本周hzangs在最新文献中选取了8篇分享给大家，第1篇文章介绍了焦亡囊泡作为癌症疫苗的设计；第3篇文章介绍了促焦亡囊泡调控蒽环类化疗药物心脏毒性的潜在作用机制；第5篇文章综述了细菌细胞外囊泡发生机制和作用；第6篇文章介绍了线粒体囊泡在肿瘤治疗中的潜在应用价值；第8篇文章介绍了细胞外囊泡在抗衰老领域的研究进展和前景。
- Engineering pyroptotic vesicles as personalized cancer vaccines.
设计焦亡囊泡作为个性化癌症疫苗。
[Nat Nanotechnol] PMID: 40379868
Abstract: Tumour vaccines are designed to stimulate the host's immune system against existing tumours or tumour recurrence. However, individual differences, tumour heterogeneity and side effects hinder the applications of current tumour vaccines and require the development of personalized cancer vaccines. To overcome these challenges, we engineered pyroptotic vesicles-extracellular vesicles formed during tumour cell pyroptosis-as a tumour vaccine platform. The extracted pyroptotic vesicles possess abundant tumour antigens and potent immune-stimulating ability and, loaded into a biocompatible hydrogel, they can be implanted into post-surgical tumour cavities to prevent tumour recurrence. The pyroptotic-vesicle-based vaccine outperforms both exosome- and apoptotic-body-based vaccines in inhibiting tumour recurrence and metastasis in different post-surgical mouse models. Mechanistic studies reveal that the pyroptotic-vesicle-based vaccine could stimulate robust antigen-specific dendritic cell and T cell immune responses against both artificial OVA antigens and cancer neoantigens. In sum, our vaccine platform can be tailored to stimulate robust antitumour immune responses for treating individual cancer patients.
- Calpains orchestrate secretion of annexin-containing microvesicles during membrane repair.
钙蛋白酶在膜修复过程中协调含有膜联蛋白的微泡的分泌。
[J Cell Biol] PMID: 40377476
Abstract: Microvesicles (MVs) are membrane-enclosed, plasma membrane-derived particles released by cells from all branches of life. MVs have utility as disease biomarkers and may participate in intercellular communication; however, physiological processes that induce their secretion are not known. Here, we isolate and characterize annexin-containing MVs and show that these vesicles are secreted in response to the calcium influx caused by membrane damage. The annexins in these vesicles are cleaved by calpains. After plasma membrane injury, cytoplasmic calcium-bound annexins are rapidly recruited to the plasma membrane and form a scab-like structure at the lesion. In a second phase, recruited annexins are cleaved by calpains-1/2, disabling membrane scabbing. Cleavage promotes annexin secretion within MVs. Our data support a new model of plasma membrane repair, where calpains relax annexin-membrane aggregates in the lesion repair scab, allowing secretion of damaged membrane and annexins as MVs. We anticipate that cells experiencing plasma membrane damage, including muscle and metastatic cancer cells, secrete these MVs at elevated levels.
- Exosomal transfer of pro-pyroptotic miR-216a-5p exacerbates anthracycline cardiotoxicity through breast cancer-heart pathological crosstalk.
促焦亡 miR-216a-5p 的外泌体转移通过乳腺癌-心脏病理串扰加剧了蒽环类药物的心脏毒性。
[Signal Transduct Target Ther] PMID: 40360476
Abstract: Doxorubicin (DOX) is the most effective chemotherapeutic for breast cancer, but it is usually associated with severe cardiotoxicity. Further investigation to alleviate its side effects is essential. The present study investigated the mechanism of the cross-organ communication between tumors and the heart and potential intervention targets. Morphological bubble-like protrusions were observed in both adult murine ventricular cardiomyocytes (AMVCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cocultured with breast cancer cells (BCCs), along with elevated expression of pyroptosis-related proteins. Exosomes (EXOs) from DOX-treated BCCs aggravated DOX-induced cardiotoxicity (DOXIC) in an orthotopic mouse model of breast cancer. Blocking miRNAs by knocking down Rab27a or inhibiting the release of EXOs in cancer tissue by Dicer enzyme knockout attenuated this additional injury effect. Exosomal miRNA sequencing revealed that miR-216a-5p is especially upregulated in EXOs from DOX-induced BCCs. Mechanistically, miR-216a-5p was upregulated by enhanced transcription mediated by DOX-induced AMP-dependent transcription factor 3 (ATF3) and packaged into EXOs by splicing factor 3b subunit 4 (SF3B4) in BCCs. Itchy E3 ubiquitin-protein ligase (ITCH) was identified as a novel downstream target mRNA of miR-216a-5p. ITCH negatively mediated thioredoxin-interacting protein (TXNIP) ubiquitination to activate the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway, ultimately leading to cardiomyocyte pyroptosis. Our findings revealed novel cross-organ pathogenic communication between breast cancer and the heart through the exosomal miR-216a-5p-mediated ITCH/TXNIP/NLRP3 pathway, which drives cardiomyocyte pyroptosis. These findings suggest that targeting myocardial miR-216a-5p or blocking harmful EXOs from breast cancer is a potential therapeutic strategy for alleviating DOXIC.
- Mitochondrial transfer in endothelial cells and vascular health.
内皮细胞中的线粒体转移和血管健康。
[Trends Cell Biol] PMID: 40368738
Abstract: Mitochondria play a vital role in cellular energy metabolism and vascular health, with their function directly influencing endothelial cell (EC) bioenergetics and integrity. Mitochondrial transfer has emerged as a key mechanism of intercellular communication, impacting angiogenesis, tissue repair, and cellular homeostasis. This review highlights recent findings on mitochondrial transfer, including natural mechanisms - such as tunneling nanotubes (TNTs) and extracellular vesicles (EVs) - and artificial approaches like mitochondrial transplantation. These processes enhance EC function and support vascularization under pathological conditions, including ischemia. While early clinical trials demonstrate therapeutic potential, challenges such as mitochondrial instability and scaling host-derived mitochondria persist. Continued research is essential to optimize mitochondrial transfer and advance its application as a therapeutic strategy for restoring vascular health.
- Biogenesis mechanisms, regulatory strategies, and applications of bacterial extracellular vesicles.
细菌胞外囊泡的生物发生机制、调控策略及应用。
[Crit Rev Biotechnol] PMID: 40368580
Abstract: Bacterial extracellular vesicles (EVs) are produced by both Gram-negative and Gram-positive bacteria. These EVs are composed of lipid bilayers and various components derived from parent bacteria, including proteins, lipids, and nucleic acids. Previous studies have indicated the significant role of bacterial EVs in interactions between bacteria and between bacteria and hosts. Moreover, bacterial EVs are emerging as promising delivery vectors capable of transporting drug molecules over long distances to tissues. Therefore, understanding the biogenesis of bacterial EVs and how to regulate their production holds great importance for expanding their applications. In this review, we provide an overview of bacterial EVs, especially focusing on the distinct mechanisms of EVs biogenesis and the regulation of EVs production in both Gram-negative and Gram-positive bacteria. Additionally, we discuss various methods for cargos loading into bacteria EVs, as well as their diverse applications in vaccines, cancer therapy, and drug delivery. We anticipate that this review will advance the field of bacterial EVs, contributing to both the enhancement of existing applications and the emergence of novel applications.
- Mitochondria-derived vesicles: A promising and potential target for tumour therapy.
线粒体衍生的囊泡：肿瘤治疗的一个有希望的潜在目标。
[Clin Transl Med] PMID: 40356246
Abstract: Mitochondria-derived vesicles (MDVs) participate in early cellular defence mechanisms initiated in response to mitochondrial damage. They maintain mitochondrial quality control (MQC) by clearing damaged mitochondrial components, thereby ensuring the normal functioning of cellular processes. This process is crucial for cell survival and health, as mitochondria are the energy factories of cells, and their damage can cause cellular dysfunction and even death. Recent studies have shown that MDVs not only maintain mitochondrial health but also have a significant impact on tumour progression. MDVs selectively encapsulate and transport damaged mitochondrial proteins under oxidative stress and reduce the adverse effects of mitochondrial damage on cells, which may promote the survival and proliferation of tumour cells. Furthermore, it has been indicated that after cells experience mild stress, the number of MDVs significantly increases within 2-6 h, whereas mitophagy, a process of clearing damaged mitochondria, occurs 12-24 h later. This suggests that MDVs play a critical role in the early stress response of cells. Moreover, MDVs also have a significant role in intercellular communication, specifically in the tumour microenvironment. They can carry and transmit various bioactive molecules, such as proteins, nucleic acids, and lipids, which regulate tumour cell's growth, invasion, and metastasis. This intercellular communication may facilitate tumour spread and metastasis, making MDVs a potential therapeutic target. Advances in MDV research have identified novel biomarkers, clarified regulatory mechanisms, and provided evidence for clinical use. These breakthroughs pave the way for novel MDV-targeted therapies, offering improved treatment alternatives for cancer patients. Further research can identify MDVs' role in tumour development and elucidate future cancer treatment horizons.
- The gut-brain axis in Alzheimer's disease is shaped by commensal gut microbiota derived extracellular vesicles.
阿尔茨海默病中的肠脑轴是由共生肠道微生物群衍生的细胞外囊泡形成的。
[Gut Microbes] PMID: 40355382
Abstract: Emerging clinical and experimental evidence highlight the involvement of gut microbiota in the onset and progression of neurodegenerative diseases such as Alzheimer's disease (AD) via neuroinflammatory processes along the gut-brain axis. Despite this, the precise mechanisms governing gut microbial involvement in AD remain elusive. In this study, we observed thatAppNL-G-F AD mice raised under germ-free (GF) conditions, display a reduced amyloid-β (Aβ) pathology, accompanied by a shift in microglial cells toward a less inflammatory state and increased phagocytotic efficiency. In addition, we demonstrate that gut microbiota depletion can protect against synaptic deficits in AD mice. Notably, administering bacterial extracellular vesicles (bEVs), i.e. nano-sized particles packed with bacterial components, derived from fecal slurry from specific pathogen-free housed AppNL-G-F AD mice, reversed the effects of GF conditions on both microglial activation and Aβ plaque accumulation. These findings reveal for the first time that commensal gut microbiota-derived bEVs have a major impact on AD pathology progression.
- Extracellular vesicle as therapeutic agents in anti-aging: Mechanistic insights and future potential.
细胞外囊泡作为抗衰老治疗剂：机制见解和未来潜力。
[J Control Release] PMID: 40348131
Abstract: Aging is a multifaceted biological process marked by a gradual decline in physiological functions, driven by cellular senescence, oxidative stress, chronic inflammation, and stem cell exhaustion. Extracellular vesicles (EVs), naturally occurring nanoscale vesicles secreted by various cell types, have gained attention as potential therapeutic agents due to their ability to mediate intercellular communication by delivering bioactive molecules, including proteins, lipids, and RNAs. This review provides a comprehensive overview of EV biogenesis, cargo composition, and their mechanistic roles in counteracting aging processes. EVs from diverse sources-such as mesenchymal stem cells, embryonic stem cells, dermal fibroblasts, and colostrum-exhibit regenerative properties by modulating immune responses, enhancing tissue repair, and promoting extracellular matrix homeostasis. Recent preclinical and clinical studies further highlight their potential in addressing age-related diseases and skin rejuvenation. However, significant challenges remain, including standardization of EV production, large-scale manufacturing, safety profiling, and regulatory approval. By leveraging advancements in EV engineering, targeted delivery systems, and combination strategies with existing anti-aging interventions, EV-based therapies hold promise as next-generation approaches in regenerative medicine and longevity enhancement.
今天的整理就到这里。希望大家可以有所收获。大家下周见！
