Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage.
View Article and Find Full Text PDFObesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat diet from 3 to 15 weeks.
View Article and Find Full Text PDFPurpose: Hodgkin's lymphoma (HL) is associated with the presence of EBV in Reed-Sternberg (RS) cells in ∼40% of cases. Here, we studied the presence of human herpesvirus type 6 (HHV-6) variant B in RS cells of HL patients and correlated results with clinical parameters. We then examined the implication of HHV-6 DR7B protein in cell deregulation.
View Article and Find Full Text PDFBackground: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR).
Methods: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60.
Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. Results using whole genome Illumina microarrays show that ritonavir modulates a number of genes implicated in lipid metabolism, inflammation and atherosclerosis.
View Article and Find Full Text PDFUnlabelled: INVESTIGATIONAL PRODUCT: Rosuvastatin (Crestor; Astra Zeneca).
Active Ingredients: Rosuvastatin (5 mg).
Study Title: Prevention of Atherosclerosis in Patients Living with HIV.
We investigated the relationship between ritonavir concentrations and changes in lipids, vascular inflammation markers, CD36, and adipophilin expression in volunteers randomly assigned to groups receiving 100 mg of ritonavir once daily or twice daily. In both groups decreases in high-density lipoprotein (HDL) (6%, P = 0.010; and 10%, P < 0.
View Article and Find Full Text PDFHuman immunodeficiency virus (HIV)-infected patients are at a significantly higher risk from coronary heart diseases (CHD) and myocardial infarction (MI) compared to gender- and age-matched non-infected individuals. Combination antiretroviral therapy (cART) has transformed a fatal illness into a chronic stable condition. However, cART induces metabolic abnormalities in HIV-infected patients, while its role in vascular atherosclerosis is still under investigation.
View Article and Find Full Text PDFOxLDL uptake and cholesterol efflux inhibition in macrophages play a key role in atherosclerotic plaque formation, rupture, and thrombotic ischemia. This study investigates genes implicated in OxLDL uptake (CD36, SRA), cholesterol efflux inhibition (adipophilin, ADFP), and inflammatory recruitments of leukocytes (IL-8) in plaque lesion areas (PLAs) compared to nonplaque lesion areas (NPLAs) in human carotid endarterectomy specimens. Gene and protein expressions were assayed using quantitative PCR and quantitative immunohistochemistry.
View Article and Find Full Text PDFThe uptake of OxLDLs (oxidized low density lipoproteins) by CD36-expressing macrophages in the arterial intima and the subsequent 'foam cell' formation represents a crucial step in the initiation and development of atherosclerotic plaques. The present study has addressed the function of the CD36 N-terminal cytoplasmic domain in the binding and internalization of OxLDL. A selection of CD36 N-terminal cytoplasmic domain mutants were generated and stably expressed in HEK-293 (human embryonic kidney) cells.
View Article and Find Full Text PDFThe aim of this chapter is to present and identify potential pharmacological targets in endothelial cell-monocyte interactions leading to vascular syndrome and involving inflammation, coagulation, vascular remodelling and thrombosis. Increasing evidence is indicating that endothelial cells play a key role in atherothombosis by their capacity to attract, bind and allow the extravasation of monocytes to sites of inflammation. Surface expression and/or activation of constituent cell adhesion molecules (for e.
View Article and Find Full Text PDFCD36 is a multi-ligand scavenger receptor present on the surface of a number of cells such as platelets, monocytes/macrophages, endothelial and smooth muscle cells. Monocyte/macrophage CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and endocytose oxidized low density lipoproteins (OxLDL), and it is implicated in the formation of foam cells. However, the significance of CD36 in atherosclerosis has recently been called into question by different studies, and therefore its exact role still needs to be clarified.
View Article and Find Full Text PDFPrimarily statin drugs inhibit hepatic 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the reduction in circulating low-density lipoprotein (LDL) cholesterol. Several findings from recent research studies indicate that statins have multiple actions that favorably influence key factors involved in the atherogenic process. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity.
View Article and Find Full Text PDFHuman tumor suppressor protein p53 plays a major role in the cell cycle, orchestrating a number of important genes involved in cell-cycle control and apoptosis, and seems to be one of the most important molecules protecting cells from malignant transformation. Mutations in the p53 gene are observed in about 50% of primary tumors, inducing defective p53 protein no longer capable of binding DNA and of activating transcription. Certain DNA viruses are thought to act in a similar way and may also contribute to the progression of invasive cancer in infected tissue.
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