Mihael Vucur
A5081728678- Liver Disease Diagnosis and Treatment
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cell death mechanisms and regulation
- Liver physiology and pathology
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver Disease and Transplantation
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Liver Diseases and Immunity
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Hepatitis B Virus Studies
- Extracellular vesicles in disease
- Pancreatic and Hepatic Oncology Research
- Pediatric Hepatobiliary Diseases and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Drug Transport and Resistance Mechanisms
Heinrich Heine University Düsseldorf
2021-2025
Düsseldorf University Hospital
2021-2025
RWTH Aachen University
2010-2020
Universitätsklinikum Aachen
2010-2020
European Foundation for the Study of Chronic Liver Failure
2016
Canon (Japan)
2016
University of Turin
2010
Bielefeld University
2008
Liver fibrosis is orchestrated by a complex network of signaling pathways regulating the deposition extracellular matrix proteins during fibrogenesis. MicroRNAs (miRNAs) represent family small noncoding RNAs controlling translation and transcription many genes. Recently, miRNAs have been suggested to crucially modulate cellular processes in liver such as hepatocarcinogenesis. However, their role not well understood. We systematically analyzed regulation mouse model carbon...
<h3>Objective</h3> Monocyte chemoattractant protein-1 (MCP-1, CCL2), the primary ligand for chemokine receptor C–C 2 (CCR2), is increased in livers of patients with non-alcoholic steatohepatitis (NASH) and murine models fibrosis. It was recently shown that monocyte/macrophage infiltration into liver upon injury critically regulated by CCL2/CCR2 axis functionally important perpetuating hepatic inflammation fibrogenesis. The structured L-enantiomeric RNA oligonucleotide mNOX-E36 (a so-called...
Programmed necrosis (necroptosis) represents a newly identified mechanism of cell death combining features both apoptosis and necrosis. Like apoptosis, necroptosis is tightly regulated by distinct signalling pathways. A key regulatory role in programmed has been attributed to interactions the receptor-interacting protein kinases, RIP1 RIP3. However, specific functional RIP3-dependent heart unknown. The aims this study were thus assess significance RIP3 context myocardial...
Abstract Non‐alcoholic fatty liver disease ( NAFLD ) represents the most common in Western countries and often progresses to non‐alcoholic steatohepatitis NASH leading ultimately fibrosis cancer. The occurrence of hepatocyte cell death—so far characterized as apoptosis—represents a fundamental step from benign steatosis toward progressive steatohepatitis. In contrast, function RIP 3‐dependent “necroptosis” ‐induced is currently unknown. We show that 3 upregulated human dietary mouse model...
It is currently not well known how necroptosis and responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of signaling hepatocytes, fundamentally affecting immune hepatocarcinogenesis. Concomitant necrosome NF-κB activation which physiologically express low concentrations receptor-interacting kinase 3 (RIPK3), did lead to immediate cell death but forced them into prolonged "sublethal" state with leaky membranes, functioning...
The progression of non-alcoholic steatohepatitis (NASH) to fibrosis and hepatocellular carcinoma (HCC) is aggravated by auto-aggressive T cells. gut-liver axis contributes NASH, but the mechanisms involved consequences for NASH-induced liver cancer remain unknown. We investigated role gastrointestinal B cells in development HCC.
<h3>Background</h3> Hepatocellular carcinoma (HCC) is a typical inflammation-associated cancer, but may also provoke antitumour immune responses whose significance and underlying mechanisms are incompletely understood. <h3>Objective</h3> To characterise in the diethylnitrosamine (DEN)-liver cancer mouse model. <h3>Design</h3> Tumour development cell functions upon DEN treatment were compared between C57BL/6 wild-type (WT), chemokine scavenging receptor D6-deficient, B cell- (Igh6), CD4 T...
MicroRNA (miRNA) levels in serum have recently emerged as potential novel biomarkers for various diseases. miRNAs are routinely measured by standard quantitative real-time PCR (qPCR); however, the high sensitivity of qPCR demands appropriate normalization to correct nonbiological variation. Presently, RNU6B (U6) is used data circulating many studies. However, it was suggested that U6 themselves might differ between individuals. Therefore, no consensus has been reached on best strategy...
Background and Aims Down-regulation of miR-150 was recently linked to inflammation bacterial infection. Furthermore, reduced serum levels were reported from a small cohort patients with sepsis. We thus aimed at evaluating the diagnostic prognostic value in critically illness Methods analyzed 223 ill which 138 fulfilled sepsis criteria compared 76 healthy controls. Results correlated clinical data extensive sets routine experimental biomarkers. Measurements concentrations revealed only...
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent HCC development via proliferation- replication-associated DNA damage. Proliferation-associated replication stress, damage, genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels determine predict subsequent hepatocarcinogenesis. damage sensed by complex...
For years, the term "apoptosis" was used synonymously with programmed cell death. However, it recently discovered that receptor interacting protein 3 (RIP3)-dependent "necroptosis" represents an alternative death pathway activated in many inflamed tissues. Here, we show a genetic model of chronic hepatic inflammation activation RIP3 limits immune responses and compensatory proliferation liver parenchymal cells (LPC) by inhibiting Caspase-8-dependent Jun-(N)-terminal kinase LPC nonparenchymal...
Serum levels of microRNA have been proposed as biomarkers in various inflammatory diseases. However, up to now, their clinical relevance critical illness and sepsis is unclear.Single-center study.Fourteen-bed medical ICU the University Hospital Aachen, university laboratory research unit.Experimental model C57Bl/6 mice; 223 critically ill patients comparison with 76 healthy volunteers.We used cecal pole ligation puncture for induction polymicrobial mice measured alterations serum six...
Abstract Background & Aims Serum concentrations of miR‐122 were proposed as a marker for various inflammatory diseases, but the mechanisms driving alterations in serum levels are unknown. Methods We analysed and hepatic expression mice after ischaemia reperfusion (I/R) injury. These data compared with from caecal pole ligation puncture ( CLP ) procedure. To translate these into human, we cohort 223 patients critical illness 57 cirrhosis. Results detected strongly elevated I/R...
Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting it might be privileged pharmacological target. However, its function glucose homeostasis and obesity has been unknown. Here we show RIPK3 is over expressed the white adipose tissue (WAT) obese mice fed with choline-deficient high-fat diet. Genetic inactivation Ripk3 increased Caspase-8-dependent adipocyte apoptosis WAT...
Acetaminophen (APAP) overdose remains a frequent cause of acute liver failure, which is generally accompanied by increased levels serum bile acids (BAs). However, the pathophysiological role BAs elusive. Herein, we investigated in APAP-induced hepatotoxicity.We performed intravital imaging to investigate BA transport mice, quantified endogenous concentrations mice and patients with APAP overdose, analyzed tissue mass spectrometry MALDI-mass imaging, assessed integrity blood-bile barrier...
Inflammation, particularly that mediated by bacterial components translocating from the gut to liver and binding toll-like receptors (TLRs), is central cholestatic injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling exerts a protective role in hepatocellular injury carcinogenesis. This study aims evaluate of TREM-2 cholestasis.
Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there no specific treatment. We revisited its pathophysiology with the aim identifying novel therapeutic strategies.
Background and Aims Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles cirrhosis were identified screening approaches on parenchyma, mostly rodent models. Therefore, the present study we performed a systematic approach order to identify altered levels serum patients disease cirrhosis. Methods We systematic, array-based miRNA expression analysis samples from In functional...
Pathogen‐ and injury‐related danger signals as well cytokines released by immune cells influence the functional differentiation of macrophages in chronic inflammation. Recently, liver‐derived plasma protein, histidine‐rich glycoprotein (HRG), was demonstrated, mouse tumor models, to mediate transition alternatively activated (M2) proinflammatory (M1) macrophages, which limit growth metastasis. We hypothesized that HRG is a critical endogenous modulator hepatic macrophage functionality...