A5077246050- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Diet, Metabolism, and Disease
- MicroRNA in disease regulation
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Extracellular vesicles in disease
- Diet and metabolism studies
- Epigenetics and DNA Methylation
- Nutrition and Health in Aging
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Influenza Virus Research Studies
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Polyamine Metabolism and Applications
- Folate and B Vitamins Research
- Photoreceptor and optogenetics research
- Cancer-related gene regulation
- Protein purification and stability
- Food composition and properties
- Complement system in diseases
- Chemistry and Stereochemistry Studies
CIC bioGUNE
2011-2023
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2011-2020
Medical Research Network
2018
Centro de Investigación Biomédica en Red
2017
Society of Environmental Toxicology and Chemistry
2005-2008
Vrije Universiteit Amsterdam
2005-2007
Kiadis Pharma (Netherlands)
2007
BackgroundFibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with brain through enteric nervous system (ENS); its disruption has been associated psychiatric and gastrointestinal disorders. To gain an insight into pathogenesis of fibromyalgia identify diagnostic biomarkers, we combined different omics techniques to analyse serum composition.MethodsWe collected faeces blood samples...
Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD) which sets stage for further damage. The mechanism progression NASH involves multiple parallel hits including oxidative stress, mitochondrial dysfunction, inflammation and others. Manipulation any these pathways may be an approach to prevent development progression. Aramchol (arachidyl-amido cholanoic acid) presently in a phase IIb study. aim this study was investigate Aramchol's action its...
Abstract Hepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although importance of EVs in intercellular communication is already recognized, metabolic impact carried by these still unclear. We evaluated global effect enzymatic activities performing untargeted metabolomic profiling serum samples after their exposure to EVs. This approach revealed a significant change abundance 94 signals. Our study shows that modify concentration...
Abstract Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify P-gp overexpressing cells be involved development and, ii) potential for EVs acquisition Two different pairs their...
We describe the practical aspects of developing a semiautomated, higher-throughput plasma protein binding (PPB) assay. The assay has capacity 32 PPB measurements per screen using triplicate incubations measurement, and it is flexible with respect to number compounds types used. described method based on 48-well format rapid equilibrium dialysis (RED) device in combination robotic liquid handling platform quantitative bioanalysis. RED was optimized equilibration time. Method validation...
S-Adenosylmethionine (SAMe) is the principal methyl donor of cell and synthesized via an ATP-driven process by methionine adenosyltransferase (MAT) enzymes. It tightly linked with proliferation in liver colon cancer. In humans, there are three genes, mat1A, mat2A mat2B, which encode MAT mat2B transcribe MATα2 MATβ enzyme subunits, respectively, catalytic regulatory roles. The MATα2β complex expressed nearly all tissues thought to be essential providing necessary SAMe flux for methylation DNA...
Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those human iCCA. Carcinogenic changes therapeutic vulnerabilities may be captured by investigations bile, where we performed bile proteomic metabolomic analyses that help discovery yet unknown pathways relevant to iCCA.Cholangiocarcinogenesis was induced (TAA) mice (JnkΔhepa + CCl4 DEN model). We from control CCA-bearing rats....
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers adaptive cellular responses in major organs of body. Here, we show that mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor nutrition fine-tune catabolic-fasting response modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production liver, together with FGF21-mediated...
Here we present a high-resolution screening (HRS) methodology for postcolumn on-line profiling of metabolites with affinity the estrogen receptor α (ERα). Tamoxifen, which is metabolized into multiple metabolites, was used as model compound. Most 14 detected exhibited ERα. The HRS shows great potential metabolite bio-affinity and application in drug discovery development.
A high-resolution screening platform, coupling online affinity detection for mammalian cytochrome P450s (Cyt P450s) to gradient reversed-phase high-performance liquid chromatography (HPLC), is described. To this end, the Cyt P450 enzyme (EAD) system was optimized (beta-NF-induced rat liver microsomes), probe substrate (ethoxyresorufine), and organic modifier (methanol or acetonitrile). The EAD has first been evaluated in a flow injection analysis (FIA) mode with 7 known ligands of 1A1/1A2...
Most plant species develop stress symptoms when exposed to high ammonium (NH4+) concentrations. The root is the first organ in contact with NH4+ and therefore barrier cope stress. In this work, we focused on adaptation nutrition model Brachypodium distachyon. Proteome analysis revealed changes associated primary metabolism, cell wall remodelling, redox homeostasis. addition, it showed a strong induction of proteins related methionine (Met) metabolism phytosiderophore (PS) synthesis...
Lyme carditis is an extracutaneous manifestation of disease characterized by episodes atrioventricular block varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over course infection are poorly understood. Here, we identify broad transcriptomic proteomic in heart during that reveal a profound down-regulation mitochondrial components. We also describe long-term functional modulation macrophages exposed live...
We have developed a fully automated bioreactor coupled to an on-line receptor affinity detection system. This analytical system provides detailed information on pharmacologically active metabolites of selective estrogen modulators (SERMs) generated by cytochromes P450 (P450s). demonstrated this novel concept investigating the metabolic activation tamoxifen and raloxifene P450-containing pig rat liver microsomes. The high resolution screening (HRS) is based coupling P450-bioreactor HPLC-based...
A high-resolution screening (HRS) technology is described, which couples 2 parallel enzyme affinity detection (EAD) systems for substrates and inhibitors of rat cytosolic glutathione-S-transferases (cGSTs) purified human GST P1 to gradient reversed-phase high-performance liquid chromatography (HPLC). The cGSTs EAD were optimized validated first in flow injection analysis (FIA) mode, values subsequently used HPLC mode. IC(50) 8 ligands thus obtained online agreed well with the microplate...
We present a fully automated and hyphenated bioanalytical method for metabolic profiling of potentially harmful xenoestrogens. The system consists an on-line cytochrome P450 bioreactor coupled to reversed-phase, gradient high-performance liquid chromatograph. A C18 solid-phase extraction (SPE) unit is used as interface between the HPLC column. column linked high-resolution screening (HRS)-estrogen receptor α affinity detection (ERAD) assay. In effect, produces metabolites that are...
A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The so-called enzyme affinity (EAD) contained, respectively, liver microsomes from rats induced by β-naphthoflavone (CYP1A activity), phenobarbital (CYP2B and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate,...
Reactive oxygen species (ROS) can damage proteins, cause lipid peroxidation, and react with DNA, ultimately resulting in harmful effects. Antioxidants constitute one of the defense systems used to neutralize pro-oxidants. Since pro-oxidants antioxidants are found ubiquitously nature, pro-and antioxidant effects individual compounds mixtures receive much attention scientific research. A major bottleneck these studies, however, is identification mixtures. Here, we describe development...
Steroid hormones play a vital role in the regulation of cellular processes, and dysregulation these metabolites can provoke or aggravate pathological issues, such as autoimmune diseases cancer. Regulation steroid involves different organs biological compartments. Therefore, it is important to accurately determine their levels tissues biofluids monitor changes after challenge during disease. In this work, we have developed optimized extraction quantification 11 key members classes, including...