{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:40:52Z","timestamp":1776066052322,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed to explore the role of ferroptosis\u2010related genes in Pb\u2010induced acute kidney injury (AKI) using bioinformatics and animal experiments, potentially providing a new direction for future research. Differentially expressed genes related to Pb\u2010induced AKI mediated by ferroptosis were identified using databases. Subsequently, hub genes were identified through enrichment and protein\u2013protein interaction analyses. Western blot and immunohistochemistry were used to verify the expression of hub genes and ferroptosis marker protein GPX4, and the levels of Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , GSH, and MDA in tissues were determined. Drug prediction was performed using the DSigDB database and molecular docking. The hub genes were screened: heme oxygenase 1 (HMOX1), CD44 molecule (CD44), arachidonate 15\u2010lipoxygenase (ALOX15), and NADPH quinone dehydrogenase 1 (NQO1). In 600 mg\/kg lead acetate\u2013induced AKI rat models, kidney tissues exhibited significantly lower levels of HMOX1, CD44, NQO1, and glutathione peroxidase 4 (GPX4) proteins, while showing higher levels of ALOX15 protein. Furthermore, significantly elevated levels of Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and malondialdehyde were observed, accompanied by decreased levels of reduced glutathione; potential therapeutic drugs may include resveratrol, retinoic acid, valproic acid, and\n                    <jats:italic>tert<\/jats:italic>\n                    \u2010butylhydroquinone. Our study reveals an association between Pb exposure and the dysregulation of ferroptosis\u2010related genes (HMOX1, CD44, ALOX15, and NQO1). We hypothesize that these genetic alterations may contribute to ferroptosis and subsequent AKI. Further research with larger sample sizes and additional experimental validation is needed.\n                  <\/jats:p>","DOI":"10.1002\/jat.4866","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T05:10:19Z","timestamp":1753506619000},"page":"2688-2699","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening Hub Genes of Ferroptosis in Pb\u2010Induced Acute Kidney Injury Based on GEO Database Bioinformatics and Experimental Validation"],"prefix":"10.1002","volume":"45","author":[{"given":"Xin","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Public Health Jilin University  Changchun Jilin Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shidi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health Jilin University  Changchun Jilin Province 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