{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T17:11:41Z","timestamp":1770570701037,"version":"3.49.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY1259"],"award-info":[{"award-number":["2023KY1259"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY354"],"award-info":[{"award-number":["2023KY354"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2024KY1719"],"award-info":[{"award-number":["2024KY1719"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016114","name":"Zhejiang Medical Association","doi-asserted-by":"publisher","award":["2024ZYCZ112"],"award-info":[{"award-number":["2024ZYCZ112"]}],"id":[{"id":"10.13039\/501100016114","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Signalling"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.cellsig.2025.112300","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T23:54:44Z","timestamp":1765238084000},"page":"112300","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Gentianine suppresses renal cell carcinoma progression via direct interaction with KDM5B and ferroptosis activation"],"prefix":"10.1016","volume":"139","author":[{"given":"Jintao","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangrong","family":"Ying","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gangfeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenggang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenghao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haojie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.cellsig.2025.112300_bb0005","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.eururo.2022.08.019","article-title":"Epidemiology of renal cell carcinoma: 2022 update","volume":"82","author":"Bukavina","year":"2022","journal-title":"Eur. Urol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0010","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1001\/jama.2024.12848","article-title":"Renal cell carcinoma: a review","volume":"332","author":"Rose","year":"2024","journal-title":"JAMA"},{"key":"10.1016\/j.cellsig.2025.112300_bb0015","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41585-024-00876-w","article-title":"Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma","volume":"21","author":"Liao","year":"2024","journal-title":"Nat. Rev. Urol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2024.102801","article-title":"Targeting HIF-2\u03b1 and anemia: a therapeutic breakthrough for clear-cell renal cell carcinoma","volume":"129","author":"Rioja","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"10.1016\/j.cellsig.2025.112300_bb0025","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11934-025-01276-2","article-title":"Multiomics in renal cell carcinoma: current landscape and future directions for precision medicine","volume":"26","author":"Gavi","year":"2025","journal-title":"Curr. Urol. Rep."},{"key":"10.1016\/j.cellsig.2025.112300_bb0030","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12929-024-01111-9","article-title":"Tumor-initiating and metastasis-initiating cells of clear-cell renal cell carcinoma","volume":"32","author":"Pham","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.cellsig.2025.112300_bb0035","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41581-023-00800-2","article-title":"Metabolic alterations in hereditary and sporadic renal cell carcinoma","volume":"20","author":"Coffey","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0040","doi-asserted-by":"crossref","first-page":"706","DOI":"10.2174\/0109298665330781240830042601","article-title":"Association between higher expression of Vav1 in hepatocellular carcinoma and unfavourable clinicopathological features and prognosis","volume":"31","author":"Ye","year":"2024","journal-title":"Protein Pept. Lett."},{"key":"10.1016\/j.cellsig.2025.112300_bb0045","article-title":"At the crossroads of TNF \u03b1 signaling and cancer","volume":"17","author":"Manohar","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0050","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41585-022-00676-0","article-title":"Prognostic and predictive biomarkers for immunotherapy in advanced renal cell carcinoma","volume":"20","author":"Rosellini","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0055","first-page":"1","article-title":"The selection of targeted therapies for relapsed or refractory advanced renal cell carcinoma","author":"Giri","year":"2025","journal-title":"Expert Rev. Anticancer Ther."},{"key":"10.1016\/j.cellsig.2025.112300_bb0060","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1007\/s10753-017-0583-8","article-title":"Protective effect of gentianine, a compound from Du Huo Ji Sheng Tang, against Freund\u2019s complete adjuvant-induced arthritis in rats","volume":"40","author":"Wenjin","year":"2017","journal-title":"Inflammation"},{"key":"10.1016\/j.cellsig.2025.112300_bb0065","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/ptr.4763","article-title":"Anti-diabetic activity of swertiamarin is due to an active metabolite, gentianine, that upregulates PPAR-\u03b3 gene expression in 3T3-L1 cells","volume":"27","author":"Vaidya","year":"2013","journal-title":"Phytother. Res."},{"key":"10.1016\/j.cellsig.2025.112300_bb0070","first-page":"460","article-title":"Gentiana scabra reduces SR-A expression and oxidized-LDL uptake in human macrophages","volume":"32","author":"Lin","year":"2016","journal-title":"Acta Cardiol. Sin."},{"key":"10.1016\/j.cellsig.2025.112300_bb0075","article-title":"Gentiana scabra restrains hepatic pro-inflammatory macrophages to ameliorate non-alcoholic fatty liver disease","volume":"12","author":"Zheng","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0080","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1248\/bpb.28.750","article-title":"Effects of gentianine on the production of pro-inflammatory cytokines in male Sprague-Dawley rats treated with lipopolysaccharide (LPS)","volume":"28","author":"Kwak","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.cellsig.2025.112300_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105913","article-title":"Machine learning enables discovery of gentianine targeting TLR4\/NF-\u03baB pathway to repair ischemic stroke injury","volume":"173","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.cellsig.2025.112300_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111214","article-title":"Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4\/NLRP3-mediated pyroptosis","volume":"126","author":"Li","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0095","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00018-025-05812-8","article-title":"Ferroptosis in cancer: revealing the multifaceted functions of mitochondria","volume":"82","author":"Ding","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.cellsig.2025.112300_bb0100","doi-asserted-by":"crossref","DOI":"10.1007\/s10495-025-02192-z","article-title":"The impact of lipid metabolism on ferroptosis in myocardial ischemia-reperfusion injury","author":"Li","year":"2025","journal-title":"Apoptosis"},{"key":"10.1016\/j.cellsig.2025.112300_bb0105","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s12943-025-02457-w","article-title":"Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: metabolic vulnerabilities and therapeutic targeting","volume":"24","author":"Deng","year":"2025","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.cellsig.2025.112300_bb0110","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41420-025-02744-x","article-title":"Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance","volume":"11","author":"Singh","year":"2025","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.cellsig.2025.112300_bb0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.20517\/cdr.2024.151","article-title":"Ferroptosis-related signaling pathways in cancer drug resistance","volume":"8","author":"Yang","year":"2025","journal-title":"Cancer Drug Resist."},{"key":"10.1016\/j.cellsig.2025.112300_bb0120","doi-asserted-by":"crossref","DOI":"10.1002\/imt2.70070","article-title":"The microbiome in cancer","author":"Lin","year":"2025","journal-title":"IMeta"},{"key":"10.1016\/j.cellsig.2025.112300_bb0125","first-page":"32","article-title":"Heterogeneity of intratumoral microbiota within the tumor microenvironment and relationship to tumor development","volume":"1","author":"Gao","year":"2025","journal-title":"Med. Res."},{"key":"10.1016\/j.cellsig.2025.112300_bb0130","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41418-024-01257-x","article-title":"Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16\/TOP2A axis","volume":"31","author":"Zhang","year":"2024","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.cellsig.2025.112300_bb0135","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41392-025-02163-5","article-title":"Epstein-Barr virus hijacks histone demethylase machinery to drive epithelial malignancy progression through KDM5B upregulation","volume":"10","author":"Zhou","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.cellsig.2025.112300_bb0140","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.15252\/embr.201642198","article-title":"Capture-C reveals preformed chromatin interactions between <scp>HIF<\/scp> \u2212binding sites and distant promoters","volume":"17","author":"Platt","year":"2016","journal-title":"EMBO Rep."},{"key":"10.1016\/j.cellsig.2025.112300_bb0145","article-title":"Mitochondrial reactive oxygen species formation determines ACSL4\/LPCAT2-mediated ferroptosis","volume":"12","author":"Merkel","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"10.1016\/j.cellsig.2025.112300_bb0150","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1210\/en.2014-1029","article-title":"ROS are critical for endometrial breakdown via NF-\u03baB-COX-2 signaling in a female mouse menstrual-like model","volume":"155","author":"Wu","year":"2014","journal-title":"Endocrinology"},{"key":"10.1016\/j.cellsig.2025.112300_bb0155","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1016\/j.apsb.2021.03.036","article-title":"Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1","volume":"11","author":"Kong","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.cellsig.2025.112300_bb0160","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.7150\/ijbs.77979","article-title":"Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation","volume":"19","author":"Zhou","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.cellsig.2025.112300_bb0165","article-title":"USP38 couples histone ubiquitination and methylation via KDM5B to resolve inflammation","volume":"7","author":"Zhao","year":"2020","journal-title":"Adv. Sci. (Weinh.)"},{"key":"10.1016\/j.cellsig.2025.112300_bb0170","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.cellsig.2025.112300_bb0175","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1021\/acs.chemrestox.3c00347","article-title":"Chemoproteomic profiling of erastin-interacting proteins","volume":"37","author":"Li","year":"2024","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0180","article-title":"Regulating miRNAs expression by resveratrol: novel insights based on molecular mechanism and strategies for cancer therapy","volume":"17","author":"Keshavarzmotamed","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0185","doi-asserted-by":"crossref","DOI":"10.2174\/0118761429273223231124072223","article-title":"Molecular insight into the apoptotic mechanism of cancer cells: an explicative review","volume":"17","author":"Karati","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.112300_bb0190","doi-asserted-by":"crossref","first-page":"786","DOI":"10.21037\/tlcr-22-318","article-title":"Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance","volume":"11","author":"Zhang","year":"2022","journal-title":"Transl. Lung Cancer Res."},{"key":"10.1016\/j.cellsig.2025.112300_bb0195","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1186\/s12885-025-14729-1","article-title":"METTL16-dependent GPX4 m6A modification links ferroptosis to NSCLC TKIs resistance","volume":"25","author":"Zeng","year":"2025","journal-title":"BMC Cancer"},{"key":"10.1016\/j.cellsig.2025.112300_bb0200","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cpan.2024.12.002","article-title":"Advances in drug discovery based on network pharmacology and omics technology","volume":"21","author":"Liu","year":"2024","journal-title":"Curr. Pharm. Anal."},{"key":"10.1016\/j.cellsig.2025.112300_bb0205","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cpan.2024.12.001","article-title":"Emerging trends and hot topics in the application of multi-omics in drug discovery: a bibliometric and visualized study","volume":"21","author":"Wang","year":"2024","journal-title":"Curr. Pharm. Anal."}],"container-title":["Cellular Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825007156?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825007156?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:56:56Z","timestamp":1770494216000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0898656825007156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":41,"alternative-id":["S0898656825007156"],"URL":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.112300","relation":{},"ISSN":["0898-6568"],"issn-type":[{"value":"0898-6568","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gentianine suppresses renal cell carcinoma progression via direct interaction with KDM5B and ferroptosis activation","name":"articletitle","label":"Article Title"},{"value":"Cellular Signalling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.112300","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112300"}}