{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:06:04Z","timestamp":1791324364019,"version":"4.3.1"},"reference-count":105,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82160171"],"award-info":[{"award-number":["No. 82160171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Non-alcoholic steatohepatitis (NASH) progression is strongly associated with deteriorating hepatic function, primarily driven by free cholesterol (FC) accumulation-induced lipotoxicity. Emerging evidence highlights the regulatory role of mammalian Ste20-like kinase 1 (MST1) in modulating intrahepatic lipid homeostasis, suggesting its therapeutic potential for non-alcoholic fatty liver disease (NAFLD) management. This investigation seeks to elucidate the pathophysiological mechanisms through which MST1 modulates NASH progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The experimental design employed two murine genetic models\u2014wild-type (WT) controls and MST1-knockout (MST1-KO) specimens\u2014subjected to a nutritionally modified Western diet (WD) enriched with saturated fats, simple carbohydrates, and dietary cholesterol to induce non-alcoholic steatohepatitis (NASH) pathogenesis. Lentiviral transduction techniques facilitated targeted MST1 overexpression in WT animals maintained on this dietary regimen. Parallel in vitro investigations utilized HepG2 hepatocyte cultures exposed to free fatty acid (FFA) cocktails comprising palmitic and oleic acids, coupled with CRISPR-mediated MST1 suppression and complementary gain-of-function manipulations to delineate molecular mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>NASH triggers hepatic sterol biosynthesis activation, resulting in pathological FC overload concurrent with MST1 transcriptional suppression. Genetic ablation of MST1 amplifies intrahepatic FC retention and potentiates histopathological inflammation, while MST1 reconstitution mitigates steatotic FC deposition and attenuates inflammatory cascades. Mechanistic profiling revealed MST1-mediated AMPK\u03b1 phosphorylation at Thr172, which suppresses cholesterogenic enzyme expression via sterol regulatory element-binding transcription factor 2 (SREBP2) axis modulation. This phosphorylation cascade demonstrates dose-dependent inhibition of HMGCR activity, resolving FC-induced hepatotoxicity. Crucially, MST1 orchestrates AMPK\/SREBP2 crosstalk to maintain sterol homeostasis, with knockout models exhibiting 67% elevated SREBP2 nuclear translocation compared to controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The regulatory axis involving MST1-mediated AMPK phosphorylation emerges as a promising therapeutic modality for modulating hepatic sterol metabolism. It demonstrates significant potential in arresting the progression of inflammatory cascades and extracellular matrix remodeling characteristic of NASH pathogenesis. Mechanistic studies confirm that this phosphorylation cascade effectively suppresses de novo lipogenesis while enhancing cholesterol efflux capacity, thereby establishing a dual-target strategy against both metabolic dysfunction and fibrotic transformation in preclinical models.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40001-025-02557-9","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:21:18Z","timestamp":1744863678000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mammalian Ste20-like kinase 1 regulates AMPK to mitigate the progression of non-alcoholic fatty liver disease"],"prefix":"10.1186","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3957-8860","authenticated-orcid":false,"given":"Lijuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-0040","authenticated-orcid":false,"given":"Chenglei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-3243","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5459-844X","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"2557_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73\u201384. https:\/\/doi.org\/10.1002\/hep.28431.","journal-title":"Hepatology"},{"key":"2557_CR2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.14218\/JCTH.2023.00252","volume":"12","author":"J Tidwell","year":"2024","unstructured":"Tidwell J, Wu GY. Unique genetic features of lean NAFLD: a review of mechanisms and clinical implications. J Clin Transl Hepatol. 2024;12:70\u20138. https:\/\/doi.org\/10.14218\/JCTH.2023.00252.","journal-title":"J Clin Transl Hepatol"},{"key":"2557_CR3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.14218\/JCTH.2023.00197","volume":"12","author":"W Liu","year":"2024","unstructured":"Liu W, Zhang Chen Z, Yang C, Fan Y, Qiao L, Xie S, Cao L. Update on the STING signaling pathway in developing nonalcoholic fatty liver disease. J Clin Transl Hepatol. 2024;12:91\u20139. https:\/\/doi.org\/10.14218\/JCTH.2023.00197.","journal-title":"J Clin Transl Hepatol"},{"key":"2557_CR4","doi-asserted-by":"publisher","unstructured":"Karim G, Department of Medicine, Mount Sinai Israel, New York, NY, USA, Bansal MB, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Resmetirom: an orally administered, small-molecule, liver-directed, \u03b2-selective THR agonist for the treatment of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Eur Endocrinol. 2023;19:60. https:\/\/doi.org\/10.17925\/EE.2023.19.1.60","DOI":"10.17925\/EE.2023.19.1.60"},{"key":"2557_CR5","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1080\/13543784.2020.1763302","volume":"29","author":"S Fiorucci","year":"2020","unstructured":"Fiorucci S, Biagioli M, Sepe V, Zampella A, Distrutti E. Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020;29:623\u201332. https:\/\/doi.org\/10.1080\/13543784.2020.1763302.","journal-title":"Expert Opin Investig Drugs"},{"key":"2557_CR6","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.hest.2023.01.004","volume":"4","author":"T Adeniji","year":"2023","unstructured":"Adeniji T, Nadasan T, Michael Olagbegi O, Dada O. Telerehabilitation-based exercises with or without transcranial direct current stimulation for pain, motor and cognitive function in older adults with mild cognitive impairments post-stroke: a multi-arm parallel-group randomized controlled trial study protocol. Brain Hemorrhages. 2023;4:122\u20138. https:\/\/doi.org\/10.1016\/j.hest.2023.01.004.","journal-title":"Brain Hemorrhages"},{"key":"2557_CR7","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.hest.2023.10.001","volume":"5","author":"T Takano","year":"2024","unstructured":"Takano T, Ito M. An extensive basal ganglia hemorrhage in a preexisting neonatal asphyxiated lesion after mRNA-based SARS-CoV-2 vaccination: a fatal adult case of cerebral palsy. Brain Hemorrhages. 2024;5:38\u201341. https:\/\/doi.org\/10.1016\/j.hest.2023.10.001.","journal-title":"Brain Hemorrhages"},{"key":"2557_CR8","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2024-0002","author":"J Trivedi","year":"2024","unstructured":"Trivedi J, Yasir M, Maurya RK, Tripathi AS. Aptamer-based theranostics in oncology: design strategies and limitations. BIOI. 2024. https:\/\/doi.org\/10.15212\/bioi-2024-0002.","journal-title":"BIOI"},{"key":"2557_CR9","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2024-0003","author":"VV Kshatriya","year":"2024","unstructured":"Kshatriya VV, Kumbhare MR, Jadhav SV, Thorat PJ, Bhambarge RG. Updated review on recent advances in silver nanoclusters in bioanalytical and biomedical applications. BIOI. 2024. https:\/\/doi.org\/10.15212\/bioi-2024-0003.","journal-title":"BIOI"},{"key":"2557_CR10","doi-asserted-by":"publisher","first-page":"0378","DOI":"10.34133\/research.0378","volume":"7","author":"Y-S Shi","year":"2024","unstructured":"Shi Y-S, Yang T-N, Wang Y-X, Ma X-Y, Liu S, Zhao Y, Li J-L. Melatonin mitigates atrazine-induced renal tubular epithelial cell senescence by promoting parkin-mediated mitophagy. Research. 2024;7:0378. https:\/\/doi.org\/10.34133\/research.0378.","journal-title":"Research"},{"key":"2557_CR11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/hep4.1801","volume":"6","author":"CL Horn","year":"2022","unstructured":"Horn CL, Morales AL, Savard C, Farrell GC, Ioannou GN. Role of cholesterol-associated steatohepatitis in the development of NASH. Hepatol Commun. 2022;6:12\u201335. https:\/\/doi.org\/10.1002\/hep4.1801.","journal-title":"Hepatol Commun"},{"key":"2557_CR12","doi-asserted-by":"publisher","first-page":"3280","DOI":"10.3390\/biomedicines11123280","volume":"11","author":"N Li","year":"2023","unstructured":"Li N, Li X, Ding Y, Liu X, Diggle K, Kisseleva T, Brenner DA. SREBP regulation of lipid metabolism in liver disease, and therapeutic strategies. Biomedicines. 2023;11:3280. https:\/\/doi.org\/10.3390\/biomedicines11123280.","journal-title":"Biomedicines"},{"key":"2557_CR13","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/abbs\/gms112","volume":"45","author":"X Xiao","year":"2013","unstructured":"Xiao X, Song B-L. SREBP: a novel therapeutic target. ABBS. 2013;45:2\u201310. https:\/\/doi.org\/10.1093\/abbs\/gms112.","journal-title":"ABBS"},{"key":"2557_CR14","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.bbamem.2011.06.014","volume":"1818","author":"BN Olsen","year":"2012","unstructured":"Olsen BN, Schlesinger PH, Ory DS, Baker NA. Side-chain oxysterols: from cells to membranes to molecules. Biochimica et Biophysica Acta (BBA) Biomembranes. 2012;1818:330\u20136. https:\/\/doi.org\/10.1016\/j.bbamem.2011.06.014.","journal-title":"Biochimica et Biophysica Acta (BBA) Biomembranes"},{"key":"2557_CR15","doi-asserted-by":"publisher","first-page":"6496","DOI":"10.1073\/pnas.0701774104","volume":"104","author":"R Schekman","year":"2007","unstructured":"Schekman R. How sterols regulate protein sorting and traffic. Proc Natl Acad Sci USA. 2007;104:6496\u20137. https:\/\/doi.org\/10.1073\/pnas.0701774104.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2557_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2022.101198","volume":"89","author":"C Celik","year":"2023","unstructured":"Celik C, Lee SYT, Yap WS, Thibault G. Endoplasmic reticulum stress and lipids in health and diseases. Prog Lipid Res. 2023;89: 101198. https:\/\/doi.org\/10.1016\/j.plipres.2022.101198.","journal-title":"Prog Lipid Res"},{"key":"2557_CR17","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1053\/jhep.2003.50351","volume":"38","author":"O Coll","year":"2003","unstructured":"Coll O, Colell A, Garc\u00eda-Ruiz C, Kaplowitz N, Fern\u00e1ndez-Checa JC. Sensitivity of the 2\u2013Oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology. 2003;38:692\u2013702. https:\/\/doi.org\/10.1053\/jhep.2003.50351.","journal-title":"Hepatology"},{"key":"2557_CR18","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1194\/jlr.M072454","volume":"58","author":"GN Ioannou","year":"2017","unstructured":"Ioannou GN, Subramanian S, Chait A, Haigh WG, Yeh MM, Farrell GC, Lee SP, Savard C. Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH. J Lipid Res. 2017;58:1067\u201379. https:\/\/doi.org\/10.1194\/jlr.M072454.","journal-title":"J Lipid Res"},{"key":"2557_CR19","doi-asserted-by":"publisher","first-page":"1255727","DOI":"10.3389\/fphar.2023.1255727","volume":"14","author":"A Attiq","year":"2023","unstructured":"Attiq A, Afzal S. Trinity of inflammation, innate immune cells and cross-talk of signalling pathways in tumour microenvironment. Front Pharmacol. 2023;14:1255727. https:\/\/doi.org\/10.3389\/fphar.2023.1255727.","journal-title":"Front Pharmacol"},{"key":"2557_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100599","volume":"5","author":"R Wang","year":"2024","unstructured":"Wang R, Peng X, Yuan Y, Shi B, Liu Y, Ni H, Guo W, Yang Q, Liu P, Wang J, et al. Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis. Innovation. 2024;5: 100599. https:\/\/doi.org\/10.1016\/j.xinn.2024.100599.","journal-title":"Innovation"},{"key":"2557_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102255","volume":"52","author":"C Ding","year":"2025","unstructured":"Ding C, Wang J, Wang J, Niu J, Xiahou Z, Sun Z, Zhao Z, Zeng D. Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: implications for prognosis and immunotherapy. Transl Oncol. 2025;52: 102255. https:\/\/doi.org\/10.1016\/j.tranon.2024.102255.","journal-title":"Transl Oncol"},{"key":"2557_CR22","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1186\/s40001-024-02176-w","volume":"29","author":"Z Jia","year":"2024","unstructured":"Jia Z, Wang Z, Pan H, Zhang J, Wang Q, Zhou C, Liu J. Crosstalk between fat tissue and muscle, brain, liver, and heart in obesity: cellular and molecular perspectives. Eur J Med Res. 2024;29:637. https:\/\/doi.org\/10.1186\/s40001-024-02176-w.","journal-title":"Eur J Med Res"},{"key":"2557_CR23","doi-asserted-by":"publisher","first-page":"5250","DOI":"10.2174\/13816128113199990344","volume":"19","author":"F Marra","year":"2013","unstructured":"Marra F, Lotersztajn S. Pathophysiology of NASH: perspectives for a targeted treatment. CPD. 2013;19:5250\u201369. https:\/\/doi.org\/10.2174\/13816128113199990344.","journal-title":"CPD"},{"key":"2557_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2025.102280","volume":"52","author":"G Ni","year":"2025","unstructured":"Ni G, Sun Y, Jia H, Xiahou Z, Li Y, Zhao F, Zang H. MAZ-mediated tumor progression and immune evasion in hormone receptor-positive breast cancer: targeting tumor microenvironment and PCLAF+ subtype-specific therapy. Transl Oncol. 2025;52: 102280. https:\/\/doi.org\/10.1016\/j.tranon.2025.102280.","journal-title":"Transl Oncol"},{"key":"2557_CR25","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/j.bbadis.2015.05.015","volume":"1852","author":"G Arguello","year":"2015","unstructured":"Arguello G, Balboa E, Arrese M, Zanlungo S. Recent insights on the role of cholesterol in non-alcoholic fatty liver disease. Biochimica et Biophys Acta (BBA) Mol Bas Dis. 2015;1852:1765\u201378. https:\/\/doi.org\/10.1016\/j.bbadis.2015.05.015.","journal-title":"Biochimica et Biophys Acta (BBA) Mol Bas Dis"},{"key":"2557_CR26","doi-asserted-by":"publisher","first-page":"467","DOI":"10.3389\/fmed.2020.00467","volume":"7","author":"P Malhotra","year":"2020","unstructured":"Malhotra P, Gill RK, Saksena S, Alrefai WA. Disturbances in cholesterol homeostasis and non-alcoholic fatty liver diseases. Front Med. 2020;7:467. https:\/\/doi.org\/10.3389\/fmed.2020.00467.","journal-title":"Front Med"},{"key":"2557_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2021.101109","volume":"83","author":"H Li","year":"2021","unstructured":"Li H, Yu X-H, Ou X, Ouyang X-P, Tang C-K. Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis. Prog Lipid Res. 2021;83: 101109. https:\/\/doi.org\/10.1016\/j.plipres.2021.101109.","journal-title":"Prog Lipid Res"},{"key":"2557_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/8746114","volume":"2021","author":"X Zhang","year":"2021","unstructured":"Zhang X, Wang K, Zhu L, Wang Q. Reverse cholesterol transport pathway and cholesterol efflux in diabetic retinopathy. J Diabetes Res. 2021;2021:1\u201311. https:\/\/doi.org\/10.1155\/2021\/8746114.","journal-title":"J Diabetes Res"},{"key":"2557_CR29","doi-asserted-by":"publisher","first-page":"5732812","DOI":"10.1155\/2023\/5732812","volume":"2023","author":"S Murasawa","year":"2023","unstructured":"Murasawa S, Kageyama K, Usutani M, Asari Y, Kinoshita N, Nakada Y, Watanuki Y, Takayasu S, Daimon M. Biochemical evaluation by confirmatory tests after unilateral adrenalectomy for primary aldosteronism. J Renin Angiotensin Aldosterone Syst. 2023;2023:5732812. https:\/\/doi.org\/10.1155\/2023\/5732812.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR30","doi-asserted-by":"publisher","first-page":"3431612","DOI":"10.1155\/2023\/3431612","volume":"2023","author":"H Luoyi","year":"2023","unstructured":"Luoyi H, Yan P, Qihong F. Relationship between angiotensin-converting enzyme insertion\/deletion polymorphism and the Risk of COVID-19: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2023;2023:3431612. https:\/\/doi.org\/10.1155\/2023\/3431612.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR31","doi-asserted-by":"publisher","first-page":"147032032412940","DOI":"10.1177\/14703203241294037","volume":"25","author":"Y Park","year":"2024","unstructured":"Park Y, Kang D, Sinn DH, Kim H, Hong YS, Cho J, Gwak G-Y. Effect of renin-angiotensin system inhibitor in incident cancer among chronic hepatitis B patients: an emulated target trial using a nationwide cohort. J Renin Angiotensin Aldosterone Syst. 2024;25:14703203241294036. https:\/\/doi.org\/10.1177\/14703203241294037.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR32","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.cell.2015.10.044","volume":"163","author":"F-X Yu","year":"2015","unstructured":"Yu F-X, Zhao B, Guan K-L. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163:811\u201328. https:\/\/doi.org\/10.1016\/j.cell.2015.10.044.","journal-title":"Cell"},{"key":"2557_CR33","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12885-025-13539-9","volume":"25","author":"J-G Lee","year":"2025","unstructured":"Lee J-G, Park I, Lee H, Nam S, Kim J, Lee W-S, Kang M, Kim JH. Integrating E-cadherin expression levels with TNM staging for enhanced prognostic prediction in colorectal cancer patients. BMC Cancer. 2025;25:150. https:\/\/doi.org\/10.1186\/s12885-025-13539-9.","journal-title":"BMC Cancer"},{"key":"2557_CR34","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1016\/j.apsb.2023.01.015","volume":"13","author":"Y Yin","year":"2023","unstructured":"Yin Y, Tan M, Han L, Zhang L, Zhang Y, Zhang J, Pan W, Bai J, Jiang T, Li H. The hippo kinases MST1\/2 in cardiovascular and metabolic diseases: a promising therapeutic target option for pharmacotherapy. Acta Pharmaceutica Sinica B. 2023;13:1956\u201375. https:\/\/doi.org\/10.1016\/j.apsb.2023.01.015.","journal-title":"Acta Pharmaceutica Sinica B"},{"key":"2557_CR35","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.bbrc.2016.02.059","volume":"471","author":"C Geng","year":"2016","unstructured":"Geng C, Zhang Y, Gao Y, Tao W, Zhang H, Liu X, Fang F, Chang Y. Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. Biochem Biophys Res Commun. 2016;471:444\u20139. https:\/\/doi.org\/10.1016\/j.bbrc.2016.02.059.","journal-title":"Biochem Biophys Res Commun"},{"key":"2557_CR36","doi-asserted-by":"publisher","first-page":"IA09","DOI":"10.1158\/1557-3125.HIPPO19-IA09","volume":"18","author":"S-H Jeong","year":"2020","unstructured":"Jeong S-H, Lim D-S. Abstract IA09: The crosstalk between Hippo-YAP\/TAZ and PTEN-AKT signaling in liver metabolic dysregulation and tumorigenesis. Mol Cancer Res. 2020;18:IA09\u2013IA09. https:\/\/doi.org\/10.1158\/1557-3125.HIPPO19-IA09.","journal-title":"Mol Cancer Res"},{"key":"2557_CR37","doi-asserted-by":"publisher","first-page":"8248","DOI":"10.1073\/pnas.0912203107","volume":"107","author":"K-P Lee","year":"2010","unstructured":"Lee K-P, Lee J-H, Kim T-S, Kim T-H, Park H-D, Byun J-S, Kim M-C, Jeong W-I, Calvisi DF, Kim J-M, et al. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA. 2010;107:8248\u201353. https:\/\/doi.org\/10.1073\/pnas.0912203107.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2557_CR38","doi-asserted-by":"publisher","first-page":"0277","DOI":"10.34133\/research.0277","volume":"7","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Feng G, He T, Yang M, Lin J, Huang P. Traceable lactate-fueled self-acting photodynamic therapy against triple-negative breast cancer. Research. 2024;7:0277. https:\/\/doi.org\/10.34133\/research.0277.","journal-title":"Research"},{"key":"2557_CR39","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.cell.2011.12.017","volume":"148","author":"WA Freed-Pastor","year":"2012","unstructured":"Freed-Pastor WA, Mizuno H, Zhao X, Langer\u00f8d A, Moon S-H, Rodriguez-Barrueco R, Barsotti A, Chicas A, Li W, Polotskaia A, et al. Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell. 2012;148:244\u201358. https:\/\/doi.org\/10.1016\/j.cell.2011.12.017.","journal-title":"Cell"},{"key":"2557_CR40","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41418-017-0026-y","volume":"25","author":"A Parrales","year":"2018","unstructured":"Parrales A, Thoenen E, Iwakuma T. The interplay between mutant p53 and the mevalonate pathway. Cell Death Differ. 2018;25:460\u201370. https:\/\/doi.org\/10.1038\/s41418-017-0026-y.","journal-title":"Cell Death Differ"},{"key":"2557_CR41","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/s12276-020-0430-0","volume":"52","author":"SH Lee","year":"2020","unstructured":"Lee SH, Lee J-H, Im S-S. The cellular function of SCAP in metabolic signaling. Exp Mol Med. 2020;52:724\u20139. https:\/\/doi.org\/10.1038\/s12276-020-0430-0.","journal-title":"Exp Mol Med"},{"key":"2557_CR42","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-024-01231-2","author":"H-S Chen","year":"2024","unstructured":"Chen H-S, Chen M-R, Cui Y, Shen X-Y, Zhang H, Lu J, Zhao L-W, Duan Y-J, Li J, Wang Y-M, et al. Tenecteplase plus butyphthalide for stroke within 4.5\u20136 hours of onset (EXIT-BT): a phase 2 study. Transl Stroke Res. 2024. https:\/\/doi.org\/10.1007\/s12975-024-01231-2.","journal-title":"Transl Stroke Res"},{"key":"2557_CR43","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-024-01261-w","author":"SS Veeturi","year":"2024","unstructured":"Veeturi SS, Hall S, Fujimura S, Mossa-Basha M, Sagues E, Samaniego EA, Tutino VM. Imaging of intracranial aneurysms: a review of standard and advanced imaging techniques. Transl Stroke Res. 2024. https:\/\/doi.org\/10.1007\/s12975-024-01261-w.","journal-title":"Transl Stroke Res"},{"key":"2557_CR44","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1007\/s12072-020-10096-0","volume":"14","author":"Y Li","year":"2020","unstructured":"Li Y, Luan Y, Li J, Song H, Li Y, Qi H, Sun B, Zhang P, Wu X, Liu X, et al. Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism. Hepatol Int. 2020;14:1057\u201374. https:\/\/doi.org\/10.1007\/s12072-020-10096-0.","journal-title":"Hepatol Int"},{"key":"2557_CR45","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1161\/CIRCRESAHA.122.321322","volume":"131","author":"M Quan","year":"2022","unstructured":"Quan M, Lv H, Liu Z, Li K, Zhang C, Shi L, Yang X, Lei P, Zhu Y, Ai D. MST1 suppresses disturbed flow induced atherosclerosis. Circ Res. 2022;131:748\u201364. https:\/\/doi.org\/10.1161\/CIRCRESAHA.122.321322.","journal-title":"Circ Res"},{"key":"2557_CR46","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/ng1197-314","volume":"17","author":"T Kafri","year":"1997","unstructured":"Kafri T, Bl\u00f6mer U, Peterson DA, Gage FH, Verma IM. Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors. Nat Genet. 1997;17:314\u20137. https:\/\/doi.org\/10.1038\/ng1197-314.","journal-title":"Nat Genet"},{"key":"2557_CR47","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2023-0012","author":"S Luo","year":"2023","unstructured":"Luo S, Wang L, Xiao Y, Cao C, Liu Q, Zhou Y. Single-Cell RNA-sequencing integration analysis revealed immune cell heterogeneity in five human autoimmune diseases. BIOI. 2023. https:\/\/doi.org\/10.15212\/bioi-2023-0012.","journal-title":"BIOI"},{"key":"2557_CR48","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2023-0013","author":"Q Fu","year":"2024","unstructured":"Fu Q, Yang H, Huang J, Liu F, Fu Y, Saw PE, Wang Y. The CircHAS2\/RPL23\/MMP9 axis facilitates brain tumor metastasis. BIOI. 2024. https:\/\/doi.org\/10.15212\/bioi-2023-0013.","journal-title":"BIOI"},{"key":"2557_CR49","doi-asserted-by":"publisher","DOI":"10.15212\/bioi-2022-0025","author":"S He","year":"2023","unstructured":"He S, Xiao X, Lei R, Chen J, Huang H, Yilihamu A, Guo M, Tan C, Li X, Zhuang Z, et al. Establishment of breast phyllodes tumor cell lines preserving the features of phyllodes tumors. BIOI. 2023. https:\/\/doi.org\/10.15212\/bioi-2022-0025.","journal-title":"BIOI"},{"key":"2557_CR50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127991","volume":"10","author":"MV Machado","year":"2015","unstructured":"Machado MV, Michelotti GA, Xie G, De Almeida TP, Boursier J, Bohnic B, Guy CD, Diehl AM. Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease. PLoS ONE. 2015;10: e0127991. https:\/\/doi.org\/10.1371\/journal.pone.0127991.","journal-title":"PLoS ONE"},{"key":"2557_CR51","doi-asserted-by":"publisher","first-page":"G825","DOI":"10.1152\/ajpgi.00145.2011","volume":"301","author":"M Charlton","year":"2011","unstructured":"Charlton M, Krishnan A, Viker K, Sanderson S, Cazanave S, McConico A, Masuoko H, Gores G. Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition. Am J Physiol Gastroint Liver Physiol. 2011;301:G825\u201334. https:\/\/doi.org\/10.1152\/ajpgi.00145.2011.","journal-title":"Am J Physiol Gastroint Liver Physiol"},{"key":"2557_CR52","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.jhep.2016.05.005","volume":"65","author":"A Asgharpour","year":"2016","unstructured":"Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, Kumar DP, Daita K, Min H-K, Mirshahi F, et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol. 2016;65:579\u201388. https:\/\/doi.org\/10.1016\/j.jhep.2016.05.005.","journal-title":"J Hepatol"},{"key":"2557_CR53","doi-asserted-by":"publisher","first-page":"G483","DOI":"10.1152\/ajpgi.00079.2013","volume":"305","author":"JR Clapper","year":"2013","unstructured":"Clapper JR, Hendricks MD, Gu G, Wittmer C, Dolman CS, Herich J, Athanacio J, Villescaz C, Ghosh SS, Heilig JS, et al. Diet-induced mouse model of fatty liver disease and nonalcoholic steatohepatitis reflecting clinical disease progression and methods of assessment. Am J Physiol Gastroint Liver Physiol. 2013;305:G483\u201395. https:\/\/doi.org\/10.1152\/ajpgi.00079.2013.","journal-title":"Am J Physiol Gastroint Liver Physiol"},{"key":"2557_CR54","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1016\/j.ajpath.2014.01.034","volume":"184","author":"JK Dowman","year":"2014","unstructured":"Dowman JK, Hopkins LJ, Reynolds GM, Nikolaou N, Armstrong MJ, Shaw JC, Houlihan DD, Lalor PF, Tomlinson JW, H\u00fcbscher SG, et al. Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat\/fructose diet and sedentary lifestyle. Am J Pathol. 2014;184:1550\u201361. https:\/\/doi.org\/10.1016\/j.ajpath.2014.01.034.","journal-title":"Am J Pathol"},{"key":"2557_CR55","doi-asserted-by":"publisher","first-page":"0338","DOI":"10.34133\/research.0338","volume":"7","author":"X Chen","year":"2024","unstructured":"Chen X, Fan K, Lu J, Zhang S, Dong J, Qin J, Fan W, Wang Y, Zhang Y, Peng H, et al. Selecting monoclonal cell lineages from somatic reprogramming using robotic-based spatial-restricting structured flow. Research. 2024;7:0338. https:\/\/doi.org\/10.34133\/research.0338.","journal-title":"Research"},{"key":"2557_CR56","doi-asserted-by":"publisher","first-page":"5445548","DOI":"10.1155\/2023\/5445548","volume":"2023","author":"H Tian","year":"2023","unstructured":"Tian H, Liang Q, Shi Z, Zhao H. Hyperoside ameliorates renal tubular oxidative damage and calcium oxalate deposition in rats through AMPK\/Nrf2 signaling axis. J Renin Angiotensin Aldosterone Syst. 2023;2023:5445548. https:\/\/doi.org\/10.1155\/2023\/5445548.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR57","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40779-024-00514-x","volume":"11","author":"MM Kami\u0144ski","year":"2024","unstructured":"Kami\u0144ski MM. ADP-dependent glucokinase: the ancient, archaeal key to prostate cancer. Mil Med Res. 2024;11:10. https:\/\/doi.org\/10.1186\/s40779-024-00514-x.","journal-title":"Mil Med Res"},{"key":"2557_CR58","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2024.1216","author":"ML Barcena","year":"2024","unstructured":"Barcena ML, Aslam M, Norman K, Ott C, Ladilov Y. Role of AMPK and sirtuins in aging heart: basic and translational aspects. Aging Dis. 2024. https:\/\/doi.org\/10.14336\/AD.2024.1216.","journal-title":"Aging Dis"},{"key":"2557_CR59","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.cmet.2011.03.009","volume":"13","author":"Y Li","year":"2011","unstructured":"Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY-J, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376\u201388. https:\/\/doi.org\/10.1016\/j.cmet.2011.03.009.","journal-title":"Cell Metab"},{"key":"2557_CR60","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","volume":"15","author":"Z Younossi","year":"2018","unstructured":"Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11\u201320. https:\/\/doi.org\/10.1038\/nrgastro.2017.109.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2557_CR61","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","volume":"158","author":"TG Cotter","year":"2020","unstructured":"Cotter TG, Rinella M. Nonalcoholic fatty liver disease 2020: the state of the disease. Gastroenterology. 2020;158:1851\u201364. https:\/\/doi.org\/10.1053\/j.gastro.2020.01.052.","journal-title":"Gastroenterology"},{"key":"2557_CR62","doi-asserted-by":"publisher","first-page":"5458","DOI":"10.3390\/cancers15225458","volume":"15","author":"BM Motta","year":"2023","unstructured":"Motta BM, Masarone M, Torre P, Persico M. From non-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC): epidemiology, incidence, predictions, risk factors, and prevention. Cancers. 2023;15:5458. https:\/\/doi.org\/10.3390\/cancers15225458.","journal-title":"Cancers"},{"key":"2557_CR63","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","volume":"18","author":"DQ Huang","year":"2021","unstructured":"Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223\u201338. https:\/\/doi.org\/10.1038\/s41575-020-00381-6.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2557_CR64","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1002\/hep.26604","volume":"59","author":"K Tomita","year":"2014","unstructured":"Tomita K, Teratani T, Suzuki T, Shimizu M, Sato H, Narimatsu K, Okada Y, Kurihara C, Irie R, Yokoyama H, et al. Free cholesterol accumulation in hepatic stellate cells: mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice. Hepatology. 2014;59:154\u201369. https:\/\/doi.org\/10.1002\/hep.26604.","journal-title":"Hepatology"},{"key":"2557_CR65","doi-asserted-by":"publisher","first-page":"e1879","DOI":"10.1038\/cddis.2015.248","volume":"6","author":"C Lebeaupin","year":"2015","unstructured":"Lebeaupin C, Proics E, De Bieville CHD, Rousseau D, Bonnafous S, Patouraux S, Adam G, Lavallard VJ, Rovere C, Le Thuc O, et al. ER stress induces NLRP3 inflammasome activation and hepatocyte death. Cell Death Dis. 2015;6:e1879\u2013e1879. https:\/\/doi.org\/10.1038\/cddis.2015.248.","journal-title":"Cell Death Dis"},{"key":"2557_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102691","volume":"62","author":"Y Xiao","year":"2023","unstructured":"Xiao Y, Zhao C, Tai Y, Li B, Lan T, Lai E, Dai W, Guo Y, Gan C, Kostallari E, et al. STING mediates hepatocyte pyroptosis in liver fibrosis by Epigenetically activating the NLRP3 inflammasome. Redox Biol. 2023;62: 102691. https:\/\/doi.org\/10.1016\/j.redox.2023.102691.","journal-title":"Redox Biol"},{"key":"2557_CR67","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1097\/JS9.0000000000001080","volume":"110","author":"Z Wu","year":"2024","unstructured":"Wu Z, Shang G, Zhang K, Wang W, Fan M, Lin R. A nomogram incorporating treatment data for predicting overall survival in gastroenteropancreatic neuroendocrine tumors: a population-based cohort study. Int J Surg. 2024;110:2178\u201386. https:\/\/doi.org\/10.1097\/JS9.0000000000001080.","journal-title":"Int J Surg"},{"key":"2557_CR68","doi-asserted-by":"publisher","first-page":"1181913","DOI":"10.3389\/fendo.2023.1181913","volume":"14","author":"M Yang","year":"2023","unstructured":"Yang M, Liu C, Jiang N, Liu Y, Luo S, Li C, Zhao H, Han Y, Chen W, Li L, et al. Myostatin: a potential therapeutic target for metabolic syndrome. Front Endocrinol. 2023;14:1181913. https:\/\/doi.org\/10.3389\/fendo.2023.1181913.","journal-title":"Front Endocrinol"},{"key":"2557_CR69","doi-asserted-by":"publisher","first-page":"33","DOI":"10.53388\/TMR20230829002","volume":"9","author":"W-B Huang","year":"2024","unstructured":"Huang W-B, Qin S-Y, Zou J-B, Li X, Kang W-L, Yuan P-W. Efficacy of Juanbi capsule on ameliorating knee osteoarthritis: a network pharmacology and experimental verification-based study. Tradit Med Res. 2024;9:33. https:\/\/doi.org\/10.53388\/TMR20230829002.","journal-title":"Tradit Med Res"},{"key":"2557_CR70","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1016\/j.jconrel.2024.11.004","volume":"376","author":"S Nagpal","year":"2024","unstructured":"Nagpal S, Palaniappan T, Wang J-W, Wacker MG. Revisiting nanomedicine design strategies for follow-on products: a model-informed approach to optimize performance. J Control Release. 2024;376:1251\u201370. https:\/\/doi.org\/10.1016\/j.jconrel.2024.11.004.","journal-title":"J Control Release"},{"key":"2557_CR71","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.cmet.2012.04.004","volume":"15","author":"H-K Min","year":"2012","unstructured":"Min H-K, Kapoor A, Fuchs M, Mirshahi F, Zhou H, Maher J, Kellum J, Warnick R, Contos MJ, Sanyal AJ. Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease. Cell Metab. 2012;15:665\u201374. https:\/\/doi.org\/10.1016\/j.cmet.2012.04.004.","journal-title":"Cell Metab"},{"key":"2557_CR72","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1007\/s00125-013-3149-9","volume":"57","author":"Y Takeshita","year":"2014","unstructured":"Takeshita Y, Takamura T, Honda M, Kita Y, Zen Y, Kato K, Misu H, Ota T, Nakamura M, Yamada K, et al. The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia. 2014;57:878\u201390. https:\/\/doi.org\/10.1007\/s00125-013-3149-9.","journal-title":"Diabetologia"},{"key":"2557_CR73","doi-asserted-by":"publisher","first-page":"40161","DOI":"10.1074\/jbc.M112.417014","volume":"287","author":"A-C Tosello-Trampont","year":"2012","unstructured":"Tosello-Trampont A-C, Landes SG, Nguyen V, Novobrantseva TI, Hahn YS. Kupffer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-\u03b1 production. J Biol Chem. 2012;287:40161\u201372. https:\/\/doi.org\/10.1074\/jbc.M112.417014.","journal-title":"J Biol Chem"},{"key":"2557_CR74","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1002\/hep.23337","volume":"51","author":"R Stienstra","year":"2010","unstructured":"Stienstra R, Saudale F, Duval C, Keshtkar S, Groener JEM, Van Rooijen N, Staels B, Kersten S, M\u00fcller M. Kupffer cells promote hepatic steatosis via interleukin-1\u03b2\u2013dependent suppression of peroxisome proliferator-activated receptor \u03b1 activity. Hepatology. 2010;51:511\u201322. https:\/\/doi.org\/10.1002\/hep.23337.","journal-title":"Hepatology"},{"key":"2557_CR75","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.devcel.2011.05.010","volume":"20","author":"S Ohlig","year":"2011","unstructured":"Ohlig S, Farshi P, Pickhinke U, van den Boom J, H\u00f6ing S, Jakuschev S, Hoffmann D, Dreier R, Sch\u00f6ler HR, Dierker T, et al. Sonic hedgehog shedding results in functional activation of the solubilized protein. Dev Cell. 2011;20:764\u201374. https:\/\/doi.org\/10.1016\/j.devcel.2011.05.010.","journal-title":"Dev Cell"},{"key":"2557_CR76","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.765","volume":"5","author":"N Wang","year":"2024","unstructured":"Wang N, Hong W, Wu Y, Chen Z, Bai M, Wang W, Zhu J. Next-generation spatial transcriptomics: unleashing the power to gear up translational oncology. MedComm. 2024;5: e765. https:\/\/doi.org\/10.1002\/mco2.765.","journal-title":"MedComm"},{"key":"2557_CR77","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.hest.2022.04.004","volume":"4","author":"GK Wong","year":"2023","unstructured":"Wong GK, Cheung EY, Ng RY, Yu SC, Chan DY, Zhuang JT. Middle meningeal embolization for chronic subdural Hematoma: a case series of 7 patients and review of time course of resolution. Brain Hemorrhages. 2023;4:30\u20133. https:\/\/doi.org\/10.1016\/j.hest.2022.04.004.","journal-title":"Brain Hemorrhages"},{"key":"2557_CR78","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1111\/j.1440-1746.2010.06560.x","volume":"26","author":"L Zhao","year":"2011","unstructured":"Zhao L, Chen Y, Tang R, Chen Y, Li Q, Gong J, Huang A, Varghese Z, Moorhead JF, Ruan XZ. Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis. J of Gastro Hepatol. 2011;26:875\u201383. https:\/\/doi.org\/10.1111\/j.1440-1746.2010.06560.x.","journal-title":"J of Gastro Hepatol"},{"key":"2557_CR79","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1210\/me.2007-0531","volume":"23","author":"X Xie","year":"2009","unstructured":"Xie X, Liao H, Dang H, Pang W, Guan Y, Wang X, Shyy JY-J, Zhu Y, Sladek FM. Down-regulation of hepatic HNF4\u03b1 gene expression during hyperinsulinemia via SREBPs. Mol Endocrinol. 2009;23:434\u201343. https:\/\/doi.org\/10.1210\/me.2007-0531.","journal-title":"Mol Endocrinol"},{"key":"2557_CR80","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1053\/j.gastro.2011.06.040","volume":"141","author":"DM Van Rooyen","year":"2011","unstructured":"Van Rooyen DM, Larter CZ, Haigh WG, Yeh MM, Ioannou G, Kuver R, Lee SP, Teoh NC, Farrell GC. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology. 2011;141:1393-1403.e5. https:\/\/doi.org\/10.1053\/j.gastro.2011.06.040.","journal-title":"Gastroenterology"},{"key":"2557_CR81","doi-asserted-by":"publisher","first-page":"147032032412940","DOI":"10.1177\/14703203241294029","volume":"25","author":"D Ramirez-Hernandez","year":"2024","unstructured":"Ramirez-Hernandez D, Lezama-Martinez D, Velazco-Bejarano B, Valencia-Hernandez I, Lopez-Sanchez P, Fonseca-Coronado S, Flores-Monroy J. The beneficial effects of swimming training preconditioning on reducing vascular reactivity in chronic myocardial infarction: independent of NO production. J Renin Angiotensin Aldosterone Syst. 2024;25:14703203241294028. https:\/\/doi.org\/10.1177\/14703203241294029.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR82","doi-asserted-by":"publisher","first-page":"7550197","DOI":"10.1155\/2023\/7550197","volume":"2023","author":"B Nandhini","year":"2023","unstructured":"Nandhini B, Sureshraj Y, Kaviya M, Sangeetha T, Bharathi K, Balamuralikrishnan B, Manikantan P, Arun M, Haripriya KB, Karthika P, et al. Review on the biogenesis of platelets in lungs and its alterations in SARS-CoV-2 infection patients. J Renin Angiotensin Aldosterone Syst. 2023;2023:7550197. https:\/\/doi.org\/10.1155\/2023\/7550197.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR83","doi-asserted-by":"publisher","first-page":"147032032412652","DOI":"10.1177\/14703203241265218","volume":"25","author":"Y Chong","year":"2024","unstructured":"Chong Y, Wu X, Wang Y, Gu Q, Zhang J, Meng X, Li Y, Yang W, Li N, Liu H, et al. USP18 reduces the inflammatory response of LPS-induced SA-AKI by inhibiting the PI3K-AKT-NF-\u03baB pathway and regulate apoptosis of cells. J Renin Angiotensin Aldosterone Syst. 2024;25:14703203241265218. https:\/\/doi.org\/10.1177\/14703203241265218.","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"2557_CR84","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.cmet.2020.03.010","volume":"31","author":"X Wang","year":"2020","unstructured":"Wang X, Cai B, Yang X, Sonubi OO, Zheng Z, Ramakrishnan R, Shi H, Valenti L, Pajvani UB, Sandhu J, et al. Cholesterol stabilizes TAZ in hepatocytes to promote experimental non-alcoholic steatohepatitis. Cell Metab. 2020;31:969-986.e7. https:\/\/doi.org\/10.1016\/j.cmet.2020.03.010.","journal-title":"Cell Metab"},{"key":"2557_CR85","doi-asserted-by":"publisher","first-page":"3616","DOI":"10.1111\/jcmm.14262","volume":"23","author":"Z Shu","year":"2019","unstructured":"Shu Z, Gao Y, Zhang G, Zhou Y, Cao J, Wan D, Zhu X, Xiong W. A functional interaction between Hippo-YAP signalling and SREBPs mediates hepatic steatosis in diabetic mice. J Cell Mol Med. 2019;23:3616\u201328. https:\/\/doi.org\/10.1111\/jcmm.14262.","journal-title":"J Cell Mol Med"},{"key":"2557_CR86","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1101\/gad.274167.115","volume":"30","author":"Y Aylon","year":"2016","unstructured":"Aylon Y, Gershoni A, Rotkopf R, Biton IE, Porat Z, Koh AP, Sun X, Lee Y, Fiel M-I, Hoshida Y, et al. The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation. Genes Dev. 2016;30:786\u201397. https:\/\/doi.org\/10.1101\/gad.274167.115.","journal-title":"Genes Dev"},{"key":"2557_CR87","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.freeradbiomed.2018.02.031","volume":"118","author":"R Gopoju","year":"2018","unstructured":"Gopoju R, Panangipalli S, Kotamraju S. Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis. Free Radical Biol Med. 2018;118:85\u201397. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2018.02.031.","journal-title":"Free Radical Biol Med"},{"key":"2557_CR88","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1002\/hep4.1532","volume":"4","author":"X Wang","year":"2020","unstructured":"Wang X, Dong L, Gai Q, Ai W, Wu Y, Xiao W, Zhang J, An W. Lack of augmenter of liver regeneration disrupts cholesterol homeostasis of liver in mice by inhibiting the AMPK pathway. Hepatol Commun. 2020;4:1149\u201367. https:\/\/doi.org\/10.1002\/hep4.1532.","journal-title":"Hepatol Commun"},{"key":"2557_CR89","doi-asserted-by":"publisher","first-page":"6499","DOI":"10.1038\/s41467-022-34241-5","volume":"13","author":"E Setten","year":"2022","unstructured":"Setten E, Castagna A, Nava-Sede\u00f1o JM, Weber J, Carriero R, Reppas A, Volk V, Schmitz J, Gwinner W, Hatzikirou H, et al. Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context. Nat Commun. 2022;13:6499. https:\/\/doi.org\/10.1038\/s41467-022-34241-5.","journal-title":"Nat Commun"},{"key":"2557_CR90","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.celrep.2018.12.036","volume":"26","author":"D Garcia","year":"2019","unstructured":"Garcia D, Hellberg K, Chaix A, Wallace M, Herzig S, Badur MG, Lin T, Shokhirev MN, Pinto AFM, Ross DS, et al. Genetic liver-specific AMPK activation protects against diet-induced obesity and NAFLD. Cell Rep. 2019;26:192-208.e6. https:\/\/doi.org\/10.1016\/j.celrep.2018.12.036.","journal-title":"Cell Rep"},{"key":"2557_CR91","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/764618","volume":"2011","author":"M Fedele","year":"2011","unstructured":"Fedele M, Gualillo O, Vecchione A. Animal models of human pathology. Biomed Res Int. 2011;2011: 764618. https:\/\/doi.org\/10.1155\/2011\/764618.","journal-title":"Biomed Res Int"},{"key":"2557_CR92","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.bcp.2013.06.020","volume":"87","author":"BA Ruggeri","year":"2014","unstructured":"Ruggeri BA, Camp F, Miknyoczki S. Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. Biochem Pharmacol. 2014;87:150\u201361. https:\/\/doi.org\/10.1016\/j.bcp.2013.06.020.","journal-title":"Biochem Pharmacol"},{"key":"2557_CR93","doi-asserted-by":"publisher","first-page":"22","DOI":"10.53388\/TMR20220809001","volume":"8","author":"F-C Wang","year":"2023","unstructured":"Wang F-C, Han P, Li H, Ye H-Y, Zhou P-X, Tian W, Xiao Y, Wei Y, Wang K, Lu X-C, et al. Advantages and prospects of traditional Chinese medicine in treating COVID-19. Tradit Med Res. 2023;8:22. https:\/\/doi.org\/10.53388\/TMR20220809001.","journal-title":"Tradit Med Res"},{"key":"2557_CR94","doi-asserted-by":"publisher","first-page":"10","DOI":"10.53388\/TMR20230516001","volume":"9","author":"P-Y Wang","year":"2024","unstructured":"Wang P-Y, Shen J-F, Zhang S, Lan Q, Ma G-D, Wang T, Zhang Y-Z. A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification. Tradit Med Res. 2024;9:10. https:\/\/doi.org\/10.53388\/TMR20230516001.","journal-title":"Tradit Med Res"},{"key":"2557_CR95","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.574","volume":"5","author":"Q Wang","year":"2024","unstructured":"Wang Q, Guo F, Zhang Q, Hu T, Jin Y, Yang Y, Ma Y. Organoids in gastrointestinal diseases: from bench to clinic. MedComm. 2024;5: e574. https:\/\/doi.org\/10.1002\/mco2.574.","journal-title":"MedComm"},{"key":"2557_CR96","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.7150\/ijbs.85145","volume":"19","author":"DW Han","year":"2023","unstructured":"Han DW, Xu K, Jin Z-L, Xu Y-N, Li Y-H, Wang L, Cao Q, Kim K-P, Ryu D, Hong K, et al. Customized liver organoids as an advanced in vitro modeling and drug discovery platform for non-alcoholic fatty liver diseases. Int J Biol Sci. 2023;19:3595\u2013613. https:\/\/doi.org\/10.7150\/ijbs.85145.","journal-title":"Int J Biol Sci"},{"key":"2557_CR97","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1529","volume":"11","author":"A Chatzigoulas","year":"2021","unstructured":"Chatzigoulas A, Cournia Z. Rational design of allosteric modulators: challenges and successes. WIREs Comput Mol Sci. 2021;11: e1529. https:\/\/doi.org\/10.1002\/wcms.1529.","journal-title":"WIREs Comput Mol Sci"},{"key":"2557_CR98","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1021\/cb300663j","volume":"8","author":"Z Fang","year":"2013","unstructured":"Fang Z, Gr\u00fctter C, Rauh D. Strategies for the selective regulation of kinases with allosteric modulators: exploiting exclusive structural features. ACS Chem Biol. 2013;8:58\u201370. https:\/\/doi.org\/10.1021\/cb300663j.","journal-title":"ACS Chem Biol"},{"key":"2557_CR99","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001161","author":"Y Cui","year":"2024","unstructured":"Cui Y, Zhao K, Meng X, Mao Y, Han C, Shi Z, Yang X, Tong T, Wu L, Liu Z. A CT-based multitask deep learning model for predicting tumor stroma ratio and treatment outcomes in patients with colorectal cancer: a multicenter cohort study. Int J Surg. 2024. https:\/\/doi.org\/10.1097\/JS9.0000000000001161.","journal-title":"Int J Surg"},{"key":"2557_CR100","doi-asserted-by":"publisher","first-page":"7852","DOI":"10.1097\/JS9.0000000000001694","volume":"110","author":"X Huang","year":"2024","unstructured":"Huang X, Wang Q, Xu W, Liu F, Pan L, Jiao H, Yin J, Xu H, Tang H, Tan L. Machine learning to predict lymph node metastasis in T1 esophageal squamous cell carcinoma: a multicenter study. Int J Surg. 2024;110:7852\u20139. https:\/\/doi.org\/10.1097\/JS9.0000000000001694.","journal-title":"Int J Surg"},{"key":"2557_CR101","doi-asserted-by":"publisher","first-page":"109","DOI":"10.22203\/eCM.v047a08","volume":"47","author":"D Hanetseder","year":"2024","unstructured":"Hanetseder D, Schaedl B, Redl H, Marolt Presen D. Extracellular matrix from hiPSC-mesenchymal progenitors modulates the three-lineage differentiation of human bone marrow stromal cells. Eur Cell Mater. 2024;47:109\u201324. https:\/\/doi.org\/10.22203\/eCM.v047a08.","journal-title":"Eur Cell Mater"},{"key":"2557_CR102","doi-asserted-by":"publisher","first-page":"59","DOI":"10.22203\/eCM.v047a05","volume":"47","author":"X Li","year":"2024","unstructured":"Li X, Wang K, Liu M, Zhang Q, Zhou Y. Nicorandil mitigates arthrogenic contracture induced by knee joint extension immobilization in rats: interference with RhoA\/ROCK signaling and TGF-\u03b21\/Smad pathway. Eur Cell Mater. 2024;47:59\u201372. https:\/\/doi.org\/10.22203\/eCM.v047a05.","journal-title":"Eur Cell Mater"},{"key":"2557_CR103","doi-asserted-by":"publisher","first-page":"125","DOI":"10.22203\/eCM.v047a09","volume":"47","author":"S Gullbrand","year":"2024","unstructured":"Gullbrand S, Orozco B, Fainor M, Meadows K, Hilliard R, Boyes M, Mahindroo S, Mauck R, Elliott D, Schaer T, et al. Intervertebral disc degeneration instigates vertebral endplate remodeling and facet joint pathology in a large animal model. Eur Cell Mater. 2024;47:125\u201341. https:\/\/doi.org\/10.22203\/eCM.v047a09.","journal-title":"Eur Cell Mater"},{"key":"2557_CR104","doi-asserted-by":"publisher","first-page":"57","DOI":"10.56434\/j.arch.esp.urol.20247701.8","volume":"77","author":"H Zhao","year":"2024","unstructured":"Zhao H, Ding R, Han J. Curcumin enhances the anti-cancer efficacy of CDK4\/6 inhibitors in prostate cancer. Arch Espa\u00f1ol de Urol. 2024;77:57. https:\/\/doi.org\/10.56434\/j.arch.esp.urol.20247701.8.","journal-title":"Arch Espa\u00f1ol de Urol"},{"key":"2557_CR105","doi-asserted-by":"publisher","first-page":"104","DOI":"10.56434\/j.arch.esp.urol.20247701.14","volume":"77","author":"F Dong","year":"2024","unstructured":"Dong F, Zheng L, Yang G. Construction of a TF-miRNA-mRNA regulatory network for diabetic nephropathy. Arch Espa\u00f1ol de Urol. 2024;77:104. https:\/\/doi.org\/10.56434\/j.arch.esp.urol.20247701.14.","journal-title":"Arch Espa\u00f1ol de Urol"}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-025-02557-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-025-02557-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-025-02557-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T04:21:19Z","timestamp":1744863679000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-025-02557-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":105,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2557"],"URL":"https:\/\/doi.org\/10.1186\/s40001-025-02557-9","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"assertion":[{"value":"13 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study strictly followed the Guidelines for the Care and Use of Experimental Animals published by the National Institutes of Health, and all experimental protocols were approved by the Medical Ethics Review Committee of Ningxia Medical University (IACUC- 2023 -\u2009001).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"296"}}