{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:28:48Z","timestamp":1786379328056,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Quzhou Municipal Bureau of Science and Technology of Zhejiang Province, China","award":["2021Y012"],"award-info":[{"award-number":["2021Y012"]}]},{"name":"Quzhou Municipal Bureau of Science and Technology of Zhejiang Province, China","award":["2022K54"],"award-info":[{"award-number":["2022K54"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify immune-related molecular targets in polycystic ovary syndrome (PCOS) and evaluate the role of integrin beta-2 (ITGB2) and the potential modulation by rutin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Follicular fluid cytokines from 30 women with PCOS and 30 control women were profiled. Transcriptomic (GSE34526) and DNA methylation (GSE138573) data were integrated to identify overlapping genes, followed by functional enrichment analyses, protein\u2013protein interaction (PPI), and molecular docking analyses. LPS-stimulated granulosa cells, in the presence or absence of ITGB2 overexpression and rutin treatment, were assessed for gene expression, viability, cytokine secretion, and NF-\u03baB activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Women with PCOS had higher IL-5 but lower IL-1\u03b2 and IL-12p70. ITGB2, ITGAM, and CD86 were upregulated and hypomethylated. Among these, ITGB2 bound rutin with the lowest energy (\u2212\u20097.8\u00a0kcal\/mol). Rutin reduced ITGB2 expression, restored viability, suppressed cytokine release, and inhibited NF-\u03baB activation, even under ITGB2 overexpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ITGB2 is associated with inflammatory responses in granulosa cells and may contribute to PCOS-related immune dysregulation via NF-\u03baB activation. Rutin attenuates these inflammatory responses, supporting a potential involvement of the ITGB2\/NF-\u03baB axis as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43032-026-02137-0","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:41:47Z","timestamp":1786376507000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomic and DNA Methylation Analysis Reveals ITGB2-Mediated Immune Dysregulation in Polycystic Ovary Syndrome and Its Modulation by Rutin"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1832-1783","authenticated-orcid":false,"given":"Peng","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suqing","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"1","key":"2137_CR1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s41043-025-01002-1","volume":"44","author":"L Lin","year":"2025","unstructured":"Lin L, et al. Global trends in polycystic ovarian syndrome over 30 years: an age-period-cohort study of 204 countries and territories (1990\u20132021). J Health Popul Nutr. 2025;44(1):242.","journal-title":"J Health Popul Nutr"},{"issue":"3","key":"2137_CR2","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1007\/s00404-024-07607-x","volume":"310","author":"N Salari","year":"2024","unstructured":"Salari N, et al. Global prevalence of polycystic ovary syndrome in women worldwide: a comprehensive systematic review and meta-analysis. Arch Gynecol Obstet. 2024;310(3):1303\u201314.","journal-title":"Arch Gynecol Obstet"},{"issue":"56","key":"2137_CR3","doi-asserted-by":"publisher","first-page":"96351","DOI":"10.18632\/oncotarget.19180","volume":"8","author":"T Ding","year":"2017","unstructured":"Ding T, et al. The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis. Oncotarget. 2017;8(56):96351\u20138.","journal-title":"Oncotarget"},{"key":"2137_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073789","author":"E Rudnicka","year":"2021","unstructured":"Rudnicka E, et al. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22073789.","journal-title":"Int J Mol Sci"},{"issue":"11","key":"2137_CR5","doi-asserted-by":"publisher","first-page":"10689","DOI":"10.1007\/s11033-022-07695-5","volume":"49","author":"M Shamsi","year":"2022","unstructured":"Shamsi M, et al. The immune system\u2019s role in PCOS. Mol Biol Rep. 2022;49(11):10689\u2013702.","journal-title":"Mol Biol Rep"},{"key":"2137_CR6","doi-asserted-by":"publisher","first-page":"1169232","DOI":"10.3389\/fimmu.2023.1169232","volume":"14","author":"J Wang","year":"2023","unstructured":"Wang J, Yin T, Liu S. Dysregulation of immune response in PCOS organ system. 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