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| 1 | Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases显示文摘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 probes.RESULTS: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 population.In NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease.However,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 alterations.The 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 NAFLD.CONCLUSION: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. | Johannes W Rey Andrea Noetel Aline Hardt Ali Canbay Hakan Alakus Axel zur Hausen Hans Peter Dienes Uta Drebber Margarete Odenthal | 2010 | World Journal of Gastroenterology2010，16，46： | 11 |
| 2 | 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显示文摘BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given 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/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org 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,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To 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 out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway. | Sara M Atwa Heba Handoussa Karim M Hosny Margarete Odenthal Hend M El Tayebi | 2020 | World Journal of Hepatology2020，12，12： | 9 |
| 3 | Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases显示文摘AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC.RESULTS: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P < 0.0001) and correlated with dedifferentiation (P < 0.0001). Interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P < 0.002) and HB611 (P < 0.001) cell lines as compared to HBV-negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver. | Martina Knoess Anna Kordelia Kurz Olga Goreva Nuran Bektas Kai Breuhahn Magarethe Odenthal Peter Schirmacher Hans Peter Dienes C Thomas Bock Hanswalter Zentgraf Axel zur Hausen | 2006 | World Journal of Gastroenterology2006，12，36： | 4 |
| 4 | Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis显示文摘 | Jonel Trebicka Evrim Anadol Natalia Elfimova Ingo Strack Michael Roggendorf Sergei Viazov Inga Wedemeyer Uta Drebber Jürgen Rockstroh Tilman Sauerbruch Hans-Peter Dienes Margarete Odenthal | 2012 | Journal of Hepatology2012，，： | 2 |
| 5 | Altered levels of the onco-microRNA 21 and the tumor-supressor microRNAs143 and 145 in advanced rectal cancer indicate successful neoadjuvant chemoradiotherapy显示文摘 | Uta Drebber Max Lay Inga Wedemeyer Daniel Vallb?hmer Elfriede Bollschweiler Jan Brabender Stefan M?nig Arnulf H?lscher Hans Dienes Margarete Odenthal | 2011 | International Journal of Oncology2011，，： | 2 |
| 6 | Advantageous numerical simulation of the converter blowing process 显示文摘 | Odenthal H J Kempken J Schliiter J | 2007 | Iron & Steel Technology2007，4，11： | 1 |
| 7 | Numerical and Physical Simulation of Tundish Fluid Flow Phenomena显示文摘 | Han Jürgen Odenthal Ralf Boelling Herbert Pfeifer | 2003 | Steel Research2003，74，1： | 1 |
| 8 | Robust Vehicle Steering Control Design Based on the Disturbance Observer显示文摘 | Tilman Biinte Dirk Odenthal Bilin Aksun-Giiven Levent Giiven | 2002 | Annual Reviews in Control2002，26，2： | 1 |
| 9 | Advantageous numerical simulation of the converter blowing process 显示文摘 | Odenthal H Kempken J Schluter J et aI | 2007 | Iron & Steel Technology2007，4，11： | 1 |
| 10 | Intrahepatic IL-8 producing Foxp3 + CD4 + regulatory T cells and fibrogenesis in chronic hepatitis C<!-- Doctopic: VH -->显示文摘 | Bettina Langhans Benjamin Kr?mer Marcell Louis Hans Dieter Nischalke Robert Hüneburg Andrea Staratschek-Jox Margarethe Odenthal Steffen Manekeller Michael Schepke J?rg Kalff Hans-Peter Fischer Joachim L. Schultze Ulrich Spengler | 2013 | Journal of Hepatology2013，，2： | 1 |
| 11 | Analysis of a zebrafish VEGF receptor mutant reveals specific disruption of angiogenesis 显示文摘 | Habeck H Odenthal J Watderich B | 2002 | Curr Biol2002，12，16： | 1 |
| 12 | Factors of transforming growt h factor beta signalling are co-regulated in human hepatocellular carcinoma显示文摘 | Longerich T Breuhahn K Odenthal M | 2004 | Virchows Arch2004，445，6： | 1 |
| 13 | Mutations affecting the formation of the notochord in the zebrafish,Danio rerio显示文摘 | Odenthal J Haffter P Vogelsang E | 1996 | Development1996，123，： | 1 |
| 14 | The role of insulin-like growth factor Ⅱ in the malignant transformation of rat liver oval cells显示文摘 | Zhang N Siegel K Odenthal M | 1997 | Hepatol1997，25，4： | 1 |
| 15 | 2-Dimensional Transition Metal Dichalcogenides with Tunable Direct Band Gaps MoSm-x Se2x Monolayers显示文摘 | Mann J Ma Q Odenthal P M | 2014 | Advanced Materials2014，26，9： | 1 |
| 16 | Robust vehicle steering control design based on the disturbance observer显示文摘 | Odenthal Dirk Aksun-Güven Bilin | 2002 | Annual Reviews in Control Volume2002，26，11： | 1 |
| 17 | Long-term follow-up of the corneal endothelium after Artisan lens implantation for unilateral traumatic and unilateral congenital cataract in children two case series显示文摘 | ODENTHAL M P SMINIA M L PRICK L J | 2006 | Cornea2006，25，10： | 1 |
| 18 | Clinicalpharmacokinetics of trospium chloride 显示文摘 | Doroshyenko O Jetter A Odenthal K P | 2005 | Clin Pharmacokinet2005，44，： | 1 |
| 19 | Expression and functional interaction of hepatocyte growth factor-scatter factor and its receptor c-met in mammalian brain显示文摘 | Jung W Castren E Odenthal M | 1994 | J Cell Biol1994，126，2： | 1 |
| 20 | Anomalous unilateral single pulmonary vein versus scimitar syndrome:Comparison of two paediatric cases and a review of the literature显示文摘 | Odenthal C Sarikwal A | 2012 | J Med Imaging Radiat Oncol2012，56，3： | 1 |
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