A5102909146- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Liver Diseases and Immunity
- Pediatric Hepatobiliary Diseases and Treatments
- Law and Political Science
- Diet, Metabolism, and Disease
- Helicobacter pylori-related gastroenterology studies
- Public Administration and Political Analysis
- Liver physiology and pathology
- Lipid metabolism and biosynthesis
- Gastroesophageal reflux and treatments
- Diet and metabolism studies
- Criminal Law and Policy
- Esophageal and GI Pathology
- Liver Disease and Transplantation
- Eosinophilic Esophagitis
- Diverse Legal and Medical Studies
- Photodynamic Therapy Research Studies
- Organ Transplantation Techniques and Outcomes
- Macrophage Migration Inhibitory Factor
- Peroxisome Proliferator-Activated Receptors
- Nanoplatforms for cancer theranostics
- European and International Law Studies
- Laser Applications in Dentistry and Medicine
- Drug-Induced Hepatotoxicity and Protection
Medical University of Vienna
2015-2024
Evangelisches Krankenhaus Kalk
2023-2024
University of Basel
2019-2022
Swiss Tropical and Public Health Institute
2022
Stiftung Wissenschaft und Politik, German Institute for International and Security Affairs
2022
Vienna General Hospital
2021
University of Cologne
2017-2020
Klinik und Poliklinik für Psychosomatik und Psychotherapie
2020
BOKU University
2020
University Hospital Cologne
2018
Abstract Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2) 1 , could represent a new chemoprophylactic approach for COVID-19 that complements vaccination 2,3 . However, the mechanisms control expression of ACE2 remain unclear. Here we show farnesoid X receptor (FXR) is direct regulator transcription in several tissues affected COVID-19, including gastrointestinal and respiratory systems. We then use over-the-counter compound...
Approximately 95% of bile acids (BAs) excreted into are reabsorbed in the gut and circulate back to liver for further biliary secretion. Therefore, pharmacological inhibition ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic duct injury.Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model injury sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - highly potent selective ASBT inhibitor or chow diet. Liver was...
•TGR5 is downregulated in cholangiocytes PSC and Abcb4-/- livers a cell type-specific manner.•Interleukin-8 reduces TGR5 levels biliary epithelial cells organoids.•Biliary damage aggravated Tgr5-deficient mice attenuated overexpressing Tgr5.•ScRNA-seq shows that overexpression of Tgr5 ameliorates the activated, inflammatory phenotype.•norUDCA treatment restores Tgr5-expression mice. Background & AimsPrimary sclerosing cholangitis (PSC) characterized by chronic inflammation progressive...
Nonalcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation and endoplasmic reticulum (ER) stress. Because acids (FAs) may trigger ER stress, we hypothesized that the absence of adipose lipase (ATGL/PNPLA2)-the main enzyme for intracellular lipolysis, releasing FAs, closest homolog to adiponutrin (PNPLA3) recently implicated in pathogenesis NAFLD-protects against hepatic Wild-type (WT) ATGL knockout (KO) mice were challenged with tunicamycin (TM) induce Serum...
Background and aims Interruption of the enterohepatic circulation bile acids (BAs) may protect against BA-mediated cholestatic liver duct injury. BA sequestrants are established to treat pruritus, but their impact on underlying cholestasis is still unclear. We aimed explore therapeutic effects mechanisms sequestrant colesevelam in a mouse model sclerosing cholangitis. Methods Mdr2 −/− mice received for 8 weeks. Gene expression profiles homeostasis, inflammation fibrosis were explored liver,...
Cholestasis is characterized by intrahepatic accumulation of potentially cytotoxic bile acids (BAs) subsequently leading to liver injury with disruption hepatocellular integrity, inflammation, fibrosis and ultimately cirrhosis. Bile salt export pump (BSEP/ABCB11) the main canalicular BA transporter therefore rate limiting step for hepatobiliary excretion. In this study we aimed investigate role BSEP/ABCB11 in development acquired cholestatic duct injury.Wild-type (WT) BSEP knockout (BSEP-/-)...
•NorUDCA reduces the number of hepatic innate and adaptive immune cells, including CD8+ T in Mdr2-/- model sclerosing cholangitis.•Independent its anticholestatic effects, NorUDCA exhibits direct immunomodulatory properties cells.•NorUDCA targets mTORC1 to modulate (phospho-) proteomic metabolic landscape cells.•Circulating cells from PSC patients show enhanced clonal expansion activity which are restricted by NorUDCA. Background & Aims24-Norursodeoxycholic acid (NorUDCA) is a novel...
Glucagon-like peptide (GLP)-2 may exert antifibrotic effects on hepatic stellate cells (HSCs). Thus, we aimed to test whether application of the GLP-2 analogue teduglutide has hepatoprotective and in Mdr2/Abcb4-/- mouse model sclerosing cholangitis displaying inflammation fibrosis.Mdr2-/- mice were injected daily for 4 weeks with followed by gene expression profiling (bulk liver; isolated HSCs) immunohistochemistry. Activated HSCs (LX2 cells) immortalized human hepatocytes intestinal...
Hepatic triacylglycerol accumulation and insulin resistance are key features of NAFLD. However, NAFLD development progression rather triggered by the aberrant generation lipid metabolites signaling molecules including diacylglycerol (DAG) lysophosphatidylcholine (lysoPC). Recent studies showed decreased expression carboxylesterase 2 (CES2) in liver NASH patients hepatic DAG was linked to low CES2 activity obese individuals. The mouse genome encodes several Ces2 genes with Ces2a showing...
Abstract Background and aims Experimental studies linked dysfunctional Farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling to liver disease. This study investigated key intersections of the FXR-FGF19 pathway along gut–liver axis their link disease severity in patients with cirrhosis. Methods Patients cirrhosis undergoing hepatic venous pressure gradient measurement (cohort-I n = 107, including 53 concomitant biopsy; 5 healthy controls) or colonoscopy ileum biopsy...
Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory fibrotic processes. The Na + ‐Taurocholate Cotransporting Polypeptide (NTCP) is the major uptake transporter BSs, can be specifically inhibited by myrcludex B. We hypothesized that inhibition NTCP dampens cholestatic liver injury. Acute was induced in mice a 3.5‐diethoxycarbonyl‐1.4‐dihydrocollidine (DDC) diet or duct ligation (BDL). Chronic investigated Atp8b1 ‐G308V Abcb4/ Mdr2...
Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven S. infection.Adult NMRI were infected 50 cercariae after 12 weeks received either norUDCA- or ursodeoxycholic (UDCA)-enriched diet (0.5% wt/wt)...
Increased fatty acid (FA) flux from adipose tissue to the liver contributes development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting triglyceride lipase (ATGL)/patatin-like phospholipase domain containing 2 (PNPLA2), main enzyme driving lipolysis, may attenuate steatohepatitis.Hepatocyte-specific ATGL knockout (ATGL LKO) mice were challenged with methionine-choline-deficient (MCD) or high-fat high-carbohydrate (HFHC) diet. Serum...
Objective Although the background of laser therapy by means low level energy and power is still only partially understood, there are nevertheless promising reports from clinical studies concerning pain treatment, acceleration wound healing, modulation cell functions. In order to contribute understanding such a phototherapeutic procedure experiments were performed. Materials Methods The influence light (λ = 410, 488, 630, 635, 640, 805, 1,064 nm broad band white light) on proliferation cells...
In cirrhotic patients, portal hypertension (PHT) deteriorates survival, yet treatment options are limited. A major contributor to increased intrahepatic vasoconstriction in PHT is dysfunctional nitric-oxide signaling. Soluble guanylate cyclase (sGC) the receptor of and can be stimulated by riociguat. Riociguat approved for pulmonary but has not been studied liver cirrhosis. this study we assessed effects riociguat on fibrosis cholestatic (bile duct ligation, BDL) toxic (carbon-tetrachloride,...
Cholestasis comprises aetiologically heterogeneous conditions characterized by accumulation of bile acids in the liver that actively contribute to damage. Sirtuin 1 (SIRT1) regulates regeneration and acid metabolism modulating farnesoid X receptor (FXR); we here investigate its role cholestatic disease. We determined SIRT1 expression livers from patients with disease, two experimental models cholestasis, as well human murine cells response loading. SIRT1‐overexpressing (SIRT oe )...