DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation

ObjectiveIschemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and...

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Main Authors: Wei Hu, Ping Li, Nianju Zeng, Sheng Tan
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2023.1079977/full
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author Wei Hu
Wei Hu
Ping Li
Nianju Zeng
Sheng Tan
author_facet Wei Hu
Wei Hu
Ping Li
Nianju Zeng
Sheng Tan
author_sort Wei Hu
collection DOAJ
description ObjectiveIschemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and adjusting treatment strategies because neurological assessment after stroke treatment is mostly performed using scales and imaging. Therefore, there is an urgent need to find biomarkers that can help us evaluate and optimize the treatment plan.MethodsWe used data-independent acquisition (DIA) technology to screen differentially expressed proteins (DEPs) before and after ischemic stroke rehabilitation treatment, and then performed Gene Ontology (GO) and pathway enrichment analysis of DEPs using bioinformatics tools such as KEGG pathway and Reactome. In addition, the protein–protein interaction (PPI) network and modularity analysis of DEPs were integrated to identify the hub proteins (genes) and hub signaling pathways for neurological recovery in ischemic stroke. PRM-targeted proteomics was also used to validate some of the screened proteins of interest.ResultsAnalyzing the serum protein expression profiles before and after rehabilitation, we identified 22 DEPs that were upregulated and downregulated each. Through GO and pathway enrichment analysis and subsequent PPI network analysis constructed using STRING data and subsequent Cytoscape MCODE analysis, we identified that complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammatory and immune pathways are the major pathways involved in the improvement of neurological function after stroke rehabilitation.ConclusionComplement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammation and immunity pathways are not only key pathways in the pathogenesis of ischemic stroke but also the main pathways of action of rehabilitation therapy. In addition, IGHA1, LRG1, IGHV3-64D, and CP are upregulated in patients with ischemic stroke and downregulated after rehabilitation, which may be used as biomarkers to monitor neurological impairment and recovery after stroke.
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spelling doaj.art-8fd3b6cb79b7438687c3553621a0e5bc2023-03-07T04:29:19ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-03-011410.3389/fneur.2023.10799771079977DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitationWei Hu0Wei Hu1Ping Li2Nianju Zeng3Sheng Tan4Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Rehabilitation, Xiangya Bo'ai Rehabilitation Hospital, Changsha, ChinaDepartment of Rehabilitation, Xiangya Bo'ai Rehabilitation Hospital, Changsha, ChinaDepartment of Rehabilitation, Xiangya Bo'ai Rehabilitation Hospital, Changsha, ChinaDepartment of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaObjectiveIschemic stroke (IS) is a common disease that causes severe and long-term neurological disability in people worldwide. Although rehabilitation is indispensable to promote neurological recovery in ischemic stroke, it is limited to providing a timely and efficient reference for developing and adjusting treatment strategies because neurological assessment after stroke treatment is mostly performed using scales and imaging. Therefore, there is an urgent need to find biomarkers that can help us evaluate and optimize the treatment plan.MethodsWe used data-independent acquisition (DIA) technology to screen differentially expressed proteins (DEPs) before and after ischemic stroke rehabilitation treatment, and then performed Gene Ontology (GO) and pathway enrichment analysis of DEPs using bioinformatics tools such as KEGG pathway and Reactome. In addition, the protein–protein interaction (PPI) network and modularity analysis of DEPs were integrated to identify the hub proteins (genes) and hub signaling pathways for neurological recovery in ischemic stroke. PRM-targeted proteomics was also used to validate some of the screened proteins of interest.ResultsAnalyzing the serum protein expression profiles before and after rehabilitation, we identified 22 DEPs that were upregulated and downregulated each. Through GO and pathway enrichment analysis and subsequent PPI network analysis constructed using STRING data and subsequent Cytoscape MCODE analysis, we identified that complement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammatory and immune pathways are the major pathways involved in the improvement of neurological function after stroke rehabilitation.ConclusionComplement-related pathways, lipoprotein-related functions and effects, thrombosis and hemostasis, coronavirus disease (COVID-19), and inflammation and immunity pathways are not only key pathways in the pathogenesis of ischemic stroke but also the main pathways of action of rehabilitation therapy. In addition, IGHA1, LRG1, IGHV3-64D, and CP are upregulated in patients with ischemic stroke and downregulated after rehabilitation, which may be used as biomarkers to monitor neurological impairment and recovery after stroke.https://www.frontiersin.org/articles/10.3389/fneur.2023.1079977/fullischemic strokerehabilitationdata-independent acquisitionparallel response monitoringbiomarkersbioinformatics
spellingShingle Wei Hu
Wei Hu
Ping Li
Nianju Zeng
Sheng Tan
DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
Frontiers in Neurology
ischemic stroke
rehabilitation
data-independent acquisition
parallel response monitoring
biomarkers
bioinformatics
title DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
title_full DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
title_fullStr DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
title_full_unstemmed DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
title_short DIA-based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
title_sort dia based technology explores hub pathways and biomarkers of neurological recovery in ischemic stroke after rehabilitation
topic ischemic stroke
rehabilitation
data-independent acquisition
parallel response monitoring
biomarkers
bioinformatics
url https://www.frontiersin.org/articles/10.3389/fneur.2023.1079977/full
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