{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T14:16:55Z","timestamp":1777731415102,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Microglia play an important role in ischemic stroke (IS). However, the molecular regulatory mechanisms underlying microglial ferroptosis in IS remain incompletely understood. In this study, blood samples were collected from 20 IS patients and 15 healthy volunteers. Microglia BV\u20102 subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) and mice undergoing middle cerebral artery occlusion\u2010reperfusion (MCAO\/R) surgery were used to establish IS models. Our results revealed that in blood samples from IS patients and in OGD\/R\u2010treated BV\u20102 cells, ZFP36 ring finger protein like 1 (ZFP36L1) and Acyl\u2010CoA synthetase long chain family member 1 (ACSL1) expression was increased, while the fat mass and obesity\u2010associated (FTO) protein expression was decreased. ACSL1 silencing attenuated ferroptosis and inflammation in OGD\/R\u2010treated microglia, as evidenced by decreased levels of malondialdehyde, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , lipid peroxidation, inflammatory factors, along with an increased Glutathione\/Glutathione disulfide ratio. Additionally, ZFP36L1 silencing suppressed the OGD\/R\u2010induced promotion of ferroptosis and inflammation in microglia and alleviated cerebral ischemic injury in MCAO\/R mice, whereas ACSL1 overexpression reversed these alterations caused by ZFP36L1 silencing. Mechanistically, ZFP36L1 decreased FTO messenger RNA (mRNA) stability and reduced FTO expression. FTO overexpression reduced ACSL1 N6\u2010methyladenosine (m6A) modification and ACSL1 expression. In conclusion, ZFP36L1 increased ACSL1 m6A modification and ACSL1 expression to promote microglial ferroptosis, neuroinflammatory response, and cerebral ischemic injury in IS by reducing FTO mRNA stability.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70212","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:01:53Z","timestamp":1777460513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ZFP36L1<\/scp>\n                    Enhances Microglial Ferroptosis in Ischemic Stroke by Reducing\n                    <scp>FTO<\/scp>\n                    \u2010Mediated\n                    <scp>N6<\/scp>\n                    \u2010Methyladenosine Demethylation of\n                    <scp>ACSL1 mRNA<\/scp>"],"prefix":"10.1002","author":[{"given":"Ai\u2010Xia","family":"Song","sequence":"first","affiliation":[{"name":"Department of Neurology The First Hospital of Hebei Medical University  Shijiazhuang Hebei Province People's Republic of China"},{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han\u2010Xu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan\u2010Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Hui","family":"Kou","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Ning","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan\u2010Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting\u2010Ting","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Hebei North University  Zhangjiakou Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2344-1525","authenticated-orcid":false,"given":"Ping","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Hebei Medical University  Shijiazhuang Hebei Province People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"issue":"11","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1001\/jama.2020.26867","article-title":"Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review","volume":"325","author":"Mendelson S. J.","year":"2021","journal-title":"Jama"},{"issue":"10446","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1016\/S0140-6736(24)00642-1","article-title":"Stroke","volume":"403","author":"Hilkens N. A.","year":"2024","journal-title":"Lancet"},{"issue":"1","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/med.21817","article-title":"Mechanisms of Neuronal Cell Death in Ischemic Stroke and Their Therapeutic Implications","volume":"42","author":"Tuo Q. Z.","year":"2022","journal-title":"Medicinal Research Reviews"},{"issue":"11","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24119144","article-title":"Microglia and the Blood\u2010Brain Barrier: An External Player in Acute and Chronic Neuroinflammatory Conditions","volume":"24","author":"Gullotta G. S.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"issue":"5","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00401-018-1930-z","article-title":"Post\u2010Stroke Inflammation\u2010Target or Tool for Therapy?","volume":"137","author":"Lambertsen K. L.","year":"2019","journal-title":"Acta Neuropathologica"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2022.889442","article-title":"Microglia: The Hub of Intercellular Communication in Ischemic Stroke","volume":"16","author":"Zhang Y.","year":"2022","journal-title":"Frontiers in Cellular Neuroscience"},{"issue":"4","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, Biology and Role in Disease","volume":"22","author":"Jiang X.","year":"2021","journal-title":"Nature Reviews. Molecular Cell Biology"},{"issue":"2","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell B. R.","year":"2017","journal-title":"Cell"},{"issue":"1","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12974-019-1430-7","article-title":"Iron Accentuated Reactive Oxygen Species Release by NADPH Oxidase in Activated Microglia Contributes to Oxidative Stress In\u00a0Vitro","volume":"16","author":"Yauger Y. J.","year":"2019","journal-title":"Journal of Neuroinflammation"},{"issue":"6","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cmet.2020.10.010","article-title":"TANK\u2010Binding Kinase 1 Regulates the Localization of Acyl\u2010CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation","volume":"32","author":"Huh J. Y.","year":"2020","journal-title":"Cell Metabolism"},{"issue":"7","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.107145","article-title":"ACSL1 Is a Key Regulator of Inflammatory and Macrophage Foaming Induced by Short\u2010Term Palmitate Exposure or Acute High\u2010Fat Feeding","volume":"26","author":"Al\u2010Rashed F.","year":"2023","journal-title":"iScience"},{"issue":"12","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","DOI":"10.3390\/v13122383","article-title":"Inhibiting ACSL1\u2010Related Ferroptosis Restrains Murine Coronavirus Infection","volume":"13","author":"Xia H.","year":"2021","journal-title":"Viruses"},{"issue":"16","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"8237","DOI":"10.18632\/aging.204966","article-title":"Single\u2010Cell RNA Sequencing and Multiple Bioinformatics Methods to Identify the Immunity and Ferroptosis\u2010Related Biomarkers of SARS\u2010CoV\u20102 Infections to Ischemic Stroke","volume":"15","author":"Zhao X.","year":"2023","journal-title":"Aging (Albany NY)"},{"issue":"9","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkad200","article-title":"Rolling Circle Extension\u2010Assisted Loop\u2010Mediated Isothermal Amplification (Rol\u2010LAMP) Method for Locus\u2010Specific and Visible Detection of RNA N6\u2010Methyladenosine","volume":"51","author":"Li J.","year":"2023","journal-title":"Nucleic Acids Research"},{"issue":"9","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1007\/s12035-024-04029-3","article-title":"Role of m6A RNA Methylation in Ischemic Stroke","volume":"61","author":"Xu Y.","year":"2024","journal-title":"Molecular Neurobiology"},{"issue":"3","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.sbi.2005.04.004","article-title":"Multiple Modes of RNA Recognition by Zinc Finger Proteins","volume":"15","author":"Hall T. M.","year":"2005","journal-title":"Current Opinion in Structural Biology"},{"issue":"1","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202302222","article-title":"Synergistic Roles of Tristetraprolin Family Members in Myeloid Cells in the Control of Inflammation","volume":"7","author":"Snyder B. L.","year":"2024","journal-title":"Life Science Alliance"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.921394","article-title":"EGCG Protects the Mouse Brain Against Cerebral Ischemia\/Reperfusion Injury by Suppressing Autophagy via the AKT\/AMPK\/mTOR Phosphorylation Pathway","volume":"13","author":"Wang L.","year":"2022","journal-title":"Frontiers in Pharmacology"},{"issue":"1","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible Middle Cerebral Artery Occlusion Without Craniectomy in Rats","volume":"20","author":"Longa E. Z.","year":"1989","journal-title":"Stroke"},{"issue":"1","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41420-023-01385-2","article-title":"ACSL1\u2010Induced Ferroptosis and Platinum Resistance in Ovarian Cancer by Increasing FSP1 N\u2010Myristylation and Stability","volume":"9","author":"Zhang Q.","year":"2023","journal-title":"Cell Death Discovery"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.pneurobio.2016.01.005","article-title":"The Biphasic Function of Microglia in Ischemic Stroke","volume":"157","author":"Ma Y.","year":"2017","journal-title":"Progress in Neurobiology"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"9459","DOI":"10.1007\/s12035-024-04133-4","article-title":"TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation","volume":"61","author":"Tang J.","year":"2024","journal-title":"Molecular Neurobiology"},{"key":"e_1_2_10_24_1","article-title":"New Target for Prevention and Treatment of Neuroinflammation: Microglia Iron Accumulation and Ferroptosis","volume":"14","author":"Liu S.","year":"2022","journal-title":"ASN Neuro"},{"issue":"1","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12951-024-02560-y","article-title":"Anti\u2010Ferroptosis Exosomes Engineered for Targeting M2 Microglia to Improve Neurological Function in Ischemic Stroke","volume":"22","author":"Wang Y.","year":"2024","journal-title":"Journal of Nanobiotechnology"},{"issue":"5","key":"e_1_2_10_26_1","first-page":"1394","article-title":"ACSL1, CH25H, GPCPD1, and PLA2G12A as the Potential Lipid\u2010Related Diagnostic Biomarkers of Acute Myocardial Infarction","volume":"15","author":"Liu Z. Y.","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"e_1_2_10_27_1","article-title":"Identification of Cell Death\u2010Related Biomarkers and Immune Infiltration in Ischemic Stroke Between Male and Female Patients","volume":"14","author":"Chen W.","year":"2023","journal-title":"Frontiers in Immunology"},{"issue":"1","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1186\/s12864-023-09829-w","article-title":"Integrative Analyses and Validation of Ferroptosis\u2010Related Genes and Mechanisms Associated With Cerebrovascular and Cardiovascular Ischemic Diseases","volume":"24","author":"Liao W.","year":"2023","journal-title":"BMC Genomics"},{"issue":"3","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1021\/acs.jproteome.3c00830","article-title":"PRMT7\u2010Dependent Transcriptional Activation of Hmgb2 Aggravates Severe Acute Pancreatitis by Promoting Acsl1\u2010Induced Ferroptosis","volume":"23","author":"Su M.","year":"2024","journal-title":"Journal of Proteome Research"},{"issue":"6409","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1126\/science.aau1646","article-title":"RNA Modifications Modulate Gene Expression During Development","volume":"361","author":"Frye M.","year":"2018","journal-title":"Science"},{"issue":"13","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"7239","DOI":"10.1093\/nar\/gkab378","article-title":"A Comprehensive Review of m6A\/m6Am RNA Methyltransferase Structures","volume":"49","author":"Oerum S.","year":"2021","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2024.111304","article-title":"METTL14\u2010Mediated N6\u2010Methyladenosine Modification of TCP1 mRNA Promotes Acute Myeloid Leukemia Progression","volume":"122","author":"Zhang M.","year":"2024","journal-title":"Cellular Signalling"},{"key":"e_1_2_10_33_1","first-page":"313","article-title":"The FTO Mediated N6\u2010Methyladenosine Modification of DDIT4 Regulation With Tumorigenesis and Metastasis in Prostate Cancer","volume":"7","author":"Zhao Y.","year":"2024","journal-title":"Research (Wash D C)"},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2023.110751","article-title":"FTO Alleviates Cerebral Ischemia\/Reperfusion\u2010Induced Neuroinflammation by Decreasing cGAS mRNA Stability in an m6A\u2010Dependent Manner","volume":"109","author":"Yu Z.","year":"2023","journal-title":"Cellular Signalling"},{"issue":"2","key":"e_1_2_10_35_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1158\/0008-5472.CAN-18-2796","article-title":"RNA\u2010Binding Protein ZFP36L1 Suppresses Hypoxia and Cell\u2010Cycle Signaling","volume":"80","author":"Loh X. Y.","year":"2020","journal-title":"Cancer Research"},{"issue":"1","key":"e_1_2_10_36_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1186\/s12935-021-02177-3","article-title":"The Oncogenic Role of HIF\u20101\u03b1\/miR\u2010182\u20105p\/ZFP36L1 Signaling Pathway in Nasopharyngeal Carcinoma","volume":"21","author":"Wang G.","year":"2021","journal-title":"Cancer Cell International"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.yjmcc.2024.04.012","article-title":"ZFP36L1 Controls KLF16 mRNA Stability in Vascular Smooth Muscle Cells During Restenosis After Vascular Injury","volume":"192","author":"Chen N.","year":"2024","journal-title":"Journal of Molecular and Cellular Cardiology"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.711633","article-title":"Post\u2010Transcriptional Regulation of Immune Responses and Inflammatory Diseases by RNA\u2010Binding ZFP36 Family Proteins","volume":"12","author":"Makita S.","year":"2021","journal-title":"Frontiers in Immunology"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70212","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/kjm2.70212","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:01:58Z","timestamp":1777460518000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/kjm2.70212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":37,"alternative-id":["10.1002\/kjm2.70212"],"URL":"https:\/\/doi.org\/10.1002\/kjm2.70212","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"value":"1607-551X","type":"print"},{"value":"2410-8650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"2025-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70212"}}