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Vol 19, No 6 (2021)

Articles

MicroRNA and its’ targets: basics of boiinformatic search

Shestakov A.V., Mikhailova A.A., Saprina T.V., Onkhonova O.E.

Abstract

MicroRNAs are defined as short non-coding molecules that regulate gene expression at the post-transcriptional level through complementary binding to the corresponding mRNA. This pairing leads to inhibiting offurther translation by mRNA degradation, in other words, microRNA is a crucial example of epigenetic regulation. Recent reports have suggested an important role of these signaling molecules in numerous chronic non-infectious diseases development, including different types of cancer. This linking in the onset and progression of various pathological conditions makes it possible to considermicroRNAs as promising candidates for creating effective diagnostic, prognostic and therapeutic technologies. The main problem in the design of research related to miRNA functional studies is the necessity to predict the effective miRNAs: mRNA interaction because of the multi-target effect on corresponding genes. In order to overcome this barrier and to anticipate potential miRNAs targets effects for the further guidance of the experimental stage, a number of bioinformatics research tools have been developed. In this review we will consider the basic molecular principles that underlie the bioinformatics algorithms for predicting targets and miRNAs: mRNA interactions. Furthermore, the key parameters as well as bases of their interpretation for the most used web tools, such as TargetScan and DIANA Tools, will be described.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):3-10
pages 3-10 views

Molecular mechanisms of possible use of metabolites for prevention, therapy and rehabilitation of patients with COVID-19

Mashkovtseva E.V., Nartsissov Y.R.

Abstract

The purpose of this review was to describe information about the etiology and pathogenesis of the main manifestations in patients with coronavirus infection COVID-19 and the molecular mechanisms of the possible use of metabolite drugs. Material and methods. The full-text search has been carried out in the Medline (Pubmed) and Scopus databases over the past 15 years. Results. Based on the results of the analysis the mechanisms of microcirculation disorders, possible ways of the virus penetration into the central nervous system and its effect on brain cells are described in detail. Neuronal damage and disruption of their normal functioning can lead to long-term consequences of infection. The use of metabolites to correct the cell state can soflty reduce inflammation through a range of molecular mechanisms. Conclusions. The proven cytoprotective and immunomodulatory effect of glycine determines its possible use in the therapy of COVID-19. The use of antioxidants such as glutathione is pathogenetically justified for the correction of endothelial dysfunction and neuronal hypoxia.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):11-18
pages 11-18 views

HPgV infection: literature review

Litvinov V.V., Freynd G.G., Korobov V.P., Shestakova A.D.

Abstract

Objective: to analyze the literature data on HPgV infection caused by the Human pegivirus-1 virus (formerly hepatitis G, HGV, GBV-C). Materials and methods: search, by keywords, publications in Scopus, PubMed and Elibrary databases for the period from 1995 to 2020. Results: the history of the study of the virus, its structure, genetic heterogeneity, as well as the problem of epidemiology, tropism and pathogenesis of this infection are described. Due to the presence of a number of the virus properties, possible prospects of HPgV infection research for population genetics and gene therapy are reflected. The modern data on the relationship of HPgV infection with HIV infection, lymphomas and some other diseases are presented. A brief description of a relatively recently described HPgV-2 is presented. The problems of diagnosis and interpretation of HPgV infection in the Russian Federation and foreign countries are outlined. Conclusion: Although HPgV was originally described as the cause of hepatitis, it is not a cytopathic virus, and infection is not associated with the development of pathological processes.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):19-26
pages 19-26 views

The influence of L-amino acids on the viability of neuroendocrine PC 12 cells line

Linkova N.S., Chalisova N.I., Ryzhak G.A., Gutop E.O., Ivko O.M.

Abstract

Introduction. It was shown, that L-amino acids can take part in regulation of the main physiological processes. Various combination of L-amino acids takin into account of its biological activity can apply for peptide drugs synthesis for target therapy of social significant diseases. The aim. Estimation of the influence of 20L-amino acids on the viability of PC12 cell line. Methods. The investigation was based on MTT test applying for viability estimation of PC12 cell line. Results. Methionine, arginine, asparagine, glutamic acid and histidine increased the viability of PC12 cell line on 54, 56, 51, 63 and 27% accordingly. Conclusion. The molecular mechanism of histidine and arginine activity can be connected with epigenetic genes regulation of cell metabolism. Previously it was shown that 5 amino acids stimulated nerve and pancreatic tissues grown in various aged animals. It can be constructed short peptides on the base of methionine, arginine, asparagine, glutamic acid and histidine. These peptides can be perspectives substances for prevention and therapy age-related neuroendocrine pathology.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):27-30
pages 27-30 views

Mitochondria proteins of cardiomyocytes as molecular targets of the preparation V007

Kvetnoy I.M., Mironova E.S., Krylova Y.S., Zubareva T.S., Leont’eva D.O., Polyakova V.O.

Abstract

Introduction. Mitochondria are one of the most important cellular organelles that provide cells with energy, take part in cellular renewal and the implementation of endogenous mechanisms of cellular immunity. The study of the structural and functional organization of mitochondria is extremely important and promising for the development of targeted routes of action of pharmacological drugs in various pathologies and aging. The aim of the study. The aim was to study the effect of the V007 preparation on the expression of mitochondrial biomarkers in the myocardial cells of old rats in vivo to elucidate the possible mechanism of its targeted action. Methods. Molecular biological methods were used to study the expression of key mitochondrial proteins: Tom70, Tom20, VDAC, DRP1, prohibitin, Parkin, PINK1 in the myocardium of old rats in normal conditions and with the use of the innovative drug V007. Results. The study made it possible to reveal that V007 is a drug that regulates and normalizes the functions of mitochondria. The concept of the targeted action of V007at the molecular level has been detailed, intracellular and interstitial signaling molecules, which may be targets of its pharmacological action, have been additionally verified, which makes it possible to expand the indications and scope of its application for the prevention and treatment of socially significant diseases. Conclusion. This study opens up wide opportunities for further study of V007 as a promising drug with a general regulatory and geroprotective effect.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):31-36
pages 31-36 views

Saliva concentration of sirtuins: perspectives of application for coronary heart disease diagnostics and aging rate

Linkova N.S., Pychalskaya A.E., Il’nitskii A.N., Novak-Bobarikina U.A., Osipova O.A., Rozhdestvenskaya O.A., Kozlov K.L.

Abstract

The aim is the comparative analysis of saliva concentration of sirtuins, in middle age and elderly people without cardiovascular pathology (CP) and with coronary heart disease (CHD). Methods. Saliva was obtained from healthy donors (73 persons without CP, «norm») and 68 CHD patients of middle age and elderly age. Sirt1, Sirt3, Sirt4, Sirt5, Sirt6, Sirt7concentrations were verified in saliva by enzymoimmunoassay. Results. Sirt1, Sirt6, Sirt7 concentrations in saliva in elderly patients from the group «norm» were 1.5-1.6 times lower in comparison with this value in middle-aged patients. Sirt1, Sirt 3, Sirt6, Sirt7 concentrations in saliva in middle-aged and elderly CHD patients were 1.4-4.2 times lower in comparison with the same values in patients of this age in group «norm». Sirt1, Sirt6, Sirt7 concentrations in saliva in elderly CHD patients were 1.5-2.1 times lower in comparison with these values in middle age CHD patients. Conclusions. The Sirt1, Sirt6, Sirt7 saliva study in healthy middle and old people can be used in a comprehensive assessment of biological age . The estimation of Sirt1, Sirt3, Sirt6, Sirt7 concentration in saliva in middle age and elderly patients may be the perspective predictive method of CHD.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):37-42
pages 37-42 views

Innate and adaptive immunity during infection and immunization with inactivated tick-borne encephalitis vaccine

Morozova O.V., Isaeva E.I.

Abstract

Introduction. Viral infections induce cellular and humoral immunity that provide virus elimination. Extracellular presentation of antigens of formaldehyde-inactivated vaccines causes mainly humoral immune response with risk of persistent infection. The aim of the study. comparison of dynamics of cytokines and antibodies IgMand IgG during infection and immunization of laboratory mice with inactivated vaccine against the tick-borne encephalitis. Methods: reverse transcription - real time PCR (RT2-PCR); ELISA to detect IgM and IgG antibodies. Results: All studied cytokine mRNA were found in the virus-infected mice whereas IL1fi, IL4 and TNFa RNA were missing after vaccination. Cytokine gene expression began in 1-2 days postinfection with maximal values in 4-8 days and subsequent decline, however, after vaccination cytokine RNA were revealed in 14 days only and were detected for 42 days of observations, probably, due to 3 subsequent injections. Antibodies in infected mice were also registered earlier, in 7-14 days postinfection, whereas after immunization later - in 28-42 days after first injection and antibody titers were higher. Conclusion: During viral infection cytokine profiles were more diversified, cytokine RNA transcription and IgM and IgG secretion took place earlier than for vaccination. Titers of antibodies were higher in immunized mice after 2-3 intramuscular injections compared to infection with long-lasting IgM circulation for 42 days.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):43-48
pages 43-48 views

Effect of immobilization of glycoproteins of the baker’s yeast cell wall on their immunomodulatory activity

Ryabtseva T.V., Makarevich D.A., Ermola E.M.

Abstract

The aim of the study was to study the effect of chemical immobilization of yeast cell wall glycoproteins on their ability to activate cytokine production by human peripheral blood cells. Methods. A comparative analysis of the immunomodulatory activity of yeast cell wall glycoproteins in a free and immobilized state was carried out. The dynamics of the process of accumulation of proinflammatory cytokines (IL6, IL8, and TNFa) in the extracellular medium after contact of human blood cells with glycoproteins was studied. The source of glycoproteins was the cell lysate of Saccharomyces cerevisiae. The glycoproteins were immobilized on a polyacrylamide gel in a copolymerization reaction. The study of the effectiveness of immobilized and free glycoproteins was carried out in in vitro experiments on the whole blood of practically healthy donors. The effectiveness was evaluated by the increase in the concentration of cytokines in the blood plasma after contact with glycoproteins compared to the baseline level, as well as by comparing the effect of polyacrylamide gel without a ligand and simply incubating blood cells with saline solution. Results. It was found that immobilized glycoproteins, as well as free ones, in contact with human peripheral blood lead to the activation of the synthesis of pro-inflammatory cytokines (IL6, IL8, and TNFa) by blood cells. The study revealed the peculiarities of cytokine synthesis depending on the form of contact of blood cells with the glycoprotein. It is shown that the rate of IL8 and TNFa synthesis is higher after blood contact with immobilized glycoproteins than with free-form glycoproteins.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):49-53
pages 49-53 views

Antioxidant activity of polyphenols in licorice beans (Glycyrrhiza glabra L.)

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

Abstract

Introduction. The worldwide trend towards green technologies has increased interest in the development and use of natural, highly-efficiency and inexpensive plant antioxidants to replace existing synthetic ones. Purpose of the study. study of the composition of polyphenols in licorice beans and their antioxidant activity. Methods. The content of polyphenols was investigated in ethanol extracts of licorice beans by the Folin - Ciocalteu method, identification of polyphenols was carried out using HPLC, the assessment of antioxidant activity was carried out in three ways: the ability to trap free radicals, the reducing ability, and antioxidant activity. Results. the total content of polyphenols in the EEBS averages 37.17 μg gallic acid equivalent. HPLC identifiedglabrin, catechin, rutin, lycochalcon A, and ellagic acid. The antioxidant properties of EEBS were evaluated in vitro. It was shown that EEBS reached the maximum absorption of DPPHradicals at a concentration of 1.6 mg/ml. At an initial concentration of 0.2 mg/ml, the effect of EEBS in trapping DPPH radicals was slightly more than 35% compared to control, and grew along with the increase in EEBS concentration, bearing a pronounced dose-dependent character up to 81.0% at a maximum concentration of 1.6 mg/ml. Critical volume of EEBS required for 50% degradation of DPPH. is 0.6 mg/ml. The reducing ability of EEBS with butyryl hydroxytoluene (BHT) as a reference standard showed that it has a significant (p<0.05) dose-dependent effect, from an initial concentration of 36.0 μg/ml, to the final concentration at 320 μg/ml, the difference absorption was 0.45 (from 0.11 to 0.56). In addition, the reducing ability of EEBS was very close to that of BHT at the same concentration. Conclusion. Licorice beans, in addition to licorice root, can be used as a powerful biologically active source of natural antioxidants.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):54-58
pages 54-58 views

Role of reactive glia in modulation of neuroand synaptogenesis in vitro

Vinogradova A.V., Tuchina O.P.

Abstract

Introduction. Activation of glial cells by lipopolysaccharide leads to the release of proinflammatory cytokines and the development of neuroinflammation, which, in turn, affects the processes of neuro- and synaptogenesis. However, the specific mechanisms of neuroglial and astrocytemicroglial interactions in these processes remain the subject of discussion. Aim of the study. Our aim was to study the role of microglia in the acquisition of a reactive phenotype by astrocytes in vitro, and the effect of lipopolysaccharide and astrocyte-conditioned medium on the neuro- and synaptogenesis of hippocampal neurons in vitro by immunocytochemistry methods. Methods. The study was carried out on glial and neuronal cell cultures from rat hippocampus. Lipopolysaccharide was added to mixed glial culture and pure astrocyte culture at concentrations of 1 and 10 μg/ml for 6, 12 and 24 hours. The cells were then fixed, stained for astrocytic marker GFAP. Lipopolysaccharide at a concentration of 10 μg/ml at 6 and 12 hours, as well as an astrocyte-conditioned medium were added to the culture of hippocampal neurons which were later fixed and stained for the marker of cell proliferation Ki67, presynaptic (Syn1) andpostsynaptic (PSD95) proteins. Results. The number of GFAP increased in mixed glial cultures after 6 and 12 h of incubation with lipopolysaccharide; in astrocyte culture, GFAP on the contrary, decreased. The addition of lipopolysaccharide and astrocyte-conditioned medium to neurons led to a decrease in cell proliferation and an increase in the amount of postsynaptic protein PSD95, while the amount of Syn1 changed only in case when lipopolysaccharide was added directly to neurons. Conclusion. In our work it was determined that astrocytes acquire a characteristic reactive phenotype only in the presence of microglial cells in vitro, as evidenced by an increase in the amount of GFAP. Astrocytes incubated with lipopolysaccharide are capable of modulating neuronal proliferation and synaptogenesis processes in vitro.
Molekulyarnaya Meditsina (Molecular medicine). 2021;19(6):59-64
pages 59-64 views

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