Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue

In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg⁻¹/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.     

Lycopene in the Prevention of Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the leading cause of human mortality worldwide. Oxidative stress and inflammation are pathophysiological processes involved in the development of CVD. That is why bioactive food ingredients, including lycopene, are so important in their prevention, which seems to be a compound increasingly promoted in the diet of people with cardiovascular problems. Lycopene present in tomatoes and tomato products is responsible not only for their red color but also for health-promoting properties. It is characterized by a high antioxidant potential, the highest among carotenoid pigments. Mainly for this reason, epidemiological studies show a number of favorable properties between the consumption of lycopene in the diet and a reduced risk of cardiovascular disease. While there is also some controversy in research into its protective effects on the cardiovascular system, growing evidence supports its beneficial role for the heart, endothelium, blood vessels, and health. The mechanisms of action of lycopene are now being discovered and may explain some of the contradictions observed in the literature. This review aims to present the current knowledge in recent years on the preventive role of lycopene cardiovascular disorders.     

Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.     

Dose Maps In/Around Target and Test Cell for DONES During the Operation

DONES (DEMO-Oriented Neutron Source) is to be constructed in order to investigate materials that are intended to be used for DEMO (DEMOnstration Power Plant) since they will be irradiated with very high fluxes of neutrons. A deuteron beam will bombard a lithium target situated in the so called Test Cell (TC) shielded with concrete. Monte Carlo simulations by means of the MCNP (Monte Carlo N-Particle) code were carried out to calculate both horizontal and vertical radiation dose maps in and around of the TC facility. Three geometrical configurations of the shielding and two kinds of concrete (ordinary and magnetite ones) were examined. For each case a spatial dose distribution and an accompanying errors map were provided. Advanced techniques of variance reduction were applied to compute doses in and outside of thick concrete walls. On the grounds of the obtained results a final configuration of the shielding was selected.     

Antifungal activity of denture soft lining material modified by silver nanoparticles-a pilot study

Soft liner materials in oral cavity environments are easily colonized both by fungi and dental plaque. These factors are the cause of mucosal infections. The microorganism that most frequently colonizes soft liner materials is Candida albicans. Colonization occurs on the surface of materials and within materials. A solution to this problem might involve modification of soft liner materials with silver nanoparticles (AgNPs). In this article, we present results showing the antifungal efficacy of silicone soft lining materials modified with AgNPs. The modification process was conducted by dissolving both material components (base and catalyst) in a colloidal solution of AgNPs and evaporating the solvent. Composites with various AgNP concentrations (10, 20, 40, 80, 120 and 200 ppm) were examined. The in vitro antifungal efficacy (AFE) of composite samples was 16.3% to 52.5%.     

Conversion of a Mono‐ and Diacylglycerol Lipase into a Triacylglycerol Lipase by Protein Engineering

Despite the fact that most lipases are believed to be active against triacylglycerides, there is a small group of lipases that are active only on mono‐ and diacylglycerides. The reason for this difference in substrate scope is not clear. We tried to identify the reasons for this in the lipase from Malassezia globosa. By protein engineering, and with only one mutation, we managed to convert this enzyme into a typical triacylglycerol lipase (the wild‐type lipase does not accept triacylglycerides). The variant Q282L accepts a broad spectrum of triacylglycerides, although the catalytic behavior is altered to some extent. From in silico analysis it seems that specific hydrophobic interactions are key to the altered substrate specificity.     

轮胎噪声与滚动阻力的相关性

低滚动阻力和低噪声是对现代轮胎的要求,其目的在于保护环境和提高车辆运行的经济性。在大多数驾驶条件下,轮胎／道路噪声是车辆行驶噪声的主要来源。社会调查显示,交通噪声环境污染对人类的影响远远大于其他任何形式的污染。轮胎滚动阻力直接影响车辆的燃油消耗,并与二氧化碳和其他废气的排放密切相关。     

A surface-enhanced Raman spectroscopy study of thin graphene sheets functionalized with gold and silver nanostructures by seed-mediated growth

We describe a simple method for decorating graphene (1–5 layers) with Au and Ag nanostructures (nanoparticles, nanorods, and nanoplates). We deposit graphene electrostatically from highly-oriented pyrolytic graphite onto Si/SiO₂ surfaces functionalized with (aminopropyl)trimethoxysilane and grow the metal nanostructures by a seed-mediated growth method from hexanethiolate-coated Au monolayer-protected cluster “seeds” that are attached to graphene by hydrophobic interactions. Scanning electron microscopy reveals the selective growth of Au or Ag nanostructures on the graphene surface. In the case of Au, the low pH 2.8 growth solution causes etching of the graphene and formation of scroll-like structures. For Ag, the high pH 9.3 solution does not seem to affect the graphene. Raman spectroscopy is consistent with the graphene morphology and reveals that the presence of Au and Ag nanostructures increases the Raman scattering from the graphene by a factor of about 45 and 150, respectively. This work demonstrates a simple method for decorating graphene with noble metal nanostructures that may have interesting optical, electronic, and chemical properties for applications in nanoelectronics, sensing, and catalysis.