Search results for "CYP"
showing 10 items of 480 documents
Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
2017
AbstractThe association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL includin…
Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and …
2020
The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELIS…
Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent
2017
Abstract The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) − a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-m…
Inhabiting plant roots, nematodes, and truffles—polyphilus, a new helotialean genus with two globally distributed species
2018
Fungal root endophytes, including the common group of dark septate endophytes (DSEs), represent different taxonomic groups and potentially diverse life strategies. In this study, we investigated two unidentified helotialean lineages found previously in a study of DSE fungi of semiarid grasslands, from several other sites, and collected recently from a pezizalean truffle ascoma and eggs of the cereal cyst nematode Heterodera filipjevi. The taxonomic positions and phylogenetic relationships of 21 isolates with different hosts and geographic origins were studied in detail. Four loci, namely, nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]), partial 28S nuc rDNA (28S), partial 18S nu…
Telencephalic-olfactory bulb ventricle wall organization in Austrolebias charrua: Cytoarchitecture, proliferation dynamics, neurogenesis and migratio…
2016
Adult neurogenesis participates in fish olfaction sensitivity in response to environmental challenges. Therefore, we investigated if several populations of stem/progenitor cells that are retained in the olfactory bulbs (OB) may constitute different neurogenic niches that support growth and functional demands. By electron microscopy and combination cell proliferation and lineage markers, we found that the telencephalic ventricle wall (VW) at OB level of Austrolebias charrua fish presents three neurogenic niches (transitional 1, medial 2 and ventral 3). The main cellular types described in other vertebrate neurogenic niches were identified (transient amplifying cells, stem cells and migrating…
VDBP, CYP27B1, and 25-Hydroxyvitamin D Gene Polymorphism Analyses in a Group of Sicilian Multiple Sclerosis Patients
2016
Multiple sclerosis (MS) is a chronic demyelinating disease of central nervous system regarded as one of the most common causes of neurological disability in young adults. The exact etiology of MS is not yet known, although epidemiological data indicate that both genetic susceptibility and environmental exposure are involved. A poor vitamin D status has been proposed as the most attractive environmental factor. Several evidence have highlighted the importance of mutations in vitamin D-regulating genes for vitamin D status. The purpose of our study was to assess the genetic variants of VDBP and CYP27B1 in MS patients and in a control group. A total of 192 subjects, including 100 MS patients a…
Vitamin D and Genetic Susceptibility to Multiple Sclerosis.
2019
Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence o…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…
Metabolism and Bioactivation of Corynoline With Characterization of the Glutathione/Cysteine Conjugate and Evaluation of Its Hepatotoxicity in Mice
2018
Corynoline (CRL), an isoquinoline alkaloid, is the major constituent derived from Corydalis bungeana Herba, which is a well-known Chinese herbal medicine widely used in many prescriptions. The purpose of this study was to comprehensively investigate the metabolism and bioactivation of CRL, and identify the CYP450 isoforms involved in reactive ortho-benzoquinone metabolites formation and evaluate its hepatotoxicity in mice. Here, high resolution and triple quadrupole mass spectrometry were used for studying the metabolism of CRL. Three metabolites (M1-M3) and four glutathione conjugates (M4-M7) of CRL ortho-benzoquinone reactive metabolite were found in vitro using rat and human liver micros…
Triclosan activates aryl hydrocarbon receptor (AhR)-dependent apoptosis and affects Cyp1a1 and Cyp1b1 expression in mouse neocortical neurons.
2016
Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitizing products, such as soaps, toothpastes, and hair products. A number of studies have revealed the presence of TCS in human tissues, such as fat, liver and brain, in addition to blood and breast milk. The aim of the present study was to investigate the impact of TCS on AhR and Cyp1a1/Cyp1b1 signaling in mouse neocortical neurons in primary cultures. In addition to the use of selective ligands and siRNAs, expression levels of mRNA and proteins as well as caspase-3 activity, reactive oxygen species (ROS) formation, and lactate dehydrogenase (LDH) release have been measured. We also studied the in…