{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T03:00:45Z","timestamp":1776135645629,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Oxidative stress-prompted degeneration of the retinal pigment epithelium (RPE) notably contributes to the onset of age-related macular degeneration (AMD). However, the pathways leading to RPE deterioration and possible preventative strategies are not yet completely comprehended.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ferroptosis was assayed through the evaluation of lipid peroxidation (C11-BODIPY and MDA), reactive oxygen species (ROS), transmission electron microscopy (TEM), iron content measurement, q-PCR, western blotting, and immunofluorescence. To assess the structure and retinal function of RPE in mice, ERG (electroretinography), OCT (optical coherence tomography), and H&amp;amp;E (hematoxylin and eosin) staining were employed. Network pharmacology methods were utilized to elucidate the potential mechanisms underlying melatonin's protective effects against ferroptosis in RPE cells in AMD. Genetic engineering techniques were applied to investigate the regulatory relationships among phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT), murine double minute-2 (MDM2), protein 53 (P53), and solute carrier family 7 member 11 (SLC7A11). In vitro knockdown experiments of MDM2 were conducted to explore its regulatory role in ferroptosis within RPE cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A\u03b21-40 can trigger ferroptosis in RPE cells. Melatonin can inhibit the oxidative stress and ferroptosis induced by A\u03b21-40 in RPE cells. Melatonin exhibits a protective effect on A\u03b21-40-induced AMD, significantly improving the structure of the mouse retina and RPE layer, and facilitating the restoration of visual function. Network pharmacology methods revealed that the potential targets of melatonin in AMD are closely related to ferroptosis, and indicated that the predominant pathways are significantly associated with the PI3K\/AKT\/MDM2\/P53 signaling pathway. Knocking down the specific expression of MDM2 can significantly weaken the inhibitory effect of melatonin on oxidative stress and ferroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Melatonin can suppress cell death by ferroptosis in RPE via the PI3K\/AKT\/MDM2\/P53 pathway, thereby preventing and decelerating the progression of AMD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1543575","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:16:31Z","timestamp":1740640591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Melatonin protects retinal pigment epithelium cells against ferroptosis in AMD via the PI3K\/AKT\/MDM2\/P53 pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Ping","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxia","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinxin","family":"Shu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/j.archoralbio.2015.09.014","article-title":"Radiotherapy-induced salivary dysfunction: structural changes, pathogenetic mechanisms and therapies","volume":"60","author":"Acauan","year":"2015","journal-title":"Arch. Oral Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1038\/s41418-020-00685-9","article-title":"Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer's disease","volume":"28","author":"Bao","year":"2021","journal-title":"Cell Death Differ."},{"key":"B3","doi-asserted-by":"publisher","first-page":"568","DOI":"10.3390\/antiox13050568","article-title":"Antioxidants and mechanistic insights for managing dry age-related macular degeneration","volume":"13","author":"Basyal","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.3390\/biomedicines12071479","article-title":"Genetic insights into age-related macular degeneration","volume":"12","author":"Bhumika","year":"2024","journal-title":"Biomedicines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e12926","DOI":"10.1111\/jpi.12926","article-title":"Melatonin facts: lack of evidence that melatonin is a radical scavenger in living systems","volume":"76","author":"Boutin","year":"2024","journal-title":"J. Pineal Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"100591","DOI":"10.1016\/j.mcpro.2023.100591","article-title":"UniProt and mass spectrometry-based proteomics-A 2-way working relationship","volume":"22","author":"Bowler-Barnett","year":"2023","journal-title":"Mol. Cell Proteomics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1136\/bjophthalmol-2020-318452","article-title":"Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions","volume":"106","author":"Cabral de Guimaraes","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"4247","DOI":"10.1007\/s00210-023-02863-1","article-title":"Licochalcone A alleviates ferroptosis in doxorubicin-induced cardiotoxicity via the PI3K\/AKT\/MDM2\/p53 pathway","volume":"397","author":"Chen","year":"2024","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"102426","DOI":"10.1016\/j.redox.2022.102426","article-title":"Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR\/SREBP-1\/SCD1-mediated lipogenesis in PIK3CA-mutant colorectal cancer","volume":"55","author":"Chen","year":"","journal-title":"Redox Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e21184","DOI":"10.1096\/fj.202000645RR","article-title":"MicroRNA-191-5p ameliorates amyloid-\u03b2(1-40) -mediated retinal pigment epithelium cell injury by suppressing the NLRP3 inflammasome pathway","volume":"35","author":"Chen","year":"","journal-title":"Faseb J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6489923","DOI":"10.1155\/2022\/6489923","article-title":"A\u03b21-40 oligomers trigger neutrophil extracellular trap formation through TLR4-and NADPH oxidase-dependent pathways in age-related macular degeneration","volume":"2022","author":"Chen","year":"","journal-title":"Oxid. Med. Cell Longev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41571-020-00462-0","article-title":"Broadening horizons: the role of ferroptosis in cancer","volume":"18","author":"Chen","year":"","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s40123-023-00675-3","article-title":"Blue light exposure: ocular hazards and prevention-A narrative review","volume":"12","author":"Cougnard-Gregoire","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jprot.2017.08.002","article-title":"Merging in-silico and in vitro salivary protein complex partners using the STRING database: a tutorial","volume":"171","author":"Crosara","year":"2018","journal-title":"J. Proteomics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.gendis.2021.02.009","article-title":"Age-related macular degeneration: epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy","volume":"9","author":"Deng","year":"2022","journal-title":"Genes Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.freeradbiomed.2018.11.035","article-title":"Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration","volume":"131","author":"Dieguez","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"24317","DOI":"10.1073\/pnas.1912959116","article-title":"Elovanoids counteract oligomeric \u03b2-amyloid-induced gene expression and protect photoreceptors","volume":"116","author":"Do","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e12951","DOI":"10.1111\/jpi.12951","article-title":"Melatonin in the mammalian retina: synthesis, mechanisms of action and neuroprotection","volume":"76","author":"Felder-Schmittbuhl","year":"2024","journal-title":"J. Pineal Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-related macular degeneration: a review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"Jama"},{"key":"B20","doi-asserted-by":"publisher","first-page":"7065","DOI":"10.1080\/07391102.2023.2235589","article-title":"Pharmacological mechanism of quercetin in the treatment of colorectal cancer by network pharmacology and molecular simulation","volume":"42","author":"Fu","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e12514","DOI":"10.1111\/jpi.12514","article-title":"Melatonin and its metabolites vs oxidative stress: from individual actions to collective protection","volume":"65","author":"Galano","year":"2018","journal-title":"J. Pineal Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1080\/15548627.2022.2062887","article-title":"Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD","volume":"19","author":"Gupta","year":"2023","journal-title":"Autophagy"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/S0140-6736(22)02609-5","article-title":"Age-related macular degeneration","volume":"401","author":"Guymer","year":"2023","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"101306","DOI":"10.1016\/j.preteyeres.2024.101306","article-title":"Eye on the horizon: the metabolic landscape of the RPE in aging and disease","volume":"104","author":"Hansman","year":"2024","journal-title":"Prog. Retin Eye Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3389\/fchem.2018.00138","article-title":"Reverse screening methods to search for the protein targets of chemopreventive compounds","volume":"6","author":"Huang","year":"2018","journal-title":"Front. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1001\/jamaophthalmol.2024.1822","article-title":"Melatonin and risk of age-related macular degeneration","volume":"142","author":"Jeong","year":"2024","journal-title":"JAMA Ophthalmol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2020.07.013","article-title":"Intracellular amyloid-\u03b2 disrupts tight junctions of the retinal pigment epithelium via NF-\u03baB activation","volume":"95","author":"Jo","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"B29","doi-asserted-by":"publisher","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog. Retin Eye Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.freeradbiomed.2018.05.074","article-title":"The tumor suppressor protein p53 and the ferroptosis network","volume":"133","author":"Kang","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"102358","DOI":"10.1016\/j.arr.2024.102358","article-title":"RPE melanin and its influence on the progression of AMD","volume":"99","author":"Kaufmann","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1016\/j.devcel.2024.09.004","article-title":"Dynamic death decisions: how mitochondrial dynamics shape cellular commitment to apoptosis and ferroptosis","volume":"59","author":"Khatun","year":"2024","journal-title":"Dev. Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40266-020-00822-6","article-title":"Therapeutic options under development for nonneovascular age-related macular degeneration and geographic atrophy","volume":"38","author":"Kim","year":"2021","journal-title":"Drugs Aging"},{"key":"B34","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1080\/17460441.2016.1216967","article-title":"Getting the most out of PubChem for virtual screening","volume":"11","author":"Kim","year":"2016","journal-title":"Expert Opin. Drug Discov."},{"key":"B35","doi-asserted-by":"publisher","first-page":"115329","DOI":"10.1016\/j.bcp.2022.115329","article-title":"A PARP1 PROTAC as a novel strategy against PARP inhibitor resistance via promotion of ferroptosis in p53-positive breast cancer","volume":"206","author":"Li","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3892\/ijmm.2014.1993","article-title":"Subretinal injection of amyloid-\u03b2 peptide accelerates RPE cell senescence and retinal degeneration","volume":"35","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1080\/14728222.2020.1737015","article-title":"Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment","volume":"24","author":"Mehrzadi","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"B38","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3390\/antiox8060177","article-title":"Suppression of AMD-like pathology by mitochondria-targeted antioxidant SkQ1 is associated with a decrease in the accumulation of amyloid \u03b2 and in mTOR activity","volume":"8","author":"Muraleva","year":"2019","journal-title":"Antioxidants (Basel)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"100859","DOI":"10.1016\/j.preteyeres.2020.100859","article-title":"Secretory proteostasis of the retinal pigmented epithelium: impairment links to age-related macular degeneration","volume":"79","author":"Paraoan","year":"2020","journal-title":"Prog. Retin Eye Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4067","DOI":"10.1111\/bph.16469","article-title":"IDH2-NADPH pathway protects against acute pancreatitis via suppressing acinar cell ferroptosis","volume":"181","author":"Peng","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1080\/17460441.2017.1329296","article-title":"Harnessing public domain data to discover and validate therapeutic targets","volume":"12","author":"Reisdorf","year":"2017","journal-title":"Expert Opin. Drug Discov."},{"key":"B42","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1186\/1471-2415-12-17","article-title":"Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage","volume":"18","author":"Rosen","year":"2012","journal-title":"Mol. Vis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1016\/j.clinthera.2021.08.011","article-title":"Global burden of dry age-related macular degeneration: a targeted literature review","volume":"43","author":"Schultz","year":"2021","journal-title":"Clin. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0294236","DOI":"10.1371\/journal.pone.0294236","article-title":"SRplot: a free online platform for data visualization and graphing","volume":"18","author":"Tang","year":"2023","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: molecular mechanisms and health implications","volume":"31","author":"Tang","year":"","journal-title":"Cell Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"831660","DOI":"10.3389\/fimmu.2022.831660","article-title":"Melatonin maintains inner blood-retinal barrier by regulating microglia via inhibition of PI3K\/Akt\/Stat3\/NF-\u03baB signaling pathways in experimental diabetic retinopathy","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"101971","DOI":"10.1016\/j.redox.2021.101971","article-title":"HO-1-mediated ferroptosis as a target for protection against retinal pigment epithelium degeneration","volume":"43","author":"Tang","year":"","journal-title":"Redox Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.survophthal.2012.12.002","article-title":"Iron, zinc, and copper in retinal physiology and disease","volume":"58","author":"Ugarte","year":"2013","journal-title":"Surv. Ophthalmol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s13578-022-00879-3","article-title":"Melatonin inhibits NaIO(3)-induced ARPE-19 cell apoptosis via suppression of HIF-1\u03b1\/BNIP3-LC3B\/mitophagy signaling","volume":"12","author":"Wang","year":"2022","journal-title":"Cell Biosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"404","DOI":"10.7150\/ijbs.27912","article-title":"Melatonin stimulates STAR expression and progesterone production via activation of the PI3K\/AKT pathway in bovine theca cells","volume":"15","author":"Wang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"100672","DOI":"10.1016\/j.mcpro.2023.100672","article-title":"Proteomics, transcriptomics, and phosphoproteomics reveal the mechanism of talaroconvolutin-A suppressing bladder cancer via blocking cell cycle and triggering ferroptosis","volume":"22","author":"Xia","year":"2023","journal-title":"Mol. Cell Proteomics"},{"key":"B53","doi-asserted-by":"publisher","first-page":"783","DOI":"10.3892\/mmr.2018.9713","article-title":"PI3K\/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review)","volume":"19","author":"Xie","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/s41419-022-04924-4","article-title":"Involvement of FSP1-CoQ(10)-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis","volume":"13","author":"Yang","year":"2022","journal-title":"Cell Death Dis."},{"key":"B55","doi-asserted-by":"publisher","first-page":"118190","DOI":"10.1016\/j.jep.2024.118190","article-title":"Potential mechanisms of guizhi fuling wan in treating endometriosis: an analysis based on TCMSP and DisGeNET databases","volume":"329","author":"Yee","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1196\/annals.1356.029","article-title":"Effects of melatonin in age-related macular degeneration","volume":"1057","author":"Yi","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1038\/s41467-023-38753-6","article-title":"Lysyl oxidase-like 3 restrains mitochondrial ferroptosis to promote liver cancer chemoresistance by stabilizing dihydroorotate dehydrogenase","volume":"14","author":"Zhan","year":"2023","journal-title":"Nat. Commun."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.3390\/antiox12061173","article-title":"Melatonin alleviates retinal ischemia-reperfusion injury by inhibiting p53-mediated ferroptosis","volume":"12","author":"Zhang","year":"","journal-title":"Antioxidants (Basel)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1110146","DOI":"10.3389\/fphar.2023.1110146","article-title":"Second generation androgen receptor antagonist, TQB3720 abrogates prostate cancer growth via AR\/GPX4 axis activated ferroptosis","volume":"14","author":"Zhang","year":"","journal-title":"Front. Pharmacol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"529","DOI":"10.14336\/AD.2020.0912","article-title":"Iron accumulation and lipid peroxidation in the aging retina: implication of ferroptosis in age-related macular degeneration","volume":"12","author":"Zhao","year":"2021","journal-title":"Aging Dis."},{"key":"B61","doi-asserted-by":"publisher","first-page":"166969","DOI":"10.1016\/j.bbadis.2023.166969","article-title":"Melatonin protects photoreceptor cells against ferroptosis in dry AMD disorder by inhibiting GSK-3B\/Fyn-dependent Nrf2 nuclear translocation","volume":"1870","author":"Zhi","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B62","doi-asserted-by":"publisher","first-page":"D571","DOI":"10.1093\/nar\/gkac935","article-title":"FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations","volume":"51","author":"Zhou","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"B64","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2021.05.009","article-title":"Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis","volume":"171","author":"Zhou","year":"2021","journal-title":"Free Radic. Biol. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1543575\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T07:16:33Z","timestamp":1740640593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1543575\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":64,"alternative-id":["10.3389\/fphar.2025.1543575"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1543575","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"article-number":"1543575"}}