{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:51:19Z","timestamp":1765857079364,"version":"3.48.0"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001717"],"award-info":[{"award-number":["82001717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Achieving clinical remission in rheumatoid arthritis (RA) remains a significant challenge in current therapeutic strategies. While transplantation of human umbilical cord\u2010derived mesenchymal stem cells (UC\u2010MSCs) has shown promising outcomes, therapeutic responses vary considerably among patients. In this study, we characterized the immune profiles of nonresponders and identified elevated expression of inducible costimulator (ICOS) in peripheral immune cells as a critical barrier to effective treatment. This upregulation, combined with the presence of ICOS ligand (ICOSL) on UC\u2010MSCs, activated T cells to secrete inflammatory cytokines through the Phosphatidylinositol 3\u2010kinase \/ Protein kinase B \/ Mammalian target of rapamycin (PI3K\/AKT\/mTOR)\u00a0pathway. To overcome this limitation, we identified silybin as a potential adjunctive agent. Further investigations demonstrated that silybin acts as a competitive binding inhibitor, effectively targeting the PI3K\/AKT\/mTOR pathway and reducing downstream cytokine release. The combined application of silybin and UC\u2010MSCs significantly enhanced immunoregulatory effects, as validated through in vitro analyses with patient\u2010derived samples and in vivo experiments using a collagen\u2010induced arthritis mouse model. This study highlights a novel, personalized therapeutic approach for RA, offering insights into improving clinical outcomes through targeted interventions.<\/jats:p>","DOI":"10.1002\/mco2.70450","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:53:30Z","timestamp":1761659610000},"source":"Crossref","is-referenced-by-count":0,"title":["A Potential Approach of Mesenchymal Stem Cells Combined Silybin for Synergistic Treatment in Rheumatoid Arthritis via ICOS\/ICOSL"],"prefix":"10.1002","volume":"6","author":[{"given":"Yu Chun","family":"Wang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Biochemistry and Molecular Pharmacology Chongqing Medical University  Chongqing China"},{"name":"School of Pharmacy Faculty of Medicine Macau University of Science and Technology  Taipa Macau SAR China"},{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy Faculty of Medicine Macau University of Science and Technology  Taipa Macau SAR China"},{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Shan Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2797-6591","authenticated-orcid":false,"given":"Xin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Zhun","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Faculty of Medicine Macau University of Science and Technology  Taipa Macau SAR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling Yun","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy Faculty of Medicine Macau University of Science and Technology  Taipa Macau SAR China"},{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31651-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-018-0354-x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2015.89"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01134-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.06.016"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38674"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1541-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202202510"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.17-0002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2010.074"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701305"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17321"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.05.007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2478\/rir-2021-0008"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080823"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2017.07.017"},{"issue":"1","key":"e_1_2_10_19_1","first-page":"143","article-title":"[Action of silymarin on the fatty acid composition of the hepatic lipids of estrogenized chickens]","volume":"7","author":"Sanchez Garcia J. A.","year":"1981","journal-title":"Archivos De Farmacologia Y Toxicologia"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.572858"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046-3758.117.BJR-2021-0594.R1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1138"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200767010-00001"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba7308"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000966"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21099-2"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-015-8498-3"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31472-1"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.02.005"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2022.04.006"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S323107"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S225613"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.650"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.61950"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0944-7113(00)80017-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153339"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.03.018"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:50:14Z","timestamp":1765857014000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":36,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/mco2.70450"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70450","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"type":"print","value":"2688-2663"},{"type":"electronic","value":"2688-2663"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"article-number":"e70450"}}