{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T21:53:49Z","timestamp":1775339629149,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Fungal keratitis is a common blinding eye disease, and Fusarium is one of the main species that cause fungal keratitis. As is well known, oxidative stress plays an important role in Fusarium keratitis and it is also a significant initiating factor of ferroptosis. But the relationship between Fusarium keratitis and ferroptosis is currently unclear. This study aimed to speculate and validate potential ferroptosis-related genes in Fusarium keratitis using bioinformatics analysis, which provided ideas for further research on its specific mechanism and new targets for its treatment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The microarray expression profiling dataset (GSE58291) came from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were obtained by the limma package of the R software. The DEGs were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the DEGs were intersected with the genes in the ferroptosis database. The top 5 hub genes were obtained by the protein-protein interaction (PPI) network analysis and the cytoHubba plug-in of Cytoscape software. The hub genes were subjected to GSEA analysis. Then we analyzed the immune infiltration of the samples by CIBERSORT and ssGSEA algorithm. Finally, we validated the mRNA of hub genes by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1,368 DEGs were identified and 26 ferroptosis-related DEGs were obtained. At the same time, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. HMOX1, CYBB, GPX2, ALOX5 and SRC were obtained by the PPI network analysis and the cytoHubba plug-in of Cytoscape software. The iron metabolism and immune response related pathways were enriched using GSEA. They included hematopoietic cell lineage, lysosome and FC gamma R mediated phagocytosis. T cells follicular helper, monocytes, macrophages and mast cells might play an important role in Fusarium keratitis using analysis of immune infiltration. Finally, qPCR confirmed that the expression of HMOX1, CYBB, ALOX5 mRNA in the DON group was significantly elevated, while the expression of GPX2 were significantly decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ferroptosis may play an important role in Fusarium keratitis. HMOX1, CYBB, ALOX5 and GPX2 may be key ferroptosis-related genes in the pathogenesis of Fusarium keratitis. <\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1103471","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T04:53:27Z","timestamp":1675140807000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of hub genes and pathways of ferroptosis in Fusarium keratitis by bioinformatics methods"],"prefix":"10.3389","volume":"13","author":[{"given":"Xingbo","family":"Teng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyuan","family":"Sha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyao","family":"Diao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingxiang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1080\/13693780801961352","article-title":"Fusarium keratitis and contact lens wear: Facts and speculations","volume":"46","author":"Ahearn","year":"2008","journal-title":"Med. Mycol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7869","DOI":"10.1111\/febs.16244","article-title":"Emerging roles of ferroptosis in infectious diseases","volume":"289","author":"Bagayoko","year":"2022","journal-title":"FEBS J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1089\/ars.2019.7905","article-title":"Regulatory phenomena in the glutathione peroxidase superfamily","volume":"33","author":"Brigelius-Floh\u00e9","year":"2020","journal-title":"Antioxid Redox Signal"},{"key":"B4","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3109\/09286586.2011.595041","article-title":"Microbial keratitis in East Africa: Why are the outcomes so poor","volume":"18","author":"Burton","year":"2011","journal-title":"Ophthalmic Epidemiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1016\/j.ophtha.2016.07.009","article-title":"Prospective study of the diagnostic accuracy of the in vivo laser scanning confocal microscope for severe microbial keratitis","volume":"123","author":"Chidambaram","year":"2016","journal-title":"Ophthalmology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3390\/diagnostics12030679","article-title":"The diagnosis and treatment of fungal endophthalmitis: An update","volume":"12","author":"Danielescu","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1097\/ICL.0b013e318235c5af","article-title":"Resistant fusarium keratitis progressing to endophthalmitis","volume":"38","author":"Edelstein","year":"2012","journal-title":"Eye Contact Lens"},{"key":"B9","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1111\/imm.12910","article-title":"Implications of macrophage polarization in autoimmunity","volume":"154","author":"Funes","year":"2018","journal-title":"Immunology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ceb.2017.11.001","article-title":"To eat or not to eat-the metabolic flavor of ferroptosis","volume":"51","author":"Gao","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1016\/j.ophtha.2010.03.048","article-title":"Trends in fungal keratitis in the United States 2001 to 2007","volume":"117","author":"Gower","year":"2010","journal-title":"Ophthalmology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/j.ccell.2019.04.002","article-title":"Targeting ferroptosis to iron out cancer","volume":"35","author":"Hassannia","year":"2019","journal-title":"Cancer Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"10421","DOI":"10.1038\/s41598-017-09636-w","article-title":"ROS-induced oxidative injury involved in pathogenesis of fungal keratitis via p38 MAPK activation","volume":"7","author":"Hua","year":"2017","journal-title":"Sci. Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.exer.2014.10.014","article-title":"Role of activated macrophages in experimental fusarium solani keratitis","volume":"129","author":"Hu","year":"2014","journal-title":"Exp. Eye Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1097\/01.icl.0000249595.27520.2e","article-title":"Fungal keratitis: Emerging trends and treatment outcomes","volume":"32","author":"Iyer","year":"2006","journal-title":"Eye Contact Lens"},{"key":"B16","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":"B17","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1093\/infdis\/jir426","article-title":"Expression of innate and adaptive immune mediators in human corneal tissue infected with aspergillus or fusarium","volume":"204","author":"Karthikeyan","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"852","DOI":"10.4103\/ijo.IJO_999_21","article-title":"Clinical profile and treatment outcomes of fusarium keratitis","volume":"70","author":"Khurana","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41420-019-0146-x","article-title":"Three cell deaths and a funeral: Macrophage clearance of cells undergoing distinct modes of cell death","volume":"5","author":"Kl\u00f6ditz","year":"2019","journal-title":"Cell Death Discovery"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1158\/2159-8290.CD-19-0338","article-title":"Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of slc7a11","volume":"9","author":"Lang","year":"2019","journal-title":"Cancer Discov"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1172\/JCI63239","article-title":"Fungal antioxidant pathways promote survival against neutrophils during infection","volume":"122","author":"Leal","year":"2012","journal-title":"J. Clin. Invest."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00139","article-title":"Mechanisms of ferroptosis and relations with regulated cell death: A review","volume":"10","author":"Lei","year":"2019","journal-title":"Front. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"512","DOI":"10.18240\/ijo.2016.04.06","article-title":"Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis","volume":"9","author":"Li","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2915019","DOI":"10.1155\/2021\/2915019","article-title":"RSL3 drives ferroptosis through NF-\u03baB pathway activation and GPX4 depletion in glioblastoma","volume":"2021","author":"Li","year":"2021","journal-title":"Oxid. Med. Cell Longev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"346","DOI":"10.4103\/0301-4738.185592","article-title":"Recent advances in diagnosis and management of mycotic keratitis","volume":"64","author":"Maharana","year":"2016","journal-title":"Indian J. Ophthalmol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1097\/ICO.0b013e318033b504","article-title":"Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis","volume":"26","author":"Mitchell","year":"2007","journal-title":"Cornea"},{"key":"B27","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"B28","doi-asserted-by":"publisher","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF-kappaB family of transcription factors and its regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1001\/jamaophthalmol.2016.4096","article-title":"Effect of oral voriconazole on fungal keratitis in the mycotic ulcer treatment trial II (MUTT II): A randomized clinical trial","volume":"134","author":"Prajna","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"108941","DOI":"10.1016\/j.exer.2022.108941","article-title":"Resolvin D1 protects against aspergillus fumigatus keratitis in diabetes by blocking the MAPK-NF-\u03baB pathway","volume":"216","author":"Qin","year":"2022","journal-title":"Exp. Eye Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"104919","DOI":"10.1016\/j.phrs.2020.104919","article-title":"The application of ferroptosis in diseases","volume":"159","author":"Qiu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.mib.2021.07.018","article-title":"Pathogenic aspergillus and fusarium as important causes of blinding corneal infections - the role of neutrophils in fungal killing, tissue damage and cytokine production","volume":"63","author":"Ratitong","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/myc.12718","article-title":"Inflammation and oxidative stress in corneal tissue in experimental keratitis due to fusarium solani: Amelioration following topical therapy with voriconazole and epigallocatechin gallate","volume":"61","author":"Ruban","year":"2018","journal-title":"Mycoses"},{"key":"B34","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0955-0674(00)00194-0","article-title":"HIF-1 and mechanisms of hypoxia sensing","volume":"13","author":"Semenza","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/eye.2011.275","article-title":"Diagnosis of infectious diseases of the eye","volume":"26","author":"Sharma","year":"2012","journal-title":"Eye (Lond)"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1097\/ICO.0000000000001365","article-title":"Comparison of oral voriconazole versus oral ketoconazole as an adjunct to topical natamycin in severe fungal keratitis: A randomized controlled trial","volume":"36","author":"Sharma","year":"2017","journal-title":"Cornea"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1007\/s10753-013-9657-4","article-title":"5-lipoxygenase inhibitor zileuton inhibits neuronal apoptosis following focal cerebral ischemia","volume":"36","author":"Shi","year":"2013","journal-title":"Inflammation"},{"key":"B38","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/00055735-200408000-00008","article-title":"Fungal keratitis","volume":"15","author":"Srinivasan","year":"2004","journal-title":"Curr. Opin. Ophthalmol."},{"key":"B39","doi-asserted-by":"publisher","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","year":"2017","journal-title":"Cell"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2749173","DOI":"10.1155\/2019\/2749173","article-title":"Emerging roles of 5-lipoxygenase phosphorylation in inflammation and cell death","volume":"2019","author":"Sun","year":"2019","journal-title":"Oxid. Med. Cell Longev"},{"key":"B41","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/1469-0691.12126","article-title":"Mycotic keratitis: Epidemiology, diagnosis and management","volume":"19","author":"Thomas","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1136\/bjo.2005.076315","article-title":"Characteristic clinical features as an aid to the diagnosis of suppurative keratitis caused by filamentous fungi","volume":"89","author":"Thomas","year":"2005","journal-title":"Br. J. Ophthalmol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.mib.2020.09.011","article-title":"Eradicating, retaining, balancing, swarming, shuttling and dumping: A myriad of tasks for neutrophils during fungal infection","volume":"58","author":"Urban","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"B44","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.1007\/s12035-018-1403-3","article-title":"Ferroptosis and its role in diverse brain diseases","volume":"56","author":"Weiland","year":"2019","journal-title":"Mol Neurobiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"8365","DOI":"10.1038\/s41598-018-26798-3","article-title":"Mast cell activation protects cornea by promoting neutrophil infiltration via stimulating ICAM-1 and vascular dilation in fungal keratitis","volume":"8","author":"Xie","year":"2018","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1016\/j.ophtha.2006.05.035","article-title":"Spectrum of fungal keratitis in north China","volume":"113","author":"Xie","year":"2006","journal-title":"Ophthalmology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1158\/1541-7786.MCR-19-0691","article-title":"A TAZ-ANGPTL4-NOX2 axis regulates ferroptotic cell death and chemoresistance in epithelial ovarian cancer","volume":"18","author":"Yang","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1182\/blood-2017-12-822619","article-title":"Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion","volume":"131","author":"Youssef","year":"2018","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1167\/iovs.08-3104","article-title":"Role of adaptive immunity in the pathogenesis of candida albicans keratitis","volume":"50","author":"Zhang","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.semcancer.2019.03.002","article-title":"Ferroptosis is a type of autophagy-dependent cell death","volume":"66","author":"Zhou","year":"2020","journal-title":"Semin. Cancer Biol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1103471\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T04:53:30Z","timestamp":1675140810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1103471\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":50,"alternative-id":["10.3389\/fcimb.2023.1103471"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1103471","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]},"article-number":"1103471"}}