bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022‒10‒23
ninety-two papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Natural products targeting human lactate dehydrogenases for cancer therapy: A mini review.
  2. Rerouting the drug response: Overcoming metabolic adaptation in KRAS-mutant cancers.
  3. Therapeutic effect of natural polyphenols against glioblastoma.
  4. Deregulated transcription factors in cancer cell metabolisms and reprogramming.
  5. Nanomaterials in anticancer applications and their mechanism of action - A review.
  6. A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.
  7. Chitosan-based therapeutic systems and their potentials in treatment of oral diseases.
  8. Recent advances in flavonoid-based nanocarriers as an emerging drug delivery approach for cancer chemotherapy.
  9. Kaempferol: A potential agent in the prevention of colorectal cancer.
  10. Nanostructured lipid carriers for oral delivery of a corticosteroid: Role of formulation on biopharmaceutical performance.
  11. Application of hyaluronic acid in tissue engineering, regenerative medicine, and nanomedicine: A review.
  12. Effect of Curcumin-loaded Photoactivatable Polymeric Nanoparticle on peri-implantitis-related biofilm.
  13. Micellar nanoparticles inhibit the postoperative inflammation, recurrence and pulmonary metastasis of 4T1 breast cancer by blocking NF-κB pathway and promoting MDSCs depletion.
  14. Histone deacetylases modulate resistance to the therapy in lung cancer.
  15. Current trends in the use of human serum albumin for drug delivery in cancer.
  16. Functional bioinspired nanomaterials for anticancer activity with generation of reactive oxygen species.
  17. Metabolic effects of prolactin and the role of dopamine agonists: A review.
  18. Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells.
  19. Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.
  20. Nanovesicles-Mediated Drug Delivery for Oral Bioavailability Enhancement.
  21. Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.
  22. NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.
  23. Phytotherapeutic applications of alkaloids in treating breast cancer.
  24. Nanotechnological approaches for diagnosis and treatment of ovarian cancer: a review of recent trends.
  25. Cancer therapy by antibody-targeted Cerenkov light and metabolism-selective photosensitization.
  26. Recent developments in plant-derived edible nanoparticles as therapeutic nanomedicines.
  27. Recent updates on anticancer mechanisms of polyphenols.
  28. Role of Plant-Derived Flavonoids in Cancer Treatment.
  29. Targeting cellular metabolism in head and neck cancer precision medicine era: a promising strategy to overcome therapy resistance.
  30. Natural products targeting the ATR-CHK1 signaling pathway in cancer therapy.
  31. Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities.
  32. Meticulous parade on naringin respecting its pharmacological activities and novel formulations.
  33. Biomimetic cytomembrane-coated ZIF-8-loaded DMDD nanoparticle and sonodynamic co-therapy for cancer.
  34. Ferroptosis in glioma treatment: Current situation, prospects and drug applications.
  35. Preparation, physical properties, and evaluation of antioxidant capacity of aqueous grape extract loaded in chitosan-TPP nanoparticles.
  36. Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials.
  37. Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency.
  38. Recent advances in mesoporous silica nanoparticle-based targeted drug-delivery systems for cancer therapy.
  39. Quercetin-ferrum nanoparticles enhance photothermal therapy by modulating the tumor immunosuppressive microenvironment.
  40. Chinese medicinal herbs as potential prodrugs for obesity.
  41. Disulfiram enhances chemotherapeutic effects of doxorubicin liposomes against human hepatocellular carcinoma via activating ROS-induced cell stress response pathways.
  42. Mesoporous Silica Nanoparticles Loaded with Resveratrol Are Used for Targeted Breast Cancer Therapy.
  43. A combination of novel NSC small molecule inhibitor along with doxorubicin inhibits proliferation of triple-negative breast cancer through metabolic reprogramming.
  44. Phytochemical Analysis, Total Phenolic, Flavonoid Contents, and Anticancer Evaluations of Solvent Extracts and Saponins of H. digitata.
  45. The role of lipids in cancer progression and metastasis.
  46. Pulmonary delivery of curcumin-loaded glycyrrhizic acid nanoparticles for anti-inflammatory therapy.
  47. Chitosan/xanthan gum-based (Hydroxypropyl methylcellulose-co-2-Acrylamido-2-methylpropane sulfonic acid) interpenetrating hydrogels for controlled release of amorphous solid dispersion of bioactive constituents of Pueraria lobatae.
  48. Encapsulation of thymus vulgaris essential oil in caseinate/gelatin nanocomposite hydrogel: In vitro antibacterial activity and in vivo wound healing potential.
  49. A light-responsive injectable hydrogel with remodeling tumor microenvironment for light-activated chemodynamic therapy.
  50. GAPDH in neuroblastoma: Functions in metabolism and survival.
  51. Nano-liposomal encapsulation of Artemisia aucheri phenolics as a potential phytobiotic against Campylobacter jejuni infection in mice.
  52. Tumor-Specific Cyclic Amplification of Oxidative Stress by Disulfide-Loaded Fluoropolymer Nanogels.
  53. Chlorogenic acid for cancer prevention and therapy: Current status on efficacy and mechanisms of action.
  54. Natural product inspired leads in the discovery of anticancer agents: an update.
  55. Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.
  56. Chitosan Nanoparticles for Intranasal Delivery of Olmesartan Medoxomil: Pharmacokinetic and Pharmacodynamic Perspectives.
  57. Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression.
  58. Effects of chloroquine and hydroxychloroquine on the sensitivity of pancreatic cancer cells to targeted therapies.
  59. Intracellular and extracellular enzymatic responsive micelle for intelligent therapy of cancer.
  60. Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy.
  61. Current perspectives and trend of nanomedicine in cancer: A review and bibliometric analysis.
  62. Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy.
  63. Oxidative Stress and Intervertebral Disc Degeneration: Pathophysiology, Signaling Pathway, and Therapy.
  64. Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells.
  65. Lemongrass (Cymbopogon citratus)-incorporated chitosan bioactive films for potential skincare applications.
  66. Hypericum perforatum: Traditional uses, clinical trials, and drug interactions.
  67. Dietary Intervention for Preventing Colorectal Cancer: A Practical Guide for Physicians.
  68. Recent advances in the extraction, chemical composition, therapeutic potential, and delivery of cardamom phytochemicals.
  69. Exogenous Ketones and Lactate as a Potential Therapeutic Intervention for Brain Injury and Neurodegenerative Conditions.
  70. Formulation of ciprofloxacin-loaded oral self-emulsifying drug delivery system to improve the pharmacokinetics and antibacterial activity.
  71. Reprogramming of sentinel lymph node microenvironment during tumor metastasis.
  72. Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles.
  73. Nutraceuticals: A Promising Approach Towards Diabetic Neuropathy.
  74. Highly Efficient Photodynamic Therapy with Mitochondria-Targeting Aggregation-induced Emission Photosensitizer for Retinoblastoma.
  75. Dietary β-carotene and vitamin A and risk of Parkinson disease: A protocol for systematic review and meta-analysis.
  76. Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways.
  77. Vitamin K: A new guardian against ferroptosis.
  78. The Application of Nanotechnology and Nanomaterials in Cancer Diagnosis and Treatment: A Review.
  79. Elucidating the Beneficial Effects of Ginger (Zingiber officinale Roscoe) in Parkinson's Disease.
  80. Reprogramming of glycolysis by chemical carcinogens during tumor development.
  81. Inhibition of NADPH Oxidase-ROS Signal using Hyaluronic Acid Nanoparticles for Overcoming Radioresistance in Cancer Therapy.
  82. Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.
  83. A Review of Herbal Medicine-Based Phytochemical of Garcinia as Molecular Therapy for Breast Cancer.
  84. Ketones: the double-edged sword of SGLT2 inhibitors?
  85. Suprasomes Based on Host-Guest Molecular Recognition: An Excellent Alternative to Liposome in Cancer Theranostics.
  86. Lipid-polymer nanocarrier platform enables X-ray induced photodynamic therapy against human colorectal cancer cells.
  87. Managing Cancer Drug Resistance from the Perspective of Inflammation.
  88. Thermosensitive Polymer Conjugated Prodrug-Activating Enzyme with Enhanced Tumor Retention and Antitumor Efficacy.
  89. Design of cysteine-based self-assembling polymer drugs for anticancer chemotherapy.
  90. Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.
  91. Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.
  92. Mechanism of metformin regulation in central nervous system: Progression and future perspectives.
  1. Front Chem. 2022 ;10 1013670
    Natural products targeting human lactate dehydrogenases for cancer therapy: A mini review.
    Huankai Yao, Feng Yang, Yan Li.
      Reprogramming cancer metabolism has become the hallmark of cancer progression. As the key enzyme catalyzing the conversion of pyruvate to lactate in aerobic glycolysis of cancer cells, human lactate dehydrogenase (LDH) has been a promising target in the discovery of anticancer agents. Natural products are important sources of new drugs. Up to now, some natural compounds have been reported with the activity to target LDH. To give more information on the development of LDH inhibitors and application of natural products, herein, we reviewed the natural compounds with inhibition of LDH from diverse structures and discussed the future direction of the discovery of natural LDH inhibitors for cancer therapy.
    Keywords:  Warburg effect; cancer metabolism; inhibitors; lactate dehydrogenase; natural products
    DOI:  https://doi.org/10.3389/fchem.2022.1013670
  2. Sci Signal. 2022 Oct 18. 15(756): eabj3490
    Rerouting the drug response: Overcoming metabolic adaptation in KRAS-mutant cancers.
    Deborah Y Moss, Christopher McCann, Emma M Kerr.
      Mutations in guanosine triphosphatase KRAS are common in lung, colorectal, and pancreatic cancers. The constitutive activity of mutant KRAS and its downstream signaling pathways induces metabolic rewiring in tumor cells that can promote resistance to existing therapeutics. In this review, we discuss the metabolic pathways that are altered in response to treatment and those that can, in turn, alter treatment efficacy, as well as the role of metabolism in the tumor microenvironment (TME) in dictating the therapeutic response in KRAS-driven cancers. We highlight metabolic targets that may provide clinical opportunities to overcome therapeutic resistance and improve survival in patients with these aggressive cancers.
    DOI:  https://doi.org/10.1126/scisignal.abj3490
  3. Front Cell Dev Biol. 2022 ;10 1036809
    Therapeutic effect of natural polyphenols against glioblastoma.
    Ozal Beylerli, Aferin Beilerli, Alina Shumadalova, Xiaoxiong Wang, Mingchun Yang, Hanran Sun, Lei Teng.
      Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system, which has a highly invasive growth pattern, which creates poor prospects for patient survival. Chemotherapy and tumor surgery are limited by anticancer drug resistance and tumor invasion. Evidence suggests that combinations of treatments may be more effective than single drugs alone. Natural polyphenolic compounds have potential as drugs for the treatment of glioblastoma and are considered as potential anticancer drugs. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood-brain barrier permeability. Many of them have a significant effect on reducing the progression of glioblastoma through mechanisms such as reduced migration and cell invasion or chemosensitization. Various chemical formulations have been proposed to improve their pharmacological properties. This review summarizes natural polyphenolic compounds and their physiological effects in glioblastoma models by modulating signaling pathways involved in angiogenesis, apoptosis, chemoresistance, and cell invasion. Polyphenolic compounds are emerging as promising agents for combating the progression of glioblastoma. However, clinical trials are still needed to confirm the properties of these compounds in vitro and in vivo.
    Keywords:  anticancer therapy; curcumin; flavonoids; glioblastoma; polyphenols
    DOI:  https://doi.org/10.3389/fcell.2022.1036809
  4. Semin Cancer Biol. 2022 Oct 13. pii: S1044-579X(22)00205-X. [Epub ahead of print]
    Deregulated transcription factors in cancer cell metabolisms and reprogramming.
    Rajni Kant, Rajesh Kumar Manne, Mohammad Anas, Vasudevarao Penugurti, Tingjin Chen, Bo-Syong Pan, Che-Chia Hsu, Hui-Kuan Lin.
      Metabolic reprogramming is an important cancer hallmark that plays a key role in cancer malignancies and therapy resistance. Cancer cells reprogram the metabolic pathways to generate not only energy and building blocks but also produce numerous key signaling metabolites to impact signaling and epigenetic/transcriptional regulation for cancer cell proliferation and survival. A deeper understanding of the mechanisms by which metabolic reprogramming is regulated in cancer may provide potential new strategies for cancer targeting. Recent studies suggest that deregulated transcription factors have been observed in various human cancers and significantly impact metabolism and signaling in cancer. In this review, we highlight the key transcription factors that are involved in metabolic control, dissect the crosstalk between signaling and transcription factors in metabolic reprogramming, and offer therapeutic strategies targeting deregulated transcription factors for cancer treatment.
    Keywords:  Cancer treatment; Cell metabolism; Metabolic Reprogramming; Transcription Factors; signaling metabolites
    DOI:  https://doi.org/10.1016/j.semcancer.2022.10.001
  5. Nanomedicine. 2022 Oct 14. pii: S1549-9634(22)00099-5. [Epub ahead of print]47 102613
    Nanomaterials in anticancer applications and their mechanism of action - A review.
    C G Anjali Das, V Ganesh Kumar, T Stalin Dhas, V Karthick, C M Vineeth Kumar.
      The current challenges in cancer treatment using conventional therapies have made the emergence of nanotechnology with more advancements. The exponential growth of nanoscience has drawn to develop nanomaterials (NMs) with therapeutic activities. NMs have enormous potential in cancer treatment by altering the drug toxicity profile. Nanoparticles (NPs) with enhanced surface characteristics can diffuse more easily inside tumor cells, thus delivering an optimal concentration of drugs at tumor site while reducing the toxicity. Cancer cells can be targeted with greater affinity by utilizing NMs with tumor specific constituents. Furthermore, it bypasses the bottlenecks of indiscriminate biodistribution of the antitumor agent and high administration dosage. Here, we focus on the recent advances on the use of various nanomaterials for cancer treatment, including targeting cancer cell surfaces, tumor microenvironment (TME), organelles, and their mechanism of action. The paradigm shift in cancer management is achieved through the implementation of anticancer drug delivery using nano routes.
    Keywords:  Drug delivery system; Mechanism of action; Nanomaterials; Targeting; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.nano.2022.102613
  6. Front Pharmacol. 2022 ;13 965131
    A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.
    Guanglin Zhu, Bing Wang, Guo Feng, Zhirong Zhou, Wei Li, Wen Liu, Hongmei Su, Wenjing Wang, Tiejie Wang, Xie-An Yu.
      Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.
    Keywords:  daphnoretin; nano-preparation; natural product; targeting delivery system for the liver; therapeutical efficacy in HCC
    DOI:  https://doi.org/10.3389/fphar.2022.965131
  7. Int J Biol Macromol. 2022 Oct 14. pii: S0141-8130(22)02331-5. [Epub ahead of print]
    Chitosan-based therapeutic systems and their potentials in treatment of oral diseases.
    Hongyu Gao, Nan Wu, Nini Wang, Jie Li, Jie Sun, Qiang Peng.
      The increasing morbidity of oral diseases, such as dental caries, periodontitis and oral cancer, has greatly compromised the life quality of humans. With the rapid development of biomaterials and nanotechnology, various biomaterials-based systems have been reported to treat oral diseases. As the biocompatible, biodegradable and bioadhesive polysaccharide biomaterials, chitosan and its derivatives have also been widely used for the oral disease therapy, either as the antibacterial agents, drug delivery carriers or tissue engineering scaffolds. It has been well demonstrated that chitosan can significantly enhance the therapy efficacy for various oral diseases, due to its intrinsic antibacterial activity and controlled drug release feature. Herein, we aim to provide a comprehensive understanding of the biological functions of chitosan, such as antimicrobial, anticancer and remineralization activity, and summarize the applications of chitosan-based therapeutic systems in treating the typical oral diseases, including dental caries, endodontic diseases, periodontal diseases, oral cancer, oral and maxillofacial surgery, and oral mucosal diseases. In addition, the concerns and possible solutions of the clinical use of chitosan are also discussed.
    Keywords:  Antimicrobial; Cancer therapy; Chitosan; Hydrogel; Nanoparticles
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.10.090
  8. Drug Discov Today. 2022 Oct 17. pii: S1359-6446(22)00402-0. [Epub ahead of print] 103409
    Recent advances in flavonoid-based nanocarriers as an emerging drug delivery approach for cancer chemotherapy.
    Saikat Dewanjee, Pratik Chakraborty, Hiranmoy Bhattacharya, Sachin Kumar Singh, Kamal Dua, Abhijit Dey, Niraj Kumar Jha.
      Flavonoids are an interesting class of biomolecules that exhibit cancer-inhibitory effects through both chemopreventive and chemotherapeutic activities. However, poor pharmacokinetics (PK) and biopharmaceutical attributes affect their therapeutic efficacy. One of the most promising approaches to resolve these issues is to formulate flavonoids in nanosystems. Different flavonoid nanoformulations have shown therapeutic superiority over free flavonoids. Functionalization of nanoparticles (NPs) further improves their therapeutic efficacy by facilitating site-specific delivery and reducing nonspecific toxicities. In this review, we highlight recent developments in the field of flavonoid-based NPs to gain translational insights into the potential applications of flavonoid-based nanocarriers in cancer management. Teaser: This review summarizes recent advances in flavonoid-based nanocarriers to achieve better therapeutic efficacy in the fight against cancer.
    Keywords:  bioavailability; cancer therapeutics; flavonoids; nanocarriers; site-specific delivery
    DOI:  https://doi.org/10.1016/j.drudis.2022.103409
  9. Physiol Rep. 2022 Oct;10(20): e15488
    Kaempferol: A potential agent in the prevention of colorectal cancer.
    Hamid Reza Nejabati, Leila Roshangar.
      Colorectal cancer (CRC) is the third most prevalent cancer in relation to incidence and mortality rate and its incidence is considerably increasing annually due to the change in the dietary habit and lifestyle of the world population. Although conventional therapeutic options, such as surgery, chemo- and radiotherapy have profound impacts on the treatment of CRC, dietary therapeutic agents, particularly natural products have been regarded as the safest alternatives for the treatment of CRC. Kaempferol (KMP), a naturally derived flavonol, has been shown to reduce the production of reactive oxygen species (ROS), such as superoxide ions, hydroxyl radicals, and reactive nitrogen species (RNS), especially peroxynitrite. Furthermore, this flavonol inhibits xanthine oxidase (XO) activity and increases the activities of catalase, heme oxygenase-1 (HO), and superoxide dismutase (SOD) in a wide range of cancer and non-cancer cells. Based on several studies, KMP is also a hopeful anticancer which carries out its anticancer action via suppression of angiogenesis, stimulation of apoptosis, and cell cycle arrest. Due to various applications of KMP as an anticancer flavonol, this review article aims to highlight the current knowledge regarding the role of KMP in CRC.
    Keywords:  anticancer; colorectal cancer; flavonol; kaempferol
    DOI:  https://doi.org/10.14814/phy2.15488
  10. J Pharm Sci. 2022 Oct 18. pii: S0022-3549(22)00471-3. [Epub ahead of print]
    Nanostructured lipid carriers for oral delivery of a corticosteroid: Role of formulation on biopharmaceutical performance.
    Shaimaa S Ibrahim.
      Corticosteroids are potent anti-inflammatory and immunosuppressive drugs widely used world-wide for treatment of diverse conditions. However, their use is restricted by their poor bioavailability and high risk-benefit ratio. Therefore, the aim of this study was to develop nanostructred lipid carriers (NLC) of prednisolone acetate (PA) to improve the drug's therapeutic outcome by altering its pharmacokinetic profile and/or allow preferential targeting to inflammatory tissues. PA-loaded NLCs were formulated by solvent injection method using Compritol (solid lipid), oleic acid (liquid lipid) and Tween 80 or Pluronic F68 (surfactant). Formulation conditions, such as liquid lipid concentration, total lipids, drug:lipid ratio and surfactant type were optimized based on particle size (PS), polydispersity index (PDI), and encapsulation efficiency (EE%) results. Optimized formulation was further characterized for its surface morphology, thermal properties, storage stability and anti-inflammatory activity in an animal acute inflammation model. Selected NLCs displayed PS of 170.7nm, EE% of 67.4%, sustained release over 72 hours and good stability for 30 days at refrigeration conditions. PA NLCs displayed superior anti-inflammatory activity of 83.9 ± 4.46% compared to PA suspension (40.5 ± 7.03%) and drug-free NLCs (54.7 ± 6.12%). The current work delineates the potential of NLCs for distinctly improved biopharmaceutical performance of PA.
    Keywords:  Colloid; Corticosteroids; Drug delivery system; Lipid Nanoparticles (LNP); Oral drug delivery; Targeted drug delivery; controlled release; formulation
    DOI:  https://doi.org/10.1016/j.xphs.2022.10.014
  11. Int J Biol Macromol. 2022 Oct 12. pii: S0141-8130(22)02296-6. [Epub ahead of print]
    Application of hyaluronic acid in tissue engineering, regenerative medicine, and nanomedicine: A review.
    Kandasamy Saravanakumar, SeonJu Park, Sugavaneswaran Siva Santosh, Archchana Ganeshalingam, Gobika Thiripuranathar, Anbazhagan Sathiyaseelan, Sampathkumar Vijayasarathy, Akila Swaminathan, Veeraraghavan Vishnu Priya, Myeong-Hyeon Wang.
      Hyaluronic acid (HA) plays a vital role in cellular processes and its contribution to physical and immunological barriers is considered to be an important property for the formulation of modern therapeutics. With the increasing demand for non-toxic and targeted therapeutics, HA-based therapies are a spot-on approach due to their tendency to bio-mimic the hosts. Moreover, HA is a versatile compound in the generation of HA-based products such as hydrogels, nanofibers, and 3D materials. These have been implemented in various medical domains, such as bone and tissue regeneration, topical gels for wound healing, and cancer treatment via HA-loaded drug delivery approaches. Herein, we have discussed the characteristics of HA and its significance in drug delivery in addition to synergistic effects with other therapeutic compounds in the fields of nanomedicine, tissue engineering, and regenerative medicine.
    Keywords:  Drug delivery; Hyaluronic acid; Regenerative medicine; Wound healing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.10.055
  12. Photodiagnosis Photodyn Ther. 2022 Oct 13. pii: S1572-1000(22)00436-7. [Epub ahead of print] 103150
    Effect of Curcumin-loaded Photoactivatable Polymeric Nanoparticle on peri-implantitis-related biofilm.
    Caroline Coradi Tonon, Beatriz Panariello, Marlus Chorilli, Denise Madalena Palomari Spolidorio, Simone Duarte.
      Curcumin has been used as a photosensitizer (PS) for antimicrobial photodynamic chemotherapy (PACT). However, its low solubility, instability, and poor bioavailability challenge its in vivo application. This study aimed to synthesize curcumin-loaded polymeric nanoparticles (curcumin-NP) and determine their antimicrobial and cytotoxic effects. Nanoparticles (NP) were synthesized using polycaprolactone (PCL) as a polymer by the nanoprecipitation method. Curcumin-NP was characterized by particle size, polydispersity index and zeta potential, scanning electron microscopy, and curcumin encapsulation efficiency (EE). Curcumin-NP was compared to free curcumin solubilized in 10% DMSO as photosensitizers for PACT in single and multispecies Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus oralis biofilms. Chlorhexidine 0.12% (CHX) and ultrapure water were used as positive and negative controls. The cytotoxic effect of curcumin-NP was evaluated on human periodontal ligament fibroblast cells (HPLF). Data were analyzed by ANOVA (α=0.05). Curcumin-NP exhibited homogeneity and stability in solution, small particle size, and 67.5% EE of curcumin. Curcumin-NP presented reduced antibiofilm activity at 500 µg/ml, although in planktonic cultures it showed inhibitory and bactericidal effect. Curcumin-NP and curcumin with and without photoactivation were not cytotoxic to HPLF cells. Curcumin-NP has antimicrobial and antibiofilm properties, with better effects when associated with blue light, being a promising therapy for preventing and treating peri-implant diseases.
    Keywords:  Curcumin; Fusobacterium nucleatum; Nanoparticle; Photo-inactivation; Porphyromonas gingivalis; Streptococcus oralis
    DOI:  https://doi.org/10.1016/j.pdpdt.2022.103150
  13. Int J Pharm. 2022 Oct 17. pii: S0378-5173(22)00858-4. [Epub ahead of print] 122303
    Micellar nanoparticles inhibit the postoperative inflammation, recurrence and pulmonary metastasis of 4T1 breast cancer by blocking NF-κB pathway and promoting MDSCs depletion.
    Zhengze Lu, Ling Ma, Ling Mei, Kebai Ren, Man Li, Ling Zhang, Xiuxiu Liu, Qin He.
      The progression of breast cancer can stimulate the production of myeloid-derived suppressor cells (MDSCs). These cells with significant immunosuppressive activity play a key role in promoting the formation of pulmonary inflammatory and immunosuppressive microenvironment, namely pre-metastatic niche (PMN). Surgical resection of tumors often leads to strong inflammatory reactions, and the produced circulating tumor cells (CTCs) can implant into PMN to promote the recurrence and pulmonary metastasis of breast cancer. Therefore, we developed a hyaluronic acid (HA)-coated chitosan oligosaccharide-all-trans-retinoic-acid (COS-ATRA) micellar nanoparticle loaded with chemotherapeutic drug doxorubicin (DOX) (HA@CA/DOX NPs). The hydrophilic segment COS and hydrophobic segment ATRA both blocked NF-κB inflammatory signaling pathway in 4T1 tumor cells and MDSCs and alleviated the inflammation after resection. Besides, ATRA also significantly depleted MDSCs in lungs and tumors, thereby regulating the inflammatory and immunosuppressive microenvironment and inhibiting the formation of PMN. HA coated on the surface of nanoparticles shielded the excessive positive charge and achieved tumor targeting through CD44 on the surface of tumor cells. This drug delivery system combined with anti-inflammation and chemotherapy significantly inhibited the postoperative recurrence and pulmonary metastasis of breast cancer.
    Keywords:  Breast cancer; NF-κB inflammatory signaling pathway; inflammation; metastasis; myeloid-derived suppressor cells
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122303
  14. Front Genet. 2022 ;13 960263
    Histone deacetylases modulate resistance to the therapy in lung cancer.
    Estefanía Contreras-Sanzón, Heriberto Prado-Garcia, Susana Romero-Garcia, David Nuñez-Corona, Blanca Ortiz-Quintero, Cesar Luna-Rivero, Victor Martínez-Cruz, Ángeles Carlos-Reyes.
      The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.
    Keywords:  HDACs inhibitors; histone deacetylases (HDACs); lung cancer; natural compounds; resistance to therapy
    DOI:  https://doi.org/10.3389/fgene.2022.960263
  15. Expert Opin Drug Deliv. 2022 Oct 17. 1-22
    Current trends in the use of human serum albumin for drug delivery in cancer.
    Milan Paul, Asif Mohd Itoo, Balaram Ghosh, Swati Biswas.
      INTRODUCTION: Human serum albumin is the most abundant transport protein in plasma, which has recently been extensively utilized to form nanoparticles for drug delivery in cancer. The primary reason for selecting albumin protein as drug delivery cargo is its excellent biocompatibility, biodegradability, and non-immunogenicity. Moreover, the albumin structure containing three homologous domains constituted of a single polypeptide (585 amino acid) incorporates various hydrophobic drugs by non-covalent interactions. Albumin shows active tumor targeting via their interaction with gp60 and SPARC proteins abundant in the tumor-associated endothelial cells and the tumor microenvironment.AREAS COVERED: The review discusses the importance of albumin as a drug-carrier system, general procedures to prepare albumin NPs, and the current trends in using albumin-based nanomedicines to deliver various chemotherapeutic agents. The various applications of albumin in the nanomedicines, such as NPs surface modifier and fabrication of hybrid/active-tumor targeted NPs, are delineated based on current trends.
    EXPERT OPINION: Nanomedicines have the potential to revolutionize cancer treatment. However, clinical translation is limited majorly due to the lack of suitable nanomaterials offering systemic stability, optimum drug encapsulation, tumor-targeted delivery, sustained drug release, and biocompatibility. The potential of albumin could be explored in nanomedicines fabrication for superior treatment outcomes in cancer.
    Keywords:  Albumin; anticancer drug; cancer; chemotherapeutic agents; conjugation; loading; nanoparticles; targeting
    DOI:  https://doi.org/10.1080/17425247.2022.2134341
  16. Chemosphere. 2022 Oct 15. pii: S0045-6535(22)03378-1. [Epub ahead of print] 136885
    Functional bioinspired nanomaterials for anticancer activity with generation of reactive oxygen species.
    Allah Dittah Khalid, Naeem Ur-Rehman, Ghulam Hasnain Tariq, Sana Ullah, Saeed Ahmed Buzdar, Sadia Saghar Iqbal, Emina Karahmet Sher, Norah Salem Alsaiari, Graham J Hickman, Farooq Sher.
      Cancer is a debilitating and deadly disease caused by the uncontrolled growth of aberrant cell populations. This disease cannot always be controlled with traditional therapies and medicines. Different medicines are being used for this purpose, however these medicines have their side effects and are harmful to healthy cells. A better way to cure cancer disease is by limiting the agglomeration of cancer cells, minimizing their growth and their population by destroying these harmful cells. This could be achieved by controlling the function of mitochondria and DNA in cancer cells with the use of biocompatible materials with tuneable physical properties. Accordingly, research is ongoing as to the use of nanomaterials and nanotechnology in medicine. Zinc oxide semiconductor nanoparticles have displayed good anticancer behaviour. They have unique properties such as biocompatibility, good stability, and are environmentally friendly. Owing to these characteristics, they are focused on biological applications such as drug delivery and cancer therapy. In the present research work, zinc oxide, titanium dioxide nanoparticles and titanium oxide-zinc oxide nanocomposites were successfully trailed for anti-cancer activity. Pure zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO2 NPs) and their nanocomposites (TiO2 -ZnO NPs) were prepared by the co-precipitation technique. The structural properties were investigated by X-ray diffraction, which confirmed the Wurtzite structure of pure ZnO NPs. The morphology of the NPs was checked by scanning electron microscopy. For incident light having a higher energy band gap of nanomaterials, the electrons are excited to the conduction band and these electrons generate reactive oxygen species (ROS). The efficacy of these nanomaterials was checked by exposing the NPs to the human liver cancer cell HepG2. The MTT assay describes anticancer activity via cell viability. The cell viability of composites was observed to be greater than pure ZnO NPs. Their results showed that the structure of ZnO NPs remains the same with composites of TiO2 NPs, but the band gap of the composite was intermediate for individual samples. It also showed that the anticancer activity of composites was also less than pure ZnO NPs which is due to the reduction of ROS generation. This is observed that nanocomposites of ZnO and TiO2 could be effective in the development of a treatment of human liver cancer cells.
    Keywords:  Anticancer activity; Biocompatibility; Highly ROS; MTT assay And distracted mitochondria; TiO(2)–ZnO nanoparticles
    DOI:  https://doi.org/10.1016/j.chemosphere.2022.136885
  17. Front Endocrinol (Lausanne). 2022 ;13 1002320
    Metabolic effects of prolactin and the role of dopamine agonists: A review.
    Polly Kirsch, Jessica Kunadia, Shruti Shah, Nidhi Agrawal.
      Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.
    Keywords:  dopamine agonist; hyperprolactinemia; metabolic dysfunction; metabolic syndrome; pituitary; prolactin; prolactinoma
    DOI:  https://doi.org/10.3389/fendo.2022.1002320
  18. PLoS One. 2022 ;17(10): e0276579
    Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells.
    Ahmet Hatipoglu, Deepak Menon, Talia Levy, Maria A Frias, David A Foster.
      Metabolic reprogramming is now considered a hallmark of cancer cells. KRas-driven cancer cells use glutaminolysis to generate the tricarboxylic acid cycle intermediate α-ketoglutarate via a transamination reaction between glutamate and oxaloacetate. We reported previously that exogenously supplied unsaturated fatty acids could be used to synthesize phosphatidic acid-a lipid second messenger that activates both mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2). A key target of mTORC2 is Akt-a kinase that promotes survival and regulates cell metabolism. We report here that mono-unsaturated oleic acid stimulates the phosphorylation of ATP citrate lyase (ACLY) at the Akt phosphorylation site at S455 in an mTORC2 dependent manner. Inhibition of ACLY in KRas-driven cancer cells in the absence of serum resulted in loss of cell viability. We examined the impact of glutamine (Gln) deprivation in combination with inhibition of ACLY on the viability of KRas-driven cancer cells. While Gln deprivation was somewhat toxic to KRas-driven cancer cells by itself, addition of the ACLY inhibitor SB-204990 increased the loss of cell viability. However, the transaminase inhibitor aminooxyacetate was minimally toxic and the combination of SB-204990 and aminooxtacetate led to significant loss of cell viability and strong cleavage of poly-ADP ribose polymerase-indicating apoptotic cell death. This effect was not observed in MCF7 breast cancer cells that do not have a KRas mutation or in BJ-hTERT human fibroblasts which have no oncogenic mutation. These data reveal a synthetic lethality between inhibition of glutamate oxaloacetate transaminase and ACLY inhibition that is specific for KRas-driven cancer cells and the apparent metabolic reprogramming induced by activating mutations to KRas.
    DOI:  https://doi.org/10.1371/journal.pone.0276579
  19. Bioact Mater. 2023 Apr;22 239-253
    Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.
    Yuemin Wang, Duan Wang, Yuyue Zhang, Hong Xu, Luxuan Shen, Jing Cheng, Xinyuan Xu, Hong Tan, Xingyu Chen, Jianshu Li.
      Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.
    Keywords:  Cell membranes; Chemodynamic therapy; Glucose oxidase; Homologous targeting; Perfluoropentane; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.bioactmat.2022.09.025
  20. Int J Nanomedicine. 2022 ;17 4861-4877
    Nanovesicles-Mediated Drug Delivery for Oral Bioavailability Enhancement.
    Yuehong Ren, Linghui Nie, Shiping Zhu, Xingwang Zhang.
      Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.
    Keywords:  bioavailability; exosomes; liposomes; niosomes; oral drug delivery; vesicles
    DOI:  https://doi.org/10.2147/IJN.S382192
  21. Oxid Med Cell Longev. 2022 ;2022 9354555
    Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.
    Mohamed Joonus Aynul Fazmiya, Arshiya Sultana, Khaleequr Rahman, Md Belal Bin Heyat, Sumbul, Faijan Akhtar, Salabat Khan, Seth Christopher Yaw Appiah.
      C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity, diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol, and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial, anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.
    DOI:  https://doi.org/10.1155/2022/9354555
  22. Redox Biol. 2022 Oct 09. pii: S2213-2317(22)00269-5. [Epub ahead of print]57 102497
    NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.
    Balaraman Kalyanaraman.
      N-acetylcysteine (NAC) has been used as a direct scavenger of reactive oxygen species (hydrogen peroxide, in particular) and an antioxidant in cancer biology and immuno-oncology. NAC is the antioxidant drug most frequently employed in studies using tumor cells, immune cells, and preclinical mouse xenografts. Most studies use redox-active fluorescent probes such as dichlorodihydrofluorescein, hydroethidine, mitochondria-targeted hydroethidine, and proprietary kit-based probes (i.e., CellROX Green and CellROX Red) for intracellular detection of superoxide or hydrogen peroxide. Inhibition of fluorescence by NAC was used as a key experimental observation to support the formation of reactive oxygen species and redox mechanisms proposed for ferroptosis, tumor metastasis, and redox signaling in the tumor microenvironment. Reactive oxygen species such as superoxide and hydrogen peroxide stimulate or abrogate tumor cells and immune cells depending on multiple factors. Understanding the mechanism of antioxidants is crucial for interpretation of the results. Because neither NAC nor the fluorescent probes indicated above react directly with hydrogen peroxide, it is critically important to reinterpret the results to advance our understanding of the mechanism of action of NAC and shed additional mechanistic insight on redox-regulated signaling in tumor biology. To this end, this review is focused on how NAC could affect multiple pathways in cancer cells, including iron signaling, ferroptosis, and the glutathione-dependent antioxidant and redox signaling mechanism, and how NAC could inhibit oxidation of the fluorescent probes through multiple mechanisms.
    Keywords:  Antioxidant thiols; Ferroptosis; Fluorescent probes; Mitochondrial reactive oxygen species; Transferrin iron; Tumor metastasis
    DOI:  https://doi.org/10.1016/j.redox.2022.102497
  23. Biomed Pharmacother. 2022 Nov;pii: S0753-3322(22)01149-0. [Epub ahead of print]155 113760
    Phytotherapeutic applications of alkaloids in treating breast cancer.
    Shailima Rampogu, Thananjeyan Balasubramaniyam, Joon-Hwa Lee.
      Breast cancer is one of the major causes of mortality in women worldwide. The current treatments available are radiation therapy (RT), surgery, endocrine (hormone) therapy (ET), chemotherapy (CT), and targeted therapy. These treatments are associated with certain side effects that demand the use of natural compounds due to their lower to negligible side effects. One such category of natural compounds is alkaloids. Alkaloids are a group of natural compounds that have gained widespread attention due to their use as potential therapeutics. Alkaloids exert anti-inflammatory and antiviral properties along with antimicrobial activities. In the current review, 12 alkaloids are reviewed in detail for their potential in treating breast cancer. These alkaloids have been shown to induce apoptosis, decrease tumor volume, inhibit cell proliferation and migration, and induce autophagy and they can also be used as a component of combination therapy. This review provides comprehensive information on the in vitro and in vivo therapeutic abilities of alkaloids to counteract breast cancer.
    Keywords:  Alkaloids; Breast cancer; Natural compounds; Phytotherapy
    DOI:  https://doi.org/10.1016/j.biopha.2022.113760
  24. Drug Deliv. 2022 Dec;29(1): 3218-3232
    Nanotechnological approaches for diagnosis and treatment of ovarian cancer: a review of recent trends.
    Haigang Ding, Juan Zhang, Feng Zhang, Yan Xu, Wenqing Liang, Yijun Yu.
      Formulations from nanotechnology platform promote therapeutic drug delivery and offer various advantages such as biocompatibility, non-inflammatory effects, high therapeutic output, biodegradability, non-toxicity, and biocompatibility in comparison with free drug delivery. Due to inherent shortcomings of conventional drug delivery to cancerous tissues, alternative nanotechnological-based approaches have been developed for such ailments. Ovarian cancer is the leading gynecological cancer with higher mortality rates due to its reoccurrence and late diagnosis. In recent years, the field of medical nanotechnology has witnessed significant progress in addressing existing problems and improving the diagnosis and therapy of various diseases including cancer. Nevertheless, the literature and current reviews on nanotechnology are mainly focused on its applications in other cancers or diseases. In this review, we focused on the nanoscale drug delivery systems for ovarian cancer targeted therapy and diagnosis, and different nanocarriers systems including dendrimers, nanoparticles, liposomes, nanocapsules, and nanomicelles for ovarian cancer have been discussed. In comparison to non-functionalized counterparts of nanoformulations, the therapeutic potential and preferential targeting of ovarian cancer through ligand functionalized nanoformulations' development has been reviewed. Furthermore, numerous biomarkers such as prostatic, mucin 1, CA-125, apoptosis repeat baculoviral inhibitor-5, human epididymis protein-4, and e-cadherin have been identified and elucidated in this review for the assessment of ovarian cancer. Nanomaterial biosensor-based tumor markers and their various types for ovarian cancer diagnosis are explained in this article. In association, different nanocarrier approaches for the ovarian cancer therapy have also been underpinned. To ensure ovarian cancer control and efficient detection, there is an urgent need for faster and less costly medical tools in the arena of oncology.
    Keywords:  Ovarian cancer; diagnosis and treatment; drug nanocarriers; nanotechnology
    DOI:  https://doi.org/10.1080/10717544.2022.2132032
  25. J Control Release. 2022 Oct 14. pii: S0168-3659(22)00684-8. [Epub ahead of print]352 25-34
    Cancer therapy by antibody-targeted Cerenkov light and metabolism-selective photosensitization.
    Chihoon Jo, Heesu Ahn, Ji Hwan Kim, Yong Jin Lee, Jung Young Kim, Kyo Chul Lee, Chi Soo Kang, Sehoon Kim.
      Photodynamic therapy (PDT) is an effective cancer treatment option, but it suffers from penetration limit of light, making it available only for superficial and endoscopically accessible cancers. Recently, there have been reports that Cerenkov luminescence originated from radioisotopes can be utilized as an excitation source for PDT without external light illumination. Here, cancer-selective agents, i.e., (1) clinically available 5-aminolevulinic acid (5-ALA), which promotes cancer metabolism-specific accumulation of protoporphyrin IX (PpIX), and (2) 64Cu-DOTA-trastuzumab, which has HER2-expressing cancer selective uptake, are separately applied as a photosensitizer and an in situ radiator, respectively, to potentiate tumor-specific Cerenkov luminescence energy transfer (CLET) from 64Cu to PpIX for high-precision PDT of cancer. It is shown that the combinational administration and tumor colocalization of 5-ALA and 64Cu-DOTA-trastuzumab exert significant in vitro cytotoxicity (cell viability <9%) as well as in vivo antitumor effects (tumor volume ratio of 0.50 on 14 days post-injection) on HER2-expressing breast and gastric cancer models. This study proves that high-precision treatment regimen using dual-targeted CLET-based PDT is feasible for HER2-expressing cancers. Furthermore, the results offer great potential for clinical translation to the dual-targeted CLET-based PDT because the treatment regimen uses components, 5-ALA and 64Cu-DOTA-trastuzumab, which are already in clinical uses.
    Keywords:  (64)Cu-DOTA-trastuzumab; 5-aminolevulinic acid; Cerenkov luminescence energy transfer; HER2-expressing cancer; Photodynamic therapy; Protoporphyrin IX
    DOI:  https://doi.org/10.1016/j.jconrel.2022.10.014
  26. J Food Biochem. 2022 Oct 21. e14479
    Recent developments in plant-derived edible nanoparticles as therapeutic nanomedicines.
    Neha Jain, Manisha Pandey, Palak Sharma, Gaurav Gupta, Bapi Gorain, Kamal Dua.
      The use of nanotechnology in the treatment of numerous disorders has proven effective. The predicted development of plant-derived edible nanoparticles (PDNPs) as potential therapeutic agents for treating illness or in the delivery of drugs is inevitable. PDNPs generated from plants resemble mammal-extracted exosomes structurally. In contrast to their excellent biocompatibility with healthy cells, PDNPs are skewed toward malignancies by selectively targeting those cells via unique endocytic pathways. They can be generated in large quantities, are nontoxic, and have tissue-specific targeting abilities. Thus, with fewer off-target effects, using these PDNPs could broaden the breadth of pharmacological therapy. In this discussion, we emphasize the properties and biological activities of PDNPs isolated from fruits and vegetables and discuss the promising implications of these particles as nanomedicines. PRACTICAL APPLICATIONS: PDNPs have reportedly been employed for therapeutic applications for several ailments and are believed to have characteristics in common with exosomes generated from mammals. The advantages of PDNPs over mammalian-derived exosomes are numerous. Firstly, they may be produced on a commercial scale using a variety of efficient renewable sources. Secondly, the PDNPs' natural components developed in plant cells promise improved cytocompatibility, tolerability, low cytotoxicity, or other adverse effects. We evaluated some current studies on the applications and potential of PDNPs in this article. PDNPs could create new opportunities for drug discovery because of recent advancements in medicine and drug delivery system nanotechnology. Unfortunately, the precise mechanisms behind PDNP's functions and interaction in pathogenic processes have not yet been completely elucidated; as a result, the potential consequences of their clinical use are uncertain. Overall, PDNPs show a wide range of therapeutic possibilities that may be advantageous to patients and might eventually make up the next generation of pharmaceuticals.
    Keywords:  exosomes; miRNAs; nanovesicles; plant-derived edible nanoparticles; therapeutic delivery
    DOI:  https://doi.org/10.1111/jfbc.14479
  27. Front Cell Dev Biol. 2022 ;10 1005910
    Recent updates on anticancer mechanisms of polyphenols.
    Eshita Sharma, Dharam Chand Attri, Priyanka Sati, Praveen Dhyani, Agnieszka Szopa, Javad Sharifi-Rad, Christophe Hano, Daniela Calina, William C Cho.
      In today's scenario, when cancer cases are increasing rapidly, anticancer herbal compounds become imperative. Studies on the molecular mechanisms of action of polyphenols published in specialized databases such as Web of Science, Pubmed/Medline, Google Scholar, and Science Direct were used as sources of information for this review. Natural polyphenols provide established efficacy against chemically induced tumor growth with fewer side effects. They can sensitize cells to various therapies and increase the effectiveness of biotherapy. Further pharmacological translational research and clinical trials are needed to evaluate theirs in vivo efficacy, possible side effects and toxicity. Polyphenols can be used to design a potential treatment in conjunction with existing cancer drug regimens such as chemotherapy and radiotherapy.
    Keywords:  anticancer molecular mechanisms; cancer; invasion; migration; pharmacology; phytochemicals; polyphenols
    DOI:  https://doi.org/10.3389/fcell.2022.1005910
  28. Nutr Cancer. 2022 Oct 20. 1-20
    Role of Plant-Derived Flavonoids in Cancer Treatment.
    Prabha Tiwari, Kaushala Prasad Mishra.
      Flavonoids are polyphenolic phytochemicals, which occur naturally in plants and possess both anti-oxidant and pro-oxidant properties. Flavonoids are gaining increasing popularity in the pharmaceutical industry as healthy and cost-effective compounds. Flavonoids show beneficial pharmacological activities in the treatment and prevention of various types of diseases. They are natural and less toxic agents for cancer chemotherapy and radiotherapy via regulation of multiple cell signaling pathways and pro-oxidant effects. In this review, we have summarized the mechanisms of action of selected flavonoids, and their pharmacological implications and potential therapeutic applications in cancer therapy.
    DOI:  https://doi.org/10.1080/01635581.2022.2135744
  29. Oral Dis. 2022 Oct 19.
    Targeting cellular metabolism in head and neck cancer precision medicine era: a promising strategy to overcome therapy resistance.
    Xiaohu Lin, Wenkai Zhou, Zheqi Liu, Wei Cao, Chengzhong Lin.
      OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancer worldwide, with the most severe impact on quality of life of patients. Despite the development of multimodal therapeutic approaches, the clinical outcomes of HNSCC are still unsatisfactory, mainly caused by relatively low responsiveness to treatment and severe drug resistance. Metabolic reprogramming is currently considered to play a pivotal role in anticancer therapeutic resistance. This review aims to define the specific metabolic programs and adaptations in HNSCC therapy resistance.METHODS: An extensive literature review of HNSCC was conducted via the PubMed including metabolic reprogramming, chemo- or immune-therapy resistance.
    RESULTS: Glucose metabolism, fatty acid metabolism and amino acid metabolism are closely related to the malignant biological characteristics of cancer, anti-tumor drug resistance, and adverse clinical results. For HNSCC, pyruvate, lactate and almost all lipid categories are related to the occurrence and maintenance of drug resistance, and targeting amino acid metabolism can prevent tumor development and enhance the response of drug-resistant tumors to anti-cancer therapy.
    CONCLUSIONS: This review will provide a better understanding of the altered metabolism in therapy-resistance of HNSCC and promote the development of new therapeutic strategies against HNSCC, thereby contribute to a more efficacious precision medicine.
    Keywords:  Cancer drug resistance; Combination therapy; Head and neck cancer; Metabolic regulations; Tumor metabolism
    DOI:  https://doi.org/10.1111/odi.14411
  30. Biomed Pharmacother. 2022 Nov;pii: S0753-3322(22)01186-6. [Epub ahead of print]155 113797
    Natural products targeting the ATR-CHK1 signaling pathway in cancer therapy.
    Salman Ahmed, Waqas Alam, Michael Aschner, Khalaf F Alsharif, Ashraf Albrakati, Luciano Saso, Haroon Khan.
      Cancer is one of the most severe medical conditions in the world, causing millions of deaths each year. Chemotherapy and radiotherapy are critical for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer requires novel efficacious treatment modalities. Natural remedies offer feasible alternative options against malignancy in contrast to available synthetic medication. Selective killing of cancer cells is privileged mainstream in cancer treatment, and targeted therapy represents the new tool with the potential to pursue this aim. The discovery of innovative therapies targeting essential components of DNA damage signaling and repair pathways such as ataxia telangiectasia mutated and Rad3 related Checkpoint kinase 1 (ATR-CHK1)has offered a possibility of significant therapeutic improvement in oncology. The activation and inhibition of this pathway account for chemopreventive and chemotherapeutic activity, respectively. Targeting this pathway can also aid to overcome the resistance of conventional chemo- or radiotherapy. This review enlightens the anticancer role of natural products by ATR-CHK1 activation and inhibition. Additionally, these compounds have been shown to have chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Ideally, this review will trigger interest in natural products targeting ATR-CHK1 and their potential efficacy and safety as cancer lessening agents.
    Keywords:  ATR-CHK1; Chemopreventive; Chemotherapeutic; MDR cancer; Natural products targeting ATR-CHK1
    DOI:  https://doi.org/10.1016/j.biopha.2022.113797
  31. Cancer Commun (Lond). 2022 Oct 20.
    Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities.
    Tongxin Ge, Xiang Gu, Renbing Jia, Shengfang Ge, Peiwei Chai, Ai Zhuang, Xianqun Fan.
      Reversible, spatial, and temporal regulation of metabolic reprogramming and epigenetic homeostasis are prominent hallmarks of carcinogenesis. Cancer cells reprogram their metabolism to meet the high bioenergetic and biosynthetic demands for vigorous proliferation. Epigenetic dysregulation is a common feature of human cancers, which contributes to tumorigenesis and maintenance of the malignant phenotypes by regulating gene expression. The epigenome is sensitive to metabolic changes. Metabolism produces various metabolites that are substrates, cofactors, or inhibitors of epigenetic enzymes. Alterations in metabolic pathways and fluctuations in intermediate metabolites convey information regarding the intracellular metabolic status into the nucleus by modulating the activity of epigenetic enzymes and thus remodeling the epigenetic landscape, inducing transcriptional responses to heterogeneous metabolic requirements. Cancer metabolism is regulated by epigenetic machinery at both transcriptional and post-transcriptional levels. Epigenetic modifiers, chromatin remodelers and non-coding RNAs are integral contributors to the regulatory networks involved in cancer metabolism, facilitating malignant transformation. However, the significance of the close connection between metabolism and epigenetics in the context of cancer has not been fully deciphered. Thus, it will be constructive to summarize and update the emerging new evidence supporting this bidirectional crosstalk and deeply assess how the crosstalk between metabolic reprogramming and epigenetic abnormalities could be exploited to optimize treatment paradigms and establish new therapeutic options. In this review, we summarize the central mechanisms by which epigenetics and metabolism reciprocally modulate each other in cancer and elaborate upon and update the major contributions of the interplays between epigenetic aberrations and metabolic rewiring to cancer initiation and development. Finally, we highlight the potential therapeutic opportunities for hematological malignancies and solid tumors by targeting this epigenetic-metabolic circuit. In summary, we endeavored to depict the current understanding of the coordination between these fundamental abnormalities more comprehensively and provide new perspectives for utilizing metabolic and epigenetic targets for cancer treatment.
    Keywords:  RNA epigenetics; cancer; epigenetics; metabolic reprogramming; therapy
    DOI:  https://doi.org/10.1002/cac2.12374
  32. Avicenna J Phytomed. 2022 Sep-Oct;12(5):12(5): 457-474
    Meticulous parade on naringin respecting its pharmacological activities and novel formulations.
    Mahboob Alam, Farogh Ahsan, Tarique Mahmood, Arshiya Shamim, Saba Parveen, Mohammad Shariq, Vaseem Ahmad Ansari.
      Objective: Medicinal plants having antioxidant potential possess numerous constituents which are responsible for different beneficial effects and are used as an alternative resource of medicine to lessen diseases linked with oxidative stress. Flavonoids are identified in the plants since ages and display wide spectrum of biological actions that might be able to stimulate the steps which are disturbed in different diseases. Flavonoids are significant natural compounds with various biologic properties, among which the most common is the anti-oxidant potential. Citrus flavonoids establish an important stream of flavonoids. Naringin, very common flavonoids present in the diet, belongs to the family of flavanone. It is the principal constituent of citrus family that contains flavonoids for example tomatoes, grapefruits and oranges.Materials and Methods: In this article, we reviewed naringin with respect to sources, chemical property, pharmacokinetics, pharmacological activity, and novel formulations. The literature survey has been done by searching different databases such as Psyc INFO, Science Direct, PubMed, EMBASE, Google, Google Scholar, Medline.
    Results: Naringin is known to behave as an antioxidant and possess anti-inflammatory, anti-apoptotic, anti-atherosclerotic, neuroprotective, anti-psychotic, anti-asthmatic, anti-diabetic, hepatoprotective, anti-tussive, cardioprotective, and anti-obesity activity. Further clinical studies using large sample sizes remain essential to obtain the appropriate dose and form of naringin for averting diseases. Furthermore, the therapeutic approach of these bioflavonoids is significantly inappropriate due to the lack of clinical evidence. Different plants must be explored further to find these bioflavonoids in them.
    Conclusion: The results of this exploration provides biological actions of bioflavonoid (naringin), predominantly on pharmacological and novel dosage forms of naringin.
    Keywords:  Flavonoids; Formulations; Naringin; Pharmacokinetics Pharmacological activity
    DOI:  https://doi.org/10.22038/AJP.2022.20001
  33. Ann Transl Med. 2022 Sep;10(18): 971
    Biomimetic cytomembrane-coated ZIF-8-loaded DMDD nanoparticle and sonodynamic co-therapy for cancer.
    Shuqi Zhao, Meifeng Chen, Zhu Yu, Thi Thai Hoa Pham, Shutian Mo, Yongfei He, Tianyi Liang, Wenlong Cao, Chuangye Han.
      Background: Breast cancer (BC) is the most common type of cancer affecting females. It is also a leading cause of cancer-related death in women worldwide.Methods: Sonodynamic therapy (SDT) is an emerging therapeutic strategy for cancer treatment. SDT ensures non-invasive penetration of deep tumors and results in activation of non-toxic sonosensitizers administered in deep tumor sites to become cytotoxic. It has been reported that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has a significant anti-tumor effect against various cancer types including BC. However, DMDD is hydrophobic. Therefore, a one-step encapsulation method was used in the current study to construct zeolitic imidazole frameworks-8 (ZIF-8) loaded with DMDD and sonosensitizer chlorin e6 (Ce6). ZIF-8 was further modified by coating it with a biomimetic cell membrane to improve targeted delivery.
    Results: In vitro and in vivo results indicated that the nanomedicines had great biocompatibility properties and targeting ability. The nanocomposite exhibited a higher release rate under an acidic tumor microenvironment. The tumor killing effect of reactive oxygen species (ROS) generated from Ce6 and inhibition of tumor growth was enhanced after ultrasound (US) treatment, which might be caused by the increase in apoptosis rate.
    Conclusions: These findings show that the combination of nanomedicine and SDT provides a potential therapeutic method for BC.
    Keywords:  2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD); Breast cancer (BC); ZIF-8 nanoparticles; metal-organic framework; sonodynamic therapy
    DOI:  https://doi.org/10.21037/atm-22-3646
  34. Front Oncol. 2022 ;12 989896
    Ferroptosis in glioma treatment: Current situation, prospects and drug applications.
    Yuhang Zhou, Chaoyou Fang, Houshi Xu, Ling Yuan, Yibo Liu, Xiaoyu Wang, Anke Zhang, Anwen Shao, Danyang Zhou.
      Ferroptosis is a regulatory form of iron-dependent cell death caused by the accumulation of lipid-based reactive oxygen species (ROS) and differs from apoptosis, pyroptosis, and necrosis. Especially in neoplastic diseases, the susceptibility of tumor cells to ferroptosis affects prognosis and is associated with complex effects. Gliomas are the most common primary intracranial tumors, accounting for disease in 81% of patients with malignant brain tumors. An increasing number of studies have revealed the particular characteristics of iron metabolism in glioma cells. Therefore, agents that target a wide range of molecules involved in ferroptosis may regulate this process and enhance glioma treatment. Here, we review the underlying mechanisms of ferroptosis and summarize the potential therapeutic options for targeting ferroptosis in glioma.
    Keywords:  ferroptosis; glioma; iron metabolism; reactive oxygen species; targeting treatment
    DOI:  https://doi.org/10.3389/fonc.2022.989896
  35. Food Sci Nutr. 2022 Oct;10(10): 3272-3281
    Preparation, physical properties, and evaluation of antioxidant capacity of aqueous grape extract loaded in chitosan-TPP nanoparticles.
    Sepideh Soleymanfallah, Zhaleh Khoshkhoo, Seyed Ebrahim Hosseini, Mohammad Hossein Azizi.
      Grape extract is reportedly rich in phenolic compounds that possess strong antioxidant activities. Encapsulation of such extracts in nanoparticles (NPs) is an effective way to preserve various food products. In the present study, grapes were first extracted, and the amount of total phenolic content and different types of phenolic acids was determined. The extracts at different chitosan/extract weight ratios (1:0.25, 1:0.5, 1:0.75, and 1:1) were then encapsulated in chitosan nanoparticles (NPs) using the ionic gelation method. The extract-loaded chitosan nanoparticles were characterized by their physicochemical properties using the dynamic light scattering (DLS) technique, chemical properties using Fourier-transform infrared (FTIR) spectroscopy, and X-ray powder diffraction technique (XRD), the morphological properties using scanning electron microscopy (SEM), and the antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. The encapsulation efficiency (EE) and loading capacity (LC) were also assessed. Our findings showed that the free radical inhibition effect of NPs significantly increased with an increase in extract concentration. Chitosan NPs presented acceptable encapsulation efficiency and loading capacity (LC), and the encapsulation process enhanced the antioxidant activity of the free grape extracts. At the weight ratio of 1:0.5, the particle size and zeta potential of the NPs were 177.5 ± 2.12 nm and 32.95 ± 0.49 mV, respectively. FTIR and XRD analyses verified the credibility of the encapsulated grape extract in chitosan NPs. These NPs can be an efficient way to increase the shelf-life of food products.
    Keywords:  antioxidant; antioxidant activity; chitosan nanoparticles; food preservation; grape extract; ionic gelation
    DOI:  https://doi.org/10.1002/fsn3.2891
  36. Front Pharmacol. 2022 ;13 993562
    Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials.
    Maira Javed, Ammara Saleem, Anne Xaveria, Muhammad Furqan Akhtar.
      Daphnetin (DAP), a coumarin derivative extracted from Daphne species, is biologically active phytochemical with copious bioactivities including anti-inflammatory, anti-oxidant, neuroprotective, analgesic, anti-pyretic, anti-malarial, anti-bacterial, anti-arthritic, neuroprotective, hepatoprotective, nephroprotective, and anti-cancer activities. A wide range of studies have been conducted exploring the significance and therapeutic potential of DAP. This study reviewed various databases such as NCBI, PubMed, Web of Science, Scopus and Google Scholar for published research articles regarding the sources, synthesis, and various bioactivities of DAP using different key words, including but not limited to "pharmacological activities," "sources," "neuroprotective effect," "synthesis," "cancer," "anti-inflammatory effect" of "daphnetin." Furthermore, this review encompasses both in-vivo and in-vitro studies on DAP for treating various diseases. A comprehensive review of the literature revealed that the DAP had a promising pharmacological and safety profile, and could be employed as a pharmaceutical moiety to treat a variety of illnesses including microbial infections, cancer, arthritis, hepatic damage, inflammation and neurological anomalies. The current review intends to provide an in-depth focus on all pharmacological activities and therapeutic approaches for the pharmaceutical and biomedical researchers.
    Keywords:  anti-bacterial; anti-inflammatory; daphnetin; neuroprotective; psoriasis
    DOI:  https://doi.org/10.3389/fphar.2022.993562
  37. ACS Omega. 2022 Oct 11. 7(40): 35875-35884
    Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency.
    Sooho Yeo, Min Je Kim, Young Key Shim, Il Yoon, Woo Kyoung Lee.
      Curcumin (Cur) has anticancer properties but exhibits poor aqueous solubility, permeability, and photostability. In this study, we aimed to develop a solid lipid nanoparticle (SLN) system to enhance Cur bioavailability. The characteristics of Cur-loaded SLNs prepared by sonication were evaluated using UV-vis and Fourier transform infrared spectroscopy. The mean particle size of the stearic acid-based, lauric acid-based, and palmitic acid-based SLNs was 14.70-149.30, 502.83, and 469.53 nm, respectively. The chemical interactions between Cur and lipids involved hydrogen bonding and van der Waals forces. The formulations with high van der Waals forces might produce a neat arrangement between Cur and lipids, leading to a decrease in particle size. The Cur formulations showed enhanced cytotoxicity in HeLa, A549, and CT-26 cells compared with pure Cur. Additionally, the anticancer effect is dependent on particle size and the type of cell line. Therefore, Cur-loaded SLNs have the potential for use in anticancer therapy.
    DOI:  https://doi.org/10.1021/acsomega.2c04407
  38. Nanomedicine (Lond). 2022 Oct 17.
    Recent advances in mesoporous silica nanoparticle-based targeted drug-delivery systems for cancer therapy.
    Ying Li, Guoxing Deng, Xianlong Hu, Chenyang Li, Xiaodong Wang, Qinchang Zhu, Kai Zheng, Wei Xiong, Haiqiang Wu.
      Targeted drug-delivery systems are a growing research topic in tumor treatment. In recent years, mesoporous silica nanoparticles (MSNs) have been extensively studied and applied in noninvasive and biocompatible drug-delivery systems for tumor therapy due to their outstanding advantages, which include high surface area, large pore volume, tunable pore size, easy surface modification and stable framework. The advances in the application of MSNs for anticancer drug targeting are covered and highlighted in this review, and the challenges and prospects of MSN-based targeted drug-delivery systems are discussed. This review provides new insights for researchers interested in targeted drug-delivery systems against cancer.
    Keywords:  cancer therapy; mesoporous silica; passive/active targeting; stimuli-responsive release; targeted delivery
    DOI:  https://doi.org/10.2217/nnm-2022-0023
  39. Acta Biomater. 2022 Oct 12. pii: S1742-7061(22)00664-X. [Epub ahead of print]
    Quercetin-ferrum nanoparticles enhance photothermal therapy by modulating the tumor immunosuppressive microenvironment.
    Lin Li, Mengxing Zhang, Tiantian Liu, Jing Li, Shili Sun, Junjie Chen, Zhenmi Liu, Zhirong Zhang, Ling Zhang.
      Photothermal therapy (PTT) was reported to induce synergistic immunogenic cell death (ICD) which may convert tumor cells into "therapeutic vaccines". However, this is often insufficient to prevent tumor recurrence, in part because of the immunosuppressive microenvironment in tumors. Therefore, remodeling tumor microenvironment is of great importance to enhance the therapeutic efficacy of PTT. We herein fabricated a versatile nano-photosensitizer by assembling quercetin and Ferrum ion (QFN). The released quercetin from QFN could reduce programmed death ligand 1 (PD-L1) in tumor cells by inhibiting the phosphorylation of JAK2 and STAT3, and reshape extracellular matrix (ECM) by down-regulating α-SMA+ fibroblast in tumors. Moreover, QFN could capture tumor antigen and deliver it to the tumor-draining lymph nodes after PTT, which further enhanced the activation of antigen-presenting cells. As a result, QFN-based PTT eliminated melanoma and induced long-term immune memory to prevent tumor metastasis and recurrence. This study provides an effective and translationally feasible photothermic agent for photothermal/immunotherapy. STATEMENT OF SIGNIFICANCE: The efficacy of photothermal therapy (PTT) in cancer treatment is often limited by the immunosuppressive microenvironment in tumors. Herein, we prepared a versatile photosensitizer by assembling quercetin and Ferrum ion (QFN). Upon near-infrared light irradiation, QFN-PTT induced cancer cells destruction and tumor antigen release. QFN then captured antigen and delivered it to the tumor-draining lymph nodes, thus promoting dendritic cell maturation and T cells activation. Quercetin released from QFN in tumors improved T cells infiltration and activation in tumor by regulating immunosuppressive microenvironment. The QFN-PTT-treated mice exhibited significantly elongated survival time, and gained strong anti-tumor immune memory to prevent tumor metastasis and recurrence. Thus, this work provided a simple and versatile photothermic agent, and it has important implications for designing effective and translationally feasible photosensitizers for PTT.
    Keywords:  PD-L1; Quercetin-Ferrum Nanoparticles; photothermal therapy; tumor extracellular matrix; tumor-draining lymph node
    DOI:  https://doi.org/10.1016/j.actbio.2022.10.008
  40. Front Pharmacol. 2022 ;13 1016004
    Chinese medicinal herbs as potential prodrugs for obesity.
    Siu Kan Law, Yanping Wang, Xinchen Lu, Dawn Ching Tung Au, Wesley Yeuk Lung Chow, Albert Wing Nang Leung, Chuanshan Xu.
      Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.
    Keywords:  active ingredient; bioavailability; herbal medicine; medicinal plants; nanotechnology; obesity; prodrug; traditional Chinese medicine (TCM)
    DOI:  https://doi.org/10.3389/fphar.2022.1016004
  41. Cancer Chemother Pharmacol. 2022 Oct 17.
    Disulfiram enhances chemotherapeutic effects of doxorubicin liposomes against human hepatocellular carcinoma via activating ROS-induced cell stress response pathways.
    Hai Lin, Fengjie Sun, Tingting Li, Yihan Zhang, Xiaochun Guo, Ming Li, Min Liang, Xinke Zhou, Zhiyuan Fang.
      PURPOSE: Increasing evidences have revealed the anti-cancer effect of disulfiram. Current disulfiram-based cancer therapies still have limitations, such as poor tumor-targeting ability and insufficient studies on anti-tumor mechanisms.METHODS: In the present study, tumor-targeting liposomes were prepared as drug carriers to increase retention of disulfiram in tumor cells. Then, anti-tumor efficacy of liposomes and the underlying mechanisms were investigated in in vitro, in vivo, and transcriptomic level.
    RESULTS: The results showed that disulfiram enhanced sensitivity of human hepatocellular carcinoma cells to doxorubicin by 15-27-fold, and increased reactive oxygen species (ROS) production as well as caspase-dependent apoptosis. Inhibition of tumor migration and invasion by doxorubicin were further enhanced by disulfiram. In vivo study showed that disulfiram additive doxorubicin liposomes had better performance in suppressing tumor growth than single doxorubicin liposomes. Gene expression profiling found that cellular components destruction, cell stress, check point regulation, and immunoregulation were the main anti-tumor mechanisms of disulfiram. More importantly, disulfiram possessed a great potential to be a protein ubiquitination and murine double minute 4 (MDM4) targeting compound.
    CONCLUSIONS: Due to its low price and good safety, it is worth to repurposing disulfiram as a chemotherapeutic drug. Furthermore, MDM4 may act as a biomarker for observation the clinical effect of disulfiram-based treatment.
    Keywords:  Disulfiram; Doxorubicin; Hepatocellular carcinoma; ROS; Tumor targeting liposome
    DOI:  https://doi.org/10.1007/s00280-022-04481-9
  42. J Oncol. 2022 ;2022 8471331
    Mesoporous Silica Nanoparticles Loaded with Resveratrol Are Used for Targeted Breast Cancer Therapy.
    Yifan Gu, Zhewei Fei.
      Objective: The characteristics of poor pharmacokinetics, stability, and low solubility seriously limited the clinical application of resveratrol (Res) in breast cancer. Thus, this study intends to develop a delivery system for Res which could be better used in breast cancer therapy.Methods: Resveratrol-modified mesoporous silica nanoparticles (MSN-Res) were chemically constructed. Their shape and encapsulation were detected by transmission electron microscope, Fourier transforms infrared spectrometer, and UV spectroscopy, respectively. MGF-7 tumor-bearing mice were established by subcutaneous injection, and the pathological changes were detected by hematoxylin-eosin staining. CCK-8 and Ki-67 immunohistochemical staining were used for proliferation evaluation in vitro and in vivo. Flow cytometry, TUNEL, wound healing, and transwell assay detected cell apoptosis, invasion, and migration.
    Results: MSN-Res was successfully prepared with high biosafety. MSN-Res inhibited MGF-7 cell proliferation, invasion, and migration and promoted apoptosis in vitro. Furthermore, MSN-Res showed better performance compared Res in breast cancer mouse models. In addition, we found that MSN-Res inhibited tumor growth via inhibiting the NF-κB signaling pathway.
    Conclusion: MSN-Res inhibited breast cancer progression with better efficacy compared with Res treatment alone by inhibiting the NF-κB signaling pathway, suggesting that MSN-Res is a more effective adjuvant treatment method for breast cancer. Thus, our findings may provide a new and safer means of using phytochemicals in combinatorial therapy of breast cancer.
    DOI:  https://doi.org/10.1155/2022/8471331
  43. Oncogene. 2022 Oct 15.
    A combination of novel NSC small molecule inhibitor along with doxorubicin inhibits proliferation of triple-negative breast cancer through metabolic reprogramming.
    Hassan Yousefi, Maninder Khosla, Lothar Lauterboeck, Samuel C Okpechi, David Worthylake, Jone Garai, Jovanny Zabaleta, Jessie Guidry, Mohammad Amin Zarandi, Dorota Wyczechowska, Janarthanan Jayawickramarajah, Qinglin Yang, Joseph Kissil, Suresh K Alahari.
      Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to the absence of well-defined molecular targets and the highly invasive and proliferative nature of TNBC cells. Current treatments against TNBC have shown little promise due to high recurrence rate in patients. Consequently, there is a pressing need for novel and efficacious therapies against TNBC. Here, we report the discovery of a novel small molecule inhibitor (NSC33353) with potent anti-tumor activity against TNBC cells. The anti-proliferative effects of this small molecule inhibitor were determined using 2D and 3D cell proliferation assays. We found that NSC33353 significantly reduces the proliferation of TNBC cells in these assays. Using proteomics, next generation sequencing (NGS), and gene enrichment analysis, we investigated global regulatory pathways affected by this compound in TNBC cells. Proteomics data indicate a significant metabolic reprograming affecting both glycolytic enzymes and energy generation through oxidative phosphorylation. Subsequently, using metabolic (Seahorse) and enzymatic assays, we validated our proteomics and NGS analysis findings. Finally, we showed the inhibitory and anti-tumor effects of this small molecule in vitro and confirmed its inhibitory activity in vivo. Doxorubicin is one of the most effective agents in the treatment of TNBC and resistance to this drug has been a major problem. We show that the combination of NSC33353 and doxorubicin suppresses the growth of TNBC cells synergistically, suggesting that NSC33353 enhances TNBC sensitivity to doxorubicin. In summary, our data indicate that the small molecule inhibitor, NSC33353, exhibits anti-tumor activity in TNBC cells, and works in a synergistic fashion with a well-known chemotherapeutic agent.
    DOI:  https://doi.org/10.1038/s41388-022-02497-2
  44. Biomed Res Int. 2022 ;2022 9051678
    Phytochemical Analysis, Total Phenolic, Flavonoid Contents, and Anticancer Evaluations of Solvent Extracts and Saponins of H. digitata.
    Osama M Alshehri, Saleh Alshamrani, Mater H Mahnashi, Mohammed Merae Alshahrani, Jalwa Ali Khan, Muhammad Shah, Mohammed Ali Alshehri, Rehman Zafar, Muhammad Zahoor, Muhammad Saeed Jan, Syed Shams Ul Hassan, Abdul Sadiq.
      Cancer is one of the most challenging diseases in the modern era for the researchers and investigators. Extensive research worldwide is underway to find novel therapeutics for prevention and treatment of diseases. The extracted natural sources have shown to be one of the best and effective treatments for cell proliferation and angiogenesis. Different approaches including disc potato model, brine shrimp, and chorioallantoic membrane (CAM) assay were adopted to analyze the anticancer effects. Habenaria digitata was also evaluated for MTT activity against NIH/3T3 cell line. The dexamethasone, etoposide, and vincristine sulfate were used as a positive control in these assays. All of the extracts including crude extracts (Hd.Cr), saponin (Hd.Sp), n-hexane (Hd.Hx), chloroform (Hd.Chf), ethyl acetate (Hd.EA), and aqueous fraction (Hd.Aq) were shown excellent results by using various assays. For example, saponin and chloroform have displayed decent antitumor and angiogenic activity by using potato tumor assay. The saponin fraction and chloroform were shown to be the most efficient in potato tumor experiment, demonstrating 87.5 and 93.7% tumor suppression at concentration of 1000 μg/ml, respectively, with IC50 values of 25.5 and 18.3 μg/ml. Additionally, the two samples, chloroform and saponins, outperformed the rest of the test samples in terms of antiangiogenic activity, with IC50 28.63 μg/ml and 16.20 μg/ml, respectively. In characterizing all solvent fractions, the chloroform (Hd.Chf) and saponin (Hd.Sp) appeared to display good effectiveness against tumor and angiogenesis but very minimal activity against A. tumefaciens. The Hd.Chf and Hd.Sp have been prospective candidates in the isolation of natural products with antineoplastic properties.
    DOI:  https://doi.org/10.1155/2022/9051678
  45. Cell Metab. 2022 Oct 14. pii: S1550-4131(22)00447-8. [Epub ahead of print]
    The role of lipids in cancer progression and metastasis.
    Miguel Martin-Perez, Uxue Urdiroz-Urricelqui, Claudia Bigas, Salvador Aznar Benitah.
      Lipids have essential biological functions in the body (e.g., providing energy storage, acting as a signaling molecule, and being a structural component of membranes); however, an excess of lipids can promote tumorigenesis, colonization, and metastatic capacity of tumor cells. To metastasize, a tumor cell goes through different stages that require lipid-related metabolic and structural adaptations. These adaptations include altering the lipid membrane composition for invading other niches and overcoming cell death mechanisms and promoting lipid catabolism and anabolism for energy and oxidative stress protective purposes. Cancer cells also harness lipid metabolism to modulate the activity of stromal and immune cells to their advantage and to resist therapy and promote relapse. All this is especially worrying given the high fat intake in Western diets. Thus, metabolic interventions aiming to reduce lipid availability to cancer cells or to exacerbate their metabolic vulnerabilities provide promising therapeutic opportunities to prevent cancer progression and treat metastasis.
    Keywords:  lipid metabolism; metastasis; metastatic-initiating cells; tumor storm
    DOI:  https://doi.org/10.1016/j.cmet.2022.09.023
  46. Biomater Sci. 2022 Oct 20.
    Pulmonary delivery of curcumin-loaded glycyrrhizic acid nanoparticles for anti-inflammatory therapy.
    Chunxian Piao, Chuanyu Zhuang, Minji Kang, Jihun Oh, Minhyung Lee.
      Acute lung injury (ALI) is an inflammatory disease of the lungs. Curcumin (Cur) shows protective effects in ALI animal models. However, Cur is a hydrophobic drug and its administration into the lungs is inefficient due to its low bioavailability. In this study, glycyrrhizic acid (GA) micelles were produced and evaluated as a carrier of Cur for treatment of ALI. Cur-loaded GA (GA-Cur) nanoparticles were produced using an oil-in-water emulsion/solvent evaporation method. The size and surface charge of the GA-Cur nanoparticles were 159 nm and -23 mV, respectively. In lipopolysaccharide-activated RAW264.7 cells, the GA-Cur nanoparticles decreased the pro-inflammatory cytokine levels more efficiently than GA, Cur, or a simple mixture of GA and Cur (GA + Cur). This suggests that the GA-Cur nanoparticles improved the therapeutic efficiency by enhanced delivery of GA and Cur. GA-Cur inhibited the nuclear translocation of nuclear factor-κb and induced endogenous heme oxygenase-1 more efficiently than the other treatments. Furthermore, an in vitro toxicity test showed that GA-Cur had little cytotoxicity. In vivo therapeutic effects of GA-Cur were evaluated in ALI mouse models. GA-Cur was administered into the animals by intratracheal instillation. The results showed that GA-Cur reduced pro-inflammatory cytokines in a dose-dependent manner and did so more efficiently than GA, Cur, or GA + Cur. Furthermore, the hemolysis and infiltration of monocytes into the lungs were more effectively inhibited by GA-Cur than the other treatments. The data indicate that GA is an efficient carrier of Cur and an anti-inflammatory drug. Owing to their delivery efficiency and safety, GA-Cur nanoparticles will be useful for treatment of ALI.
    DOI:  https://doi.org/10.1039/d2bm00756h
  47. Int J Biol Macromol. 2022 Oct 17. pii: S0141-8130(22)02373-X. [Epub ahead of print]
    Chitosan/xanthan gum-based (Hydroxypropyl methylcellulose-co-2-Acrylamido-2-methylpropane sulfonic acid) interpenetrating hydrogels for controlled release of amorphous solid dispersion of bioactive constituents of Pueraria lobatae.
    Yongmei Guan, Chengqun Yu, Zhenzhong Zang, Xinhao Wan, Abid Naeem, Rui Zhang, Weifeng Zhu.
      Pueraria lobatae (Willd) Ohwi is a traditional Chinese medicine used to treat alcohol intoxication, diabetes, cerebrovascular and cardiovascular diseases. Some of its active components include the flavonoids puerarin, daidzin, daidzein, and genistin. The therapeutic efficacy of these agents is hampered by their poor pharmacokinetic profiles (rapid systemic clearance, low oral bioavailability, short half-life) and physicochemical properties (such as poor aqueous solubility and stability). In the current study, chitosan/xanthan gum-based (hydroxypropyl methylcellulose-co-2-acrylamido-2-methylpropane sulfonic acid) hydrogels for the controlled release of Pueraria lobata-solid dispersion (SD) were successfully prepared and characterized. A total of 61 compounds were identified in the Pueraria lobatae-SD using UHPLC-Q-TOF-MS analysis. Hydrogel structure was confirmed by FTIR, XRD, TGA, DSC, and SEM showed a porous structure. Correlations between hydrogels structural properties was also investigated. The hydrogels showed higher swelling after 48 h at pH 1.2 (21.15 %) than pH 7.4 (15.91 %). In vitro drug release study demonstrated that drug release was maximum at pH 1.2 (63 %) compared to pH 7.4 (49 %) after 48 h. The gel fraction of the synthesized hydrogel was increased with the increase in the polymer and crosslinker concentrations. Furthermore, in vitro studies demonstrated that the developed hydrogels possess good antioxidant and antimicrobial properties.
    Keywords:  Anti-oxidant; Antimicrobial; Herbal medicine; Hydrogel; UHPLC-Q-TOF-MS
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.10.131
  48. Int J Pharm. 2022 Oct 12. pii: S0378-5173(22)00835-3. [Epub ahead of print] 122280
    Encapsulation of thymus vulgaris essential oil in caseinate/gelatin nanocomposite hydrogel: In vitro antibacterial activity and in vivo wound healing potential.
    Sara A Alsakhawy, Hoda H Baghdadi, Moustafa A El-Shenawy, Sally A Sabra, Lobna S El-Hosseiny.
      Essential oils, derived from aromatic plants, exhibit various pharmacological properties. Nevertheless, their clinical applications are confronted by various limitations, such as chemical instability, low aqueous solubility, and poor bioavailability. Nanoencapsulation is one of the approaches that may circumvent these restraints. Accordingly, the present study encapsulated thyme essential oil (TEO) in sodium caseinate (Na CAS) nanomicelles and formulated a gelatin nanocomposite hydrogel, which was investigated as a drug delivery platform for in vitro antibacterial and in vivo wound healing potential. TEO loaded Na CAS nanomicelles showed particle size of 336±17.35 nm, zeta potential of -44.0 mV and EE% of 75±5%. The release profile of TEO loaded nanocomposite hydrogel revealed a sustained release pattern compared to TEO loaded micelles and free oil. The TEO loaded nanomicelles exhibited a significantly higher antibacterial effect than free TEO, as denoted by leakage of alkaline phosphatase and cell membrane disruptions. Furthermore, the TEO loaded nanocomposite hydrogel significantly promoted wound contraction, reduced interleukin-6, and increased transforming growth factor-β1and vascular endothelial growth factor levels, versus control or blank hydrogel group. Hence, the present study is putting forth the fabricated nanocomposite hydrogel as a multifunctional delivery system for TEO in wound healing applications.
    Keywords:  Antibacterial; Nanocomposite hydrogel; Nanomicelles; Sodium caseinate; Thyme essential oil; Wound healing
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122280
  49. Macromol Biosci. 2022 Oct 17. e2200329
    A light-responsive injectable hydrogel with remodeling tumor microenvironment for light-activated chemodynamic therapy.
    Zeming Liu, Hongbo Chen, Chunyu Huang, Qinqin Huang.
      Chemodynamic therapy (CDT) based on Fenton-like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, in this study, we designed a hydrogel-based system to enhance the redox stress (EOH) by loading the composite nanomaterial Cu-Hemin-Au, into the agarose hydrogels. The hydrogels could reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near-infrared light, the Cu-Hemin-Au loaded into the EOH acted as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu-Hemin-Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)-like activity of the Au nanoparticles (NPs), glucose in the tumor cells was largely consumed, and H2 O2 was generated in situ, and then Cu-Hemin-Au reacted with sufficient H2 O2 to generate a large amount of ROS to kill the tumors, which promoted the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieved good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy. This article is protected by copyright. All rights reserved.
    Keywords:  Chemodynamic therapy; Fenton reaction; Hydrogel; Photothermal therapy
    DOI:  https://doi.org/10.1002/mabi.202200329
  50. Front Oncol. 2022 ;12 979683
    GAPDH in neuroblastoma: Functions in metabolism and survival.
    Kevin Cornett, Anna Puderbaugh, Olivia Back, Rolf Craven.
      Neuroblastoma is a pediatric cancer of neural crest cells. It develops most frequently in nerve cells around the adrenal gland, although other locations are possible. Neuroblastomas rely on glycolysis as a source of energy and metabolites, and the enzymes that catalyze glycolysis are potential therapeutic targets for neuroblastoma. Furthermore, glycolysis provides a protective function against DNA damage, and there is evidence that glycolysis inhibitors may improve outcomes from other cancer treatments. This mini-review will focus on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), one of the central enzymes in glycolysis. GAPDH has a key role in metabolism, catalyzing the sixth step in glycolysis and generating NADH. GAPDH also has a surprisingly diverse number of localizations, including the nucleus, where it performs multiple functions, and the plasma membrane. One membrane-associated function of GAPDH is stimulating glucose uptake, consistent with a role for GAPDH in energy and metabolite production. The plasma membrane localization of GAPDH and its role in glucose uptake have been verified in neuroblastoma. Membrane-associated GAPDH also participates in iron uptake, although this has not been tested in neuroblastoma. Finally, GAPDH activates autophagy through a nuclear complex with Sirtuin. This review will discuss these activities and their potential role in cancer metabolism, treatment and drug resistance.
    Keywords:  autophagy; glucose; glycolysis; metabolism; neuroblastoma
    DOI:  https://doi.org/10.3389/fonc.2022.979683
  51. Food Sci Nutr. 2022 Oct;10(10): 3314-3322
    Nano-liposomal encapsulation of Artemisia aucheri phenolics as a potential phytobiotic against Campylobacter jejuni infection in mice.
    Asmae Mehdizadeh, Ehsan Karimi, Ehsan Oskoueian.
      Background: Artemisia aucheri contains antibacterial phenolic compounds. The current work was implemented to evaluate the effectiveness of a nanoliposome-encapsulated phenolic-rich fraction (PRF-NLs), as a dietary phytobiotic derived from Artemisia aucheri's areal parts, on the inhibition of enteropathogenic Campylobacter jejuni (C. jejuni) infection in mice.Methods: The phenolic-rich fraction was loaded into the nanoliposome structure to obtain a nanometer-scale size liposome with homogenous dispersion. Next, 40 white male balb/c mice were assigned to 4 treatment groups. The PRF-NLs antibacterial potential was evaluated by evaluating the blood parameters, liver lipid peroxidation, and gene expression profiling in the mice challenged by C. jejuni infection.
    Results: Mice infected by C. jejuni showed impairment in food intake, weight gain, liver function, ileum morphometric features, and ileum tissue inflammation. The diet of fortified food with the nonencapsulated and nanoliposome-encapsulated phenolic compounds was found to improve these parameters at 10 mg TPC/kg BW/day concentration. Our data indicated that the nanoliposome-encapsulated PRF was more effective in promoting the health parameters in mice as compared to nonencapsulated PRF.
    Conclusion: It could be concluded that the liposomal encapsulation can promote the solubility, availability, and effectiveness of Artemisia aucheri phenolic compounds playing a key role as phytobiotic in mice intervened by enteropathogenic C. jejuni.
    Keywords:  antibiotic alternatives; drug delivery; nanoliposome; natural products; phytogenic
    DOI:  https://doi.org/10.1002/fsn3.2921
  52. Eur J Pharm Biopharm. 2022 Oct 17. pii: S0939-6411(22)00237-5. [Epub ahead of print]
    Tumor-Specific Cyclic Amplification of Oxidative Stress by Disulfide-Loaded Fluoropolymer Nanogels.
    Ruihong Xie, Peng Zhang, Liu Cai, Ranran Guo, Leyu Wang, Xiaozhong Qiu, Ye Tian.
      Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. Herein, the effect of a disulfide, 2,2'-dithiobis(5-aminopyridine) (BAPS), is revealed on depleting glutathione (GSH) circularly and generating superoxide anion (O2•-) spontaneously to manipulate intracellular redox homeostasis. Thus, BAPS is able to work as an oxidative stress amplifier in cancer cells with high GSH concentrations and kill them efficiently. Moreover, leveraging a new class of water-soluble fluoropolymers poly(N-(2-((2,2,2-trifluoroethyl)sulfonyl)ethyl)acrylamide) (PFSNM), BAPS, together with oxygen, can be effectively delivered into hypoxic tumor cells through circulation and significantly inhibit the tumor growth. Therefore, BAPS-loaded PFSNM is an oxidative regulation nanosystem with remarkable therapeutic efficacy for chemodynamic therapy.
    Keywords:  deplete GSH circularly; disulfide; fluoropolymer; oxidative stress; superoxide anion
    DOI:  https://doi.org/10.1016/j.ejpb.2022.10.010
  53. Pharmacol Res. 2022 Oct 12. pii: S1043-6618(22)00451-0. [Epub ahead of print] 106505
    Chlorogenic acid for cancer prevention and therapy: Current status on efficacy and mechanisms of action.
    Ashutosh Gupta, Atanas G Atanasov, Yutong Li, Neeraj Kumar, Anupam Bishayee.
      Chlorogenic acid (CA), also known as 5-O-caffeoylquinic acid, is a dietary phenolic acid produced by various plant species. CA, is the most ubiquitous compound among the phenolic acid group, is also present in tea and green coffee extracts. Its consumption reduces the risk of numerous diseases as validated by preclinical and clinical studies. CA possesses a wide range of pharmacological properties, such as hepatoprotective, antimicrobial, immunomodulatory, antioxidant, antidiabetic, and anticancer activities. It has been extensively used in the food, chemical, medicine, and health care industries. Available reports revealed that CA can exert anticancer activity by inhibiting the cell cycle, triggering apoptosis, and suppressing the proliferation of cancer cells. It upregulates the expression of nuclear factor of activated T cells 2 (NFATC2) and NFATC3 genes involved in immune pathway and downregulates B cell-specific moloney murine leukemia virus integration site 1 protein and SRY-box transcription factor 2 gene expression to facilitate tumor cell destruction. It promotes intracellular DNA impairment and topoisomerase I- and topoisomerase-II-DNA complex formation that perform a key function in apoptosis. In addition, CA has been documented to be an effective natural anticancer drug and was approved by the China Food and Drug Administration. Several previously published reports have provided fragmented summary of various anticancer activities of CA. Therefore, this review aims to deliver up-to-date and comprehensive assessment about the natural sources of CA, its bioavailability, metabolism, and anticancer property with an emphasis on the molecular mechanisms associated with several signaling pathways in tumor cells.
    Keywords:  Chlorogenic acid; anticancer; molecular mechanism; phenolic acid; signaling pathways
    DOI:  https://doi.org/10.1016/j.phrs.2022.106505
  54. J Biomol Struct Dyn. 2022 Oct 18. 1-24
    Natural product inspired leads in the discovery of anticancer agents: an update.
    Firdoos Ahmad Sofi, Nahida Tabassum.
      Natural products have emerged as major leads for the discovery and development of new anti-cancer drugs. The plant-derived anti-cancer drugs account for approximately 60% and the quest for new anti-cancer agents is in progress. Anti-cancer leads have been isolated from plants, animals, marine organisms, and microorganisms from time immemorial. The process of semisynthetic modifications of the parent lead has led to the generation of new anti-cancer agents with improved therapeutic efficacy and minimal side effects. The various chemo-informatics tools, bioinformatics, high-throughput screening, and combinatorial synthesis are able to deliver the new natural product lead molecules. Plant-derived anticancer agents in either late preclinical development or early clinical trials include taxol, vincristine, vinblastine, topotecan, irinotecan, etoposide, paclitaxel, and docetaxel. Similarly, anti-cancer agents from microbial sources include dactinomycin, bleomycin, mitomycin C, and doxorubicin. In this review, we highlighted the importance of natural products leads in the discovery and development of novel anti-cancer agents. The semisynthetic modifications of the parent lead to the new anti-cancer agent are also presented. Further, the leads in the preclinical settings with the potential to become effective anticancer agents are also reviewed.Communicated by Ramaswamy H. Sarma.
    Keywords:  Anti-cancer; SAR; combretastatins; natural product lead; podophyllotoxin; vinca alkaloids
    DOI:  https://doi.org/10.1080/07391102.2022.2134212
  55. Phytother Res. 2022 Oct 18.
    Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues.
    Sudip Kumar Mandal, Santosh Kumar Rath, Rajan Logesh, Siddhartha Kumar Mishra, Hari Prasad Devkota, Niranjan Das.
      Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca2+ -dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca2+ -dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.
    Keywords:  Capsicum annuum; anticancer; capsaicinoids; cardioprotective; pharmacology; traditional use
    DOI:  https://doi.org/10.1002/ptr.7660
  56. Int J Pharm. 2022 Oct 12. pii: S0378-5173(22)00833-X. [Epub ahead of print] 122278
    Chitosan Nanoparticles for Intranasal Delivery of Olmesartan Medoxomil: Pharmacokinetic and Pharmacodynamic Perspectives.
    Rinada H Hassan, Heba A Gad, Sahar Badr El-Din, Dalia S Shaker, Rania A H Ishak.
      Nasal drug delivery has the potential to improve the systemic bioavailability of drugs with low oral bioavailability. Olmesartan medoxomil (OLM) is one of the most popular drugs for the treatment of hypertension with poor oral bioavailability of approximately 26%. In this context, the goal of this work was to synthesize chitosan nanoparticles (CS NPs) loaded with OLM using the ionotropic gelation method to enhance the bioavailability and decrease oral side effects through nasal route. The particle size (PS), zeta potential (ZP), entrapment efficiency (%EE), and ex-vivo transmucosal permeation study of CS NPs were all evaluated. The pharmacokinetic and pharmacodynamic studies of selected formula compared to oral and nasal OLM suspensions were conducted. Successful formation of spherically shaped OLM CS NPS in the nano-range (240.02-344.45 nm) favorable for the intranasal absorption with high %EE (75.2-83.51%) was achieved. The ability of OLM CS NPs to permeate efficiently across the nasal mucosa was proven in an ex vivo permeation experiment. Pharmacokinetic study demonstrated that the intranasal administration of OLM CS NPs exhibited improved bioavailability by 11.3-folds relative to oral OLM suspension as indicated by higher AUC value. The superior effect of intranasal OLM CS NPs was also accentuated in L-NAME induced hypertensive rats compared to intranasal and oral OLM suspension by reducing the high blood pressure (BP) and improving the heart rate (HR) of the induced group. Histological examinations revealed no damage occurred to nasal mucosa. In conclusion, OLM CS NPs had the ability to significantly improve the bioavailability of OLM and decrease BP and HR, suggesting the potential application of CS NPs as a promising carrier for the systemic delivery of OLM via intranasal route.
    Keywords:  Bioavailability; Chitosan nanoparticles; Hypertension; Intranasal; L-NAME; Olmesartan medoxomil
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122278
  57. Nat Commun. 2022 Oct 20. 13(1): 6239
    Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression.
    Zhongchi Li, Vivien Low, Valbona Luga, Janet Sun, Ethan Earlie, Bobak Parang, Kripa Shobana Ganesh, Sungyun Cho, Jennifer Endress, Tanya Schild, Mengying Hu, David Lyden, Wenbing Jin, Chunjun Guo, Noah Dephoure, Lewis C Cantley, Ashley M Laughney, John Blenis.
      The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) fostering cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite also produced by aggressive cancer cells, activates fibroblasts in the TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways. EV-associated IL-6 functions as a stroma-tumor messenger, activating the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promoting pro-aggressive behaviors. Our findings define the role of MMA in CAF activation to drive metastatic reprogramming, unveiling potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.
    DOI:  https://doi.org/10.1038/s41467-022-33862-0
  58. Adv Biol Regul. 2022 Sep 29. pii: S2212-4926(22)00057-4. [Epub ahead of print] 100917
    Effects of chloroquine and hydroxychloroquine on the sensitivity of pancreatic cancer cells to targeted therapies.
    James A McCubrey, Stephen L Abrams, Matilde Y Follo, Lucia Manzoli, Stefano Ratti, Alberto M Martelli, Melchiorre Cervello.
      Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is a cancer which is difficult to effectively treat as it is often detected late in the disease process. Almost all PDACs (over 90%) have activating mutations in the GTPase gene KRAS. These mutations result in constitutive KRas activation and the mobilization of downstream pathways such as the Raf/MEK/ERK pathway. Small molecule inhibitors of key components of the KRas/Raf/MEK/ERK pathways as well as monoclonal antibodies (MoAbs) specific for upstream growth factor receptors such insulin like growth factor-1 receptor (IGF1-R) and epidermal growth factor receptors (EGFRs) have been developed and have been evaluated in clinical trials. An additional key regulatory gene frequently mutated (∼75%) in PDAC is the TP53 tumor suppressor gene which controls the transcription of multiple genes involved in cell cycle progression, apoptosis, metabolism, cancer progression and other growth regulatory processes. Small molecule mutant TP53 reactivators have been developed which alter the structure of mutant TP53 protein and restore some of its antiproliferative activities. Some mutant TP53 reactivators have been examined in clinical trials with patients with mutant TP53 genes. Inhibitors to the TP53 negative regulator Mouse Double Minute 2 (MDM2) have been developed and analyzed in clinical trials. Chloroquine and hydroxychloroquine are established anti-malarial and anti-inflammatory drugs that also prevent the induction of autophagy which can have effects on cancer survival. Chloroquine and hydroxychloroquine have also been examined in various clinical trials. Recent studies are suggesting effective treatment of PDAC patients may require chemotherapy as well as targeting multiple pathways and biochemical processes.
    Keywords:  Chloroquine; KRas; PDAC; TP53; Targeted therapy
    DOI:  https://doi.org/10.1016/j.jbior.2022.100917
  59. Nano Res. 2022 Oct 14. 1-8
    Intracellular and extracellular enzymatic responsive micelle for intelligent therapy of cancer.
    Dong Wan, Qinan Zhu, Jianxin Zhang, Xi Chen, Fangzhou Li, Yi Liu, Jie Pan.
      Recently, the incidence of cancer keeps increasing, seriously endangers human health, and has evolved into the main culprit of human death. Conventional chemotherapeutic drugs, such as paclitaxel and doxorubicin (DOX), have some disadvantages, including low therapeutic effect, poor water solubility, high toxic side effects, short blood circulation time in the body, and so on. To improve the anti-tumor effect of the drug in vivo and reduce its side effects on the body, researchers have designed and developed a variety of responsive nanocarriers. In this work, we synthesized D-α-tocopherol polyethylene glycol 3350 succinate (TPGS3350)-Gly-Pro-Leu-Gly-Val-Arg (GPLGVR)-DOX (TPD) prodrugs in response to extracellular enzymes of matrix metalloproteinase (MMP-9) in the tumor microenvironment and FA-Asp-Glu-Val-Asp (DEVD)-DOX (FPD) prodrugs responsive to intracellular enzymes of caspase-3. Then, intracellular and extracellular enzyme-responsive TPD&FPD micelles with DOX (TPD&FPD&D) were successfully prepared through dialysis method. The outer layer of TPGS3350 can prolong the blood circulation time of micelles in vivo, followed by accumulation of micelles at tumor tissue through enhanced permeability and retention (EPR) effect. The peptide of GPLGVR can be cleaved by MMP-9 enzymes to remove the outer layer of TPGS3350, exposing the targeting molecule of folate, and then the micelles are engulfed by tumor cells through folate receptor-mediated endocytosis. After entering the tumor cells, the free DOX loaded in the micelles is released, which induces tumor cell apoptosis to activate caspase-3 in the cells, cutting the peptide DEVD to accelerate the intracellular release of the DOX, which further enhances cytotoxicity to improve antitumor effect.Electronic Supplementary Material: Supplementary material () is available in the online version of this article at 10.1007/s12274-022-4967-1.
    Keywords:  cancer; enzyme-responsive; folate; micelle; peptide
    DOI:  https://doi.org/10.1007/s12274-022-4967-1
  60. Nat Commun. 2022 Oct 20. 13(1): 6238
    Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy.
    Gang He, Yashi Li, Muhammad Rizwan Younis, Lian-Hua Fu, Ting He, Shan Lei, Jing Lin, Peng Huang.
      5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.
    DOI:  https://doi.org/10.1038/s41467-022-33837-1
  61. J Control Release. 2022 Oct 18. pii: S0168-3659(22)00693-9. [Epub ahead of print]
    Current perspectives and trend of nanomedicine in cancer: A review and bibliometric analysis.
    Zerong Pei, Shuting Chen, Liqin Ding, Jingbo Liu, Xinyi Cui, Fengyun Li, Feng Qiu.
      The limitations of traditional cancer treatments are driving the creation and development of new nanomedicines. At present, with the rapid increase of research on nanomedicine in the field of cancer, there is a lack of intuitive analysis of the development trend, main authors and research hotspots of nanomedicine in the field of cancer, as well as detailed elaboration of possible research hotspots. In this review, data collected from the Web of Science Core Collection database between January 1st, 2000, and December 31st, 2021, were subjected to a bibliometric analysis. The co-authorship, co-citation, and co-occurrence of countries, institutions, authors, literature, and keywords in this subject were examined using VOSviewer, Citespace, and a well-known online bibliometrics platform. We collected 19,654 published papers, China produced the most publications (36.654%, 7204), followed by the United States (29.594%, 5777), and India (7.780%, 1529). An interesting fact is that, despite China having more publications than the United States, the United States still dominates this field, having the highest H-index and the most citations. Acs Nano, Nano Letters, and Biomaterials are the top three academic publications that publish articles on nanomedicine for cancer out of a total of 7580 academic journals. The most significant increases were shown for the keywords "cancer nanomedicine", "tumor microenvironment", "nanoparticles", "prodrug", "targeted nanomedicine", "combination", and "cancer immunotherapy" indicating the promising area of research. Meanwhile, the development prospects and challenges of nanomedicine in cancer are also discussed and provided some solutions to the major obstacles.
    Keywords:  Bibliometrics; Cancer; Immunotherapy; Nanomedicine; Nanoparticle; Visualization
    DOI:  https://doi.org/10.1016/j.jconrel.2022.10.023
  62. Drug Dev Ind Pharm. 2022 Oct 21. 1-36
    Formulation, biopharmaceutical evaluation and in-vitro screening of polyherbal phytosomes for breast cancer therapy.
    Lalitha K Govindaram, Mohammed Al Bratty, Hassan A Alhazmi, Ruckmani Kandasamy, Neelaveni Thangavel, Angum M Ibrahim, Gover Antoniraj Mariya, Kumar Ponnuchamy.
      Saudi Arabia has a rich culture of folk medicines and three such common herbs used by Saudi people for therapy of breast cancer are Turmeric (Kurkum) Curcuma longa, Chamomile (Babunaj) Matricaria chamomilla, and Aswaghantha (Aswaghadh) Withania somnifera. Hence, the present study aims to develop a polyherbal phytosome formulation by thin film hydration technique with a synergistic anti-cancer effect for the treatment of breast cancer. The phytosomes were standardized for their phytoconstituents by HPTLC and showed the best optimal properties with a mean vesicle diameter of less than 200 nm, zeta potential in the range of -24.43 to -35.70 mV, and relatively integrated structure with fairly uniform size on TEM. The in vitro MTT assay on MCF-7 breast cancer cell lines and MDA MB 231 breast adenocarcinoma cell lines was carried out. MTT assay on MCF-7 breast cancer cell lines indicated that plant extract-loaded phytosomes exhibited enhanced cytotoxic effects at IC50 values. of 55, 50, 45, 52, 42, 44, and 20µg/mL compared to the extracts of C. longa, M. chamomilla, W. somnifera, and their combined extracts (80, 82, 74, 60, 70, 60, and 35 µg/mL respectively). Moreover, intracellular reactive oxygen species production was found to be higher for phytosomes treated cells at respective IC50 concentrations when compared to extracts. Overall, the developed polyherbal phytosomes were found to be effective and afford synergistic effects for breast cancer therapy.
    Keywords:  Breast cancer; Curcuma longa; MCF-7 cell lines; MDA MB 231 cell lines; Matricaria chamomilla; Phytosomes; Withania somnifera
    DOI:  https://doi.org/10.1080/03639045.2022.2138911
  63. Oxid Med Cell Longev. 2022 ;2022 1984742
    Oxidative Stress and Intervertebral Disc Degeneration: Pathophysiology, Signaling Pathway, and Therapy.
    Yanrun Li, Lu Chen, Yu Gao, Xuenong Zou, Fuxin Wei.
      Intervertebral disc degeneration (IDD), characterized as decreased proteoglycan content, ossification of endplate, and decreased intervertebral height, is one of the major reasons of low back pain, which seriously affects the quality of life and also brings heavy economic burden. However, the mechanisms leading to IDD and its therapeutic targets have not been fully elucidated. Oxidative stress refers to the imbalance between oxidation and antioxidant systems, between too many products of reactive oxygen species (ROS) and the insufficient scavenging function. Excessive ROS can damage cell lipids, nucleic acids and proteins, which has been proved to be related to the development of a variety of diseases. In recent years, an increasing number of studies have reported that oxidative stress is involved in the pathological process of IDD. Excessive ROS can accelerate the IDD process via inducing the pathological activities, such as inflammation, apoptosis, and senescence. In this review, we focused on pathophysiology and molecular mechanisms of oxidative stress-induced IDD. Moreover, the present review also summarized the possible ideas for the future therapy strategies of oxidative stress-related IDD.
    DOI:  https://doi.org/10.1155/2022/1984742
  64. Bratisl Lek Listy. 2022 ;123(11): 813-821
    Anti-cancer effects of selective cannabinoid agonists in pancreatic and breast cancer cells.
    Nergiz Hacer Turgut, Guliz Armagan, Gozde Kasapligil, Mumin Alper Erdogan.
      OBJECTIVE: Cancer ranks first among the causes of morbidity and mortality all over the world, and it is expected to continue to be the main cause of death in the coming years. Therefore, new molecular targets and therapeutic strategies are urgently needed. In many cases, some reports show increased levels of endocannabinoids and their receptors in cancer, a condition often associated with tumour aggressiveness. Recent studies have suggested that cannabinoid-1/2 receptors contribute to tumour growth in a variety of cancers, including pancreatic, colon, prostate, and breast cancer. Understanding how cannabinoids can regulate key cellular processes involved in tumorigenesis, such as: cell proliferation and cell death, is crucial to improving existing and new therapeutic approaches for the cancer patients. The present study was aimed to characterize the in-vitro effect of L-759633 (a selective CB2 receptor agonist), ACPA (a selective CB1 receptor agonist) and ACEA (a selective CB1 receptor agonist) on the cell proliferation, clonogenicity, and apoptosis in pancreatic (PANC1) and breast (MDA-MB-231) cancer cells.METHODS: The viability and/or proliferation of cells were detected by MTS assay. A clonogenic survival assay was used to detect the ability of a single cell to grow into a colony. Apoptosis was determined with Annexin V staining (Annexin V-FITC/PI test) and by analyzing the expression of Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2).
    RESULTS: We found that selective CB1/2 agonists suppressed cell proliferation, clonogenicity and induced proapoptotic function in human PANC1 pancreatic and MDA-MB-231 breast cancer cells. Based on our findings, these agonists led to the inhibition of both cell viability and clonogenic growth in a dose dependent manner. CB1/2 agonists were observed to induce intrinsic apoptotic pathway by upregulating Bax, while downregulating Bcl-2 expression levels.
    CONCLUSION: Our data suggests that CB1/2 agonists have the therapeutic potential through the inhibition of survival of human PANC1 pancreatic and MDA-MB-231 breast cancer cells and also might be linked with further cellular mechanisms for the prevention (Fig. 5, Ref. 49).
    Keywords:  ACEA; ACPA; L-759633; apoptosis; pancreatic cancer breast cancer.
    DOI:  https://doi.org/10.4149/BLL_2022_130
  65. Int J Pharm. 2022 Oct 18. pii: S0378-5173(22)00856-0. [Epub ahead of print] 122301
    Lemongrass (Cymbopogon citratus)-incorporated chitosan bioactive films for potential skincare applications.
    Ana L Gaspar, Ana B Gaspar, Luana R F Contini, Mariangela F Silva, Eduardo G L Chagas, Juliana O Bahú, Viktor O C Concha, Rosemary A Carvalho, Patricia Severino, Eliana B Souto, Patrícia S Lopes, Cristiana M P Yoshida.
      Circular economy, and concerns about environmental waste, is fostering the development of sustainable alternative products in a range of industries. In the dermo-cosmetic field, the market for sustainable anti-aging skincare products has increasingly grown over the last years. The innovation of this work was to develop chitosan films incorporating lemongrass essential oil (LEO) that could potentially be applied as a green cosmetic skin treatment due to their anti-oxidant and antimicrobial properties, using renewable and biodegradable materials. Different concentrations of LEO (i.e., 0.5, 1.0, and 1.5% w/w) were formulated into chitosan filmogenic matrices, forming skincare bioactive films. Their antioxidant properties and water vapor permeability were strongly governed by the LEO concentration. Chitosan bioactive films containing 0.5% LEO showed cellular viability over 70%, while those with 1.5% LEO had similar antioxidant capacity as NAC (N-acetyl-L-cysteine), used as the positive control to inactivate intracellular reactive oxygen species (ROS) in HaCat cells not treated with H2O2. The developed bioactive films showed activity against Escherichia coli and Staphylococcus aureus. Our LEO-loaded chitosan biofilms may be used as sheet masks with antioxidant and antimicrobial properties for skincare, with high flexibility and selected permeability, and without cytotoxic risks.
    Keywords:  Antimicrobial; Antioxidant; Biopolymer; Chitosan; Circular economy; Lemongrass essential oil
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122301
  66. Iran J Basic Med Sci. 2022 Sep;25(9): 1045-1058
    Hypericum perforatum: Traditional uses, clinical trials, and drug interactions.
    Seyedeh Zahra Nobakht, Maryam Akaberi, Amir Hooshang Mohammadpour, Ali Tafazoli Moghadam, Seyed Ahmad Emami.
      Hypericum perforatum (Hypericaceae), known as Saint John's wort (SJW), has been used in different systems of traditional medicine such as Chinese traditional medicine, Greek traditional medicine, and Islamic traditional medicine. The plant and its active constituents such as hyperforin and hypericin have a wide range of medicinal uses, particularly as anti-depressant, wound-healing, and antibacterial agents. In recent decades, many clinical trials have been performed to investigate the safety and efficacy of this medicinal plant. However, to the best on our knowledge, there is no comprehensive review article in this regard. In the current study, we aim to have a comprehensive review of the clinical trials of SJW to evaluate its efficacy and safety as well as its application in traditional medicine. Clinical studies investigating the safety, interactions, and efficacy of SJW were identified and summarized, including contributions from 2000 until December 2021. According to the results, these clinical studies were divided into three main categories based on the type of disease: psychiatric, endocrine, and skin problems. Important details of the studies, including the type and duration of the study, the type and percentage of the effective compounds or the extract used, the number of patients, and the obtained results were also discussed. In addition, co-administration and drug interaction of SJW with other drugs were summarized. SJW is a valuable medicinal plant, especially for psychiatric disorders. However, precautions should be taken while administrating the plant.
    Keywords:  Clinical trials; Hyperforin; Hypericaceae; Hypericin; Hypericum perforatum; St. John’s wort
    DOI:  https://doi.org/10.22038/IJBMS.2022.65112.14338
  67. J Cancer Prev. 2022 Sep 30. 27(3): 139-146
    Dietary Intervention for Preventing Colorectal Cancer: A Practical Guide for Physicians.
    Sang Hoon Kim, Jeong Yeon Moon, Yun Jeong Lim.
      Colorectal cancer (CRC) is a disease with high prevalence and mortality. Estimated preventability for CRC is approximately 50%, indicating that altering modifiable factors, including diet and body weight, can reduce CRC risk. There is strong evidence that dietary factors including whole grains, high-fiber, red and processed meat, and alcohol can affect the risk of CRC. An alternative strategy for preventing CRC is use of a chemopreventive supplement that provides higher individual exposure to nutrients than what can be obtained from the diet. These include calcium, vitamin D, folate, n-3 polyunsaturated fatty acids, and phytochemicals. Several intervention trials have shown that these dietary chemopreventives have positive protective effects on development and progression CRC. Research on chemoprevention with phytochemicals that possess anti-inflammatory and/or, anti-oxidative properties is still in the preclinical phase. Intentional weight loss by bariatric surgery has not been effective in decreasing long-term CRC risk. Physicians should perform dietary education for patients who are at high risk of cancer for changing their dietary habits and behaviour. An increased understanding of the role of individual nutrients linked to the intestinal micro-environment and stages of carcinogenesis would facilitate the development of the best nutritional formulations for preventing CRC.
    Keywords:  Calcium; Chemoprevention; Colorectal neoplasms; Diet; Fatty acids; omega-3
    DOI:  https://doi.org/10.15430/JCP.2022.27.3.139
  68. Front Nutr. 2022 ;9 1024820
    Recent advances in the extraction, chemical composition, therapeutic potential, and delivery of cardamom phytochemicals.
    Abdullah, Naveed Ahmad, Wenni Tian, Song Zengliu, Yucheng Zou, Shahzad Farooq, Qingrong Huang, Jie Xiao.
      Dietary phytochemicals including plant-derived alkaloids, carotenoids, organosulfur compounds, phenolics, and phytosterols, are health-promoting bioactive compounds that help in the prevention and mitigation of chronic diseases and microbial infections beyond basic nutrition supply. This article covers recent advances in the extraction, chemical composition, therapeutic potential (nutraceutical and antimicrobial), and delivery of black and green cardamom-derived phytochemicals. In recent years, advance extraction techniques (e.g., enzyme- assisted-, instant controlled pressure drop-, microwave- assisted-, pressurized liquid-, sub- critical-, supercritical fluid-, and ultrasound-assisted extractions) have been applied to obtain phytochemicals from cardamom. The bioactive constituents identification techniques, specifically GC-MS analysis revealed that 1,8-cineole and α-terpinyl acetate were the principle bioactive components in black and green cardamom. Regarding therapeutic potential, research findings have indicated desirable health properties of cardamom phytochemicals, including antioxidant-, anti-hypercholesterolemic, anti-platelet aggregation, anti-hypertensive, and gastro-protective effects. Moreover, antimicrobial investigations revealed that cardamom phytochemicals effectively inhibited growth of pathogenic microorganisms (bacteria and fungi), biofilm formation inhibition (Gram-negative and Gram-positive bacteria) and bacterial quorum sensing inhibition. Encapsulation and delivery vehicles, including microcapsules, nanoparticles, nanostructured lipid carriers, and nanoliposomes were effective strategies to enhance their stability, bioavailability and bioefficacy. In conclusion, cardamom phytochemicals had promising therapeutic potentials (antioxidant and antimicrobial) due to polyphenols, thus could be used as functional additive to increase shelf life, inhibit oxidative rancidity and confer pleasant aroma to commercial edibles as well as mitigate oxidative stress and lifestyle related chronic diseases (e.g., cardiovascular and gastrointestinal diseases). A future perspective concerning the fabrication of functional foods, nutraceuticals and antibiotics to promote cardamom phytochemicals applications as biotherapeutic agents at large-scale requires thorough investigations, e.g., optimum dose and physical form of supplementation to obtain maximum health benefits.
    Keywords:  bioactivities; bioavailability; cardamom; encapsulation and delivery; extraction techniques; phytochemicals
    DOI:  https://doi.org/10.3389/fnut.2022.1024820
  69. Front Hum Neurosci. 2022 ;16 846183
    Exogenous Ketones and Lactate as a Potential Therapeutic Intervention for Brain Injury and Neurodegenerative Conditions.
    Naomi Elyse Omori, Geoffrey Hubert Woo, Latt Shahril Mansor.
      Metabolic dysfunction is a ubiquitous underlying feature of many neurological conditions including acute traumatic brain injuries and chronic neurodegenerative conditions. A central problem in neurological patients, in particular those with traumatic brain injuries, is an impairment in the utilization of glucose, which is the predominant metabolic substrate in a normally functioning brain. In such patients, alternative substrates including ketone bodies and lactate become important metabolic candidates for maintaining brain function. While the potential neuroprotective benefits of ketosis have been recognized for up to almost a century, the majority of work has focused on the use of ketogenic diets to induce such a state, which is inappropriate in cases of acute disease due to the prolonged periods of time (i.e., weeks to months) required for the effects of a ketogenic diet to be seen. The following review seeks to explore the neuroprotective effects of exogenous ketone and lactate preparations, which have more recently become commercially available and are able to induce a deep ketogenic response in a fraction of the time. The rapid response of exogenous preparations makes their use as a therapeutic adjunct more feasible from a clinical perspective in both acute and chronic neurological conditions. Potentially, their ability to globally moderate long-term, occult brain dysfunction may also be relevant in reducing lifetime risks of certain neurodegenerative conditions. In particular, this review explores the association between traumatic brain injury and contusion-related dementia, assessing metabolic parallels and highlighting the potential role of exogenous ketone and lactate therapies.
    Keywords:  brain; exogenous; injury; ketones; lactate; metabolism dysfunction; neurodegenerative; traumatic
    DOI:  https://doi.org/10.3389/fnhum.2022.846183
  70. Front Pharmacol. 2022 ;13 967106
    Formulation of ciprofloxacin-loaded oral self-emulsifying drug delivery system to improve the pharmacokinetics and antibacterial activity.
    Asghar Ali Asghar, Muhammad Akhlaq, Aamir Jalil, Abul Kalam Azad, Junaid Asghar, Muhammad Adeel, Ghadeer M Albadrani, Amin A Al-Doaiss, Mohamed Kamel, Ahmed E Altyar, Mohamed M Abdel-Daim.
      This study aims to increase the aqueous solubility of ciprofloxacin (CPN) to improve oral bioavailability. This was carried out by formulating a stable formulation of the Self-Emulsifying Drug Delivery System (SEDDS) using various ratios of lipid/oil, surfactant, and co-surfactant. A pseudo-ternary phase diagram was designed to find an area of emulsification. Eight formulations (F1-CPN-F8-CPN) containing oleic acid oil, silicone oil, olive oil, castor oil, sunflower oil, myglol oil, polysorbate-80, polysorbate-20, PEO-200, PEO-400, PEO-600, and PG were formulated. The resultant SEDDS were subjected to thermodynamic study, size, and surface charge studies to improve preparation. Improved composition of SEDDS F5-CPN containing 40% oil, 60% polysorbate-80, and propylene glycol (Smix ratio 6: 1) were thermodynamically stable emulsions having droplet size 202.6 nm, charge surface -13.9 mV, and 0.226 polydispersity index (PDI). Fourier transform infra-red (FT-IR) studies revealed that the optimized formulation and drug showed no interactions. Scanning electron microscope tests showed the droplets have an even surface and spherical shape. It was observed that within 5 h, the concentration of released CPN from optimized formulations F5-CPN was 93%. F5-CPN also showed a higher antibacterial action against S. aurous than free CPN. It shows that F5-CPN is a better formulation with a good release and high antibacterial activity.
    Keywords:  ciprofloxacin; oral bioavailability; pseudo-ternary phase diagram; self-emulsifying drug delivery system; solubility
    DOI:  https://doi.org/10.3389/fphar.2022.967106
  71. J Biomed Sci. 2022 Oct 20. 29(1): 84
    Reprogramming of sentinel lymph node microenvironment during tumor metastasis.
    Yen-Liang Li, Wen-Chun Hung.
      Metastasis is a major cause of death in patients with cancer. The two main routes for cancer cell dissemination are the blood and lymphatic systems. The underlying mechanism of hematogenous metastasis has been well characterized in the past few decades. However, our understanding of the molecular basis of lymphatic metastasis remains at a premature stage. Conceptually, cancer cells invade into lymphatic capillary, passively move to collecting lymphatic vessels, migrate into sentinel lymph node (SLN;, the first lymph node to which cancer cells spread from the primary tumor), and enter the blood circulatory system via the subclavian vein. Before arriving, cancer cells release specific soluble factors to modulate the microenvironment in SLN to establish a beachhead for successful colonization. After colonization, cancer cells inhibit anti-tumor immunity by inducing the recruitment of regulatory T cell and myeloid-derived suppressor cells, suppressing the function of dendritic cell and CD8+ T cell, and promoting the release of immunosuppressive cytokines. The development of novel strategies to reverse cancer cell-triggered SLN remodeling may re-activate immunity to reduce beachhead buildup and distant metastasis. In addition to being a microanatomic location for metastasis, the SLN is also an important site for immune modulation. Nanotechnology-based approaches to deliver lymph node-tropic antibodies or drug-conjugated nanoparticles to kill cancer cells on site are a new direction for cancer treatment. Conversely, the induction of stronger immunity by promoting antigen presentation in lymph nodes provides an alternate way to enhance the efficacy of immune checkpoint therapy and cancer vaccine. In this review article, we summarize recent findings on the reprogramming of SLN during lymphatic invasion and discuss the possibility of inhibiting tumor metastasis and eliciting anti-tumor immunity by targeting SLN.
    Keywords:  Immune; Lymph node; Metastasis; Microenvironment
    DOI:  https://doi.org/10.1186/s12929-022-00868-1
  72. Sci Rep. 2022 Oct 19. 12(1): 17431
    Preparation, physicochemical characterization, and bioactivity evaluation of berberine-entrapped albumin nanoparticles.
    Fatema A Younis, Samar R Saleh, Sahar S Abd El-Rahman, Al-Sayeda A Newairy, Maha A El-Demellawy, Doaa A Ghareeb.
      Berberine (BBR) is an isoquinoline alkaloid with several clinical therapeutic applications. Its low water solubility, absorption, and cellular bioavailability diminish BBR's therapeutic efficacy. In this study, BBR was encapsulated into bovine serum albumin nanoparticles (BSA NPs) core to reduce BBR limitations and enhance its clinical therapeutic properties. Several physicochemical characterization tools, such as Dynamic Light Scattering and Ultraviolet-Visible spectroscopic measurements, field emission transmission electron microscopy surface morphology, Fourier transforms infrared spectroscopy, thermal stability analysis, and releasing studies, were used to evaluate the BBR-BSA NPs. Compared to BBR, BBR-BSA nanoparticles demonstrated superior free radical scavenging and antioxidant capacities, anti-hemolytic and anticoagulant efficacies, and antimicrobial activities, as demonstrated by the findings of the in vitro studies. Furthermore, a stressed pancreatic rat model was induced using a high-fat, high-sucrose diet plus carbon tetrachloride injection. The in vivo results revealed that BBR-BSA NPs substantially restored peripheral glucose metabolism and insulin sensitivity. Oral administration of BBR-BSA NPs also improved pancreatic β-cells homeostasis, upregulated pancreatic antioxidant mechanisms, inhibited oxidants generation, and attenuated oxidative injury in the stressed pancreatic tissues. In conclusion, our in vitro and in vivo results confirmed that BBR-BSA NPs demonstrated more potent antioxidant properties and restored pancreatic homeostasis compared to BBR.
    DOI:  https://doi.org/10.1038/s41598-022-21568-8
  73. Endocr Metab Immune Disord Drug Targets. 2022 Oct 18.
    Nutraceuticals: A Promising Approach Towards Diabetic Neuropathy.
    Sakshi Bajaj, Sumeet Gupta.
      BACKGROUND: Various nutraceuticals from different sources have various beneficial actions and have been reported for many years. The important findings from the research conducted using various nutraceuticals exhibiting significant physiological and pharmacological activities have been summarized.METHODS: An extensive investigation of literature was done using several worldwide electronic scientific databases like PUBMED, SCOPUS, Science Direct, Google Scholar, etc. The entire manuscript is available in the English language that is used for our various compounds of interest. These databases were thoroughly reviewed and summarized.
    RESULTS: Nutraceuticals obtained from various sources play a vital role in the management of peripheral neuropathy associated with diabetes. Treatment with nutraceuticals has been beneficial as an alternative in preventing the progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DPN.
    CONCLUSION: Nutraceuticals obtained from different sources like a plant, an animal, and marine have been properly utilized for the safety of health. In our opinion, this review could be of great interest to clinicians, as it offers a complementary perspective on the management of DPN. Trials with a well-defined patient and symptom selection have shown robust pharmacological design as pivotal points to let these promising compounds become better accepted by the medical community.
    Keywords:  Antioxidant; Health benefit; Neuroinflammation; Neuropathy; Nutraceuticals
    DOI:  https://doi.org/10.2174/1871530323666221018090024
  74. Adv Healthc Mater. 2022 Oct 22. e2202219
    Highly Efficient Photodynamic Therapy with Mitochondria-Targeting Aggregation-induced Emission Photosensitizer for Retinoblastoma.
    Lingbo Zhou, Luojia Chen, Sijie Chen, Zeyuan Pu, Meijia Gu, Yin Shen.
      Retinoblastoma (RB) is an aggressive eye cancer in infancy and childhood, lethal by metastasis if left untreated. Currently, the survival rate and the chance of saving vision depend on the severity of the disease. In this work, a highly efficient photodynamic ophthalmic therapy for RB is reported by employing an isoquinolinium-based aggregation-induced-emission (AIE) photosensitizer (PS) TPE-IQ-2O for photodynamic inactivation (PDI). TPE-IQ-2O is an efficient mitochondria-targeting photosensitizer as an efficient guided photodynamic therapy (PDT) agent against cancer cells. Maximizing cancer-selectively damage to tumors with minimized side effects on normal tissue is essential for effective anticancer PDT and provides long-lasting protection against metastasis. In addition, TPE-IQ-2O can effectively reduce the degree of tissue inflammation by inhibiting the expression of related inflammatory factors. TPE-IQ-2O also exhibits excellent biocompatibility with neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications in the treatment of RB. This article is protected by copyright. All rights reserved.
    Keywords:  aggregation-induced emission; mitochondria-targeting; photodynamic; retinoblastoma
    DOI:  https://doi.org/10.1002/adhm.202202219
  75. Medicine (Baltimore). 2022 Oct 14. 101(41): e31002
    Dietary β-carotene and vitamin A and risk of Parkinson disease: A protocol for systematic review and meta-analysis.
    Ling-Yu Wu, Jing-Xin Chen, Gui-Sheng Chen, Hua Gao, Jing-Hong Huo, Yu-Fei Pang, Qing-Han Gao.
      BACKGROUND: The beneficial effects of dietary β-carotene and vitamin A on Parkinson disease (PD) have been confirmed, but some studies have yielded questionable results. Therefore, this meta-analysis investigated the effect of dietary β-carotene and vitamin A on the risk of PD.METHODS: The following databases were searched for relevant paper: PubMed, Embase, Medline, Scopus, Cochrane Library, CNKI, Wanfang Med online, and Weipu databases for the relevant paper from 1990 to March 28, 2022. The studies included were as follows: β-carotene and vitamin A intake was measured using scientifically recognized approaches, such as food frequency questionnaire (FFQ); evaluation of odds ratios using OR, RR, or HR; β-carotene and vitamin A intake for three or more quantitative categories; and PD diagnosed by a neurologist or hospital records.
    RESULTS: This study included 11 studies (four cohort studies, six case-control studies, and one cross-sectional study). The high β-carotene intake was associated with a significantly lower chance of developing PD than low β-carotene intake (pooled OR = 0.83, 95%CI = 0.74-0.94). Whereas the risk of advancement of PD was not significantly distinctive among the highest and lowest vitamin A intake (pooled OR = 1.08, 95%CI = 0.91-1.29).
    CONCLUSIONS: Dietary β-carotene intake may have a protective effect against PD, whereas dietary vitamin A does not appear to have the same effect. More relevant studies are needed to include into meta-analysis in the further, as the recall bias and selection bias in retrospective and cross-sectional studies cause misclassifications in the assessment of nutrient intake.
    DOI:  https://doi.org/10.1097/MD.0000000000031002
  76. Front Pharmacol. 2022 ;13 997598
    Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways.
    Tianwei Meng, Xinghua Li, Chengjia Li, Jiawen Liu, Hong Chang, Nan Jiang, Jiarui Li, Yabin Zhou, Zhiping Liu.
      Atherosclerosis (AS) is a prevalent arteriosclerotic vascular disease that forms a pathological basis for coronary heart disease, stroke, and other diseases. Inflammatory and oxidative stress responses occur throughout the development of AS. Treatment for AS over the past few decades has focused on administering high-intensity statins to reduce blood lipid levels, but these inevitably damage liver and kidney function over the long term. Natural medicines are widely used to prevent and treat AS in China because of their wide range of beneficial effects, low toxicity, and minimal side effects. We searched for relevant literature over the past 5 years in databases such as PubMed using the keywords, "atherosclerosis," "traditional Chinese medicine," "natural medicines," "inflammation," and "oxidative stress." We found that the PI3K/AKT, TLR4, JAK/STAT, Nrf2, MAPK, and NF-κB are the most relevant inflammatory and oxidative stress pathways in AS. This review summarizes studies of the natural alkaloid, flavonoid, polyphenol, saponin, and quinone pathways through which natural medicines used to treat AS. This study aimed to update and summarize progress in understanding how natural medicines treat AS via inflammatory and oxidative stress-related signaling pathways. We also planned to create an information base for the development of novel drugs for future AS treatment.
    Keywords:  atherosclerosis; inflammatory factor; natural medicines; pathological mechanism; receptor
    DOI:  https://doi.org/10.3389/fphar.2022.997598
  77. Mol Cell. 2022 Oct 20. pii: S1097-2765(22)00958-3. [Epub ahead of print]82(20): 3760-3762
    Vitamin K: A new guardian against ferroptosis.
    Tal Hirschhorn, Brent R Stockwell.
      The dietary factor vitamin K has been found to protect against ferroptosis, a form of cell death driven by lipid peroxidation. This reveals new dietary links to cancers and degenerative conditions and a key factor involved in warfarin poisoning.
    DOI:  https://doi.org/10.1016/j.molcel.2022.10.001
  78. Cureus. 2022 Sep;14(9): e29059
    The Application of Nanotechnology and Nanomaterials in Cancer Diagnosis and Treatment: A Review.
    Chinmay Kher, Sunil Kumar.
      Cancer is one of the deadliest diseases worldwide in present times, with its incidence on a tremendous rise. It is caused by uncontrolled cell growth. Cancer therapies have advanced substantially, but there is a need for improvement in specificity and fear of systemic toxicity. Early detection is critical in improving patients' prognosis and quality of life, and recent advancements in technology, especially in dealing with biomaterials, have aided in that surge. Nanotechnology possesses the key to solving many of the downsides of traditional pharmaceutical formulations. Indeed, significant progress has been made in using customized nanomaterials for cancer diagnosis and treatment with high specificity, sensitivity, and efficacy. Nanotechnology is the integration of nanoscience into medicine by the use of nanoparticles. The advent of nanoscience in cancer diagnosis and treatment will help clinicians better assess and manage patients and improve the healthcare system and services. This review article gives an account of the clinical applications of nanoscience in the modern management of cancer, the different modalities of nanotechnology used, and the limitations and possible side effects of this new tool.
    Keywords:  cancer; diagnosis; nanomedicine; nanotechnology; prognosis; treatment
    DOI:  https://doi.org/10.7759/cureus.29059
  79. ACS Pharmacol Transl Sci. 2022 Oct 14. 5(10): 838-848
    Elucidating the Beneficial Effects of Ginger (Zingiber officinale Roscoe) in Parkinson's Disease.
    Efthalia Angelopoulou, Yam Nath Paudel, Sokratis G Papageorgiou, Christina Piperi.
      Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD), and its pathogenesis remains obscure. Current treatment approaches mainly including levodopa and dopamine agonists provide symptomatic relief but fail to halt disease progression, and they are often accompanied by severe side effects. In this context, natural phytochemicals have received increasing attention as promising preventive or therapeutic candidates for PD, given their multitarget pharmaceutical mechanisms of actions and good safety profile. Ginger (Zingiber officinale Roscoe, Zingiberaceae) is a very popular spice used as a medicinal herb throughout the world since the ancient years, for a wide range of conditions, including nausea, diabetes, dyslipidemia, and cancer. Emerging in vivo and in vitro evidence supports the neuroprotective effects of ginger and its main pharmaceutically active compounds (zingerone, 6-shogaol, and 6-gingerol) in PD, mainly via the regulation of neuroinflammation, oxidative stress, intestinal permeability, dopamine synaptic transmission, and possibly mitochondrial dysfunction. The regulation of several transcription factors and signaling pathways, including nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3K)/Ak strain transforming (Akt), extracellular signal-regulated kinase (ERK) 1/2, and AMP-activated protein kinase (AMPK)/proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) have been shown to contribute to the protective effects of ginger. Herein, we discuss recent findings on the beneficial role of ginger in PD as a preventive agent or potential supplement to current treatment strategies, focusing on potential underlying molecular mechanisms.
    DOI:  https://doi.org/10.1021/acsptsci.2c00104
  80. Semin Cancer Biol. 2022 Oct 17. pii: S1044-579X(22)00208-5. [Epub ahead of print]
    Reprogramming of glycolysis by chemical carcinogens during tumor development.
    Leonard Clinton D'Souza, Anusmita Shekher, Kishore B Challagundla, Anurag Sharma, Subash Chandra Gupta.
      Indiscriminate usage and mismanagement of chemicals in the agricultural and industrial sectors have contaminated different environmental compartments. Exposure to these persistent and hazardous pollutants like heavy metals, endocrine disruptors, aromatic hydrocarbons, and pesticides can result in various health adversities, including cancer. Chemical carcinogens follow a similar pattern of carcinogenesis, like oxidative stress, chromosomal aberration, DNA double-strand break, mismatch repair, and misregulation of oncogenic and/or tumor suppressors. Out of several cancer-associated endpoints, cellular metabolic homeostasis is the commonest to be deregulated upon chemical exposure. Chemical carcinogens hamper glycolytic reprogramming to fuel the malignant transformation of the cells and/or promote cancer progression. Several regulators like Akt, ERK, Ras, c-Myc, HIF-1α, and p53 regulate glycolysis in chemical-induced carcinogenesis. However, the deregulation of the anabolic biochemistry of glucose during chemical-induced carcinogenesis remains to be uncovered. This review comprehensively covers the environmental chemical-induced glycolytic shift during carcinogenesis and its mechanism. The focus is also to fill the major gaps associated with understanding the fairy tale between environmental carcinogens and metabolic reprogramming. Although evidence from studies regarding glycolytic reprogramming in chemical carcinogenesis provides valuable insights into cancer therapy, exposure to a mixture of toxicants and their mechanism of inducing carcinogenesis still needs to be studied.
    Keywords:  Cancer progression; Environmental carcinogens; Glycolytic reprogramming; Malignancy; Warburg energetics
    DOI:  https://doi.org/10.1016/j.semcancer.2022.10.004
  81. ACS Nano. 2022 Oct 18.
    Inhibition of NADPH Oxidase-ROS Signal using Hyaluronic Acid Nanoparticles for Overcoming Radioresistance in Cancer Therapy.
    Lei Zhu, Yi Zhao, Tongrui Liu, Minglong Chen, Wei Ping Qian, Binghua Jiang, Benjamin G Barwick, Lumeng Zhang, Toncred M Styblo, Xiaoxian Li, Lily Yang.
      Upregulation of NADPH oxidases (NOXs) in cancer cells leads to chronic increase in intracellular reactive oxygen species (ROS) and adaptation to a high ROS level for cell survival and, thereby, low sensitivity to radiotherapy. To overcome resistance to radiotherapy, we have developed a bioactive and CD44 targeted hyaluronic acid nanoparticle encapsulated with an NOX inhibitor, GKT831 (HANP/GKT831). We found that HANP/GKT831 had stronger inhibitory effects on ROS generation and cell proliferation than that of GKT831 alone in cancer cells. Systemic delivery of HANP/GKT831 led to the targeted accumulation in breast cancer patient derived xenograft (PDX) tumors in nude mice. Importantly, the combination of systemic delivery of HANP/GKT831 with a low dose of local radiotherapy significantly enhanced tumor growth inhibition in breast cancer PDX models. Our results showed that HANP/GKT831 primed tumor cells to radiation-induced DNA damage and cell death by downregulation of DNA repair function and oncogenic signal pathways.
    Keywords:  GKT831; NADPH oxidases; Redox imbalance; hyaluronic acid nanoparticle (HANP); radiotherapy resistance; reactive oxygen species; targeted cancer therapy
    DOI:  https://doi.org/10.1021/acsnano.2c07440
  82. Proc Natl Acad Sci U S A. 2022 Oct 25. 119(43): e2204481119
    Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.
    Lauren Wallon, Imran Khan, Kai Wen Teng, Akiko Koide, Mariyam Zuberi, Jianping Li, Gayatri Ketavarapu, Nathaniel J Traaseth, John P O'Bryan, Shohei Koide.
      RAS mutants are major therapeutic targets in oncology with few efficacious direct inhibitors available. The identification of a shallow pocket near the Switch II region on RAS has led to the development of small-molecule drugs that target this site and inhibit KRAS(G12C) and KRAS(G12D). To discover other regions on RAS that may be targeted for inhibition, we have employed small synthetic binding proteins termed monobodies that have a strong propensity to bind to functional sites on a target protein. Here, we report a pan-RAS monobody, termed JAM20, that bound to all RAS isoforms with nanomolar affinity and demonstrated limited nucleotide-state specificity. Upon intracellular expression, JAM20 potently inhibited signaling mediated by all RAS isoforms and reduced oncogenic RAS-mediated tumorigenesis in vivo. NMR and mutation analysis determined that JAM20 bound to a pocket between Switch I and II, which is similarly targeted by low-affinity, small-molecule inhibitors, such as BI-2852, whose in vivo efficacy has not been demonstrated. Furthermore, JAM20 directly competed with both the RAF(RBD) and BI-2852. These results provide direct validation of targeting the Switch I/II pocket for inhibiting RAS-driven tumorigenesis. More generally, these results demonstrate the utility of tool biologics as probes for discovering and validating druggable sites on challenging targets.
    Keywords:  drug discovery; synthetic binding protein; target validation; tool biologic
    DOI:  https://doi.org/10.1073/pnas.2204481119
  83. Drug Des Devel Ther. 2022 ;16 3573-3588
    A Review of Herbal Medicine-Based Phytochemical of Garcinia as Molecular Therapy for Breast Cancer.
    Komang Suma Triyasa, Ajeng Diantini, Melisa Intan Barliana.
      Data from globocan statistic in 2020 indicate that breast cancer has become highest incidence rate of cancer. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are known immunohistochemistry (IHC) markers that mediate cell growth and survival signaling. Furthermore, regulator proteins, receptors, and their downstream signaling pathways have emerged as critical components in breast cancer formation and proliferation, and have become well-established therapeutic targets and the core focus of breast cancer therapy research. Garcinia is a big genus in the Clusiaceae family that contains a wide spectrum of biologically active metabolites for the chemical composition of their isolated fruits, stem barks, seeds, leaves, and roots, have resulted including polyisoprenylated benzophenones, polyphenols, bioflavonoids, xanthones, lactones, and triterpenes. This review article aimed to analyze the potential of Garcinia phytochemicals as a molecular therapy of breast cancer. The results showed that phytochemicals of Garcinia (i.e., α-mangostin, Cambogin, Gambogic Acid [GA], Garcinol, Griffipavixanthone, Friedolanostane triterpenoid, Hexane, Neobractatin, 7-Epiclusianone, xanthochymol - guttiferone E, and isoxanthochymol - cycloxanthochymol) have anticancer properties, including apoptosis, inhibition of proliferation, and metastasis. This review is important to provide information regarding phytochemicals of Garcinia as an alternative treatment for breast cancer patients. This article selected 28 article researches based on inclusion criteria with the keyword "Garcinia" and "Breast cancer", in English, and available in full text and abstract searching on PubMed.
    Keywords:  Garcinia spp; Indonesia; breast cancer; molecular therapy
    DOI:  https://doi.org/10.2147/DDDT.S358229
  84. Diabetologia. 2022 Oct 18.
    Ketones: the double-edged sword of SGLT2 inhibitors?
    Beatrice C Lupsa, Richard G Kibbey, Silvio E Inzucchi.
      Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications used by individuals with type 2 diabetes that reduce hyperglycaemia by targeting glucose transport in the kidney, preventing its reabsorption, thereby inducing glucosuria. Besides improving HbA1c and reducing body weight and blood pressure, the SGLT2 inhibitors have also been demonstrated to improve cardiovascular and kidney outcomes, an effect largely independent of their effect on blood glucose levels. Indeed, the mechanisms underlying these benefits remain elusive. Treatment with SGLT2 inhibitors has been found to modestly increase systemic ketone levels. Ketone bodies are an ancillary fuel source substituting for glucose in some tissues and may also possess intrinsic anti-oxidative and anti-inflammatory effects. Some have proposed that ketones may in fact mediate the cardio-renal benefits of this drug category. However, a rare complication of SGLT2 inhibition is ketoacidosis, sometimes with normal or near-normal blood glucose concentrations, albeit occurring more frequently in patients with type 1 diabetes who are treated (predominately off-label) with one of these agents. We herein explore the notion that an underpinning of one of the more serious adverse effects of SGLT2 inhibitors may, in fact, explain, at least in part, some of their benefits-a potential 'double-edged sword' of this novel drug category.
    Keywords:  Cardiovascular; Diabetes; Ketoacidosis; Ketones; Renal; Review; SGLT2 inhibitor
    DOI:  https://doi.org/10.1007/s00125-022-05815-1
  85. Angew Chem Int Ed Engl. 2022 Oct 19.
    Suprasomes Based on Host-Guest Molecular Recognition: An Excellent Alternative to Liposome in Cancer Theranostics.
    Kai Yang, Bin Hua, Shaolong Qi, Bing Bai, Chunyang Yu, Feihe Huang, Guocan Yu.
      Liposomes and polymersomes, typical vesicular drug delivery systems (DDSs), have faced some limitations in cancer theranostics. Suprasomes, supramolecular vesicles assembled from amphiphiles linked by noncovalent interactions, show potential as new generation of vesicular DDSs. We construct suprasomes based on host-guest recognition, by which the desired functions can be integrated into carriers without tedious synthesis. Photothermally active host-guest complex is formed between a functional guest and pillar[5]arene, which further self-assembles into hollow suprasomes. A supramolecular nanomedicine is developed by encapsulating cisplatin in the suprasomes. The obtained cisplatin@Suprasomes achieve excellent anticancer efficacy and anti-metastasis combining chemotherapy and photothermal therapy, which ablate the tumors without relapse and metastasis. This work demonstrates the facile functionalization of suprasomes, holding promise as alternatives to liposomes and polymersomes.
    Keywords:  cancer theranostics * drug delivery system * host-guest recognition * supramolecular chemistry * vesicles
    DOI:  https://doi.org/10.1002/anie.202213572
  86. Biomed Pharmacother. 2022 Nov;pii: S0753-3322(22)01226-4. [Epub ahead of print]155 113837
    Lipid-polymer nanocarrier platform enables X-ray induced photodynamic therapy against human colorectal cancer cells.
    Rui Sang, Fei Deng, Alexander Engel, Ewa Goldys, Wei Deng.
      In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU) and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells' growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.
    Keywords:  5-FU; Colorectal cancer; Targeted lipid-polymer nanoparticles; Verteporfin; X-PDT
    DOI:  https://doi.org/10.1016/j.biopha.2022.113837
  87. J Oncol. 2022 ;2022 3426407
    Managing Cancer Drug Resistance from the Perspective of Inflammation.
    Shuaijun Lu, Yang Li, Changling Zhu, Weihua Wang, Yuping Zhou.
      The development of multidrug resistance in cancer chemotherapy is a major obstacle to the effective treatment of human malignant tumors. Several epidemiological studies have demonstrated that inflammation is closely related to cancer and plays a key role in the development of both solid and liquid tumors. Therefore, targeting inflammation and the molecules involved in the inflammatory process may be a good strategy for treating drug-resistant tumors. In this review, we discuss the molecular mechanisms underlying inflammation in regulating anticancer drug resistance by modulating drug action and drug-mediated cell death pathways. Inflammation alters the effectiveness of drugs through modulation of the expression of multidrug efflux transporters (e.g., ABCG2, ABCB1, and ABCC1) and drug-metabolizing enzymes (e.g., CYP1A2 and CYP3A4). In addition, inflammation can protect cancer cells from drug-mediated cell death by regulating DNA damage repair, downstream adaptive response (e.g., apoptosis, autophagy, and oncogenic bypass signaling), and tumor microenvironment. Intriguingly, manipulating inflammation may affect drug resistance through various molecular mechanisms validated by in vitro/in vivo models. In this review, we aim to summarize the underlying molecular mechanisms that inflammation participates in cancer drug resistance and discuss the potential clinical strategies targeting inflammation to overcome drug resistance.
    DOI:  https://doi.org/10.1155/2022/3426407
  88. Biomacromolecules. 2022 Oct 20.
    Thermosensitive Polymer Conjugated Prodrug-Activating Enzyme with Enhanced Tumor Retention and Antitumor Efficacy.
    Xiang Zhang, Fei Duan, Fan Zhang, Xuliang Deng, Weiping Gao.
      Enzyme-activated prodrug therapy has emerged as an effective strategy for cancer therapy. However, the inefficient delivery of prodrug-activating enzymes into tumor tissues leads to unsatisfactory antitumor efficacy and undesirable toxicity to normal tissues. Herein, we report in situ growth of a thermosensitive polymer of poly(diethylene glycol) methyl ether methacrylate (PDEGMA) from horseradish peroxidase (HRP) to yield a HRP-PDEGMA conjugate with well-retained activity as compared to HRP. The conjugate shows a sharp phase transition behavior with a lower critical solution temperature of 23 °C. The conjugate catalyzes the conversion of non-cytotoxic indole-3-acetic acid (IAA) into cytotoxic species for killing tumor cells. Notably, the PDEGMA conjugation not only increases the stability and cellular uptake of HRP but also prolongs the tumor retention time of HRP upon intratumoral injection. As a result, in mice bearing melanoma, the conjugate inhibits the growth of melanoma much more efficiently than HRP. These results demonstrate that the thermosensitive polymer conjugation of an enzyme is an effective strategy that can enhance the antitumor efficacy of an enzyme-activated prodrug.
    DOI:  https://doi.org/10.1021/acs.biomac.2c01006
  89. Colloids Surf B Biointerfaces. 2022 Oct 12. pii: S0927-7765(22)00593-8. [Epub ahead of print]220 112909
    Design of cysteine-based self-assembling polymer drugs for anticancer chemotherapy.
    Yuta Koda, Yukio Nagasaki.
      Reactive oxygen species (ROS) play essential roles in the body, such as the production of energy in oxidative phosphorylation and signal transduction for homeostasis. Redox balance in biological systems gradually collapses due to various environmental factors, including aging and disease, and induces oxidative stress in the body. None of the natural or synthetic antioxidants have been approved clinically, owing to their adverse effects. Herein, we developed L-cysteine (Cys)-based polymer micelles as new self-assembling antioxidants to reduce the adverse effects of conventional antioxidants. Poly(ethylene glycol)-block-poly(L-cysteine) (PEG-block-PCys) was synthesized via anionic ring-opening polymerization. Because the free SH groups in the side chains of the PCys segment were protected by disulfide bonds, the obtained block copolymers were amphiphilic and formed polymer micelles (NanoCyss) of tens of nanometers in size in aqueous media. The stability of NanoCyss in the presence of bovine serum albumin (BSA) was increased by increasing the molecular weight (MW) of the PCys segments, which was analyzed using dynamic light scattering (DLS). The size and coagulation tendency of NanoCyss were also analyzed using DLS measurements by changing the pH and NaCl concentration. NanoCyss were confirmed to be less toxic both in vitro and in vivo than N-acetylcysteine (NAC) because of their size and biocompatible PEG surface layer. Intraperitoneal (i.p.) administration of NanoCyss to the tumor xenograft mouse model successfully suppressed tumor growth. Interestingly, this effect depended on the MW of the PCys segments.
    Keywords:  Anticancer chemotherapy; Antioxidants; Cysteine; Polymer drugs; Reactive oxygen species
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112909
  90. Arch Toxicol. 2022 Oct 19.
    Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.
    Silvia Vivarelli, Chiara Costa, Michele Teodoro, Federica Giambò, Aristidis Michael Tsatsakis, Concettina Fenga.
      Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.
    Keywords:  Bioaccessibility; Bioactivity; Bioavailability; Chronic non-communicable diseases; Delivery nanosystems; Gut microbiota; Personalized medicine; Polyphenols
    DOI:  https://doi.org/10.1007/s00204-022-03391-2
  91. Adv Sci (Weinh). 2022 Oct 17. e2201609
    Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.
    Qiurong Yang, Jing Xu, Jianmei Gu, Hui Shi, Jiayin Zhang, Jianye Zhang, Zhe-Sheng Chen, Xinjian Fang, Taofeng Zhu, Xu Zhang.
      Extracellular vesicles (EVs) are cell-derived nanosized vesicles that mediate cell-to-cell communication via transporting bioactive molecules and thus are critically involved in various physiological and pathological conditions. EVs contribute to different aspects of cancer progression, such as cancer growth, angiogenesis, metastasis, immune evasion, and drug resistance. EVs induce the resistance of cancer cells to chemotherapy, radiotherapy, targeted therapy, antiangiogenesis therapy, and immunotherapy by transferring specific cargos that affect drug efflux and regulate signaling pathways associated with epithelial-mesenchymal transition, autophagy, metabolism, and cancer stemness. In addition, EVs modulate the reciprocal interaction between cancer cells and noncancer cells in the tumor microenvironment (TME) to develop therapy resistance. EVs are detectable in many biofluids of cancer patients, and thus are regarded as novel biomarkers for monitoring therapy response and predicting prognosis. Moreover, EVs are suggested as promising targets and engineered as nanovehicles to deliver drugs for overcoming drug resistance in cancer therapy. In this review, the biological roles of EVs and their mechanisms of action in cancer drug resistance are summarized. The preclinical studies on using EVs in monitoring and overcoming cancer drug resistance are also discussed.
    Keywords:  cancer therapy; drug delivery; drug resistance; extracellular vesicles; nanomedicine
    DOI:  https://doi.org/10.1002/advs.202201609
  92. Biomed Pharmacother. 2022 Oct 13. pii: S0753-3322(22)01075-7. [Epub ahead of print]156 113686
    Mechanism of metformin regulation in central nervous system: Progression and future perspectives.
    Gui Cao, Ting Gong, Yue Du, Yicun Wang, Tongtong Ge, Jingyu Liu.
      Metformin as a first-line drug for type 2 diabetes mellitus(T2DM) treatment is widely studied. Metformin can reduce liver glucose output and improve insulin resistance. Recent evidence from in vivo and in vitro has confirmed that metformin can transport across the blood-brain barrier(BBB) and activate specific neurons and neuroglia to exert neurological actions, however, the specific effect of metformin regulation on CNS is still obscure. In this review, we summarized current evidence from preclinical evidence focusing on the regulatory role of metformin in CNS and found that metformin can exert potential neuroprotective, neurotrophic, and neurogenesis-stimulated actions; besides, metformin also exerts antiinflammatory effect by inhibiting microglial activates and regulating microglial polarization. These findings indicate there might be extensive pharmacological efficacy and therapeutic insights of metformin in neurological diseases' clinical application.
    Keywords:  AMPK activation; BDNF; Neurogenesis; Neuroinflammation; Neuroprotection
    DOI:  https://doi.org/10.1016/j.biopha.2022.113686
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