The cytotoxic and antiproliferative properties of ruthenium nitrosyl complexes and their modulation effect on cytochrome P450 in the HepG2 cell line.

Ruthenium nitrosyl complexes are actively investigated as antitumor agents. Evaluation of potential interactions between cytochromes P450 (CYPs) with new compounds is carried out regularly during early drug development. In this study we have investigated the cytotoxic and antiproliferative activities of ruthenium nitrosyl complexes with methyl/ethyl esters of nicotinic and isonicotinic acids and γ-picoline against 2D and 3D cultures of human hepatocellular carcinoma HepG2 and non-cancer human lung fibroblasts MRC-5, assessed their photoinduced activity at λrad = 445 nm, and also evaluated their modulating effect on CYP3A4, CYP2C9, and CYP2C19.

Hepatotropic activity of a betulonic acid based compound.

Using the model of cyclophosphamide (CP)-induced immunosuppression in C57BL/6 mice, the hepatotropic effects of a conjugate of betulonic acid with 9-(4-methylpiperazin-1-ylmethyl)-2-(1,2,3-triazolyl) oreozelone (BABC) have been studied. In the liver of treated animals the expression of genes for cytochromes (CYP 1A1, CYP 1A2, CYP 3A44, CYP 2B10, CYP 2C29, CYP 17A1), PPARA, and cytokines (TNF-α, IL-1β, IL-12α, IL-10) and the relative levels of NF-κB p65, GST-π, and NAT-1 proteins were determined. On day six after administration of the compound and CP to animals a significant (3.

Carbon and hydrogen dynamic isotope equations are used to describe the dominant processes of waste biodegradation: Effect of aeration in methanogenic phase of the landfill.

The sequence of microbiological processes occurring during the decomposition of fresh and old organic wastes from landfills is analyzed using the developed dynamic models, which are verified on the basis of experimental data previously obtained in anaerobic and aerobic laboratory reactors. The models are based on the material balances of the heavy and light isotopes of carbon and hydrogen during the biodegradation of cellulosic waste as a relatively poorly degradable substrate. According to the models, under anaerobic conditions, dissolved carbon dioxide is a substrate for hydrogenotrophic methanogenesis, which leads to an increase in the isotope signature of carbon in carbon dioxide and its subsequent stabilization.

Design, Synthesis and Assay of Novel Methylxanthine-Alkynylmethylamine Derivatives as Acetylcholinesterase Inhibitors.

Xanthine derivatives have been a great area of interest for the development of potent bioactive agents. Thirty-eight methylxanthine derivatives as acetylcholinesterase inhibitors (AChE) were designed and synthesized. Suzuki-Miyaura cross-coupling reactions of 8-chlorocaffeine with aryl(hetaryl)boronic acids, the CuAAC reaction of 8-ethynylcaffeine with several azides, and the copper(I) catalyzed one-pot three-component reaction (A-coupling) of 8-ethynylcaffeine, 1-(prop-2-ynyl)-, or 7-(prop-2-ynyl)-dimethylxanthines with formaldehyde and secondary amines were the main approaches for the synthesis of substituted methylxanthine derivatives (yield 53-96%).

Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in / Diabetic Mice.

mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in mice and to study inflammation dysregulation and the suitability of chitinases' expression levels as diabetes markers. Thirty-eight male mice and C57/BL mice (control) were used.

Anaerobic oxidation of methane coupled with sulphate reduction: high concentration of methanotrophic archaea might be responsible for low stable isotope fractionation factors in methane.

The changes in CH and CHH during sulphate-dependent anaerobic oxidation of methane (AOM) were described using dynamic modelling. The batch sulphate-dependent AOM at the nearly linear dynamics of methane oxidation with different enriched cultures originating from three marine sediments was simulated. The traditional Rayleigh equation for carbon and hydrogen stable isotopes in methane was derived from the basic dynamic isotope equation.

Analyzing the relationship between the cytokine profile of invasive breast carcinoma, its histopathological characteristics and metastasis to regional lymph nodes.

This study was aimed at analyzing the relations of metastasis to regional lymph nodes (RLNs) with histopathological indicators of invasive breast carcinoma of no special type (IC-NST) and its cytokine profile. Enzyme-linked immunosorbent assays were performed to determine concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A, and MCP-1 in the culture supernatant of IC-NST samples from 48 female patients. Histopathological indicators (degree of tumor cell differentiation, mitoses, and others) and ER, PR, Her2/neu, Ki-67, and CD34 expression levels were determined.

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency.

Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5'-iodolappaconitine with aryl acetylene and Mo (CO) as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines.

Effects of polyclonal activators on cell differentiation and cytokine production of cultured invasive breast carcinoma of no special type, their association with tumour histopathological parameters and lymph node metastasis.

Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples.

Using kinetic isotope effect to evaluate the significance of the sequential and parallel steps: formation of microbial consortium during reversible anaerobic methane oxidation coupled with sulfate reduction.

The purpose of this study was to describe the dynamics of anaerobic oxidation of methane (AOM) coupled with sulfate reduction (SR) using experimental data from a continuous incubation experiments published earlier in order to show that formation of consortia of anaerobic archaea (ANME) and Desulfosarcina-like bacteria (DSS) may have a significant effect on sulfur isotope fractionation. The dynamic simulation of reversible AOM by ANME coupled with SR by DSS was performed. This simulation took into account biomass growth and fractionation of stable isotopes of sulfur.

Personalized Approach to Assessing mRNA Expression of Histidine-Rich Glycoprotein and Immunohistochemical Markers in Diseases of the Breast.

Biopsy material of patients with malignant and benign breast diseases was examined. HRG mRNA expression was detected in 70% of cases in biopsy material obtained from patients with nonspecific invasive carcinoma and in 66.7% of cases in biopsy material of patients with benign breast diseases.

Modelling the specific pathway of CH and CO formation using carbon isotope fractionation: an example for a boreal mesotrophic fen.

We described mathematically the process of peat methanization in a boreal mesotrophic fen. Gaseous and dissolved CH and CO as well as their δC signatures were considered in the dynamic equations for incubation bottles. In accordance with the model, acetate, H, and CO were produced during cellulose hydrolysis and acidogenesis.

Mitochondrial Dysfunction as a Predictor and Driver of Alzheimer's Disease-Like Pathology in OXYS Rats.

Growing evidence suggests that mitochondrial dysfunction is an early event in sporadic Alzheimer's disease (AD), but the impact of mitochondrial dysfunction on the transition from healthy aging to AD remains elusive. Here we estimated the influence of mitochondrial dysfunction on the initiation of AD signs in OXYS rats, which simulate key characteristics of sporadic AD. We assessed the mitochondrial ultrastructure of pyramidal neurons of the hippocampus at the age preceding the development (age 20 days), during manifestation (4-5 months), and at the well-pronounced stages (18-24 months) of the AD-like pathology in OXYS rats.

The gene expression profile of a drug metabolism system and signal transduction pathways in the liver of mice treated with tert-butylhydroquinone or 3-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate of sodium.

Tert-butylhydroquinone (tBHQ) is a highly effective phenolic antioxidant used in edible oils and fats in foods as well as in medicines and cosmetics. TBHQ has been shown to have both chemoprotective and carcinogenic effects. Furthermore, it has potential anti-inflammatory, antiatherogenic, and neuroprotective activities.

Dynamic changes of carbon isotope apparent fractionation factor to describe transition to syntrophic acetate oxidation during cellulose and acetate methanization.

To identify predominant metabolic pathway for cellulose methanization new equations that take into account dynamics of 13C are added to the basic model of cellulose methanization. The correct stoichiometry of hydrolysis, acidogenesis, acetogenesis and methanogenesis steps including biomass is considered. Using experimental data by Laukenmann et al.

Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene.

Non-linear dynamics of stable carbon and hydrogen isotope signatures based on a biological kinetic model of aerobic enzymatic methane oxidation.

The non-linear dynamics of stable carbon and hydrogen isotope signatures during methane oxidation by the methanotrophic bacteria Methylosinus sporium strain 5 (NCIMB 11126) and Methylocaldum gracile strain 14 L (NCIMB 11912) under copper-rich (8.9 µM Cu(2+)), copper-limited (0.3 µM Cu(2+)) or copper-regular (1.

Nitrate denitrification with nitrite or nitrous oxide as intermediate products: Stoichiometry, kinetics and dynamics of stable isotope signatures.

A kinetic analysis of nitrate denitrification by a single or two species of denitrifying bacteria with glucose or ethanol as a carbon source and nitrite or nitrous oxide as intermediate products was performed using experimental data published earlier (Menyailo and Hungate, 2006; Vidal-Gavilan et al., 2013). Modified Monod kinetics was used in the dynamic biological model.

Filaggrin mutations in a Western siberian population and their association with atopic dermatitis in children.

We determined the frequencies of null mutations of the FLG gene--2282del4, R501X, R2447X, 3702delG, S3247X, and the 12-repeat allele (rs12730241)--among 460 Caucasians of the city of Novosibirsk, Russia. The frequency was 17.7% for rs12730241, 2.

Effect of 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate sodium on expression of GSTP1 and NQO1 genes and protein transcription factors in BALB/c mouse liver.

The study examined dynamics of the effect of novel phenol antioxidant preparation 3-(3'-tertbutyl- 4'-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on expression of antioxidant protection enzymes genes GSTP1 and NQO1 and on the content of protein transcription factors NF-κB and ATF-2 in mouse liver. Expression of GSTP1 gene decreased significantly on days 4 and 7 after per os administration of TS-13 (100 mg/kg), but increased on post-administration day 14. On days 7 and 14 post-administration, expression of NQO1 gene was significantly increased.

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

Objective: This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation.

Methods: Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis.

Fatty acids in energy metabolism of the central nervous system.

In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain.

Cytochrome P450 4F2 polymorphism in patients with liver cirrhosis.

1297C/T polymorphism of CYP4F2 gene was studied in 108 patients with chronic liver diseases. No significant correlation with predisposition to rapid liver cirrhosis was revealed without consideration for cirrhosis etiology (OR=0.93, 95% CI=0.

Effects of simvaglyzin and atorvaglyzin on the expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase in rat liver.

Activity and levels of protein and mRNA of 3-hydroxy-3-methyl-glutaryl-CoA reductase were estimated in rat liver after the administration of atorvastatin and simvastatin and their complexes with glycyrrhizic acid (atorvaglyzin and simvaglyzin). The amount of 3-hydroxy-3-methyl-glutaryl-CoA reductase protein in rats decreased by 13 and 25% (p<0.05) 24 h after treatment with atorvaglyzin and simvaglyzin, respectively.