Vol 21, No 4 (2023)

Introduction. The study of the level of the so-called «youth proteins» TIMP-2 and irisin in diseases of the cardiovascular system is not only of theoretical interest, but also of practical importance, as it outlines new ways to treat these diseases.

Purpose of study was to summarize the literature data and also the authors presentation of proper results of a study of the changes in TIMP-2 and irisin levels and their relation to the indicators of the cardiovascular system activity, lipid metabolism, hemostasis system and sex hormones level in female hypertensive patients (HP).

Material and methods. The investigation was in women group treated with drugs (HP-1) and in women group systematically taking, over several years, at least 3 courses of kinesiotherapy (HP-2). Relatively healthy women of the same age served as the control group.

Results. TIMP-2 level was found to increase in the GB-1 group and to return to normal in the GB-2 group. Similar data were obtained for other cardiovascular diseases as well. Irisin concentration in HP-1 and HP-2 patients does not change in comparison to the control group.

Conclusion. Literature data on irisin content in case of cardiovascular diseases are contradictory. However the authors of this study found the relationships in the control group, in HP-1 and HP-2 patients, between the levels of TIMP-2 and irisin, on the one hand, and cardiovascular system functions, as well as values of lipid spectrum, hemostasis, and sex hormones, on the other.

Introduction. Currently, clinical diagnosis of myocarditis is a difficult task. The diagnosis of the disease is made on the basis of category IV criteria, which include data of electrocardiography, Holter monitoring, echocardiography and MRI, laboratory biomarkers of necrosis, inflammation and heart failure, morphological study of endomyocardial biopsy specimens.

Objective. To analyze literature data on the potential of different miRNAs determination for diagnostics of myocarditis.

Material and methods. Literature search was carried out in Google Scholar for the last 15 years.

Results and discussion. miR-208b in blood mononuclear and cardiac tissues can be considered as a promising marker for myocarditis diagnosis, and circulating miR-27b-3p, miR-126-3p, miR-142- 5p and miR-143-3p for DCM diagnosis. The presence of miR-15b-5p and miR-106a-5p in plasma allows us to distinguish between patients with ischemic and idiopathic DCM. Acute viral myocarditis is characterized by the presence of miR-208b and miR-499-5p in cardiac tissues, while fulminant myocarditis is characterized by increased levels of circulating miR-30a, miR-192, miR-146a, miR-155 and miR-320a. It should be noted that no specific miRNAs for chronic myocarditis have been found.

Introduction. The review is devoted to the analysis of modern concepts of the neurodegenerative properties of depression. Depression is now regarded as the most common mental illness with significant social consequences.

The aim of the study is to determine the pathogenetic role of changes in the metabolism of neurotransmitters and an excess amount of excitatory transmitters in the implementation of the mechanisms of neuronal plasticity disorders in depressive states, leading to the formation of neurodegenerative changes.

Material and methods. The scientific literature was searched in the National Library of Medicine (ncbi), PubMed, e-library databases mainly for the last decade. An analysis of the literature data of domestic and foreign sources was carried out using the deconstruction method, aspect analysis, as well as a descriptive method that allows one to be based on «descripts» (depression, neurodegeneration, neuronal plasticity, neurotrophins, neuropeptides), focusing on the most important aspects of the object of study.

Results and discussion. The role of pro-inflammatory cytokines, hormones, neurotrophins, neuropeptides in the implementation of the pathogenetic mechanisms of depressive disorder is described. It should be noted a number of advantages of neuropeptides as endogenous regulators of the functioning of the central nervous system, manifested in high physiological activity, the presence of several binding groups for different cell receptors, the regulatory ability to express other signaling molecules, the minimum half-life, the absence of most side effects, the ability to penetrate through the blood-brain barrier, as well as the manifestation of trophic, anti-inflammatory, growth, mediator and effector properties, which leads to a high interest in endogenous peptide compounds and their synthetic analogues as promising therapeutic agents. The lack of a unified theory of the development of depression definitely contributes to an active research interest, which in recent years has been directed to the search for more accurate biological markers of the disease and new therapeutic agents, using innovative achievements in the synthesis of new compounds, as well as the use of agents that have proven their effectiveness and safety.

Despite significant advance in clear cell renal cell carcinoma treatment, immune checkpoint inhibitors (ICIs) still have limited therapeutic efficacy. Taking into account the resistance to immunotherapy, observed in malignant neoplasms, the search for predictive markers of response to ICI therapy in patients with clear cell renal cell carcinoma (ccRCC) is under active investigation. Recent scientific studies demonstrate that exosomal miRNAs are key modulators of tumor signaling and determinants of the tumor microenvironment. Dysregulation of miRNAs can affect the immunogenicity of ccRCCs and response to ICI therapy, making them attractive as predictive molecular genetic biomarkers and targets for potential therapeutic developments.

The aim of the study was to evaluate the expression levels of exosomal miRNAs-424,-503,-885,-149 in ccRCC patients who received ICI therapy.

Material and methods: The study included 42 patients from whom venous blood samples were taken before and after ICI therapy. Expression analysis was performed by quantitative real-time PCR.

Results: For miRNA-424 statistically significant differences in expression levels in the comparison groups were demonstrated. It was shown that the expression level of microRNA-424 increased after therapy (M±SM 1.202±0.15) compared with the expression level before treatment with nivolumab (M±SM 0.63±0.17; p-value=0.03). Despite the fact that miRNA-424 and miRNA-503 are clustered, miRNA-503, like other examined miRNAs, did not show any differences in expression levels between the compared groups.

Conclusion: miRNA-424 can be used to create a panel of molecular markers within other previously discovered markers to assess the effectiveness of ICI therapy. Despite the fact that this study is pilot and requires validation on larger samples, it confirms the possibility of using miRNAs as additional prognostic markers for ICI therapy.

Introduction. There is a steady increase in the incidence of type 2 diabetes worldwide. One of the most formidable complications of this pathology is the development of diabetic foot syndrome, which is accompanied by up to 50% of cases of high amputations, disability, increased mortality and a decrease in the quality of life of patients.

The aim of the study: to study the prevalence of genotype and allele variants of the T1565C polymorphism of the ITGB3 gene, the G1691A polymorphism of the FV gene, and the G20210A polymorphism of the FII gene in patients with the development of diabetic foot syndrome, as well as in the control group living in the Trans-Baikal Territory.

Material and methods. Polymorphism T1565C of the ITGB3 gene, G1691A polymorphism of the FV gene, and G20210A polymorphism of the FII gene were studied by PCR methods in 100 apparently healthy individuals and 198 patients with a mixed form of diabetic foot syndrome. The statistical significance of differences was assessed using Pearson’s chi-square test.

Results. The T/T genotype of T1565C polymorphism of the ITGB3 gene among healthy individuals was found in 70%, among patients with diabetic foot – 60.3%. The T/C genotype of the studied polymorphism of the ITGB3 gene in the control group was recorded in 29%, in the group of patients in 37.7%. The C/C genotype was detected in 1% of healthy individuals and 2% of diabetic foot patients.

The G/G genotype of the G1691A polymorphism of the FV gene was observed in 97% of healthy individuals and in 94% of patients among patients. The G/A genotype was detected in 3% in the control group and in 6% in the group of diabetic foot patients. The homozygous A/A genotype was not registered in the studied groups.

The G/G genotype of the G20210A polymorphism of the FII gene was registered in 92% of healthy individuals and in 95.5% of patients with diabetic foot. The G/A genotype was detected in 8% of cases in the control group and 4.5% of cases among patients with diabetic foot. The homozygous A/A genotype was not detected in the examined groups.

Conclusion: we did not find significant differences in the frequency of occurrence of genotype variants and alleles of the studied polymorphisms of the ITGB3, FV, FII genes among healthy individuals and patients with diabetic foot living in the Trans-Baikal Territory.