Exendin-4 restores glucolipotoxicity-induced gene expression in human coronary artery endothelial cells

Exendin-4, a stable GLP-1 receptor agonist, has been shown to stimulate insulin secretion. It has also been shown to exert beneficial effects on endothelial function that are independent of its glycemic effects. The molecular mechanisms underlying the protective actions of exendin-4 against diabetic glucolipotoxicity in endothelial cells largely remain elusive. We have investigated the long-term in vitro effect of palmitate or high glucose (simulating the diabetic milieu) and the role of exendin-4 on gene expression in human coronary artery endothelial cells. Gene expression profiling in combination with Western blotting revealed that exendin-4 regulates expression of a number of genes involved in angiogenesis, inflammation and thrombogenesis under glucolipotoxic conditions. Our results indicate that exendin-4 may improve endothelial cell function in diabetes through regulating expression of the genes, whose expression was disrupted by glucolipotoxicity. As endothelial dysfunction appears to be an early indicator of vascular damage, and predicts both progression of atherosclerosis and incidence of cardiovascular events, exendin-4 and possibly other incretin-based strategies may confer additional cardiovascular benefit beyond improved glycemic control.     

Spatial distribution of 222Rn concentrations and dose estimations in various waters

In this article, the levels of ²²²Rn concentrations, annual effective doses, and excess lifetime cancer risk estimations were investigated for water samples in the city of Osmaniye, located in the southern part of Turkey. The measurements were conducted using a radon gas analyzer (AlphaGUARD PQ 2000 PRO). The arithmetic average of ²²²Rn concentrations was 0.44 Bq.L^?1 with a geometric standard deviation of 0.19 and geometric average 0.41 Bq.L^?1. The results obtained were compared with the findings of other studies. All measured radon concentrations were below the values recommended by the World Health Organization and the U.S. Environmental Protection Agency. The associated radiological parameters such as annual effective doses (AED) and excess lifetime cancer risk (ELCR) from consumption of these waters were calculated. The computed average annual effective doses for ingestion and inhalation as well as excess lifetime cancer risk were estimated to be 1.13 μSv.y^?1, 1.10 μSv.y^?1, and 3.95 × 10^?6, respectively. ²²²Rn concentration, AED, and ELCR interpolated values of the region were determined and mapped using the Kriging method. The results of radon concentrations in this study provide a data baseline for future studies on subsequent evaluations of possible future environmental contamination of Osmaniye Province.     

Endothelial dysfunction induced by triglycerides is not restored by exenatide in rat conduit arteries ex vivo

Exenatide (synthetic exendin-4) is a stable analogue of glucagon-like peptide 1 (GLP-1) and has recently been approved for clinical use against type 2 diabetes. Exenatide is believed to exert its effects via the GLP-1 receptor with almost the same potency as GLP-1 in terms of lowering blood glucose. Short term exenatide treatment normalizes the altered vascular tone in type 2 diabetic rats, probably due to the reduction in glycemia. The aim of this study was to investigate whether exenatide directly protects against triglyceride-induced endothelial dysfunction in rat femoral arterial rings ex vivo. Short term pre-incubation with Intralipid^® (0.5 and 2%) was found to dose-dependently induce endothelial dysfunction, in that it elicited a significant reduction in ACh-induced vasorelaxation by 29% and 35%, respectively. Paradoxically, this occurred with a concomitant increase in endothelial nitric oxide synthase (eNOS) activity. No such reduction in vasorelaxation by Intralipid^® was seen in response to the NO donor sodium nitroprusside (SNP), revealing an endothelium-dependent vascular dysfunction by Intralipid^®. However, exenatide did not protect against Intralipid^®-induced endothelial dysfunction. More surprisingly, the maximum vasorelaxation induced by exenatide (without Intralipid^®) was only 3 ± 2%, compared to the 23 ± 4%, 38 ± 4%, 79 ± 3% and 97 ± 4% relaxations induced by GLP-1, GLP-1 (9-36), ACh and SNP, respectively. This unexpected finding prompted us to ascertain that the exenatide preparation was biologically active, and both exenatide (10^− 11 mol/l) and GLP-1 (10^− 9 mol/l) significantly increased insulin secretion in pancreatic β-cells from ob/ob mice in vitro. In conclusion, exenatide could neither confer any acute protective effects against triglyceride-induced endothelial dysfunction nor exert any significant vasorelaxant actions in this model of rat conduit arteries ex vivo.     

An investigation into the structural,electronic, and non-linear optical properties in CN (N = 20, 24, 26, 28, 30, 32, 34, 36, and 38) fullerene cages

Journal of Molecular Modeling -     

Vibrational (FT-IR and FT-Raman) spectral investigations of 7-aminoflavone with density functional theoretical simulations

FT-Raman and FT-IR spectra of the 7-aminoflavone have been recorded and analysed. The detailed interpretation of the vibrational spectra has been carried out with the aid of normal coordinate analysis following the scaled quantum mechanical force field methodology. The various intramolecular interactions that are responsible for stabilisation of the molecule were revealed by natural bond orbital analysis. The obtained vibrational wavenumbers and optimised geometric parameters were observed to be in good agreement with the experimental data. The carbonyl stretching vibrations have been lowered due to conjugation and hydrogen bonding in the molecules.     

Construction and characterization of a de novo draft genome of garden cress (Lepidium sativum L.)

Functional & Integrative Genomics - Garden cress (Lepidium sativum L.) is a Brassicaceae crop recognized as a healthy vegetable and a medicinal plant. Lepidium is one of the largest genera in...