{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T06:54:54Z","timestamp":1766386494767,"version":"3.48.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lead (Pb), a pervasive environmental toxicant, exerts substantial nephrotoxic effects in mammalian organisms. However, the molecular mechanisms underlying Pb\u2010induced renal toxicity remain poorly elucidated. In this study, we employed an integrative bioinformatics approach to identify pivotal hub genes associated with Pb nephrotoxicity through comprehensive analysis of the GEO data set GSE59913. Comparative transcriptomic analysis of renal tissues from PbAc\u2082\u2010exposed (600\u2009mg\/kg) and control rats identified 541 differentially expressed genes (DEGs), showing predominant enrichment in response to xenobiotic stimulus, signal transduction, and response to toxic substance. Multilayer pathway analysis revealed significant convergence on metabolic homeostasis networks, PI3K\u2010Akt, AMPK, MAPK, Jak\u2010STAT, PPAR, and cytokine\u2212cytokine receptor interaction pathways. Utilizing protein\u2212protein interaction networks, we identified ten pivotal hub genes implicated in Pb\u2010induced nephrotoxicity\u2014including\n                    <jats:italic>IL6<\/jats:italic>\n                    (interleukin 6),\n                    <jats:italic>CDK1<\/jats:italic>\n                    (cyclin\u2010dependent kinase 1), and\n                    <jats:italic>CCNA2<\/jats:italic>\n                    (cyclin\u2010A2)\u2014which are functionally associated with IL\u201017, JAK\u2010STAT, TNF signaling, DNA replication, and cell cycle regulation pathways. This study provides the mechanistic framework for Pb nephrotoxicity, uncovering potential therapeutic targets for environmental heavy metal toxicity.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70628","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T07:07:03Z","timestamp":1764659223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Mechanisms of Lead (II)\u2010Induced Nephrotoxicity via Integrative Bioinformatics Analysis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0563-3694","authenticated-orcid":false,"given":"Xiaofeng","family":"Li","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Ningxia University Yinchuan China"},{"name":"College of Animal Science Anhui Science and Technology University Fengyang China"},{"name":"State Key Laboratory of Animal Biotech Breeding, College of Animal Science and Technology China Agricultural University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8048-2018","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science Anhui Science and Technology University Fengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2429-5439","authenticated-orcid":false,"given":"Mei","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Animal Science Anhui Science and Technology University Fengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7313-0855","authenticated-orcid":false,"given":"Zhongyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science Anhui Science and Technology University Fengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-2158","authenticated-orcid":false,"given":"Bing","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Ningxia University Yinchuan China"},{"name":"College of Animal Science Anhui Science and Technology University Fengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-023-01045-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2009.07.020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2017.04.036"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.135844"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2024.127420"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2018.07.075"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2019.134901"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2024.104396"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2005.03.022"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-019-0508-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab447"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx441"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki078"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baq020"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172468"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.08.052"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116424"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-025-04570-9"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000001647"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.3834"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.02.006"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087433"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-021-02087-x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-77933-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2018.1558321"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03783-0"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318160d6f9"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CB00155A"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20231107"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110621"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu326"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.27410"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103623108"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069607"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70628","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T06:51:21Z","timestamp":1766386281000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jbt.70628"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70628","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"type":"print","value":"1095-6670"},{"type":"electronic","value":"1099-0461"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70628"}}