Search

Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium.

The gasotransmitter hydrogen sulfide (H2S) produced by the transsulfuration pathway (TSP) is an important biological mediator, involved in many physiological and pathological processes in multiple higher organisms, including humans. Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) enzymes play a central role in H2S production and metabolism. Here, we investigated the role of H2S in learning and memory processes by exploring several Drosophila melanogaster strains with single and double deletions of CBS and CSE developed by the CRISPR/Cas9 technique. We monitored the learning and memory parameters of these strains using the mating rejection courtship paradigm and demonstrated that the deletion of the CBS gene, which is expressed predominantly in the central nervous system, and double deletions completely block short- and long-term memory formation in fruit flies. On the other hand, the flies with CSE deletion preserve short- and long-term memory but fail to exhibit long-term memory retention. Transcriptome profiling of the heads of the males from the strains with deletions in Gene Ontology terms revealed a strong down-regulation of many genes involved in learning and memory, reproductive behavior, cognition, and the oxidation–reduction process in all strains with CBS deletion, indicating an important role of the hydrogen sulfide production in these vital processes.

In this paper, Er:Y2O3 optical ceramics were fabricated and details of the synthesis were presented. The spectral–luminescent properties of Er3+:Y2O3 optical ceramics were investigated. The absorption and emission cross-section spectra were determined. The luminescence kinetics at near 1.6 µm was single exponential and the lifetime of erbium 4I13/2 energy level was determined. In the frame of the conventional Judd–Ofelt theory, the emission properties of the energy levels of erbium 4I13/2 and 4I11/2 involved in laser operation at near 1.6 µm were calculated. The gain coefficient curves for typical values of the relative population of the upper laser level 4I13/2 were presented. The composition and structure were studied using the SEM, XRD, FTIR spectroscopy, and X-ray computer tomography techniques.

Platelet aggregation causes various diseases and therefore challenges the development of novel antiaggregatory drugs. In this study, we report the possible mechanism of platelet aggregation suppression by newly synthesized myrtenol-derived monoterpenoids carrying different heteroatoms (sulphur, oxygen, or nitrogen). Despite all tested compounds suppressed the platelet aggregation in vitro, the most significant effect was observed for the S-containing compounds. The molecular docking confirmed the putative interaction of all tested compounds with the platelet’s P2Y12 receptor suggesting that the anti-aggregation properties of monoterpenoids are implemented by blocking the P2Y12 function. The calculated binding force depended on heteroatom in monoterpenoids and significantly decreased with the exchanging of the sulphur atom with oxygen or nitrogen. On the other hand, in NMR studies on dodecyl phosphocholine (DPC) as a membrane model, only S-containing compound was found to be bound with DPC micelles surface. Meanwhile, no stable complexes between DPC micelles with either O- or N-containing compounds were observed. The binding of S-containing compound with cellular membrane reinforces the mechanical properties of the latter, thereby preventing its destabilization and subsequent clot formation on the phospholipid surface. Taken together, our data demonstrate that S-containing myrtenol-derived monoterpenoid suppresses the platelet aggregation in vitro via both membrane stabilization and blocking the P2Y12 receptor and, thus, appears as a promising agent for hemostasis control.

Integrin-dependent adhesion of neutrophils to tissue, accompanied by the development of neutrophil-induced inflammation, occurs both in the focus of infection and in the absence of infection in metabolic disorders such as reperfusion after ischemia, diabetes mellitus, or the development of pneumonia in patients with cystic fibrosis or viral diseases. Hyaluronic acid (HA) plays an important role in the recruitment of neutrophils to tissues. 4-methylumbilliferon (4-MU), an inhibitor of HA synthesis, is used to treat inflammation, but its mechanism of action is unknown. We studied the effect of 4-MU on neutrophil adhesion and concomitant secretion using adhesion to fibronectin as a model for integrin-dependent adhesion. 4-MU reduced the spreading of neutrophils on the substrate and the concomitant secretion of granule proteins, including pro-inflammatory components. 4-MU also selectively blocked adhesion-induced release of the free amino acid hydroxylysine, a product of lysyl hydroxylase, which can influence cell invasion by modifying the extracellular matrix. Finally, 4-MU inhibited the formation of cytonemes, the extracellular membrane secretory structures containing the pro-inflammatory bactericides of the primary granules. The anti-inflammatory effect of 4-MU may be associated with the suppression of secretory processes that ensure the neutrophil invasion and initiate inflammation. We suggest that HA, due to the peculiarities of its synthesis, can promote the release of secretory carriers from the cell and 4-MU can block this process.

Specific inhibitors of mitochondrial 2-oxoglutarate dehydrogenase (OGDH) are administered to animals to model the downregulation of the enzyme as observed in neurodegenerative diseases. Comparison of the effects of succinyl phosphonate (SP, 0.02 mmol/kg) and its uncharged precursor, triethyl succinyl phosphonate (TESP, 0.02 and 0.1 mmol/kg) reveals a biphasic response of the rat brain metabolism and physiology to increasing perturbation of OGDH function. At the low (TE)SP dose, glutamate, NAD+, and the activities of dehydrogenases of 2-oxoglutarate and malate increase, followed by their decreases at the high TESP dose. The complementary changes, i.e., an initial decrease followed by growth, are demonstrated by activities of pyruvate dehydrogenase and glutamine synthetase, and levels of oxidized glutathione and citrulline. While most of these indicators return to control levels at the high TESP dose, OGDH activity decreases and oxidized glutathione increases, compared to their control values. The first phase of metabolic perturbations does not cause significant physiological changes, but in the second phase, the ECG parameters and behavior reveal decreased adaptability and increased anxiety. Thus, lower levels of OGDH inhibition are compensated by the rearranged metabolic network, while the increased levels induce a metabolic switch to a lower redox state of the brain, associated with elevated stress of the animals.

Background. Heart valve bioprostheses made from glutaraldehyde-treated bovine and porcine pericardia are widely used in open and transcatheter valve surgeries. However, the glutaraldehyde cross-linkage leads to bioprosthetic calcification in many patients. Epoxides are advantageous alternatives to glutaraldehyde, since they engender the biomaterial with better calcification resistance. The cross-linking features of an epoxy compound depend on its chemical structure and have not been fully studied so far. Aim. The study is aimed at comparing the effectiveness and molecular mechanisms of biomaterial treatment using diepoxide vs pentaepoxide compounds. Methods. We studied the stability of diepoxide and pentaepoxide in water and aqueous buffered solutions, as well as the amino acid composition, type of epoxide links with collagen matrix (infrared spectroscopy) and mechanical properties of bovine and porcine pericardia treated with 5% diepoxide, a mixture of 2% diepoxide and 1% pentaepoxide, and with alternating 5% diepoxide and 2% pentaepoxide treatments. Results. Diepoxide and pentaepoxide are both stable in aqueous buffer solutions (pH 7.4). Diepoxide provides high linkage density in bovine and porcine pericardia due to reactions with the amino groups of the OHLys, Lys, His, and Arg residues, and the hydroxyl groups of OHPro, Ser, and Tyr, while pentaepoxide reacts only with Met. Pentaepoxide enhances the strength and elasticity of the xenopericardium. Specimens consecutively treated with diepoxide and pentaepoxide were significantly thinner and featured the highest maximal tensile stress, maximal strain and elastic modulus in comparison with tissues treated with 5% diepoxide and diepoxide-pentaepoxide mixture. Conclusion. The alternating diepoxide-pentaepoxide combination for biomaterial cross-linking is a promising trend for bioprosthetic pericardium treatment.

This report was prepared by the staff of the Institute for Economic Forecast of the Russian Academy of Sciences and the Financial University under the Government of the Russian Federation. It gives suggestions to implement priority measures to facilitate the transfer the Russian economy to the direction defined by the Decree of the President of the Russian Federation (est. May 7, 2018). The report also highlights priority directions of the economic policy, primarily in investment activity, development of the domestic market, as well as financial and organizational support for the suggested actions.

Imidazoline receptor agonists are one of the groups of contemporary antihypertensive drugs with the pleiotropic cardiovascular effects. In this review, the historical, physiological, pathophysiological aspects concerning imidazoline receptor agonists and possible mechanisms for their participation in endothelioprotection were considered. Illuminated the molecular biology of each subtype of imidazoline receptors and their significance in the pharmacological correction of cardiovascular disease. IR type 1 are localized in the brain nucleus, carrying out the descending tonic control of sympathetic activation, as well as in the endothelial cells of the vessels and kidneys. Their activation leads to a decrease in blood pressure, slowing the remodeling of the vascular wall and increasing sodium nares. IR type 2 is expressed predominantly in the adrenal gland, fat and muscle tissues. The physiological effects of their stimulation are associated with an increase in glucose utilization by peripheral tissues. IR type 3 are mainly present in pancreatic cells and are associated with the regulation of insulin secretion. Their stimulation leads to an increase in insulin liberation. Thus, IR agonists are able to improve endothelial function through various mechanisms, including blood pressure reduction, improvement in metabolic profile, and direct positive effects on the vascular wall. Current information on the pharmacological effects of this group compounds allows us to conclude that they are a promising group for correcting endothelial dysfunction and complications associated with it.

Introduction: The importance of the problem of endothelial dysfunction makes it essential to improve approaches to its evaluation. Due to the high diagnostic potential of ultrasound dopplerography, this method is promising in the study of endothelial function. Objective:To study endothelial function when conducting vascular pharmacological tests in the norm and with the blockade of the nitric oxide synthesis by means of the ultrasound method for examining the central blood flow velocity in the femoral artery of the rat in comparison with changes of systemic haemodynamics and microcirculation velocity in the medial vastus muscle using laser Doppler flowmetry. Materials and methods: In the norm and in conditions of deficiency of endogenous nitric oxide, three methods for assessing haemodynamics were used simultaneously: 1) dopplerography using the ultrasoundDoppler system (Minimax-Doppler-K, St Petersburg); 2) laser doppler flowmetry using the TDS144 sensor (Biopac MP-150, USA); 3) recording the arterial pressure in the carotid artery by means of a catheter connected to a TDS-160-A sensor (Biopac MP-150, USA). To study the vasoregulatory function of the endothelium under conditions of multicomponent monitoring of haemodynamics, functional vascular tests were performed using acetylcholine and sodium nitroprusside. Results: Quantification of endothelial dysfunction when conducting pharmacological tests with endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation is most significant when calculating the coefficient reflecting the ratio of areas of vascular response. Theblood flow velocity parameters recorded by using Doppler ultrasound showed a high correlation level with both arterial pressure and with a linear microcirculation rate. The most comprehensive dopplerographic indices for evaluating the function of the endothelium by conducting pharmacological tests in the norm and in the case of pathology, are the estimated systolic-diastolic difference in blood flow velocities (ΔVs-Vd) in the femoral artery. The study of the endothelial function when conducting vascular pharmacological tests in the norm and with nitric oxide synthesis blockaded, by means of the ultrasound examination of the central blood flow velocity in the femoral artery, is comparable to changing the haemodynamics parameters as well as velocity in microcirculation of the medial vastus muscle using laser Doppler flowmetry. Conclusions: Ultrasonic dopplerography using the Minimax-Doppler-K device reflects the systemic and local vascular response to the administration of vasodilators both in the norm and with the blockade of the nitric oxide synthesis and makes it possible to conduct an informative assessment of the endothelial function.

Topic. The article examines the problems associated with forecasting of the development prospects of the economy.Purpose. The creation of a model used to predict the replenishment of budgets of all levels. Analysis of the state of the Russian economy in general and its 85 re gions.Methodology. The research was conducted on the basis of economic and statistical techniques, system analysis, and scientific methods of comparison and mapping. The work applied the proposed the authors the term “macroeconomic production function” — an analog of the production function, which expresses the dependence of production results of the enterprise and factors of production. We used data on tax revenues for all kinds of taxes, employment and gross regional product contained in consolidated informationanalytical system of regional tax revenues “Taxes of Russia”. Data analysis and estimation of parameters was performed using the programs of statistical data processing — IBM SPSS Statistics 20. In the multiple regression procedure of SPSS it was used methods of inclusion, allowing step-by-step selection in a regression equation only the significant independent variables.Results. Based on the proposed model, we conducted the comparison of actual and estimated values of tax revenues for all the subjects of the Russian Federation in 2011 and 2014. We obtained the values of point estimates of the model parameters of macroeconomic production functions. Further, we provided simulation of the values of tax revenues for all the subjects of the Russian Federation for 2014 year. Next, we compared the actual and calculated (from the model) values of tax revenues. Finally, we present the results of comparing the actual and estimated (from the model) values of tax revenues for all the subjects of the Russian Federation for 2014 year. Conclusions. The dependence of tax revenues from the factor of labor productivity is constant for every year. With the growth of capital, the amount of tax incomes of subjects of the Russian Federation was threefold higher than increase in productivity of labor. It can be used for planning of economic development of regions.