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Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

World Journal of Gastroenterology 2010年第46期16卷 5830-5837页

作者： Johannes W Rey Andrea Noetel Aline Hardt Ali Canbay Hakan Alakus Axel zur Hausen Hans Peter Dienes Uta Drebber margarete odenthal Institute for Pathology University Hospital of Freiburg Department of Gastroenterology and Hepatology University Hospital of Essen Department of General Visceral and Cancer SurgeryUniversity Hospital of Cologne

AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific ***:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele,differing from only 1.5% cases in the healthy *** NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver ***,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,P=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory *** linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of ***:In AFLD patients,the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.

关键词： Single nucleotide polymorphism Peroxisome proliferator-activated receptor γ Non-alcoholic steatohepatitis Alcoholic steatohepatitis Inflammation Fibrosis Hepatitis Steatosis Steatohepatitis

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Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma

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World Journal of Hepatology 2020年第12期12卷 1211-1227页

作者： Sara M Atwa Heba Handoussa Karim M Hosny margarete odenthal Hend M El Tayebi Pharmaceutical Biology Department German University in CairoCairo 11865Egypt Department of General Surgery Faculty of MedicineCairo UniversityCairo 11562Egypt Institute for Pathology University Hospital CologneCologne 50924Germany Molecular Pharmacology Research Group Department of Pharmacology and ToxicologyFaculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the ***,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint ***-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic *** the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/***,nutraceutical therapeutics in cancers have received increasing ***,it is interesting to study the impact of oleuropein on the respective study key *** To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/*** Bioinformatics tools including *** and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,*** addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and *** and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 *** study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried *** Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and ***-1 and XIST were predicted to target PD-L1 ***-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely ***-194 induced expression elevated the expression of PD-L1,XIST and ***,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MA

关键词： Hepatocellular carcinoma X-inactive specific transcript MiR-155-5p MiR-194-5p Programmed cell-death protein 1/Programmed death ligand 1 Immune checkpoint

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