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Vol 17, No 3 (2019)

Articles

The role of neurotrophic factors of placenta in development of the fetus brain in hyperhomocysteinemia

Arutjunyan A.V., Milyutina Y.P., Zalozniaia I.V., Shcherbitskaia A.D., Kerkeshko G.O.

Abstract

This review article focuses on modern ideas about the role of neurotrophic factors (BDNF, NGF, NRG1, etc.) in the formation of the placenta and their impact on the development of the nervous system in early ontogenesis. Data on the common effect of neurotrophic factors with vascular endothelial growth factor and metalloproteinases on angiogenesis in the placenta and fetal brain are presented. Issues related to the effect of pro-inflammatory cytokines and oxidative stress on the neurotrophin expression in the placenta, as well as on the fetal brain development are discussed. Thepro-apoptotic effect of L-homocysteine on trophoblast cells is associated with oxidative stress, while neurotrophins expressed in the placenta display an anti-apoptotic effect. The oxidative stress is shown to be crucial for long-term impairments in the development of the nervous system and cognitive function in the offspring in hyperhomocysteinemia. This disorder also causes an increase in DYRK1A protein brain level, accompanied by neurodegeneration, the decline in BDNF protein brain level in the mature brain, and impaired brain development in fetuses, leading to cognitive impairment in the offspring. The molecular mechanisms of the effect of prenatal hyperhomocysteinemia on the level of neurotrophins and their precursors in the placenta and fetal brain do not seem completely clear and need further study.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):3-7
pages 3-7 views

Inflamaging: molecular-cellular mechanisms of female reproductive system aging

Rodichkina V.R., Kvetnoy I.M., Polyakova V.O.

Abstract

Aging is a complex biological process, the main aspect of which is the accumulation of somatic changes in the body during life. Late reproductive age is associated with infertility and possible complications of pregnancy. Aging at the cellular and organ levels negatively affects reproductive function. Immune cells are proved to play a crucial role in the physiology of the reproductive system. Senescent cells are viable in vitro, in contrast to the apoptotic cells prone to programmed cell death. Senescent cells express pro-inflammatory cytokines, growth factors, and matrix metalloproteinases totally called the aging-associated secretory phenotype (SASP). Inflamaging (inflammatory aging) is an aging-associated, a chronic and systemic inflammatory condition caused by cells acquired senescence-associated secretory phenotype (SASP). In this type of cells, there is marked depression of the p16INK4a gene, which maintains the viability of the aging cells, preventing their apoptosis. This review examines the effect of cellular, «inflammatory» and immune aging on the female reproductive function.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):8-14
pages 8-14 views

The role of NF-kB and von Hippel-Lindau protein in the creation of a molecular portrait of kidney cancers

Spirina L.V., Slonimskaya E.M., Yurmazov Z.A., Usynin E.A., Lushnikova N.A., Tarasenko N.V., Kondakova I.V.

Abstract

The review presents data on the role of the nuclear factor NF-kB and the von Hippel-Lindau protein (VHL) in the development of kidney cancer. Chemo- and radioresistance, specific for renal cell carcinoma, represented a significant problem in the treatment of patients. The discovery of the key mechanism of tumor progression was a significant breakthrough for this disease, where surgical approaches prevailed for a long time. The majority of renal cell carcinoma cases is known to be are associated with germ or somatic mutations of the VHL protein, realized through overexpression of the nuclear hypoxia-induced factor (HIF-1) and hyperproduction ofvascular endothelial growth factor (VEGF). However, the use of targeted drugs blocking key molecules associated with the angiogenesis fails to increase the number of objective responses in patients. In addition, the role of inflammatory reactions and, in particular, their key mediator, NF-kB, in the oncogenesis of kidney cancer has already been proven. Thus, the concept of a tumor molecular portrait has emerged, which is largely mediated by the production of a number of oncoproteins and oncosuppressors, activating nuclear factors NF-kB and HIF-1. In the development of kidney cancer, the VHL protein is crucial due to the capacity of triggering a cascade of molecular reactions associated with the neoangiogenesis, as well as the regulation of inflammatory responses. Consequently, the determination of the biological features of the tumor is significant in creating the optimal approaches for the personalized treatment of kidney cancer patients.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):15-19
pages 15-19 views

Sensitivity analysis of the proton transport through the half-channels of F0F1-ATP synthase to transmembrane potential changes

Ivontsin L.A., Mashkovtseva E.V., Nartsissov Y.R.

Abstract

Introduction. ATP is one of the most frequently updated molecules in the organism. The presence of a transmembrane gradient of H+ electrochemical potential is a crucial condition for the synthesis of ATP using FFfATP synthase enzyme, which affects proton transport through the Fo factor. The aim of the study was to evaluate the effect of the transmembrane potential on the proton transport parameters through the inlet halfchannel of FFfATP synthase taking into account its possible spatial polymorphism. Methods. A combined approach is used for proton motion modeling. Probability of proton transfer is determined by a quantum-mechanical approach of one-dimensional motion and the problem of proton transport through a sequence of charged centers in the halfchannel is considered in the framework of the stochastic approach. Results. The values of the proton transport times obtained in the model of 10-10-10-s s are in a good accordance with the experimental estimates of the ion transfer time in various biological objects for the certain physicochemical characteristics. In the range of physiological values of the membrane potential, the time was almost unchanged. Linear dependence between the transport time and the membrane potential was established for the transmembrane oriented 1C17 pdb-structure, which led to a time increase by 11% without the potential. In case of the laterally oriented 5T4O pdb-structure the transport became slower, however, no apparent linear dependence has been identified. Conclusion. The results obtained in this work can be used to evaluate the proton current through the half-channel and the contribution of transport time to the total time of ATP synthesis. In addition, proton transport adaptability analysis enlightens the additional vulnerability points of the catalytic cycle of FFfATP synthase in case of integrality problems and membrane characteristics changes.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):20-26
pages 20-26 views

Analysis of polymorphism of genes of the hemostasis system in pregnant women suffering a migraine

Bakirov B.A., Derevyanko K.P., Kudlay D.A.

Abstract

Introduction. The study of the genetic mechanisms of migraines is based on the investigation of genes of possible susceptibility and analysis of the influence of gene polymorphism in combination with environmental factors that form the pathogenetic chain of the disease. Purpose of the study. Evaluation of the polymorphism of the hemostatic system genes in women with migraine attacks during pregnancy. Methods. The examination of 94 women during pregnancy with a migraine history was performed at the Department of Pregnancy Pathology at the Clinic of Bashkir State Medical University. The diagnosis of migraine was made according to the diagnostic criteria of the International Society for the Study of Headache. The was examination of hemostasis of patients: FGB: - 455, F2:20210, F5: 1691, F7: 10976, F13, PAI-1:-675, ITGB3:-1565, MTHFR:677. Results. MTHFR allele carriers: 677 T were detected in 47,2% of patients with migraine and 7,7% among the control group (p=0,01). Among patients with migraine, carriers of the 1565C allele in the ITGB3 gene were more common (13,3 versus 11,3% in the control group, p=0,08). In the group of patients with migraine the increase in the frequency of occurrence of the homozygous genotype of fibrinogen FGB: -455AA compared with the control group was observed: 12,5 versus 10,8% respectively (p> 0.05). Conclusion. Understanding of genetically determined thrombophilic states will help in an interdisciplinary approach in genodiagnostics and personalized prevention of the pathology of hemostasis in case of migraines during pregnancy.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):27-31
pages 27-31 views

The humoral immune response to the antigen immobilized on nanoparticles of copolymer of polylactic acid and polyethylene glycol

Sakhabeev R.G., Polyakov D.S., Grudinina N.A., Vishnya A.A., Kozlovskaia A.A., Sinitsyna E.S., Korzhikov-Vlakh V.A., Tennikova T.B., Shavlovsky M.M.

Abstract

Introduction. Currently, polymer nano-and microparticles are a promising material for the targeted delivery of drugs to human organs and tissues. The influence of these particles on humoral and cellular immune responses has not been studied. The aim of the study. The aim of the work was to study the immunogenicity of the protein associated with polymer biodegradable nanoparticles based on polylactic acid copolymer with polyethylene glycol. Methods. Activated nanoparticles were used for covalent binding of the model protein. Two groups of 40 mice were immunized. Nanoparticles from the copolymer of polylactic acid and polyethylene glycol, which were covalently bound to the model protein, were introduced to the experiment group. The control group was immunized with a mixture of the same protein and unmodified nanoparticles. 4 immunizations were carried out at intervals of 2 weeks. Blood sampling of mice was carried out 13 days after each immunization. The content of specific antibodies to the model antigen in the serum of mice was determined by the ELISA method. Results. According to confocal microscopy, the model protein fi2M-sfGFP was strongly adsorbed on the surface of nanoparticles. The amount of immobilized protein was shown to amount of 10 ^g per 1 mg of nanoparticles. aonclusion. Using the non-parametric statistical Mann-Whitney test, it was shown that at each stage of immunization the content of antibodies in the control group was significantly higher than in the experiment group (p<0,001).
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):32-36
pages 32-36 views

Comparative evaluation of the efficiency of the impact of Aquashine line preparations on skin fibroblasts under aging in vitro (cell-molecular research)

Polyakova V.O., Gazitaeva Z.I., Kleimenova T.S., Drobintseva A.O., Prokopov A.Y., Kvetnoy I.M.

Abstract

Introduction. Skin aging is a natural process that cannot be stopped. However, there are many ways to help stop premature aging of the skin and reduce the signs that have already appeared. One of them is the subcutaneous administration of preparations containing biomimetic peptides capable of interacting with growth factor receptors and providing an anti-aging clinical effect. The purpose of this study was to compare the geroprotective properties of the preparations Aquashine and Aquashine HA. Methods. To study the aging of skin fibroblasts in culture, the cell culture method was used, and immunocytochemistry and confocal microscopy were used to identify markers of aging. Results. The preparation Aquashine HA has the ability to activate proliferative processes in the skin, and, by virtue of its properties, regulates the processes of cell renewal through increased cell apoptosis. Conclusion. Aquashine HA has a more pronounced geroprotective effect compared to Aquashine.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):37-42
pages 37-42 views

Comparative characteristics of the susceptibility of Kupffer cells and macrophages of bone-background origin to activation factors

Lokhonina A.V., Elchaninov A.V., Makarov A.V., Nikitina M.P., Goldshtein D.V., Paltsev M.A., Fatkhudinov T.K.

Abstract

Introduction. In mammals, there are several populations of macrophages, developing from bone marrow progenitors and resident macrophages, developing from the embryonic precursors of the yolk. One of the reasons for the coexistence of several populations of macrophages may be their different role in inflammatory responses, which is associated with different susceptibility to activation factors. The aim of the study. To compare the susceptibility of macrophages of bone marrow and embryonic origin to the activation factors of M1- and M2-phenotypes. Materials and methods. As macrophages of embryonic origin, Kupffer cells of the liver were studied, they were compared with macrophages of monocytic (bone marrow) origin, obtained from intact male Wistar rats. Results. Gene expression of cytokines IL1b, IL6, and TNFa in Kupffer cells was found to increase only under the influence of elevated concentrations of LPS (100 ng/ml) or IL4 (40 ng/ml) and IL10 (40 ng/ml), except for the IL10 gene, the expression of which in liver macrophages increased under the influence of a medium containing 50 ng/ml LPS. The expression of the cytokine genes IL1b, IL6, IL10, and TNFa in monocytic macrophages increased under the influence of minimal concentrations of LPS (50 ng/ml) or IL4 (20 ng/ml) and IL10 (20 ng/ml). Conclusion. Kupffer cells and monocytic macrophages response to different inductors in a similar way and they simultaneously increase the expression of both pro-and anti-inflammatory markers. At the same time, macrophages of bone marrow (monocytic) origin in general compared with resident liver macrophages are more prone to activation factors, and especially to endotoxin, which is likely due to the development of LPS tolerance in Kupffer cells.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):43-49
pages 43-49 views

Expression of inhibitor of cyclindependent kinases р16ink4a in patients with endometrial hyperplasia and secondary infertility associated with external genital endometriosis and uterine myoma

Tolibova G.H., Tral' T.G., Tatsiy I.D., Kleimenova T.S., Kvetnoy I.M.

Abstract

Introduction. The endometrial hyperplasia is a current problem in connection with the high frequency in reproductiveaged patients with infertility associated with external genital endometriosis and uterine myoma. The aim ofthe study was the comparative evaluation of sex steroids expression, inflammatory markers and an inhibitor of cyclindependent kinases p16ink4a in the endometrial hyperplasia. Methods. The study included 54patients with endometrial hyperplasia. 1st group: 30patients with secondary infertility and external genital endometriosis degree I-II, 2nd group: 24patients with secondary infertility and uterine myoma (intramural and subserous form, the diameter of the nodes does not exceed of 3.0 cm). The expression of ER and PgR receptors, inflammatory markers (CD8+, CD20+, CD4+, SD138+) and inhibitor of cyclindependent kinase p16ink4a was studied by the immunohistochemical and immunofluorescent methods. Results. Patients with endometrial hyperplasia showed the same distribution of ER and PR expression in both endometrial histogenetic structures, a high incidence of chronic endometritis, and positive expression of the inhibitor of cyclindependent kinases p16ink4a in the endometrial glands and stroma. Conclusion. The high frequency of chronic endometritis and positive expression of the inhibitor of cyclindependent kinases p16ink4a in the glands and the stroma of the endometrium indicates a violation of the cell cycle of endometrial cells against the background of a chronic inflammatory process and activation of proliferative processes.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):50-53
pages 50-53 views

Fast monitoring of long-range order in the ensemble of collagen domains in the achilles tendons and human knees in vivo

Zubow K., Zubow A., Zubow V.A.

Abstract

Aim. The dynamics of the collagen domain structure in the Achilles tendons and knees when they are stretched. Research method. A new non-invasive gravitational mass spectroscopy (GMS) method for operational (1...20 s) long-range order (LRO) monitoring in human tendons (achilles tendom and lateral collateral ligament) at the level of their molecular domains in vivo. As probands, members of the same family from 8 to 67 years old were involved. Results. Structural changes were detected in the forms of activated collagen domains in tendons at stretching. The domain masses range from 200 Daltons to 3,5 billion Daltons. Age differences and differences by gender in LRO were found. The domain ensemble itself has been established to be structured and represented by several sub-ensembles, reflecting the dynamics of giant micellar structures, structures in the NC1 range, as well as conformational constructions of domains inside the NC1 hexamer itself in the collagen. Conclusion. The method can be proposed for objective control of the state of wide tendons populations
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):54-60
pages 54-60 views

BSMI polymorphism (283G>A) VDR gene and phosphorus-calcium exchange parameters

Malyavskaya S.I., Kostrova G.N., Lebedev A.V.

Abstract

Introduction. Vitamin D is one of the main regulators of phosphorus-calcium metabolism. Vitamin D availability is determined by both external and genetic factors. The genetic contribution to the 25 (OH) D level is estimated to range from 23 to 77%. According to the literature, one of the candidate genes responsible for the efficiency of the endocrine system of vitamin D in the body is the gene encoding the vitamin D receptor (VDR), through which vitamin D realizes his functions. One of the most significant polymorphisms of the VDR gene is BSMI (283G>A). The aim of the study is to evaluate the effect of the BSMI VDR polymorphism on the level of 25 (OH) D and the parameters of calcium-phosphorus metabolism. Methods. A cross-sectional clinical and laboratory study included 124 persons (31 men (27,6%), 93 women (72,4%)). The sample age was of 18,44+0,25 years. During the study, the participants analyzed the level of 25 (OH) D, party hormone, total calcium, phosphorus, alkaline phosphatase, and the BSMI polymorphism of the VDR gene was determined. Results. In the total sample, the prevalence of genotypes of the VDR gene was: AA - 7%, GA - 41%, GG - 52%. The frequency of an occurrence of the A allele was 27,4%, and that of the G allele - 72,6%. The analysis did not reveal statistically significant differences in indices of phosphorus-calcium metabolism in carriers of different genotypes. There were no statistically significant differences between the distribution of genotypes in the presence and absence of vitamin D deficiency, as well as the influence of the genotype on the level ofparathyroid hormone. Conclusion. The results indicate the need to continue research on the role of genetic factors in the regulation of calcium-phosphorus metabolism, taking into account environmental influences.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(3):61-64
pages 61-64 views

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