Project description:The progression from steatosis to nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) patients is one of the major causes of liver-related death worldwide and have limited effective therapies. We comparing the circular RNomics of liver fibroblasts isolated from patients with NAFLD-caused cirrhosis and the ones without NAFLD.
Project description:Immune dysregulation and inflammation by hepatic-resident leukocytes is considered a key step in disease progression of Non-alcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) toward cirrhosis and hepatocellular carcinoma (HCC). Here we provide a robust protocol for isolation and characterization of liver-resident immune cells from fine needle biopsies of rodent model and human. Various downstream applications can then be applied to gain an appreciation of the functional activity of liver-resident leukocyte populations.
Project description:Non-alcoholic fatty liver disease (NAFLD) is a predominant form of chronic liver disease, affecting nearly 25 % of the global population. The progression from steatosis to nonalcoholic steatohepatitis (NASH) in NAFLD patients is one of the major causes of liver-related death worldwide. We assessed the miRNA expression profiles of the exosomes derived from the peripheral blood of NASH patients or healthy controls.
Project description:We used microarray to study the global transcriptomic changes in the livers of SIRT7 KO mice, which develop spontaneous nonalcoholic fatty liver disease.
Project description:There is growing evidence that genomic DNA sequence changes occur in individual somatic cells during the lifetime of an individual and accumulation of these changes may influence aging and disease. In light of this, and contradicting reports regarding discordant copy number profiles between MZ twins(BARANZINI et al. 2010; BRUDER et al. 2008), we set out to identify de novo somatic copy number mutations in DNA from blood for MZ twin pairs of Mexican American descent who were participants of the San Antonio Family Heart Study (SAFHS) or San Antonio Family Diabetes/Gallbladder study (SAFDGS). By applying circular binary segmentation (CBS) to B-allele ratio differences we determined that the 3 MZ twin pairs in this study had concordant copy number profiles. We also detected 2 de novo germ-line CNVs in 2 MZ twin pairs from the SAFHS. This study includes data for 4 monozygotic (MZ) twin pairs, and both parents of 2 of these MZ twin pairs. The purpose of this study was to compare concordance of copy number profiles between MZ twins.
Project description:This is a prospective observational case-control study conducted in septic VLBW dizygotic twins and their non-septic twin controls. Fecal samples were used for genome-wide expression analysis of exfoliated intestinal cells.
Project description:There is growing evidence that genomic DNA sequence changes occur in individual somatic cells during the lifetime of an individual and accumulation of these changes may influence aging and disease. In light of this, and contradicting reports regarding discordant copy number profiles between MZ twins(BARANZINI et al. 2010; BRUDER et al. 2008), we set out to identify de novo somatic copy number mutations in DNA from blood for MZ twin pairs of Mexican American descent who were participants of the San Antonio Family Heart Study (SAFHS) or San Antonio Family Diabetes/Gallbladder study (SAFDGS). By applying circular binary segmentation (CBS) to B-allele ratio differences we determined that the 3 MZ twin pairs in this study had concordant copy number profiles. We also detected 2 de novo germ-line CNVs in 2 MZ twin pairs from the SAFHS.
Project description:Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis, which lead to progressed cirrhosis and hepatocellular carcinoma. Despite its increasing prevalence on a global scale, the pathogenesis of NASH progression is not well understood. To elucidate the underlying mechanisms of NASH progression, we conducted transcriptome analyses of Japanese NAFLD cohort in our facility.
Project description:Immunosenescence and exhaustion are involved in the development and progression of type 2 diabetes (T2D) and metabolic liver diseases, including fatty liver, fibrosis, and cirrhosis, in humans. However, the relationships of the senescence and exhaustion of T cells with insulin resistance-associated liver diseases remain incompletely understood. To better define the relationship of T2D with nonalcoholic fatty liver disease, 59 patients with T2D were studied.
Project description:Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis (NASH), that often progresses to hepatocellular carcinoma (HCC) through a largely undefined mechanism. NASH and HCC both depend on inflammatory signaling whose master regulator is the NFκB transcription factor family, activated by canonical and non-canonical pathways. Here, we investigated non-canonical NFκB-inducing kinase (NIK/MAP3K14) in metabolic NASH, NASH to HCC transition as well as in DEN-induced HCC. We revealed that hepatocyte-specific NIK deficiency (NIKLKO) ameliorated metabolic NASH complications and reduced hepatocarcinogenesis however, independent of its role in NFB pathway. Instead, hepatic NIK attenuated hepatoprotective JAK2/STAT5 signaling that is a prerequisite for NASH and NASH to HCC progression in mice and humans. Our data suggest NIK-mediated inhibitory JAK2 phosphorylation at serine 633 that might be amenable for future therapeutic interventions in patients.
