{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:25:02Z","timestamp":1786991102151,"version":"build-2736575974"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["22JCYBJC01230"],"award-info":[{"award-number":["22JCYBJC01230"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0710802"],"award-info":[{"award-number":["2020YFA0710802"]}],"id":[{"id":"10.13039\/501100012166","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":[[2023,11]]},"DOI":"10.1016\/j.intimp.2023.110810","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T12:33:13Z","timestamp":1692793993000},"page":"110810","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"PA","title":["Metronomic capecitabine with rapamycin exerts an immunosuppressive effect by inducing ferroptosis of CD4+ T cells after liver transplantation in rat"],"prefix":"10.1016","volume":"124","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruining","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenglu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashu","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-7084","authenticated-orcid":false,"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2023.110810_b0005","doi-asserted-by":"crossref","unstructured":"B.D. Fleming, D.J. Urban, M.D. Hall, T. Longerich, T.F. Greten, I. Pastan, M. Ho, Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention, Hepatology (Baltimore, Md.) 71(5) (2020) 1696-1711.","DOI":"10.1002\/hep.30949"},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0010","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrgastro.2016.193","article-title":"Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches","volume":"14","author":"Sapisochin","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"5","key":"10.1016\/j.intimp.2023.110810_b0015","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/SLA.0b013e3181896278","article-title":"Liver transplantation for hepatocellular carcinoma under calcineurin inhibitors: reassessment of risk factors for tumor recurrence","volume":"248","author":"Vivarelli","year":"2008","journal-title":"Ann. Surg."},{"issue":"5","key":"10.1016\/j.intimp.2023.110810_b0020","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/lt.20391","article-title":"Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression","volume":"11","author":"Vivarelli","year":"2005","journal-title":"Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society"},{"issue":"10","key":"10.1016\/j.intimp.2023.110810_b0025","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1111\/apt.15253","article-title":"Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma","volume":"49","author":"Grigg","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0030","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1038\/s41467-019-11174-0","article-title":"A novel rapamycin analog is highly selective for mTORC1 in vivo","volume":"10","author":"Schreiber","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.intimp.2023.110810_b0035","doi-asserted-by":"crossref","unstructured":"M. Bhat, N. Sonenberg, G.J. Gores, The mTOR pathway in hepatic malignancies, Hepatology (Baltimore, Md.) 58(2) (2013) 810-8.","DOI":"10.1002\/hep.26323"},{"issue":"15","key":"10.1016\/j.intimp.2023.110810_b0040","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1089\/scd.2014.0488","article-title":"iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation","volume":"24","author":"Cheng","year":"2015","journal-title":"Stem Cells Dev."},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0045","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3350\/cmh.2021.0038","article-title":"Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma","volume":"27","author":"Kang","year":"2021","journal-title":"Clin. Mol. Hepatol."},{"issue":"5","key":"10.1016\/j.intimp.2023.110810_b0050","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1111\/j.1600-6143.2011.03961.x","article-title":"Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation","volume":"12","author":"Liefeldt","year":"2012","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant Surg."},{"issue":"3","key":"10.1016\/j.intimp.2023.110810_b0055","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1097\/TP.0b013e3181e64217","article-title":"A novel clinically relevant approach to tip the balance toward regulation in stringent transplant model","volume":"90","author":"D'Addio","year":"2010","journal-title":"Transplantation"},{"key":"10.1016\/j.intimp.2023.110810_b0060","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.3389\/fimmu.2020.02155","article-title":"The Immunological Basis of Liver Allograft Rejection","volume":"11","author":"Ronca","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2023.110810_b0065","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.840610","article-title":"T Cell Metabolism in Infection","volume":"13","author":"Wik","year":"2022","journal-title":"Front. Immunol."},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0070","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1089\/ars.2010.3496","article-title":"Differential dependence on cysteine from transsulfuration versus transport during T cell activation","volume":"15","author":"Garg","year":"2011","journal-title":"Antioxid. Redox Signal."},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0075","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1084\/jem.20140857","article-title":"T cell lipid peroxidation induces ferroptosis and prevents immunity to infection","volume":"212","author":"Matsushita","year":"2015","journal-title":"J. Exp. Med."},{"issue":"7498","key":"10.1016\/j.intimp.2023.110810_b0080","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0085","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.bbrc.2018.12.039","article-title":"Lipid storage and lipophagy regulates ferroptosis","volume":"508","author":"Bai","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"19","key":"10.1016\/j.intimp.2023.110810_b0090","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1007\/s00018-017-2547-4","article-title":"Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure","volume":"74","author":"M\u00fcller","year":"2017","journal-title":"Cell. Mol. Life Sci. CMLS"},{"issue":"11","key":"10.1016\/j.intimp.2023.110810_b0095","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/s41419-021-04306-2","article-title":"Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells","volume":"12","author":"Sun","year":"2021","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.intimp.2023.110810_b0100","article-title":"Capecitabine Can Induce T Cell Apoptosis: A Potential Immunosuppressive Agent With Anti-Cancer Effect","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2023.110810_b0105","doi-asserted-by":"crossref","first-page":"1012509","DOI":"10.1155\/2022\/1012509","article-title":"Capecitabine Regulates HSP90AB1 Expression and Induces Apoptosis via Akt\/SMARCC1\/AP-1\/ROS Axis in T Cells","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"20","key":"10.1016\/j.intimp.2023.110810_b0110","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.3748\/wjg.v29.i20.3084","article-title":"Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients\u2019","volume":"29","author":"Wang","year":"2023","journal-title":"T cell ferroptosis., World journal of gastroenterology"},{"issue":"12","key":"10.1016\/j.intimp.2023.110810_b0115","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1136\/gutjnl-2014-308971","article-title":"Host cell mTORC1 is required for HCV RNA replication","volume":"65","author":"St\u00f6hr","year":"2016","journal-title":"Gut"},{"issue":"2S Suppl 1","key":"10.1016\/j.intimp.2023.110810_b0120","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/TP.0000000000001806","article-title":"mTOR Inhibition Role in Cellular Mechanisms","volume":"102","author":"Zaza","year":"2018","journal-title":"Transplantation"},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0125","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/00007890-197907000-00011","article-title":"Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage","volume":"28","author":"Kamada","year":"1979","journal-title":"Transplantation"},{"issue":"6","key":"10.1016\/j.intimp.2023.110810_b0130","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1111\/his.14058","article-title":"Clinicopathological features and outcomes of parenchymal rejection in liver transplant biopsies","volume":"76","author":"Fels Elliott","year":"2020","journal-title":"Histopathology"},{"issue":"2","key":"10.1016\/j.intimp.2023.110810_b0135","first-page":"214","article-title":"Hepatic parenchymal changes and histologic eosinophilia as predictors of subsequent acute liver allograft rejection","volume":"14","author":"Demirhan","year":"2008","journal-title":"Livertransplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society"},{"key":"10.1016\/j.intimp.2023.110810_b0140","unstructured":"Banff schema for grading liver allograft rejection: an international consensus document, Hepatology (Baltimore, Md.) 25(3) (1997) 658-63."},{"key":"10.1016\/j.intimp.2023.110810_b0145","doi-asserted-by":"crossref","first-page":"4609702","DOI":"10.1155\/2019\/4609702","article-title":"Iron Redox Chemistry and Implications in the Parkinson's Disease Brain","volume":"2019","author":"Abeyawardhane","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.intimp.2023.110810_b0150","doi-asserted-by":"crossref","first-page":"1594963","DOI":"10.1155\/2017\/1594963","article-title":"Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress","volume":"2017","author":"Chen","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"3","key":"10.1016\/j.intimp.2023.110810_b0155","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2174\/1570159X13666151030102718","article-title":"Anti-Oxidants in Parkinson's Disease Therapy: A Critical Point of View","volume":"14","author":"Filograna","year":"2016","journal-title":"Curr. Neuropharmacol."},{"issue":"2","key":"10.1016\/j.intimp.2023.110810_b0160","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"issue":"12","key":"10.1016\/j.intimp.2023.110810_b0165","first-page":"1713","article-title":"Capecitabine in advanced hepatocellular carcinoma: A multicenter experience, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the","volume":"51","author":"Pelizzaro","year":"2019","journal-title":"Liver"},{"issue":"26","key":"10.1016\/j.intimp.2023.110810_b0170","first-page":"3140","article-title":"High incidence of biliary complications in rat liver transplantation: can we avoid it?","volume":"17","author":"Li","year":"2011","journal-title":"World J. Gastroenterol."},{"issue":"5","key":"10.1016\/j.intimp.2023.110810_b0175","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.coi.2004.07.011","article-title":"New spectrum of allorecognition pathways: implications for graft rejection and transplantation tolerance","volume":"16","author":"Jiang","year":"2004","journal-title":"Curr. Opin. Immunol."},{"issue":"12","key":"10.1016\/j.intimp.2023.110810_b0180","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1084\/jem.20050419","article-title":"IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo","volume":"201","author":"Sawitzki","year":"2005","journal-title":"J. Exp. Med."},{"issue":"2","key":"10.1016\/j.intimp.2023.110810_b0185","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat. Rev. Immunol."},{"issue":"3","key":"10.1016\/j.intimp.2023.110810_b0190","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1182\/blood-2011-04-325225","article-title":"Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey","volume":"119","author":"Aggarwal","year":"2012","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0195","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/j.1600-6143.2010.03018.x","article-title":"Treg-therapy allows mixed chimerism and transplantation tolerance without cytoreductive conditioning","volume":"10","author":"Pilat","year":"2010","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant Surg."},{"issue":"38","key":"10.1016\/j.intimp.2023.110810_b0200","doi-asserted-by":"crossref","first-page":"6962","DOI":"10.3748\/wjg.v23.i38.6962","article-title":"Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats","volume":"23","author":"Hamdani","year":"2017","journal-title":"World J. Gastroenterol."},{"issue":"10","key":"10.1016\/j.intimp.2023.110810_b0205","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nrneph.2016.108","article-title":"Roles of mTOR complexes in the kidney: implications for renal disease and transplantation","volume":"12","author":"Fantus","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"issue":"2","key":"10.1016\/j.intimp.2023.110810_b0210","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41590-017-0013-y","article-title":"Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway","volume":"19","author":"Holze","year":"2018","journal-title":"Nat. Immunol."},{"issue":"23","key":"10.1016\/j.intimp.2023.110810_b0215","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1182\/blood-2017-12-822619","article-title":"Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion","volume":"131","author":"Youssef","year":"2018","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0220","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1523-1755.2001.00460.x","article-title":"Rapamycin in transplantation: a review of the evidence","volume":"59","author":"Saunders","year":"2001","journal-title":"Kidney Int."},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0225","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1038\/s41467-019-10991-7","article-title":"Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis","volume":"10","author":"Yoshida","year":"2019","journal-title":"Nat. Commun."},{"issue":"1\u20132","key":"10.1016\/j.intimp.2023.110810_b0230","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41417-020-0182-y","article-title":"Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death","volume":"28","author":"Liu","year":"2021","journal-title":"Cancer Gene Ther."},{"issue":"4","key":"10.1016\/j.intimp.2023.110810_b0235","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.chembiol.2020.03.014","article-title":"Achieving Life through Death: Redox Biology of Lipid Peroxidation in Ferroptosis","volume":"27","author":"Bay\u0131r","year":"2020","journal-title":"Cell Chem. Biol."},{"issue":"1","key":"10.1016\/j.intimp.2023.110810_b0240","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1038\/s41467-021-21841-w","article-title":"mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576923011359?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576923011359?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T18:03:37Z","timestamp":1761588217000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576923011359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":48,"alternative-id":["S1567576923011359"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2023.110810","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metronomic capecitabine with rapamycin exerts an immunosuppressive effect by inducing ferroptosis of CD4+ T cells after liver transplantation in rat","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2023.110810","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"110810"}}