本周hzangs在最新文献中选取了6篇分享给大家，第1篇文章介绍了微波诱导的肿瘤来源微粒可以增强肺癌的免疫原性反应；第2篇文章介绍了机械刺激对肿瘤细胞外囊泡的调节作用；第3篇文章介绍了胃癌来源囊泡的DNA全甲基化分析可以用于细胞间通讯特征分析；第6篇文章介绍了血小板来源线粒体通过细胞外囊泡来调控非酒精性脂肪肝细胞的脂代谢。
- Tumour-derived microparticles obtained through microwave irradiation induce immunogenic cell death in lung adenocarcinoma.
通过微波辐射获得的肿瘤衍生微粒可诱导肺腺癌的免疫原性细胞死亡。
[Nat Nanotechnol] PMID: 40389640
Abstract: Tumour-derived microparticles (TMPs), extracellular vesicles traditionally obtained upon ultraviolet (UV) radiation of tumour cells, hold promise in tumour immunotherapies and vaccines and have demonstrated potential as drug delivery systems for tumour treatment. However, concerns remain regarding the limited efficacy and safety of UV-derived TMPs. Here we introduce a microwave (MW)-assisted method for preparing TMPs, termed MW-TMPs. Brief exposure of tumour cells to short-wavelength MW radiation promotes the release of TMPs showing superior in vivo antitumour activity and safety compared with UV-TMPs. MW-TMPs induce immunogenic cell death and reprogramme suppressive tumour immune microenvironments in different lung tumour models, enabling dual targeting of tumour cells by natural killer and T cells. We show that they can efficiently deliver methotrexate to tumours, synergistically boosting the efficacy of PD-L1 blockade. This MW-TMP development strategy is simpler, more efficient and safer than traditional UV-TMP methods.
- Mechanical regulation of extracellular vesicle activity during tumour progression.
肿瘤进展过程中细胞外囊泡活动的机械调节。
[Nat Biomed Eng] PMID: 40770502
Abstract: Extracellular vesicles (EVs) are naturally occurring membrane-bound vesicles secreted by cells. Functionalized with surface-targeting molecules and carrying signalling proteins and nucleic acids as cargo, EVs can rewire pathways and alter biological processes in recipient cells. Tumour-derived EVs have key roles in cancer progression, particularly in metastasis, by promoting tumour cell invasion and the establishment of pre-metastatic niches. An evolving understanding of EVs in cancer highlights a complex intercellular communication network within and beyond the tumour microenvironment that involves cancer cells and non-cancerous cell types, such as fibroblasts and endothelial cells. More recently, EVs have also been recognized for their role in modulating interactions between host and immune cells and in reprogramming the tumour immune microenvironment. In this Review, we discuss EV biogenesis and function in diverse mechanobiological and mechanoimmunological contexts, highlighting how mechanical cues influence EV targeting and activity. The intricate interplay between mechanical forces and EV dynamics contributes to tumour progression and links EVs to key disease hallmarks.
- Whole-genome methylation profiling of extracellular vesicle DNA in gastric cancer identifies intercellular communication features.
胃癌细胞外囊泡 DNA 的全基因组甲基化分析可识别细胞间通讯特征。
[Nat Commun] PMID: 40883299
Abstract: Extracellular vesicles (EVs) are promising biomarkers for cancer diagnosis and prognosis due to their ability to carry specific biomolecular cargo, including DNA. However, the clinical utility of DNA methylation-based liquid biopsies using EV-DNA remains underexplored. The low quantity and relatively long length of EV-DNA complicate whole-genome methylation profiling. To address this, we develop Tn5-assisted Enzymatic Methyl-sequencing with Post-conversion Tailing (TEMPT), a bisulfite-free whole-genome profiling method for EV-DNA. TEMPT employs single-adapter Tn5 tagmentation, enzymatic conversion of unmodified cytosines, and post-conversion tailing to generate high-depth whole-genome EV-DNA methylomes. We apply TEMPT to EV-DNA from 58 gastric cancer and polyp samples, generating methylomes from sub-nanogram inputs and identifying differentially methylated regions (DMRs) that distinguish cancer from controls. We identify potential cancer biomarkers through DMR-associated genes, highlighting the roles of EVs in cellular communication. Our findings suggest that immune cells may serve as an alternative source of EV-DNA. This approach holds significant promise for advancing EV-DNA research and its applications in early disease diagnosis.
- Extracellular vesicles derived from aspirin-treated macrophages promote osteochondral tissue regeneration.
来自阿司匹林治疗的巨噬细胞的细胞外囊泡促进骨软骨组织再生。
[J Control Release] PMID: 40683602
Abstract: Despite significant advancements in osteochondral tissue engineering, the treatment of osteochondral defect remains a challenging clinical issue due to the limited availability of seed cells and persistent inflammation at the defect site. Modulating the local immune microenvironment can facilitate tissue repair. Herein, we prepared extracellular vesicles (EVs) derived from aspirin-treated M1macrophages (A-EVs) and loaded them into a thermosensitive hydrogel composed of mono-functional polyhedral oligomeric silsesquioxane (MPOSS), polyethylene glycol (PEG), and polypropylene glycol (PPG) (mPEP). This hydrogel formulation serves as a sustained-release system for A-EVs. More importantly, the A-EVs showed the capacity to promote in vitro polarization of M1 to M2-like macrophages and mesenchymal stem cells (MSCs) chondrogenesis, which significantly promote in vivo osteochondral regeneration compared to EVs from untreated M1 macrophages (1-EVs) without the use of exogenous cells and growth factors. Dual-luciferase assay revealed that aspirin can reprogram the M1 macrophage through PPARα/NF-κB. The miRNA microarray analysis showed that multiple miRNAs (e.g., miR-127, miR-132 and miR-155, especially miR-140) in A-EVs can activate multiple signaling pathways related to repolarization of macrophages and MSC chondrogenesis. In summary, this study reveals a novel therapeutic application for aspirin in managing osteochondral defects through macrophage-derived EVs, preventing the issue of delayed healing by using aspirin directly.
- Red blood cell-derived microparticles induce kidney injury by triggering endothelial cell ferroptosis in intravascular hemolysis.
红细胞衍生的微粒通过触发血管内溶血中的内皮细胞铁死亡来诱发肾脏损伤。
[Redox Biol] PMID: 40669208
Abstract: Intravascular hemolysis is a common event in the pathogenesis of numerous diseases with heterogeneous etiologies and clinical features. A frequent adverse effect of massive hemolysis is kidney injury, which is a major cause of increased morbidity and mortality in chronic hemolytic diseases. However, the role of crosstalk between red blood cell-derived microparticles (RMPs) and endothelial cells (ECs) in hemolysis remains unknown, especially in hemolysis-mediated kidney injury. To answer this question, we established an in vitro co-incubation model of hemolysis-derived RMPs and ECs as well as a mouse model intravenously injected with hemolytic RMPs. We found that a large number of internalized RMPs contributed to the ferroptosis of ECs via iron overload, amino acid metabolism disorder, and the miR-130a/ACSL4 axis. Furthermore, RMPs-induced endothelial ferroptosis could enhance oxidative stress, aggravate histopathological damage, and promote loss of renal function in mice. These pathological effects were significantly ameliorated in mice treated with ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). In conclusion, our study demonstrated that RMPs-induced ferroptosis of ECs plays an important role in the development and progression of kidney damage associated with hemolysis, and inhibition of ferroptosis may be a potential therapeutic approach to prevent renal injury in patients with severe hemolytic crisis.
- Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis through extracellular vesicles.
血小板衍生的线粒体通过细胞外囊泡调节非酒精性脂肪性肝炎中的脂质代谢。
[Hepatology] PMID: 39509377
Abstract: Background and aims: Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell-derived EVs in the pathogenesis of NASH are unclear. Approach and results: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects, a rat model, and an in vitro cell-based assay. There was increased platelet activation, accompanied by pEVs release, in NASH patients/rat model, and palmitate-treated cells. The mitochondria in the platelets and pEVs from NASH patients/rats were increased but dysfunctional, including a reduction in fatty acid β-oxidation, inactivated acetyl-CoA carboxylase 2, and suppressed oxidative phosphorylation system complex II/III/IV activity. These damaged mitochondria could be transferred to hepatocytes through pEVs to increase the number of lipid droplet-bound mitochondria. An increase in dysfunctional lipid droplet-bound mitochondria in hepatocytes affects lipid metabolism, resulting in excessive LD accumulation, elevated mitochondrial reactive oxygen species production, and apoptosis. Conclusions: We offer a novel molecular mechanism that connects platelets, pEVs, and excessive LD accumulation to the development of NASH. Our results suggest that NASH progression may be alleviated by specifically inhibiting the production and release of pEVs, or by targeting pEV components and inhibiting their uptake. Additional experiments are required to confirm this potentiality.
今天的整理就到这里。希望大家可以有所收获。大家下周见！
