Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors Reduce Platelet Activation Modulating ox-LDL Pathways

Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p < 0.001). The decrease of TxB2 correlates with that of ox-LDL, while ox-LDL reduction correlated with PCSK9 and sNOX2-dp delta. In vitro study demonstrated that wPLTs resuspended in plasma from HeFH after PCSK9i treatment induced lower PA and sNOX2-dp release than those obtained using plasma before PCSK9i treatment. This reduction was vanished by adding ox-LDL. ox-LDL-induced PA was blunted by CD36, LOX1, and NOX2 inhibition. Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients.     

Immune parameters in female workers exposed to urban pollutants

Urban outside workers, such as traffic police, are daily exposed to air pollutants and psychosocial stressors: for these workers, the working environment corresponds to the living environment of the general population. Studies in the literature have shown that immune parameters could be affected by chronic exposure to various chemical pollutants. The aim of this study is to evaluate whether occupational exposure to urban pollutants can cause alterations in NK, IL-2, IFN-gamma and C3 plasma levels in female traffic police compared to a control group. After excluding subjects with the principal confounding factors, 86 female traffic police and 87 controls were matched by age, years of police work and habitual alcohol consumption. The distribution of NK values in female traffic police and controls was significantly different (p=0.000); NK values above the upper limit of the normal laboratory range were observed in 23 female traffic police and in 2 controls (p=0.000). IL-2 mean levels were higher in traffic police compared to controls, but the difference was not significant. The mean and the distribution of IFN-gamma values in female traffic police and controls were not different. C3 mean levels were higher in female traffic police versus controls, but the difference was not significant. Considering that the subjects with the principal confounding factors were excluded from the study and that female traffic police and controls were matched by the above-mentioned variables, our results suggest that chronic occupational exposure to low doses of chemical stressors, which may interact with and add to psychosocial ones, can affect both innate and adaptative immunity.     

Techno-functional properties of dry-fractionated plant-based proteins and application in food product development: a review

Dry-fractionated protein concentrates are gaining attention because they are produced using a versatile and sustainable technology, which can be applied to a wide range of plant material. To facilitate their utilization in new product development, it is crucial to obtain a comprehensive overview of their techno-functional properties. The present review aims to examine the techno-functional properties of dry-fractionated protein concentrates and describe their primary applications in food products, considering the published works in the last decade. The techno-functional properties of proteins, including water absorption capacity, emulsifying and foaming properties, gelling ability or protein solubility, are relevant factors to consider during food formulation. However, these properties are significantly influenced by the extraction technology, the type of protein and its characteristics. Overall, dry-fractionated proteins are characterized by high protein solubility, high foaming ability and foam stability, and high gelling ability. Such properties have been exploited in the development of food, such as bakery products and pasta, with the aim of increasing the protein content and enhancing the nutritional value. Additionally, innovative foods with distinctive textural and nutritional characteristics, such as meat and dairy analogues, have been developed by using dry-fractionated proteins. The results indicate that the study of these ingredients still needs to be improved, including their application with a broader range of plant materials. Nevertheless, this review could represent an initial step to obtaining an overview of the techno-functional properties of dry-fractionated proteins, facilitating their use in foods. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Lysines Acetylome and Methylome Profiling of H3 and H4 Histones in Trichostatin A—Treated Stem Cells

Trichostatin A ([R-(E,E)]-7-[4-(dimethylamino) phenyl]-N-hydroxy- 4,6-dimethyl- 7-oxo-2,4-heptadienamide, TSA) affects chromatin state through its potent histone deacetylase inhibitory activity. Interfering with the removal of acetyl groups from lysine residues in histones is one of many epigenetic regulatory processes that control gene expression. Histone deacetylase inhibition drives cells toward the differentiation stage, favoring the activation of specific genes. In this paper, we investigated the effects of TSA on H3 and H4 lysine acetylome and methylome profiling in mice embryonic stem cells (ES14), treated with trichostatin A (TSA) by using a new, untargeted approach, consisting of trypsin-limited proteolysis experiments coupled with MALDI-MS and LC-MS/MS analyses. The method was firstly set up on standard chicken core histones to probe the optimized conditions in terms of enzyme:substrate (E:S) ratio and time of proteolysis and, then, applied to investigate the global variations of the acetylation and methylation state of lysine residues of H3 and H4 histone in the embryonic stem cells (ES14) stimulated by TSA and addressed to differentiation. The proposed strategy was found in its simplicity to be extremely effective in achieving the identification and relative quantification of some of the most significant epigenetic modifications, such as acetylation and lysine methylation. Therefore, we believe that it can be used with equal success in wider studies concerning the characterization of all epigenetic modifications.     

Effect of magnetic relaxation times on electromagnetic pulseshielding

The penetration of an electromagnetic pulse (EMP) through a ferromagnetic conducting thin film is investigated for the case in which the magnetization of the material has a characteristic time delay τ. Both saturation and hysteresis effects of he magnetization are considered and the susceptibility is defined in the nonlinear region as dM/dh. It is found that the response time τ has a significant effect on the shielding factor with optimum shielding when τ is on the order of twice the rise time of the pulse     

Propagation losses in dielectric image guides

The authors calculated the propagation losses of a dielectric image guide using the effective dielectric constant (EDC) method to a higher order of approximation. It was found that there exist a minimum in the waveguide attenuation that has not been alluded to in the literature, and also a peak in the imaginary parts of the transverse propagation constant relate to dimensional resonances within the waveguide. These results imply that the propagation losses will be lowered and the fields will be more effectively confined within the waveguide at frequencies close to the cutoff     

New formulation of dyadic Green's function applied to a microstripline

We have modified the conventional two-layer dyadic Green's function analysis to include finite metal conductivity. The modified Green's function allows us to calculate the current distributions and conductor losses in microstrip circuits. A sample calculation has been applied to a microstrip line     

Nonlinear mixer gain calculations for Josephson junctions

We have numerically solved the steady-state solutions of the initial value problem associated with a current-driven Josephson weak-link junction shunted by an ohmic resistance. The nonlinear mixing action of the junction leads to Shapiro steps in the DC response with step height in units of the mixing frequency. Mixer gains have been calculated with a wide range of parameter values and intrinsic chaos is observed whenever Shapiro steps are prevalent     

AC-Hall effect in multilayered semiconductors

A new technique is presented which exploits ac-Hall effect in the characterization of layered semiconductor structures. The method involves the use of laser signals by means of optical fibers in the presence of a dc magnetic bias field. Upon incidence the polarization of the optical signal is rotated via a Lorentz force due to the ac-Hall effect. As such, the reflected waves carry informations on the Hall mobility of the charge carriers. The calculations show that ac-Hall reflection coefficient warrants sufficient intensity to be measured. Our theory is complete in the sense that depth profiling has been explicitly incorporated in the formulation