{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:25:13Z","timestamp":1787063113182,"version":"build-2736575974"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274189"],"award-info":[{"award-number":["82274189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.intimp.2025.114735","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T19:42:01Z","timestamp":1745696521000},"page":"114735","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Regulation of P-glycoprotein through CaMKII\/cPLA2 pathway in lymphocytes for treating refractory rheumatoid arthritis by manidipine"],"prefix":"10.1016","volume":"156","author":[{"given":"Yan-Hua","family":"YAN","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Lu","family":"LI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"QU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Chan","family":"HUAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan-Tong","family":"QIU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"QU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"ZHOU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"XIE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2025.114735_bb0005","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1001\/jama.2022.0786","article-title":"What is rheumatoid arthritis?","volume":"327","author":"Smith","year":"2022","journal-title":"JAMA"},{"key":"10.1016\/j.intimp.2025.114735_bb0010","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1016\/S0140-6736(17)31491-5","article-title":"Novel treatment strategies in rheumatoid arthritis","volume":"389","author":"Burmester","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.intimp.2025.114735_bb0015","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1136\/annrheumdis-2017-212862","article-title":"Defining refractory rheumatoid arthritis","volume":"77","author":"Buch","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.intimp.2025.114735_bb0020","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s40265-020-01309-9","article-title":"Understanding refractory rheumatoid arthritis: implications for a therapeutic approach","volume":"80","author":"Melville","year":"2020","journal-title":"Drugs"},{"key":"10.1016\/j.intimp.2025.114735_bb0025","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1136\/ard.2007.070821","article-title":"Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis","volume":"67","author":"Tsujimura","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.intimp.2025.114735_bb0030","doi-asserted-by":"crossref","first-page":"512","DOI":"10.3899\/jrheum.090048","article-title":"Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis","volume":"37","author":"Suzuki","year":"2010","journal-title":"J. Rheumatol."},{"key":"10.1016\/j.intimp.2025.114735_bb0035","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/(SICI)1097-0215(19960301)65:5<613::AID-IJC10>3.0.CO;2-8","article-title":"Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate","volume":"65","author":"Norris","year":"1996","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.intimp.2025.114735_bb0040","article-title":"Overexpression of P-glycoprotein on fibroblast-like synoviocytes in refractory rheumatoid arthritis patients: a potential mechanism for multidrug resistance in rheumatoid arthritis treatment","volume":"15","author":"Liu","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"10.1016\/j.intimp.2025.114735_bb0045","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1080\/14397595.2017.1341458","article-title":"Relevance of P-glycoprotein on CXCR4(+) B cells to organ manifestation in highly active rheumatoid arthritis","volume":"28","author":"Tsujimura","year":"2018","journal-title":"Mod. Rheumatol."},{"key":"10.1016\/j.intimp.2025.114735_bb0050","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s10067-008-1071-1","article-title":"Expression of multidrug resistance-1 protein correlates with disease activity rather than the refractoriness to methotrexate therapy in rheumatoid arthritis","volume":"28","author":"Agarwal","year":"2009","journal-title":"Clin. Rheumatol."},{"key":"10.1016\/j.intimp.2025.114735_bb0055","doi-asserted-by":"crossref","first-page":"3619320","DOI":"10.1155\/2018\/3619320","article-title":"Methotrexate combined with 4-Hydroperoxycyclophosphamide downregulates multidrug-resistance P-glycoprotein expression induced by methotrexate in rheumatoid arthritis fibroblast-like Synoviocytes via the JAK2\/STAT3 pathway","volume":"2018","author":"Qin","year":"2018","journal-title":"J Immunol Res"},{"key":"10.1016\/j.intimp.2025.114735_bb0060","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1038\/s41401-021-00801-6","article-title":"Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery system","volume":"43","author":"Qu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.intimp.2025.114735_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.109432","article-title":"Regulation of CP-25 on P-glycoprotein in synoviocytes of rats with adjuvant arthritis","volume":"119","author":"Tang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.intimp.2025.114735_bb0070","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0002-8703(93)90215-U","article-title":"Efficacy and mode of action of manidipine: a new calcium antagonist","volume":"125","author":"Iimura","year":"1993","journal-title":"Am. Heart J."},{"key":"10.1016\/j.intimp.2025.114735_bb0075","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2165\/00003495-200464170-00011","article-title":"Manidipine: a review of its use in the management of hypertension","volume":"64","author":"McKeage","year":"2004","journal-title":"Drugs"},{"key":"10.1016\/j.intimp.2025.114735_bb0080","first-page":"C620","article-title":"Effect of ouabain on CFTR gene expression in human Calu-3 cells","volume":"284","author":"Baudouin-Legros","year":"2003","journal-title":"Am. J. Phys. Cell Phys."},{"key":"10.1016\/j.intimp.2025.114735_bb0085","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/j.1476-5381.2009.00117.x","article-title":"Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression","volume":"156","author":"Riganti","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.intimp.2025.114735_bb0090","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0928-0987(02)00082-9","article-title":"Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression","volume":"16","author":"Takara","year":"2002","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.intimp.2025.114735_bb0095","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.phrs.2010.03.004","article-title":"Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages","volume":"62","author":"Costa","year":"2010","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.intimp.2025.114735_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.108644","article-title":"Methotrexate improves the anti-arthritic effects of Paeoniflorin-6\u2019-O-benzene sulfonate by enhancing its pharmacokinetic properties in adjuvant-induced arthritis rats","volume":"112","author":"Asenso","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.intimp.2025.114735_bb0105","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0112545","article-title":"Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis","volume":"9","author":"Bienkowska","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.intimp.2025.114735_bb0110","doi-asserted-by":"crossref","first-page":"D1263","DOI":"10.1093\/nar\/gkac812","article-title":"DRESIS: the first comprehensive landscape of drug resistance information","volume":"51","author":"Sun","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.intimp.2025.114735_bb0115","first-page":"295","article-title":"Calcium\/calmodulin-dependent protein kinases","volume":"5","author":"Nairn","year":"1994","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.intimp.2025.114735_bb0120","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.taap.2009.07.026","article-title":"Digoxin and ouabain induce P-glycoprotein by activating calmodulin kinase II and hypoxia-inducible factor-1alpha in human colon cancer cells","volume":"240","author":"Riganti","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.intimp.2025.114735_bb0125","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/194541","article-title":"Research Progress on the role of ABC transporters in the drug resistance mechanism of intractable epilepsy","volume":"2015","author":"Xiong","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.intimp.2025.114735_bb0130","doi-asserted-by":"crossref","first-page":"H2306","DOI":"10.1152\/ajpheart.00571.2004","article-title":"Angiotensin II-induced Akt activation is mediated by metabolites of arachidonic acid generated by CaMKII-stimulated Ca2(+)-dependent phospholipase A2","volume":"288","author":"Li","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.intimp.2025.114735_bb0135","first-page":"30","article-title":"Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome","volume":"67","author":"Llorente","year":"2000","journal-title":"Joint Bone Spine"},{"key":"10.1016\/j.intimp.2025.114735_bb0140","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s10787-018-0459-z","article-title":"Predicting methotrexate resistance in rheumatoid arthritis patients","volume":"26","author":"Yu","year":"2018","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.intimp.2025.114735_bb0145","first-page":"595","article-title":"High expression of multidrug resistance Gene-1 can aggravate resistance to methotrexate in rheumatoid arthritis patients","volume":"41","author":"Wang","year":"2019","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"10.1016\/j.intimp.2025.114735_bb0150","first-page":"815","article-title":"Over-expression of mdr1\/P-gp is associated with methotrexate resistance in patients with rheumatoid arthritis","volume":"33","author":"Yao","year":"2017","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"10.1016\/j.intimp.2025.114735_bb0155","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.774387","article-title":"Paeonol protects against methotrexate-induced nephrotoxicity via upregulation of P-gp expression and inhibition of TLR4\/NF-kappaB pathway","volume":"13","author":"Morsy","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.intimp.2025.114735_bb0160","doi-asserted-by":"crossref","first-page":"1051082","DOI":"10.3389\/fimmu.2022.1051082","article-title":"Systemic complications of rheumatoid arthritis: focus on pathogenesis and treatment","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Immunol."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925007258?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925007258?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T21:49:55Z","timestamp":1762552195000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925007258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":32,"alternative-id":["S1567576925007258"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114735","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Regulation of P-glycoprotein through CaMKII\/cPLA2 pathway in lymphocytes for treating refractory rheumatoid arthritis by manidipine","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114735","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"114735"}}