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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toll-like receptors (TLRs) are critical components of innate immunity. This study was designed to evaluate differential expression of genes for TLR and associated signal transduction molecules in critically ill patients developing sepsis compared with those with sterile inflammation. Uninfected critically ill patients with systemic inflammatory response syndrome were prospectively followed daily for development of sepsis. They were divided into two groups and compared in a case-control manner: (a) preseptic patients (n = 45) who subsequently developed sepsis, and (b) uninfected systemic inflammatory response syndrome patients (n = 45) who remained uninfected. Whole blood RNA was collected (PAXGene tube) at study entry and 1, 2, and 3 days before clinical sepsis diagnosis (or time-matched uninfected control) and analyzed via Affymetrix Hg_U133 Plus 2.0 microarrays. Genes were considered differentially expressed if they met univariate significance controlled for multiple comparisons at P < 0.005. Differentially expressed probes were uploaded into the Database for Annotation, Visualization and Integrated Discovery. The TLR pathway (Kyoto Encyclopedia of Genes and Genomes-KEGG) significance was determined via Expression Analysis Systematic Explorer (EASE) scoring. A total of 2,974 Affymetrix probes representing 2,190 unique genes were differentially expressed 1 day before sepsis diagnosis. Thirty-six probes representing 25 genes were annotated to the TLR pathway (KEGG) via the Database for Annotation, Visualization and Integrated Discovery with an EASE score at P < 0.0004. Notable TLR genes demonstrating increased expression include TLR-4 (median, 1.43-fold change), TLR-5 (2.08-fold change), and MAPK14 (1.90-fold change). An additional 11 unique genes were manually annotated into the TLR pathway based on known relevance such as TLR-8 (1.54-fold change). The total 36 genes contained 28 showing increased expression and 8 showing decreased expression. Differential gene expression was noted for TLR receptors (eight genes), TLR intracellular signal transduction cascade molecules (27 genes), and TLR-related effector molecules (one gene). The TLR and downstream signaling genes are differentially expressed in critically ill patients developing sepsis compared with those with sterile inflammation. These expression differences occur before phenotypic-based diagnosis of clinical sepsis.
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PMID:Differential expression of toll-like receptor genes: sepsis compared with sterile inflammation 1 day before sepsis diagnosis. 2008 96

Sepsis is a life-threatening syndrome causing thousands of deaths yearly worldwide. Sepsis is a result of infection and could lead to systemic inflammatory responses and organ failures. Additionally, blood cells, as the main cells in the immune systems, could be also affected by sepsis. Here, we have used different network analysis approaches, including Weighted Gene Co-expression Network Analysis (WGCNA), Protein-Protein Interaction (PPI), and gene regulatory network, to dissect system-level response to sepsis by the main white blood cells. Gene expression profiles of Neutrophils (NTs), Dendritic Cells (DCs), and Peripheral Blood Mononuclear Cells (PBMCs) that were exposed to septic plasma were obtained and analyzed using bioinformatics approaches. Individual gene expression matrices and the list of differentially expressed genes (DEGs) were prepared and used to construct several networks. Consequently, key regulatory modules and hub genes were detected through network analysis and annotated through ontology analysis extracted from DAVID database. Our results showed that septic plasma affected the regulatory networks in NTs, PBMCs more than the network in DCs. Gene ontology of DEGs revealed that signal transduction and immune cells responses are the most important biological processes affected by sepsis. On the other hand, network analysis detected modules and hub genes in each cell types. It was found that pathways involved in immune cells, signal transduction, and apoptotic processes are among the most affected pathways in the responses to sepsis. Altogether, we have found several hub genes including ADORA3, CD83 CDKN1A, FFAR2, GNAQ, IL1B, LTB, MAPK14, SAMD9L, SOCS1, and STAT1, which might specifically respond to sepsis infection. In conclusion, our results uncovered the system-level responses of the main white blood cells to sepsis and identified several hub genes with potential applications for therapeutic and diagnostic purposes.
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PMID:Network analysis of inflammatory responses to sepsis by neutrophils and peripheral blood mononuclear cells. 3008 51

Sepsis is one of the leading causes of mortality in intensive care units (ICU). The growing incidence rate of sepsis and its high mortality rate result are very important sociosanitary problems. Sepsis is a result of infection which can cause systemic inflammatory and organ failure. But the pathogenesis and the molecular mechanisms of sepsis is still not well understood. The aim of the present study was to identify the candidate key genes in the progression of sepsis.Microarray datasets GSE28750, GSE64457, and GSE95233 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Furthermore, to verify the results of the bioinformatics analyses, the expression levels of selected DEGs were quantified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in libobolysaccharide (LPS)-induced Human Umbilical Vein Endothelial Cells (HUVECs) to support the result of bioinformatics analysis.Thirteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in apoptotic process, inflammatory response, innate immune response. Hub genes with high degrees, including MAPK14, SLC2A3, STOM, and MMP8, were demonstrated to have an association with sepsis. Furthermore, RT-PCR results showed that SLC2A3 and MAPK14 were significantly upregulated in the HUVECs induced by LPS compared with controls.In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms of sepsis, and provide candidate targets for diagnosis and treatment of sepsis.
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PMID:Screening and identification of key gene in sepsis development: Evidence from bioinformatics analysis. 3262 54