A5069586805- Pharmacogenetics and Drug Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Liver physiology and pathology
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Metabolomics and Mass Spectrometry Studies
- Organ Transplantation Techniques and Outcomes
- Computational Drug Discovery Methods
- Photodynamic Therapy Research Studies
- Animal testing and alternatives
- Eicosanoids and Hypertension Pharmacology
- Inflammatory mediators and NSAID effects
- Pluripotent Stem Cells Research
- Metabolism and Genetic Disorders
- 3D Printing in Biomedical Research
- Liver Disease and Transplantation
- Cannabis and Cannabinoid Research
- Skin Protection and Aging
- bioluminescence and chemiluminescence research
- Carcinogens and Genotoxicity Assessment
- Pesticide Exposure and Toxicity
- CRISPR and Genetic Engineering
- X-ray Diffraction in Crystallography
- Cytokine Signaling Pathways and Interactions
Universitat de València
2016-2025
Instituto de Investigación Sanitaria La Fe
2016-2025
Instituto de Salud Carlos III
2016-2025
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2015-2024
Leitat Technological Center
2003-2024
Centro de Investigación Biomédica en Red
2007-2024
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2023
Hospital Universitari i Politècnic La Fe
2008-2022
Universitat Politècnica de Catalunya
2015
Universidad de León
2015
The three monokines interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), and interleukin‐6 (IL‐6) modulate acute phase plasma protein synthesis in adult human hepatocytes. Only IL‐6 stimulates the of full spectrum proteins as seen inflammatory states humans, i.e. secretion C‐reactive protein, serum amyloid A, fibrinogen, 1 ‐antitrypsin, ‐antichymotrypsin haptoglobin are increased while albumin, transferrin fibronectin decreased. IL‐1β well TNFα, although having a moderate effect on...
Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved induction of acute-phase response human liver. Hepatocytes incubated with increasing amounts recombinant interleukin1β;, interleukin-6 and tumor necrosis factor-α. Synthesis C-reactive protein was studied at mRNA levels. Only capable inducing protein—mRNA protein—protein synthesis. Also, fibrinogen α−1-antitrypsin synthesis measured by immunoprecipitation specific antisera increased...
Recombinant human IL‐6 (rhIL‐6) is a potent inducer of the synthesis acute phase proteins in adult hepatocytes. A wide spectrum regulated by this mediator. After labeling rhIL‐6 stimulated hepatocytes with [ 35 S]methionine protein was measured immunoprecipitation. Serum amyloid A, C‐reactive protein, haptoglobin, α 1 ‐antichymotrypsin and fibrinogen were strongly induced (26‐, 23‐, 8.6‐, 4.6‐ 3.8‐fold increases, respectively). Moderate increases found for ‐antitrypsin (2.7‐fold) ‐acid...
1. Cultured hepatic cells have reduced cytochrome P450 (CYP) activities in comparison with human liver, but the mechanism(s) that underlies this circumstance is not clear. We investigated causes of low CYP activity by analysing activity, protein, mRNA and heterologous nuclear RNA contents most important CYPs involved drug metabolism (1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5) cultured hepatocytes, HepG2 Mz-Hep-1 hepatoma cell lines. 2. After 24 h culture, hepatocytes retained their...
Bile acids (BAs) are a group of chemically related steroids recognized as regulatory molecules whose profiles can change in different physio-pathological situations. We have developed sensitive, fast, and reproducible ultraperformance liquid chromatography/multiple reaction monitoring/mass spectrometry method to determine the tissue sera BA species (human, rat, mouse) by quantifying 31 major minor single 21-min run. The has been validated according FDA guidelines, it generally provides good...
The plasma half‐life of recombinant human interleukin‐6 (rhIL‐6) was determined in rats by measuring the disappearance biological activity as well radioactivity 125 I‐rhIL‐6 from circulation. kinetics clearance were biphasic. It consisted a rapid initial corresponding to 3 min, and second slow one about 55 min. By cellulose‐acetate electrophoresis it shown that rhIL‐6 binds protein resulting complex migrating β–γ region; 20 min after intravenous injection, 80% had disappeared circulation...
Diclofenac, a 2-arylacetic acid, nonsteroidal anti-inflammatory drug, has been reported to cause adverse hepatic effects in certain individuals. To discriminate among possible mechanisms of hepatotoxicity, we examined the diclofenac on human and rat hepatocytes cell lines (HepG2, FaO), investigated major biochemical events course cytotoxicity (calcium homeostasis, lipid peroxidation, mitochondrial dysfunction), whether could be related drug metabolism by cytochrome P-450. Acute...
Hepatocyte nuclear factor 4 (HNF4) is a member of the receptor super-family that has shown activating effects on particular cytochrome P450 (CYP) promoters from several species. However, its role in regulation human CYPs liver still poorly understood, as no comprehensive studies human-relevant models have been performed. In present study, we investigated whether HNF4 plays general expression 7 major CYP genes primary cultured hepatocytes. To this end, developed an adenoviral vector for...
In this study we describe a battery of fluorescence assays for rapid measurement in intact cells the activity nine cytochromes P450 (P450s) involved drug metabolism. The are based on direct incubation monolayers expressing individual enzymes with fluorogenic substrate followed by fluorimetric quantification product formed and released into medium. For each activity, different probes were examined, one showing best properties (highest metabolic rates, lowest background fluorescence) was...
The hepatic drug-metabolizing cytochrome P-450 (CYP) enzymes are down-regulated during inflammation. In vitro studies with hepatocytes have shown that the cytokines released inflammatory responses largely responsible for this CYP repression. However, signaling pathways and cytokine-activated factors involved remain to be properly identified. Our research has focused on negative regulation of CYP3A4 (the major human CYP) by interleukin 6 (IL-6) principal regulator acute-phase response)....
On September 6 and 7, 2009 a meeting was held in London to identify discuss what are perceived be current roadblocks effective hepatocyte transplantation as it is currently practiced the clinics and, where possible, offer suggestions overcome blocks improve outcomes for this cellular therapy. Present were representatives of most active clinical transplant programs along with other scientists who have contributed substantial basic research field. Over 2-day sessions based on experience...
Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons liver transplant outcomes management recipients among within centers. We sought to develop a model for the quantitative assessment early function [Model Allograft Function Scoring (MEAF)] after transplantation. retrospective study including 1026 consecutive transplants was performed MEAF score development. Multivariate data analysis used select...
Steatosis, or excessive accumulation of lipids in the liver, is a generally accepted previous step to development more severe conditions like nonalcoholic steatohepatitis, fibrosis, and cirrhosis. We aimed characterize metabolic profile that defines simple steatosis human tissue identify potential disturbances hepatic metabolism could favor switch progressive liver damage. A total 46 samples, 23 from steatotic nonsteatotic livers, were analyzed following holistic LC-MS-based metabonomic...