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MicroRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93172 | GEO | 2017/01/06

SECONDARY ACCESSION(S): PRJNA360230

REPOSITORIES: GEO

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microRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

Project description:microRNA-mRNA integral analysis in CD4+ T cell in primay biliary cholangitis (PBC)

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mRNA profile in CD4+ T cell in healthy control and Primay biliary cholangitis (PBC) [mRNA]

Project description:Primary biliary cholangitis (PBC), formally known as primary biliary cirrhosis, is an autoimmune liver disease of unknown pathogenesis. Consequently, therapeutic targets for PBC have yet to be identified. As CD4+ T cells play a pivotal role in immunological dysfunction observed in PBC, we analyzed microRNA(miRNA) and mRNA expression in CD4+ T cells to investigate PBC pathogenesis and identify novel therapeutic targets.

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microRNA profile in CD4+ T cell in healthy control and Primay biliary cholangitis (PBC) [miRNA]

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The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines.

Project description:Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67?× upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.

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The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC.

Project description:The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA-induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA-induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.

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Digital expression profiling highlights a distinct live RNA signature in high-risk Primary Biliary Cholangitis (PBC)

Project description:Using outcome after long term follow-up to define risk at disease presentation high risk (n=9 who went on to require liver transplantation) and low risk (n=7 who responded fully to UDCA) patients were identified and their first liver biopsies retrieved. RNA was successfully extracted and analysed using nanostringÂ® transcriptomics. Patients with progressive disease appear to have a distinct molecular signature. high risk (n=9 who went on to require liver transplantation) and low risk (n=7 who responded fully to UDCA) patient material was processed along with non-diseased control liver (n=8)

2016-04-02 | E-GEOD-79850 | biostudies-arrayexpress

Digital expression profiling highlights a distinct live RNA signature in high-risk Primary Biliary Cholangitis (PBC)

Project description:Using outcome after long term follow-up to define risk at disease presentation high risk (n=9 who went on to require liver transplantation) and low risk (n=7 who responded fully to UDCA) patients were identified and their first liver biopsies retrieved. RNA was successfully extracted and analysed using nanostring® transcriptomics. Patients with progressive disease appear to have a distinct molecular signature.

2016-04-02 | GSE79850 | GEO

NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2017-05-03 | E-GEOD-68469 | biostudies-arrayexpress