Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1309012 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background: Of Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), 85%-90% of cases develop from liver cirrhosis, and circular RNAs (circRNAs) have important roles in this process; however, differences in serum circRNA expression profiles between patients with HBV-related cirrhosis and those with HCC have not been studied. Methods: Serum RNA was extracted from patients with HCC and cirrhosis (n = 5 per group) and used for microarray analysis of circRNA expression profiles. Bioinformatics analyses, including clustering, differential expression, and construction of a ceRNA network, were performed. Quantitative real-time reverse transcription PCR validation analysis was conducted using samples from patients with HBV-related cirrhosis (n = 88) and HCC (n = 73). Further, statistical analyses were used to analyze the potential function and value of selected circRNAs with expression differing between the HBV-related cirrhosis and HCC groups. Results: Cluster analysis revealed 8 up-regulated and 80 down-regulated circRNAs. Further, qRT-PCR analysis showed that circRNA_0000367 expression was consistent with that detected by microarray experiments, with significantly lower levels in patients with HBV-related HCC than those with HBV-related cirrhosis. CircRNA_0000367 expression levels were also significantly lower in patients with drug-resistant HBV and those with HBV-related cirrhosis with Model for End-Stage Liver Disease score < 10. Further, circRNA_00000367 expression levels were lower in patients with HBV-related cirrhosis who progressed to HCC. Analysis of the lncRNA-miRNA-mRNA ceRNA network identified 39 miRNAs and 24 mRNAs involved in circRNA_00000367 networks; these target genes were involved in various biological processes and signaling pathways. Conclusion: Serum cicrRNA_0000367 is a potential HCC biomarker in patients with HBV-related cirrhosis, where down-regulation of cicrRNA_0000367 in HBV-related cirrhosis may be associated with progression to HCC.
2025-02-10 | E-MTAB-12717 | biostudies-arrayexpress
Project description:Patients with chronic liver disease (CLD), including cirrhosis, are at increased risk of intractable viral infections and are hyporesponsive to vaccination. Hallmarks of CLD and cirrhosis include microbial translocation and elevated levels of type I interferon (IFN-I). We aimed to investigate the relevance of microbiota-induced IFN-I in the impaired adaptive immune responses observed in CLD. We combined bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver injury with vaccination or lymphocytic choriomeningitis virus infection in transgenic mice lacking IFN-I in myeloid cells (LysM-Cre IFNARflox/flox), IFNAR-induced IL-10 (MX1-Cre IL10flox/flox) or IL-10R in T cells (CD4-DN IL-10R). Key pathways were blocked in vivo with specific antibodies (anti-IFNAR and anti-IL10R). We assessed T-cell responses and antibody titers after HBV and SARS-CoV-2 vaccinations in patients with CLD and healthy individuals in a proof-of-concept clinical study. We demonstrate that BDL- and CCL4-induced prolonged liver injury leads to impaired T-cell responses to vaccination and viral infection in mice, subsequently leading to persistent infection. We observed a similarly defective T-cell response to vaccination in patients with cirrhosis. Innate sensing of translocated gut microbiota induced IFN-I signaling in hepatic myeloid cells that triggered excessive IL-10 production upon viral infection. IL-10R signaling in antigen-specific T cells rendered them dysfunctional. Antibiotic treatment and inhibition of IFNAR or IL-10Ra restored antiviral immunity without detectable immune pathology in mice. Notably, IL-10Ra blockade restored the functional phenotype of T cells from vaccinated patients with cirrhosis. Innate sensing of translocated microbiota induces IFN-/IL-10 expression, which drives the loss of systemic T-cell immunity during prolonged liver injury.
2023-09-11 | GSE158261 | GEO
Project description:Background: Hepatitis B virus (HBV) infection is an important public health burden. Chronic HBV infection always leads to chronic hepatitis, liver fibrosis and increases the incidence of liver cancer. However, the mechanism of liver fibrosis caused by persistent HBV infection remains unclear. Methods: In present study, we isolated and enriched primary human hepatic stellate cells (HSCs) from chronically HBV infected patients with liver cirrhosis. The differences expression of mRNA and protein were analyzed by combining proteomics, transcriptomics, and biological network analysis. Results: After bioinformatics analysis with transcriptomics and proteomics data, a total of 2,156 genes and 711 proteins were differently expressed between the liver cirrhosis group and control group. GO enrichment analysis and KEGG analysis indicated those differently expressed molecules were mainly involved in oxidative stress, glycometabolism, and fibrous repair. Moreover, a total of 110 overlapping biomarker were identified and two of them (PKM2 and EHD2) were validated as candidates correlated with liver fibrosis by qRT-PCR and immunofluorescence from primary human HSCs and in vitro cellular hepatic fibrosis model. Conclusion: Our results indicated that PKM2 and EHD2 were overexpressed in chronically HBV infected patients with liver cirrhosis, suggesting them as potential biomarkers and therapeutic targets for liver fibrosis.
2025-12-13 | GSE221083 | GEO
Project description:MaternalWestern-style diet (WD) disrupts early life gut microbiota in the offspring and is associated with pediatric nonalcoholic fatty liver disease (NAFLD). Here, we report that oral supplementation with gut-derived tryptophan metabolites indole (Ind) or indole-3-acetate (I3A) during pregnancy and lactation in WD-fed dams had persistent effects in offspring liver, acting on key upstream regulators in WD-challenged offspring that suppress pathways for steatosis, fibrosis, and oxidative stress. Maternal Ind or I3A activated aryl hydrocarbon receptor (AHR) signaling, leading to increases in long-chain and very long-chain (VLC) ceramides in offspring liver and small intestine. These effects were evident as early as postnatal day 14. The tryptophan metabolite 5-hydroxyindoleacetate (5-HIAA), an AHR ligand, was depleted in offspring by maternal WD and restored by maternal I3A treatment. Fecal transplantation studies demonstrated that VLC ceramides and liver fibrosis remodeling were mediated by maternal indoles altering the gut microbiota, with strong associations with Lactobacillaceae. Collectively, these findings define a novel and persistent protective effect of maternal Ind and I3A to prevent NAFLD, acting both directly on the liver and through the microbiota. These tryptophan metabolites may serve as therapeutic targets for future interventional studies aimed at prevention of pediatric NAFLD.
2026-01-21 | GSE247323 | GEO
Project description:Chronic hepatitis B virus (HBV) infection is the main etiology of liver fibrosis (LF), leading to cirrhosis and liver tumors. DNA methylation caused by HBV protein changes the liver microenvironment and activates hepatic stellate cells, which is an important mechanism of liver fibrosis. However, the exact mechanism remains unclear. DNA methyltransferase 3A (DNMT3A) is a major enzyme that promotes DNA methylation. HBV infection promotes the expression of DNMT3A. To determine the specific roles of DNMT3A, we used lentivirus to overexpress DNMT3A in hepatocellular carcinoma cell line (HepG2). And the changes of transcriptome were analysed by RNA-seq.
2024-12-23 | GSE284401 | GEO
Project description:Chronic hepatitis B virus (HBV) infection is the main etiology of liver fibrosis (LF), leading to cirrhosis and liver tumors. DNA methylation caused by HBV protein changes the liver microenvironment and activates hepatic stellate cells, which is an important mechanism of liver fibrosis. However, the exact mechanism remains unclear. DNA methyltransferase 3A (DNMT3A) is a major enzyme that promotes DNA methylation. HBV infection promotes the expression of DNMT3A. To determine the specific roles of DNMT3A, we used lentivirus to overexpress DNMT3A in hepatocellular carcinoma cell line (HepG2). And the changes of epigenome were analysed by RRBS.
2025-01-06 | GSE285876 | GEO
Project description:The samples of human liver tissues from the healthy donors, the HBV-infected patients without cirrhosis, and the HBV-infected patients with cirrhosis were collected. The tissues were then analyzed by the m6A-mRNA&lncRNA Epitranscriptomic miroarray. The Goal of this experiment was to determine the different of gene expression and m6a methylation of liver tissues among the healthy donors, the HBV-infected patients with and without cirrhosis.
2024-05-21 | GSE252249 | GEO
Project description:Intestinal barrier dysfunction, driven by increased oxidative phosphorylation (OXPHOS) activity that leads to tissue hypoxia, contributes to the progression of cirrhosis, particularly impacting the upper intestine. This study explores the interplay between intestinal OXPHOS, gut microbiota changes, and the effects of fecal microbiota transplant (FMT) in cirrhotic patients. We investigated 32 age-matched men across three groups: healthy controls, compensated cirrhosis, and decompensated cirrhosis. Each underwent endoscopy with duodenal and ascending colon biopsies. Subsequently, in a follow-up study, nine patients with hepatic encephalopathy, previously enrolled in a randomized controlled trial for FMT capsules, underwent repeat pre and post-FMT upper endoscopy. Our bioinformatics analysis highlighted a significant upregulation of nuclear-encoded OXPHOS genes in both intestinal regions of cirrhosis patients compared to controls, with further dysregulation in the decompensated group. We also observed a strong correlation between shifts in gut microbiota composition, Model for End-Stage Liver Disease (MELD) scores, and OXPHOS activity. Following FMT, patients displayed a significant reduction in OXPHOS gene expression in the duodenum, suggesting that FMT may restore intestinal barrier function and offer a therapeutic avenue to mitigate liver disease progression. The findings indicate that managing intestinal OXPHOS and microbiota through FMT could be relevant in modulating microbially-based therapies.
2024-12-26 | GSE285291 | GEO