{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:53Z","timestamp":1792806473424,"version":"4.5.0"},"reference-count":171,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology","award":["2024B32"],"award-info":[{"award-number":["2024B32"]}],"id":[{"id":"https:\/\/ror.org\/00p991c53","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a multifaceted systemic condition, with the mechanisms linking intrahepatic lesions to systemic complications remaining a significant enigma in the field. This review posits that extracellular vesicles (EVs) serve as pivotal mediators facilitating communication between the liver and the entire organism. Within the hepatic environment, lipotoxic hepatocyte-derived EVs modulate macrophage populations and stellate cells, thereby promoting inflammatory and fibrotic processes. Systemically, the liver engages in bidirectional communication with adipose tissue, the intestinal tract, the cardiovascular system, and the pancreas via EVs, thus orchestrating metabolic homeostasis. Furthermore, we critically evaluate non-invasive diagnostic strategies and emerging therapies, including both natural and engineered EVs, based on EV-based interventions. We highlight the substantial potential and current challenges associated with achieving precision medicine in MASLD through targeted modulation of this specific communication network.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010116","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:28:12Z","timestamp":1768555692000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease"],"prefix":"10.3390","volume":"18","author":[{"given":"Yu","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current status and future trends of the global burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1136\/gutjnl-2023-330595","article-title":"MASLD: A systemic metabolic disorder with cardiovascular and malignant complications","volume":"73","author":"Targher","year":"2024","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1111\/apt.70020","article-title":"Addressing the High and Rising Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): From the Growing Prevalence to Payors\u2019 Perspective","volume":"61","author":"Younossi","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"156004","DOI":"10.1016\/j.metabol.2024.156004","article-title":"Metabolic dysfunction-associated steatotic liver disease and its link to cancer","volume":"160","author":"Kalligeros","year":"2024","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41573-024-01084-2","article-title":"Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)","volume":"24","author":"Do","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41572-025-00599-1","article-title":"Metabolic dysfunction-associated steatotic liver disease in adults","volume":"11","author":"Huang","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","unstructured":"(2024). European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol., 81, 492\u2013542."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tcb.2016.11.003","article-title":"Extracellular Vesicles: Unique Intercellular Delivery Vehicles","volume":"27","author":"Maas","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101242","DOI":"10.1016\/j.jhepr.2024.101242","article-title":"Macrophage Notch1 signaling modulates regulatory T cells via the TGFB axis in early MASLD","volume":"7","author":"Zhang","year":"2025","journal-title":"JHEP Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.7150\/ijbs.57610","article-title":"Lipotoxic hepatocytes promote nonalcoholic fatty liver disease progression by delivering microRNA-9-5p and activating macrophages","volume":"17","author":"Liu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liao, C.Y., Song, M.J., Gao, Y., Mauer, A.S., Revzin, A., and Malhi, H. (2018). Hepatocyte-Derived Lipotoxic Extracellular Vesicle Sphingosine 1-Phosphate Induces Macrophage Chemotaxis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02980"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/hep.31050","article-title":"Lipotoxic Hepatocyte-Derived Exosomal MicroRNA 192-5p Activates Macrophages Through Rictor\/Akt\/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease","volume":"72","author":"Liu","year":"2020","journal-title":"Hepatology"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1007\/s00125-025-06445-z","article-title":"Effect of lipotoxic hepatocyte-derived extracellular vesicles in pancreas inflammation: Essential role of macrophage TLR4 in beta cell functionality","volume":"68","author":"Alen","year":"2025","journal-title":"Diabetologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrgastro.2017.71","article-title":"Extracellular vesicles in liver disease and potential as biomarkers and therapeutic targets","volume":"14","author":"Szabo","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e0448","DOI":"10.1097\/HC9.0000000000000448","article-title":"Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD","volume":"8","author":"Sakane","year":"2024","journal-title":"Hepatol. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.jhep.2020.07.014","article-title":"Extracellular vesicles as biomarkers in liver diseases: A clinician\u2019s point of view","volume":"73","author":"Thietart","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13287-025-04228-2","article-title":"Mesenchymal stem cell-derived small extracellular vesicles reduced hepatic lipid accumulation in MASLD by suppressing mitochondrial fission","volume":"16","author":"Chen","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13578-023-01122-3","article-title":"Mesenchymal stromal\/stem cells and their extracellular vesicles in liver diseases: Insights on their immunomodulatory roles and clinical applications","volume":"13","author":"Huai","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113816","DOI":"10.1016\/j.addr.2021.05.026","article-title":"Role of extracellular vesicles in liver diseases and their therapeutic potential","volume":"175","author":"Kostallari","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2501349","DOI":"10.1002\/adhm.202501349","article-title":"Molecular Mechanisms of Extracellular Vesicle Biogenesis and Their Impact on the Design of Custom EVs","volume":"14","author":"Pereira","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcdb.2017.08.022","article-title":"Biogenesis and function of ESCRT-dependent extracellular vesicles","volume":"74","author":"Juan","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1073\/pnas.1817898116","article-title":"Growth factor stimulation promotes multivesicular endosome biogenesis by prolonging recruitment of the late-acting ESCRT machinery","volume":"116","author":"Quinney","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-specific regulation of extracellular vesicle biogenesis and cargo selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature08849","article-title":"Molecular mechanism of multivesicular body biogenesis by ESCRT complexes","volume":"464","author":"Wollert","year":"2010","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nature07836","article-title":"Membrane scission by the ESCRT-III complex","volume":"458","author":"Wollert","year":"2009","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.aat1839","article-title":"ATP-dependent force generation and membrane scission by ESCRT-III and Vps4","volume":"362","author":"Schoneberg","year":"2018","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/ncb2502","article-title":"Syndecan-syntenin-ALIX regulates the biogenesis of exosomes","volume":"14","author":"Baietti","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/aps.2017.178","article-title":"Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools","volume":"39","author":"Li","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/s12276-024-01209-y","article-title":"Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer","volume":"56","author":"Lee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1126\/science.1155750","article-title":"Cell biology. No ESCRTs for exosomes","volume":"319","author":"Marsh","year":"2008","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"163","DOI":"10.7150\/ijbs.53671","article-title":"Regulation of exosome production and cargo sorting","volume":"17","author":"Wei","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4146","DOI":"10.1073\/pnas.1200448109","article-title":"Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein","volume":"109","author":"Nabhan","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12951-023-01969-1","article-title":"Apoptotic bodies: Bioactive treasure left behind by the dying cells with robust diagnostic and therapeutic application potentials","volume":"21","author":"Yu","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s12951-025-03362-6","article-title":"Migrasomes as intercellular messengers: Potential in the pathological mechanism, diagnosis and treatment of clinical diseases","volume":"23","author":"Zhang","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.ymthe.2023.02.013","article-title":"Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading","volume":"31","author":"Radler","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113951","DOI":"10.1016\/j.colsurfb.2024.113951","article-title":"Harnessing extracellular vesicle membrane for gene therapy: EVs-biomimetic nanoparticles","volume":"239","author":"Briffault","year":"2024","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113869","DOI":"10.1016\/j.addr.2021.113869","article-title":"Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis","volume":"176","author":"Kumar","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1053\/j.gastro.2015.12.037","article-title":"Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles from Hepatocytes","volume":"150","author":"Hirsova","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1053\/j.gastro.2020.06.031","article-title":"IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis","volume":"159","author":"Dasgupta","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jhep.2019.09.014","article-title":"Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1","volume":"72","author":"Jiang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.metabol.2016.02.014","article-title":"Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease","volume":"65","author":"Mota","year":"2016","journal-title":"Metabolism"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1194\/jlr.M063412","article-title":"Hepatocytes release ceramide-enriched pro-inflammatory extracellular vesicles in an IRE1alpha-dependent manner","volume":"57","author":"Kakazu","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/hep.31031","article-title":"Interleukin-22 Ameliorates Neutrophil-Driven Nonalcoholic Steatohepatitis Through Multiple Targets","volume":"72","author":"Hwang","year":"2020","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165753","DOI":"10.1016\/j.bbadis.2020.165753","article-title":"Chemical hypoxia induces pro-inflammatory signals in fat-laden hepatocytes and contributes to cellular crosstalk with Kupffer cells through extracellular vesicles","volume":"1866","author":"Hernandez","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/hep.28252","article-title":"Mixed lineage kinase 3 mediates release of C-X-C motif ligand 10-bearing chemotactic extracellular vesicles from lipotoxic hepatocytes","volume":"63","author":"Ibrahim","year":"2016","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111738","DOI":"10.1016\/j.yexcr.2019.111738","article-title":"Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122-5p","volume":"387","author":"Zhao","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s12967-024-05283-8","article-title":"Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD","volume":"22","author":"Yang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.freeradbiomed.2022.12.085","article-title":"Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells","volume":"195","author":"Yao","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100756","DOI":"10.1016\/j.jhepr.2023.100756","article-title":"Saturated fatty acid-enriched small extracellular vesicles mediate a crosstalk inducing liver inflammation and hepatocyte insulin resistance","volume":"5","author":"Alen","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jhep.2019.07.019","article-title":"Integrin beta(1)-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH","volume":"71","author":"Guo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Koenen, M.T., Brandt, E.F., Kaczor, D.M., Caspers, T., Heinzmann, A.C.A., Fischer, P., Heinrichs, D., Wirtz, T.H., Trautwein, C., and Koenen, R.R. (2022). Extracellular Vesicles from Steatotic Hepatocytes Provoke Pro-Fibrotic Responses in Cultured Stellate Cells. Biomolecules, 12.","DOI":"10.3390\/biom12050698"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1002\/hep.32662","article-title":"Hepatocyte-derived MASP1-enriched small extracellular vesicles activate HSCs to promote liver fibrosis","volume":"77","author":"Liu","year":"2023","journal-title":"Hepatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s11658-024-00596-4","article-title":"Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy","volume":"29","author":"Li","year":"2024","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.omtn.2021.10.022","article-title":"Hepatocyte-derived exosomal miR-27a activateshepatic stellate cells through the inhibitionof PINK1-mediated mitophagy in MAFLD","volume":"26","author":"Luo","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e2415941","DOI":"10.1002\/advs.202415941","article-title":"LIMA1 O-GlcNAcylation Promotes Hepatic Lipid Deposition through Inducing beta-catenin-Regulated FASn Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"12","author":"Yang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cmet.2022.07.006","article-title":"Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis","volume":"34","author":"Gao","year":"2022","journal-title":"Cell Metab."},{"key":"ref_60","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-gamma","volume":"1","author":"Povero","year":"2015","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"e0759","DOI":"10.1097\/HC9.0000000000000759","article-title":"Hepatocyte-derived Pumilio1-enriched exosomes inhibit HSC activation by suppressing tropomyosin-4 translation","volume":"9","author":"Wan","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/hep.31680","article-title":"Two Faces of Neutrophils in Liver Disease Development and Progression","volume":"74","author":"Cho","year":"2021","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e54446","DOI":"10.15252\/embr.202154446","article-title":"NLRP3 activation in neutrophils induces lethal autoinflammation, liver inflammation, and fibrosis","volume":"23","author":"Kaufmann","year":"2022","journal-title":"EMBO Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"107609","DOI":"10.1016\/j.intimp.2021.107609","article-title":"Neutrophil: An emerging player in the occurrence and progression of metabolic associated fatty liver disease","volume":"97","author":"Chen","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jare.2025.03.015","article-title":"Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis","volume":"79","author":"Xu","year":"2026","journal-title":"J. Adv. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e141513","DOI":"10.1172\/JCI141513","article-title":"Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis","volume":"131","author":"He","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.jhep.2017.02.026","article-title":"Targeting hepatic macrophages to treat liver diseases","volume":"66","author":"Tacke","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41575-018-0082-x","article-title":"The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"16","author":"Kazankov","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41574-022-00675-6","article-title":"Macrophage functional diversity in NAFLD\u2014More than inflammation","volume":"18","author":"Barreby","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.7150\/ijbs.47143","article-title":"Kupffer Cells in Non-alcoholic Fatty Liver Disease: Friend or Foe?","volume":"16","author":"Chen","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e35197","DOI":"10.1016\/j.heliyon.2024.e35197","article-title":"Macrophage-derived exosomal miR-155 regulating hepatocyte pyroptosis in MAFLD","volume":"10","author":"He","year":"2024","journal-title":"Heliyon"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/hep.31658","article-title":"Myeloid-Cell-Specific IL-6 Signaling Promotes MicroRNA-223-Enriched Exosome Production to Attenuate NAFLD-Associated Fibrosis","volume":"74","author":"Hou","year":"2021","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ncrna.2025.04.007","article-title":"Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells","volume":"13","author":"Boonkaew","year":"2025","journal-title":"Noncoding RNA Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s10020-025-01275-6","article-title":"BMDM-derived ORP8 suppresses lipotoxicity and inflammation by relieving endoplasmic reticulum stress in mice with MASH","volume":"31","author":"Chen","year":"2025","journal-title":"Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41575-018-0020-y","article-title":"Liver sinusoidal endothelial cells\u2014Gatekeepers of hepatic immunity","volume":"15","author":"Shetty","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jhep.2019.02.012","article-title":"Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease","volume":"70","author":"Hammoutene","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s12964-024-01720-9","article-title":"Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease","volume":"22","author":"He","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"167020","DOI":"10.1016\/j.bbadis.2024.167020","article-title":"Extracellular vesicles derived from liver sinusoidal endothelial cells inhibit the activation of hepatic stellate cells and Kupffer cells in vitro","volume":"1870","author":"Wang","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12072-023-10559-0","article-title":"Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation","volume":"18","author":"Chen","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"eabd1206","DOI":"10.1126\/scitranslmed.abd1206","article-title":"Targeting epigenetically maladapted vascular niche alleviates liver fibrosis in nonalcoholic steatohepatitis","volume":"13","author":"Zhang","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101506","DOI":"10.1016\/j.diabet.2023.101506","article-title":"Steatotic liver disease, MASLD and risk of chronic kidney disease","volume":"50","author":"Bilson","year":"2024","journal-title":"Diabetes Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12072-024-10660-y","article-title":"MAFLD as part of systemic metabolic dysregulation","volume":"18","author":"Zhao","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature21365","article-title":"Adipose-derived circulating miRNAs regulate gene expression in other tissues","volume":"542","author":"Thomou","year":"2017","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1053\/j.gastro.2021.05.008","article-title":"Associations Among Adipose Tissue Immunology, Inflammation, Exosomes and Insulin Sensitivity in People With Obesity and Nonalcoholic Fatty Liver Disease","volume":"161","author":"Fuchs","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2017.08.035","article-title":"Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity","volume":"171","author":"Ying","year":"2017","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.bbrc.2019.05.113","article-title":"Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance","volume":"515","author":"Liu","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wei, Q., Geng, X., and Fang, G. (2024). Long-Term Aerobic Exercise Enhances Hepatoprotection in MAFLD by Modulating Exosomal miR-324 via ROCK1. Metabolites, 14.","DOI":"10.3390\/metabo14120692"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ajpath.2024.10.006","article-title":"Peroxisome Proliferator-Activated Receptor alpha\/gamma and Cannabinoid Receptor 2 Agonist Attenuated Nonalcoholic Steatohepatitis Exosome-Related Abnormalities in Mice","volume":"195","author":"Huang","year":"2025","journal-title":"Am. J. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2337\/db20-0146","article-title":"A High-Fat Diet Attenuates AMPK alpha1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development In Vivo","volume":"70","author":"Yan","year":"2021","journal-title":"Diabetes"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s42003-024-06171-z","article-title":"Adipocyte-derived exosomes from obstructive sleep apnoea rats aggravate MASLD by TCONS_00039830\/miR-455-3p\/Smad2 axis","volume":"7","author":"Yang","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.freeradbiomed.2020.12.011","article-title":"ER stress-induced adipocytes secrete-aldo-keto reductase 1B7-containing exosomes that cause nonalcoholic steatohepatitis in mice","volume":"163","author":"Gu","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.3748\/wjg.v29.i29.4528","article-title":"Antagonizing adipose tissue-derived exosome miR-103-hepatocyte phosphatase and tensin homolog pathway alleviates autophagy in non-alcoholic steatohepatitis: A trans-cellular crosstalk","volume":"29","author":"Lu","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1053\/j.gastro.2025.03.033","article-title":"Adipose Tissue Macrophages in Metabolic Dysfunction-Associated Steatohepatitis Secrete Extracellular Vesicles That Activate Liver Fibrosis in Obese Male Mice","volume":"169","author":"Rohm","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Lipotoxicity and the gut-liver axis in NASH pathogenesis","volume":"68","author":"Marra","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.3350\/cmh.2024.1090","article-title":"Interventions targeting the gut-liver axis: A potential treatment strategy for metabolic dysfunction-associated steatotic liver disease","volume":"31","author":"Jin","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1136\/gutjnl-2024-332398","article-title":"Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma","volume":"74","author":"Ha","year":"2024","journal-title":"Gut"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2304157","DOI":"10.1080\/19490976.2024.2304157","article-title":"Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus","volume":"16","author":"Forlano","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12951-025-03259-4","article-title":"Extracellular vesicle-mediated bidirectional communication between the liver and other organs: Mechanistic exploration and prospects for clinical applications","volume":"23","author":"Mo","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"G485","DOI":"10.1152\/ajpgi.00362.2020","article-title":"Bacterial and eukaryotic extracellular vesicles and nonalcoholic fatty liver disease: New players in the gut-liver axis?","volume":"320","author":"Villard","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e0048421","DOI":"10.1128\/Spectrum.00484-21","article-title":"The Protective Effects of Live and Pasteurized Akkermansia muciniphila and Its Extracellular Vesicles against HFD\/CCl4-Induced Liver Injury","volume":"9","author":"Ashrafian","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e13827","DOI":"10.1111\/apha.13827","article-title":"Microbial DNA enrichment promotes liver steatosis and fibrosis in the course of non-alcoholic steatohepatitis","volume":"235","author":"Luo","year":"2022","journal-title":"Acta Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1053\/j.gastro.2020.10.042","article-title":"CRIg(+) Macrophages Prevent Gut Microbial DNA-Containing Extracellular Vesicle-Induced Tissue Inflammation and Insulin Resistance","volume":"160","author":"Luo","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e12303","DOI":"10.1002\/jev2.12303","article-title":"Faeces-derived extracellular vesicles participate in the onset of barrier dysfunction leading to liver diseases","volume":"12","author":"Fizanne","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_105","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_106","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12934-021-01709-w","article-title":"Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice","volume":"20","author":"Ashrafian","year":"2021","journal-title":"Microb. Cell Fact."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e70022","DOI":"10.1002\/imt2.70022","article-title":"HLF and PPARalpha axis regulates metabolic-associated fatty liver disease through extracellular vesicles derived from the intestinal microbiota","volume":"4","author":"Yang","year":"2025","journal-title":"Imeta"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1186\/s12967-025-06334-4","article-title":"Colorectal cancer cells-derived exosomal miR-188-3p promotes liver metastasis by creating a pre-metastatic niche via activation of hepatic stellate cells","volume":"23","author":"Li","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13046-024-03204-7","article-title":"Exosomal miR-106a-5p from highly metastatic colorectal cancer cells drives liver metastasis by inducing macrophage M2 polarization in the tumor microenvironment","volume":"43","author":"Liang","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.cmet.2023.04.013","article-title":"Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment","volume":"35","author":"Wang","year":"2023","journal-title":"Cell Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12943-025-02350-6","article-title":"GP73-dependent regulation of exosome biogenesis promotes colorectal cancer liver metastasis","volume":"24","author":"Huang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1136\/gutjnl-2023-331003","article-title":"Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease","volume":"73","author":"Lee","year":"2024","journal-title":"Gut"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"106004","DOI":"10.1016\/j.phrs.2021.106004","article-title":"Overexpression of PDE4D in mouse liver is sufficient to trigger NAFLD and hypertension in a CD36-TGF-beta1 pathway: Therapeutic role of roflumilast","volume":"175","author":"Tao","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.ajpath.2022.12.007","article-title":"Contribution of Hepatic Steatosis-Intensified Extracellular Vesicle Release to Aggravated Inflammatory Endothelial Injury in Liver-Specific Asah1 Gene Knockout Mice","volume":"193","author":"Yuan","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"106690","DOI":"10.1016\/j.ejps.2024.106690","article-title":"Communication between nonalcoholic fatty liver disease and atherosclerosis: Focusing on exosomes","volume":"193","author":"Zhao","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jhep.2023.08.023","article-title":"Hepatic steatosis aggravates atherosclerosis via small extracellular vesicle-mediated inhibition of cellular cholesterol efflux","volume":"79","author":"Chen","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1186\/s12951-021-01137-3","article-title":"Hepatic small extracellular vesicles promote microvascular endothelial hyperpermeability during NAFLD via novel-miRNA-7","volume":"19","author":"Zuo","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e2408660","DOI":"10.1002\/advs.202408660","article-title":"Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle-Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells","volume":"12","author":"Zeng","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1111\/liv.15654","article-title":"Steatotic hepatocyte-derived extracellular vesicles promote beta-cell apoptosis and diabetes via microRNA-126a-3p","volume":"43","author":"Chen","year":"2023","journal-title":"Liver Int."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"a029827","DOI":"10.1101\/cshperspect.a029827","article-title":"Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise","volume":"8","author":"Safdar","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2017.12.001","article-title":"Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise","volume":"27","author":"Whitham","year":"2018","journal-title":"Cell Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cmet.2025.02.009","article-title":"Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk","volume":"37","author":"Zhao","year":"2025","journal-title":"Cell Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e2410439","DOI":"10.1002\/advs.202410439","article-title":"Liver-Secreted Extracellular Vesicles Promote Cirrhosis-Associated Skeletal Muscle Injury Through mtDNA-cGAS\/STING Axis","volume":"12","author":"Fan","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.7150\/thno.108280","article-title":"ROS-responsive MnO(2) mesoporous hydrogel to modulate liver-muscle crosstalk and mitigate NAFLD-associated sarcopenia via exosomal miR-582-5p delivery","volume":"15","author":"Jiang","year":"2025","journal-title":"Theranostics"},{"key":"ref_125","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_126","doi-asserted-by":"crossref","first-page":"106937","DOI":"10.3748\/wjg.v31.i22.106937","article-title":"Extracellular vesicles as biomarkers for metabolic dysfunction-associated steatotic liver disease staging using explainable artificial intelligence","volume":"31","author":"Trifylli","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/hep4.1556","article-title":"Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH","volume":"4","author":"Povero","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1111\/liv.15604","article-title":"Role of EpCAM+ CD133+ extracellular vesicles in steatosis to steatohepatitis transition in NAFLD","volume":"43","author":"Gato","year":"2023","journal-title":"Liver Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"102430","DOI":"10.1016\/j.nano.2021.102430","article-title":"Circulating extracellular vesicles are a biomarker for NAFLD resolution and response to weight loss surgery","volume":"36","author":"Nakao","year":"2021","journal-title":"Nanomedicine"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1007\/s12072-023-10520-1","article-title":"Exosome GLUT1 derived from hepatocyte identifies the risk of non-alcoholic steatohepatitis and fibrosis","volume":"17","author":"Zhang","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/JLB.5A1217-501R","article-title":"Leukocyte extracellular vesicle concentration is inversely associated with liver fibrosis severity in NAFLD","volume":"104","author":"Welsh","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"100838","DOI":"10.1016\/j.bj.2025.100838","article-title":"A panel of miRNAs in the serum extracellular vesicles serve as novel diagnostic biomarkers for MASLD","volume":"48","author":"Hu","year":"2025","journal-title":"Biomed. J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1111\/liv.15581","article-title":"Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis","volume":"43","author":"Rey","year":"2023","journal-title":"Liver Int."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Newman, L.A., Useckaite, Z., Johnson, J., Sorich, M.J., Hopkins, A.M., and Rowland, A. (2022). Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010195"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12951-022-01540-4","article-title":"Lipidomic identification of urinary extracellular vesicles for non-alcoholic steatohepatitis diagnosis","volume":"20","author":"Zhu","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"19186","DOI":"10.1021\/acs.analchem.5c02797","article-title":"In Situ Imaging of Extracellular Vesicles and Non-Alcoholic Fatty Liver Disease with a Near-Infrared Fluorescent Viscosity Probe","volume":"97","author":"Li","year":"2025","journal-title":"Anal. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1002\/ptr.8528","article-title":"Nuciferine Exerts Anti-Inflammatory Effects in Mice With Non-Alcoholic Steatohepatitis by Regulating the miR-23a-3p-SIRT1-NF-kappaB Pathway and Akkermansia muciniphila-Extracellular Vesicles","volume":"39","author":"Zhu","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"119376","DOI":"10.1016\/j.jep.2025.119376","article-title":"Total saponins from Panax japonicus reduced lipid deposition and inflammation in hepatocyte via PHD2 and hepatic macrophage-derived exosomal miR-463-5p","volume":"342","author":"Yang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1002\/hep.29025","article-title":"Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis","volume":"65","author":"McCommis","year":"2017","journal-title":"Hepatology"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Scavo, M.P., Lisco, G., Depalo, N., Rizzi, F., Volpe, S., Arre, V., Carrieri, L., Notarnicola, M., De Nunzio, V., and Curri, M.L. (2024). Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031493"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"30087","DOI":"10.3402\/jev.v4.30087","article-title":"Applying extracellular vesicles based therapeutics in clinical trials\u2014An ISEV position paper","volume":"4","author":"Lener","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.freeradbiomed.2024.04.214","article-title":"RNF31 alleviates liver steatosis by promoting p53\/BNIP3-related mitophagy in hepatocytes","volume":"219","author":"Chen","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jconrel.2023.10.045","article-title":"Multifaceted action of stem cell-derived extracellular vesicles for nonalcoholic steatohepatitis","volume":"364","author":"Kim","year":"2023","journal-title":"J. Control Release"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"100746","DOI":"10.1016\/j.jhepr.2023.100746","article-title":"Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate liver steatosis by promoting fatty acid oxidation and reducing fatty acid synthesis","volume":"5","author":"Yang","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.freeradbiomed.2022.08.037","article-title":"Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate experimental non-alcoholic steatohepatitis via Nrf2\/NQO-1 pathway","volume":"192","author":"Kang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Kim, B., Ronaldo, R., Kweon, B.N., Yoon, S., Park, Y., Baek, J.H., Lee, J.M., and Hyun, C.K. (2024). Mesenchymal Stem Cell-Derived Exosomes Attenuate Hepatic Steatosis and Insulin Resistance in Diet-Induced Obese Mice by Activating the FGF21-Adiponectin Axis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910447"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"116073","DOI":"10.1016\/j.bcp.2024.116073","article-title":"Apical papilla stem cell-derived exosomes regulate lipid metabolism and alleviate inflammation in the MCD-induced mouse NASH model","volume":"222","author":"Nie","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ymthe.2019.10.016","article-title":"HLSC-Derived Extracellular Vesicles Attenuate Liver Fibrosis and Inflammation in a Murine Model of Non-alcoholic Steatohepatitis","volume":"28","author":"Bruno","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13287-025-04197-6","article-title":"Huc-MSCs-derived exosomes alleviate non-alcoholic steatohepatitis by regulating macrophages polarization through miR-24-3p\/STING axis","volume":"16","author":"Jiang","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"114624","DOI":"10.1016\/j.bcp.2021.114624","article-title":"Upregulation of miR-96-5p by bone marrow mesenchymal stem cells and their exosomes alleviate non-alcoholic steatohepatitis: Emphasis on caspase-2 signaling inhibition","volume":"190","author":"AbdelHamid","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1080\/21623945.2022.2098583","article-title":"Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p","volume":"11","author":"Niu","year":"2022","journal-title":"Adipocyte"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.reth.2020.03.012","article-title":"Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles","volume":"14","author":"Watanabe","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12951-021-01120-y","article-title":"Cargo proteins in extracellular vesicles: Potential for novel therapeutics in non-alcoholic steatohepatitis","volume":"19","author":"Kim","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"114325","DOI":"10.1016\/j.yexcr.2024.114325","article-title":"Exosomes derived from diabetic microenvironment-preconditioned mesenchymal stem cells ameliorate nonalcoholic fatty liver disease and inhibit pyroptosis of hepatocytes","volume":"443","author":"Wang","year":"2024","journal-title":"Exp. Cell Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e70125","DOI":"10.1002\/jev2.70125","article-title":"Umbilical Cord-Mesenchymal Stromal Cell-Derived Extracellular Vesicles Target the Liver to Improve Neurovascular Health in Type 2 Diabetes With Non-Alcoholic Fatty Liver Disease","volume":"14","author":"Du","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1186\/s13287-022-03201-7","article-title":"Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model","volume":"13","author":"Shi","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.freeradbiomed.2025.09.010","article-title":"Neonatal liver-derived FTH1-enriched extracellular vesicles attenuate ferroptosis and ameliorate MASLD pathogenesis","volume":"240","author":"Zeng","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"154679","DOI":"10.1016\/j.phymed.2023.154679","article-title":"Garlic-derived exosomes regulate PFKFB3 expression to relieve liver dysfunction in high-fat diet-fed mice via macrophage-hepatocyte crosstalk","volume":"112","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"101039","DOI":"10.1016\/j.crfs.2025.101039","article-title":"Bovine colostrum-derived extracellular vesicles protect against non-alcoholic steatohepatitis by modulating gut microbiota and enhancing gut barrier function","volume":"10","author":"Mun","year":"2025","journal-title":"Curr. Res. Food Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"eade5041","DOI":"10.1126\/sciadv.ade5041","article-title":"Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis","volume":"9","author":"Tong","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e70094","DOI":"10.1002\/jev2.70094","article-title":"Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery","volume":"14","author":"Obuchi","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"31027","DOI":"10.3402\/jev.v5.31027","article-title":"A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery","volume":"5","author":"Hung","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1080\/15548627.2022.2140557","article-title":"LC3-dependent EV loading and secretion (LDELS) promotes TFRC (transferrin receptor) secretion via extracellular vesicles","volume":"19","author":"Gardner","year":"2023","journal-title":"Autophagy"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"103488","DOI":"10.1016\/j.redox.2025.103488","article-title":"Exosome-equipped TNF antisense oligodeoxynucleotide or 2-deoxy-D-glucose ameliorated nonalcoholic steatohepatitis by modulating superoxide dismutase 1 in mice","volume":"80","author":"He","year":"2025","journal-title":"Redox Biol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"9854","DOI":"10.1021\/acsami.3c18029","article-title":"Orally Deliverable Sequence-Targeted Fucoxanthin-Loaded Biomimetic Extracellular Vesicles for Alleviation of Nonalcoholic Fatty Liver Disease","volume":"16","author":"Wu","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"8993","DOI":"10.2147\/IJN.S510937","article-title":"Protective Effects of GalNac-Modified Red Blood Cell-Derived Extracellular Vesicles Against Liver Diseases","volume":"20","author":"Huang","year":"2025","journal-title":"Int. J. Nanomedicine"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"123140","DOI":"10.1016\/j.biomaterials.2025.123140","article-title":"Exosomal miRNA combined with anti-inflammatory hyaluronic acid-based 3D bioprinted hepatic patch promotes metabolic reprogramming in NAFLD-mediated fibrosis","volume":"318","author":"Saha","year":"2025","journal-title":"Biomaterials"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"eaav8521","DOI":"10.1126\/scitranslmed.aav8521","article-title":"Advances in therapeutic applications of extracellular vesicles","volume":"11","author":"Wiklander","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0223-5","article-title":"Extracellular vesicle-based therapeutics: Natural versus engineered targeting and trafficking","volume":"51","author":"Murphy","year":"2019","journal-title":"Exp. Mol. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:33:28Z","timestamp":1768556008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":171,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["pharmaceutics18010116"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18010116","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}