Project description:We report that the transcriptomic profiles of iPSC-Heps from NAFLD patients are distinct from those of healthy controls. This is in contrast to the transcriptomic profiles of the parent iPSC, which are similar between NAFLD patients and healthy controls.
Project description:RNA was isolated from the mixed samples of liver tissues from 5 liver tissues from NAFLD patients and 5 healthy controls. Total RNA was reverse-transcribed with biotin end-labeled random oligonucleotide primers.
Project description:Background & Aims: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this study is to define transcriptional changes in early, non-fibrotic NAFLD using a biopsy-proven non-fibrotic NAFLD cohort. Methods: We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 with NAS ≤3, 17 with NAS ≥5) and 21 healthy controls and compared changes in expression of 594 genes involved in innate immune function. Results: Compared to healthy controls, NAFLD patients with NAS ≥5 had differential expression of 211 genes, while those with NAS ≤3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS ≤3, 8.28-fold in NAS ≥5) and CXCL10 (2.27-fold in NAS ≤3, 8.28-fold in NAS ≥5) gene expression were significantly upregulated with histologic progression of NAFLD.
Project description:<p>Nonalcoholic fatty liver disease (NAFLD) is a major public health problem due to the high incidence affecting approximately one-third of the world’s population. NAFLD is usually linked to obesity and excessive weight. A subset of patients with NAFLD express normal or low body mass index; thus, the condition is called nonobese NAFLD or lean NAFLD. However, patients and healthcare professionals have little awareness and understanding of NAFLD in nonobese individuals. Furthermore, preclinical results from nonobese animal models with NAFLD are unclear. Gut microbiota and their metabolites in nonobese/lean NAFLD patients differ from those in obese NAFLD patients. Therefore, we analyzed the biochemical indices, intestinal flora and intestinal metabolites in a nonobese NAFLD mouse model established using a methionine-choline deficient (MCD) diet. The significantly lean MCD mice had a remarkable fatty liver with lower serum triglyceride and free fatty acid levels as well as higher alanine transaminase and aspartate transaminase levels than normal mice. 16s RNA sequencing of fecal DNA showed that the overall richness and diversity of the intestinal flora decreased in MCD mice, whereas the Firmicutes/Bacteroidota ratio was increased. <em>g_Tuzzerella, s_Bifidobacterium pseudolongum</em> and <em>s_Faecalibaculum rodentium</em> were the predominant species in nonobese NAFLD mice. Fecal metabolomics using LC-MS/MS revealed the potential biomarkers for the prognosis and diagnosis of nonobese NAFLD, including high levels of tyramine glucuronide, 9,12,13-TriHOME and pantetheine 4'-phosphate, and low levels of 3-carbamoyl-2-phenylpropionaldehyde, N-succinyl-L,L-2,6-diaminopimelate, 4-methyl-5-thiazoleethanol, homogentisic acid and estriol. Our findings could be useful to identify and develop drugs to treat nonobese NAFLD and lean NAFLD.</p>
Project description:The data provides a unique opportunity for investigating the differences in the hepatic transcriptome in health and liver disease through studying gene expression in a cohort of patients with NAFLD, cirrhosis, and healthy controls. The randomization of patients and healthy controls between the fasting and fed state further enables exploration of differences in the liver transcriptome.
Project description:This project involves a comparative proteomic analysis of blood samples from 10 healthy individuals and 20 patients with Non-Alcoholic Fatty Liver Disease (NAFLD). The aim is to identify biomarkers and understand the molecular mechanisms underlying NAFLD.
Project description:Purpose The role of intestinal flora in carcinogenesis and chemotherapy efficacy has been increasingly studied; however, comparisons between oral and intestinal flora remain limited. This study aimed to identify the microbial changes in urothelial carcinoma (UC) by analyzing oral saliva and stool samples from healthy individuals and patients. We also examined the association between microbial composition and immune checkpoint inhibitor (ICI) response. Methods A total of 20 healthy individuals and 38 patients with UC were analyzed. Among them, 27 patients with UC underwent ICI treatment. Oral saliva and stool samples were analyzed for 16S rRNA sequences to assess bacterial composition. Operational taxonomic units were generated, and phylogenetic analysis was performed using the 16S Metagenomics app whithin the Illumina BaseSpace Sequence Hub. Results Patients with UC showed higher Veillonellaceae and Prevotellaceae levels in saliva and stool, with lower levels of these bacteria associated with more prolonged overall survival and progression-free survival, particularly Veillonellaceae in stool. A higher neutrophil-to-lymphocyte ratio correlated with increased levels of these bacteria. Conclusion Veillonellaceae and Prevotellaceae are potential microbial biomarkers of survival outcomes and ICI efficacy in patients with UC. Non-invasive oral microbial sampling may facilitate personalized cancer treatment strategies.
Project description:Comparison of faecal flora of three healthy individuals and a patient suffering from Ulcerative Colitis during disease and remission states. Faecal samples were taken and frozen at -80 within one hour.
Project description:Herein, we evaluated the regulation of plantaricin NC8 on gut microbiota by in vitro simulation system, and assessed their modulation on different intestinal types, namely enterotype 1 (ET B) and enterotype 2 (ET P), for the first time. Plantaricin NC8 could not significantly promote or inhibit the production short chain fatty acids (SCFAs) by the gut flora in the fecal samples from eight subjects to produce through Gas chromatography (GC) determining, neither ET B nor ET P. 16S rDNA sequencing showed that plantaricin NC8 shortened the Shannon index of ET B and the Simpson index of ET P, but their β diversity change was not statistically significant. In addition, plantaricin NC8 could promote the growth of beneficial bacteria. Results showed that plantaricin NC8 mainly increased the abundance of Actinobacterias, Bacteroides, Bifidobacterium, Megamonas, Escherichia-Shigella, and decreased the abundance of Streptococcus in ET B. And it also increased the abundance of Prevotella_9, Bifidobacterium, Escherichia-Shigella, Mitsuokella and others in ET P. Plantaricin NC8 can influence intestinal microorganisms, but the influence were different for different enterotypes.