A5075648269- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Liver Disease and Transplantation
- Body Contouring and Surgery
- CAR-T cell therapy research
- Lipid metabolism and disorders
- Genomics, phytochemicals, and oxidative stress
- Cholesterol and Lipid Metabolism
- Hepatitis C virus research
- Adipokines, Inflammation, and Metabolic Diseases
- Liver physiology and pathology
- Growth Hormone and Insulin-like Growth Factors
- Immunotherapy and Immune Responses
- Pancreatic function and diabetes
- Hepatitis B Virus Studies
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Intramuscular injections and effects
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- NF-κB Signaling Pathways
- Folate and B Vitamins Research
RWTH Aachen University
2013-2022
Harvard University
2019-2022
Massachusetts General Hospital
2019-2022
Universitätsklinikum Aachen
2014-2019
Liver fibrosis plays a critical role in the evolution of most chronic liver diseases and is characterized by buildup extracellular matrix, which can progress to cirrhosis, hepatocellular carcinoma, failure, or death. Now, there are no noninvasive methods available accurately assess disease activity (fibrogenesis) sensitively detect early onset response treatment. Here, we hypothesized that allysine aldehyde (Lys Ald ) pairs formed collagen oxidation during active could be target for...
Flow cytometry is a laser-based technology generating scattered and fluorescent light signal that enables rapid analysis of the size granularity particle or single cell. In addition, it offers opportunity to phenotypically characterize collect cell with use variety reagents. These reagents include but are not limited fluorochrome-conjugated antibodies, expressing protein-, viability-, DNA-binding dyes. Major developments in reagents, electronics, software within last 30 years have greatly...
Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of pathogenesis. The aim this study was identify hepatic gene-expression patterns associated with different injury in a high-risk cohort adults obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression 795 genes, hypothesized be involved fibrosis, inflammation, and steatosis, tissue from 318 Liver specimens were categorized into four distinct NAFLD...
Abstract Insulin receptor (IR) signaling is central to normal metabolic control and dysregulated in diseases such as type 2 diabetes. We report here that IR incorporated into dynamic clusters at the plasma membrane, cytoplasm nucleus of human hepatocytes adipocytes. stimulation promotes further incorporation these insulin-sensitive cells but not insulin-resistant cells, where both accumulation behavior are reduced. Treatment with metformin, a first-line drug used treat diabetes, can rescue...
Non-alcoholic steatohepatitis (NASH) is the leading cause of chronic liver injury and third most common reason for transplantations in Western countries. It unclear so far how different fat sources diets (WD) influence development non-alcoholic steatohepatitis. Our study investigates impact non trans (NTF) corn oil (Corn) as source a WD mouse model on disease progression. C57/B6J wildtype (WT) mice were fed "standard" (WD-Std), WD-NTF or WD-Corn 24 weeks. WT animals treated with exhibit...
CD62L (L-Selectin) dependent lymphocyte infiltration is known to induce inflammatory bowel disease (IBD), while its function in the liver, especially non-alcoholic steatohepatitis (NASH), remains unclear. We here investigated functional role of NASH humans as well two mouse models steatohepatitis. Hepatic expression a soluble form (sCD62L) was measured patients with steatosis and NASH. Furthermore, CD62L−/− mice were fed methionine choline deficient (MCD) diet for 4 weeks or high fat (HFD)...
Platelet factor 4 (PF4) is a pleiotropic inflammatory chemokine, which has been implicated in various disorders including liver fibrosis. However, its role acute diseases not yet elucidated. Here we describe an unexpected, anti-inflammatory of PF4. Serum concentrations PF4 were measured patients and mice with diseases. Acute injury was induced either by carbon tetrachloride or D-galactosamine hydrochloride lipopolysaccharide. levels decreased PF4-/- displayed increased damage both models...
<b><i>Background:</i></b> Antimicrobial peptides (AMP) are an important defense mechanism of the innate immune system and can modulate course various diseases. However, their significance during liver pathogenesis is currently not well defined. <b><i>Methods:</i></b> Patients with diseases were analyzed for LL-37/CRAMP, human beta-defensin-2 (hBD2), complement 5a (C5a) serum levels. Mice deficient in CRAMP (Cathelicidin-related Peptide), mouse...
Nonalcoholic steatohepatitis (NASH) is the most common chronic, progressive liver disease in Western countries. The significance of cellular interactions HGF/c-Met axis different cell subtypes and its relation to oxidative stress response remains unclear so far. Hence, present study aimed at investigating role c-Met interaction with during NASH development mice humans. Conditional knockout (KO) lines (LysCre for Kupffer cells/macrophages, GFAPCre α-SMA+ CK19+ cells MxCre bone marrow-derived...
We have recently shown that hepatocyte‐specific c‐met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting augmented production reactive oxygen species and accelerated development fibrosis. The aim this study focuses on elucidation underlying cellular mechanisms driven by Nrf2 overactivation hepatocytes lacking receptor characterized a severe unbalance between pro‐oxidant antioxidant functions. Control mice (c‐met fx/fx ), single...
Tumor necrosis factor (TNF) is a well-known mediator of sepsis. In many cases, sepsis results in multiple organ injury including the lung with acute respiratory distress syndrome (ARDS). More than 20-year-old studies have suggested that TNF may be directly responsible for during However, these old are inconclusive, because they relied on human rather conspecific TNF, which was contaminated endotoxin most studies. this study, we characterized direct effects intravenous murine endotoxin-free...
Infiltrating CD4 and CD8 T cells have been shown to worsen inflammatory liver damage in non-alcoholic steatohepatitis (NASH). Inhibitory cell receptors such as the programmed death protein 1 (PD1) natural killer receptor 2B4 regulate activity of therefore play an important role immune tolerance required liver. In this study, we investigated expression profile inhibitory on a mouse model NASH. Male B57BL/6J mice were fed Western diet for 24 weeks. The levels surface intrahepatic peripheral...
A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate model is one most important steps in design NASH studies. In addition to histopathological metabolic findings NASH, a sufficient should guarantee robust clinical status good animal welfare. Three different diets, high-fat diet (HFD60), western (WD), cafeteria (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline before scheduled sacrifice, liver...
Abstract Background Overweight/obesity are associated with relative growth hormone (GH) deficiency, and GH deficiency has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD its progressive form, steatohepatitis (NASH), significant morbidity mortality, no approved therapies currently exist. We hypothesized that administration would reduce hepatic steatosis, inflammation fibrosis individuals overweight/obesity NAFLD. Methods A randomized, double-blind,...
Background: We recently showed that hepatocyte-specific c-met deficiency accelerates the progression of non-alcoholic steatohepatitis in experimental murine models resulting increased hepatic lipotoxicity, augmented production reactive oxygen species and accelerated development fibrosis. The aim this study focuses on elucidation underlying cellular mechanisms driven by Nrf2 over-activation hepatocytes lacking receptor characterized a severe unbalance between pro-oxidant anti-oxidant functions.