Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

Impedance analysis of a phosphatidylcholine-phosphatidylethanolamine system in bilayer lipid membranes

Electrochemical impedance spectroscopy was used for the study of two-component lipid membranes. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were to be investigated, because of their presence in biological membranes. Capacitance values of pure components are 0.62 and 0.32 μF cm⁻², respectively. The 1:1 complex was formed during formation of the PC-PE lipid membrane. Formation of the complex can explain the deviation from the additivity rule. This equilibrium was described by mathematical equations and was further verified experimentally. Adequate equations let us calculate such parameters as: capacitance of the complex molecule, area occupied by the complex molecule as well as the stability constant of the complex.     

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.     

Catalytic graphene formation in coal tar pitch- derived carbon structure in the presence of SiO2 nanoparticles

A simple and effective way to manufacture graphene from a coal tar pitch (CTP) is demonstrated. Silica (SiO₂) nanoparticles were used to modify the CTP as carbon precursor. A silica nanofiller introduced into the CTP matrix underwent carboreduction during heat treatment to 2000 °C, resulting in the formation of silicon carbide. Surfaces of SiC grains were sites for graphene formation. The influence of SiO₂ on the structure and microstructure of CTP- based carbon matrix, after annealing up to 2800 °C, was studied. Carbon samples were analyzed using X- ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Raman Spectroscopy. Crystallite sizes (L_a, L_c) and interplanar distance (d₀₀₂) were determined. The presence of SiO₂ in CTP carbon precursor favored the crystallites’ growth in the ‘a′ crystallographic graphite direction, and inhibited their growth on the ‘c′ axis. The crystallites composing of graphene layers, were characterized by an elongated dimension in the ‘a′ axis direction. Above 2000 °C silicon carbide decomposed, followed by the sublimation of silicon from the carbon matrix.     

Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis

Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin–angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1–7), is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1–7) and thus favors Ang-(1–7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator, diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE^−/− mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE^−/− mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in the atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated levels of HDL in the plasma, decreased levels of triglycerides, and increased biosynthesis and concentration of taurine in the liver of apoE^−/− mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.     

Polyphenol content and antioxidative activity in apple purées with rhubarb juice supplement

The purpose of the present study was to evaluate the effect of rhubarb juice addition and peeling in apple purée production and storage on its phenolic composition, antioxidant activity and colour. The apple material used in this study was of two varieties: Sampion and Idared. The apple purées prepared in three variants (control purées, peeling purées and purées with 5% of rhubarb juice) were stored for 3 and 6 months at 30 °C. Apple purées were investigated for their antioxidant activity, change of colour and contents of phenolic compounds plus the polymer procyanidins and degree of polymerization (DP). The preparation of purées from apples without peeling and the addition of rhubarb juice during purée preparation had significant influence on polyphenol content. The purée prepared from peeled apples of Idared variety had phenolic content 2.2 times lower than the control sample (non‐peeled apples). The highest level of total polyphenols was found in Idared + rhubarb sample (129.82 mg 100 g^?1 purée). The content of this compound in Idared control sample was more than 2.8 times lower than in Idared purées with rhubarb. The use of non‐peeled Idared apples and 5% of rhubarb juice in purée preparation significantly increased polymeric procyanidins from 11.68 to 75.20 mg 100 g^?1 and other phenolics from 9.23 to 54.62 mg/100 g. This effect for Sampion apples was smaller. The procyanidins during purées storage were more stable in samples with rhubarb juice addition. The purée samples with the addition of rhubarb juice had higher antioxidant activity measured using ABTS (2,2′azinobis‐(3‐ethylbenzthiazoline‐6‐sulphonic acid)) than purée samples without the addition (two times higher for Idared variety) of rhubarb juice. After 3 and 6 months of storage at temperature 30 °C, the antioxidant capacity decreased in all purées. Rhubarb juice had only high and positive effect on L* value in the case of Idared variety. The results showed that all Sampion apple purées had higher L* values than Idared.     

Fabrication of CdSe‐Nanofibers with Potential for Biomedical Applications

The design and synthesis of nanostructured functional hybrid biomaterials are essential for the next generation of advanced diagnostics and the treatment of disease. A simple route to fabricate semiconductor nanofibers by self‐assembled, elastin‐like polymer (ELP)‐templated semiconductor nanoparticles is reported. Core–shell nanostructures of CdSe nanoparticles with a shell of ELPs are used as building blocks to fabricate functional one‐dimensional (1D) nanostructures. The CdSe particles are generated in situ within the ELP matrix at room temperature. The ELP controls the size and the size‐distribution of the CdSe nanoparticles in an aqueous medium and simultaneously directs the self‐assembly of core–shell building blocks into fibril architectures. It was found that the self‐assembly of core–shell building blocks into nanofibers is strongly dependent on the pH value of the medium. Results of cytotoxicity and antiproliferation of the CdSe‐ELP nanofibers demonstrate that the CdSe‐ELP does not exhibit any toxicity towards B14 cells. Moreover, these are found to be markedly capable of crossing the cell membrane of B14. In contrast, unmodified CdSe nanoparticles with ELPs cause a strong toxic response and reduction in the cell proliferation. This concept is valid for the fabrication of a variety of metallic and semiconductor 1D‐architectures. Therefore, it is believed that these could be used not only for biomedical purposes but for application in a wide range of advanced miniaturized devices.