{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:35Z","timestamp":1792510775659,"version":"4.5.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Tissue and Cell"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.tice.2025.103172","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T15:20:09Z","timestamp":1759591209000},"page":"103172","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["The role of HIF signal mediated autophagy dysfunction in synovial fibroblasts in rheumatoid arthritis and the targeted regulation of kaempferol"],"prefix":"10.1016","volume":"98","author":[{"given":"Meng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0611-4298","authenticated-orcid":false,"given":"Chao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tice.2025.103172_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cyto.2019.154813","article-title":"IL-17, IL-21 and IL-22 polymorphisms in rheumatoid arthritis: a systematic review and meta-analysis","volume":"125","author":"Agonia","year":"2020","journal-title":"Cytokine"},{"key":"10.1016\/j.tice.2025.103172_bib2","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.2174\/1381612829666230904150808","article-title":"Role of Th17 and IL-17 cytokines on inflammatory and auto-immune diseases","volume":"29","author":"Akhter","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.tice.2025.103172_bib3","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1007\/s10753-023-01878-3","article-title":"Novel HIF-1\u03b1 inhibitor AMSP-30m mitigates the pathogenic cellular behaviors of Hypoxia-Stimulated Fibroblast-Like synoviocytes and alleviates Collagen-Induced arthritis in rats via inhibiting sonic hedgehog pathway","volume":"46","author":"Cai","year":"2023","journal-title":"Inflammation"},{"key":"10.1016\/j.tice.2025.103172_bib4","first-page":"49","article-title":"HIF-1\u03b1 dependent RhoA as a novel therapeutic target to regulate rheumatoid arthritis fibroblast-like synoviocytes migration in vitro and in vivo","volume":"40","author":"Chen","year":"2023","journal-title":"J. Orthop. Transl."},{"key":"10.1016\/j.tice.2025.103172_bib5","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1002\/art.41748","article-title":"Notch-1 and Notch-3 mediate Hypoxia-Induced activation of synovial fibroblasts in rheumatoid arthritis","volume":"73","author":"Chen","year":"2021","journal-title":"Arthritis Rheuma"},{"key":"10.1016\/j.tice.2025.103172_bib6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11926-023-01117-6","article-title":"A review of Difficult-to-Treat rheumatoid arthritis: definition, clinical presentation, and management","volume":"25","author":"Conran","year":"2023","journal-title":"Curr. Rheuma Rep."},{"key":"10.1016\/j.tice.2025.103172_bib7","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1093\/bioinformatics\/btw519","article-title":"shinyGEO: a web-based application for analyzing gene expression omnibus datasets","volume":"32","author":"Dumas","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.tice.2025.103172_bib8","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1002\/med.21842","article-title":"The immunosuppressive activity of artemisinin-type drugs towards inflammatory and autoimmune diseases","volume":"41","author":"Efferth","year":"2021","journal-title":"Med Res Rev."},{"key":"10.1016\/j.tice.2025.103172_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.113357","article-title":"Study of kaempferol in the treatment of rheumatoid arthritis through modulation of the NLRP3\/CASP1\/GSDMD axis and T-cell activation: based on network pharmacology, single-cell analysis, and experimental validation","volume":"143","author":"He","year":"2024","journal-title":"Int Immunopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111378","article-title":"The HIF-1\/ BNIP3 pathway mediates mitophagy to inhibit the pyroptosis of fibroblast-like synoviocytes in rheumatoid arthritis","volume":"127","author":"Hong","year":"2024","journal-title":"Int Immunopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib11","article-title":"Bioinformatics-Led discovery of osteoarthritis biomarkers and inflammatory infiltrates","volume":"13","author":"Hu","year":"2022","journal-title":"Front Immunol."},{"key":"10.1016\/j.tice.2025.103172_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117734","article-title":"Role of autophagy in the pathogenesis of rheumatoid arthritis: latest evidence and therapeutic approaches","volume":"254","author":"Karami","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.tice.2025.103172_bib13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41584-022-00790-8","article-title":"Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission","volume":"18","author":"Kurowska-Stolarska","year":"2022","journal-title":"Nat. Rev. Rheuma"},{"key":"10.1016\/j.tice.2025.103172_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104581","article-title":"Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1\u03b1","volume":"152","author":"Lee","year":"2020","journal-title":"Pharm. Res"},{"key":"10.1016\/j.tice.2025.103172_bib15","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.actbio.2022.08.054","article-title":"An ROS-responsive artesunate prodrug nanosystem co-delivers dexamethasone for rheumatoid arthritis treatment through the HIF-1\u03b1\/NF-\u03baB cascade regulation of ROS scavenging and macrophage repolarization","volume":"152","author":"Li","year":"2022","journal-title":"Acta Biomater."},{"key":"10.1016\/j.tice.2025.103172_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2024.116598","article-title":"Targeting IL-17 and its receptors: a feasible way for natural herbal medicines to modulate fibroblast-like synoviocytes in rheumatoid arthritis","volume":"230","author":"Liang","year":"2024","journal-title":"Biochem Pharm."},{"key":"10.1016\/j.tice.2025.103172_bib17","article-title":"Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis","volume":"9","author":"Lin","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.tice.2025.103172_bib18","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pop.2018.02.010","article-title":"Early diagnosis and treatment of rheumatoid arthritis","volume":"45","author":"Littlejohn","year":"2018","journal-title":"Prim. Care"},{"key":"10.1016\/j.tice.2025.103172_bib19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.15586\/aei.v53i3.1278","article-title":"The efficacy and safety of biologic or targeted synthetic DMARDs in rheumatoid arthritis treatment: one year of review 2024","volume":"53","author":"Liu","year":"2025","journal-title":"Allergol. Immunopathol. (Madr. )"},{"key":"10.1016\/j.tice.2025.103172_bib20","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1002\/tox.23802","article-title":"HDAC2 exacerbates rheumatoid arthritis progression via the IL-17-CCL7 signaling pathway","volume":"38","author":"Mao","year":"2023","journal-title":"Environ. Toxicol."},{"key":"10.1016\/j.tice.2025.103172_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/cells10113017","article-title":"Recent advances in understanding the pathogenesis of rheumatoid arthritis: new treatment strategies","volume":"10","author":"Mueller","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.tice.2025.103172_bib22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.intimp.2017.12.011","article-title":"Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway","volume":"55","author":"Pan","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232315054","article-title":"Kaempferol: antimicrobial properties, sources, clinical, and traditional applications","volume":"23","author":"Periferakis","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.tice.2025.103172_bib24","doi-asserted-by":"crossref","DOI":"10.3390\/cells10112857","article-title":"Management of rheumatoid arthritis: an overview","volume":"10","author":"Radu","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.tice.2025.103172_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.117382","article-title":"Nyctanthes arbor-tristis bioactive extract ameliorates LPS-induced inflammation through the inhibition of NF-\u03baB signalling pathway","volume":"320","author":"Sharma","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2020.102425","article-title":"Insights into the treatment of rheumatoid arthritis: a paradigm in Medicine","volume":"110","author":"Smolen","year":"2020","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.tice.2025.103172_bib27","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20192048","article-title":"Interleukin-17 in rheumatoid arthritis: trials and tribulations","volume":"217","author":"Taams","year":"2020","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.tice.2025.103172_bib28","doi-asserted-by":"crossref","first-page":"vi12","DOI":"10.1093\/rheumatology\/keab609","article-title":"Recent progress in treatments of rheumatoid arthritis: an overview of developments in biologics and small molecules, and remaining unmet needs","volume":"60","author":"Tanaka","year":"2021","journal-title":"Rheumatol. Oxf."},{"key":"10.1016\/j.tice.2025.103172_bib29","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.biopha.2018.07.027","article-title":"Novel drug delivery systems for NSAIDs in management of rheumatoid arthritis: an overview","volume":"106","author":"Thakur","year":"2018","journal-title":"Biomed. Pharm."},{"key":"10.1016\/j.tice.2025.103172_bib30","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.3389\/fimmu.2018.01577","article-title":"Autophagy and rheumatoid arthritis: current knowledges and future perspectives","volume":"9","author":"Vomero","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.tice.2025.103172_bib31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1182\/blood.2021011010","article-title":"Neutrophil HIF-1\u03b1 stabilization is augmented by mitochondrial ROS produced via the glycerol 3-phosphate shuttle","volume":"139","author":"Willson","year":"2022","journal-title":"Blood"},{"key":"10.1016\/j.tice.2025.103172_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118061","article-title":"Fangji huangqi decoction alleviates rheumatoid arthritis through regulating HIF-1\u03b1 mediated the angiogenesis and the balance between autophagy and apoptosis","volume":"329","author":"Xu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib33","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003847","article-title":"Internalisation of neutrophils extracellular traps by macrophages aggravate rheumatoid arthritis via Rab5a","volume":"10","author":"Ye","year":"2024","journal-title":"RMD Open"},{"key":"10.1016\/j.tice.2025.103172_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.117019","article-title":"Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways","volume":"318","author":"Yu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib35","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s10020-024-00929-1","article-title":"Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1\/STAT3\/HIF-1\u03b1 signaling","volume":"30","author":"Zhang","year":"2024","journal-title":"Mol. Med."},{"key":"10.1016\/j.tice.2025.103172_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.119615","article-title":"Ermiao san attenuating rheumatoid arthritis via PI3K\/AKT\/mTOR signaling activate HIF-1\u03b1 induced glycolysis","volume":"345","author":"Zhang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.tice.2025.103172_bib37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12920-023-01713-6","article-title":"Genetic association between interleukin-17 and susceptibility to rheumatoid arthritis","volume":"16","author":"Zhao","year":"2023","journal-title":"BMC Med. Genom."},{"key":"10.1016\/j.tice.2025.103172_bib38","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1394108","article-title":"Macrophage polarization in rheumatoid arthritis: signaling pathways, metabolic reprogramming, and crosstalk with synovial fibroblasts","volume":"15","author":"Zheng","year":"2024","journal-title":"Front. Immunol."}],"container-title":["Tissue and Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625004549?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0040816625004549?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:09:21Z","timestamp":1785298161000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0040816625004549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":38,"alternative-id":["S0040816625004549"],"URL":"https:\/\/doi.org\/10.1016\/j.tice.2025.103172","relation":{},"ISSN":["0040-8166"],"issn-type":[{"value":"0040-8166","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The role of HIF signal mediated autophagy dysfunction in synovial fibroblasts in rheumatoid arthritis and the targeted regulation of kaempferol","name":"articletitle","label":"Article Title"},{"value":"Tissue and Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tice.2025.103172","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"103172"}}