Vol 20, No 1 (2022)

Among a very significant number of possible variants of posttranslational modifications (PTM) affecting the contractile function of the myocardium, the most significant effect is exerted by posttranslational phosphorylation of protein components of the contractile apparatus. This type of PTM is carried out due to the action of kinase enzymes (phosphotransferases) that catalyze the transfer of a phosphate group to amino acid residues of proteins of the contractile apparatus. A change in the phosphorylation activity leads to a change in the function of the corresponding modified protein, which is accompanied by a change in the contractile function of the entire myocardium. At the same time, the phosphorylation activity of certain contractile proteins can change both in physiological conditions and in some cardiovascular diseases (CVD), including heart failure, acute myocardial infarction and cardiac arrhythmias. In addition, with these pathological conditions, the activity of proteolytic enzymes that cause fragmentation of protein molecules significantly changes. The purpose. To systematize information about the main mechanisms of posttranslational phosphorylation and fragmentation of the cardiac troponin T (cTnT) molecule and note their importance in the pathogenesis and diagnosis of CVD. Material and methods. Analysis of the main foreign and domestic sources on PubMed/Medline, Embase, RSCI/elibrary databases over the past 30 years. Results. According to the results of the review, a significant effect of the discussed PTMs on the pathophysiology and laboratory diagnosis of CVD was shown: 1) an increase in cTnT phosphorylation is mainly accompanied by a decrease in myocardial contractile function; the level of phosphorylated cTnT molecules in blood serum may reflect the status of intracellular phosphorylation, and, accordingly, be used for diagnostic and prognostic purposes; 2) fragmentation of the cTnT molecule into smaller fragments promotes earlier release from cardiomyocytes, and by identifying these fragments using immunoassays, early diagnosis of CVD can be improved; these small cTnTfragments can also pass through a hematosalivary and glomerular filter, allowing the use of saliva and oral fluid as a non-invasively obtained biological material, 3) the cleavage of the cTnT molecule by the enzyme thrombin in the myocardium of patients sufferingfrom cardiomyopathy can be considered as an additional pathophysiological mechanism that disrupts the contractile function of the myocardium.

Introduction. Oxidative stress and mitochondrial dysfunction are observed in virtually any disease associated with premature aging. Signaling molecules produced by mitochondria can act as specific targets for the action of pharmacological agents in order to regulate the processes of cellular aging, which opens up new possibilities for the search and development of drugs for effective pharmacotherapy of age-associated pathologies conditions. The aim of the study. To study the effect of V007 on the expression of mitochondrial biomarkers in rat liver cells in vivo to elucidate the possible mechanism of its geroprotective action. Methods. Molecular biological methods were used to study the expression of key mitochondrial proteins: Tom70, Tom20, VDAC, DRP1, prohibitin, Parkin, PINK1 in liver cells of young and old rats in normal conditions and with the use of the innovative drug V007. Results. The data obtained indicate that when using the V007preparation, there is a statistically significant increase in the expression of all studied mitochondrial proteins in hepatocytes of old rats to the level of young animals: DRP1 by 1.3 times; Parkin 1.2 times; PINK11.2 times; Prohibitin 1.4 times; Tom 201.3 times; Tom 701.2 times; VDAC 1.2 times. This change in the expression of mitochondrial proteins is due to the activation of their synthesis and increased activity of the mitochondrial transport systems. Conclusion. V007has a general regulatory and geroprotective effect, being a targeted pharmacological agent that regulates the functions of hepatocytes during aging by normalizing the expression of key mitochondrial proteins.

Introduction. Buccal epithelium (BE), in which cells the expression of signal molecules reflecting the state of homeostasis of the body in normal and pathological conditions is verified, is used as a diagnostic material for a number of diseases in adults. The aim of the research was to study the circadian rhythm of melatonin receptor (MT) expression in the buccal epithelium ofpregnant women and their newborn children for the possible development of a non-invasive method for molecular prediction of delayed postnatal pathology. Methods. The MT in blood serum and receptors MT1 and MT2 in BE was studied in 13 pregnant women and their newborns on the 3rd day of life at 12.00pm and at 04.00 am. Results. The concentration of MT in the blood of healthy pregnant women (group 1) differed during the day and at night time (12.2±0.1 and 81.6±7.0 pg/ml, p<0,001, respectively). In patients with obesity and gestational diabetes (group 2), there were no circadian fluctuations in the level of MT (31.9±1.5 and 35.9±1.0 pg/ml, respectively, p>0.05). A similar pattern was also observed in newborns of both groups, but the concentration of MT in the blood was significantly lower than in mothers. The expression of MT receptors in the buccal epithelium in pregnant women of both groups had the same pattern of changes as the concentration of MT in the blood: the circadian rhythm ofMT1 and MT2 receptors expression in patients of the first group and its absence in the second group. The children of group 1 had circadian fluctuations in the expression ofMT1 and MT2, while they were absent in the second group. During the daytime in the first group, blood MT level correlated with the expression of MT2 ((R=0.5), and at night with MT1(R=0.78) and MT2 (R=0.4). In children of the second group, there were no correlation between the blood MT levels and the expression of receptors. Conclusion. The results obtained give reason to consider the use of this non-invasive method promising for predicting the risk of delayed postnatal pathology, the development of which may be associated with intrauterine disruption of the formation of the circadian rhythm of MT.

Introduction. To this date the search for new substances with antitumor activity is an urgent task of pharmacology and medicine. Carrageenans are sulfated galactans of red algae, they are promising substances for the basis of future drugs, as well as for t he creation of preventive antitumor agents. In this work, we investigated the antitumor effect of carrageenans, different in structure and molecular weight, isolated from the algae Chondrus armatus on the cell lines by colon carcinomas and colorectal carcinoma. Aim of the study: comparative study of the antitumor effect of κ- and λ-carrageenans from the red alga Chondrus armatus and their oligosaccharides on tumor cell lines RKO and HCT-116. Material and methods. Carrageenans κ- and λ- and their oligosaccharide derivatives (κ- and λ-) were derived, characterized by structure (IR spectrometry) and molecular weight (Choromatography), and tested on RKO colon carcinoma and HCT-116 colorectal carcinoma cell lines. The antitumor effect was assessed using the MTT assay-cell proliferation assay and using fluorescent cell dyes of vivo Hoechst staining and propidium iodide to stain living and dead cells. Results and discussion. According to these data, carrageenans and their oligosaccharides exhibit a pronounced inhibitory effect on the proliferation of intestinal carcinoma tumor cells. Carrageenans κ- and λ- had a significant antitumor effect at a maximum concentration of 400 μg / ml during incubation for 24 and 48 hours in the investigated cell lines of intestinal carcinomas RKO and HCT-116. Conclusion. It was shown that oligosaccharides κ- and λ-carrageenans, isolated from the red alga Chondrus armatus, exhibit a pronounced inhibitory effect on the proliferation of human intestinal cancer tumor cells, without increasing the percentage of dead cells. Consequently, these carrageenans exhibit a pronounced antitumor effect blocking cell growth

Introduction. Currently, scientists are paying increasing attention to the genetic condition of various pathologies. According to recent studies, cytokines play an essential role in the immune response in various pathological processes. The detection of genetic defects in the genes of anti-inflammatory cytokines may be accompanied by their various production and result in individual characteristics of the infectious process in carriers of polymorphic mutations. Objective of the study. To study the IL-10 gene polymorphic marker (G-1082A, C-819T) genotypes frequency in the uncomplicated course of chicken pox in conscripts of Zabaikalsky Krai. Methods. SNP genes were determined by PCR. When conducting statistical analysis, the authors were guided by the uniform requirements for manuscripts submitted to biomedical journals and the recommendations «Statistical analysis and methods in the published literature» (SAMPLE). Statistical processing of the research results was carried out using the IBM SPSS Statistics Version 25.0 software package (International Business Machines Corporation, Iicense No. Z125-3301-14, USA). Results. GA genotype of the IL-10 gene (G1082A) frequency in servicemen with chickenpox was 28 times higher compared to the healthy group (χ2=86.1, p=0.001). In turn, the GG genotype of the IL-10 gene (G1082A) was detected 3.5 times more often in healthy individuals than in patients with chickenpox (χ2=86.1, p=0.001). CT genotype of the IL-10 gene (C819T) frequency in servicemen with chickenpox was 2.4 times higher compared to the healthy group (χ2=24.0, p=0.001). In turn, the CC genotype of the IL-10 gene (C819T) was detected 2.0 times more often than in patients with chickenpox (χ2=24.0, p=0.001). Conclusion. The prevalence of genotypes GA IL-10 (G1082A) and CT of the IL-10 gene (C819T) is higher in conscripted servicemen in the Trans-Baikal Territory, which allows us to conclude that there is an association of these polymorphisms with the incidence of chickenpox. Also, according to the results, it can be assumed that the genotypes GG IL-10 (G1082A) and C of the IL-10 gene (C819T) are a protector association of polymorphisms from the incidence of chickenpox.