Endothelial Glycocalyx as a Regulator of Fibrotic Processes

The endothelial glycocalyx, the gel layer covering the endothelium, is composed of glycosaminoglycans, proteoglycans, and adsorbed plasma proteins. This structure modulates vessels’ mechanotransduction, vascular permeability, and leukocyte adhesion. Thus, it regulates several physiological and pathological events. In the present review, we described the mechanisms that disturb glycocalyx stability such as reactive oxygen species, matrix metalloproteinases, and heparanase. We then focused our attention on the role of glycocalyx degradation in the induction of profibrotic events and on the possible pharmacological strategies to preserve this delicate structure.     

Investigation of the changes in physical properties of PES/PVC fabrics after aging

The aim of this work was to investigate the physical and mechanical performance of architectural polyester (PES)–poly(vinyl chloride) (PVC) membranes exposed to different artificial aging conditions. Two commercially available architectural membranes were chosen as research objects. The durability of the PES/PVC fabrics was evaluated by the loss in mechanical performance, scanning electron microscopy, and X-ray diffraction analysis in order to understand the effect of the degradation agents on the surface of the membranes. The mechanical performance of the PES/PVC membranes was unchanged. Scanning electron microscopy images of the tested materials showed initial cracks after aging. The X-ray fluorescence analysis showed that at the time of aging, the amount of Cl and Si decreased slightly, while Ti decreased by half, and Ca by volume increased twice. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47523.     

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

Development of low-alcohol isotonic beer by interrupted fermentation

Alcohol-free beer with isotonic properties is getting more popular and its production can be carried out by different production strategies; however, interrupted fermentation is still a challenge. Therefore, the objective of this study was to develop a low-alcohol isotonic beer (<0.5% v/v) by interrupted fermentation. Moreover, the major objective is to compare the developed product to commercial beverages (sports drinks, ‘Pilsen' regular beer, alcohol-free beers and low-alcohol isotonic beer). The beverages were evaluated based on pH, alcohol content (% v/v), total titratable acidity (mEq L⁻¹), osmolality (mOsmol kg⁻¹), bitterness International Bitterness Units, colour European Brewery Convention, total phenolic compounds (mg L⁻¹ gallic acid), reducing and total sugars (%) and Na and K contents (mg L⁻¹). The developed low-alcohol isotonic beer presented characteristics similar to sports drinks, with the advantage of being richer in phenolic compounds and suitable osmolality. Despite salts were added in its formulation, the grades attributed to all beers employed in the sensory evaluation, as well as the purchase intention did not present significant differences.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields

cDNA selection was used to isolate coding sequences from cosmids mapping to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere. The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cerevisiae SMT3 protein, whose gene was previously isolated as a suppressor of mutations in the MIF2 gene. The yeast MIF2 gene encodes an essential centromeric protein and shows homology to mammalian CENP-C, an integral component of active kinetochores. SMT3A was found to be highly homologous to two other recently isolated human genes, suggesting the presence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants. Moreover, all predicted proteins show significant homology to ubiquitin. The proposed role of yeast SMT3 as centromeric protein and the strong evolutionary conservation of the SMT3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore.