Search results for "EOT"
showing 10 items of 4111 documents
Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis.
2017
Major reactive oxygen species (ROS)–producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemi…
ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
2017
AbstractPreviously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10−08). A meta-analysis of rs6874700 of our previous and prese…
Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of…
2017
International audience; PurposeCongenital anomalies and intellectual disability (CA/ID) are a major diagnostic challenge in medical genetics—50% of patients still have no molecular diagnosis after a long and stressful diagnostic “odyssey.” Solo clinical whole-exome sequencing (WES) was applied in our genetics center to improve diagnosis in patients with CA/ID.MethodsThis retrospective study examined 416 consecutive tests performed over 3 years to demonstrate the effectiveness of periodically reanalyzing WES data. The raw data from each nonpositive test was reanalyzed at 12 months with the most recent pipeline and in the light of new data in the literature. The results of the reanalysis for …
Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors
2015
Background Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. Objectives The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications. Methods Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, m…
Mobility of a Mononucleotide within a Lipid Matrix: A Neutron Scattering Study
2017
International audience; An essential question in studies on the origins of life is how nucleic acids were first synthesized and then incorporated into compartments about 4 billion years ago. A recent discovery is that guided polymerization within organizing matrices could promote a non-enzymatic condensation reaction allowing the formation of RNA-like polymers, followed by encapsulation in lipid membranes. Here, we used neutron scattering and deuterium labelling to investigate 5'-adenosine monophosphate (AMP) molecules captured in a multilamellar phospholipid matrix. The aim of the research was to determine and compare how mononucleotides are captured and differently organized within matric…
Identification and Characterization of Extracellular Vesicles and Its DNA Cargo Secreted During Murine Embryo Development
2020
Extracellular vesicles (EVs) are known to transport DNA, but their implications in embryonic implantation are unknown. The aim of this study was to investigate EVs production and secretion by preimplantation embryos and assess their DNA cargo. Murine oocytes and embryos were obtained from six- to eight-week-old females, cultured until E4.5 and analyzed using transmission electron microscopy to examine EVs production. EVs were isolated from E4.5-day conditioned media and quantified by nanoparticle tracking analysis, characterized by immunogold, and their DNA cargo sequenced. Multivesicular bodies were observed in murine oocytes and preimplantation embryos together with the secretion of EVs t…
Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models
2019
Myotonic dystrophy type 1 (DM1) is a life-threatening and chronically debilitating neuromuscular disease caused by the expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. The mutant RNA forms insoluble structures capable of sequestering RNA binding proteins of the Muscleblind-like (MBNL) family, which ultimately leads to phenotypes. In this work, we demonstrate that treatment with the antiautophagic drug chloroquine was sufficient to up-regulate MBNL1 and 2 proteins in Drosophila and mouse (HSA LR ) models and patient-derived myoblasts. Extra Muscleblind was functional at the molecular level and improved splicing events regulated by MBNLs in all disease models. In vivo,…
Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy
2020
Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts contain 50 or more repetitions due to the sequestration of the muscleblind-like (MBNL) family of proteins. Depletion of MBNLs causes alterations in splicing patterns in transcripts that contribute to clinical symptoms such as myotonia and muscle weakness and wasting. We previously found that microRNA (miR)-23b directly regulates MBNL1 in DM1 myoblasts and mice and that antisense technology (“antagomiRs”) blocking this microRNA (miRNA) boost…
Anti-proliferative and apoptosis-inducing effect of theabrownin against non-small cell lung adenocarcinoma A549 cells
2016
With the highest cancer incidence rate, lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer death in the world. Tea (leaves of Camellia sinensis) has been widely used as a traditional beverage beneficial to human health, including anti-NSCLC activity. Theabrownin (TB) is one major kind of tea pigment responsible for the beneficial effects of tea liquor. However, its effect on NSCLC is unknown. The aim of the present study was to evaluate anti-proliferative and apoptosis-inducing effect of TB on NSCLC (A549) cells, using MTT assay, morphological observation (DAPI staining), in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) ass…
CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells.
2017
ObjectiveCancer stem cells (CSCs) are responsible for tumour formation and spreading, and their targeting is required for tumour eradication. There are limited therapeutic options for advanced colorectal cancer (CRC), particularly for tumours carrying RAS-activating mutations. The aim of this study was to identify novel CSC-targeting strategies.DesignTo discover potential therapeutics to be clinically investigated as single agent, we performed a screening with a panel of FDA-approved or investigational drugs on primary CRC cells enriched for CSCs (CRC-SCs) isolated from 27 patients. Candidate predictive biomarkers of efficacy were identified by integrating genomic, reverse-phase protein mic…