Journal of Extracellular Vesicles最新文献

{"title":"Extracellular Vesicles Containing MDP Derived from Lactobacillus rhamnosus GG Inhibit HSV-2 Infection by Activating the NOD2-IFN-I Signalling Pathway","authors":"Jingyu Wang,&nbsp;Haoming Chen,&nbsp;Mei Huang,&nbsp;Yuqi Du,&nbsp;Ruyi Zhang,&nbsp;Yiyi Huang,&nbsp;Yuling Lin,&nbsp;Ruoru Pan,&nbsp;Yubing Wang,&nbsp;Wanqin Cui,&nbsp;Qian Wang,&nbsp;Lei Zheng,&nbsp;Xiumei Hu","doi":"10.1002/jev2.70152","DOIUrl":"10.1002/jev2.70152","url":null,"abstract":"<p>The immune evasion strategies and lifelong latency of herpes simplex virus type 2 (HSV-2) present significant challenges for effective treatment. Recent studies have demonstrated that the commensal microbiota plays an important role in regulating immunity against viral infections. We previously reported that <i>Lactobacillus rhamnosus</i> GG (LGG) activates the expression of type I interferons (IFN-I) to inhibit HSV-2 infection. However, the specific molecular mechanisms remain unclear. Bacterial extracellular vesicles (EVs) are small lipid bilayer-bound particles secreted by bacteria, which can serve as intercellular communication vehicles between the host and pathogens, functioning as immunomodulatory vectors defending against viral infections. In this study, we confirmed that LGG-EVs activate the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)-IFN-I signalling pathway, inducing the expression of interferon-stimulated genes (ISGs) to combat HSV-2 infection both in vivo and in vitro. Furthermore, we explored the specific components within LGG-EVs and identified the presence of muramyl dipeptide (MDP). We demonstrated that MDP-enriched LGG-EVs effectively inhibit HSV-2 infection via activation of the NOD2-IFN-I pathway. These findings suggest that LGG-EVs could serve as a novel therapeutic strategy for HSV-2 and provide a mechanistic foundation for future antiviral research.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles From Limosilactobacillus johnsonii Enhance Milk Fat Synthesis by Inducing CD36 Dynamic Palmitoylation and Activating PPARγ Signalling","authors":"Qihui Li,&nbsp;Baofeng Li,&nbsp;Qianzi Zhang,&nbsp;Dongpang Chen,&nbsp;Siyu Yuan,&nbsp;Hanyu Jing,&nbsp;Haobin Li,&nbsp;Wutai Guan,&nbsp;Shihai Zhang","doi":"10.1002/jev2.70143","DOIUrl":"10.1002/jev2.70143","url":null,"abstract":"<p>Mammals support offspring survival through efficient milk production, ensuring the transfer of essential nutrients and energy. Extracellular vesicles (EVs) released by gut microorganisms function as signalling molecules that influence host physiology. In this study, we observed an association between gut microbiota and lactation performance, with <i>Limosilactobacillus johnsonii</i> showing potential in promoting milk fat synthesis. Using a mouse model, we demonstrated that <i>L. johnsonii</i>-derived EVs enhance mammary gland function, leading to increased milk fat content and improved pup growth. Mechanistically, palmitic acid (C16:0) from <i>L. Johnsonii</i> EVs was found to induce the dynamic changes in CD36 palmitoylation in mammary epithelial cells, thereby facilitating fatty acid uptake as substrates for milk fat synthesis. Additionally, the increased availability of fatty acids further promotes the activation of peroxisome proliferator-activated receptor-γ (PPARγ), reinforcing its role in regulating milk fat synthesis. These findings provide new insights into the gut-mammary gland axis and its role in lactation regulation.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells\"","authors":"","doi":"10.1002/jev2.70144","DOIUrl":"10.1002/jev2.70144","url":null,"abstract":"<p>Tan, J., Y. Hu,L. Zheng, et al. 2025. “Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells.” <i>Journal of Extracellular Vesicles</i> 14: e70053. https://doi.org/10.1002/jev2.70053</p><p>In the originally published article, author Jiayi Tan was left off the author list. The correct author list appears below. This has been updated in the online version of the article.</p><p>Jiayi Tan,¹ Yunxia Hu,^2,3,4 Lijuan Zheng,^2,3,4 Zheng Zheng,⁵ Mali Fu,⁵ Haiying Peng,⁶ Shaohua Ma^2,3,4</p><p>¹Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, China</p><p>²Institute of Biopharmaceutical and Health Engineering (iBHE), Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, China</p><p>³Key Lab of Industrial Biocatalysis, Ministry of Education, Shenzhen, China</p><p>⁴Key Lab of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Tsinghua Shenzhen International Graduate School, Shenzhen, China</p><p>⁵Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, China</p><p>⁶General Hospital of the Southern Theater Command of the Chinese People's Liberation Army, Guangzhou, China</p><p>Additionally, Figure 1d in this paper partially duplicates Figure 3a from Cao et al. 2022. The authors have replaced the duplicated live/dead staining image in Figure 1d with data from another batch of repeat experiments (see below).</p><p>The caption for Figure 2, which appears below, has been revised because Figure 2c, which presents the size distribution and concentration of hMSC-EVs as measured by NTA, also appeared in Appendix S25 of the publication by Cao et al., 2022.</p><p>Figure 2 Characterisation and comparison of hMSC-EVs derived from microbeads and 2D groups. (a) The experimental workflow of EV collection and isolation. (b) Representative TEM image of hMSC-EVs. Scale bar, 200 nm. (c) Size distribution and concentration of hMSC-EVs measured by NTA. Data in this panel were replicated from Appendix S25 of Cao et al., 2022. (d) Comparison of size distribution and concentration results measured by NTA of hMSC-EVs. (e–f) Average diameter and normalised particle concentration of hMSC-EVs based on NTA results. (g, h) Protein and RNA content in hMSC-EVs. (i) Western blot analysis of marker proteins (Hsp70, TSG101, CD63) in hMSC-EVs. ^*<i>p</i> &lt; 0.05; ^**<i>p</i> &lt; 0.01; ^***<i>p</i> &lt; 0.001; ^****<i>p</i> &lt; 0.0001.</p><p>We apologize for these error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP Synthase Abundance in Neuronal Extracellular Vesicles Reflects Changes in the Mitochondria of Parent Neurons","authors":"Pamela J. Yao,&nbsp;Carlos Nogueras-Ortiz,&nbsp;Krishna Ananthu Pucha,&nbsp;Dimitrios Kapogiannis","doi":"10.1002/jev2.70140","DOIUrl":"10.1002/jev2.70140","url":null,"abstract":"<p>Mitochondrial proteins are found in extracellular vesicles (EVs) such as neuron-derived EVs (NEVs). Yet whether and how NEV-borne mitochondrial proteins relate to the state of mitochondria in the parent neurons is unclear. Studying the mitochondrial ATP synthase in primary hippocampal neurons and their released EVs, we discovered that the abundance of ATP synthase in NEVs echoes the catalytic activity level of ATP synthase in neurons. We also observed, unexpectedly, that within the neuron, the quantity of ATP synthase remains constant irrespective of the level of its activity. Using non-canonical amino acid tagging coupled with proximity ligation assay, we found that the amount of nascent ATP synthase is linearly correlated to its activity, which may contribute to maintaining the overall quantity of ATP synthase in the neuron stable. Furthermore, we identified a sub-population of mitochondria-derived vesicles (MDVs) that carry ATP synthase and are not targeted to lysosomal degradation. Our findings suggest a strategy used by neurons in regulating and fine-tuning mitochondrial ATP synthase through MDV and NEV generation. Further studies are needed to elucidate the relationship between ATP synthase–containing-NEVs and -MDVs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of Tax1-PDZ Interactions Block HTLV-1 Viral Transmission by Changing EV Composition","authors":"Jedidja Puttemans,&nbsp;Yasmine Brammerloo,&nbsp;Karim Blibek,&nbsp;Jeremy Blavier,&nbsp;Thandokuhle Ntombela,&nbsp;Inge Van Molle,&nbsp;Julie Joseph,&nbsp;Julien Olivet,&nbsp;Deeya Saha,&nbsp;Manon Degey,&nbsp;Malik Hamaidia,&nbsp;Pooja Jain,&nbsp;Piel Geraldine,&nbsp;Pascale Zimmermann,&nbsp;Dae-Kyum Kim,&nbsp;Dominique Baiwir,&nbsp;Makon-Sébastien Njock,&nbsp;Franck Dequiedt,&nbsp;Kourosh Salehi-Ashtiani,&nbsp;Steven Ballet,&nbsp;Alexander N. Volkov,&nbsp;Jean-Claude Twizere,&nbsp;Sibusiso B. Maseko","doi":"10.1002/jev2.70137","DOIUrl":"10.1002/jev2.70137","url":null,"abstract":"<p>Extracellular vesicles (EVs) are known to facilitate infection by enveloped RNA viruses including the Human T-cell leukemia virus type-1 (HTLV-1). HTLV-1-encoded proteins, like the transactivator and oncoprotein Tax-1, are loaded into EVs but their precise impact on EV cargos is not yet known. Here, we report a comprehensive interaction map between Tax-1 and the human PDZ (PSD95/DLG/ZO-1) proteins that regulate EVs formation and composition. We show that Tax-1 interacts with more than one-third of hPDZome components, including proteins involved in cell cycle, cell–cell junctions, cytoskeleton organization and membrane complex assembly. We extensively characterized Tax-1 interaction with syntenin-1, an evolutionary conserved PDZ hub that controls EV biogenesis. Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the structural basis of the interaction between the <i>C</i>-terminal PDZ binding motif of Tax-1, and two PDZ domains of syntenin-1. Importantly, we show that a small molecule able to inhibit HTLV-1 cell-to-cell transmission breaks the Tax-1/syntenin-1 interaction, impacts the levels of syntenin-1 and viral proteins in EVs, and shifts the EV composition toward cellular antiviral proteins and microRNAs, including the miR-320 family. Consequently, we demonstrate that mimics of miR-320c, encapsulated into EVs, have antiviral activities with a potential to be used against HTLV-1 induced diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Vault Particles in Cancer Cell Line-Derived Extracellular Vesicle Preparations","authors":"Xinming Liu,&nbsp;Zubair Ahmed Nizamudeen,&nbsp;Christopher J. Hill,&nbsp;Christopher Parmenter,&nbsp;Kenton P. Arkill,&nbsp;Daniel W. Lambert,&nbsp;Stuart Hunt","doi":"10.1002/jev2.70142","DOIUrl":"10.1002/jev2.70142","url":null,"abstract":"<p>Extracellular vesicles (EVs) may contain a variety of molecular cargo, including proteins and nucleic acids. Vault particle components have been repeatedly reported in the literature as EV cargo. Here, we demonstrated that vault RNA (vtRNA) and major vault protein (MVP) were highly abundant in EV pellets enriched by differential centrifugation (DC) by qPCR and western blotting, respectively. RNase and proteinase treatment of DC-derived pellets demonstrated that most vtRNA and MVP were not enclosed and protected within an EV membrane. Vault-like particles were visualised in 100k DC pellets by cryo-transmission electron microscopy. EVs were enriched by size exclusion chromatography, and western blotting of individual fractions showed co-elution of EV markers and vault particle proteins. Immunocapture of EVs post-ultracentrifugation (100k DC pellet) showed co-purification of MVP, whereas EVs isolated by direct immunocapture from conditioned medium were MVP-negative. The current study highlights the importance of determining the topology of putative EV-associated components to determine if they are EV cargo or contaminants that have been co-purified.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse Tumor Tissue-Derived Extracellular Vesicles Induce Angiogenesis Through VEGF Production From Macrophages","authors":"Yae Jin Yoon,&nbsp;Seoyoon Bae,&nbsp;Eun-Jeong Choi,&nbsp;Sang Soo Kim,&nbsp;Solchan Won,&nbsp;Anita Basukala,&nbsp;HaYoung Shin,&nbsp;Jaewook Lee,&nbsp;Jie-Oh Lee,&nbsp;Dong-Sup Lee,&nbsp;Yong Song Gho","doi":"10.1002/jev2.70138","DOIUrl":"10.1002/jev2.70138","url":null,"abstract":"<p>Extracellular vesicles (EVs) are nano-sized, spherical, and lipid bilayered particles secreted by most types of cells. Tumor microenvironment is a complex system and highly regulated by dynamic interaction of cancer cells with stromal cells, such as immune cells and endothelial cells. Angiogenesis, a process of new capillary formation from pre-existing vasculatures, plays a critical role in tumorigenesis and cancer progression by providing oxygen and nutrients to proliferating cancer cells. Since EVs have emerged as important mediators of intercellular communication in pathophysiological circumstances, several studies have reported pro-angiogenic activities of EVs derived from in vitro cultured cancer cells and other cells. However, the angiogenic role of EVs directly isolated from in vivo tumor tissues has not been investigated. Here, we isolated EVs directly from mouse primary tumor tissues with high purity and investigated the angiogenic potential of in vivo tumor tissue-derived EVs (tEVs). The purified tumor tEVs showed EV-like features with nano-sized, spherical, and lipid bilayered structures, and enriched with EV marker proteins such as tetraspanins, while being de-enriched with proteins from Golgi apparatus and nucleus. Interestingly, tumor tEVs promoted extensive neovascularization and numerous macrophage infiltrations in vivo Matrigel plug assay. In addition, the angiogenic properties of tumor tEVs were mediated by the infiltrated macrophages through producing vascular endothelial growth factor (VEGF), a pro-angiogenic molecule. These results suggested that tumor tEVs have potent in vivo angiogenic activity by directly promoting macrophage recruitment and activating infiltrated macrophages to produce VEGF. Our study provides the first direct evidence for a key role of infiltrated macrophage VEGF production in tumor tEV-mediated neovascularization in the tumor microenvironment.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Cortical Actin Depolymerisation in 3D Cell Culture Enhances Extracellular Vesicle Secretion and Therapeutic Effects”","authors":"","doi":"10.1002/jev2.70136","DOIUrl":"10.1002/jev2.70136","url":null,"abstract":"<p>Yang, Z., Li, X., Lin, Q., Zhou, F., Liang, K., Li, J.J., Niu, Y., Meng, Q., Zhao, T., Li, H., Wang, D., Lin, J., Li, H., Wang, B., Liu, W., Du, Y., Lin, J. and Xing, D. (2025), Cortical Actin Depolymerisation in 3D Cell Culture Enhances Extracellular Vesicle Secretion and Therapeutic Effects. J Extracell Vesicles., 14: e70109. https://doi.org/10.1002/jev2.70109</p><p>In the originally published article, the funding information was incorrect. The correct funding information is included below and has been updated in the online version of the article.</p><p>Incorrect</p><p>Funding: This work was funded by grants from Beijing Natural Science Foundation (L222087), Peking University Clinical Scientist Training Program (BMU2024PYJH015, supported by “the Fundamental Research Funds for the Central Universities”), Natural Science Foundation of China (82272538), and Innovation Fund for Outstanding Doctoral Students of Peking University Health Science Center.</p><p>Correct</p><p>Funding: This work was funded by the National Key Research and Development Program of China (Grant Number: 2024YFA1108603), Peking University Clinical Scientist Training Program, supported by the Fundamental Research Funds for the Central Universities (Grant Number: BMU2024PYJH015), National Natural Science Foundation of China (Grant Numbers: 82472482, 82272538), Innovation Fund for Outstanding Doctoral Students of Peking University Health Science Center, and the Natural Science Foundation of Beijing Municipality (Grant Number: L222087).</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exomeres From Adventitial Fibroblasts of Spontaneously Hypertensive Rats Promote Vascular Remodelling via Transferring Osteopontin","authors":"Jing-Xiao Wang,&nbsp;Xiao-Yu Xu,&nbsp;Hong-Ke Dong,&nbsp;Yi-Ming Wang,&nbsp;Min Dai,&nbsp;Bing Zhou,&nbsp;Yue-Hua Li,&nbsp;Guo-Qing Zhu,&nbsp;Xiao-Qing Xiong","doi":"10.1002/jev2.70146","DOIUrl":"10.1002/jev2.70146","url":null,"abstract":"<p>Vascular adventitial fibroblasts (VAFs) contribute to vascular remodelling in hypertension. However, the mechanisms by which VAFs regulate vascular smooth muscle cells (VSMCs) in vascular remodelling are not well known. Here we report the crucial roles of extracellular nanoparticles exomeres (EMs) derived from VAFs in promoting VSMCs proliferation, migration and vascular remodelling in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). VSMCs' proliferation and migration were enhanced by EMs of SHR via the uptake of EMs in VSMCs, but not by EMs of WKY. Proteomics analysis showed that increased osteopontin (OPN) content may be responsible for the roles of EMs of SHR, which was confirmed by the fact that EMs of SHR pretreated with OPN knockdown lost their roles in promoting VSMCs proliferation and migration. OPN successively promoted the phosphorylation of FAK, PI3K and AKT via acting on integrin αVβ3. Inhibition of integrin αVβ3, FAK, PI3K or AKT almost abolished the effects of EMs of SHR on VSMCs proliferation and migration. Knockdown of OPN in the carotid artery attenuated local vascular remodelling in SHR. Repetitive intravenous injection of EMs of SHR increased blood pressure and promoted vascular remodelling in WKY and SHR. We conclude that EMs from VAFs of SHR promote VSMCs proliferation, migration and vascular remodelling via transferring OPN and subsequently activating integrin αVβ3/FAK/PI3K/AKT signalling pathway.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle Protein Panel Enables Early Lung Cancer Detection in a Large Clinical Cohort","authors":"Linxiao Han,&nbsp;Yuanlin Song,&nbsp;Lin Tong,&nbsp;Jiayuan Sun,&nbsp;Xiaoju Zhang,&nbsp;Shujing Chen,&nbsp;Ying Li,&nbsp;Ziqi Wang,&nbsp;Lei Gao,&nbsp;Qiaoliang Zhu,&nbsp;Yencheng Chao,&nbsp;Xiaocen Wang,&nbsp;Ge Zhang,&nbsp;Wensi Zhu,&nbsp;Ludan He,&nbsp;Jie Liu,&nbsp;Qin Wang,&nbsp;Zuoren Wu,&nbsp;Yuanyuan Ji,&nbsp;Chunxue Bai,&nbsp;Xiuzhen Lv,&nbsp;Jian Zhou","doi":"10.1002/jev2.70129","DOIUrl":"10.1002/jev2.70129","url":null,"abstract":"<p>The early detection and diagnosis of lung cancer through extracellular vesicle (EV)-based liquid biopsy show substantial promise for enhancing clinical outcomes. Nonetheless, there is a scarcity of large-scale clinical investigations validating EV-based liquid biopsy. To evaluate the EV membrane protein panel as a diagnostic tool for early-stage cancer detection and validate its efficacy and clinical applicability, a cohort comprised of 302 individuals without cancer and 645 with lung cancer was recruited. Participants were randomly divided into training and validation cohorts at a 1:1 ratio while maintaining the proportion of different subtypes. A diagnostic panel (EV early lung cancer membrane protein 5, EV^ELC-M5) consisting of five EV membrane proteins (CD81, PDL1, GLIPR1, LBR and SFTPA1) was developed using a High-throughput Nano-biochip Integrated System for Liquid Biopsy (HNCIB) to realize rapid analysis of a large cohort of patient samples at a single EV level. EV^ELC-M5 could accurately differentiate patients with early lung cancer from the control group. The area under the curve (AUC) of EV^ELC-M5 for distinguishing patients with early lung cancer from the control group in the validation cohort was 0.926, and the AUC for diagnosing patients with early lung cancer with lung nodules ≤ 8 mm was 0.931. EV-SFTPA1 proved to be the most effective marker, exhibiting a sensitivity of 89.4% in patients with early lung cancer. To our knowledge, this is the first study to use EV-SFTPA1 for early lung cancer detection, elucidating its robust tissue specificity. Collectively, the findings highlight that EV^ELC-M5 in conjunction with HNCIB is an effective diagnostic toolset for detecting early lung cancer and substantially promotes its diagnosis.</p><p><b>Trial Registration</b>: ClinicalTrials.gov identifier: ChiCTR2300072317</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 8","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}