bims-mitrat Biomed News
on Mitochondrial Transplantation and Transfer
Issue of 2024‒06‒09
fourteen papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute
  1. The effects of exercise and mitochondrial transplantation alone or in combination against Doxorubicin-induced skeletal muscle atrophy.
  2. Mitochondria Transplantation Promotes Corneal Epithelial Wound Healing.
  3. Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease.
  4. Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.
  5. Redox regulation of UPR signalling and mitochondrial ER contact sites.
  6. The role of mitochondria in sex- and age-specific gene expression in a species without sex chromosomes.
  7. Heterogeneous distribution of mitochondria and succinate dehydrogenase activity in human airway smooth muscle cells.
  8. Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics.
  9. Extracellular vesicles promote autophagy in human microglia through lipid raft-dependent mechanisms.
  10. Skeletal muscle PGC-1α remodels mitochondrial phospholipidome but does not alter energy efficiency for ATP synthesis.
  11. Role of cellular senescence in inflammation and regeneration.
  12. Exosome-based anticancer vaccines: From Bench to Bedside.
  13. Microwave radiation and thermal effects on the bioenergetics of isolated mitochondria.
  14. Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts.
  1. J Muscle Res Cell Motil. 2024 Jun 01.
    The effects of exercise and mitochondrial transplantation alone or in combination against Doxorubicin-induced skeletal muscle atrophy.
    Gokhan Burcin Kubat, Oner Ulger, Ozbeyen Atalay, Tugba Fatsa, Ibrahim Turkel, Berkay Ozerklig, Ertugrul Celik, Emrah Ozenc, Gulcin Simsek, Meltem Tuncer.
      Doxorubicin (DOX) is a chemotherapy drug used to treat various types of cancer, but it is associated with significant side effects such as skeletal muscle atrophy. Exercise has been found to prevent skeletal muscle atrophy through the modulation of mitochondrial pathways. Mitochondrial transplantation (MT) may mitigate toxicity, neurological disorders, kidney and liver injury, and skeletal muscle atrophy. The objective of this study was to evaluate the effects of MT, exercise, and MT with exercise on DOX-induced skeletal muscle atrophy. Male Sprague Dawley rats were randomly assigned to the following groups: control, DOX, MT with DOX, exercise with DOX, and exercise with MT and DOX. A 10-day treadmill running exercise and MT (6.5 µg/100 µL) to tibialis anterior (TA) muscle were administered prior to a single injection of DOX (20 mg/kg). Our data showed that exercise and MT with exercise led to an increase in cross-sectional area of the TA muscle. Exercise, MT and MT with exercise reduced inflammation and maintained mitochondrial enzyme activity. Additionally, exercise and MT have been shown to regulate mitochondrial fusion/fission. Our findings revealed that exercise and MT with exercise prevented oxidative damage. Furthermore, MT and MT with exercise decreased apoptosis and MT with exercise triggered mitochondrial biogenesis. These findings demonstrate the importance of exercise in the prevention of skeletal muscle atrophy and emphasize the significant benefits of MT with exercise. To the best of our knowledge, this is the first study to demonstrate the therapeutic effects of MT with exercise in DOX-induced skeletal muscle atrophy.
    Keywords:  Doxorubicin; Exercise; Mitochondria; Mitochondrial transplantation; Skeletal muscle atrophy
    DOI:  https://doi.org/10.1007/s10974-024-09676-6
  2. Invest Ophthalmol Vis Sci. 2024 Jun 03. 65(6): 14
    Mitochondria Transplantation Promotes Corneal Epithelial Wound Healing.
    Daniel Raz, Keren Ben-Yaakov, Michal Levi, Marina Bertolin, Stefano Ferrari, Diego Ponzin, Massimo Busin, Hana Leiba, Arie L Marcovich, Avital Eisenberg-Lerner, Ziv Rotfogel.
      Purpose: The integrity of the corneal epithelium is essential in maintaining normal corneal function. Conditions disrupting the corneal epithelial layer range from chemical burns to dry eye disease and may result in impairment of both corneal transparency and sensation. Identifying factors that regulate corneal wound healing is key for the development of new treatment strategies. Here, we investigated a direct role of mitochondria in corneal wound healing via mitochondria transplantation.Methods: Human corneal epithelial cells (hCECs) were isolated from human corneas and incubated with mitochondria which were isolated from human ARPE-19 cells. We determined the effect of mitochondria transplantation on wound healing and proliferation of hCECs. In vivo, we used a mouse model of corneal chemical injury. Mitochondria were isolated from mouse livers and topically applied to the ocular surface following injury. We evaluated the time of wound repair, corneal re-epithelization, and stromal abnormalities.
    Results: Mitochondria transplantation induced the proliferation and wound healing of primary hCECs. Further, mitochondria transplantation promoted wound healing in vivo. Specifically, mice receiving mitochondria recovered twice as fast as control mice following corneal injury, presenting both enhanced and improved repair. Corneas treated with mitochondria demonstrated the re-epithelization of the wound area to a multi-layer appearance, compared to thinning and complete loss of the epithelium in control mice. Mitochondria transplantation also prevented the thickening and disorganization of the corneal stromal lamella, restoring normal corneal dehydration.
    Conclusions: Mitochondria promote corneal re-epithelization and wound healing. Augmentation of mitochondria levels via mitochondria transplantation may serve as an effective treatment for inducing the rapid repair of corneal epithelial defects.
    DOI:  https://doi.org/10.1167/iovs.65.6.14
  3. Int J Cardiol. 2024 Jun 04. pii: S0167-5273(24)00849-0. [Epub ahead of print] 132227
    Safety and efficacy of platelet-derived mitochondrial transplantation in ischaemic heart disease.
    Fatemeh Baharvand, Mehryar Habibi Roudkenar, Zahra Pourmohammadi-Bejarpasi, Nima Najafi Ghalehlou, Alireza Feizkhah, Somaye Bashiri Aliabadi, Arsalan Salari, Amaneh Mohammadi Roushandeh.
      BACKGROUND: Acute ST-elevation myocardial infarction (STEMI) remains a globally significant health challenge in spite of improvement in management strategy. Being aware that mitochondrial dysfunction plays a crucial role in ischaemia-reperfusion injury (IRI) modulation, empirical evidence suggests functional mitochondrial transplantation strikes as a reliable therapeutic approach for patients with acute myocardial infarction.METHODS AND RESULTS: We conducted a prospective, triple-blinded, parallel-group, blocked randomised clinical trial to investigate the therapeutic effects and clinical outcomes of platelet-derived mitochondrial transplantation in 30 patients with acute STEMI, such that the 15 subjects in the control group were given standard of care treatment, whereas the subjects in the intervention group received autologous platelet-derived mitochondria through the intracoronary injection. We observed that within 40 days, the intervention group had a slightly greater improvement in the left ventricular ejection fraction (LVEF) compared to the control group and experienced a significant enhancement in the exercise capacity (p < 0.001). Moreover, major adverse cardiac events (MACE), arrhythmia, fever, and tachycardia were compared between the groups and lack of significant difference marks the safety of mitochondrial transplantation (p > 0.05). Furthermore, the two groups were not significantly distinct as regards the average length of stay for a hospitalisation (p > 0.05).
    CONCLUSION: We suggest platelet-derived mitochondrial transplantation appears as a beneficial and highly promising therapeutic option for patients of ischaemic heart disease (IHD); however, we are aware that further in-depth studies with larger sample sizes along with longer follow-up periods are necessary for validating the clinical implications of our findings.
    Keywords:  Acute ST-elevation myocardial infarction; Acute myocardial infarction; Ischaemia-reperfusion injury; Mitochondrial transplantation
    DOI:  https://doi.org/10.1016/j.ijcard.2024.132227
  4. Adv Drug Deliv Rev. 2024 Jun 05. pii: S0169-409X(24)00177-7. [Epub ahead of print] 115355
    Mitochondrial endogenous substance transport-inspired nanomaterials for mitochondria-targeted gene delivery.
    Yi Wang, Jing-Song Yang, Min Zhao, Jia-Qi Chen, Hai-Xin Xie, Hao-Yuan Yu, Na-Hui Liu, Zi-Juan Yi, Hui-Lin Liang, Lei Xing, Hu-Lin Jiang.
      Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summary mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involving in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing detail on the design of mitochondria-targeted delivery systems and limitations regarding the varying technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.
    Keywords:  Drug delivery system; Gene delivery; Mitochondrial endogenous transport; Mitochondrial genome; Nanomaterials
    DOI:  https://doi.org/10.1016/j.addr.2024.115355
  5. Cell Mol Life Sci. 2024 Jun 07. 81(1): 250
    Redox regulation of UPR signalling and mitochondrial ER contact sites.
    Jose C Casas-Martinez, Afshin Samali, Brian McDonagh.
      Mitochondria and the endoplasmic reticulum (ER) have a synergistic relationship and are key regulatory hubs in maintaining cell homeostasis. Communication between these organelles is mediated by mitochondria ER contact sites (MERCS), allowing the exchange of material and information, modulating calcium homeostasis, redox signalling, lipid transfer and the regulation of mitochondrial dynamics. MERCS are dynamic structures that allow cells to respond to changes in the intracellular environment under normal homeostatic conditions, while their assembly/disassembly are affected by pathophysiological conditions such as ageing and disease. Disruption of protein folding in the ER lumen can activate the Unfolded Protein Response (UPR), promoting the remodelling of ER membranes and MERCS formation. The UPR stress receptor kinases PERK and IRE1, are located at or close to MERCS. UPR signalling can be adaptive or maladaptive, depending on whether the disruption in protein folding or ER stress is transient or sustained. Adaptive UPR signalling via MERCS can increase mitochondrial calcium import, metabolism and dynamics, while maladaptive UPR signalling can result in excessive calcium import and activation of apoptotic pathways. Targeting UPR signalling and the assembly of MERCS is an attractive therapeutic approach for a range of age-related conditions such as neurodegeneration and sarcopenia. This review highlights the emerging evidence related to the role of redox mediated UPR activation in orchestrating inter-organelle communication between the ER and mitochondria, and ultimately the determination of cell function and fate.
    Keywords:   C. elegans ; Contact-sites; Hormesis; Mitochondrial dynamics; Redox signalling; Skeletal muscle
    DOI:  https://doi.org/10.1007/s00018-024-05286-0
  6. Proc Natl Acad Sci U S A. 2024 Jun 11. 121(24): e2321267121
    The role of mitochondria in sex- and age-specific gene expression in a species without sex chromosomes.
    Ning Li, Ben A Flanagan, Suzanne Edmands.
      Mitochondria perform an array of functions, many of which involve interactions with gene products encoded by the nucleus. These mitochondrial functions, particularly those involving energy production, can be expected to differ between sexes and across ages. Here, we measured mitochondrial effects on sex- and age-specific gene expression in parental and reciprocal F1 hybrids between allopatric populations of Tigriopus californicus with over 20% mitochondrial DNA divergence. Because the species lacks sex chromosomes, sex-biased mitochondrial effects are not confounded by the effects of sex chromosomes. Results revealed pervasive sex differences in mitochondrial effects, including effects on energetics and aging involving nuclear interactions throughout the genome. Using single-individual RNA sequencing, sex differences were found to explain more than 80% of the variance in gene expression. Males had higher expression of mitochondrial genes and mitochondrially targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level. Comparison of reciprocal F1 hybrids allowed insights into the nature of mito-nuclear interactions, showing both mitochondrial effects on nuclear expression, and nuclear effects on mitochondrial expression. While based on a small set of crosses, sex-specific increases in mitochondrial expression with age were associated with longer life. Network analyses identified nuclear components of strong mito-nuclear interactions and found them to be sexually dimorphic. These results highlight the profound impact of mitochondria and mito-nuclear interactions on sex- and age-specific gene expression.
    Keywords:  RNA-seq; hybrid; longevity; mitochondria; sex differences
    DOI:  https://doi.org/10.1073/pnas.2321267121
  7. FASEB Bioadv. 2024 Jun;6(6): 159-176
    Heterogeneous distribution of mitochondria and succinate dehydrogenase activity in human airway smooth muscle cells.
    Sanjana Mahadev Bhat, Gary C Sieck.
      Succinate dehydrogenase (SDH) is a key mitochondrial enzyme involved in the tricarboxylic acid cycle, where it facilitates the oxidation of succinate to fumarate, and is coupled to the reduction of ubiquinone in the electron transport chain as Complex II. Previously, we developed a confocal-based quantitative histochemical technique to determine the maximum velocity of the SDH reaction (SDHmax) in single cells and observed that SDHmax corresponds with mitochondrial volume density. In addition, mitochondrial volume and motility varied within different compartments of human airway smooth muscle (hASM) cells. Therefore, we hypothesize that the SDH activity varies relative to the intracellular mitochondrial volume within hASM cells. Using 3D confocal imaging of labeled mitochondria and a concentric shell method for analysis, we quantified mitochondrial volume density, mitochondrial complexity index, and SDHmax relative to the distance from the nuclear membrane. The mitochondria within individual hASM cells were more filamentous in the immediate perinuclear region and were more fragmented in the distal parts of the cell. Within each shell, SDHmax also corresponded to mitochondrial volume density, where both peaked in the perinuclear region and decreased in more distal parts of the cell. Additionally, when normalized to mitochondrial volume, SDHmax was lower in the perinuclear region when compared to the distal parts of the cell. In summary, our results demonstrate that SDHmax measures differences in SDH activity within different cellular compartments. Importantly, our data indicate that mitochondria within individual cells are morphologically heterogeneous, and their distribution varies substantially within different cellular compartments, with distinct functional properties.
    Keywords:  airway smooth muscle; confocal microscope; intracellular distribution; mitochondria; succinate dehydrogenase
    DOI:  https://doi.org/10.1096/fba.2024-00047
  8. J Nanobiotechnology. 2024 Jun 06. 22(1): 316
    Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics.
    Song Yang, Yiran Sun, Chenchen Yan.
      Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.
    Keywords:  Adipose-derived stem cell; Extracellular vesicle; Regenerative medicine; Therapeutic effect; Tissue regeneration; Underlying mechanism
    DOI:  https://doi.org/10.1186/s12951-024-02603-4
  9. FEBS J. 2024 Jun 05.
    Extracellular vesicles promote autophagy in human microglia through lipid raft-dependent mechanisms.
    Diana Romenskaja, Ugnė Jonavičė, Augustas Pivoriūnas.
      Autophagy dysfunction has been closely related with pathogenesis of many neurodegenerative diseases and therefore represents a potential therapeutic target. Extracellular vesicles (EVs) may act as potent anti-inflammatory agents and also modulators of autophagy in target cells. However, the molecular mechanisms by which EVs modulate autophagy flux in human microglia remain largely unexplored. In the present study, we investigated the effects of EVs derived from human oral mucosa stem cells on the autophagy in human microglia. We demonstrate that EVs promoted autophagy and autophagic flux in human microglia and that this process was dependent on the integrity of lipid rafts. Lipopolysaccharide (LPS) also activated autophagy, but combined treatment with EVs and LPS suppressed autophagy response, indicating interference between these signaling pathways. Blockage of Toll-like receptor 4 (TLR4) with anti-TLR4 antibody suppressed EV-induced autophagy. Furthermore, inhibition of the EV-associated heat shock protein (HSP70) chaperone which is one of the endogenous ligands of the TLR4 also suppressed EV-induced lipid raft formation and autophagy. Pre-treatment of microglia with a selective inhibitor of αvβ3/αvβ5 integrins cilengitide inhibited EV-induced autophagy. Finally, blockage of purinergic P2X4 receptor (P2X4R) with selective inhibitor 5-BDBD also suppressed EV-induced autophagy. In conclusion, we demonstrate that EVs activate autophagy in human microglia through interaction with HSP70/TLR4, αVβ3/αVβ5, and P2X4R signaling pathways and that these effects depend on the integrity of lipid rafts. Our findings could be used to develop new therapeutic strategies targeting disease-associated microglia.
    Keywords:  autophagy; extracellular vesicles; immune receptors; lipopolysaccharide; microglia
    DOI:  https://doi.org/10.1111/febs.17192
  10. bioRxiv. 2024 May 26. pii: 2024.05.22.595374. [Epub ahead of print]
    Skeletal muscle PGC-1α remodels mitochondrial phospholipidome but does not alter energy efficiency for ATP synthesis.
    Takuya Karasawa, Ran Hee Choi, Cesar A Meza, J Alan Maschek, James E Cox, Katsuhiko Funai.
      Background: Exercise training is thought to improve the mitochondrial energy efficiency of skeletal muscle. Some studies suggest exercise training increases the efficiency for ATP synthesis by oxidative phosphorylation (OXPHOS), but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes could contribute to improved OXPHOS efficiency (ATP produced by O2 consumed or P/O). Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional co-activator that coordinately regulates exercise-induced adaptations including mitochondria. We hypothesized that increased PGC-1α activity is sufficient to remodel mitochondrial membrane lipids and promote energy efficiency.Methods: Mice with skeletal muscle-specific overexpression of PGC-1α (MCK-PGC-1α) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by western blot assay. High-resolution respirometry and fluorometry analysis were used to characterize mitochondrial bioenergetics (ATP production, O2 consumption, and P/O) for permeabilized fibers and isolated mitochondria.
    Results: Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK-PGC-1α mice revealed that PGC-1α increases the concentrations of cone-shaped lipids such as phosphatidylethanolamine (PE), cardiolipin (CL), and lysophospholipids, while decreases the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidic acid (PA). However, while PGC-1α overexpression increased the abundance of OXPHOS enzymes in skeletal muscle and the rate of O2 consumption (JO2), P/O values were unaffected with PGC-1α in permeabilized fibers or isolated mitochondria.
    Conclusions: Collectively, overexpression of PGC-1α promotes the biosynthesis of mitochondrial PE and CL but neither PGC-1α nor the mitochondrial membrane lipid remodeling induced in MCK-PGC-1α mice is sufficient to increase the efficiency for mitochondrial ATP synthesis. These findings suggest that exercise training may increase OXPHOS efficiency by a PGC-1α-independent mechanism, and question the hypothesis that mitochondrial lipids directly affect OXPHOS enzymes to improve efficiency for ATP synthesis.
    Keywords:  exercise; mitochondria; phospholipids; skeletal muscle
    DOI:  https://doi.org/10.1101/2024.05.22.595374
  11. Inflamm Regen. 2024 Jun 03. 44(1): 28
    Role of cellular senescence in inflammation and regeneration.
    Yuki Saito, Sena Yamamoto, Takako S Chikenji.
      Cellular senescence is the state in which cells undergo irreversible cell cycle arrest and acquire diverse phenotypes. It has been linked to chronic inflammation and fibrosis in various organs as well as to individual aging. Therefore, eliminating senescent cells has emerged as a potential target for extending healthy lifespans. Cellular senescence plays a beneficial role in many biological processes, including embryonic development, wound healing, and tissue regeneration, which is mediated by the activation of stem cells. Therefore, a comprehensive understanding of cellular senescence, including both its beneficial and detrimental effects, is critical for developing safe and effective treatment strategies to target senescent cells. This review provides an overview of the biological and pathological roles of cellular senescence, with a particular focus on its beneficial or detrimental functions among its various roles.
    Keywords:  Aging; Cell cycle arrest; Cellular senescence; Fibrosis; Senescence-associated secretory phenotype (SASP); Tissue remodeling
    DOI:  https://doi.org/10.1186/s41232-024-00342-5
  12. Cancer Lett. 2024 May 31. pii: S0304-3835(24)00383-5. [Epub ahead of print] 216989
    Exosome-based anticancer vaccines: From Bench to Bedside.
    Guo Zhao, Yuning Wang, Shujun Xing, Yale Jiang, Jiatong Ding, Yuanting Cai, Peiwen Ma, Huilei Miao, Yuan Fang, Ning Jiang, Dandan Cui, Yue Yu, Qiyu Tang, Shuhang Wang, Ning Li.
      Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction.
    Keywords:  Exosomes; cancer vaccines; clinical translation; immunotherapy; tumor immunity
    DOI:  https://doi.org/10.1016/j.canlet.2024.216989
  13. Int J Radiat Biol. 2024 Jun 06. 1-11
    Microwave radiation and thermal effects on the bioenergetics of isolated mitochondria.
    Aline S Perez, Natalia M Inada, Natasha F Mezzacappo, Jose D Vollet-Filho, Vanderlei S Bagnato.
      Aims. This study proposes to investigate the effects of microwave radiation and its thermal effects, compared to thermal effects alone, on the bioenergetics of mitochondria isolated from mouse liver.Methods. The main parameters investigated in this study are mitochondrial respiration (coupled states: S3 and S4; uncoupled state), using a high-resolution respirometer, and swelling, using a spectrophotometer.
    Results. Mitochondria irradiated at 2.45 GHz microwave with doses 0.085, 0.113 and 0.141 kJ/g, presented a decrease in S3 and uncoupled state, but an increase in S4. Conversely, mitochondria thermally treated at 40, 44 and 50 °C presented an increasing in S3 and S4, while uncoupled state was unaltered. Mitochondrial swelling increases as a function of the dose or temperature, indicating membrane damages in both cases.
    Conclusion. Microwave radiation and thermal effect alone indicated different bioenergetics mitochondria response. These results imply that the effects due to microwave in medical treatment are not exclusively due to the increase in temperature, but a combination of electromagnetic and thermal effects.
    Keywords:  Electromagnetic radiation; bioenergetics; microwave; mitochondria; thermal effects
    DOI:  https://doi.org/10.1080/09553002.2024.2348073
  14. NPJ Microgravity. 2024 Jun 05. 10(1): 60
    Spaceflight on the ISS changed the skeletal muscle proteome of two astronauts.
    Marta Murgia, Jörn Rittweger, Carlo Reggiani, Roberto Bottinelli, Matthias Mann, Stefano Schiaffino, Marco V Narici.
      Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses.
    DOI:  https://doi.org/10.1038/s41526-024-00406-3
This page is being maintained by Thomas Krichel. It was last updated on 2024‒06‒09 at 9:16.