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Vol 21, No 4 (2023)

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Proteins timp-2, irisin and situation with hemostasis, lipid metabolism and sex hormones in female cardiovascular patients

Smolyakov Y.N., Chalisova N.I., Guseva E.S., Kuznik B.I., Lareva N.V.


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.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):3-10
pages 3-10 views

The role of chromosomal V(D)J recombination of lymphocytes in the formation of antitumor immunity and the effectiveness of immunotherapy

Sultanbaev A.V., Musin S.I., Menshikov K.V., Izmailov A.A., Nasretdinov A.F., Sultanbaevа N.I., Menshikova I.A., Tsimafeyeu I.V., Lipatov D.O., Sultanbaev M.V., Lipatov O.N., Kudlay D.A.


Introduction. The effectiveness of antitumor immunity is determined by various mechanisms of recognition of tumor antigens, while the diversity of the repertoire of antigenic receptors is determined by V(D)J recombinations in maturing T and B cells.

The aim of this work is to review scientific literature data on the role of chromosomal V(D)J recombinations of immune system cells in the mechanisms of antitumor immunity.

Material and methods. This review presents data on the main mechanisms of antitumor immunity and the role of T- and B-cell receptor gene rearrangement in its formation.

Results. From the presented analysis of literary sources, it follows that carcinogenesis is accompanied by suppression of the antitumor activity of the immune system. As a result, immunodeficiency states are observed in patients with malignant neoplasms.

By-products of chromosomal V(D)J recombinations are DNA excision circles TREC and KREC. Their quantitative analysis in cancer patients makes it possible to determine the presence of immunodeficiency, as well as to evaluate the effectiveness of the formation of antitumor immunity.

It is also noted that in immunocompromised cancer patients, the possibility of using personalized immunostimulation methods should be considered, which will improve control over the malignant process.

Conclusions. The review reflects the mechanisms of the immune system response to carcinogenesis. The main stages of the interaction of the tumor antigen with the patient’s immune system are considered. Methods for evaluating the viability of antitumor immunity are described.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):11-19
pages 11-19 views

MicroRNAs as biomarkers of miocarditis and dilating cardiomiopathy

Ryabinina O.M., Melnikova E.A., Makarova O.V.


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.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):20-24
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Molecular genetic basis of cervical cancer

Lenkova K.V., Khusainova R.I., Minniakhmetov I.R.


Introduction. Cervical cancer is one of the most common cancers of the female reproductive system, killing more than 250,000 women each year. The etiological agent that causes cervical cancer is well known. HPV infection with high oncogenic risk is the cause of more than 99% of cases of the disease. However, not all infections lead to cervical cancer: in the vast majority of women, the virus eliminates itself spontaneously within 2 years. Formation of HPV-associated cervical cancer depends on genetic and epigenetic factors, but the molecular pathogenesis of the disease is still insufficiently disclosed.

The aim of the article is to analyze, systematize and summarize the available literature on the problems of prevalence, diagnosis, treatment, prevention, molecular genetic component.

Material and methods. When writing this work, the main Internet resources were used: scientific electronic library (e-Library), Scopus, PubMed. The literature search was performed mainly for the previous 10 years.

Results: The review contains articles describing genetic and epigenetic mechanisms of cervical cancer, modern methods of molecular-genetic diagnostics, as well as available statistical data on prevalence, prospects of prevention, diagnosis and treatment of this malignant disease.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):25-33
pages 25-33 views

Analysis of modern concepts of neurodegenerative properties of depression

Yasenyavskaya A.L., Tsybizova A.A., Samotrueva M.A.


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.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):34-39
pages 34-39 views

Original research

Exosomal mirnas as possible predictors of immune checkpoint inhibitors therapy response in clear cell renal cell carcinoma

Gilyazova I.R., Asadullina D.D., Ivanova E.A., Izmailov A.A., Kudlay D.A., Gilyazova G.R., Galimova E.F., Ermakov I.B., Rakhimov R.R., Popova E.V., Nasretdinov A.F., Sultanbaev A.V., Khusnutdinova E.K., Pavlov V.N.


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.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):40-48
pages 40-48 views

Thyroidogenesis and trace elements: predictor possibilities

Logvinenko A.A., Morozova G.D., Poleschuk V.V., Sadykov A.R., Yurasov V.V., Skalny A.V.


Introduction. Trace elements are widely involved in various metabolic processes in humans, including thyroid hormones. Iodine is a part of thyroid hormones, is actively involved in the work of thyroid enzymes, copper, zinc and manganese are included in the composition of antioxidant enzymes, which, in particular, in iron, need the synthesis of hormones.

Purpose: to study the correlation between the levels of trace elements in the blood serum and thyroid hormones and TSH; determination of the prognostic sensitivity of the determination of trace elements, thyroid hormones and TSH in human serum.

Material and methods. The study was performed on the basis of a database of analyzes collected in the course of laboratory practice. Iodine, selenium, copper, zinc, manganese were measured in blood serum by the ICP-MS method, thyroid hormones and TSH were measured by the immunochemiluminescent method. The total number of examined patients was 4162 people. In order to evaluate the quality of models for predicting deficiency or excess of an elevated ratio of thyroid hormones or TSH and vice versa, we used the ROC curve model, which is widely used to determine the diagnostic value of new markers.

Results. The possibility of using TSH as a predictor of iodine deficiency in women was revealed. Also, the content of T4 can be predictors of iodine disease for sexes, and according to the content of total T3 and total T3 can only be predicted by iodine deficiency, also for sexes. Based on the study data, it was revealed that the concentration of thyroid hormones and TSH can be dangerous with the likelihood of an excess or deficiency of selenium, copper, zinc in both women and men. In turn, the level of thyroid hormones and TSH can be called as a predictor of excess or deficiency of sugar in the blood.

Conclusion. Trace elements play an important role in thyroidogenesis and may be useful in the diagnosis and detection of cases of thyroid disease

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):49-59
pages 49-59 views

Analysis of the relationship of itgb3, fv, and fii gene polymorphism with the development of diabetic foot syndrome

Troitskaya N.I., Shapovalov K.G.


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.

Molekulyarnaya Meditsina (Molecular medicine). 2023;21(4):60-64
pages 60-64 views

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