Neutrophil Gene expression in Acute-on-chronic liver failure (ACLF), Chronic liver disease (CLD) and Healthy Controls_AIIMSND_Aug2020
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PROVIDER: PRJNA657743 | ENA |
REPOSITORIES: ENA
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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.
2021-09-28 | GSE156382 | GEO
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
Project description: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.
2021-05-19 | GSE168048 | GEO
Project description:Hepatitis B virus (HBV)-associated acute on chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. To explore potential biomarkers of HBV-ACLF for clinical applications, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified and quantified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples (p<0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.
2018-10-23 | PXD007975 | Pride
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.
2023-04-04 | GSE228610 | GEO
Project description:Gene expression profiling patients with cirrhosis and acute on chronic liver failure (ACLF)
| PRJNA596427 | ENA
Project description:BACKGROUND: The molecular mechanisms driving the progression from early chronic liver disease (eCLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Thus, the aim of this work is to develop a network-based approach to investigate molecular pathways driving progression from eCLD to ACLF. We created 9 liver-specific biological networks capturing key pathophysiological processes potentially related to CLD. We used these networks as framework to perform gene set enrichment analyses(GSEA) and create dynamic profiles of disease progression. RESULTS: Principal component analyses revealed that samples clustered according to the disease stage. GSEA analyses of the defined processes showed an up-regulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between CC and DC, while ACLF showed acute expression changes in all the defined liver-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated to ACLF onset. Functional analyses showed that ascending profiles were associated to inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the up-regulation of 4 genes of the ascending profile CXCL-6, KRT-18, SPINK-1, and ITGA2, and validated our findings on an independent patient’s cohort. CONCLUSION: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis processes. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting thus the hypothesis that ACLF should be considered a distinct entity.
2021-09-11 | GSE139602 | GEO
Project description:Gene expression profiling of immune cells from patients with acute on chronic liver failure (ACLF)
| PRJNA596432 | ENA
Project description:Background and aims: Acute-on-chronic liver failure (ACLF) is characterized by rapid deterioration of liver function and organ failure, whereby immunoparesis and susceptibility to infections often precipitate this syndrome. Here we characterized the events triggering immune dysfunction in monocytes within alcoholic liver disease. Methods: We evaluated the frequency of monocyte subsets, their intracellular IL10 production, surface HLA-DR expression, and phagocytic and oxidative burst capacity in patients with decompensated cirrhosis, -alcoholic hepatitis or ACLF. RNAsequencing of ACLF patient-derived CD14+ monocytes were performed either immediately or after 12-hour culture in the presence or absence of plasma from ACLF patients. In this in vitro model of ACLF induction in CD14+ monocytes we characterized the early molecular, immunological and functional changes. Results: Besides a redistribution of monocyte subset composition, ACLF patient-derived monocytes featured elevated frequencies of IL-10-producing cells, reduced HLA-DR expression and impaired phagocytic- and oxidative burst capacity. RNAsequencing revealed a reprogramming of ACLF monocytes, whereby they undergo a transition from a pro-inflammatory to an immunosuppressive- and altered metabolic status. Culturing healthy monocytes in the presence of ACLF plasma, blunted their phagocytic capacity and triggered a gene expression pattern comparable to ACLF patients. Conversely, culturing patient monocytes in normal plasma restored their phagocytic capacity. Finally, plasma IL-10 levels correlated with patient survival. Conclusion: ACLF monocytes featured a defective immunosuppressive and -glycolytic profile, an attribute which could be mimicked by culturing healthy monocytes in the presence of ACLF patient plasma. Our data implicate a role for IL-10 signaling pathways in triggering monocytes dysfunction and opens up new avenues for therapeutic targeting.
2019-02-06 | GSE93265 | GEO
Project description:Gene expression profiling of neutrophils from patients with cirrhosis and acute on chronic liver failure (ACLF)
| PRJNA596431 | ENA