Objective. The purpose of the present study is to screen the hub genes associated with sepsis, comprehensively understand the occurrence and progress mechanism of sepsis, and provide new targets for clinical diagnosis and treatment of sepsis. Methods. The microarray data of GSE9692 and GSE95233 were downloaded from the Gene Expression Omnibus (GEO) database. The dataset GSE9692 contained 29 children with sepsis and 16 healthy children, while the dataset GSE95233 included 102 septic subjects and 22 healthy volunteers. Differentially expressed genes (DEGs) were screened by GEO2R online analysis. The DAVID database was applied to conduct functional enrichment analysis of the DEGs. The STRING database was adopted to acquire protein-protein interaction (PPI) networks. Results. We identified 286 DEGs (217 upregulated DEGs and 69 downregulated DEGs) in the dataset GSE9692 and 357 DEGs (236 upregulated DEGs and 121 downregulated DEGs) in the dataset GSE95233. After the intersection of DEGs of the two datasets, a total of 98 co-DEGs were obtained. DEGs associated with sepsis were involved in inflammatory responses such as T cell activation, leukocyte cell-cell adhesion, leukocyte-mediated immunity, cytokine production, immune effector process, lymphocyte-mediated immunity, defense response to fungus, and lymphocyte-mediated immunity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that sepsis was connected to bacterial and viral infections. Through PPI network analysis, we screened the most important hub genes, including ITK, CD247, MMP9, CD3D, MMP8, KLRK1, and GZMK. Conclusions. In conclusion, the present study revealed an unbalanced immune response at the transcriptome level of sepsis and identified genes for potential biomarkers of sepsis, such as ITK, CD247, MMP9, CD3D, MMP8, KLRK1, and GZMK.
Background The role of platelet-derived extracellular vesicles (PEVs) in the development of sepsis was investigated in this study. Methods After collection of blood samples from sepsis patients and normal volunteers, the extracellular vesicles (EVs) were separated, followed by the isolation of PEVs from the blood of rats. Next, a sepsis rat model was constructed by cecal ligation and puncture (CLP), and rats received tail vein injection of PEVs to explore the role of PEVs in sepsis. Subsequently, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were adopted to determine the diameter of EVs and observe the morphology of PEVs, respectively; flow cytometry to detect the percentage of CD41-and CD61-positive EVs in isolated EVs; and ELISA to assess neutrophil extracellular trap (NET) formation, endothelial function injury-related markers in clinical samples or rat blood and serum inflammatory factor level. Results Compared with normal volunteers, the percentage of CD41- and CD61-positive EVs and the number of EVs were significantly elevated in sepsis patients. Moreover, sepsis patients also presented notably increased histone H3, myeloperoxidase (MPO), angiopoietin-2 and endocan levels in the blood, and such increase was positively correlated with the number of EVs. Also, animal experiments demonstrated that PEVs significantly promoted NET formation, mainly manifested as up-regulation of histone H3, high mobility group protein B1 (HMGB1), and MPO; promoted endothelial dysfunction (up-regulation of angiopoietin-2, endocan, and syndecan-1); and stimulated inflammatory response (up-regulation of interleukin (IL) -1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP) -1) in the blood of sepsis rats. Conclusion PEVs aggravate endothelial function injury and inflammatory response in sepsis by promoting NET formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.