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Vol 20, No 4 (2022)

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Articles

Kisspeptins: molecular mechanisms of respiratory system pathology

Paltsev M.A., Drobintseva A.O., Mironova E.S., Paltseva E.M., Do N.H., Novak-Bobarykina U.A., Leontyeva D.O.

Abstract

The pathology of the respiratory organs is the leading one in the structure of the general human morbidity. Every year the number of diseases of the respiratory system increases, and the associated mortality increases in parallel. The study of the causes and mechanisms of development of lung pathology, as well as the development of adequate methods for diagnosing, treating and preventing diseases of the respiratory system, carried out at the molecular and cellular levels, is not only an important, but also an extremely urgent task of biomedicine. As is known, the violation of homeostasis between cell proliferation and apoptosis leads to inflammatory changes and/or fibrosis of the lung tissue. The purpose of this review was to systematize scientific data on the expression of kisspeptins and their function in the pathology of the respiratory system. Material and methods. The expression of kisspeptins and their receptors was analyzed in pulmonary fibrosis, bronchial asthma, and non-small cell lung cancer. In addition, the role of kisspeptins in the development of the body’s immune response to viral infections in the cells of the ciliated epithelium of the upper respiratory tract has been shown. Conclusion. More and more data from modern studies demonstrate the involvement of kisspeptins and their participation in the regulation of the cell cycle, limiting cell metastasis, and other processes.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):3-8
pages 3-8 views

SASP of endothelium and vascular smooth muscle cells: role in the pathogenesis and therapy of atherosclerosis

Savitsky D.V., Linkova N.S., Kozhevnikova E.O., Saraev G.B., Kozlov K.L., Kvetnoy I.M.

Abstract

The senescence-associated secretory phenotype (SASP) is one of the causes of age-associated diseases, including atherosclerosis. The purpose of the review is to analyze data on the role of SASP cells of the cardiovascular system in the pathogenesis and pharmacotherapy of atherosclerosis. In the formation of SASP endotheliocytes and vascular smooth muscle cells, an important role is played by an increase in the synthesis of pro-inflammatory cytokines (IL1, IL6, IL8, TNF, MCP), a decrease in the production of the anti-inflammatory cytokine IL4, apoptosis factors (p16, p53), activation thrombosis factor PAI-1, MMP and other signaling molecules. SASP of senescent cells alters the functions of their microenvironment and induces a chronic inflammatory response (inflamm-aging) that contributes to vascular damage. In experimental studies, some senolytic cardio- andgeroprotectors (metformin, resveratrol, digoxin, rapamycin, quercetin, etc.) prevent the formation of SASP by endothelial and smooth muscle cells and prevent the development of atherosclerosis. The search for substances that prevent the formation of SASP and prevent the development of atherosclerosis is an important goal of gerontology and molecular medicine.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):9-15
pages 9-15 views

Сellular senescence: molecular biology and morphology

Igrunkova A.V., Valieva Y.M., Kalinichenko A.M., Kurkov A.V., Popova K.Y., Shestakov D.Y., Zaborova V.A.

Abstract

Cellular senescence is a reaction of cells to damage, which consists in a full stop of the cell cycle, changes of the signaling pathways and secretory activity associated with aging. Regardless the inducing factor, cellular aging of different types have a similar morphological and molecular profile. The purpose of this review was to systematize scientific data on the molecular and morphological mechanisms of cellular aging. Material and methods: the main foreign and domestic sources were analyzed using the PubMed/Medline, RSCI/elibrary databases. Conclusion: The short-term persistence of biologically active substances, secreted by senescent cells, promote cell proliferation and regeneration of organs and tissues. The long-term presence of these cells, on the contrary, contributes to the inhibition of cell proliferation and synthetic activity, maintaining the pro-inflammatory environment. It negatively affects the structure and function of tissues and leads to chronic diseases, including atherosclerosis, hypertension, osteoarthritis and others, as well as oncology. The senescent cells detection in tissues is difficult due to the lack of morphologic features of these cells in standard light microscopy. It requires complex histochemical and immunohistochemical studies with several antibodies. Nowadays, various methods of regulating the number and secretory activity of senescence cells are studied. Two main directions include senolytic andsenomorphic therapy. The first is aimed at the selective initiation of apoptosis in senescent cells, the second is aimed at reducing the synthetic activity in them. Different types of cellular senescence have similar morphological, biochemical and molecular features and pronounced effect on tissue structures. Deepening the knowledge about cellular senescence will allow developing universal pathogenetic drugs for the prevention and treatment of many diseases with persistence of cells with the senescent phenotype.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):16-21
pages 16-21 views

Ihe role of physical activity in the processes of neurogenesis in the hippocampus

Vinogradova A.V., Smirnova P.A., Yakovchuk Z.Y., Tuchina O.P.

Abstract

The purpose of this review was to determine the role of physical activity as an integral component of environmental enrichment in the processes of neurogenesis in the rodent hippocampus. Material and methods. The full-text search has been carried out in the Medline (Pubmed) and Scopus databases over the past 15 years. Results. Physical activity affects neuronal precursors of the dentate gyrus of the hippocampus, probably acting through several molecular mechanisms: 1) an increase in the systemic concentration of glycolysis products (primarily lactate) promotes increased blood supply to the dentate gyrus and angiogenesis; 2) muscle-released myokines stimulate the expression of neurotrophic factors such as brain-derived neurotrophic factor BDNF; 3) a decrease in the number of adipocytes and a decrease in the concentration of leptin with regular training changes leukopoiesis, inhibiting the proliferation of potentially pro-inflammatory leukocytes; 4) stimulation of the vagus nerve contributes to the regulation of systemic inflammation and depolarization of granule cells, which probably stimulates the differentiation of neuronal progenitors. Conclusion. Physical activity, regardless of other components of the enriched environment, stimulates the proliferation and survival of neuronal precursors of the dentate gyrus of the hippocampus.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):22-27
pages 22-27 views

Galectin-3, haptoglobin and proangiogenic factors in gastric cancer

Kovaleva O.V., Zybina N.N., Gratchev A.N., Chang V.L., Ognerubov N.A., Stilidi I.S., Kushlinskii N.E.

Abstract

Introduction. Stomach cancer in Russia occupies the 4th place among most frequent malignant neoplasms, after tumors of the lung, breast and colon. The search for new diagnostic and prognostic markers of this pathology is an urgent task of modern molecular oncology. The purpose of the study is a comprehensive analysis of the content of soluble forms of galectin-3, haptoglobin, as well as pro-angiogenic molecules VEGF, sVEGFR1 and sVEGFR2 in patients with gastric cancer. Material and methods. The study included plasma and serum samples from 60 patients with gastric cancer and from 32 healthy donors. The concentrations of galectin-3, haptoglobin, as well as VEGF, sVEGFR1 and sVEGFR2 were determined using ELISA. The Mann-Whitney test was used to analyze the statistically significant differences in independent groups. Correlation analysis was performed using the Spearman rank correlation coefficient. Overall survival was analyzed by constructing survival curves using the Kaplan-Meier method. Differences were considered statistically significant atp<0.05. Results. The data of a complex comparative study of the content of soluble forms of galectin-3, haptoglobin, as well as VEGF, sVEGFR1 and sVEGFR2 are presented. The diagnostic significance of galectin-3 and haptoglobin was determined. The study showed that the content of galectin-3 and haptoglobin was statistically significantly lower in the group of healthy donors compared to patients with gastric cancer. Further we showed that the content of galectin-3 and haptoglobin is associated with the localization of the tumor in the stomach. Statistically significant correlations were found between the soluble forms of some of the studied markers, indicating the presence of independent mechanisms of their regulation in gastric cancer, which may explain the ambiguous clinical significance for this type of tumor. Conclusion. The results will help to better understand the biology of gastric cancer and improve the efficiency of its diagnostics and therapy.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):28-34
pages 28-34 views

Eosinophils are predictors of susceptibility to thrombosis and severe course of Covid-19 in various types of therapy

Kuznik B.I., Smolyakov Y.N., Shapovalov K.G., Kazantseva L.S., Chalisova N.I.

Abstract

The creation by COVID-19 of methods for prophylactic of these complications as blood hypercoagulation, leading to thrombosis and polyorganic insufficiency, is an urgent task of modern biology and medicine. The aim of the study was to develop the simple methods, by which it is possible make prognosis of the changes in the blood coagulation peculiarities by this illness and by different methods of treatment. Methods. The patients with severe COVID-19 were separated to 3 groups. 1- control (basic scheme of treatment), 2- (basic scheme of treatment and Tocilizumab), 3- (basic scheme of treatment and Thymalin). Evaluation of the dynamic of eosinophil and thrombocytes number was performed using hemoanalyzer PENTRA-80 Horiba ABX Diagnostics. The detection of basic index of coagulogramm was performed using the coagulometer Sysmex. The connection of eosinophil number to the changes of the basic rate of coagulogramm. Results. It was established, that eosinophils are the are the predictors of change both of coagulation and of thromb formation in the blood. The positive effect of Thymalin, as compared to Tocilizumab, on the blood coagulation system by sever COVID-19 is established. Conclusion. It is established that by immunocorector using by sever COVID-19 Thymalin is mostly effective for treatment and prophylactic of complications.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):35-42
pages 35-42 views

Signal transduction of inefficient elimation of small stones from the middle third of the ureter

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

Abstract

Aim of the study was to evaluate the activity of receptors that control contraction (α2-adrenergic receptor, purine P2X1 and P2Yreceptors, angiotensin AT1 receptor, TxA2 receptor) and relaxation of smooth myocytes (adenosine A2 receptor) during standard lithokinetic therapy (LCT) in patients with localization of small (<6mm) stones in the middle third of the ureter. Material and methods. The study was prospective and included 17 patients with ineffective elimination of small stones during 9 days of standard LCT. Analysis of the receptors activity that modulate ureteral motility was performed in vitro on a platelet suspension. The following agonists 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. At the stage of hospitalization of patients (before the start of LCT), hyperreactivity of the angiotensin ATt receptor, purine P2Xj and P2Yreceptors, α2-adrenergic receptor, TxA2 receptor and adenosine A2 receptor was revealed. This reflects the presence of signal transduction in nephrolithiasis, which is capable of modulating the contraction and relaxation of smooth muscle tissue of the ureter. After 3 days of LCT, intracellular signaling is characterized by hyperreactivity of the ATt receptor and normoreactivity of the a2 adrenoreceptor, P2Xj receptor, and P2Yreceptors; The revealed relationship of the AT1 receptor with the α2-adrenergic receptor and P2Xt receptors does not provide an increase in ureteral motility. After 6 days of LCT, insufficient contractile activity of the muscular layer may be associated with limited activation of the α2-adrenergic receptor, as well as a weak interaction of the ATt receptor with purine P2X1 and P2Y receptors. After 9 days of LCT, the violation of the traffic of small stones in the ureter is associated with desensitization of the α2-adrenoreceptor and P2X1 receptor, as well as hyperreactivity and interaction of the AT1 receptor and P2Y receptors. Conclusion. The variability of intracellular signaling in case of ineffective elimination of small calculi from the middle third ureter is determined by the influence of nephrolithiasis pathogenesis factors and the low specificity of LCT in relation to the processes of contraction and relaxation of smooth muscle tissue.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):43-49
pages 43-49 views

Induction of apoptosis of prostate cancer cells by the extract of the freshwater sponge

Nikolaev A.A., Gudinskaya N.I., Ushakova M.V.

Abstract

Introduction. Prostate cancer (PC) is by far the most commonly diagnosed malignant neoplasm of the urinary system. The pathogenesis and molecular mechanisms of prostate cancer remain incompletely understood. There are reports of the presence in the extracts of several species of marine and freshwater sponges of bioactive metabolites that reduce the proliferative activity of cancer cells and, in particular, prostate cancer cells. Purpose. The purpose of our study was the effect of freshwater badyagi extract on the viability and apoptosis of prostate cancer cells LNCAP clone FSK (ECACC 89110211) and the associated mechanism. Material and methods. In the work, we used an extract of the Commonweed (EPHYDATIA FLUVIATILIS), LNCAP cells of the FSK clone (ECAC 89110211), Analysis of cell proliferation was performed by a standard MTT test, Analysis of apoptosis was performed by flow cytometry using an Attune® NxT flow cytometer ANNEXIN Apoptosis Detection Kit V-FITC APOPTOSIS DETECTION KIT I (BD Pharmingem™, USA) was used for further confirmation of apoptosis. To determine the effect of bodyaga extract on the signaling pathway involved in this study, pro-apoptotic and anti-apoptotic proteins in LNCAP cells were assessed by Western blot analysis. Results and discussion. A preliminary study of the effect of EBR on LNCAP cell proliferation showed that EBR exhibited the maximum growth inhibition effect on LNCAP cells starting from the second day of incubation. The further experiment pursued the goal of elucidating the dependence of the inhibitory effect on the concentration of EBR in the cultivation medium. A strong dose-response relationship between EBR and LNCAP cell viability was shown. However, it was shown that EBR caused a slight significant increase in cell viability between 0 μg/ml (control) and 6.25 μg/ml. This reaction can be explained by the well-known hormesis effect. An assessment of the safety profile of EBR showed a selectivity index of 7.24. It was shown that it was apoptosis that contributed to the decrease in the viability of LNCAP prostate cancer cells after exposure to EBR. Moreover, there is a direct dependence of the level of apoptosis on the concentration of EBR in the culture liquid. Western blot analysis of LNCAP cells treated with various concentrations (0, 50, 100 and 200 mg/ml) of EBR to assess the expression of Bcl-2, Bax proteins showed that the level of Bax was rising and Bcl-2 was falling. Conclusion. EBR has an inhibitory effect on the growth and viability of prostate cancer cells. causing apoptosis of prostate cancer cells. EBR treatment also increased the Bax/Bcl2 expression ratio, indicating involvement of a mitochondria-mediated intrinsic apoptotic pathway.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):50-55
pages 50-55 views

Effect of dipeptides on cellular growth in organotypic culture of tissues from young and old rats

Chalisova N.I., Ryzhak G.A., Khavinson V.K.

Abstract

Dipeptides are physiological products of protein degradation and informational molecules. Asp-Pro, Asp-Ala, Glu-Ala peptides have geroprotective, reparative properties. The aim of the work is to evaluate the effect of the Asp-Pro, Asp-Ala и Glu-Ala peptides on the development of organotypic tissue culture (bronchi, vessels, brain subcortical structures)in young and old rats. Material and methods. Tissues for organotypic cultivation of bronchi, vessels, brain subcortical structures were obtained from young (2-3 months) and old (18-20 months) Wistar rats. Results. Asp-Pro peptide stimulated cell growth in bronchi tissues of young and old animals. Asp-Ala peptide activated cell proliferation in vessels tissues of young and old rats. Glu-Ala peptide had a stimulating effect on the brain subcortical structures tissue of young and old rats. Conclusion. Asp-Pro, Asp-Ala, Glu-Ala peptides have effects on corresponding tissues obtained from animals of different ages. This indicates the possibility of base formation for working of preparations, including the geroprotective, perfecting the functional activity of bronchi, vessels, brain subcortical structures.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):56-59
pages 56-59 views

Activity of the 4-1BB/4-1BBL signaling pathway in patients with colon tumors

Chetveryakov A.V., Tsepelev V.L.

Abstract

Background. Protein 4-1BB (CD137) enhances the activity of T-cells, prevents their death, and promotes the production of cytokines, which makes it a powerful co-stimulating agent. Currently, the use of this glycoprotein is being studied in order to influence the key links of carcinogenesis. Objective. We aimed to assess 4-1BB level in blood serum, tumor tissue and lymph nodes in patients with colon tumors. Methods. The study was carried out in the Regional Oncology Dispensary in Chita and included 44patients with colorectal cancer and 25 patients with benign tumor of the colon who were treated between 2019 to 2020. The control group comprised 25 patients who had been operated due to colon injury at the Regional Clinical Hospital in Chita. We determined 4-1BB concentration in blood serum, the supernatant of the homogenate of tumor tissue and lymph nodes using the flow cytofluometry method. Results. It was found that in patients with colon cancer the concentration of the soluble form 4-1BB in the blood serum increased by 1.88 times, in patients with benign tumor of the colon - by 1.86 times compared to the control group. The concentration of 4-1BB in tumor tissue in patients with colorectal cancer exceeded this indicator by 2.06 times compared to the control group and it increased by 1.43 times in comparison with the group of patients with benign tumor. Conclusion. The 4-1BB/4-1BBL signaling pathway is involved in the cascade of innate and acquired immunity reactions and is one of the carcinogenesis links in patients with colorectal cancer.

Molekulyarnaya Meditsina (Molecular medicine). 2022;20(4):60-63
pages 60-63 views

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