Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs in existence. However, they can cause numerous side effects. Therefore, it is crucial to develop approaches to reducing the severity of their side effects. The purpose of this study is to investigate the effect of mexidol on the anti-inflammatory activity of NSAIDs, such as selective cyclooxygenase (COX)-2 inhibitor etoricoxib and non-selective COX inhibitor diclofenac sodium. Materials and methods. Effect of a single oral dose of the drugs was evaluated in rats and mice with carrageenan-induced edema by measuring the severity of edema over a period of 4 and 6 hrs, respectively. Results. Diclofenac sodium at doses of 1 and 10 mg/kg exhibits a dosedependent antiexudative effect, the effect of etoricoxib at these doses is comparable, mexidol at a dose of 25 mg/kg does not exhibit an antiexudative effect. In mice, the effect of a combination of diclofenac sodium at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is non-inferior to diclofenac sodium at a dose of 10 mg/kg and superior the effect of diclofenac sodium at a dose of 1 mg/kg. In rats, the combination of diclofenac sodium and mexidol significantly reduces the severity of edema at 4 hrs after its induction compared with diclofenac sodium at a dose of 1 mg/ kg only. In mice, a combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is more effective than etoricoxib at doses of 1 and 10 mg/kg. In rats, etoricoxib at a dose of 10 mg/kg and the combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg have a comparable effect. Conclusion. Mexidol at a low dose (25 mg/kg) enhances the antiexudative effect of diclofenac sodium and etoricoxib. And, therefore, a decrease in the dose of NSAIDs in combination with mexidol will help to reduce the side effects of these drugs.

Music with embedded binaural beats (BBs) is promising non-invasive tools for insomnia treatment. This work tests the hypothesis of “entrainment” effect of that kind of music on human EEG rhythm as physiological mechanism of sleep improvement. The spectrum of auditory steady state response has been compared in the group of 21 subjects during daytime sleep onset, with music embedded with BBs of 2 Hz and 4 Hz (stimulus condition) and without any stimulus (control condition). Significant difference in auditory steady state response power has been found between conditions at 14 Hz (“sleep spindle” frequency). However, no significant difference has been found at frequencies 2 Hz and 4 Hz embedded to add somnogenic feature to the music stimulus according to hypothesis tested. The results obtained do not support the hypothesis of “entrainment” effect of the stimulus examined on sleep; yet they support conclusion made in the previous authors’ paper that it improves daytime sleep quality.

For the diagnosis of many humans, animals and plant diseases, environmental monitoring, highly sensitive, specific, fast and easy-to-use diagnostic methods for the detection of nucleic acids of pathogens are required. Alternative to the PCR method, which requires expensive laboratory equipment, approaches based on the use of the natural ability of bacterial CRISPR/Cas9 systems to recognize DNA sequences with high specificity under isothermal conditions. The development of methods for signal registration during the formation of a DNA/RNA/Cas9-protein complex is a separate bioengineering task. In this work, we have designed and studied the applicability of a biosensor system based on a combination of the ability of dCas9-proteins to bind to target DNA sequences (without cutting them) and the capabilities of reporter split-enzymes for detecting spatial colocalization of protein complexes. Using molecular modeling methods we determined possible mutual positions of two dCas9-proteins at the target locus of genomic DNA, which allow optimal interaction of the domains of the split-enzyme attached to them. The optimal distances between the DNA binding sites of dCas9-proteins in different orientations were determined; the dependence of the system structure on the distance between the binding sites of dCas9-proteins was modeled. The genomes of a number of bacteria and viruses (including SARS-CoV-2) have been analyzed using bioinformatics methods, the possibility of targeting the dCas9-protein pairs to specific genomic loci in optimal positions has been shown. The possibility of using dCas9-proteins from various bacteria differing by PAMsequences was analyzed. Our results indicate the conceptual possibility of creating highly specific biosensors of nucleic acids based on a combination of CRISPR/Cas9 technologies and enzymatic protein split systems.

Clones of two morphotypes corresponding to two species of pennate araphids diatoms, Ulnaria ulna and U. acus, were isolated from samples taken in Europe. Clonal cultures entered heterothallic sexual reproduction in combinations appropriate to their mating types. Following the concept of biological species, we tested reproductive compatibility between all representatives of geographically distant populations. Isolated clones turned out to be reproductively compatible within the limits of each of the species, the progeny (generation F1) were viable and fertile, freely entering into backcrossing. No cases of interspecies hybridization were found. The absence of intraspecific reproductive isolation between distant populations in these two species suggests that the populations of both U. ulna and U. acus are conspecific.

Birds acquired endothermy and four-chambered heart independently from mammals in the course of evolution. Though avian embryos are widely used in experiments, little is known about adult avian heart. Recent studies have shown that despite of big evolutionary distance, the set of repolarizing potassium currents in avian myocardium resembles that in mammalian heart as well as in humans. That allows to propose birds as a potential model in experimental cardiology. The present study for the first time describes inward rectifier potassium currents in working myocardium of quail. Using patch clamp method, we recorded main background inward rectifier current I_K1 in isolated atrial and ventricular cardiomyocytes of quail. Both inward and outward components of I_K1 in ventricular cells were larger than those in atrial cells, while there were no differences in voltage dependence of inward rectification. Acetylcholine and carbachol induced activation of acetylcholine-dependent inward rectifier current I_KACh in atrial, but not in ventricular myocytes. I_KACh in atrial myocytes was sensitive to tertiapin. Constitutively active I_KACh has not been detected. In multicellular preparations of quail right atrium carbachol induced hyperpolarization and shortening of action potentials, while in preparations of right ventricle no such effects were observed. Activation of I_KACh upon application of carbachol was dose-dependent with EC₅₀=4,922∙10^-7М. The described distribution of inward rectifier currents in avian myocardium is similar to that in mammalian species, which are widely used as model objects in experimental cardiology.

Extracellular proteinase of the opportunistic Aspergillus fumigatus D-1 strain (molecular weight ~ 33 kDa, pI 4.6) was isolated. It has been shown that proteinase hydrolyzes casein, fibrin, fibrinogen, albumin, and hemoglobin to varying degrees. However, proteolytic activity in relation to globular proteins of blood plasma was comparable to fibrinolytic activity. Proteinase did not coagulate human fibrinogen, bovine fibrinogen, and also did not coagulate human and rabbit blood plasma without dilution and twice diluted. A plasminogen activating activity of A. fumigatus D-1 extracellular proteinase was found, which may indicate its ability to indirect fibrinolysis.