{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:06:52Z","timestamp":1767168412273,"version":"build-2238731810"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hainan Province Clinical Medical Center","award":["20A200387"],"award-info":[{"award-number":["20A200387"]}]},{"name":"Hainan Province Clinical Medical Center","award":["819QN347"],"award-info":[{"award-number":["819QN347"]}]},{"name":"Hainan Medical and Health Research Project of China","award":["20A200387"],"award-info":[{"award-number":["20A200387"]}]},{"name":"Hainan Medical and Health Research Project of China","award":["819QN347"],"award-info":[{"award-number":["819QN347"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["20A200387"],"award-info":[{"award-number":["20A200387"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["819QN347"],"award-info":[{"award-number":["819QN347"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computational and Mathematical Methods in Medicine"],"published-print":{"date-parts":[[2022,2,17]]},"abstract":"<jats:p>Background. Researches have confirmed that the abnormal signals of OX40 and PD-1 lead to the changes of T cell biological behavior, thus participating the immunopathological process of RA. However, the pathogenesis of RA immunopathological process has not been clarified yet. Methods. 30 DBA\/1 mice were randomly divided into 5 groups (6 mice per group): control group, collagen-induced arthritis (CIA) group, PD-1-Fc\/CIA group, OX40-Fc\/CIA group, and PD-1-Fc\u2009+\u2009OX40-Fc\/CIA group. The pathological changes in mice joints were observed by H&amp;E staining. The proportion of CD4+ T, CD8+ T, CD28+, and CD19+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Serum inflammatory factors (CRP, IL-2, IL-4, IL-1\u03b2, INF-\u03b3) and bone metabolism-related genes (CTX-I, TRACP-5b, BALP) were detected by ELISA assay. Western blotting was applied to measure the NF-\u03baB signaling pathway-related protein (p-IKK\u03b2, p-I\u03baB\u03b1, p50) expression in synovial tissue of mice joint. Results. Compared with the control group, CIA mice showed significant increases in arthritis score and pathological score. In the CIA group, a marked decrease was identified in the proportion of CD8+ T, CD19+, and CD68+ cells. Additionally, the CIA group was associated with upregulation of secretion of inflammatory factors in serum and expression of bone metabolism-related genes and NF-\u03baB pathway-related proteins. Compared with the CIA group, the same indexes above showed a further aggravation in the PD-1-Fc group while all indexes improved in the OX40-Fc group. Besides, OX40-Fc fusion protein slowed down significantly the further deterioration of CIA mouse pathological process caused by PD-1-Fc fusion protein. Conclusion. OX40-Fc fusion protein alleviates PD-1-Fc-aggravated RA by inhibiting inflammatory response. This research provides biological markers with clinical significance for diagnosis and prognosis of RA, as well as offers theoretical and experimental foundation to the new targets for immune intervention.<\/jats:p>","DOI":"10.1155\/2022\/6244175","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T19:05:08Z","timestamp":1645124708000},"page":"1-11","source":"Crossref","is-referenced-by-count":2,"title":["OX40-Fc Fusion Protein Alleviates PD-1-Fc-Aggravated Rheumatoid Arthritis by Inhibiting Inflammatory Response"],"prefix":"10.1155","volume":"2022","author":[{"given":"Yanyan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-4815","authenticated-orcid":true,"given":"Shudian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatism and Immunity, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31491-5"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.006"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31472-1"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0016-9"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.13103"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02892-y"},{"issue":"3","key":"7","first-page":"347","article-title":"One year in review 2019: pathogenesis of rheumatoid arthritis","volume":"37","author":"C. 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