Effect of Aminaphtone on in vitro vascular permeability and capillary–like maintenance

Aminaphtone (AMNA), a naphtohydrochinone used in the treatment of capillary disorders, may affect oedema in chronic venous insufficiency (CVI). Aim of study is to investigate the effect of AMNA on vascular endothelial permeability in vitro and its effects on three-dimensional capillary-like structures formed by Human Umbilical Vein Endothelial Cells (HUVECs). HUVECs were treated with 50 ng/ml VEGF for 2h and AMNA for 6h. Permeability assay, VE-cadherin expression and Matrigel assay were performed. VEGF-induced permeability was significantly decreased by AMNA in a range concentration of 1-20 μg/ml. AMNA restored VE-cadherin expression. Finally, 6h pretreatment with AMNA significantly preserved capillary-like structures formed by HUVECs on Matrigel up to 48 h compared to untreated cells. AMNA significantly protects endothelium permeability and stabilises endothelial cells organised in capillary-like structures, modulating VE-cadherin expression. These data might explain the clinical benefict of AMNA on CVI

Chitosan-Based Nanoparticles Containing Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress

Cherries are known for their nutraceutical properties, in particular for their antioxidant ability due to their polyphenol content, which causes a reduction of cardiovascular disease (CVD) risk factors. However, once ingested these molecules are degraded in the Gastrointestinal (GI) tract before reaching the blood, which is the action site. The object of the present work is to evaluate the ability of cherry extract (CE), encapsulated in nanoparticles (NPs) based on different chitosan (Ch) derivatives, to promote a protective effect of human umbilical vein endothelial cells (HUVECs) involved in vascular dysfunction against oxidative stress. CE-loaded NPs based on quaternary ammonium chitosan (NP1) and an S-protected thiolated derivative thereof (NP2) were prepared. The mean particle size (NP1 344.9 ± 17.8, NP2 339.9 ± 68.2 nm), the polydispersity index, the encapsulation efficiency (NP1 78.4 ± 4.5, NP2 79.8 ± 0.6%), and the zeta potential (NP1 14.8 ± 0.3, NP2 15.8 ± 0.5 mV) did not appear to be significantly different. Both NP types improved the CE apparent permeation parameters with respect to the control. Conversely, CE-loaded NP2 protected HUVECs from oxidative stress and reduced reactive oxygen species (ROS) production more than CE-loaded NP1 and free CE. In addition to promoting HUVEC resistance, NP2 could be a useful tool to overcome the problem of cherry seasonality

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements