{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:06:17Z","timestamp":1787169977799,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Glycogen synthase kinase-3b (GSK3\u03b2), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I\/R) injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 6) and P12 cells oxygen-glucose deprivation\/reoxygenation (OGD\/R) model was analyzed using short hairpin GSK3\u03b2 lentivirus and overexpression of FTO lentivirus (\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      ), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3\u03b2, FTO, TLR4 expression, and GSK3\u03b2 activity, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      After GSK3\u03b2 knockdown in the OGD\/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3\u03b2 reversed the OGD\/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3\u03b2\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , the reduction of FTO in mice suffering from MCAO was reversed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our research shows that GSK3\u03b2\/FTO\/TLR4 pathway contributes to cerebral I\/R injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/bc.bc_3_23","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T01:45:51Z","timestamp":1695692751000},"page":"162-171","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["Glycogen synthase kinase-3\u03b2 mediates toll-like receptors 4\/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein"],"prefix":"10.4103","volume":"9","author":[{"given":"Kaiwei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxiu","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchang","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"R1-20240830","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0140-6736(13)61953-4","article-title":"Global and regional burden of stroke during 1990-2010: Findings from the global burden of disease study 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