Identification of potential biomarkers and pathogenesis in neutrophil-predominant severe asthma: A comprehensive bioinformatics analysis.
Ajmaline
Aminoglutethimide
Asthma
/ genetics
Bethanechol
Biomarkers
Cefaclor
Computational Biology
Cytokines
Dimenhydrinate
Ethionamide
Gene Expression Profiling
Humans
Iloprost
Indoprofen
JNK Mitogen-Activated Protein Kinases
Levobunolol
Mimosine
Mitogen-Activated Protein Kinases
Myeloid Differentiation Factor 88
NF-kappa B
NLR Proteins
Neutrophils
Receptors, Cytokine
Toll-Like Receptor 2
Trapidil
Triggering Receptor Expressed on Myeloid Cells-1
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
23 Sep 2022
23 Sep 2022
Historique:
entrez:
5
10
2022
pubmed:
6
10
2022
medline:
12
10
2022
Statut:
ppublish
Résumé
Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis. Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified. Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma. This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.
Sections du résumé
BACKGROUND
BACKGROUND
Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis.
METHODS
METHODS
Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified.
RESULTS
RESULTS
Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma.
CONCLUSION
CONCLUSIONS
This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.
Identifiants
pubmed: 36197221
doi: 10.1097/MD.0000000000030661
pii: 00005792-202209230-00067
pmc: PMC9509178
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Myeloid Differentiation Factor 88
0
NF-kappa B
0
NLR Proteins
0
Receptors, Cytokine
0
Toll-Like Receptor 2
0
Triggering Receptor Expressed on Myeloid Cells-1
0
Bethanechol
004F72P8F4
Aminoglutethimide
0O54ZQ14I9
Ajmaline
1PON08459R
Mimosine
500-44-7
Cefaclor
69K7K19H4L
Indoprofen
CPE46ZU14N
JNK Mitogen-Activated Protein Kinases
EC 2.7.11.24
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Trapidil
EYG5Y6355E
Levobunolol
G6317AOI7K
Dimenhydrinate
JB937PER5C
Iloprost
JED5K35YGL
Ethionamide
OAY8ORS3CQ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e30661Informations de copyright
Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to disclose.
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