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Vol 20, No 5 (2022)

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Articles

SARS-CoV-2 infection as a risk factor for the development of autoimmune pathology

Timofeeva A.M., Sedykh S.E., Nevinsky G.A.

Abstract

Relevance: The review is devoted to the analyses of literature data on disorders of the immune system in COVID-19. Since some of the clinical symptoms of COVID-19 are consistent with those of autoimmune diseases, one of the fundamental questions about COVID-19 pathogenesis is whether SARS-CoV-2 infection is a risk factor for autoimmune disorders. Objective: The assessment of the possible role of the humoral response, in particular, antibodies with different specificity to COVID-19, in developing autoimmune reactions. Material and methods: Scientific publications on the autoimmune diseases published over the past 15 years and on COVID-19 for 2020-2022 were analyzed and systemized; the articles were searched in the PubMed and Scopus databases. Results: This review compares classical autoimmune diseases and COVID-19. This comparison is relevant since the use of drugs commonly prescribed for autoimmune diseases is practised in treating patients with severe COVID-19. The variety of autoantibodies in COVID-19 may reflect transient immune activation under conditions of acute infection, as well as early loss of tolerance and further development of chronic autoimmune pathology. Here we review the viral infections triggering autoimmune pathologies and possible mechanisms of autoimmunity induction in COVID-19; we classified the main groups of antibodies described in patients with COVID-19.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):3-10
pages 3-10 views

Cell technologies for endometriosis pathogenesis study

Okladnikova E.V., Ruksha T.G.

Abstract

Introduction. Endometriosis is a chronic inflammatory estrogen-dependent disease characterized by the presence of endometrial tissue outside the uterine cavity. The pathogenesis of endometriosis is not fully determined. The relevance of its study is due to the development of chronic inflammation in the lesions, which is accompanied by a pronounced pain syndrome. The appearance of ectopic foci in the reproductive system of women of fertile age can lead to the development of infertility. Animals or cell cultures can be used to study the pathogenesis of the disease. The aim of the study. To summarize the current data on the possibilities of modeling endometriosis using cell cultures, to consider the features of different models and their application to study the pathogenesis of the disease. Methods. The materials were the results of research on this topic over the past 20 years, from 2002 to 2022. The publications included in the databases «Pubmed», «Medline», «eLibrary.ru «. Results. This review provides information about the advantages and disadvantages of endometriosis modeling in vivo and in vitro. In animals, the initiation of the disease is impossible in a natural way (with the exception of primates), they require maintenance costs, their use is limited by ethical standards. Among the cell cultures used to study endometriosis, monocultures (stromal, epithelial, stem, mesothelial, immune cells) and co-cultures can be distinguished. The choice of the model is determined by the objectives of the study. The review presents some features of cell isolation from ectopic endometrial tissue, methods of cell identification and methods of their cultivation. The use of immortalized cell lines and 3D models in the study of the pathogenesis of the disease is discussed. Conclusion. Modeling of endometriosis has a number of technological problems due to both the nature of the disease and the biological properties of cells involved in the pathogenesis of endometriosis. Compared to animal models, in vitro models allow easy access to target cells to identify critical cellular and molecular factors, and to evaluate intercellular interactions that contribute to the development of the disease.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):11-17
pages 11-17 views

Fibroblast growth factors and their effect on cognitive functions and the course of central nervous system degenerative diseases

Kuznik B.I., Guseva E.S., Davidov S.O., Chalisova N.I.

Abstract

Aim of investigation. The study of characteristics of fibroblast growth factors (FGFs), as a man factor FGFd, including 22 structurally connected polypeptides, is necessary for the neuroprotection by the CNS degenerative pathology is presented playing a great role in neuroprotection, cognitive functions state. The factors FGF1, FGF2, FGF8. FGF17, FGF18, FGF20. FGF21 and their receptor (RFGF) in natural conditions plays a great role in nerve system structures preservation, in formation and preservation of long-term memory and other cognitive functions. Methods. Inroduction in old rat experiments the plasma or cerebrospinal fluid of young rats and also of recombinant FGFs. Results. The cerebrospinal fluid of young rats increased the proliferation and differentiation of oligodendrocyte cell-precursors in the hippocampus of old animals and this lead to great closing of cognitive disfunctions and reformed the leaning and memory. Conclusion. FGFs investigation create the basis for the preparation elaboration, which restore cognitive functions by aging and CNS degenerative pathology (Alzheimer and Parkinson diseases, stroke).

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):18-27
pages 18-27 views

The role of markers of intercellular interaction in the development of atopic dermatitis

Iskra E.L., Iskra A.S., Polyakova V.O., Nasyrov R.A.

Abstract

Introduction. Violation of the skin barrier can be considered as an initial stage in the development of atopic dermatitis, leading to further skin inflammation [2]. Transmembrane proteins such as claudin-1, claudin-7, occludin and E-cadherin are known to be the main components of epidermal tight junctions (TJ) [15]. Objective. The aim of the study was to research the pathogenesis of atopic dermatitis in cell culture and to assess the effect of placental hydrolysate on blood pressure. Methods. The studies were carried out on the cell culture of normal fibroblasts and the cell culture of atopic dermatitis. An immunocytochemical study was conducted to evaluate intercellular communications. Results. When the placenta hydrolysate was administered, the expression levels of occludin, claudin-1, claudin-7 and E-cadherin in blood in group IV were significantly different from those of group II. Thus, all the studied proteins contribute significantly to the development of the pathogenesis of atopic dermatitis. Conclusion. These results indicate that the studied markers play an important role in the pathogenesis of atopic dermatitis atopic dermatitis The work carried out allows us to understand in more detail the pathological processes occurring in this disease and prescribe drugs containing placental hydrolysate to restore normal epithelial differentiation.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):28-33
pages 28-33 views

Effectiveness of α1A-adrenoreceptor antagonist in the passage of middle stones from the ureter: the role of receptors coupled with G-protein

Barinov E.F., Malinin Y.Y., Grigoryan H.V.

Abstract

The study aims to analyze the dependence of an α1A-adrenoreceptor antagonist effectiveness on G-protein-coupled receptors (GPCRs) intracellular signaling in the passage of medium-sized calculi from the ureter. Material and methods. The study was prospective and included 30 patients divided into two groups: with effective (Group 1) and ineffective (Group 2) passage of stones 11-13 mm in size during 9 days of standard lithokinetic therapy (LCT), including an α1A-adrenergic receptor antagonist (α1A-A). The following antogonists were used: ATP, ADP, adenosine, epinephrine, angiotensin-2 (Sigma-Aldrich Chemie GmbH, Germany). Platelet aggregation was assessed by the turbidimetric method on a ChronoLog analyzer (USA). Results. Before the study started, the reactivity of receptors coupled with Gi-, Gq-proteins was revealed, as their signaling can cause a disturbance of medium-sized calculi movement in the ureter. After 7-9 days of LCT, the passage of calculi occurred with the normoreactivity of the purine P2X1 receptor and P2Y receptors, hyperreactivity of the α2-adrenoreceptor and A2A receptor, and desensitization of the AT1 receptor and TXA2 receptor. With ineffective passage after 7-9 days of LCT, there was hyperreactivity of receptors coupled to Gi-protein (α2-adrenoreceptor), Gq-protein (P2Y receptors, AT1 receptor and TxA2 receptor), as well as the receptor, which is a ligand-dependent. Excessive stimulation of the Gq protein-coupled receptor system can neutralize the effect of an α1A-adrenergic receptor antagonist administration by reproducing “crosstalk” of intracellular signaling resulting in the maintenance of an excess level of intracellular Ca2+. Hyporeactivity of the A2A receptor ruled out the possibility of achieving the required level of relaxation of smooth muscle tissue in the ureter. Conclusion. An in vitro analysis of intracellular signaling that regulates the entry of Ca2+ ions into the cell upon activation of the GPCR system and the passage of excess Ca2+ (adenosinergic system) makes it possible to clarify the mechanisms that maintain the balance of relaxation and contraction of SCMs during the movement of medium-sized calculi.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):34-41
pages 34-41 views

Association of polymorphic variants of non-allelic genes ADIPOQ, MTHFR, PON1, KCNJ11, TCF7L2, ITLN1 and PPARG with clinical and laboratory parameters among obese patients from Kyrgyz republic

Isakova J.T., Kipen V.N., Aitbaev K.A., Mukeeva S.B., Akynbek Kyzy Samara -., Mirrakhimov E.M.

Abstract

Introduction. In Kyrgyzstan about 60% of the adult population suffers from lipid metabolism disorders of varying degrees. Early identification of persons at increased risk of developing obesity is of great importance, which can be achieved through the study of molecular genetic mechanisms and the identification of genetic predictors of t of disease development. Aims. to quantify the association of g.15661G>T (ADIPOQgene), p.A222V (MTHFR gene), p.Q192R (PON1 gene), p.K23E (KCNJ11 gene), g.53341C>T (TCF7L2 gene), p.V109D (ITLN1 gene) and p.P12A (PPARG gene) polymorphic markers with clinical signs and blood indicators in obese subjects of Kyrgyz ethnicity. Material and methods. 130 patients with obesity (65 men and 65 women) along with 115 controls, including 62 men and 53 women were included. We used clinical, ancillary, biochemical and molecular tests in all subjects. PCR with restriction fragments was used to genotype polymorphic variants of interest. Statistical analysis was conducted in Microsoft Excel (Microsoft Corporation, USA) and SPSS v.20.0 (IBM, USA). Results. In patients with RR polymorphic variant of p.Q192R (PON1), BMI was on average 1.19 kg/m2 greater compared to those with QQ/QR alternative genotypes. T allele (CT/TT genotypes) of g.53341C>T (TCF7L2) genotype in obese patients was associated with 1.45 mmol/l higher fasting blood glucose; 0.49 mmol/l total cholesterol and 2.19 units of НОМА compared to subjects with СС genotype. We also found statistically significant correlations of L-alaninaminopeptidase (LAP) with p.K23E (KCNJ11) and p.P12A (PPARG) polymorphisms. Patients carrying KK genotype of p.K23E (KCNJ11) polymorphism, which is associated with higher risk of obesity in Kyrgyz (OR 2.36 (95% CI 1.11-5.03), p=0.031), LAP was 9.03 μIU/ml lower when compared to those with EE/EK genotype. Obese patients with AA genotype of p.P12A (PPARG) showed 20.1 μIU/ml higher LAP compared to PP/AP genotypes. Conclusions. Polymorphisms p.Q192R (PON1), g.53341C> T(TCF7L2), p.K23E (KCNJ11) and p.P12A (PPARG) are associated with clinical and biochemical indicators of obesity among patients of Kyrgyz nationality.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):42-52
pages 42-52 views

Influence of GABA derivatives on the DNA damage of placenta and fetuses’s brain at experimental preeclampsia

Sirekanyan A.G., Verle O.V., Dudchenko G.P., Perfilova V.N., Verovskiy V.E., Ostrovsky O.V., Tyurenkov I.N.

Abstract

Gestosis is a complication of the normal course of the gestational process that occurs during pregnancy, childbirth and in the first days of the postpartum period, characterized by a deep disorder of the functions of vital organs and systems. Preeclampsia (PE), as a form of gestosis, is an important health and social problem worldwide, remaining one of the main causes of perinatal and maternal morbidity and mortality. The aim of the study was to evaluate the effects of GABA derivatives on the genome integrity of placental cells of female rats with experimental PE and the state of DNA of brain cells of the offspring of these animals. Material and methods: the experiment was carried out on white nonlinear pregnant rats at the age of3 months weighing 210-230 g. After fertilization, pregnant females were moved to individual maintenance cells and an EP model was reproduced on them by replacing drinking water with 1.8% sodium chloride solution from the 1st to the 20h day of pregnancy. Increased blood pressure and registered proteinuria in the daily urine on the 1st and 20th days of gestation were considered to be signs of PE in pregnant female rats. The assessment of DNA damage was investigated by the DNA comet method. The results of the study showed a 3 and 2.6-fold increase in DNA in comet tails respectively. In animals treated with salifen (an adduct of phenibut and salicylic acid in a molar ratio of 2:1) at a dose of 15 mg/ kg once, intragastrically during pregnancy, the level of DNA damage in the corresponding organs was 3.0 and 1.4 times lower than in the group with EP. Phenibut (y-amino-ß-phenylbutyric acid hydrochloride) at a dose of 50 mg/kg and succicard (an adduct of phenotropil and succinic acid) at a dose of 44 mg/kg once, intragastrically, did not affect the level of genome damage in placenta and fetal brain cells.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):53-58
pages 53-58 views

Antigenotoxic activity of the combination «aspartame + betaine» and metformin in mice with experimental streptozotocin diabetes

Lisitsyn A.A., Zhanataev A.K., Chaika Z.V., Sevostyanova E.M., Artamonova M.P., Chernukha I.M., Oganesyants L.A., Durnev A.D.

Abstract

Introduction. An increase in DNA damage (genotoxicity) is characteristic of patients with diabetes mellitus. The main complications in diabetes are accompanied and/or initiated by DNA damage. Hence, the necessity to search for and study compounds with antigenotoxic properties for use in diabetes mellitus is obvious. Aim. Study of the antigenotoxic activity of aspartame and betaine combination in a mice diabetes mellitus model in comparison with the well-known hypoglycemic drug metformin. Material and methods. DNA damage was estimated using the «DNA comet» assay. Streptozotocin was used as a diabetogenic agent. Aspartame (35 mg/l) and betaine (175 mg/l) were given in the drinking water throughout the experiment. Metformin at a dose of 250 mg/kg was administered orally at the same time. The study was performed on BALB/c male mice. Results. After a single i.p. administration of 200 mg/kg streptozotocin or after its five-day daily administration at a dose of 40 mg/kg, hyperglycemia was observed, as well as DNA damage in the liver and kidney cells, but not in the brain, pancreas and testes cells. During the single streptozotocin injection experiment DNA damage under the influence of aspartame and betaine decreased by 58.0% in liver cells and by 53.8% in kidney cells. Metformin reduced DNA damage by 44.2 and 71.0%, respectively, in liver and kidney cells. During the repeated streptozotocin administration experiment aspartame and betaine reduced DNA damage by 52.2% in liver cells and by 46.6% in kidney cells. Metformin reduced DNA damage by 30.8 and 38.3%, respectively, in liver and kidney cells. Discussion. The data obtained demonstrate the antigenotoxic effect of the aspartame and betaine combination in experimental diabetes mellitus and confirm a similar activity in metformin, previously identified in a single study.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(5):59-64
pages 59-64 views

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