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69 Publications visible to you, out of a total of 69
Inflammation in alcohol-associated liver disease progression

Abstract (Expand)

Abstract Chronic alcohol consumption induces stress and damage in alcohol metabolising hepatocytes, which leads to inflammatory and fibrogenic responses. Besides these direct effects, alcohol disrupts …ffects, alcohol disrupts intestinal barrier functions and induces gut microbial dysbiosis, causing translocation of bacteria or microbial products through the gut mucosa to the liver and, which induce inflammation indirectly. Inflammation is one of the key drivers of alcohol-associated liver disease progression from steatosis to severe alcoholic hepatitis. The current standard of care for the treatment of severe alcoholic hepatitis is prednisolone, aiming to reduce inflammation. Prednisolone, however improves only short-term but not long-term survival rates in those patients, and even increases the risk for bacterial infections. Thus, recent studies focus on the exploration of more specific inflammatory targets for the treatment of severe alcoholic hepatitis. These comprise, among others interference with inflammatory cytokines, modulation of macrophage phenotypes or targeting of immune cell communication, as summarized in the present overview. Although several approaches give promising results in preclinical studies, data robustness and ability to transfer experimental results to human disease is still not sufficient for effective clinical translation.

Authors: Sophie Lotersztajn, Antonio Riva, Sai Wang, Steven Dooley, Shilpa Chokshi, Bin Gao

Date Published: 18th Jan 2022

Publication Type: Journal

Liver specific, systemic and genetic contributors to alcohol-related liver disease progression

Abstract (Expand)

Abstract Alcohol-related liver disease (ALD) impacts millions of patients worldwide each year and the numbers are increasing. Disease stages range from steatosis via steatohepatitis and fibrosis to …epatitis and fibrosis to cirrhosis, severe alcohol-associated hepatitis and liver cancer. ALD is usually diagnosed at an advanced stage of progression with no effective therapies. A major research goal is to improve diagnosis, prognosis and also treatments for early ALD. This however needs prioritization of this disease for financial investment in basic and clinical research to more deeply investigate mechanisms and identify biomarkers and therapeutic targets for early detection and intervention. Topics of interest are communication of the liver with other organs of the body, especially the gut microbiome, the individual genetic constitution, systemic and liver innate inflammation, including bacterial infections, as well as fate and number of hepatic stellate cells and the composition of the extracellular matrix in the liver. Additionally, mechanical forces and damaging stresses towards the sophisticated vessel system of the liver, including the especially equipped sinusoidal endothelium and the biliary tract, work together to mediate hepatocytic import and export of nutritional and toxic substances, adapting to chronic liver disease by morphological and functional changes. All the aforementioned parameters contribute to the outcome of alcohol use disorder and the risk to develop advanced disease stages including cirrhosis, severe alcoholic hepatitis and liver cancer. In the present collection, we summarize current knowledge on these alcohol-related liver disease parameters, excluding the aspect of inflammation, which is presented in the accompanying review article by Lotersztajn and colleagues.

Authors: Bernd Schnabl, Gavin E. Arteel, Felix Stickel, Jan Hengstler, Nachiket Vartak, Ahmed Ghallab, Steven Dooley, Yujia Li, Robert F. Schwabe

Date Published: 18th Jan 2022

Publication Type: Journal

MSPypeline: a python package for streamlined data analysis of mass spectrometry-based proteomics

Abstract (Expand)

Abstract Summary Mass spectrometry-based proteomics is increasingly employed in biology and medicine. To generate reliable information from large datasets and ensure comparability of results, it is …rge datasets and ensure comparability of results, it is crucial to implement and standardize the quality control of the raw data, the data processing steps and the statistical analyses. MSPypeline provides a platform for importing MaxQuant output tables, generating quality control reports, data preprocessing including normalization and performing exploratory analyses by statistical inference plots. These standardized steps assess data quality, provide customizable figures and enable the identification of differentially expressed proteins to reach biologically relevant conclusions. Availability and implementation The source code is available under the MIT license at https://github.com/siheming/mspypeline with documentation at https://mspypeline.readthedocs.io. Benchmark mass spectrometry data are available on ProteomeXchange (PXD025792). Supplementary information Supplementary data are available at Bioinformatics Advances online.

Authors: Simon Heming, Pauline Hansen, Artyom Vlasov, Florian Schwörer, Stephen Schaumann, Paulina Frolovaitė, Wolf-Dieter Lehmann, Jens Timmer, Marcel Schilling, Barbara Helm, Ursula Klingmüller

Date Published: 2022

Publication Type: Journal

The rs429358 Locus in Apolipoprotein E Is Associated With Hepatocellular Carcinoma in Patients With Cirrhosis

Abstract (Expand)

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E ( APOE ), rs2642438 …rotein E ( APOE ), rs2642438 in mitochondrial amidoxime reducing component 1 ( MARC1 ), rs2792751 in glycerol‐3‐phosphate acyltransferase ( GPAM ), and rs187429064 in transmembrane 6 superfamily member 2 ( TM6SF2 ), previously associated with progressive alcohol‐related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case‐control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP‐HCV), and one alcohol‐related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed‐effect meta‐analysis was used to determine the pooled effect size across all data sets. Across four case‐control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele ( APOE ) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61‐0.84; P  = 2.9 × 10 −5 ). Rs187429064:G ( TM6SF2 ) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45‐2.86; P  = 3.1 × 10 −6 ). In contrast, rs2792751:T ( GPAM ) was not associated with HCC (OR, 1.01; 95% CI, 0.90‐1.13; P  = 0.89), whereas rs2642438:A ( MARC1 ) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84‐1.00; P  = 0.043). Conclusion: This study associates carriage of rs429358:C ( APOE ) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.

Authors: Hamish Innes, Hans Dieter Nischalke, Indra Neil Guha, Karl Heinz Weiss, Will Irving, Daniel Gotthardt, Eleanor Barnes, Janett Fischer, M. Azim Ansari, Jonas Rosendahl, Shang‐Kuan Lin, Astrid Marot, Vincent Pedergnana, Markus Casper, Jennifer Benselin, Frank Lammert, John McLauchlan, Philip L. Lutz, Victoria Hamill, Sebastian Mueller, Joanne R. Morling, Georg Semmler, Florian Eyer, Johann von Felden, Alexander Link, Arndt Vogel, Jens U. Marquardt, Stefan Sulk, Jonel Trebicka, Luca Valenti, Christian Datz, Thomas Reiberger, Clemens Schafmayer, Thomas Berg, Pierre Deltenre, Jochen Hampe, Felix Stickel, Stephan Buch

Date Published: 2022

Publication Type: Journal

Cold shock protein YB-1 upregulates MDR1 transcription and thus contributes to cholangiocarcinoma chemoresistance to cisplatin

Abstract

Not specified

Authors: Tao Lin, Heng Liu, Jon Lindquist, Peter Mertens, Matthias Ebert, Steven Dooley, Jun Li, Stefan Munker, Honglei Weng

Date Published: 2022

Publication Type: Journal

Downregulation of ECM1 in hepatocytes as a damage response to liver injury

Abstract

Not specified

Authors: Yujia Li, Weronika Pioronska, Zeribe Nwosu, Weiguo Fan, MatthiasP.A. Ebert, Steven Dooley, Sai Wang

Date Published: 2022

Publication Type: Journal

FOXA2 inhibits hyperbilirubinemia through maintaining apical MRP2 expression in acute liver failure

Abstract

Not specified

Authors: Sai Wang, Rilu Feng, Shanshan Wang, Hui Liu, Chen Shao, Yujia Li, Link Frederik, Stefan Munker, Roman Liebe, Christoph Meyer, Elke Burgermeister, Matthias Ebert, Steven Dooley, Huiguo Ding, Honglei Weng

Date Published: 2022

Publication Type: Journal

Insulin-controlled C/EBPα expression determines the impact of TGF-β on HNF4α transcription in hepatocytes

Abstract

Not specified

Authors: Rilu Feng, Carsten Sticht, Kejia Kan, Stefan Munker, MatthiasP. Ebert, Steven Dooley, Hong-Lei Weng

Date Published: 2022

Publication Type: Journal

Multi-omics profiling identifies molecular signatures of acute-on-chronic liver failure in Abcb4KO mice upon chemical intoxication

Abstract

Not specified

Authors: Pia Erdoesi, Maren Buettner, Matthias Meyer-Bender, Rizqah Kamies, IoannisK. Deligiannis, MichaelP. Menden, Steven Dooley, CeliaP. Martinez-Jimenez, Christoph Ogris, Seddik Hammad

Date Published: 2022

Publication Type: Journal

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