Extracellular vesicles and circulating nucleic acids最新文献

{"title":"Selective DNA encapsulation in extracellular vesicles of <i>Saccharomyces cerevisiae</i>.","authors":"Ana Perea-Martínez, Miguel Mejías-Ortiz, Pilar Morales, Ramon Gonzalez","doi":"10.20517/evcna.2025.118","DOIUrl":"10.20517/evcna.2025.118","url":null,"abstract":"<p><p><b>Aim:</b> Extracellular vesicles (EVs) are emerging mediators of intercellular communication capable of transporting nucleic acids, including plasmid and genomic DNA. This study aimed to investigate the presence, enrichment, and protection of distinct DNA classes in EV-enriched fractions from <i>Saccharomyces cerevisiae</i> (<i>S. cerevisiae</i>). <b>Methods:</b> Two plasmids were analyzed: the high-copy YEp352 (2µ) and the centromeric pRS316. EV-enriched fractions were isolated from yeast culture supernatants, and the presence of plasmid, ribosomal [18S ribosomal DNA (RDN18)], and mitochondrial [cytochrome c oxidase subunit I (COX1)] DNA was assessed. DNase digestion assays were performed to evaluate DNA protection, and transformation assays were conducted using <i>S. cerevisiae</i> and <i>Escherichia coli</i>. Enrichment of endogenous <i>vs.</i> exogenously added plasmid DNA was also compared. <b>Results:</b> Both plasmids were strongly enriched in EV fractions relative to culture supernatants. However, only pRS316 exhibited partial resistance to DNase digestion, suggesting encapsulation, while YEp352 remained fully susceptible. Despite this protection, pRS316-associated EVs did not mediate transformation of yeast or bacterial recipients, indicating compromised integrity or inefficient delivery. Endogenously produced plasmid DNA showed significantly higher enrichment than exogenously added DNA. Ribosomal and mitochondrial DNA were also detectable in EVs but were highly sensitive to DNase degradation, indicating minimal protection. <b>Conclusion:</b> These findings demonstrate that selective DNA incorporation into EVs depends on both DNA type and intrinsic plasmid features. The results suggest that plasmid properties influence EV-mediated transport and protection, highlighting the selective and cargo-specific nature of DNA packaging in yeast EVs.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"448-464"},"PeriodicalIF":8.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative proteomic and functional comparison of extracellular vesicles from multiple adipose tissue mesenchymal stem cell donors.","authors":"Kyong-Su Park, Dae Hyun Ha, Jun Ho Lee, Negar Ordouzadeh, Markus Bergqvist, Hyun Ju Lee, Ella Shin, Byong Seung Cho, Jan Lötvall","doi":"10.20517/evcna.2025.173","DOIUrl":"10.20517/evcna.2025.173","url":null,"abstract":"<p><p><b>Aim:</b> Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs), known as MSC-EVs, have gained attention as potential treatments owing to their immunomodulatory functions. Despite growing clinical interest, donor-to-donor inconsistencies remain key challenges for standardizing MSC-EV production under good manufacturing practice (GMP) conditions. This work aimed to systematically compare the molecular and functional consistency of EVs derived from three independent human adipose tissue-MSC donors. <b>Methods:</b> GMP-grade EVs were initially isolated using tangential flow filtration on a large scale and then characterized by multiple biophysical analyses. To characterize the protein composition of EVs across batches, quantitative proteomic analysis was performed using tandem mass tags and mass spectrometry. For functional validation, an <i>in vitro</i> macrophage inflammation assay was conducted by treating natural lipopolysaccharide-stimulated cells with EVs, and cytokine levels were measured using enzyme-linked immunosorbent assays (ELISA). <b>Results:</b> Quantitative proteomic profiling identified 2,615 proteins, of which 84%-94% were not significantly changed across batches, highlighting a robust core proteome. Notably, 361 membrane-associated proteins were consistently conserved, including transporters, adhesion molecules, and signaling receptors, implicating these components in EV-mediated intercellular communication and immunomodulation. Functional analysis using an <i>in vitro</i> macrophage inflammation model demonstrated that all EV batches reproducibly suppressed pro-inflammatory cytokine production in a dose-dependent manner, with no significant inter-batch differences. <b>Conclusion:</b> Collectively, these findings indicate that MSC-EVs maintain both molecular and functional stability across different donors, and that a conserved proteomic signature underlies their reproducible anti-inflammatory activity. This study provides a foundation for establishing standardized quality criteria and advancing MSC-EVs toward clinical therapeutic applications.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"425-440"},"PeriodicalIF":8.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle therapeutics in Alzheimer's disease: mechanisms, progress, and prospects.","authors":"Yiduo Fang, Xiaotong Hao, Bo Fang","doi":"10.20517/evcna.2025.158","DOIUrl":"10.20517/evcna.2025.158","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, characterized by progressive cognitive decline and a current lack of effective curative treatments. In recent years, extracellular vesicle (EV) therapies have emerged as a cutting-edge approach in AD research due to their unique biological properties. This review systematically examines the role of EVs in the pathogenesis of AD, including their cellular origins and functional attributes. We detail the molecular mechanisms mediated by EVs that influence AD progression and summarize the latest advancements in EV-based therapeutic strategies. Additionally, the review addresses the challenges faced in translating these therapies from bench to bedside, such as standardization, delivery optimization, and safety concerns. Future research directions are discussed to foster the development of innovative and effective treatments for AD. By providing a comprehensive overview, this article aims to lay a theoretical foundation and offer valuable insights for the advancement of novel therapeutic interventions targeting AD.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"394-424"},"PeriodicalIF":8.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles derived from TNF-α-preconditioned mesenchymal stem cells mitigate inflammatory retinal injury.","authors":"Zhuxin Jia, Fuxiao Luan, Jingyi Shi, Yong Tao, Ying Tian","doi":"10.20517/evcna.2025.159","DOIUrl":"10.20517/evcna.2025.159","url":null,"abstract":"<p><p><b>Aim:</b> To evaluate the therapeutic efficacy and mechanisms of tumor necrosis factor-alpha (TNF-α) preconditioned mesenchymal stem cells (MSCs)-derived small extracellular vesicles (hereafter abbreviated as T-sEV), along with the control small extracellular vesicles (sEV, representing vesicles from naive/unstimulated MSCs), in mitigating inflammatory retinal injury. <b>Methods:</b> T-sEV were isolated from TNF-α-preconditioned MSCs and systematically characterized. Small RNA sequencing was performed to identify the microRNA (miRNA) cargo of T-sEV. The effect of T-sEV on lipopolysaccharide (LPS)-induced M1 macrophage polarization was assessed by flow cytometry. Integrated bioinformatic analysis linked T-sEV miRNAs to macrophage transcriptome changes. T-sEV were administered intravitreally in a murine sodium iodate (NaIO₃)-induced retinal degeneration model. Electroretinography (ERG), optical coherence tomography (OCT), flow cytometry, intraocular pressure (IOP) and systemic examinations were conducted. <b>Results:</b> T-sEV exhibited an enrichment of anti-inflammatory miRNAs, notably miR-146a-5p. They were efficiently internalized by macrophages, significantly suppressing M1 polarization, as evidenced by the decreased percentage of cluster of differentiation (CD)11b⁺/CD86⁺ cells (29.60% ± 2.30%) compared to the sEV group (34.90% ± 1.57%, <i>P</i> < 0.05). Analysis showed T-sEV miRNAs targeted and downregulated key pro-inflammatory genes such as Cd86 and Il1r1. <i>In vivo</i>, T-sEV treatment significantly preserved retinal a- and b-wave amplitudes and structural integrity. T-sEV treatment markedly reduced retinal macrophage infiltration, decreasing the proportion of F4/80⁺CD11b⁺ cells to 0.38% ± 0.13%, significantly lower than in the sEV group (1.66% ± 0.47%, <i>P</i> < 0.01). No adverse effects on IOP or systemic markers were observed. <b>Conclusion:</b> TNF-α preconditioning enhances MSC-derived sEV therapeutic capacity by enriching their anti-inflammatory miRNAs. T-sEV suppress pro-inflammatory macrophage activation and provide superior neuroprotection in a retinal degeneration model, indicating a safe and promising cell-free therapeutic strategy.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"377-393"},"PeriodicalIF":8.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced small extracellular vesicles delivery systems for <i>in situ</i> tissue engineering.","authors":"Yike Gao, Jingyi Sang, Zhuo Wan, Yue Wang, Xiaojing Yuan, Yuqing Dong, Zuoying Yuan, Yuming Zhao","doi":"10.20517/evcna.2025.149","DOIUrl":"10.20517/evcna.2025.149","url":null,"abstract":"<p><p><i>In situ</i> tissue engineering, which activates the body's innate regenerative capacity, has demonstrated superior clinical translation potential than traditional <i>ex situ</i> approaches. Small extracellular vesicles (sEVs), as natural nanovesicles, can excellently mimic the paracrine functions of cells and are thus emerging as promising cell-free alternatives for <i>in situ</i> tissue engineering. Despite advantages such as low immunogenicity, multi-target regulatory capabilities, and cross biological barriers availability, the therapeutic sustainability of sEVs is limited by their rapid clearance <i>in vivo</i>, underscoring the need for effective delivery systems. This review systematically summarizes the sources and bioactivities of sEVs, delineates the design principles and technological advances in sEVs delivery systems, and highlights their application in tissue engineering, while also outlining future trajectories for the development of intelligent delivery platforms.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"354-376"},"PeriodicalIF":8.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pomegranate-derived nanovesicles as therapeutic agents for acute pancreatitis in a murine model: anti-inflammatory, antioxidant, and endocrine-protective properties.","authors":"Isabel Torres-Cuevas, Christian M Sánchez-López, Antonio Marcilla, Salvador Pérez","doi":"10.20517/evcna.2025.145","DOIUrl":"10.20517/evcna.2025.145","url":null,"abstract":"<p><p><b>Aim:</b> Acute pancreatitis (AP) is an inflammatory disorder of the pancreas lacking specific therapy and frequently complicated by oxidative stress (OS) and long-term endocrine dysfunction, including pancreatogenic diabetes. Pomegranate-derived nanovesicles (<i>Pg</i>NVs) contain bioactive lipids, proteins, and metabolites responsible for many health benefits of pomegranate juice. This study evaluated whether prophylactic <i>Pg</i>NVs administration could mitigate pancreatic injury, OS, systemic inflammation, and subsequent endocrine impairment in a murine model of severe L-arginine-induced AP. <b>Methods:</b> Male C57BL/6J mice were distributed to three groups: control, AP, and AP + <i>Pg</i>NVs. A single subcutaneous dose of <i>Pg</i>NVs (10 µg; ≈ 5 × 10¹⁰ particles) was administered 2 h before AP induction via intraperitoneal L-arginine. Animals were analyzed at 3, 7, 30, and 60 days post-induction. <i>Pg</i>NVs were isolated using differential centrifugation, tangential-flow filtration, and size-exclusion chromatography. <b>Results:</b> <i>Pg</i>NVs pretreatment preserved pancreatic architecture, reduced edema, amylase activity, and interleukin 6 (IL-6) levels in both tissue and plasma by limiting nuclear factor-κB-p65 phosphorylation. <i>Pg</i>NVs restored redox balance by upregulating NQO1 [NAD(P)H quinone dehydrogenase 1], improving oxidized glutathione (GSSG)/reduced glutathione (GSH) and homocystine/homocysteine ratios, and maintaining PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) expression. <i>Pg</i>NVs protected β-cell mass, enhanced insulin secretion, and normalized glucose tolerance after AP. Proteomic profiling revealed that <i>Pg</i>NVs changed extracellular vesicle composition, lowering pro-inflammatory markers [fibronectin, dipeptidyl peptidase-4 (DPP4)] and restoring anti-inflammatory ITIH4 (inter-alpha-trypsin inhibitor protein heavy chain 4). <b>Conclusion:</b> <i>Pg</i>NVs exert anti-inflammatory and antioxidant protection in experimental AP and preserve long-term endocrine function, highlighting their potential as a natural nanotherapeutic strategy to prevent pancreatic injury and post-pancreatitis diabetes.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"328-353"},"PeriodicalIF":8.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic analysis of equine amniotic mesenchymal stromal cells and their extracellular vesicles: comparing their regenerative properties.","authors":"Giulia Gaspari, Alessio Soggiu, Paola Gagni, Pietro Riccaboni, Andrea Cappelleri, Fausto Cremonesi, Anna Lange-Consiglio","doi":"10.20517/evcna.2025.66","DOIUrl":"10.20517/evcna.2025.66","url":null,"abstract":"<p><p><b>Aim:</b> To compare specific functional features of equine amniotic mesenchymal cells (eAMCs) and their extracellular vesicles (EVs) through proteomic analysis. <b>Methods:</b> eAMCs were obtained by enzymatic digestion and their EVs were isolated by ultracentrifugation. Cells and EVs were characterized according to ISCT and MISEV guidelines. A proteomic analysis of both eAMCs and EVs was conducted. The raw data files were analyzed using FragPipe 22 and uniprotkb equus_caballus_reviewed database (20.02.2025) to obtain protein identifications (false discovery rate = 0.01) and their respective label-free quantification values using recommended parameters. Statistical analysis was performed based on the combined_protein.tsv file using FragPipe-Analyst. A cutoff of the adjusted <i>P</i>-value of 0.05 along with a |log2 fold change| of 1 has been applied to determine differentially expressed proteins in the comparison. <b>Results:</b> A total of 3,631 proteins were identified, of which 3,147 were identified with more than two peptides. Among these, 2,235 were exclusive to eAMCs, 697 were shared between eAMCs and EVs, and 71 were exclusive to EVs. eAMCs and EVs revealed distinguished proteomic profiles, differentially expressing proteins involved in biological processes related to tissue regeneration. Proteins promoting anti-inflammatory activity, oxidative stress resistance and angiogenesis exhibited increased expression levels in eAMCs, while extracellular matrix organization and deposition were predominantly upregulated in EVs. <b>Conclusions:</b> Equine eAMCs and EVs are characterized by a distinct proteomic profile showing the expression of different sets of proteins involved in regenerative processes and thus different therapeutic properties. This also highlights their coordinated activity on tissue homeostasis and regeneration mechanisms.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"302-327"},"PeriodicalIF":8.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory landscape for extracellular vesicle therapies: Australian context and future directions.","authors":"Christopher Rudge, Reeve McClelland, Wojciech Chrzanowski, Ryan L Davis","doi":"10.20517/evcna.2025.129","DOIUrl":"10.20517/evcna.2025.129","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are emerging as promising tools for regenerative medicine and drug delivery, offering unique therapeutic advantages. However, their clinical translation - in Australia and globally - faces persistent challenges. These are commonly framed as technical issues stemming from inherent EV variability and the absence of standardized potency assays. While no EV-based therapeutic has yet received full market approval from any major regulatory agency, this Perspective argues that the barriers to translation are not solely technical but reflect limitations within current regulatory frameworks. In Australia, the Therapeutic Goods Administration (TGA) requires biological products to be included on the Australian Register of Therapeutic Goods (ARTG) before supply to market. However, several alternative regulatory pathways exist that can facilitate clinical access to \"unapproved\" products. Through analysis of these pathways, and comparison with international approaches, this Perspective highlights how regulatory inflexibility may be as significant a barrier to translating EV medicines as the technical difficulties themselves. Drawing on insights from governmental inquiries into the approval and subsidization of emerging medicines, the Perspective calls for reform of Australia's regulatory systems - including development of EV-specific guidance and policy that introduces adaptive assessment pathways - to better support the safe and timely integration of novel biotechnologies.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"292-301"},"PeriodicalIF":8.5,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle-based therapeutic strategies for spinal cord injury.","authors":"Jingsong Liu, Xuqiang Gong, Yuanliang Sun, Yangyang Wang, Yansong Wang","doi":"10.20517/evcna.2025.142","DOIUrl":"10.20517/evcna.2025.142","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a highly disabling disorder of the central nervous system for which no curative therapy is currently available. In recent years, extracellular vesicles - particularly exosomes - have been investigated as cell-free therapeutic approaches in experimental models, owing to their low immunogenicity, favorable biocompatibility and capacity to traverse the blood-spinal cord barrier under specific conditions or delivery routes. This Review summarizes the therapeutic activities and mechanisms of exosomes from diverse sources - including mesenchymal stem cells, immune cells and neural cells - in SCI repair. Reported mechanisms include modulation of the inflammatory microenvironment; inhibition of apoptosis and pyroptosis; mitigation of ferroptosis; promotion of angiogenesis and axonal regeneration; and restriction of glial scar formation. We also discuss advances aimed at enhancing exosome efficacy through cell preconditioning, engineering strategies and integration with biomaterials. Although exosome-based approaches are promising, challenges remain in standardization, targeted delivery and long-term safety. Future work should elucidate the underlying mechanisms and advance clinical translation to robustly evaluate the therapeutic potential of exosomes for SCI repair.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"259-291"},"PeriodicalIF":8.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vesicle-like nanoparticles extracted from <i>Pueraria lobata</i> decoction alleviate colitis by modulating the intestinal microbiota.","authors":"Cai-Xiao Liu, Yi-Juan Han, Na Zhao, Qiao-Ning Wang, Run-Run Wan, Ting-Ting Cao, Xi He, Cheng-Hu Hu, Cheng-Biao Hu, Zhang Yuan","doi":"10.20517/evcna.2025.134","DOIUrl":"10.20517/evcna.2025.134","url":null,"abstract":"<p><p><b>Aim:</b> This study aimed to investigate whether vesicle-like nanoparticles derived from the GeGen decoction (GGD-PDVLNs) represent a key bioactive component responsible for its anti-colitis effects and to elucidate their underlying mechanisms, particularly focusing on gut microbiota modulation. <b>Methods:</b> The GeGen decoction (GGD) was subjected to differential centrifugation following boiling, yielding vesicle-like nanoparticles. Structural analysis confirmed that these nanoparticles have a lipid bilayer and can resist digestion by simulated gastrointestinal fluids. These nanoparticles were administered orally to mice with chronic colitis induced by dextran sulfate sodium to evaluate their therapeutic effects. <b>Results:</b> GGD-PDVLNs effectively mitigated intestinal inflammation by reducing the secretion of pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α)], elevating levels of the anti-inflammatory cytokine IL-10, alleviating intestinal damage, and enhancing intestinal barrier function, all while exhibiting a favorable biosafety profile. Notably, their therapeutic action depended on gut microbiota modulation. GGD-PDVLNs restored microbial homeostasis, increased microbial diversity, and enriched probiotic populations. In pseudo-germ-free mice, GGD-PDVLNs lost efficacy, confirming microbiota-dependent mechanisms. <b>Conclusion:</b> Vesicle-like nanoparticles are an important active component of GGD. Our findings demonstrate that GGD-PDVLNs significantly ameliorate colonic inflammation through microbiota-dependent mechanisms.</p>","PeriodicalId":520322,"journal":{"name":"Extracellular vesicles and circulating nucleic acids","volume":"7 1","pages":"234-258"},"PeriodicalIF":8.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13074279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}