Madilyn Coles, Genevieve Z Steiner-Lim, Tim Karl.
      Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by declining cognition and behavioral impairment, and hallmarked by extracellular amyloid-β plaques, intracellular neurofibrillary tangles (NFT), oxidative stress, neuroinflammation, and neurodegeneration. There is currently no cure for AD and approved treatments do not halt or slow disease progression, highlighting the need for novel therapeutic strategies. Importantly, the endocannabinoid system (ECS) is affected in AD. Phytocannabinoids, including cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), interact with the ECS, have anti-inflammatory, antioxidant, and neuroprotective properties, can ameliorate amyloid-β and NFT-related pathologies, and promote neurogenesis. Thus, in recent years, purified CBD and THC have been evaluated for their therapeutic potential. CBD reversed and prevented the development of cognitive deficits in AD rodent models, and low-dose THC improved cognition in aging mice. Importantly, CBD, THC, and other phytochemicals present in Cannabis sativa interact with each other in a synergistic fashion (the "entourage effect") and have greater therapeutic potential when administered together, rather than individually. Thus, treatment of AD using a multi-cannabinoid strategy (such as whole plant cannabis extracts or particular CBD:THC combinations) may be more efficacious compared to cannabinoid isolate treatment strategies. Here, we review the current evidence for the validity of using multi-cannabinoid formulations for AD therapy. We discuss that such treatment strategies appear valid for AD therapy but further investigations, particularly clinical studies, are required to determine optimal dose and ratio of cannabinoids for superior effectiveness and limiting potential side effects. Furthermore, it is pertinent that future in vivo and clinical investigations consider sex effects.
    Keywords:  Alzheimer’s disease; cannabidiol (CBD); cannabis extract; cannabis therapeutics; delta-9-tetrahydrocannabinol (THC); dementia; endocannabinod system
    DOI:  https://doi.org/10.3389/fnins.2022.962922
  246. Bone Rep. 2022 Dec;17 101620
    Amino acid metabolism in skeletal cells.
    Claire-Sophie Devignes, Geert Carmeliet, Steve Stegen.
      Amino acid metabolism regulates essential cellular functions, not only by fueling protein synthesis, but also by supporting the biogenesis of nucleotides, redox factors and lipids. Amino acids are also involved in tricarboxylic acid cycle anaplerosis, epigenetic modifications, next to synthesis of neurotransmitters and hormones. As such, amino acids contribute to a broad range of cellular processes such as proliferation, matrix synthesis and intercellular communication, which are all critical for skeletal cell functioning. Here we summarize recent work elucidating how amino acid metabolism supports and regulates skeletal cell function during bone growth and homeostasis, as well as during skeletal disease. The most extensively studied amino acid is glutamine, and osteoblasts and chondrocytes rely heavily on this non-essential amino acid during for their functioning and differentiation. Regulated by lineage-specific transcription factors such as SOX9 and osteoanabolic agents such as parathyroid hormone or WNT, glutamine metabolism has a wide range of metabolic roles, as it fuels anabolic processes by producing nucleotides and non-essential amino acids, maintains redox balance by generating the antioxidant glutathione and regulates cell-specific gene expression via epigenetic mechanisms. We also describe how other amino acids affect skeletal cell functions, although further work is needed to fully understand their effect. The increasing number of studies using stable isotope labelling in several skeletal cell types at various stages of differentiation, together with conditional inactivation of amino acid transporters or enzymes in mouse models, will allow us to obtain a more complete picture of amino acid metabolism in skeletal cells.
    Keywords:  Amino acids; Cell metabolism; Chondrocyte; Glutamine; Osteoblast; Osteoclast
    DOI:  https://doi.org/10.1016/j.bonr.2022.101620
  247. BMJ Open. 2022 Sep 19. 12(9): e057936
    Study protocol to determine the effects of highly absorbable oral curcumin on the indicators of cognitive functioning: a double-blind randomised controlled trial.
    Maki Komiyama, Yuka Ozaki, Hiromichi Wada, Hajime Yamakage, Noriko Satoh-Asahara, Atsuhiro Kishimoto, Yasuhiro Katsuura, Atsushi Imaizumi, Tadashi Hashimoto, Yoichi Sunagawa, Tatsuya Morimoto, Koji Hasegawa.
      INTRODUCTION: Mild cognitive impairment (MCI) refers to a state in which cognitive functions, such as memory, have diminished but daily activities are largely unhampered. MCI is often overlooked but carries the risk of leading to development of dementia later. Curcumin is the main component of the natural herbal medicine turmeric. Curcumin is widely used as a health food and is an antioxidant that has anti-inflammatory and anti-amyloid actions. The current trial was designed to determine the effects of curcumin on indicators of cognitive functioning.METHODS AND ANALYSIS: The current trial will be a single-centre randomised placebo-controlled double-blind parallel group trial. The participants will be 60 members of the general public with potential MCI, based on dementia screening using the Japanese version of the Mini Mental State Examination (MMSE-J). The investigational health food used in this trial will be a recently developed preparation for highly absorbable oral curcumin. This trial will determine the effects of the highly absorbable oral curcumin (brand name: curcuRouge) on the indicators of cognitive functioning, including the scores obtained with the MMSE-J, which is an interview-based measure of cognitive functioning, and the blood biomarkers that have been reported to be associated with dementia.
    ETHICS AND DISSEMINATION: Informed written consent will be obtained from all the participants. The Ethical Review Board of the National Hospital Organization Kyoto Medical Center approved the study protocol.
    TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN000042471).
    Keywords:  Dementia; Herbal medicine; Quality in health care
    DOI:  https://doi.org/10.1136/bmjopen-2021-057936
  248. Molecules. 2022 Sep 09. pii: 5843. [Epub ahead of print]27(18):
    Advanced Drug Delivery Micro- and Nanosystems for Cardiovascular Diseases.
    Siavash Iravani, Rajender S Varma.
      Advanced drug delivery micro- and nanosystems have been widely explored due to their appealing specificity/selectivity, biodegradability, biocompatibility, and low toxicity. They can be applied for the targeted delivery of pharmaceuticals, with the benefits of good biocompatibility/stability, non-immunogenicity, large surface area, high drug loading capacity, and low leakage of drugs. Cardiovascular diseases, as one of the primary mortalities cause worldwide with significant impacts on the quality of patients' life, comprise a variety of heart and circulatory system pathologies, such as peripheral vascular diseases, myocardial infarction, heart failure, and coronary artery diseases. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives.
    Keywords:  advanced delivery systems; biocompatibility; cardiovascular diseases; drug delivery nanosystems; targeted drug delivery
    DOI:  https://doi.org/10.3390/molecules27185843
  249. Nutrients. 2022 Sep 15. pii: 3812. [Epub ahead of print]14(18):
    Grifola frondosa Extract Containing Bioactive Components Blocks Skin Fibroblastic Inflammation and Cytotoxicity Caused by Endocrine Disrupting Chemical, Bisphenol A.
    Ju-Ha Kim, Seong-Ryeong Lim, Dae-Hwa Jung, Eun-Ju Kim, Junghee Sung, Sang Chan Kim, Chang-Hyung Choi, Ji-Woong Kang, Sei-Jung Lee.
      Grifola frondosa (GF), a species of Basidiomycotina, is widely distributed across Asia and has been used as an immunomodulatory, anti-bacterial, and anti-cancer agent. In the present study, the pharmacological activity of the GF extract against an ecotoxicological industrial chemical, bisphenol A (BPA) in normal human dermal fibroblasts (NHDFs), was investigated. GF extract containing naringin, hesperidin, chlorogenic acid, and kaempferol showed an inhibitory effect on cell death and inflammation induced by BPA in the NHDFs. For the cell death caused by BPA, GF extract inhibited the production of reactive oxygen species responsible for the unique activation of the extracellular signal-regulated kinase. In addition, GF extract attenuated the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and the pro-inflammatory cytokine IL-1β by the suppression of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-κB) in BPA-treated NHDFs. For the inflammation triggered by BPA, GF extract blocked the inflammasome-mediated caspase-1 activation that leads to the secretion of IL-1β protein. These results indicate that the GF extract is a functional antioxidant that prevents skin fibroblastic pyroptosis induced by BPA.
    Keywords:  Grifola frondosa; apoptotic cell death; bisphenol A; normal human dermal fibroblasts; pyroptosis; reactive oxygen species
    DOI:  https://doi.org/10.3390/nu14183812
  250. Curr Drug Metab. 2022 Sep 19.
    Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.
    Sajjad Ahmadpour, Mohammad Amin Habibi, Seyed Jalal Hosseinimehr.
      It is demonstrated that fasting can alter the biodistribution of radiopharmaceuticals in nuclear medicine. Various studies have highlighted that fasting is interpreted to be easy for physicians during PET study, fasting is one of the most important factors determining the usefulness of this protocol. It is well documented that fasting can suppress normal 18F-FDG PET uptake during nuclear cardiology. However, there is no consensus about the usefulness of fasting on radiopharmaceuticals, especially on 18F-FDG in PET imaging, but special attention should be paid to the setting of the fasting duration. Nevertheless, it does seem we still need extensive clinical studies in the future. The present study aims to review the various aspects of fasting, especially metabolic alteration on radiopharmaceutical biodistribution. In this study, we more focused on the effect of fasting on 18F-FDG metabolism which alter its imaging contrast in cardiology and cancer imaging. Therefore, shifting substrate metabolism from glucose to free fatty acids during fasting can be used as an alternative approach to suppress physiological myocardial uptake.
    Keywords:  18F-FDG; Fasting; biodistribution; cardiology; nuclear medicine; oncology; radiopharmaceuticals metabolism
    DOI:  https://doi.org/10.2174/1389200223666220919121354
  251. Cancers (Basel). 2022 Sep 14. pii: 4450. [Epub ahead of print]14(18):
    Extracellular Vesicles: A Novel Tool in Nanomedicine and Cancer Treatment.
    Aikaterini Stavrou, Angelica Ortiz.
      Extracellular vesicles are membrane-bound vesicles released by cells to mediate intercellular communication and homeostasis. Various external stimuli as well as inherent abnormalities result in alterations in the extracellular vesicle milieu. Changes to cells result in alterations in the content of the extracellular vesicle biogenesis, which may affect proximal and distal cells encountering these altered extracellular vesicles. Therefore, the examination of changes in the extracellular vesicle signature can be used to follow disease progression, reveal possible targets to improve therapy, as well as to serve as mediators of therapy. Furthermore, recent studies have developed methods to alter the cargo of extracellular vesicles to restore normal function or deliver therapeutic agents. This review will examine how extracellular vesicles from cancer cells differ from normal cells, how these altered extracellular vesicles can contribute to cancer progression, and how extracellular vesicles can be used as a therapeutic agent to target cancer cells and cancer-associated stroma. Here we present extracellular vesicles as a novel tool in nanomedicine.
    Keywords:  cancer; cancer treatments; cancer vaccine; drug delivery; exosomes; extracellular vesicles; gene delivery; mesenchymal stem-cell-derived extracellular vesicles; nanoparticles; protein delivery
    DOI:  https://doi.org/10.3390/cancers14184450
  252. Seizure. 2022 Sep 05. pii: S1059-1311(22)00196-0. [Epub ahead of print]101 253-261
    A review on role of metformin as a potential drug for epilepsy treatment and modulation of epileptogenesis.
    Ratnav Singh, Sudhir C Sarangi, Surender Singh, Manjari Tripathi.
      BACKGROUND: Available anti-seizure medications (ASMs) target the symptomatology of the disease rather than any significant disease/epileptogenesis modifying actions. There are critical concerns of drug resistance and seizure recurrence during epilepsy management. So, drug repurposing is evolving as a paradigm change in the quest for novel epilepsy treatment strategies. Metformin, a well-known anti-diabetic drug has shown multiple pieces of evidence of its potential antiepileptic action.OBJECTIVE: This review elucidates various mechanisms underlying the beneficial role of metformin in seizure control and modulation of the epileptogenesis process.
    METHODS: Preclinical and clinical evidence involving metformin's role in epilepsy and special conditions like tuberous sclerosis have been reviewed in this paper. The putative mechanisms of epileptogenesis modulation through the use of metformin are also summarised.
    RESULTS: This review found the efficacy of metformin in different seizure models including genetic knockout model, chemical induced, and kindling models. Only one clinical study of metformin in tuberous sclerosis has shown a reduction in seizure frequency and tumor volume compared to placebo. The suggested mechanisms of metformin relevant to epileptogenesis modulation mainly encompass AMPK activation, mTOR inhibition, protection against blood-brain-barrier disruption, inhibition of neuronal apoptosis, and reduction of oxidative stress. In addition to seizure protection, metformin has a potential role in attenuating adverse effects associated with epilepsy and ASMs such as cognition and memory impairment.
    CONCLUSION: Metformin has shown promising utility in epilepsy management and epileptogenesis modulation. The evidence in this review substantiates the need for a robust clinical trial to explore the efficacy and safety of metformin in persons with epilepsy.
    Keywords:  Drug repositioning; Epilepsy; Epileptogenesis; Metformin; mTOR
    DOI:  https://doi.org/10.1016/j.seizure.2022.09.003
  253. Molecules. 2022 Sep 10. pii: 5886. [Epub ahead of print]27(18):
    Phytochemical Characterization, Anti-Oxidant, Anti-Enzymatic and Cytotoxic Effects of Artemisia verlotiorum Lamotte Extracts: A New Source of Bioactive Agents.
    Shanoo Suroowan, Eulogio Jose Llorent-Martínez, Gokhan Zengin, Stefano Dall'Acqua, Stefania Sut, Kalaivani Buskaran, Sharida Fakurazi, Mohamad Fawzi Mahomoodally.
      Artemisia verlotiorum Lamotte is recognized medicinally given its long-standing ethnopharmacological uses in different parts of the world. Nonetheless, the pharmacological properties of the leaves of the plant have been poorly studied by the scientific community. Hence, this study aimed to decipher the phytochemicals; quantify through HPLC-ESI-MS analysis the plant's biosynthesis; and evaluate the antioxidant, anti-tyrosinase, amylase, glucosidase, cholinesterase, and cytotoxicity potential on normal (NIH 3T3) and human liver and human colon cancer (HepG2 and HT 29) cell lines of this plant species. The aqueous extract contained the highest content of phenolics and phenolic acid, methanol extracted the most flavonoid, and the most flavonol was extracted by ethyl acetate. The one-way ANOVA results demonstrated that all results obtained were statistically significant at p &lt; 0.05. A total of 25 phytoconstituents were identified from the different extracts, with phenolic acids and flavonoids being the main metabolites. The highest antioxidant potential was recorded for the aqueous extract. The best anti-tyrosinase extract was the methanolic extract. The ethyl acetate extract of A. verlotiorum had the highest flavonol content and hence was most active against the cholinesterase enzymes. The ethyl acetate extract was the best α-glucosidase and α-amylase inhibitor. The samples of Artemisia verlotiorum Lamotte in both aqueous and methanolic extracts were found to be non-toxic after 48 h against NIH 3T3 cells. In HepG2 cells, the methanolic extract was nontoxic up to 125 µg/mL, and an IC50 value of 722.39 µg/mL was recorded. The IC50 value exhibited in methanolic extraction of A. verlotiorum was 792.91 µg/mL in HT29 cells. Methanolic extraction is capable of inducing cell cytotoxicity in human hepatocellular carcinoma without damaging normal cells. Hence, A. verlotiorum can be recommended for further evaluation of its phytochemical and medicinal properties.
    Keywords:  Artemisia verlotiorum; amylase; cytotoxicity; phyto-pharmaceutics; tyrosinase
    DOI:  https://doi.org/10.3390/molecules27185886
  254. Polymers (Basel). 2022 Sep 09. pii: 3772. [Epub ahead of print]14(18):
    Polymer-Based Hydrogels Enriched with Essential Oils: A Promising Approach for the Treatment of Infected Wounds.
    Sibusiso Alven, Sijongesonke Peter, Blessing Atim Aderibigbe.
      Among the factors that delay the wound healing process in chronic wounds, bacterial infections are a common cause of acute wounds becoming chronic. Various therapeutic agents, such as antibiotics, metallic nanoparticles, and essential oils have been employed to treat infected wounds and also prevent the wounds from bacterial invasion. Essential oils are promising therapeutic agents with excellent wound healing, anti-inflammatory and antimicrobial activities, and good soothing effects. Some essential oils become chemically unstable when exposed to light, heat, oxygen, and moisture. The stability and biological activity of essential oil can be preserved via loading into hydrogels. The polymer-based hydrogels loaded with bioactive agents are regarded as ideal wound dressings with unique features, such as controlled and sustained drug release mechanisms, good antibacterial activity, non-toxicity, excellent cytocompatibility, good porosity, moderate water vapour transmission rate, etc. This review addresses the pre-clinical outcomes of hydrogels loaded with essential oils in the treatment of infected wounds.
    Keywords:  essential oils; hydrogels; infected wounds; lavender oil; polymers; tea tree oil; wound dressing
    DOI:  https://doi.org/10.3390/polym14183772
  255. Antioxidants (Basel). 2022 Aug 25. pii: 1645. [Epub ahead of print]11(9):
    Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights.
    Suzan Abdu, Nouf Juaid, Amr Amin, Mohamed Moulay, Nabil Miled.
      This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.
    Keywords:  HCC; crocin; inflammation; sorafenib; treatment
    DOI:  https://doi.org/10.3390/antiox11091645
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