{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:14:33Z","timestamp":1785406473556,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Technology","award":["109-2320-B-039-041-"],"award-info":[{"award-number":["109-2320-B-039-041-"]}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-115-127"],"award-info":[{"award-number":["DMR-115-127"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DMR-115-127"],"award-info":[{"award-number":["DMR-115-127"]}],"id":[{"id":"https:\/\/ror.org\/0368s4g32","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"publisher","award":["CMU-113-S-35"],"award-info":[{"award-number":["CMU-113-S-35"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CMU-113-S-35"],"award-info":[{"award-number":["CMU-113-S-35"]}],"id":[{"id":"https:\/\/ror.org\/00v408z34","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hualien Tzu Chi Medical Center","award":["TCRD113-069"],"award-info":[{"award-number":["TCRD113-069"]}]},{"award":["TCRD113-069"],"award-info":[{"award-number":["TCRD113-069"]}],"id":[{"id":"https:\/\/ror.org\/030k6vb67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatohepatitis (MASH; formerly non-alcoholic steatohepatitis, NASH) is characterized by oxidative stress, inflammatory activation, hepatocellular injury, and progressive liver dysfunction. However, the global transcriptomic landscape underlying stress-induced hepatic injury remains incompletely understood. In this study, we employed a methionine\u2013choline-deficient (MCD) diet-induced murine model to characterize the phenotypic and transcriptomic alterations associated with liver injury. Male C57BL\/6J mice were fed either a control or MCD diet, and hepatotoxicity was assessed by survival analysis, body and liver weight measurements, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, histopathological examination, RNA sequencing, quantitative real-time PCR (qRT-PCR), and tumor necrosis factor-alpha (TNF-\u03b1) enzyme-linked immunosorbent assay (ELISA). MCD feeding markedly reduced survival and body weight while inducing hepatomegaly and significant elevations in serum ALT and AST, indicating severe hepatocellular injury. Histopathological analysis demonstrated hepatic steatosis, hepatocellular ballooning, and lobular inflammation without histological evidence of fibrosis. Transcriptomic profiling revealed extensive gene expression remodeling, characterized by activation of inflammatory pathways, enrichment of MAPK-related signaling, dysregulation of lipid metabolism, suppression of antioxidant defense systems, impairment of cytochrome P450-mediated detoxification, and upregulation of apoptosis-associated genes. qRT-PCR further validated the differential expression of representative genes involved in inflammatory signaling (Tlr4, Nfkb1, Nlrp3, and Casp1), MAPK signaling (Fos), xenobiotic metabolism (Cyp4f18), lipid metabolism (Apoa4 and Lpl), extracellular matrix remodeling (Mmp12), and oxidative stress responses (Sod1 and Gstp1). In addition, elevated serum TNF-\u03b1 levels provided protein-level evidence supporting activation of the TLR4\/NF-\u03baB\/TNF-\u03b1\/NLRP3 inflammatory axis. Although fibrosis-associated transcriptional responses were detected, the absence of histological fibrosis suggests transcriptional priming of fibrogenic pathways rather than established fibrogenesis. Collectively, these findings provide a transcriptomic framework linking oxidative stress, impaired detoxification, inflammatory activation, and stress-responsive signaling to MCD-induced hepatic injury. The MCD model provides a valuable experimental platform for characterizing hepatic stress-response transcriptomes and for generating hypotheses that can subsequently be evaluated in environmentally relevant toxicological models. Nevertheless, caution should be exercised when extrapolating these findings to obesity-associated human MASLD, as the MCD model lacks key metabolic features of the human disease, including obesity and insulin resistance. Therefore, the present findings should be interpreted primarily as transcriptomic signatures of stress-induced hepatic injury rather than as a direct representation of the pathophysiological processes underlying human obesity-associated MASLD.<\/jats:p>","DOI":"10.3390\/ijms27136033","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Profiling Reveals Inflammatory, Fibrotic, and Apoptotic Signatures in a Methionine\u2013Choline-Deficient Diet-Induced Murine Model of Metabolism-Dysfunction-Associated Steatohepatitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-6760","authenticated-orcid":false,"given":"Yih-Dih","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"School of Pharmacy, College of Pharmacy, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yi","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"},{"name":"Graduate Institute of Clinical Pharmacy, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"},{"name":"Department of Pharmacy, College of Medicine, Tzu Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan"},{"name":"Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miau-Rong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-607X","authenticated-orcid":false,"given":"Shih-Chang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-8248","authenticated-orcid":false,"given":"Jai-Sing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3390\/biom15010140","article-title":"Drug Advances in NAFLD: Individual and Combination Treatment Strategies of Natural Products and Small-Synthetic-Molecule Drugs","volume":"15","author":"Wan","year":"2025","journal-title":"Biomolecules"},{"key":"ref_2","first-page":"568","article-title":"Non-alcoholic fatty liver disease--new view","volume":"24","author":"Lawniczak","year":"2008","journal-title":"Pol. Merkur. Lek."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1600-6143.2004.00432.x","article-title":"Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and orthotopic liver transplantation","volume":"4","author":"Burke","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97500","DOI":"10.3748\/wjg.v31.i5.97500","article-title":"What is the role of nonalcoholic fatty liver disease in pulmonary carcinoma development?","volume":"31","author":"Pan","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.clnesp.2024.11.032","article-title":"Dietary inflammatory potential and metabolic (dysfunction)-associated steatotic liver disease and its complications: A comprehensive review","volume":"65","author":"Sepehrinia","year":"2025","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41575-023-00754-7","article-title":"Nonalcoholic steatohepatitis-related hepatocellular carcinoma: Pathogenesis and treatment","volume":"20","author":"Llovet","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3390\/cells14020084","article-title":"Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD\/NASH Progression and Potential Applications in Immunotherapy-Based Strategies","volume":"14","author":"Monti","year":"2025","journal-title":"Cells"},{"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":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/ng.257","article-title":"Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease","volume":"40","author":"Romeo","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s40572-019-00232-w","article-title":"Mechanisms of Environmental Contributions to Fatty Liver Disease","volume":"6","author":"Wahlang","year":"2019","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"136865","DOI":"10.1016\/j.jhazmat.2024.136865","article-title":"A digestive system microphysiological platform for assessment of internal-exposure risks and metabolic disease mechanisms induced by multi-size nano-plastics","volume":"485","author":"Li","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.biopha.2018.08.104","article-title":"Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors","volume":"107","author":"Abass","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1210\/en.2017-00887","article-title":"Endocrine Disruptors and Developmental Origins of Nonalcoholic Fatty Liver Disease","volume":"159","author":"Trevino","year":"2018","journal-title":"Endocrinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/toxsci\/kfw018","article-title":"Tipping the Balance: Hepatotoxicity and the 4 Apical Key Events of Hepatic Steatosis","volume":"150","author":"Angrish","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jhep.2023.10.018","article-title":"Circadian dysfunction induces NAFLD-related human liver cancer in a mouse model","volume":"80","author":"Padilla","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_18","first-page":"439","article-title":"Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders","volume":"75","author":"Chen","year":"2023","journal-title":"Sheng Li Xue Bao"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1007\/s00204-021-03118-9","article-title":"Sex-dependent dynamics of metabolism in primary mouse hepatocytes","volume":"95","author":"Hochmuth","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/DDDT.S500719","article-title":"A Review of the Therapeutic Potential of Ginseng and Its Bioactive Components in Nonalcoholic Fatty Liver Disease","volume":"19","author":"Hao","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/jpn3.12402","article-title":"Pharmacological management of pediatric metabolic dysfunction-associated steatotic liver disease","volume":"80","author":"Hartmann","year":"2025","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/ptr.8362","article-title":"Lack of Efficacy of Pomegranate Supplementation on Insulin Resistance and Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"39","author":"Yin","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4166\/kjg.2013.61.5.243","article-title":"The role of diet in non-alcoholic fatty liver disease","volume":"61","author":"Jun","year":"2013","journal-title":"Korean J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.3390\/ijms25137405","article-title":"Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison","volume":"25","author":"Veskovic","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"858","DOI":"10.3390\/molecules27030858","article-title":"A Comparison of the Gene Expression Profiles of Non-Alcoholic Fatty Liver Disease between Animal Models of a High-Fat Diet and Methionine-Choline-Deficient Diet","volume":"27","author":"Alshawsh","year":"2022","journal-title":"Molecules"},{"key":"ref_26","first-page":"159545","article-title":"A methionine-choline-deficient diet induces nonalcoholic steatohepatitis and alters the lipidome, metabolome, and gut microbiome profile in the C57BL\/6J mouse","volume":"1869","author":"Gautam","year":"2024","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1080\/00365520903114912","article-title":"Antioxidants vitamin E and 1-aminobenzotriazole prevent experimental non-alcoholic steatohepatitis in mice","volume":"44","author":"Nan","year":"2009","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/hep.26749","article-title":"Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH","volume":"59","author":"Sutti","year":"2014","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejphar.2019.01.043","article-title":"Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt\/mTOR signaling in methionine-choline deficiency-induced fatty liver disease","volume":"848","author":"Veskovic","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/labinvest.2010.75","article-title":"Blockade of interleukin-6 signaling enhances hepatic steatosis but improves liver injury in methionine choline-deficient diet-fed mice","volume":"90","author":"Yamaguchi","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/labinvest.2011.2","article-title":"Blockade of IL-6 signaling exacerbates liver injury and suppresses antiapoptotic gene expression in methionine choline-deficient diet-fed db\/db mice","volume":"91","author":"Yamaguchi","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1080\/13880209.2021.1945112","article-title":"Esculin protects against methionine choline-deficient diet-induced non-alcoholic steatohepatitis by regulating the Sirt1\/NF-kappaB p65 pathway","volume":"59","author":"Yang","year":"2021","journal-title":"Pharm. Biol."},{"key":"ref_33","first-page":"653","article-title":"The role of Fas mutation on non-alcoholic steatohepatitis in mice","volume":"19","author":"Su","year":"2011","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref_34","first-page":"65","article-title":"G-Aminobutyric acid promotes methionine-choline deficient diet-induced nonalcoholic steatohepatitis","volume":"31","author":"Cho","year":"2016","journal-title":"J. Biomed. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1476-511X-10-31","article-title":"Induction of heme oxygenase-1 protects against nutritional fibrosing steatohepatitis in mice","volume":"10","author":"Wang","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_36","first-page":"680","article-title":"The role of heme oxygenase-1 in non-alcoholic steatohepatitis","volume":"18","author":"Wang","year":"2010","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Nawata, A., Noguchi, H., Mazaki, Y., Kurahashi, T., Izumi, H., Wang, K.Y., Guo, X., Uramoto, H., Kohno, K., and Taniguchi, H. (2016). Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152549"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1111\/j.1440-1746.2006.04701.x","article-title":"Essential pathogenic and metabolic differences in steatosis induced by choline or methione-choline deficient diets in a rat model","volume":"22","author":"Vetelainen","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_40","first-page":"2683","article-title":"Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL\/6 mice","volume":"6","author":"Itagaki","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/liv.14307","article-title":"Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment","volume":"40","author":"Fan","year":"2020","journal-title":"Liver Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.7150\/ijbs.92337","article-title":"NUP85 alleviates lipid metabolism and inflammation by regulating PI3K\/AKT signaling pathway in nonalcoholic fatty liver disease","volume":"20","author":"Wu","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/00365520802530861","article-title":"Rosiglitazone prevents nutritional fibrosis and steatohepatitis in mice","volume":"44","author":"Nan","year":"2009","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3892\/ijmm.2012.1029","article-title":"Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Analysis of isolated hepatic stellate cells","volume":"30","author":"Kim","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/hep4.1383","article-title":"Lipoprotein Lipase Up-regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice","volume":"3","author":"Teratani","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chen, K., Wang, J., Luo, S., Quan, Y., Wei, P., Fu, J., Ma, J., Yang, Y., Liu, Y., and Gao, Z. (2025). Exploring the mechanisms of tetrahydrocurcumin in ameliorating nonalcoholic steatohepatitis based on network pharmacology and gut microbiota analysis in vivo and in vitro. Front. Microbiol., 16, Erratum in Front. Microbiol.\u00a02025, 16, 1656225. https:\/\/doi.org\/10.3389\/fmicb.2025.1656225.","DOI":"10.3389\/fmicb.2025.1576221"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1111\/hepr.12863","article-title":"Mechanisms of the prevention and inhibition of the progression and development of non-alcoholic steatohepatitis by genetic and pharmacological decoy receptor 3 supplementation","volume":"47","author":"Lee","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117643","DOI":"10.1016\/j.bcp.2025.117643","article-title":"Artesunate reduces oxidative stress and inflammation in NAFLD by activating the Nrf2 pathway","volume":"245","author":"Meng","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"153766","DOI":"10.1016\/j.tox.2024.153766","article-title":"Targeting SIRT1, NLRP3 inflammasome, and Nrf2 signaling with chrysin alleviates the iron-triggered hepatotoxicity in rats","volume":"504","author":"Alanazi","year":"2024","journal-title":"Toxicology"},{"key":"ref_50","first-page":"2730","article-title":"Effect of Wenpi Pills on lipid metabolism in mice with non-alcoholic fatty liver disease induced by various diets","volume":"50","author":"Zhang","year":"2025","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1111\/bph.13786","article-title":"The TIR\/BB-loop mimetic AS-1 prevents non-alcoholic steatohepatitis and hepatic insulin resistance by inhibiting NLRP3-ASC inflammasome activation","volume":"174","author":"Wang","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106400","DOI":"10.1016\/j.prostaglandins.2019.106400","article-title":"Cytochrome P450-derived eicosanoids and inflammation in liver diseases","volume":"147","author":"Shoieb","year":"2020","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_53","first-page":"285","article-title":"The role of cytochrome P450 in nonalcoholic fatty liver induced by high-fat diet: A gene expression profile analysis","volume":"25","author":"Liu","year":"2017","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.clnu.2009.08.014","article-title":"Inhibition of JNK along with activation of ERK1\/2 MAPK pathways improve steatohepatitis among the rats","volume":"29","author":"Aghazadeh","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2364121","DOI":"10.1155\/2023\/2364121","article-title":"Amphiregulin Induces iNOS and COX-2 Expression through NF-kappaB and MAPK Signaling in Hepatic Inflammation","volume":"2023","author":"Heo","year":"2023","journal-title":"Mediat. Inflamm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1038\/s41598-023-30001-7","article-title":"Osteoprotegerin deficiency aggravates methionine-choline-deficient diet-induced nonalcoholic steatohepatitis in mice","volume":"13","author":"Wu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100469","DOI":"10.1016\/j.impact.2023.100469","article-title":"PEG-GNPs aggravate MCD-induced steatohepatitic injury and liver fibrosis in mice through excessive lipid accumulation-mediated hepatic inflammatory damage","volume":"31","author":"Chen","year":"2023","journal-title":"NanoImpact"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chu, X., Liu, S., Qu, B., Xin, Y., and Lu, L. (2024). Salidroside may target PPARalpha to exert preventive and therapeutic activities on NASH. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1433076"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"155758","DOI":"10.1016\/j.phymed.2024.155758","article-title":"Tryptanthrin suppresses multiple inflammasome activation to regulate NASH progression by targeting ASC protein","volume":"131","author":"Ren","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12139","DOI":"10.1038\/s41598-020-69085-w","article-title":"MCD diet-induced steatohepatitis generates a diurnal rhythm of associated biomarkers and worsens liver injury in Klf10 deficient mice","volume":"10","author":"Leclere","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s10620-014-3167-6","article-title":"Caspase 3 inactivation protects against hepatic cell death and ameliorates fibrogenesis in a diet-induced NASH model","volume":"59","author":"Thapaliya","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Jian, Y., Li, Y., Zhou, Y., and Mu, W. (2025). Pollutants in Microenvironmental Cellular Interactions During Liver Inflammation Cancer Transition and the Application of Multi-Omics Analysis. Toxics, 13.","DOI":"10.3390\/toxics13030163"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wang, Y., Cui, Z., Liu, W., Liu, B., Zeng, Q., Zhao, X., Dou, J., and Cao, J. (2023). Endocrine disrupting chemicals: A promoter of non-alcoholic fatty liver disease. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1154837"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.21873\/invivo.13178","article-title":"Liraglutide with Metformin Therapy Ameliorates Hepatic Steatosis and Liver Injury in a Mouse Model of Non-alcoholic Steatohepatitis","volume":"37","author":"Chiu","year":"2023","journal-title":"In Vivo"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Palladini, G., Di Pasqua, L.G., Cagna, M., Croce, A.C., Perlini, S., Mannucci, B., Profumo, A., Ferrigno, A., and Vairetti, M. (2022). MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126817"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36","DOI":"10.37796\/2211-8039.1468","article-title":"Advanced whole transcriptome sequencing and artificial intelligence\/machine learning (AI\/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes","volume":"14","author":"Wu","year":"2024","journal-title":"BioMedicine"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:12:58Z","timestamp":1783570378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,5]]},"references-count":66,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27136033"],"URL":"https:\/\/doi.org\/10.3390\/ijms27136033","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,5]]}}}