{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T13:40:36Z","timestamp":1794490836629,"version":"4.9.1"},"reference-count":168,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing prevalence of liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), presents considerable medical challenges, particularly given the absence of approved pharmacological treatments, which underscores the necessity to comprehend its underlying mechanisms. Extracellular vesicles (EVs), which are tiny particles released by cells, play a crucial role in facilitating communication and can transport harmful molecules that promote inflammation and tissue damage. These EVs are involved in the progression of various types of liver disorders since they aggravate inflammation and oxidative stress. Because of their critical role, it is believed that EVs are widely involved in the initiation and progression of MASLD, as well as in viral hepatitis, alcoholic liver disease, drug-induced liver injury, and hepatocellular carcinoma. This review emphasizes recent findings regarding the functions of EVs in the above liver pathologies and underscores their potential as new therapeutic targets, paving the way for innovative approaches to address those detrimental liver conditions.<\/jats:p>","DOI":"10.3390\/ijms26115033","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:35:09Z","timestamp":1747982109000},"page":"5033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of Extracellular Vesicles in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease and Other Liver Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-259X","authenticated-orcid":false,"given":"Elena","family":"Grossini","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-4688","authenticated-orcid":false,"given":"Mohammad Mostafa","family":"Ola Pour","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-2574","authenticated-orcid":false,"given":"Sakthipriyan","family":"Venkatesan","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S2468-1253(22)00062-0","article-title":"Global multi-stakeholder endorsement of the MAFLD definition","volume":"7","author":"Bugianesi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1210\/clinem\/dgac321","article-title":"Global Prevalence and Clinical Characteristics of Metabolic-associated Fatty Liver Disease: A Meta-Analysis and Systematic Review of 10 739 607 Individuals","volume":"107","author":"Chan","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e573","DOI":"10.1016\/j.cgh.2021.02.030","article-title":"Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults","volume":"20","author":"Liu","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1007\/s12072-024-10662-w","article-title":"Metabolic dysfunction associated fatty liver disease in healthy weight individuals","volume":"18","author":"Brouwer","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(21)01701-3","article-title":"The EASL-Lancet Liver Commission: Protecting the next generation of Europeans against liver disease complications and premature mortality","volume":"399","author":"Karlsen","year":"2022","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1007\/s12072-023-10568-z","article-title":"Current understanding and future perspectives on the impact of changing NAFLD to MAFLD on global epidemiology and clinical outcomes","volume":"17","author":"Vaz","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jceh.2022.12.005","article-title":"The Growing Economic and Clinical Burden of Nonalcoholic Steatohepatitis (NASH) in the United States","volume":"13","author":"Younossi","year":"2023","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1097\/MEG.0000000000000641","article-title":"Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: Potential implications for pathogenesis","volume":"28","author":"Sprengers","year":"2016","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.cld.2012.08.001","article-title":"Prevalence and natural history of alcoholic liver disease","volume":"16","author":"Schwartz","year":"2012","journal-title":"Clin. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Arroyave-Ospina, J.C., Wu, Z., Geng, Y., and Moshage, H. (2021). Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10020174"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3390\/gastroent14040041","article-title":"Microbiome and Genetic Factors in the Pathogenesis of Liver Diseases","volume":"14","author":"Miteva","year":"2023","journal-title":"Gastroenterol. Insights"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.livres.2022.05.002","article-title":"Non-alcoholic fatty liver disease development: A multifactorial pathogenic phenomena","volume":"6","author":"Bashir","year":"2022","journal-title":"Liver Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.ajpath.2022.06.007","article-title":"The role of extracellular vesicles in liver pathogenesis","volume":"192","author":"Liu","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00604-025-07147-4","article-title":"Limitations and challenges in the characterization of extracellular vesicles from stem cells and serum","volume":"192","author":"Eiro","year":"2025","journal-title":"Mikrochim. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mo, W., Peng, Y., Zheng, Y., Zhao, S., Deng, L., and Fan, X. (2025). Extracellular vesicle-mediated bidirectional communication between the liver and other organs: Mechanistic exploration and prospects for clinical applications. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03259-4"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, A., Arab, J.P., Reyes, D., Lapitz, A., Moshage, H., Ba\u00f1ales, J.M., and Arrese, M. (2020). Extracellular Vesicles in NAFLD\/ALD: From Pathobiology to Therapy. Cells, 9.","DOI":"10.3390\/cells9040817"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41423-020-0391-1","article-title":"The function and clinical application of extracellular vesicles in innate immune regulation","volume":"17","author":"Zhou","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1038\/s41467-020-18311-0","article-title":"Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"S\u0142omka, A., Mocan, T., Wang, B., Nenu, I., Urban, S.K., Gonzales-Carmona, M., Schmidt-Wolf, I.G.H., Lukacs-Kornek, V., Strassburg, C.P., and Sp\u00e2rchez, Z. (2020). EVs as Potential New Therapeutic Tool\/Target in Gastrointestinal Cancer and HCC. Cancers, 12.","DOI":"10.3390\/cancers12103019"},{"key":"ref_22","first-page":"251","article-title":"Extracellular vesicles: Function, resilience, biomarker, bioengineering, and clinical implications","volume":"36","author":"Sun","year":"2024","journal-title":"Tzu Chi Med. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1039\/D0NA00676A","article-title":"Isolation and characterization of extracellular vesicles for clinical applications in cancer\u2014time for standardization?","volume":"3","author":"Salmond","year":"2021","journal-title":"Nanoscale Adv."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hartjes, T.A., Mytnyk, S., Jenster, G.W., van Steijn, V., and van Royen, M.E. (2019). Extracellular Vesicle Quantification and Characterization: Common Methods and Emerging Approaches. Bioengineering, 6.","DOI":"10.3390\/bioengineering6010007"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Berggreen, A.H., Petersen, J.L., Lin, L., Benabdellah, K., and Luo, Y. (2023). CRISPR delivery with extracellular vesicles: Promises and challenges. J. Extracell. Biol., 2.","DOI":"10.1002\/jex2.111"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10571-016-0366-z","article-title":"Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake","volume":"36","author":"Abels","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, M., Wen, Z., Zhang, T., Zhang, L., Liu, X., and Wang, M. (2024). The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1417758"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Qiang, J., Tao, Y.F., Bao, J.W., Chen, J., Li, H.X., He, J., and Xu, P. (2018). High Fat Diet-Induced miR-122 Regulates Lipid Metabolism and Fat Deposition in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) Liver. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01422"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xie, L., Wang, H., Hu, J., Liu, Z., and Hu, F. (2024). The role of novel adipokines and adipose-derived extracellular vesicles (ADEVs): Connections and interactions in liver diseases. Biochem. Pharmacol., 222.","DOI":"10.1016\/j.bcp.2024.116104"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1016\/j.ajpath.2016.06.003","article-title":"Pathogenesis of Kupffer Cells in Cholestatic Liver Injury","volume":"186","author":"Sato","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.actbio.2021.03.075","article-title":"Tumor necrosis factor alpha and interleukin 1 beta suppress myofibroblast activation via nuclear factor kappa B signaling in 3D-cultured mitral valve interstitial cells","volume":"127","author":"Zhu","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nri3607","article-title":"Apoptotic cell clearance: Basic biology and therapeutic potential","volume":"14","author":"Poon","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhao, J., Hu, Y., and Peng, J. (2021). Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): A promising new therapy. Cell. Mol. Biol. Lett., 26.","DOI":"10.1186\/s11658-021-00254-z"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yu, J., Sane, S., Kim, J.E., Yun, S., Kim, H.J., Jo, K.B., Wright, J.P., Khoshdoozmasouleh, N., Lee, K., and Oh, H.T. (2023). Biogenesis and delivery of extracellular vesicles: Harnessing the power of EVs for diagnostics and therapeutics. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1330400"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/s41556-021-00805-8","article-title":"Supermeres are functional extracellular nanoparticles replete with disease biomarkers and therapeutic targets","volume":"23","author":"Zhang","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e16106","DOI":"10.1111\/liv.16106","article-title":"PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease","volume":"45","author":"Speliotes","year":"2025","journal-title":"Liver Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhang, L., and Dong, B. (2024). Molecular mechanisms in MASLD\/MASH-related HCC. Hepatology.","DOI":"10.1097\/HEP.0000000000000786"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/hep.29273","article-title":"The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on lipid droplets by evading ubiquitylation","volume":"66","author":"BasuRay","year":"2017","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/hep.29021","article-title":"TM6SF2 rs58542926 impacts lipid processing in liver and small intestine","volume":"65","author":"Yang","year":"2017","journal-title":"Hepatology"},{"key":"ref_43","first-page":"297","article-title":"Association of GCKR Gene Polymorphisms with the Risk of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in a Chinese Northern Han Population","volume":"7","author":"Gao","year":"2019","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wu, N., Li, J., Zhang, J., Yuan, F., Yu, N., Zhang, F., Li, D., Wang, J., Zhang, L., and Shi, Y. (2023). Waist circumference mediates the association between rs1260326 in GCKR gene and the odds of lean NAFLD. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33753-4"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Juanola, O., Mart\u00ednez-L\u00f3pez, S., Franc\u00e9s, R., and G\u00f3mez-Hurtado, I. (2021). Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18105227"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cmet.2019.12.002","article-title":"Leveraging Human Genetics to Identify Potential New Treatments for Fatty Liver Disease","volume":"31","author":"Romeo","year":"2020","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/hep.28475","article-title":"Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes","volume":"64","author":"Eslam","year":"2016","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2","DOI":"10.21037\/tgh.2019.09.06","article-title":"Genetic and epigenetic disease modifiers: Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD)","volume":"6","author":"Choudhary","year":"2021","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Katz, L.S., Baumel-Alterzon, S., Scott, D.K., and Herman, M.A. (2021). Adaptive and maladaptive roles for ChREBP in the liver and pancreatic islets. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100623"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Geiger, M., Gorica, E., Mohammed, S.A., Mongelli, A., Mengozi, A., Delfine, V., Ruschitzka, F., Costantino, S., and Paneni, F. (2024). Epigenetic Network in Immunometabolic Disease. Adv. Biol., 8.","DOI":"10.1002\/adbi.202300211"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ma, J., Zhang, Y., Li, J., Dang, Y., and Hu, D. (2025). Regulation of histone H3K27 methylation in inflammation and cancer. Mol. Biomed., 6.","DOI":"10.1186\/s43556-025-00254-x"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Perdomo, C.M., Fr\u00fchbeck, G., and Escalada, J. (2019). Impact of Nutritional Changes on Nonalcoholic Fatty Liver Disease. Nutrients, 11.","DOI":"10.3390\/nu11030677"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Muriel, P., L\u00f3pez-S\u00e1nchez, P., and Ramos-Tovar, E. (2021). Fructose and the Liver. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136969"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chait, A., and den Hartigh, L.J. (2020). Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00022"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1111\/obr.12719","article-title":"The effect of exercise training on intrahepatic triglyceride and hepatic insulin sensitivity: A systematic review and meta-analysis","volume":"19","author":"Sargeant","year":"2018","journal-title":"Obes. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1186\/s12967-023-04367-1","article-title":"Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: New insights from pathogenic mechanisms to clinically targeted therapy","volume":"21","author":"Zheng","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1265\/ehpm.23-00271","article-title":"Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease","volume":"29","author":"Cheng","year":"2024","journal-title":"Environ. Health Prev. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1055\/a-1792-4240","article-title":"Circadian Regulation of Gene Expression and Metabolism in the Liver","volume":"42","author":"Guan","year":"2022","journal-title":"Semin. Liver Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1016\/j.metabol.2016.09.006","article-title":"Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity","volume":"65","author":"Chung","year":"2016","journal-title":"Metabolism"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Della Torre, S. (2021). Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology. Cells, 10.","DOI":"10.3390\/cells10092502"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kim, S.E., Min, J.S., Lee, S., Lee, D.Y., and Choi, D. (2023). Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-42788-6"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.transproceed.2006.11.021","article-title":"Role of reactive oxygen species in mediating hepatic ischemia-reperfusion injury and its therapeutic applications in liver transplantation","volume":"39","author":"Zhang","year":"2007","journal-title":"Transplant. Proc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1210\/er.2009-0003","article-title":"The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance","volume":"31","author":"Bao","year":"2010","journal-title":"Endocr Rev."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Zhou, Y., Wang, D., Huang, Z., Xiao, X., Zheng, Q., Li, S., Long, D., and Feng, L. (2023). Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417514"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lange, N.F., Graf, V., Caussy, C., and Dufour, J.F. (2022). PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084305"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101115","DOI":"10.1016\/j.gendis.2023.101115","article-title":"Mitochondrial dysfunction: A promising therapeutic target for liver diseases","volume":"11","author":"Chen","year":"2024","journal-title":"Genes Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8837893","DOI":"10.1155\/2020\/8837893","article-title":"Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment","volume":"2020","author":"Jiang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/jcp.25098","article-title":"Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases","volume":"231","author":"Cao","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1016\/j.ajpath.2023.08.007","article-title":"The Role of Endoplasmic Reticulum in Lipotoxicity during Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathogenesis","volume":"193","author":"Venkatesan","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/s41392-023-01570-w","article-title":"Endoplasmic reticulum stress: Molecular mechanism and therapeutic targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41467-020-14450-6","article-title":"Liver governs adipose remodelling via extracellular vesicles in response to lipid overload","volume":"11","author":"Zhao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12672-023-00704-4","article-title":"Adipocyte-derived extracellular vesicles: Bridging the communications between obesity and tumor microenvironment","volume":"14","author":"Zhou","year":"2023","journal-title":"Discov. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.7150\/ijbs.59588","article-title":"MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease","volume":"17","author":"Fang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"101581","DOI":"10.1016\/j.molmet.2022.101581","article-title":"MicroRNAs in non-alcoholic fatty liver disease: Progress and perspectives","volume":"65","author":"Hochreuter","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101349","DOI":"10.1016\/j.molmet.2021.101349","article-title":"The hepatocyte IKK:NF-\u03baB axis promotes liver steatosis by stimulating de novo lipogenesis and cholesterol synthesis","volume":"54","author":"Heida","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Hajduch, E., Lachkar, F., Ferr\u00e9, P., and Foufelle, F. (2021). Roles of Ceramides in Non-Alcoholic Fatty Liver Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040792"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1038\/s12276-023-01071-4","article-title":"Lipid remodeling of adipose tissue in metabolic health and disease","volume":"55","author":"Cho","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Li, S., Cheng, F., Zhang, Z., Xu, R., Shi, H., and Yan, Y. (2024). The role of hepatocyte-derived extracellular vesicles in liver and extrahepatic diseases. Biomed. Pharmacother., 180.","DOI":"10.1016\/j.biopha.2024.117502"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"eads5249","DOI":"10.1126\/sciadv.ads5249","article-title":"Leveraging nature\u2019s nanocarriers: Translating insights from extracellular vesicles to biomimetic synthetic vesicles for biomedical applications","volume":"11","author":"Chen","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3892\/mmr.2023.13076","article-title":"Adipose tissue-derived extracellular vesicles: Systemic messengers in health and disease (Review)","volume":"28","author":"Yang","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1042\/BJ20041896","article-title":"A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver","volume":"389","author":"Knight","year":"2005","journal-title":"Biochem. J."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Xu, G.-X., Wei, S., Yu, C., Zhao, S.-Q., Yang, W.-J., Feng, Y.-H., Pan, C., Yang, K.-X., and Ma, Y. (2023). Activation of Kupffer cells in NAFLD and NASH: Mechanisms and therapeutic interventions. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1199519"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/JLB.3MIR0321-156R","article-title":"Extracellular vesicles in inflammation: Focus on the microRNA cargo of EVs in modulation of liver diseases","volume":"111","author":"Babuta","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1161\/ATVBAHA.118.311916","article-title":"Targeting NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome in Cardiovascular Disorders","volume":"38","author":"Wang","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Tao, Y., Zhao, H., and Wang, Q. (2021). Adipose Extracellular Vesicles: Messengers From and to Macrophages in Regulating Immunometabolic Homeostasis or Disorders. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.666344"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jare.2024.03.009","article-title":"The role of extracellular vesicles in non-alcoholic steatohepatitis: Emerging mechanisms, potential therapeutics and biomarkers","volume":"69","author":"Wang","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Catitti, G., De Bellis, D., Vespa, S., Simeone, P., Canonico, B., and Lanuti, P. (2022). Extracellular Vesicles as Players in the Anti-Inflammatory Inter-Cellular Crosstalk Induced by Exercise Training. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214098"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-022-00763-8","article-title":"The roles of extracellular vesicles in the immune system","volume":"23","author":"Buzas","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kolonics, F., Szeifert, V., Tim\u00e1r, C.I., Ligeti, E., and L\u0151rincz, \u00c1.M. (2020). The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell. Cells, 9.","DOI":"10.3390\/cells9122718"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Li, J., Yuan, Y., Fu, Q., Chen, M., Liang, H., Chen, X., Long, X., Zhang, B., Zhao, J., and Chen, Q. (2024). Novel insights into the role of immunomodulatory extracellular vesicles in the pathogenesis of liver fibrosis. Biomark. Res., 12.","DOI":"10.1186\/s40364-024-00669-8"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jcmgh.2015.07.007","article-title":"Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-\u03b3","volume":"1","author":"Povero","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Taboada, M., Corrales, P., Medina-G\u00f3mez, G., and Vila-Bedmar, R. (2022). Tackling the effects of extracellular vesicles in fibrosis. Eur. J. Cell Biol., 101.","DOI":"10.1016\/j.ejcb.2022.151221"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41392-024-01993-z","article-title":"Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1\/Notch1","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Gonz\u00e1lez, S., Mar\u00edn-Royo, G., Jurado-L\u00f3pez, R., Bartolom\u00e9, M.V., Romero-Miranda, A., Luaces, M., Islas, F., Nieto, M.L., Mart\u00ednez-Mart\u00ednez, E., and Cachofeiro, V. (2020). The Crosstalk between Cardiac Lipotoxicity and Mitochondrial Oxidative Stress in the Cardiac Alterations in Diet-Induced Obesity in Rats. Cells, 9.","DOI":"10.3390\/cells9020451"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Berdiaki, A., Neagu, M., Tzanakakis, P., Spyridaki, I., P\u00e9rez, S., and Nikitovic, D. (2024). Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease. Biomolecules, 14.","DOI":"10.3390\/biom14091186"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zhao, J., Jiang, M., Peng, D., Dou, X., Song, Y., and Shi, J. (2022). The Potential Role of Gut Microbial-Derived Exosomes in Metabolic-Associated Fatty Liver Disease: Implications for Treatment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.893617"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e12474","DOI":"10.1002\/jev2.12474","article-title":"Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis","volume":"13","author":"Jain","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Papadakos, S.P., Arvanitakis, K., Stergiou, I.E., Vallilas, C., Sougioultzis, S., Germanidis, G., and Theocharis, S. (2023). Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102460"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e12466","DOI":"10.1002\/jev2.12466","article-title":"Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles","volume":"13","author":"Zhang","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1159\/000450981","article-title":"Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation","volume":"35","author":"Chiang","year":"2017","journal-title":"Dig. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e12161","DOI":"10.1002\/jev2.12161","article-title":"Microbiota-derived extracellular vesicles in interkingdom communication in the gut","volume":"10","author":"Badia","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1002\/j.2040-4603.2023.tb00279.x","article-title":"Energetic Stress-Induced Metabolic Regulation by Extracellular Vesicles","volume":"13","author":"Crewe","year":"2023","journal-title":"Compr. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12944-024-02396-3","article-title":"Extracellular vesicle-mediated approaches for the diagnosis and therapy of MASLD: Current advances and future prospective","volume":"24","author":"Gurjar","year":"2025","journal-title":"Lipids Health Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e12382","DOI":"10.1002\/jev2.12382","article-title":"High-fat diets: You are what you eat\u2026.your extracellular vesicles too!","volume":"13","author":"Rome","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s10020-024-00900-0","article-title":"Antibiotic-induced gut microbiota disruption promotes vascular calcification by reducing short-chain fatty acid acetate","volume":"30","author":"Zeng","year":"2024","journal-title":"Mol. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Lozano, E., Garc\u00eda-Garc\u00eda, J., G\u00e1lvez, J., Hidalgo-Garc\u00eda, L., Rodr\u00edguez-Nogales, A., Rodr\u00edguez-Cabezas, M.E., and S\u00e1nchez, M. (2022). Novel Horizons in Postbiotics: Lactobacillaceae Extracellular Vesicles and Their Applications in Health and Disease. Nutrients, 14.","DOI":"10.3390\/nu14245296"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Li, J., Shi, M., Wang, Y., Liu, J., Liu, S., Kang, W., Liu, X., Chen, X., Huang, K., and Liu, Y. (2024). Probiotic-derived extracellular vesicles alleviate AFB1-induced intestinal injury by modulating the gut microbiota and AHR activation. J. Nanobiotechnol., 22.","DOI":"10.21203\/rs.3.rs-3628421\/v1"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s11011-025-01554-5","article-title":"Gut microbiota-derived short chain fatty acids act as mediators of the gut-liver-brain axis","volume":"40","author":"Li","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.celrep.2018.01.058","article-title":"MicroRNA-223 Suppresses the Canonical NF-\u03baB Pathway in Basal Keratinocytes to Dampen Neutrophilic Inflammation","volume":"22","author":"Zhou","year":"2018","journal-title":"Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.cmet.2025.01.016","article-title":"Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism","volume":"37","author":"Jiang","year":"2025","journal-title":"Cell Metab."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Kouroumalis, E., Tsomidis, I., and Voumvouraki, A. (2024). Extracellular Vesicles in Viral Liver Diseases. Viruses, 16.","DOI":"10.3390\/v16111785"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Wu, X., Niu, J., and Shi, Y. (2024). Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02544-y"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/cei\/uxae026","article-title":"The role of extracellular vesicle immune checkpoints in cancer","volume":"216","author":"Zhang","year":"2024","journal-title":"Clin. Exp. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Picca, A., Guerra, F., Calvani, R., Coelho-J\u00fanior, H.J., Landi, F., Bernabei, R., Romano, R., Bucci, C., and Marzetti, E. (2020). Extracellular Vesicles and Damage-Associated Molecular Patterns: A Pandora\u2019s Box in Health and Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.601740"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"706","DOI":"10.3350\/cmh.2021.0390","article-title":"The emerging roles of extracellular vesicles as intercellular messengers in liver physiology and pathology","volume":"28","author":"Lee","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Zhu, J., Wang, S., Yang, D., Xu, W., and Qian, H. (2023). Extracellular vesicles: Emerging roles, biomarkers and therapeutic strategies in fibrotic diseases. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01921-3"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.pharmthera.2018.03.009","article-title":"Extracellular vesicles as potential biomarkers for alcohol- and drug-induced liver injury and their therapeutic applications","volume":"187","author":"Cho","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s00109-020-01926-7","article-title":"Comprehensive characterization of hepatocyte-derived extracellular vesicles identifies direct miRNA-based regulation of hepatic stellate cells and DAMP-based hepatic macrophage IL-1\u03b2 and IL-17 upregulation in alcoholic hepatitis mice","volume":"98","author":"Eguchi","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11481-019-09848-z","article-title":"Extracellular Vesicles: Intercellular Mediators in Alcohol-Induced Pathologies","volume":"15","author":"Rahman","year":"2020","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.apsb.2020.12.014","article-title":"Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses","volume":"11","author":"Hu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2393272","DOI":"10.1080\/19490976.2024.2393272","article-title":"Ethanol-induced changes to the gut microbiome compromise the intestinal homeostasis: A review","volume":"16","author":"Sosnowski","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1755-1536-3-21","article-title":"Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis","volume":"3","author":"Guo","year":"2010","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jare.2024.07.002","article-title":"The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD","volume":"72","author":"Cheng","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular vesicles as tools and targets in therapy for diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1002\/hep.29732","article-title":"Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90","volume":"67","author":"Saha","year":"2018","journal-title":"Hepatology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/bs.acc.2020.08.010","article-title":"Extracellular vesicles: Roles and applications in drug-induced liver injury","volume":"102","author":"Umbaugh","year":"2021","journal-title":"Adv. Clin. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1073\/pnas.0813371106","article-title":"Circulating microRNAs, potential biomarkers for drug-induced liver injury","volume":"106","author":"Wang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-019-0105-0","article-title":"Drug-induced liver injury","volume":"5","author":"Andrade","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejps.2016.10.020","article-title":"Metabolically active extracellular vesicles released from hepatocytes under drug-induced liver-damaging conditions modify serum metabolome and might affect different pathophysiological processes","volume":"98","author":"Royo","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Seay, T.W., and Suo, Z. (2023). Roles of Extracellular Vesicles on the Progression and Metastasis of Hepatocellular Carcinoma. Cells, 12.","DOI":"10.3390\/cells12141879"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Olejarz, W., Kubiak-Tomaszewska, G., Chrzanowska, A., and Lorenc, T. (2020). Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165840"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"107419","DOI":"10.1016\/j.phrs.2024.107419","article-title":"Extracellular vesicles in the HCC microenvironment: Implications for therapy and biomarkers","volume":"209","author":"Cheng","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Belhabib, I., Zaghdoudi, S., Lac, C., Bousquet, C., and Jean, C. (2021). Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?. Cancers, 13.","DOI":"10.3390\/cancers13143466"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12943-025-02233-w","article-title":"Extracellular vesicles in tumor immunity: Mechanisms and novel insights","volume":"24","author":"Kuang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12964-021-00816-w","article-title":"Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: Biological function and potential therapy strategies","volume":"20","author":"Liu","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"100920","DOI":"10.1016\/j.jpha.2023.12.010","article-title":"Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects","volume":"14","author":"Cheng","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s13046-018-0965-2","article-title":"Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts","volume":"37","author":"Zhou","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Hu, S., Luo, Y., and He, K. (2023). Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15092365"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Mauro, M., Ugo, P., Walton, Z., Ali, S., Rastellini, C., and Cicalese, L. (2023). Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310922"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Sun, J., Zhang, D., and Li, Y. (2022). Extracellular Vesicles in Pathogenesis and Treatment of Metabolic Associated Fatty Liver Disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.909518"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Lee, Y.S., Kim, S.Y., Ko, E., Lee, J.H., Yi, H.S., Yoo, Y.J., Je, J., Suh, S.J., Jung, Y.K., and Kim, J.H. (2017). Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-03389-2"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3748\/wjg.v27.i14.1419","article-title":"Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease","volume":"27","author":"Luo","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1007\/s00535-021-01765-4","article-title":"Emerging role and therapeutic application of exosome in hepatitis virus infection and associated diseases","volume":"56","author":"Shi","year":"2021","journal-title":"J. Gastroenterol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/hep.1840160225","article-title":"Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: Association of lipid peroxidation with liver fibrogenesis","volume":"16","author":"Kamimura","year":"1992","journal-title":"Hepatology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s13679-024-00574-z","article-title":"Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review From NAFLD to MAFLD and MASLD","volume":"13","author":"Abdelhameed","year":"2024","journal-title":"Curr. Obes. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"102121","DOI":"10.1016\/j.tranon.2024.102121","article-title":"A comprehensive review on recent advances in exosome isolation and characterization: Toward clinical applications","volume":"50","author":"Dilsiz","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Rodrigues-Junior, D.M., Tsirigoti, C., Lim, S.K., Heldin, C.H., and Moustakas, A. (2022). Extracellular Vesicles and Transforming Growth Factor \u03b2 Signaling in Cancer. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.849938"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e33741","DOI":"10.1016\/j.heliyon.2024.e33741","article-title":"Extracellular vesicles-derived ferritin from lipid-induced hepatocytes regulates activation of hepatic stellate cells","volume":"10","author":"Sun","year":"2024","journal-title":"Heliyon"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Yoo, D., Jung, S.Y., Go, D., Park, J.Y., You, D.G., Jung, W.K., Li, Y., Ding, J., Park, J.H., and Um, W. (2025). Functionalized extracellular vesicles of mesenchymal stem cells for regenerative medicine. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03300-6"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Gong, Y., You, Q., Yuan, X., Zeng, F., Zhang, F., Xiao, J., Chen, H., Liu, Y., Wang, T., and Yan, X. (2025). Mesenchymal stem cell-derived extracellular vesicles attenuate ferroptosis in aged hepatic ischemia\/reperfusion injury by transferring miR-1275. Redox Biol., 81.","DOI":"10.1016\/j.redox.2025.103556"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13027-023-00549-0","article-title":"Engineered small extracellular vesicles as a novel platform to suppress human oncovirus-associated cancers","volume":"18","author":"Owliaee","year":"2023","journal-title":"Infect. Agent. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2284286","DOI":"10.1080\/22221751.2023.2284286","article-title":"Engineered extracellular vesicles for delivering functional Cas9\/gRNA to eliminate hepatitis B virus cccDNA and integration","volume":"13","author":"Zeng","year":"2024","journal-title":"Emerg. Microbes. Infect."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Li, Q., Han, J., Yang, Y., and Chen, Y. (2022). PD-1\/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1070961"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s00018-022-04256-8","article-title":"Circulating cell-specific extracellular vesicles as biomarkers for the diagnosis and monitoring of chronic liver diseases","volume":"79","author":"Newman","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Lim, H.K., Jeffrey, G.P., Ramm, G.A., and Soekmadji, C. (2020). Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.587628"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"10407","DOI":"10.1128\/JVI.01184-15","article-title":"Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection","volume":"89","author":"Reynolds","year":"2015","journal-title":"J. Virol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"De Sousa, K.P., Rossi, I., Abdullahi, M., Ramirez, M.I., Stratton, D., and Inal, J.M. (2023). Isolation and characterization of extracellular vesicles and future directions in diagnosis and therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 15.","DOI":"10.1002\/wnan.1835"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.livres.2025.02.002","article-title":"Bioengineered extracellular vesicles: The path to precision medicine in liver diseases","volume":"9","author":"Mittal","year":"2025","journal-title":"Liver Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1002\/j.2040-4603.2023.tb00263.x","article-title":"Extracellular Vesicles in Hepatobiliary Health and Disease","volume":"13","author":"Parthasarathy","year":"2023","journal-title":"Compr. Physiol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Shaba, E., Vantaggiato, L., Governini, L., Haxhiu, A., Sebastiani, G., Fignani, D., Grieco, G.E., Bergantini, L., Bini, L., and Landi, C. (2022). Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone. Proteomes, 10.","DOI":"10.20944\/preprints202203.0256.v1"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"19980","DOI":"10.1021\/acsnano.2c11298","article-title":"Analysis and Biomedical Applications of Functional Cargo in Extracellular Vesicles","volume":"16","author":"Qian","year":"2022","journal-title":"ACS Nano"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"114974","DOI":"10.1016\/j.addr.2023.114974","article-title":"Towards artificial intelligence-enabled extracellular vesicle precision drug delivery","volume":"199","author":"Greenberg","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1038\/s41596-021-00551-z","article-title":"Using single-vesicle technologies to unravel the heterogeneity of extracellular vesicles","volume":"16","author":"Royo","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"11619","DOI":"10.1021\/acsnano.2c04337","article-title":"Future of Digital Assays to Resolve Clinical Heterogeneity of Single Extracellular Vesicles","volume":"16","author":"Morales","year":"2022","journal-title":"ACS Nano"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Lawrence, S.R., and Shah, K.M. (2024). Prospects and Current Challenges of Extracellular Vesicle-Based Biomarkers in Cancer. Biology, 13.","DOI":"10.3390\/biology13090694"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/gutjnl-2023-331740","article-title":"Artificial intelligence applied to \u2018omics data in liver disease: Towards a personalised approach for diagnosis, prognosis and treatment","volume":"74","author":"Ghosh","year":"2025","journal-title":"Gut"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"4","DOI":"10.37349\/edd.2022.00002","article-title":"Extracellular vesicles in metabolic dysfunction associated fatty liver disease: Mechanisms, diagnostic and therapeutic implications","volume":"1","author":"Wu","year":"2022","journal-title":"Explor. Dig. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:39:07Z","timestamp":1760031547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":168,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115033"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115033","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]}}}