In this work, we investigate the effect of a number of pharmaceutical preparations on the expression of genes, which are used as molecular targets under the conditions of debilitating physical exercise in minipigs. In the conducted experiment, the effectiveness of the following preparations was compared: “Mio-Activ-Sport” dietary supplement, a liposomal deer musk extract, intranasal insulin, and a liposomal ginseng preparation. The selected biomarkers included the leukocyte blood fraction and mRNA expression of NFE2L2 and HMGB1 genes in lymphocytes. Among the studied preparations, the liposomal deer musk extract showed the highest effectiveness. Thus, during seven days of therapy, this preparation almost completely prevented the pro-inflammatory effect of physical load. At the same time, the liposomal deer musk extract led to a manyfold increase in the expression of NFE2L2 gene, which is responsible for antioxidant defense of the organism. In terms of action, the liposomal deer musk extract outperformed insulin – the reference drug, whose protective effects are well known from the scientific literature. These findings confirm the prospects of deer musk preparations for medical rehabilitation.

Сhronic inflammation is considered as a key factor in the development of type 2 diabetes mellitus. Impaired tolerance of the inflammatory response of monocytes is regarded as an important mechanism in the pathogenesis of chronic inflammation. In this work, we study the inflammatory activation and tolerance  of the immune response of monocytes in diabetes. In total, 40 patients with newly diagnosed diabetes   and 40 control group participants were included in the study. The level of basal, LPS-stimulated and re-stimulated secretion of the TNF-α, IL-1β, and MCP-1 cytokines was assessed in a monocyte culture isolated from the blood by immunomagnetic separation of CD14+ cells. The level of basal, LPS-stimulated and re-stimulated TNF-α secretion was significantly higher in patients with diabetes; the level of IL-1β secretion did not differ significantly between the groups; basal and re-stimulated MCP-1 secretion was also significantly higher in the diabetes group. Re-stimulated secretion of TNF-α and IL-1β was reduced compared to primary-stimulated secretion in both groups, demonstrating the tolerance of the macrophage immune response to these cytokines. Re-stimulated secretion of MCP-1 in 42% of diabetes patients was higher than primary stimulated secretion, thus revealing an impaired tolerance of the immune response of macrophages. A correlation was found between TNF-α secretion and body mass index, r=0.631, p<0.001, and with glycemic level, r=0.427, p=0.037. The results obtained demonstrate inflammatory activation     of monocytes with hypersecretion of TNF-α and MCP-1, impaired tolerance of the immune response of monocytes in diabetes regarding the secretion of MCP-1, as well as a correlation of TNF-α secretion   with body mass index and glycemic level. This indicates an important role of TNF-α and MCP-1 in the pathogenesis of chronic inflammation in type 2 diabetes, thus allowing these cytokines to be considered as potential therapeutic targets for pathogenetic therapy of type 2 diabetes.

We set out to examine the indicators of microhemodynamics and tissue oxidative metabolism in rats after their tenfold exposure to extremely high-frequency low-intensity electromagnetic radiation (EHF EMR). The aim was to elucidate the specifics of skin microcirculation and tissue oxidative metabolism following exposure to tenfold electromagnetic radiation of extremely high frequency. The experiment was carried out on 40 mature male Wistar rats weighing 200–220 g, which were kept in standard vivarium conditions under natural light regimen. The animals were divided into two groups with 20 rats each. The animals in the first group were biological controls and were exposed to false EHF EMR (placebo); the animals in the second group were exposed to mm-exposure in the morning, 10 sessions daily. On the 10th day of EMR exposure, the indicators of skin tissue fluorescence on the tail base were recorded. Tenfold exposure to low-intensity EHF EMR was shown to increase the concentration and intensity of NADH fluorescence, as well as the FAD and redox ratio. This indicates an increased cellular demand for ATP and the predominance of oxidative phosphorylation over other processes, thus demonstrating the activation of the respiratory chain. At the same time, an increase in endothelium-dependent vasodilation, a decrease in peripheral resistance, an increase in blood flow to the nutritive microvascular bed, and an improvement in venular outflow were observed in the microcirculatory bed. The conclusion is made that the modulating effect of EHF EMR is manifested in the rearrangements of correlations. Thus, the coefficient of variation comes to the fore – the final calculated indicator of microcirculation, which has strong negative associations with all indicators of tissue metabolism (FAD, NADH, RR). In addition, the amplitudes of endothelial rhythms associated with periodic releasing of nitric oxide by the endothelium show a strong negative association with FAD.

In this work, we investigate the preconditioning action of various modes of pulsed magnetic field (PMF) on the blood biochemical parameters of rats exposed to adrenal toxemia. PMF was shown to trigger adaptive response; however, its rate can differ depending on the selected PMF mode. The possibility of using low-frequency PMF as a protector of stress-induced conditions caused by adrenal toxemia is demonstrated.

In this work, we set out to compare the immunogenicity of the Gam-COVID-Vac two-component vaccine produced by GENERIUM JSC (Russia) following its intranasal or intramuscular administration of the first or both components to BALB/c mice. The immunogenicity was evaluated according to antigen-specific IgG and IgA antibodies in the blood and bronchoalveolar fluid, the number of antigen-specific IFN-γ-producing T-lymphocytes, the number of antigen-specific IFN-γ-producing CD4 and CD8 T-lymphocytes. Intranasal administration was shown to induce the mucosal immunity, significantly exceeding both qualitatively and quantitatively the effect of intramuscular administration (by the number of animals with antigen-specific IgA antibodies and the titer of antibodies in blood serum and bronchoalveolar lavage). At the same time, intramuscular administration slightly exceeded the effect obtained under intranasal administration in terms of the total number of CD8-IFN-γ-producing lymphocytes.

Anthocyanins are flavonoid compounds belonging to the group of polyphenols. A. melanocarpa (Michx.) Elliott chokeberry is known to be rich in these bioactive substances. The previously conducted chemical analysis showed that an anthocyanin-containing complex obtained from A. melanocarpa fruits comprise anthocyanins, flavonoids, phenolic acids, and catechins, with anthocyanins being the dominant components. A large amount of data indicates that Aronia fruits exhibit a wide spectrum of pharmacological activity. In this work, we assess the safety of an anthocyanin-containing complex obtained from A. melanocarpa fruits by its genotoxic study followed by an analysis of its effect on mutagenesis. To this end, a model of doxorubicin-induced genotoxicity in bone marrow cells of C57Bl/6 mice was used. The plant complex under study at a dose of 225 mg/kg had no effect the cytogenetic parameters of animal bone marrow cells after a single or double administration. The use of the anthocyanin-containing complex led to a decrease in DNA damage caused by the administration of doxorubicin, 24 and 48 hours after the introduction of a cytostatic agent. Hence, the data obtained can serve as the basis for the creation of a drug corrector for cycplasms.

Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of this work was to evaluate the efficacy and safety of the drug in ischemic stroke patients in the early recovery period. In total, 160 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with a stroke duration from 3 weeks to 2 months, mean age 63.2±8.4 years, were randomized into two treatment groups. The first group (n=80) received Direkord intramuscularly at a dose of 600 mg/day for two weeks; the second group (n=80) received a placebo. Treatment response was defined as an improvement in neurological status, functional status, and cognitive function of the patients: at least a two-fold decrease in the total NIHSS score, the total Barthel score ≥ 95, and the total MoCA score ≥ 26. The analysis of the primary endpoint of the study using exact Fisher’s test showed that Direkord was statistically significantly superior to the placebo (p=0.017) in the number of patients who responded to the therapy — 23.7 and 8.7% of patients in groups, respectively. The secondary end point analysis revealed a statistically significant superiority of Direkord over the placebo in reducing neurological deficits on the NIHSS scale (p=0.004), on the Rankin scale (p=0.0357), and on the CGI-I (p<0.001) and PGI-I (p<0.001) global clinical impression scales. Direkord has a good safety profile; thus, no statistically significant differences were found with the placebo in any of the safety parameters, including the number of adverse events, vital signs, laboratory parameters, and ECG. Overall, Direkord is statistically significantly more effective than placebo in recovering function and daily activities after ischemic stroke.