本周hzangs在最新文献中选取了6篇分享给大家，第1篇文章介绍了使用磁珠富集细胞外囊泡并用于血浆囊泡蛋白质组分析的技术流程；第2篇文章介绍了一种可以用于捕获细胞外囊泡来降低辐射引起炎症的工程化纳米贴片；第5篇文章介绍了巨噬细胞来源囊泡在肺部缺血/再灌注过程中对中性粒细胞胞外陷阱的诱导作用。
- Enrichment of extracellular vesicles using Mag-Net for the analysis of the plasma proteome.
使用 Mag-Net 富集细胞外囊泡以分析血浆蛋白质组。
[Nat Commun] PMID: 40595564
Abstract: Extracellular vesicles (EVs) in plasma are composed of exosomes, microvesicles, and apoptotic bodies. We report a plasma EV enrichment strategy using magnetic beads called Mag-Net. Proteomic interrogation of this plasma EV fraction enables the detection of proteins that are beyond the dynamic range of liquid chromatography-mass spectrometry of unfractionated plasma. Mag-Net is robust, reproducible, inexpensive, and requires <100 μL plasma input. Coupled to data-independent mass spectrometry, we demonstrate the measurement of >37,000 peptides from >4,000 proteins. Using Mag-Net on a pilot cohort of patients with neurodegenerative disease and healthy controls, we find 204 proteins that differentiate (q-value < 0.05) patients with Alzheimer's disease dementia (ADD) from those without ADD. There are also 310 proteins that differ between individuals with Parkinson's disease and without. Using machine learning we distinguish between individuals with ADD and not ADD with an area under the receiver operating characteristic curve (AUROC) = 0.98 ± 0.06.
- Nanostructured organic sheets sequestering small extracellular vesicles and reactive species to protect against radiation-induced mucositis.
纳米结构有机薄片隔离小的细胞外囊泡和活性物质，以防止辐射引起的粘膜炎。
[Nat Commun] PMID: 40610425
Abstract: Radiation-induced mucositis significantly reduces quality of life in patients undergoing radiotherapy and chemoradiotherapy for head and neck cancer. Radiation exposure increases the secretion of small extracellular vesicles carrying double-stranded DNA, which triggers excessive inflammation. To address this, we develop functionalized organic nanosheets designed to capture these inflammatory vesicles from damaged tissue. Using template-based synthesis, we create nanostructured organic sheets functionalized with CD63 aptamers, enabling selective targeting of extracellular vesicles involved in mucositis. These nanosheets show enhanced vesicle-binding capacity compared to spherical nanoparticles, efficiently suppressing inflammation by inhibiting the stimulator of interferon genes activation in macrophages. Additionally, they effectively scavenge reactive oxygen and nitrogen species, further alleviating mucosal inflammation. Flow cytometry and transcriptome analyses in irradiated animal models confirm significant mucositis mitigation. This therapeutic platform provides a promising anti-inflammatory strategy by demonstrating how biomaterial geometry and surface functionalization can modulate small extracellular vesicle-mediated inflammation in radiation-induced mucositis.
- Adipose stem cell-derived nanovesicles for cardioprotection: production and identification of therapeutic components.
脂肪干细胞衍生的纳米囊泡用于心脏保护：治疗成分的生产和鉴定。
[J Control Release] PMID: 40582645
Abstract: Extracellular vesicles (EVs) derived from stem cells have shown therapeutic benefits in myocardial injury. However, the challenges in their large-scale production and elusive molecular mechanisms underlying their therapeutic effects have been hindering their clinical translation. Here, in a mouse model of myocardial ischemia-reperfusion, EVs isolated from human adipose tissue and EV-like nanovesicles fabricated with adipose stem cells (ADSCs) via a membrane extrusion approach, termed ADSC-derived nanovesicles (ADSC-CDNs), exhibited comparable cardioprotective effects, validating this EV-mimetic strategy. CDNs generated from the human monocytic cell line U937 similarly conferred protection, whereas those from HEK293 cells did not, highlighting the importance of cell source for therapeutic efficacy. microRNA profiling identified miR-24-3p as a predominant therapeutic cargo in ADSC-EVs and ADSC-CDNs. This microRNA upregulates the cytoprotective transcription factor Nrf2, thereby suppressing cardiomyocyte apoptosis. Functional assays also confirmed that miR-24-3p was a key component mediating the cardioprotective effects of those nanovesicles. Importantly, this study introduces a cell-source-dependent, scalable, and high-yield production platform for ADSC-CDNs that preserves molecular cargo profile of the parent cells, ensuring consistent therapeutic content. This EV-mimetic platform is technically feasible and clinically translatable, demonstrating reproducible efficacy in both acute injury and post-infarction recovery phases. Taken together, the defined microRNA cargo and the robust vesicle production strategy highlight the translational potential of ADSC-CDNs as an off-the-shelf cardioprotective therapy.
- Advances and mechanisms of gut microbiota modulation in enhancing immune checkpoint inhibitor efficacy.
肠道菌群调节增强免疫检查点抑制剂疗效的进展及机制。
[Semin Cancer Biol] PMID: 40617533
Abstract: The gut microbiota is crucial for maintaining human health by regulating immune homeostasis and metabolic function. Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer immunotherapy, yet their effectiveness is often hampered by treatment resistance and immune-related adverse events (irAEs). Increasing evidence highlights gut microbiota as a critical determinant of ICI efficacy. Here, we summarize the advances from preclinical mouse models and clinical trials to systematically illustrate how gut microbiota modulation strategies, such as fecal microbiota transplantation, specific microorganism supplementation, dietary and lifestyle interventions, and prebiotic/postbiotic supplementation, can enhance ICI therapeutic outcomes and mitigate irAEs. Mechanistically, the gut microbiota shape host immune responses, influencing innate, adaptive, and mucosal immunity, as well as immune checkpoint expression, through microbial translocation, microbiota-derived metabolites, and extracellular vesicles. This review elucidates the intricate interplay between gut microbiota and ICI treatment responses, laying a theoretical groundwork for developing personalized microbiota-based strategies to optimize cancer immunotherapy.
- EMAP-II from macrophage-derived extracellular vesicles drives neutrophil extracellular traps formation via PI3K/AKT/mtROS in lung ischemia/reperfusion injury.
来自巨噬细胞衍生的细胞外囊泡的 EMAP-II 通过 PI3K/AKT/mtROS 驱动肺缺血/再灌注损伤中的中性粒细胞细胞外陷阱形成。
[Redox Biol] PMID: 40616949
Abstract: Lung ischemia/reperfusion injury (LIRI) is a significant complication following lung transplantation driven by neutrophil extracellular traps (NETs) associated with mitochondrial oxidative stress. However, the intercellular signaling mechanisms mediating oxidative stress remain unresolved. Here, we elucidated a mitochondrial reactive oxygen species (mtROS) amplification mechanism driven by extracellular vesicles (EVs). In this mechanism, EVs derived from oxygen-glucose deprivation/reperfusion (OGD/R)-activated macrophages transferred endothelial monocyte-activating polypeptide-II (EMAP-II) to neutrophils, suppressed PI3K/AKT signaling, and thereby induced mitochondrial oxidative stress that drove pathological NETs formation. Proteomic profiling identified EMAP-II as a key signaling molecule enriched in EVs secreted by OGD/R-activated macrophages. Pharmacological inhibition of mtROS or AKT activation abolished NETs formation, confirming the PI3K/AKT/mtROS as the central redox-sensitive pathway. Crucially, shRNA-mediated EMAP-II knockdown in macrophages abolished the ability of OGD/R-EVs to induce mtROS and NETs formation, mitigating pulmonary inflammation and tissue injury in mice. This study establishes EMAP-II from macrophage-derived EVs as transcellular drivers of neutrophil mitochondrial oxidative stress. We propose EMAP-II blockade as a therapeutic strategy to disrupt the pathogenic cascade in LIRI, wherein macrophage-derived EVs trigger NETs formation through PI3K/AKT/mtROS.
- Cancer-associated fibroblast-derived extracellular vesicles loaded with GLUT1 inhibitor synergize anti-PD-L1 to suppress tumor growth via degrading matrix stiffness and remodeling tumor microenvironment.
装载有 GLUT1 抑制剂的癌症相关成纤维细胞衍生的细胞外囊泡协同抗 PD-L1 作用，通过降低基质硬度和重塑肿瘤微环境来抑制肿瘤生长。
[J Control Release] PMID: 40609836
Abstract: Cancer immunotherapy has transformed cancer treatment, demonstrating the potential for lasting responses in multiple solid and hematologic malignancies and thus has revolutionized cancer treatment in clinic. However, the intricate tumor microenvironment (TME), characterized by a rigid extracellular matrix (ECM) and robust immunosuppressive environment, presents substantial hurdles to the effectiveness of cancer immunotherapy. Thus, cancer-associated fibroblasts (CAFs), the most abundant stromal cells that mediate ECM remodeling and participate in immune suppression, represent promising therapeutic targets for combination immunotherapy. In this study, by using and analyzing single-cell RNA-sequencing (scRNA-seq) in the public datasets, we have identified the elevated expression of glucose transporter 1 (GLUT1) in activated CAF subgroups within tumor sites compared to normal tissues. Moreover, the recent literature has also demonstrated that CAFs undergoing high metabolic levels have been identified to show a better response to immunotherapy. Furthermore, extracellular vesicles (EVs) secreted by CAFs remain unexplored, and their role in drug transport systems and targeting efficiency towards tumorous cells remains uninvestigated. Herein, we identified the elevated expression of glucose transporter 1 (GLUT1) as a prognostic indicator for cancer associated with poor prognosis and investigated the vulnerability of lung tumor cell lines and CAFs to pharmacological GLUT1 inhibition with BAY-876. Based on the possibility of targeting the intrinsic TME-associated metabolism by GLUT1 inhibition, we have firstly employed CAFs-derived extracellular vesicles (cEVs) as a carrier for targeted delivery of BAY-876 into GLUT1-high CAFs and tumor cells. The cEV-BAY-876 (cEVB6) treatment significantly resulted in glucose-rich, low-lactate TME, reversed the activated CAFs phenotype, enabled stromal reprogramming, decreased ECM stiffness and enhanced the infiltration of CD3 + CD8+ T cells in tumor core, thereby achieving an excellent anti-tumor efficiency. Moreover, cEV-B6 treatment synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes and exerted strong anticancer effects against mice lung tumors. Our study provides the first evidence that tumor stroma-specific therapies by targeting glucose metabolism present a promising strategy of remodeling the extracellular matrix to reverse CAFs into normal type and potentiate cytotoxic T lymphocytes (CTLs) infiltration thereby improving anticancer immunotherapy.
今天的整理就到这里。希望大家可以有所收获。大家下周见！
