{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:59:51Z","timestamp":1784563191297,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"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":["82071463"],"award-info":[{"award-number":["82071463"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ischemic stroke (IS) is known for its high incidence, disability, and mortality, and there is an urgent need to investigate the pathophysiological mechanisms and develop novel treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We aimed to investigate the mechanisms of the novel circMap2k1\/miR\u2010135b\u20105p\/Pidd1 axis in the treatment of IS progression with fluoxetine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The middle cerebral artery occlusion (MCAO) model was done in adult male Sprague\u2013Dawley (SD) rats and followed by fluoxetine treatment and the injection of adeno\u2010associated virus (AAV)\u2010sh\u2010ctr and AAV\u2010sh\u2010circMap2k1 into the bilateral hippocampal tissues of rats. Dual\u2010luciferase reporter gene assay was employed to confirm the binding between miR\u2010135b\u20105p and Pidd1. Enzyme\u2010linked immunosorbent assay was performed to measure the concentrations of the inflammatory factors TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 in the plasma. The role of circMap2k1 in cells was tested by overexpression of circMap2k1. Cell viability was assessed using Cell Counting Kit\u20108 assay, while apoptosis was measured by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Knockdown of circMap2k1 enhanced the therapeutic and protective effect of fluoxetine on IS injury in rats. Dual\u2010luciferase reporter gene assay confirmed the targeting of miR\u2010135b\u20105p to Pidd1. Additionally, fluoxetine deactivated the adsorption of miR\u2010135b\u20105p by downregulating circMap2k1, and miR\u2010135b\u20105p further exerted its inhibitory effect on Pidd1 and finally attenuated the inflammatory response caused by microglial polarization after IS. Cell experiments revealed that overexpression of circMap2k1 repressed cell viability and promoted cell apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Fluoxetine downregulated of circMap2k1 was associated ameliorate neurological injury and inflammatory responses induced by microglial polarization after IS. The manuscript is available as a preprint at this link:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.21203\/rs.3.rs-3209057\/v1\">doi.org\/10.21203\/rs.3.rs-3209057\/v1<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/fcp.13048","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T23:35:07Z","timestamp":1736292907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fluoxetine\u2010induced downregulation of circMap2k1 signaling cascade to improve neurological function after ischemic stroke"],"prefix":"10.1111","volume":"39","author":[{"given":"Langtao","family":"He","sequence":"first","affiliation":[{"name":"Department of Geriatrics The Second Clinical Medical College of Jinan University  Shenzhen 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