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Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke

Ischemic stroke (IS) is a disease characterized by rapid progression and high mortality and disability rates. Its pathophysiological process is inseparable from immune dysfunction. Recently, chromatin regulators (CRs) have been described as a class of enzymes that can recognize, form, and maintain t...

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Autores principales: Yu, Beibei, Tian, Yunze, Zhang, Yongfeng, Lv, Boqiang, Li, Jianzhong, Gong, Shouping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465164/
https://www.ncbi.nlm.nih.gov/pubmed/36105086
http://dx.doi.org/10.3389/fgene.2022.992847
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author Yu, Beibei
Tian, Yunze
Zhang, Yongfeng
Lv, Boqiang
Li, Jianzhong
Gong, Shouping
author_facet Yu, Beibei
Tian, Yunze
Zhang, Yongfeng
Lv, Boqiang
Li, Jianzhong
Gong, Shouping
author_sort Yu, Beibei
collection PubMed
description Ischemic stroke (IS) is a disease characterized by rapid progression and high mortality and disability rates. Its pathophysiological process is inseparable from immune dysfunction. Recently, chromatin regulators (CRs) have been described as a class of enzymes that can recognize, form, and maintain the epigenetic state of an organism, and are closely associated with immune regulation. Nevertheless, the role of CR-related genes in IS has not been fully elucidated. In this study, seven CR-related immune biomarkers in the GSE58294 and GSE22255 datasets were identified by combining differential gene expression analysis, weighted correlation network analysis, and single sample gene set enrichment analysis. After experimental validation using quantitative polymerase chain reaction, four genes (DPF2, LMNB1, MLLT3, and JAK2) were screened as candidate immune biomarkers. These four biomarkers demonstrated good predictive power in the clinical risk model (area under the curve, 0.775). Molecular docking simulations revealed that mevastatin, WP1066, cladribine, trichostatin A, mequitazine, and zuclomiphene may be potential immunomodulatory drugs for IS. Overall, the results of this study contribute to the identification of CR-related immune therapeutics target in IS and provide an important reference for further research.
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spelling pubmed-94651642022-09-13 Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke Yu, Beibei Tian, Yunze Zhang, Yongfeng Lv, Boqiang Li, Jianzhong Gong, Shouping Front Genet Genetics Ischemic stroke (IS) is a disease characterized by rapid progression and high mortality and disability rates. Its pathophysiological process is inseparable from immune dysfunction. Recently, chromatin regulators (CRs) have been described as a class of enzymes that can recognize, form, and maintain the epigenetic state of an organism, and are closely associated with immune regulation. Nevertheless, the role of CR-related genes in IS has not been fully elucidated. In this study, seven CR-related immune biomarkers in the GSE58294 and GSE22255 datasets were identified by combining differential gene expression analysis, weighted correlation network analysis, and single sample gene set enrichment analysis. After experimental validation using quantitative polymerase chain reaction, four genes (DPF2, LMNB1, MLLT3, and JAK2) were screened as candidate immune biomarkers. These four biomarkers demonstrated good predictive power in the clinical risk model (area under the curve, 0.775). Molecular docking simulations revealed that mevastatin, WP1066, cladribine, trichostatin A, mequitazine, and zuclomiphene may be potential immunomodulatory drugs for IS. Overall, the results of this study contribute to the identification of CR-related immune therapeutics target in IS and provide an important reference for further research. Frontiers Media S.A. 2022-08-29 /pmc/articles/PMC9465164/ /pubmed/36105086 http://dx.doi.org/10.3389/fgene.2022.992847 Text en Copyright © 2022 Yu, Tian, Zhang, Lv, Li and Gong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yu, Beibei
Tian, Yunze
Zhang, Yongfeng
Lv, Boqiang
Li, Jianzhong
Gong, Shouping
Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title_full Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title_fullStr Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title_full_unstemmed Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title_short Experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
title_sort experimental verification and validation of immune biomarkers based on chromatin regulators in ischemic stroke
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465164/
https://www.ncbi.nlm.nih.gov/pubmed/36105086
http://dx.doi.org/10.3389/fgene.2022.992847
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