Distinct Pharmacological Properties of Gaseous CO and CO-Releasing Molecule in Human Platelets

Carbon monoxide (CO)—gaseous or released by CO-RMs—both possess antiplatelet properties; however, it remains uncertain whether the mechanisms involved are the same. Here, we characterise the involvement of soluble guanylate cyclase (sGC) in the effects of CO—delivered by gaseous CO–saturated buffer (CO_G) and generated by CORM-A1—on platelet aggregation and energy metabolism, as well as on vasodilatation in aorta, using light transmission aggregometry, Seahorse XFe technique, and wire myography, respectively. ODQ completely prevented the inhibitory effect of CO_G on platelet aggregation, but did not modify antiplatelet effect of CORM-A1. In turn, CO_G did not affect, whereas CORM-A1 substantially inhibited energy metabolism in platelets. Even though activation of sGC by BAY 41-2272 or BAY 58-2667 inhibited significantly platelet aggregation, their effects on energy metabolism in platelets were absent or weak and could not contribute to antiplatelet effects of sGC activation. In contrast, vasodilatation of murine aortic rings, induced either by CO_G or CORM-A1, was dependent on sGC. We conclude that the source (CO_G vs. CORM-A1) and kinetics (rapid vs. slow) of CO delivery represent key determinants of the mechanism of antiplatelet action of CO, involving either impairment of energy metabolism or activation of sGG.     

Fat Distribution and Lipid Profile of Young Adults with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Enzyme Deficiency

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case–control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18–31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m², p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m², p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m², p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m², p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m², p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m², p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = −0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.     

Strategies To Design Selective Histone Deacetylase Inhibitors

This review classifies drug-design strategies successfully implemented in the development of histone deacetylase (HDAC) inhibitors, which have many applications including cancer treatment. Our focus is on especially demanded selective HDAC inhibitors and their structure-activity relationships in relation to corresponding protein structures. The main part of the paper is divided into six subsections each narrating how optimization of one of six structural features can influence inhibitor selectivity. It starts with the impact of the zinc binding group on selectivity, continues with the optimization of the linker placed in the substrate binding tunnel as well as the adjustment of the cap group interacting with the surface of the protein, and ends with the addition of groups targeting class-specific sub-pockets: the side-pocket-, lower-pocket- and foot-pocket-targeting groups. The review is rounded off with a conclusion and an outlook on the future of HDAC inhibitor design.     

Assessment of technological attributes of autochthonous starter cultures in Turkish dry fermented sausage (sucuk)

The study aims to evaluate the technological properties of autochthonous strains (Lactobacillus sakei S15, Lactobacillus plantarum S24, L. plantarum S91, Pediococcus pentosaceus S128b and Staphylococcus carnosus G109) in Turkish dry fermented sausage (sucuk). After 24 h of fermentaPtion, all lactic acid bacteria strains reduced the pH to below 5.0, while the pH in the control group was above 5.3. The number of lactic acid bacteria strains reached 10⁸–10⁹ cfu g⁻¹ during fermentation. Staphylococcus carnosus G109 remained at the inoculation level of 10⁶ cfu g⁻¹ during ripening. Lactobacillus sakei S15 as mono-culture showed higher TBARS values compared to other strains. The control group had the lowest L* value and autochthonous strains caused no significant difference for a* value. According to principal component analysis results, most volatile compounds were positively correlated with the group containing only L. sakei S15.     

Prediction of fish quality level with machine learning

In this study, sea bream, sea bass, anchovy and trout were captured and recorded using a digital camera during refrigerated storage for 7 days. In addition, their total viable counts (TVC) were determined on a daily basis. Based on the TVC, each fish was classified as ‘fresh’ when it was <5 log cfu per g, and as ‘not fresh’ when it was >7 log cfu per g. They were uploaded on a web-based machine learning software called Teachable Machine (TM), which was trained about the pupils and heads of the fish. In addition, images of each species from different angles were uploaded to the software in order to ensure the recognition of fish species by TM. The data of the study indicated that the TM was able to distinguish fish species with high accuracy rates and achieved over 86% success in estimating the freshness of the fish species tested.     

DFTMicroagg: a dual-level anonymization algorithm for smart grid data

International Journal of Information Security - The introduction of advanced metering infrastructure (AMI) smart meters has given rise to fine-grained electricity usage data at different levels of...     

The Nucleation Effect of PbSe Additive on Bi2Sr2CaCu2Oδ Glass Ceramics

Glass and Ceramics - The crystallisation kinetics and effects of doping on Bi2Sr2CaCu2Oδ (BSCCO) glass ceramic system with 0.0%, 0.1%, 0.3% and 0.5% PbSe were investigated in this study....