{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:25:19Z","timestamp":1793139919082,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300873"],"award-info":[{"award-number":["82300873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170787"],"award-info":[{"award-number":["82170787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic prostatitis demonstrates a prevalence rate of nearly 5%\u201310% among young and middle\u2010aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti\u2010inflammatory properties of itaconic acid (IA) and its derivative, 4\u2010Octyl itaconate (4\u2010OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti\u2010inflammatory effects in chronic prostatitis requires extensive research and validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&amp;E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune\u2010responsive gene 1 (IRG\u20101) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4\u2010OI, while the control group received injections of saline. Western blot (WB), H&amp;E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme\u2010linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IHC analysis of human prostate tissue depicts that IRG\u20101 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4\u2010OI increased Nrf2\/HO\u20101 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1\u2009h before intraperitoneal injection of 50\u2009mg\/kg 4\u2010OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti\u2010inflammatory effects of 4\u2010OI in EAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study indicates that 4\u2010OI can alleviates EAP by inhibiting the NLRP3 inflammasome\u2010induced pyroptosis through activating Nrf2\/HO\u20101 pathway, which may facilitate a novel approach toward prostatitis treatment.<\/jats:p>\n                  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