{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:01:48Z","timestamp":1792638108916,"version":"4.5.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and methods<\/jats:title>\n                    <jats:p>Hypoxia, glycolysis, and lactylation are key processes in liver fibrosis (LF) and hepatocarcinogenesis, yet the role of hypoxia-, glycolysis-, and lactylation-related genes (HGLRGs) in LF is poorly defined. Here, we systematically analyzed transcriptomic data from LF samples to identify differentially expressed HGLRGs, validate by single-cell transcriptomics, construct co-expression networks, evaluate their biological functions, diagnostic performance, immune relevance, and explore potential therapeutic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven HGLRGs\u2014CHST4, FABP5, GPC3, SOX9, SRPX, IFI16, and ISG20\u2014were significantly upregulated in LF and demonstrated strong diagnostic value. FABP5 and ISG20 were consistently elevated in activated stellate cells and human cirrhotic livers. Enrichment analyses indicated that these genes modulate metabolic pathways and drive immune-mediated fibrotic responses. Immune profiling revealed that ISG20 expression inversely correlated with resting NK cell infiltration, and SOX9 with M2 macrophage infiltration. Molecular docking identified seven FDA-approved drugs, including aspirin, Methylene blue, tamoxifen, vorinostat, valproic acid, rosiglitazone and acetaminophen, as potential HGLRG-targeting agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HGLRGs are aberrantly upregulated and actively contribute to LF progression through metabolic dysregulation and immune remodeling. FABP5 and ISG20 represents promising biomarkers and therapeutic target. This study providing novel diagnostic markers, drug repurposing opportunities, and strategies for improved clinical management of liver cirrhosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08147-5","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:36:18Z","timestamp":1778906178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The impact of hypoxia and glycolysis on liver fibrosis"],"prefix":"10.1186","volume":"24","author":[{"given":"Yun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusheng","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4838-9342","authenticated-orcid":false,"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"8147_CR1","doi-asserted-by":"publisher","first-page":"2328521","DOI":"10.1080\/07853890.2024.2328521","volume":"56","author":"Y Wang","year":"2024","unstructured":"Wang Y, Wang M, Liu C, Hao M, Wang W, Li Y, et al. Global burden of liver cirrhosis 1990\u20132019 and 20 years forecast: results from the global burden of disease study 2019. Ann Med. 2024;56:2328521. https:\/\/doi.org\/10.1080\/07853890.2024.2328521.","journal-title":"Ann Med"},{"key":"8147_CR2","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/hep.31173","volume":"72","author":"JM Paik","year":"2020","unstructured":"Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatol Baltim Md. 2020;72:1605\u201316. https:\/\/doi.org\/10.1002\/hep.31173.","journal-title":"Hepatol Baltim Md"},{"key":"8147_CR3","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","volume":"574","author":"D Zhang","year":"2019","unstructured":"Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574:575\u201380. https:\/\/doi.org\/10.1038\/s41586-019-1678-1.","journal-title":"Nature"},{"key":"8147_CR4","doi-asserted-by":"publisher","first-page":"2948","DOI":"10.3390\/biomedicines11112948","volume":"11","author":"X Zhang","year":"2023","unstructured":"Zhang X, Li Y, Chen Y. Development of a Comprehensive Gene Signature Linking Hypoxia, Glycolysis, Lactylation, and Metabolomic Insights in Gastric Cancer through the Integration of Bulk and Single-Cell RNA-Seq Data. Biomedicines. 2023;11:2948. https:\/\/doi.org\/10.3390\/biomedicines11112948.","journal-title":"Biomedicines"},{"issue":"4","key":"8147_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115457","volume":"44","author":"Lingyun Zhou","year":"2025","unstructured":"Zhou L, Liu CH, Lv D, Sample KM, Rojas \u00c1, Zhang Y, et al. Halting hepatocellular carcinoma: Identifying intercellular crosstalk in HBV-driven disease. Cell Rep. 2025;44(4):115457. https:\/\/doi.org\/10.1016\/j.celrep.2025.115457.","journal-title":"Cell Rep"},{"key":"8147_CR6","doi-asserted-by":"publisher","first-page":"114135","DOI":"10.1016\/j.yexcr.2024.114135","volume":"440","author":"S Wu","year":"2024","unstructured":"Wu S, Li J, Zhan Y. H3K18 lactylation accelerates liver fibrosis progression through facilitating SOX9 transcription. Exp Cell Res. 2024;440:114135. https:\/\/doi.org\/10.1016\/j.yexcr.2024.114135.","journal-title":"Exp Cell Res"},{"key":"8147_CR7","doi-asserted-by":"publisher","first-page":"111507","DOI":"10.1016\/j.cbi.2025.111507","volume":"414","author":"W Chen","year":"2025","unstructured":"Chen W, Wang P, Xie Y, Xie D, Wang H, Bu N, et al. Histone lactylation-augmented IRF4 is implicated in arsenite-induced liver fibrosis via modulating Th17 cell differentiation. Chem Biol Interact. 2025;414:111507. https:\/\/doi.org\/10.1016\/j.cbi.2025.111507.","journal-title":"Chem Biol Interact"},{"key":"8147_CR8","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1016\/j.cmet.2023.06.013","volume":"35","author":"H Rho","year":"2023","unstructured":"Rho H, Terry AR, Chronis C, Hay N. Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis. Cell Metab. 2023;35:1406\u2013e14238. https:\/\/doi.org\/10.1016\/j.cmet.2023.06.013.","journal-title":"Cell Metab"},{"key":"8147_CR9","doi-asserted-by":"publisher","first-page":"167659","DOI":"10.1016\/j.bbadis.2025.167659","volume":"1871","author":"C Raju","year":"2025","unstructured":"Raju C, Sankaranarayanan K. Insights on post-translational modifications in fatty liver and fibrosis progression. Biochim Biophys Acta Mol Basis Dis. 2025;1871:167659. https:\/\/doi.org\/10.1016\/j.bbadis.2025.167659.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"8147_CR10","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","volume":"41","author":"T Barrett","year":"2012","unstructured":"Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets\u2014update. Nucleic Acids Res. 2012;41:D991\u20135. https:\/\/doi.org\/10.1093\/nar\/gks1193.","journal-title":"Nucleic Acids Res"},{"key":"8147_CR11","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1093\/bioinformatics\/btv313","volume":"31","author":"M Yoo","year":"2015","unstructured":"Yoo M, Shin J, Kim J, Ryall KA, Lee K, Lee S, et al. DSigDB: drug signatures database for gene set analysis. Bioinforma Oxf Engl. 2015;31:3069\u201371. https:\/\/doi.org\/10.1093\/bioinformatics\/btv313.","journal-title":"Bioinforma Oxf Engl"},{"key":"8147_CR12","doi-asserted-by":"publisher","first-page":"W159","DOI":"10.1093\/nar\/gkac394","volume":"50","author":"Y Liu","year":"2022","unstructured":"Liu Y, Yang X, Gan J, Chen S, Xiao Z-X, Cao Y. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022;50:W159\u201364. https:\/\/doi.org\/10.1093\/nar\/gkac394.","journal-title":"Nucleic Acids Res"},{"key":"8147_CR13","doi-asserted-by":"publisher","first-page":"bbac087","DOI":"10.1093\/bib\/bbac087","volume":"23","author":"X Yang","year":"2022","unstructured":"Yang X, Liu Y, Gan J, Xiao Z-X, Cao Y. FitDock: protein-ligand docking by template fitting. Brief Bioinform. 2022;23:bbac087. https:\/\/doi.org\/10.1093\/bib\/bbac087.","journal-title":"Brief Bioinform"},{"key":"8147_CR14","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41419-024-06595-9","volume":"15","author":"Y Li","year":"2024","unstructured":"Li Y, Zhang X, Liu N, Liu R, Zhang W, Chen L, et al. RNF166 promotes colorectal cancer progression by recognizing and destabilizing poly-ADP-ribosylated angiomotins. Cell Death Dis. 2024;15:211. https:\/\/doi.org\/10.1038\/s41419-024-06595-9.","journal-title":"Cell Death Dis"},{"key":"8147_CR15","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.15252\/emmm.201707860","volume":"9","author":"VS Athwal","year":"2017","unstructured":"Athwal VS, Pritchett J, Llewellyn J, Martin K, Camacho E, Raza SM, et al. SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis. EMBO Mol Med. 2017;9:1696\u2013710. https:\/\/doi.org\/10.15252\/emmm.201707860.","journal-title":"EMBO Mol Med"},{"key":"8147_CR16","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.surg.2019.10.013","volume":"167","author":"W Udomsinprasert","year":"2020","unstructured":"Udomsinprasert W, Angkathunyakul N, Klaikeaw N, Vejchapipat P, Poovorawan Y, Honsawek S. Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia. Surgery. 2020;167:560\u20138. https:\/\/doi.org\/10.1016\/j.surg.2019.10.013.","journal-title":"Surgery"},{"key":"8147_CR17","doi-asserted-by":"publisher","first-page":"3027200","DOI":"10.1155\/2022\/3027200","volume":"2022","author":"Y-C Sun","year":"2022","unstructured":"Sun Y-C, Qiu Z-Z, Wen F-L, Yin J-Q, Zhou H. Revealing Potential Diagnostic Gene Biomarkers Associated with Immune Infiltration in Patients with Renal Fibrosis Based on Machine Learning Analysis. J Immunol Res. 2022;2022:3027200. https:\/\/doi.org\/10.1155\/2022\/3027200.","journal-title":"J Immunol Res"},{"key":"8147_CR18","doi-asserted-by":"publisher","first-page":"190","DOI":"10.21037\/atm-22-366","volume":"10","author":"Z Hu","year":"2022","unstructured":"Hu Z, Liu Y, Zhu Y, Cui H, Pan J. Identification of key biomarkers and immune infiltration in renal interstitial fibrosis. Ann Transl Med. 2022;10:190. https:\/\/doi.org\/10.21037\/atm-22-366.","journal-title":"Ann Transl Med"},{"key":"8147_CR19","doi-asserted-by":"publisher","first-page":"27858","DOI":"10.18632\/oncotarget.25559","volume":"9","author":"H Van Tong","year":"2018","unstructured":"Van Tong H, Hoan NX, Binh MT, Quyen DT, Meyer CG, Song LH, et al. Interferon-stimulated gene 20\u00a0kDa protein serum levels and clinical outcome of hepatitis B virus-related liver diseases. Oncotarget. 2018;9:27858\u201371. https:\/\/doi.org\/10.18632\/oncotarget.25559.","journal-title":"Oncotarget"},{"key":"8147_CR20","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.3892\/ijmm.2019.4291","volume":"44","author":"H-B Wang","year":"2019","unstructured":"Wang H-B, Huang R, Yang K, Xu M, Fan D, Liu M-X, et al. Identification of differentially expressed genes and preliminary validations in cardiac pathological remodeling induced by transverse aortic constriction. Int J Mol Med. 2019;44:1447\u201361. https:\/\/doi.org\/10.3892\/ijmm.2019.4291.","journal-title":"Int J Mol Med"},{"key":"8147_CR21","doi-asserted-by":"publisher","first-page":"951582","DOI":"10.3389\/fimmu.2022.951582","volume":"13","author":"S Feng","year":"2022","unstructured":"Feng S, Xu Y, Dai Z, Yin H, Zhang K, Shen Y. Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer. Front Immunol. 2022;13:951582. https:\/\/doi.org\/10.3389\/fimmu.2022.951582.","journal-title":"Front Immunol"},{"key":"8147_CR22","doi-asserted-by":"publisher","first-page":"5998","DOI":"10.7150\/thno.112247","volume":"15","author":"Q He","year":"2025","unstructured":"He Q, Chang X, Zhang H, Hao Q, Zhi J, Shi H, et al. Nuclear damage-induced DNA damage response coupled with IFI16-driven ECM remodeling underlies dilated cardiomyopathy. Theranostics. 2025;15:5998\u20136021. https:\/\/doi.org\/10.7150\/thno.112247.","journal-title":"Theranostics"},{"key":"8147_CR23","doi-asserted-by":"publisher","first-page":"E4492","DOI":"10.1073\/pnas.1316194110","volume":"110","author":"MH Orzalli","year":"2013","unstructured":"Orzalli MH, Conwell SE, Berrios C, DeCaprio JA, Knipe DM. Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA. Proc Natl Acad Sci U S A. 2013;110:E4492\u20134501. https:\/\/doi.org\/10.1073\/pnas.1316194110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8147_CR24","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/ni.1932","volume":"11","author":"L Unterholzner","year":"2010","unstructured":"Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11:997\u20131004. https:\/\/doi.org\/10.1038\/ni.1932.","journal-title":"Nat Immunol"},{"key":"8147_CR25","doi-asserted-by":"publisher","first-page":"112413","DOI":"10.1016\/j.isci.2025.112413","volume":"28","author":"A Iannucci","year":"2025","unstructured":"Iannucci A, Lacarbonara D, Caneparo V, Castiglioni F, Buttic\u00e8 A, Raviola S, et al. The PYRIN domain is required for TLR4-mediated inflammation by PYHIN family members. iScience. 2025;28:112413. https:\/\/doi.org\/10.1016\/j.isci.2025.112413.","journal-title":"iScience"},{"key":"8147_CR26","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1016\/j.celrep.2019.02.042","volume":"26","author":"K Veerman","year":"2019","unstructured":"Veerman K, Tardiveau C, Martins F, Coudert J, Girard J-P. Single-Cell Analysis Reveals Heterogeneity of High Endothelial Venules and Different Regulation of Genes Controlling Lymphocyte Entry to Lymph Nodes. Cell Rep. 2019;26:3116\u2013e31315. https:\/\/doi.org\/10.1016\/j.celrep.2019.02.042.","journal-title":"Cell Rep"},{"key":"8147_CR27","doi-asserted-by":"publisher","first-page":"554331","DOI":"10.3389\/fonc.2020.554331","volume":"10","author":"L Zhang","year":"2020","unstructured":"Zhang L, Fan Y, Wang X, Yang M, Wu X, Huang W, et al. Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors. Front Oncol. 2020;10:554331. https:\/\/doi.org\/10.3389\/fonc.2020.554331.","journal-title":"Front Oncol"},{"key":"8147_CR28","doi-asserted-by":"publisher","first-page":"eadd8945","DOI":"10.1126\/sciimmunol.add8945","volume":"8","author":"T Fabre","year":"2023","unstructured":"Fabre T, Barron AMS, Christensen SM, Asano S, Bound K, Lech MP, et al. Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation. Sci Immunol. 2023;8:eadd8945. https:\/\/doi.org\/10.1126\/sciimmunol.add8945.","journal-title":"Sci Immunol"},{"key":"8147_CR29","doi-asserted-by":"publisher","first-page":"9575","DOI":"10.1038\/s41467-024-53700-9","volume":"15","author":"M Cruz Tleugabulova","year":"2024","unstructured":"Cruz Tleugabulova M, Melo SP, Wong A, Arlantico A, Liu M, Webster JD, et al. Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade. Nat Commun. 2024;15:9575. https:\/\/doi.org\/10.1038\/s41467-024-53700-9.","journal-title":"Nat Commun"},{"key":"8147_CR30","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000542946","volume":"17","author":"J Rao","year":"2025","unstructured":"Rao J, Ye D, Ren A, He W, Zhang X, Chen P, et al. Macrophage Evolution during Progression of Hepatitis Virus B-Related Acute-on-Chronic Liver Failure. J Innate Immun. 2025;17:29\u201343. https:\/\/doi.org\/10.1159\/000542946.","journal-title":"J Innate Immun"},{"key":"8147_CR31","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jare.2021.11.011","volume":"40","author":"Q Lei","year":"2022","unstructured":"Lei Q, Yu Z, Li H, Cheng J, Wang Y. Fatty acid-binding protein 5 aggravates pulmonary artery fibrosis in pulmonary hypertension secondary to left heart disease via activating wnt\/\u03b2-catenin pathway. J Adv Res. 2022;40:197\u2013206. https:\/\/doi.org\/10.1016\/j.jare.2021.11.011.","journal-title":"J Adv Res"},{"key":"8147_CR32","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1667\/RR14901.1","volume":"189","author":"J Song","year":"2018","unstructured":"Song J, Zhang H, Wang Z, Xu W, Zhong L, Cao J, et al. The Role of FABP5 in Radiation-Induced Human Skin Fibrosis. Radiat Res. 2018;189:177\u201386. https:\/\/doi.org\/10.1667\/RR14901.1.","journal-title":"Radiat Res"},{"key":"8147_CR33","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s12013-021-00974-1","volume":"79","author":"M \u00d6zel","year":"2021","unstructured":"\u00d6zel M, Baskol M, Akal\u0131n H, Baskol G. Suberoylanilide Hydroxamic Acid (SAHA) Reduces Fibrosis Markers and Deactivates Human Stellate Cells via the Epithelial-Mesenchymal Transition (EMT). Cell Biochem Biophys. 2021;79:349\u201357. https:\/\/doi.org\/10.1007\/s12013-021-00974-1.","journal-title":"Cell Biochem Biophys"},{"key":"8147_CR34","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/hep.23334","volume":"51","author":"I Mannaerts","year":"2010","unstructured":"Mannaerts I, Nuytten NR, Rogiers V, Vanderkerken K, van Grunsven LA, Geerts A. Chronic administration of valproic acid inhibits activation of mouse hepatic stellate cells in vitro and in vivo. Hepatol Baltim Md. 2010;51:603\u201314. https:\/\/doi.org\/10.1002\/hep.23334.","journal-title":"Hepatol Baltim Md"},{"key":"8147_CR35","doi-asserted-by":"publisher","first-page":"93","DOI":"10.7150\/ijbs.28642","volume":"15","author":"P Lu","year":"2019","unstructured":"Lu P, Yan M, He L, Li J, Ji Y, Ji J. Crosstalk between Epigenetic Modulations in Valproic Acid Deactivated Hepatic Stellate Cells: An Integrated Protein and miRNA Profiling Study. Int J Biol Sci. 2019;15:93\u2013104. https:\/\/doi.org\/10.7150\/ijbs.28642.","journal-title":"Int J Biol Sci"},{"key":"8147_CR36","doi-asserted-by":"publisher","first-page":"e1362","DOI":"10.7717\/peerj.1362","volume":"3","author":"W Wang","year":"2015","unstructured":"Wang W, Yan M, Ji Q, Lu J, Ji Y, Ji J. Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-\u03baB1. PeerJ. 2015;3:e1362. https:\/\/doi.org\/10.7717\/peerj.1362.","journal-title":"PeerJ"},{"key":"8147_CR37","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.hbpd.2018.09.013","volume":"17","author":"Y Wang","year":"2018","unstructured":"Wang Y, Zhao L, Jiao F-Z, Zhang W-B, Chen Q, Gong Z-J. Histone deacetylase inhibitor suberoylanilide hydroxamic acid alleviates liver fibrosis by suppressing the transforming growth factor-\u03b21 signal pathway. Hepatobiliary Pancreat Dis Int HBPD INT. 2018;17:423\u20139. https:\/\/doi.org\/10.1016\/j.hbpd.2018.09.013.","journal-title":"Hepatobiliary Pancreat Dis Int HBPD INT"},{"key":"8147_CR38","doi-asserted-by":"publisher","first-page":"e08751","DOI":"10.1002\/advs.202508751","volume":"12","author":"Y Guan","year":"2025","unstructured":"Guan Y, Cui L, Inchai J, Fang Z, Law J, Brito AAG, et al. AI-Assisted Drug Re-Purposing for Human Liver Fibrosis. Adv Sci Weinh Baden-Wurtt Ger. 2025;12:e08751. https:\/\/doi.org\/10.1002\/advs.202508751.","journal-title":"Adv Sci Weinh Baden-Wurtt Ger"},{"key":"8147_CR39","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3892\/mmr.2022.12697","volume":"25","author":"Y Sun","year":"2022","unstructured":"Sun Y, Liu B, Xie J, Jiang X, Xiao B, Hu X, et al. Aspirin attenuates liver fibrosis by suppressing TGF\u2013\u03b21\/Smad signaling. Mol Med Rep. 2022;25:181. https:\/\/doi.org\/10.3892\/mmr.2022.12697.","journal-title":"Mol Med Rep"},{"key":"8147_CR40","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3892\/etm.2023.11931","volume":"25","author":"Z Wu","year":"2023","unstructured":"Wu Z, Wu Y, Zhong W, Zhong Q, Rao S, Yu D, et al. The hepatoprotective effect of aspirin on carbon tetrachloride\u2013induced hepatic fibrosis via inhibition of TGF\u03b2\u20131 pathway and pro\u2013inflammatory cytokines IL\u20131\u03b2 and COX\u20132 in rats. Exp Ther Med. 2023;25:232. https:\/\/doi.org\/10.3892\/etm.2023.11931.","journal-title":"Exp Ther Med"},{"key":"8147_CR41","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.18632\/aging.103002","volume":"12","author":"Y Liu","year":"2020","unstructured":"Liu Y, Nong L, Jia Y, Tan A, Duan L, Lu Y, et al. Aspirin alleviates hepatic fibrosis by suppressing hepatic stellate cells activation via the TLR4\/NF-\u03baB pathway. Aging. 2020;12:6058\u201366. https:\/\/doi.org\/10.18632\/aging.103002.","journal-title":"Aging"},{"key":"8147_CR42","doi-asserted-by":"publisher","first-page":"e70696","DOI":"10.1111\/jcmm.70696","volume":"29","author":"S Wang","year":"2025","unstructured":"Wang S, Sun M, Tang M, Yang Z, Shan J, Yang C. Aspirin Attenuates Liver Fibrosis via Autophagy Induction. J Cell Mol Med. 2025;29:e70696. https:\/\/doi.org\/10.1111\/jcmm.70696.","journal-title":"J Cell Mol Med"},{"key":"8147_CR43","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1002\/jcp.24367","volume":"228","author":"KJ Schunke","year":"2013","unstructured":"Schunke KJ, Coyle L, Merrill GF, Denhardt DT. Acetaminophen attenuates doxorubicin-induced cardiac fibrosis via osteopontin and GATA4 regulation: reduction of oxidant levels. J Cell Physiol. 2013;228:2006\u201314. https:\/\/doi.org\/10.1002\/jcp.24367.","journal-title":"J Cell Physiol"},{"key":"8147_CR44","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/j.bbrc.2019.09.084","volume":"519","author":"Z Wei","year":"2019","unstructured":"Wei Z, Zhao D, Zhang Y, Chen Y, Zhang S, Li Q, et al. Rosiglitazone ameliorates bile duct ligation-induced liver fibrosis by down-regulating NF-\u03baB-TNF-\u03b1 signaling pathway in a PPAR\u03b3-dependent manner. Biochem Biophys Res Commun. 2019;519:854\u201360. https:\/\/doi.org\/10.1016\/j.bbrc.2019.09.084.","journal-title":"Biochem Biophys Res Commun"},{"key":"8147_CR45","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.3390\/biomedicines10051209","volume":"10","author":"D \u0160isl","year":"2022","unstructured":"\u0160isl D, Flegar D, Filipovi\u0107 M, Tur\u010di\u0107 P, Planini\u0107 P, \u0160u\u0107ur A, et al. Tamoxifen Ameliorates Cholestatic Liver Fibrosis in Mice: Upregulation of TGF\u03b2 and IL6 Is a Potential Protective Mechanism. Biomedicines. 2022;10:1209. https:\/\/doi.org\/10.3390\/biomedicines10051209.","journal-title":"Biomedicines"},{"key":"8147_CR46","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1186\/s12967-023-04470-3","volume":"21","author":"T Zhao","year":"2023","unstructured":"Zhao T, Sun Z, Lai X, Lu H, Liu L, Li S, et al. Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription. J Transl Med. 2023;21:614. https:\/\/doi.org\/10.1186\/s12967-023-04470-3.","journal-title":"J Transl Med"},{"key":"8147_CR47","doi-asserted-by":"publisher","first-page":"111003","DOI":"10.1016\/j.biopha.2020.111003","volume":"133","author":"SJ Tingskov","year":"2021","unstructured":"Tingskov SJ, Jensen MS, Pedersen C-ET, de Araujo IBBA, Mutsaers HAM, N\u00f8rregaard R. Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction. Biomed Pharmacother Biomedecine Pharmacother. 2021;133:111003. https:\/\/doi.org\/10.1016\/j.biopha.2020.111003.","journal-title":"Biomed Pharmacother Biomedecine Pharmacother"},{"key":"8147_CR48","doi-asserted-by":"publisher","first-page":"e0268178","DOI":"10.1371\/journal.pone.0268178","volume":"17","author":"SH Seo","year":"2022","unstructured":"Seo SH, Choi GJ, Lee OH, Kang H. Effect of methylene blue on experimental postoperative adhesion: A systematic review and meta-analysis. PLoS ONE. 2022;17:e0268178. https:\/\/doi.org\/10.1371\/journal.pone.0268178.","journal-title":"PLoS ONE"},{"key":"8147_CR49","doi-asserted-by":"publisher","first-page":"701","DOI":"10.7326\/0003-4819-133-9-200011070-00012","volume":"133","author":"P Schenk","year":"2000","unstructured":"Schenk P, Madl C, Rezaie-Majd S, Lehr S, M\u00fcller C. Methylene blue improves the hepatopulmonary syndrome. Ann Intern Med. 2000;133:701\u20136. https:\/\/doi.org\/10.7326\/0003-4819-133-9-200011070-00012.","journal-title":"Ann Intern Med"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08147-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08147-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08147-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:30:18Z","timestamp":1783636218000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08147-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,16]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8147"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08147-5","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,16]]},"assertion":[{"value":"24 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The full study protocol was reviewed and approved by the Ethical Committee of The Fourth Hospital of Changsha (CSSDSYY-YXLL-SC-2025-02-90) and conformed to the principles of the Declaration of Helsinki. All patients provided informed consent for study participation and publication of anonymized data and images (proxies used where necessary).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"875"}}