Long noncoding RNA and messenger RNA abnormalities in pediatric sepsis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145227 | GEO | 2020/02/14
REPOSITORIES: GEO
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Project description:Long noncoding RNA and messenger RNA abnormalities in pediatric sepsis
| PRJNA606469 | ENA
Project description:BackgroundSepsis represents a complex disease with dysregulated inflammatory response and high mortality rate. Long noncoding RNAs (lncRNAs) have been reported to play regulatory roles in a variety of biological processes. However, studies evaluating the function of lncRNAs in pediatric sepsis are scarce, and current knowledge of the role of lncRNAs in pediatric sepsis is still limited. The present study explored the expression patterns of both lncRNAs and mRNAs between pediatric sepsis patients and healthy controls based on a comprehensive microarray analysis.MethodsLncRNA and mRNA microarray was used to detect the expression of lncRNAs and mRNAs in the septic and control groups. Aberrantly expressed mRNAs and lncRNAs identified were further interpreted by enrichment analysis, receiver operating characteristic (ROC) curve analysis, co-expression network analysis, and quantitative real-time PCR (qPCR).ResultsA total of 1488 differetially expressed lncRNAs and 1460 differentially expressed mRNAs were identified. A co-expression network of the identified lncRNAs and mRNAs was constructed. In this network, lncRNA lnc-RP11-1220 K2.2.1-7 is correlated with mRNA CXCR1 and CLEC4D; lncRNA lnc-ANXA3-2 is correlated with mRNA CLEC4D; lncRNA lnc-TRAPPC5-1 is correlated with mRNA DYSF and HLX; lncRNA lnc-ZNF638-1 is correlated with mRNA DYSF and HLX. Significantly different expressions between pediatric sepsis patients and controls were validated by qPCR for the 4 lncRNAs and 4 co-expressed mRNAs, validating the microarray results.ConclusionsOur study contributes to a comprehensive understading of the involvment of lncRNAs and mRNAs in pediatric sepsis, which may guide subsequent experimental research. Furthermore, our study may also provide potential candidate lncRNAs and mRNAs for the diagnosis and treatment of pediatric sepsis.
| S-EPMC7063742 | biostudies-literature
Project description:Pediatric sepsis is a leading cause of mortality in children across the world. Within pediatric sepsis, how developmental age-specific host immune response impact on the occurrence and development of pediatric sepsis is still unknown, especially between infants and toddlers, which were the major susceptible age groups in sepsis. Experimental design In this study, we applied a nested case-control study strategy and analyzed the plasma proteomes of pediatric sepsis patients between infants and toddlers in comparison to their age-matched controls respectively. Each age group consists of three subgroups with different outcomes. One hundred and ten plasma samples were pooled into 16 samples for quantitative identification by LC-MS/MS. Results It was totally quantified 677 proteins. In comparison to toddlers, infant sepsis patients were characteristic with dominant neutrophil-mediated defense, suppressed adaptive immunity and NK-mediated cytotoxicity. Besides, pentose phosphate pathway was more up-regulated in infants and associated with poor outcome. Moreover, combined Hp and Thbs1 with the AUC value of 0.958 (95%CI, 0.868, 1.000) was confirmed as potential infant-adapted prognostic marker of poor outcome in sepsis. Conclusion and clinical relevance Our proteomic analysis of age-associated pediatric sepsis combined with clinical laboratory data provided a comprehensive insight into the complex, multifactorial heterogeneous host response to pediatric sepsis and allowed identification of critical differences between infant and toddler sepsis. Moreover, we confirmed that combined Hp and Thbs1 is more infant-adapted and serves as a potential prognostic biomarker for poor outcome of infant sepsis, promoting the application of age-adapted precision medicine in pediatric sepsis.
2021-11-01 | PXD026656 | Pride
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Experiment Overall Design: Prospective observational study involving microarray-based bioinformatics.
2009-01-05 | E-GEOD-13904 | biostudies-arrayexpress
Project description:Normal children, children with SIRS, children with sepsis, and children with septic shock. Objectives: To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Keywords: Normal vs diseased
2008-12-12 | GSE13904 | GEO
Project description:The temporal evolution of sepsis was monitored by transcriptional profiling of five critically ill children with meningococcal sepsis and sepsis-induced multiple organ failure. Blood was sampled at 6 time points during the first 48 hours of their admission to pediatric intensive care, where the children received standard clinical treatment including organ support and antimicrobial therapy. Striking transcript instability was observed over the 48 hours, with increasing numbers of regulated genes over time. Most notably, proposed biomarkers for sepsis risk stratification also showed expression instability, with varied expression levels over 48 hours. This study demonstrates the extent of the complexity of temporal changes in gene expression that occur during the evolution of sepsis-induced multiple organ failure. Importantly, stratification tools that propose expression of biomarkers must take into account the temporal changes, over the use of single snapshots that may be less informative.
2013-04-03 | E-MEXP-3850 | biostudies-arrayexpress
Project description:Expression data from CD8+ T cells and CD68+ monocytes from patients with hemophagocytic lymphohistiocytosis, sepsis, and persistent systemic inflammatory response syndrome Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and persistent systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine if plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a ‘core inflammatory signature’ of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Seventeen of 135 analytes were significantly different in HLH plasma compared to SIRS/sepsis, including increased interferon-gamma (IFNg)-regulated chemokines CXCL9, CXCL10 and CXCL11. Further, a 5-analyte plasma protein classifier including these chemokines was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and CD68+ monocytes from blood were also enriched for IFNg pathway signatures in peripheral blood cells from patients with HLH compared to SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH. Further, comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFNg signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH, sepsis and SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.
2021-05-16 | GSE150707 | GEO
Project description:Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multi-organ failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a mouse model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and organ damage in spite of a high pathogen burden. We found that, both neutrophils and B cells emerged as key regulators of tissue integrity. Enduring changes in the transcriptional profile of neutrophils, included upregulated Cxcr4 expression in protected, tolerant hosts. Neutrophil Cxcr4 upregulation required the presence of B cells, suggesting that B cells promoted disease tolerance by improving tissue damage control via the suppression of neutrophils’ tissue damaging properties. Finally, therapeutic administration of a Cxcr4 agonist successfully promoted tissue damage control and prevented liver damage during sepsis. Our findings highlight the importance of a critical B-cell/neutrophil interaction during sepsis and establish neutrophil Cxcr4 activation as a potential means to promote disease tolerance during sepsis.
2022-08-04 | GSE210207 | GEO
Project description:Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. Here we present an integrated analysis of the ncRNA-transcriptome of purified human hematopoietic stem cells (HSCs) and their differentiated progenies, including granulocytes, monocytes, T-cells, NK-cells, B-cells, megakaryocytes and erythroid precursors, which we correlated with the ncRNA expression profile of 48 pediatric AML samples to establish a core lncRNA stem cell signature in AML.Linear (PCA) and nonlinear (t-SNE) dimensionality reduction of 46 pediatric AML samples including Down syndrome AMKL, core-binding factor AMLs (inv[16] or t[8;21]) and MLL-rearranged leukemias mapped most samples to a space between HSCs and differentiated cells together with the myeloid progenitors. A subset of AML-samples mapped closely to healthy HSCs, including most of the DS-AMKLs and MLL-AMLs. Following the incorporation of acute myeloid leukemia (AML) samples into the landscape, we further uncover prognostically relevant ncRNA stem cell signatures shared between AML blasts and healthy hematopoietic stem cells.
2017-05-31 | GSE98697 | GEO
Project description:There are currently no specific diagnostic biomarkers and effective pharmacological treatments for sepsis, which makes the mortality rate remains high. Although non-coding RNAs seem to be superior candidates as biomarkers and therapeutics for sepsis, the role of long noncoding RNA (lncRNA) in sepsis remains not completely understood. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells at the same time point.
2022-07-22 | GSE208550 | GEO