Vol 13, No 2 (2018)

Cover Page

Full Issue


In the memory of Yuri Ivanovich Denisov-Nikolsky

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Genes & Cells. 2018;13(2):6-8
pages 6-8 views

Aspects for generation of transgenic mammals in the USSR: little-known details of an initial step

Dyban P.A.


This paper provides well-known as well as little-known data for initial steps of the development of transgenic mammals in the USSR, namely for the collaboration of the Department of Embryology (professor A.P. Dyban) of the Research Institute of Experimental Medicine of the Academy of Medical Sciences, USSR (Leningrad) and the Laboratory of Cellular Engineering (PhD. S.I. Gorodetsky) of the Institute of General Genetics of the Academy of Sciences, USSR (Moscow), and some details about the life journey of these research unit leaders.
Genes & Cells. 2018;13(2):9-12
pages 9-12 views

Fusion-phenomenon in normal histogenesis and in pathology: part 1

Buev D.O., Emelin A.M., Deev R.V.


Various processes happening in human organism depend on cell fusion (also called "fusion-phenomenon”). This review focuses on role of this phenomenon in the histogenesis of different tissues and molecular mechanism of the cell fusion. The Part 1 describes fusion-phenomenon in the normal, physiological conditions.
Genes & Cells. 2018;13(2):13-21
pages 13-21 views

Stem (progenitor) thyroid cells and their probable applications in tissue engeniring

Sergeeva N.S., Hesuani Y.D., Poljakov A.P., Mironov V.A., Kaprin A.D.


The review presents literature data on embryogenesis, physiological and reparative thyroid gland (TG) regeneration in the postnatal period in terms of substantiating the presence of stem/progenitor cells in its tissue. The data concerning genetic and protein markers of thyroid stem cells, as well as markers of their thyroid differentiation, are systematized. Unresolved problems and perspectives of the use of thyroid stem/progenitor cells in tissue engineering are discussed.
Genes & Cells. 2018;13(2):22-24
pages 22-24 views

Therapeutic strategies for targeting cancer stem cells

Alkon N.S., Ivanova A.E., Frolova E.I., Chumakov S.P.


Cancer stem cells (CSCs) are gaining extensive acknowledge as crucial therapeutic targets for treatment of malignant tumors. CSCs are able to maintain their population and to constantly generate newly differentiated tumor cells. Cancer stem cells that escape treatment are often considered the main source of tumor relapse. Resulting clinical significance had led to extensive studies of stem phenotype-contributing signaling pathways that are often abnormally active in cancer stem cells and CSC-specific traits, that could be used as selective therapeutic targets. Many CSC-targeting therapeutic strategies are currently undergoing clinical trials and evaluation, including various stem cell-specific signaling pathway inhibitors, cancer vaccines based on CSC-primed dendritic cells, monoclonal antibodies and chimeric antigen receptors for adoptive cell immunotherapy.
Genes & Cells. 2018;13(2):25-34
pages 25-34 views

Programmed necrosis and tissue regeneration

Kopeina G.S., Zamaraev A.V., Zhivotovsky B.D., Lavrik I.N.


Programmed necrosis or necroptosis plays an important role in cell physiology. Disturbances in necroptotic process are associated with excessive cell death, the development of a number of pathological conditions, including inflammatory and neurodegenerative diseases. Accumulated evidences suggest the involvement of necroptosis in the induction of stem cell proliferation and tissue regeneration. The necrotic death can be triggered through the family of receptors of tumor necrosis factor, TRAILR1/2, FAS, as well as endosomal Toll-like and NOD-like receptors. An important role in the regulation of necroptosis belongs to proteins RIPK1 and RIPK3, which also might be essential for proliferation of stem cells and the regeneration process. Recent study has shown that necroptosis can lead to rapid activation of progenitor cells and regeneration of the hepatic tissues, as well as a necrotic-induced tissue regeneration and differentiation of c-kit+ cells in a model of myocardial infarction. Thus, the investigation of interplay between necroptosis and regeneration of damaged tissues will allow us to understand the fundamental aspects of programmed cell death and cell division.
Genes & Cells. 2018;13(2):35-38
pages 35-38 views

The effect of oxygen concentration on embryo development and assisted reproductive technologies efficiency

Zhiryaeva E.A., Kiassov A.P., Rizvanov A.A.


Many different factors have an effect on the preimplantation development of embryos under conditions in vitro. One of these factors is the oxygen concentration in the culture medium. Currently, IVF labs have ability to cultivate embryos either under conditions of atmospheric oxygen concentration or at low oxygen concentration (hypoxia). This review is focused on the analysis of up to date research and clinical results which are trying to establish an "optimal” composition of the gas mixture in the incubator to generate more viable embryos and increase the effectiveness of assisted reproductive technologies programs.
Genes & Cells. 2018;13(2):39-46
pages 39-46 views

Molecular mechanisms of neuroinflammation initiation and development in a model of post-traumatic stress disorder

Tuchina O.P., Sidorova M.V., Turkin A.V., Shvaiko D.A., Shalaginova I.G., Vakolyuk I.A.


Neuroinflammation causes morphological and functional changes in the nervous tissue and it can be triggered by different kind of stressors. Progress of neuroinflammation as a result of post-traumatic stress disorder (PTSD) is associated with morphological changes in neurons and glial cells, as well as activation of microglia, however the exact molecular mechanisms of these changes are still unknown. In this review we discuss the connections between endocrine, immune and limbic systems during stress, the contributions of each system, the role of blood-brain barrier, as well as current methods and approaches in studying neuroinflammation.
Genes & Cells. 2018;13(2):47-55
pages 47-55 views

Morphofunctional characteristic of macrophages of embryonic and monocytic origin

Lokhonina A.V., Elchaninov A.V., Arutyunyan I.V., Pokusaev A.S., Makarov A.V., Eremina I.Z., Surovtsev V.V., Bolshakova G.B., Goldshtein D.V., Fatkhudinov T.K.


Macrophages of mammals are a heterogeneous population of cells. This applies both to the functional parameters of macrophages and to the sources of their development. The comparative characteristics of macrophages of embryonic origin on the example of Kupffer cells and macrophages of bone marrow origin on the example of macrophages of monocyte derivatives were carried out. Cultures of Kupffer cells and macrophages of monocytic origin were obtained. The phenotype, profile of gene expression of native macrophages activated in direction M1 and M2 was studied. The phenotype of isolated cultures is characterized by methods of immunocytochemistry, flow cytometry. Gene expression was studied by real-time polymerase chain reaction. Under the influence of inducing factors, the phenotype of two populations of macrophages changes in a similar way: under the influence of M1-factors, the synthesis of CD86 and iNOs is activated in cells, under the influence of M2 - CD163 and Arg1. In Kupffer cells, expression of anti-inflammatory cytokines - il4, il13, is more pronounced, and in macrophages of monocytic origin of pro-inflammatory cytokines - il1b, tnfa, il12a. The induction of the genes of proinflammatory cytokines in Kupffer cells is slower compared to macrophages of monocytic origin.
Genes & Cells. 2018;13(2):56-62
pages 56-62 views

Soluble factors formed during the healing of the endometrium suppress its "fibrosis” in vitro

Eremichev R.Y., Grigorieva O.A., Kulebyakin K.Y., Efimenko A.Y., Makarevich P.I.


During each period, the uterine mucosa of women of reproductive age heals without fibrosis. Previously, we established that the soluble factors that are released in this way have an antifibrotic effect on the culture of the human endometrial mesenchymal stromal cells. The objective of this work was to evaluate the antifibrotic properties of these factors on the in vitro endometrial fibrosis model. Serum menstrual and peripheral blood were obtained from a healthy donor in one day. Mesenchymal stromal cells of the endometrium were also isolated from menstrual blood. Simulation of endometrial fibrosis in vitro was carried out by differentiation of endometrial mesenchymal stromal cells into myofibroblasts under the action of TGF-ß1 (5 ng/ml). Evaluation of the effectiveness of the menstrual blood serum antifibrotic effect on the endometrial mesenchymal stromal cells and myofibroblasts derived from them was carried out by analyzing the expression of а-smooth muscle actin by immunofluorescence. Serum of peripheral blood with equal protein concentration was used as a control. Menstrual blood serum reduces the number of stress-fibrils positive for а-smooth muscle actin (a marker of myofibroblasts), both in the culture of endometrial mesenchymal stromal cells, and in in vitro modeling of endometrial fibrosis using TGF-ß1. These results indicate the presence of soluble factors in the serum of menstrual blood with antifibrotic properties. Perhaps their identification will explain the mechanisms of endometrial healing not accompanied by fibrosis. In addition, it can help to identify the causes of fibrosis of the uterine lining in gynecological diseases and develop effective methods for their treatment.
Genes & Cells. 2018;13(2):63-66
pages 63-66 views

Tissue morphogenesis features of the laboratory rats cervix a day before and in labor

Grigoryeva Y.V., Suvorova G.N., Iukhimets S.N., Pavlova O.N., Devyatkin A.A., Tulayeva O.N., Kulakova O.V.


The series of the morphological changes allowing providing timely disclosure of the cervical channel for a free foetus expulsion from the uterus cavity are observed in cervix a day before and during labour. The processes of morphogenesis in the cervix during delivery, with all realised functioning mechanisms in this organ, is essential for the development of the most effective methods of patrimonial process management. Therefore, the purpose of our research was studying of structural transformations in cervix a day before and in labour. We used the laboratory rat as a biological model. We applied several histological methods: light microscopy (stained with hematoxilin and eosin, by Masson), immunohistochemistry with a set of antibodies to type III collagen, and an electron transmission microscopy. We established that the basic supporting protein in the cervix is collagen III type; this type defines its mechanical features and leads key role in morphogenesis processes. The particular role in the cervix during parturition assigned to the type III collagen, which probably promotes to preserve cervix structures during parturition and prevents the emergence of disruptures. Intercellular substance components secretion, including collagen, is carried out by clasmacytosis in cervix leyomyocytes.
Genes & Cells. 2018;13(2):67-71
pages 67-71 views

Induction of capacitation of bovine spermatozoa before cryopreservation increases their viability after thawing

Denisenko V.Y., Kuzmina T.I., Boytseva E.N.


Cryopreservation of sperm is an important tool of reproductive biotechnology in the solving of the problems in infertility and reproduction of animals. In despite of the achievements in this field, the mechanisms that determine the cryoresistance of male gametes require further study. The damaging effect of ultralow temperatures during cryopreservation is primarily directed to the plasma membrane of spermatozoa. The purpose of this study is to analyze the viability of thawed bull spermatozoa after preventively induced capacitation with the further cryopreservation. Ejaculates of three noninbred bulls of Ayrshire and black-and-white breeds were used in the experiments. The functional state of spermatozoa was evaluated with a chlortetracycline test. Gametes were ranked in accordance with one of the three types of fluorescence of CTC-calcium-membrane complex : uniform fluorescence throughout the head (uncapacitated cells); fluorescence-free band in the post-acrosome region (capacitated cells); low fluorescence in the entire head, except for a thin bright fluorescence band in the equatorial segment (acrosome-reactive cells). The viability of spermatozoa was assessed with propidium iodide (5 |jg / ml). Capacitation was induced by heparin (5 jg / ml) or theophylline / dbcAMP (250/100 jM). It was shown that the induction of the capacitation of bull sperm by heparin, as well as theophylline /dbcAMP before cryopreservation enhances the number of viable sperm, reduces the number of capacitated cells and increases the number of sperm with acrosome reaction after thawing. In intact (without freezing) spermatozoa after induction of capacitation such effect is not revealed, the number of viable cells remained unchanged, the induction of capacitation caused an increase number of capacitated spermatozoa. The findings expand knowledge concerning the effects of extremely low temperatures on male gametes and can be used for modernization of the cryopreservation technology for increase their survival rate after thawing.
Genes & Cells. 2018;13(2):72-76
pages 72-76 views

Dynamics of humanin release and consumption of amino acids by differentiating C2C12 myoblasts

Zhloba A.A., Subbotina T.F., Smolina N.A., Kostareva A.A.


In the differentiating culture of myoblasts, the formation of myofibrils is accompanied by the consumption of amino acids and the release of their derivatives into the medium. The enhancement of mitochondrial metabolism precedes the formation of myofibrils. In this work, the release of a humanin-like peptide (HNLP, mt-RNR-peptide) and amino acid derivatives into the medium was studied in the differentiation of C2C12 myoblasts. Cells of the C2C12 line were cultured using standard techniques in plates with control of myofibril formation and samples selection for analysis at 0 (induction), 2, 4, 7, 9 and 11 days of differentiation. HNLP was determined by enzyme immunoassay, and amino acids and their metabolites by liquid chromatography. From the essential amino acids, branched chain - Val, Leu, Ile were most intensively consumed up to day 7 of differentiation. There was observed a mutual correlation between the daily production of arginine derivatives - homoarginine (hArg) and ornithine (r = 0.53, p = 0.008) with a maximum on day 2, a significant decrease of hArg production on day 4 and trace secretion after day 7. The release of HNLP, unlike hArg, lasts up to 4 days. Secretion of HNLP in course differentiating myoblasts is an early marker of the mitochondrial metabolism development. Its decrease by day 7 is associated to inhibition of the further existence of already differentiated myocytes. The early stage of cell culture differentiation is more clearly checked not by the level of essential amino acids intake, which presented in the cultivation medium at high concentrations, but by the formation of amino acid products of specialized metabolic pathways, including hArg and ornithine. The metabolic activity of mitochondria is confirmed by the secretion of HNLP. The specific functional activity of myocytes depends on the metabolic activity of the mitochondria, which can be checked without violating the integrity of the culture, according to the level of secreted HNLP.
Genes & Cells. 2018;13(2):77-82
pages 77-82 views

Effect of transplantation of allogeneic multipotent mesenchymal bone marrow stromal cells on regeneration of liver after extended hepatectomy (experimental study)

Rudakov V.S., Deev R.V., Gubarev K.K., Astrelina T.A., Eremin I.I., Zhgutov Y.A., Onnitsev E.I., Mavlikeev M.O., Titova A.A., Voskanyan S.E.


Multipotent mesenchymal stromal cells can be a drug for treatment of acute liver failure. The purpose of this study was to assess the effect of multipotent mesenchymal stromal cells on the proliferative, mitotic activity of hepatocytes and morphometric criteria for the regeneration of liver parenchyma after 68 % partial hepatectomy in rats. The number of mitosis, PCNA positive cells, diameter of nucleus of hepatocytes, size of hepatocytes, nuclear-cytoplasmic ratio (NCR), the area of hepatic lobules were evaluated on 1, 2, 4, 14 days after surgery. The results of the study showed that intravenous administration of allogeneic mesenchymal multipotent stromal cells from bone marrow after extended hepatectomy increase the number of proliferating hepatocytes (PCNA positive cells), but does not affect the number of mitoses, the diameter of the nucleus, the area of hepatocytes, NCR and hepatic lobules. Probably, at this time, regeneration proceeds primarily through an intracellular mechanism.
Genes & Cells. 2018;13(2):83-88
pages 83-88 views

Place of the discipline "Human Anatomy” in Medical Education of the 21st Century

Pavlov A.V.


Domestic higher medical education is going through a difficult period of reform of its training programs. These reforms are aimed at integrating Russian specialists into the global professional community. At the same time, the teaching of basic morphological disciplines, such as human anatomy and topographic anatomy with operative surgery, in most universities does not correspond to the main vectors of this process. In the presented article the main problems of teaching these disciplines are examined and ways of their solution are suggested. To maintain the background level of knowledge on human anatomy, two blocks are proposed: "General Anatomy” for the first year and "Special Anatomy” for the fourth year. This from the author's point of view makes it easier to learn the basics of body structure by undergraduate students and motivates undergraduates to more detailed study of anatomy in close integration with the clinic. Teaching of topographic anatomy and operative surgery is suggested to be carried out not only on 3-4 courses, but also on the postgraduate stage of training, then the level of training of specialists in domestic medicine will be higher.
Genes & Cells. 2018;13(2):89-
pages 89- views

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