Arterioscler Thromb Vasc Biol
October 2022
Background: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown.
Methods: Common and rare genetic variants in the gene locus were used as research instruments in the UK Biobank.
Objective: GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e.
View Article and Find Full Text PDFObjective: , encoding for STAP1 (signal transducing adaptor family member 1), has been reported as a candidate gene associated with familial hypercholesterolemia. Unlike established familial hypercholesterolemia genes, expression of is absent in liver but mainly observed in immune cells. In this study, we set out to validate as a familial hypercholesterolemia gene.
View Article and Find Full Text PDFAlthough human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice.
View Article and Find Full Text PDFPurpose Of Review: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism.
Recent Findings: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway.
The senescence response is a potent tumor suppressor mechanism characterized by an irreversible growth arrest in response to potentially oncogenic signals to prevent the proliferation of damaged cells. Late in life, some of the features of senescent cells seem to mediate the development of age-related pathologies, including cancer. In the present review, we present a summary of the current knowledge regarding the causes, effector pathways and cellular features of senescence.
View Article and Find Full Text PDFIntroduction: Microbiological diagnosis of pneumonia allows the optimal use of antibiotics in mechanically ventilated patients. That is why samples of bronchoscopic bronchoalveolar lavage had been quantitatively cultivated, but this procedure is not always possible.
Objective: To evaluate the microbiological concordance between respiratory samples obtained by non-bronchoscopic protected bronchoalveolar lavage compared to the bronchoscopic ones, and to find out whether concordance was affected by previous use of antibiotics or the time of pneumonia onset.
Introduction: Human metapneumovirus (hMPV) is an important cause of lower respiratory tract infections in children, accounting for 14% to 24% of all viral respiratory infections with an etiological diagnosis. This study compares a direct fluorescent antibody (DFA) test, enzyme immunoassay (EIA), and shell-vial culture for diagnosing acute bronchiolitis in infants.
Methods: A total of 124 nasopharyngeal aspirates from 108 infants with lower respiratory tract infection were analyzed.