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Prognosis associated mRNA in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) [mRNA]

ABSTRACT: Genome wide mRNA profiling in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients of in different prognoses of 28-day. The Agilent SurePrint G3 Human Gene Expression ver. 3 8x60K Microarray was used to obtain RNA profiles in 8 survival patients and 8 dead patients in 28-day.

ORGANISM(S): Homo sapiens

PROVIDER: GSE168048 | GEO | 2021/05/19

REPOSITORIES: GEO

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Prognosis associated microRNA in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) [miRNA]

Project description:Genome wide microRNA profiling in peripheral blood mononuclear cells (PBMCs) from hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients of in different prognoses of 28-day. The Agilent Human miRNA Microarray Kit was used to obtain RNA profiles in 8 survival patients and 8 dead patients in 28-day.

2021-05-19 | GSE168046 | GEO

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Project description:To address the molecular basis of immune-dysfunction in Acute-on-chronic liver failure (ACLF), we carried out gene expression profiling of blood derived neutrophil from ACLF, belonging to both sterile inflammatory and sepsis conditions. Peripheral whole blood was subjected to PMN enrichment by double gradient centrifugation, and RNA isolation was done by TRIZOL method, followed by microarray experiment using Agilent one-color platform. We compared the gene expression of these neutrophils with that of Chronic liver disease (CLD) patients and healthy controls (HC) for baseline relative quantification, and found unique set of upregulated and downregulated genes in ACLF. We validated the expression of the most differentially expressed genes by quantitative RT-PCR and also stratified the patients into survivors and non-survivors, sepsis and sterile-inflammation. We found an upregulated 3-gene signature of ELANE-MPO-CD177 to be associated with 28-day mortality, irrespective of presence or absence of sepsis.

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Project description:The transcriptomic profiles of circulating neutrophils were compared between patients with ACLF (N=10), patients with CLC (N=10) and HC (N=10). Compared with CLC-neutrophils, the expression of 1022 genes were found to be upregulated in ACLF-neutrophils, and 1101 genes were downregulated. And compared to HC, the expression of 726 genes were up-regulated in ACLF-neutrophils, and 711 genes were down-regulated. The pathway analysis identified mutiple pathways enriched or down-regulated in ACLF-neutrophils when comparing with neutrophils from CLC or HC groups.

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Sepsis related ACLF mouse model

Project description:Background and aims: Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patients with previously stable cirrhosis. A common cause of ACLF is sepsis secondary to bacterial infection. Sepsis-associated ACLF involves a loss of differentiated liver function in the absence of direct liver injury, and its mechanism is unknown. We aimed to study the mechanism of sepsis associated ACLF using a novel mouse model. Approach and Results: Sepsis-associated ACLF was induced by cecal ligation and puncture procedure (CLP) in mice treated with thioacetamide (TAA). The combination of TAA and CLP resulted in a significant decrease in liver synthetic function and high mortality. These changes were associated with reduced metabolic gene expression and increased C/EBPβ transcriptional activity. We found that C/EBPβ binding to its target gene promoters was increased. In humans C/EBPβ chromatin binding was similarly increased in ACLF group compared to control cirrhosis. Hepatocyte specific Cebpb knockout mice had reduced mortality and increased gene expression of hepatocyte differentiation markers in TAA/CLP mice, suggesting that C/EBPβ promotes liver failure in these mice. C/EBPβ activation was associated with endothelial dysfunction, characterized by reduced Angiopoietin-1/Angiopoietin-2 ratio and increased endothelial production of HGF. Angiopoietin-1 supplementation or Hgf knockdown reduced hepatocyte C/EBPβ accumulation, restored liver function, and reduced mortality, suggesting that endothelial dysfunction induced by sepsis drives acute-on-chronic liver failure via HGF-C/EBPβ pathway. Conclusion: The transcription factor C/EBPβ is activated in both mouse and human ACLF and is a potential therapeutic target to prevent liver failure in patients with sepsis and cirrhosis.

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Gene expression analysis of stimulated primary ASM cells [mRNA]

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Circulating neutrophil transcriptomics in HBV-ACLF patients.

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Project description:Neutrophils were isolated (using Ficoll, Dextran and water to lyse the red cells) from whole blood of 5 healthy subjects, 5 patients with stable cirrhosis and 5 patients with ACLF. RNA was then extracted and amplified 100 ng of RNA per sample were then hybridized on ClarionS array (Affymetrix, Thermofischer scientific)

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Sepsis related ACLF mouse model

Project description:Sepsis related ACLF mouse model

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