{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:45:56Z","timestamp":1777045556326,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epilepsy is a common chronic nervous system disease that threatens human health. However, the role of FOXC1 and its relations with pyroptosis have not been fully studied in epilepsy. Sprague\u2013Dawley rats were obtained for constructing temporal lobe epilepsy (TLE) models. SH\u2010SY5Y cells were treated with Mg\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010free medium for inducing in\u00a0vitro cell models. H&amp;E, TIMM, and Nissl staining were employed for histological evaluation. Flow cytometry was used for measuring cell pyroptosis. ELISA was implemented for detecting the levels of inflammatory cytokines. Immunohistochemistry and immunofluorescence were performed to determine the expression and distribution of genes. ChIP, RIP, MeRIP, and dual\u2010luciferase reporter analysis were performed to investigate the intermolecular interactions. The mRNA and protein level expression of genes were examined using RT\u2010qPCR and western blotting. FOXC1 was lowly expressed in hippocampus tissue of TLE rats, and overexpression of FOXC1 alleviated neuronal damage. Overexpression of FOXC1 downregulated the levels of NLRP3, caspase 1, as well as IL\u20101\u03b2 and IL\u201018 by inhibiting NLRP3\u2010mediated pyroptosis in Mg\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010free\u2013stimulated SH\u2010SY5Y cells. Furthermore, FOXC1 bound to the promoter of NLRP3 and inhibited NLRP3 transcription. FOXC1 was found to be regulated by the METTL3\/YTHDF1 axis\u2010mediated m6A methylation. Overexpression of METTL3 attenuated Mg\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010free\u2010induced neuronal injury and pyroptosis through YTHDF1\u2010dependent regulation of FOXC1. Collectively, these data confirmed that FOXC1 suppressed neuronal injury and pyroptosis in epilepsy by transcriptionally inhibiting NLRP3, which might be correlated to METTL3\/YTHDF1 axis\u2010mediated m6A methylation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500188r","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T15:28:02Z","timestamp":1757345282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Downregulation of\n                    <scp>FOXC1<\/scp>\n                    Modified by\n                    <scp>METTL<\/scp>\n                    3\/\n                    <scp>YTHDF<\/scp>\n                    1 Axis Aggravates\n                    <scp>NLRP<\/scp>\n                    3\u2010Mediated Inflammasomes Formation and Cell Pyroptosis in Epilepsy"],"prefix":"10.1096","volume":"39","author":[{"given":"Pu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology The Third Xiangya Hospital of Central South University  Changsha Hunan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4437-6029","authenticated-orcid":false,"given":"Qian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hematology The Second Xiangya Hospital of Central South University  Changsha Hunan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"113","volume-title":"Handbook of Clinical Neurology","author":"Neligan 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