Vol 19, No 5 (2021)

A wide range of diseases: stroke, Alzheimer’s disease, brain injury, etc., is based on cerebral hypoperfusion. Vascular dementia, which is the equivalent of cerebral hypoperfusion, is one of the most common cognitive disorders in older people following Alzheimer’s disease. Physical activity is an integral component of rehabilitation measures for ischemic stroke and vascular dementia - widespread, socially essential diseases. The aim of the review is to summarize current data on the cellular mechanisms that underlie the brain effects of physical activity outside the paradigm of an enriched environment in experimental cerebral hypoxia. The materials were the results of relevant studies by domestic and foreign authors and their own published data over the past 30 years, from 1990 to 2020. The article summarizes current data demonstrating the effect of physical activity during cerebral hypoperfusion, mainly during the chronic phase of the bilateral occlusion model of common carotid arteries as an adequate model of cerebral hypoperfusion. The following physical activity targets were considered: neurogenesis, neuronal apoptosis, neurotrophins, BDNF, IGF-I, VEGF, synaptophysin, NO-mediated effects, oxidative stress, angiogenesis, cerebrovascular reactivity, structures of the blood-brain barrier, endothelial phase, leukemia, astrocytes, oligodenrogliocytes, microglia phenotype.

Introduction. Under the influence of glioma cells, peritumoral zone astrocytes may acquire tumorigenic phenotype, particularly due to the suppression of immunocompetent cells. The aim of the study. Investigate the changes in the gene expression profile of glioma-conditioned rat astrocytes and the impact of conditioned astrocyte cellular extracts (lysates) on dendritic cell maturation. Methods. We compared glioma-conditioned astrocytes with C6 glioma cells or native astrocytes. Astrocyte conditioning was achieved by indirect co-culturing of native astrocytes with C6 glioma cells. The expression profile was assessed with real-time PCR. The phenotype of dendritic cells pulsed with extracts of glioma-conditioned astrocytes, C6 glioma cells and native astrocytes was studied with flow cytometry and ELISA. Dendritic cells were also used for rat immunization. We measured serum interferon-γ dynamics and cytokine production (interferon-γ, interleukins 4 and 10) by mononuclear cells of immunized rats. Results. Conditioned astrocytes showed a tendency to upregulation of interleukin 6 mRNA. They also demonstrated lower expression of PDGFB chain mRNA. Glioma cells expressed higher levels of nestin, GFAP, and CD44 mRNA. CCL2 chemokine mRNA was expressed at lower amounts in glioma cells and glioma-conditioned astrocytes. Dendritic cells pulsed with extracts of conditioned astrocytes yielded a lower increase of serum and mononuclear-derived interferon-γ after rat immunization. These dendritic cells exposed less CD11b/c but produced more interleukin 12 in comparison. Conclusion. The findings suggest that astrocytes may undergo phenotype transformation under the influence of glioma cells and obtain traits different from glioma cells or native astrocytes and similar to both cellular types at the same time

Introduction. Single nucleotide polymorphisms rs34643859 of the KCNS1 gene, rs12804550 of the SCN4B gene, and rs4514993 of the SCN11A gene were revealed in the analysis of the results of whole exome sequencing of a group of young man died by sudden cardiac death (SCD). The aim of the study is to verify single nucleotide polymorphisms rs34643859, rs12804550, rs4514993 as SCD markers in a case-control study using routine molecular genetic methods and investigate the association with SCD of single nucleotide polymorphisms rs34643859, rs12804550, rs4514993. Methods. SCD group (n=400, average age of the deceased cases acoounted for 53.2+8.7 years, the proportion of men - 70.9%, women - 29.1%) was formed using the SCD criteria of the European Society of Cardiology from the anonymous DNA bank of the deceased sudden death (1999-2019). The control group (n=400, mean age - 53.1+8.3 years, men - 68.3%, women - 31.7%) was matched by sex and age to the SCD group from DNA banks of international projects MONICA and HAPIEE of living at the time of researches participants. Genotyping was carried out using the polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Results. There were no statistically significant differences in the frequencies of genotypes and alleles of single nucleotide polymorphisms rs12804550, rs4514993 between the SCD group and the control group (p>0.05). In the group of women under the age of 50 years, there was a statistically significant decrease in carriers of the TTgenotype rs34643859 in the SCD group (32.3%) compared with the control group (60.0%) (TTvs TC + CC: 0R=0.32, 95% CI: 0.11-0.91, p=0.04). Conclusion. The association of single nucleotide polymorphisms rs12804550 of the SCN4B gene, rs4514993 of the SCN11A gene with SCD has not been confirmed. Single nucleotide polymorphism rs34643859 of the KCNS1 gene is associated with SCD: for women under 50 years of age, the TT polymorphism genotype is associated with a protective effect against SCD.

Introduction: Urate nephrolithiasis is a common form of urolithiasis. The development of new methods for pharmacological correction of this disorder requires their practical laboratory assessment. So far, it is necessary to determine the most typical biochemical and histological signs of pathology. Aim: to study the biochemical and morphological features of experimental urate nephropathy. Methods: the experiment was carried out on 25 male Wistar rats weighing 200-330 grams, randomized into a group of intact rats (10 animals) and a control group (15 animals), in which a mixture of oxonic and uric acids was administered daily for 21 days to simulate urate nephrolithiasis. The excretion of uric acid and creatinine, the activity of lactate dehydrogenase and γ-glutamyl transferase were determined weekly in the urine of rats. At the end of the three weeks of the experiment, the indices of free radical oxidation (concentration of thiobarbiturate-reactive products, total prooxidant and total antioxidant activity, catalase, superoxide dismutase, glutathione peroxidase activity) were determined in the kidneys of rats and a morphological study was performed. Results: In intact rats, the activity of lactate dehydrogenase and γ-glutamyl transferase was stable, and in the control group, by day 21, the activity of lactate dehydrogenase increased by 6.3 times relative to the initial level and 3.8 times compared with the group of intact rats. The activity of γ-glutamyl transferase decreased by 2.6 and 3.4 times, respectively. In the control group, the concentration of thiobarbiturate- reactive products and the total antioxidant activity increased relatively in intact rats (by 3.3 times and 1.8 times, respectively), while the catalase activity was reduced by 5.1 times. Urate deposits were absent in intact rats’ kidneys. In the control group, urate deposits were detected in 76.9% of cases, their average amount was 4.2±0.8 in the field of view, and their average size was 1340.5±211.1 μm2. Conclusion: the histopathological picture of experimental urate nephropathy is characterized by increase in lactate dehydrogenase activity and decrease in γ-glutamyl transferase activity in urine, the oxidative stress and urate deposits in the kidneys

Background: The aim of this study was to investigate individual changes ofprotein expression in atherosclerotic plaques of coronary arteries at different stages of development of coronary atherosclerosis. Methods: The research object was homogenates of atherosclerotic plaques from coronary arteries at different stages of development (stable atherosclerotic plaques and unstable necrotic-dystrophic atherosclerotic plaques). The plaque proteins were separated by two-dimensional electrophoresis and the gel images were analyzed using PDQuest software. The amount ofprotein was determined in relative units of the intensity of staining of protein spots. The identification of protein fractions was based on peptide mass mapping by matrix-activated laser desorption ioniz.ation (MALDI). Results: Groups of proteins were identified whose expression differed more than 1.5-fold among the three stages of atherosclerotic-plaque development. At the stage of lipidosis and fibrosis in the stable plaque, the amounts of the following proteins were increased: actins, tubulin, tropomyosin, and keratin. At the fibrosis-and-calcinosis stage of the stable atherosclerotic plaque, we noted upregulation of the following proteins: microfibril-associated glycoprotein 4, mimecan, annexin A5, and peroxiredoxin-2. The unstable-plaque stage of the dystrophic necrotic type was characterized by overexpression of serum albumin, fibrinogen, serum amyloid (P component), and vimentin. Conclusion: Possible patterns of changes in protein expression were founded among three stages of development of atherosclerotic plaques of the coronary arteries when comparing individual gels and pools of homogenates of atherosclerotic plaques.