A5051103093- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Hormonal Regulation and Hypertension
- Anesthesia and Pain Management
- Molecular Biology Techniques and Applications
- Drug-Induced Hepatotoxicity and Protection
- 3D Printing in Biomedical Research
- Viral Infectious Diseases and Gene Expression in Insects
- PARP inhibition in cancer therapy
- Stress Responses and Cortisol
- Radiomics and Machine Learning in Medical Imaging
- Oral Health Pathology and Treatment
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Apelin-related biomedical research
- Cytokine Signaling Pathways and Interactions
- Endoplasmic Reticulum Stress and Disease
- Gene expression and cancer classification
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- Toxin Mechanisms and Immunotoxins
- Helicobacter pylori-related gastroenterology studies
- Cell Image Analysis Techniques
- Animal testing and alternatives
- Pancreatic function and diabetes
Inspire
2017-2022
Philip Morris International (Switzerland)
2013-2016
Roche (Switzerland)
2012-2013
University of Zurich
2012
Czech Academy of Sciences, Institute of Physiology
2012
University of Lausanne
2005-2012
University Hospital of Bern
2002-2005
University of Bern
2003-2004
After liver injury, the repair process comprises activation and proliferation of hepatic stellate cells (HSCs), which produce extracellular matrix (ECM) proteins. Peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in these cells, but its function remains incompletely understood. This study investigated whether PPARβ/δ with ligand GW501516 influenced fibrotic response to injury from chronic carbon tetrachloride (CCl4) treatment mice. Wild type PPARβ/δ-null...
Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was described to affect chromatin compaction. Previous reports suggested dynamic modulation of the landscape during adipocyte differentiation. We thus hypothesized PARP1 plays an important transcriptional role in adipogenesis and metabolism therefore used development function as model elucidate molecular action obesity-related diseases. Our results show PARP1-dependent ADP-ribose polymer (PAR) formation increases and,...
Capturing the effects of exposure in a specific target organ is major challenge risk assessment. Exposure to cigarette smoke (CS) implicates field tissue injury lung as well nasal and airway epithelia. Xenobiotic metabolism particular becomes an attractive tool for chemical assessment because its responsiveness against toxic compounds, including those present CS. This study describes efficient integration from transcriptomic data quantitative measures, which reflect responses xenobiotics...
Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic transcriptomic changes in mucosa correlate pre-neoplasia, cancer inflammation (e.g. periodontitis). Alteration smoking-related gene expression epithelial cells is similar to that bronchial nasal cells. Using a systems toxicology approach, we have previously assessed impact cigarette smoke (CS) seen as perturbations biological processes human organotypic culture models. Here, report...
Cigarette smoke (CS) has been reported to increase predisposition oral cancer and is also recognized as a risk factor for many conditions including periodontal diseases, gingivitis, other benign mucosal disorders. Smoking cessation remains the most effective approach minimizing of smoking-related diseases. However, reduction harmful constituents by heating rather than combusting tobacco, without modifying amount nicotine, promising new paradigm in harm reduction. In this study, we compared...
Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered the lack human translational models limitations analysis techniques for three-dimensional (3D) InSight™ microtissue (hLiMT) model recapitulates pathophysiological features disease. We established an algorithm automated phenotypic quantification fibrosis Sirius Red stained histology...
Dehydroepiandrosterone (DHEA) exerts beneficial effects on blood glucose levels and insulin sensitivity in obese rodents humans, resembling the of peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands opposing those glucocorticoids; however, underlying mechanisms remain unclear. Glucocorticoids are reactivated locally by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which is currently considered as a promising target for treatment obesity diabetes. Using...
Exposure to cigarette smoke (CS) is linked the development of respiratory diseases, and there a need understand mechanisms whereby CS causes damage. Although animal models have provided valuable insights into smoking-related tract damage, modern toxicity testing calls for reliable in vitro as alternatives experimentation. We report on repeated whole mainstream exposure nasal bronchial organotypic tissue cultures that mimic morphological, physiological, molecular attributes human tract....
Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, downstream fibrosis. Despite its increasing prevalence, there no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models studying this complex disease. Here, we present 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture primary human hepatocytes, Kupffer cells,...
ADP-ribosyltransferase Diphtheria toxinlike 1 [ARTD1; formerly called poly-ADP-ribose polymerase (PARP1)] is a chromatin-associated enzyme involved in regulating metabolic homeostasis. The liver at the core of glucose and lipid metabolism significantly affected by obesity syndrome. Here, we show that when fed high-fat diet (HFD), mice lacking ARTD1 developed exacerbated hepatic steatosis. ARTD1–/– had 19% higher weight than wild-type (WT) animals exhibited increased serum concentration...
Cigarette smoke (CS) has a major impact on lung biology and may result in the development of diseases such as chronic obstructive pulmonary disease or cancer. To understand underlying mechanisms development, it would be important to examine CS exposure directly tissues. However, this approach is difficult implement epidemiological studies because tissue sampling complex invasive. Alternatively, culture models can facilitate assessment impacts tissue. Submerged 2D cell cultures, normal human...
Hypoxia causes several renal tubular dysfunctions, including abnormal handling of potassium and sodium increased blood pressure. Therefore, we investigated the impact hypoxia on 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) enzyme, a crucial prereceptor gatekeeper for glucocorticosteroid-mediated mineralocorticoid action. The effect was assessed in vitro by incubating LLC-PK1 cells with antimycin A, an inhibitor mitochondrial oxidative phosphorylation. Antimycin A induced dose-...
The 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) regulates access of 11beta-hydroxyglucocorticoids to the mineralocorticoid receptor by reducing hydroxyl group these steroids at position 11. Previous cell culture studies revealed that tumor necrosis factor-alpha (TNF-alpha) down-regulates 11beta-HSD2 activity. Here, we demonstrate transgenic mice overexpressing TNF-alpha have decreased mRNA abundance and activity in kidney tissue, indicating this effect may occur also vivo....
The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive to active glucocorticoids. 11β-HSD1 plays a crucial role in pathogenesis obesity and controls glucocorticoid actions inflammation. Several studies have demonstrated that TNF-α increases mRNA activity various cell models. Here, we demonstrate is increased liver tissue from transgenic mice overexpressing TNF-α, indicating this effect also occurs vivo. To dissect molecular mechanism increase,...
11β-Hydroxysteroid dehydrogenase type 2 is selectively expressed in aldosterone target tissues, where it confers selectivity for the mineralocorticoid receptor by inactivating 11β-hydroxyglucocorticoids with a high affinity receptor. The present investigation aimed to elucidate mechanisms accounting rigorous control of theHSD11B2 gene humans. Using dimethyl sulfatein vivo footprinting via ligation-mediated PCR, we identified potentially important regions HSD11B2regulation human cell lines:...
Cigarette smoke (CS) has a major impact on lung biology and may result in the development of diseases such as chronic obstructive pulmonary disease or cancer. To understand underlying mechanisms development, it would be important to examine CS exposure directly tissues. However, this approach is difficult implement epidemiological studies because tissue sampling complex invasive. Alternatively, culture models can facilitate assessment impacts tissue. Submerged 2D cell cultures, normal human...
Abstract Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, downstream fibrosis. Despite its increasing prevalence, there no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models studying this complex disease. Here, we present 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture primary human hepatocytes, Kupffer...