Vol 16, No 1 (2021)

Full Issue


For the anniversary of a colleague

Odintsova I.A., Deev R.V.
Genes & Cells. 2021;16(1):6-9
pages 6-9 views

Involvement of transposons in epigenetic regulation of embryogenesis

Mustafin R.N.


The systems that control DNA methylation and histone modifications in embryonic development are still considered unknown, although their study is promising for the development of stem cell genetics. This review article is devoted to the description of evidence that the drivers of changes in epigenetic factors of stem cells in their successive divisions are species-specific patterns of activation of transposable elements formed in evolution. These patterns are due to the sensitivity of transposons to the influence of the microenvironment and environmental factors, as well as the functioning of their processed transcripts as noncoding RNAs. A large amount of evidence has been accumulated that many protein-coding genes originate from transposable elements, including those involved in DNA methylation and histone modification. Moreover, transposons are key sources of binding sites for transcription factors, promoters, enhancers, silencers, insulators, as well as small and long non-coding RNAs that have an epigenetic effect on gene expression at the transcriptional and post-transcriptional levels. In evolution, transposons were the sources of origin for spliceoso-mal introns and components of the spliceosome, alternative sites and regulators of splicing. The identification of specific transposons that serve as drivers of stem cells at certain stages can become the basis for their optimal control using noncoding RNAs.
Genes & Cells. 2021;16(1):10-14
pages 10-14 views

Establishment of breast carcinoma cell lines

Mogilenskikh A.S., Sazonov S.V.


Obtaining of a primary cell culture of breast carcinoma is necessary both for the study of molecular and cellular mechanisms of tumor growth and for the selection of personalized therapy. However, when obtaining such culture, technical difficulties arise: poor adhesion to the substrate, increased growth of fibroblasts in culture, early aging, and others. The review describes the main options for culturing breast carcinoma cells - two-dimensional cultures, three-dimensional cultures, tissue sections, and also discusses methods for their preparation. The results of studies on changes in the receptor apparatus during cultivation and assessment of the effect of anticancer drugs on breast carcinoma cells in vitro are presented.
Genes & Cells. 2021;16(1):15-23
pages 15-23 views

Cellular and molecular mechanisms of pulmonary malformations

Blinova S.A., Oripov F.S., Khamidova F.M.


Until now, the cellular and molecular mechanisms of the development of lung defects remain a poorly studied area of pulmonology. In the occurrence of anomalies in the airways of the lungs, a change in the expression of proteins that control early lung morphogenesis in normal conditions (proteins FGF, TGF, SHH, WNT) was established. Along with this, bronchial markers and markers of type 2 alveolocytes play a certain role in the occurrence of lung defects. A number of congenital malformations are caused by improper formation of the airways, which may be associated with the influence of various soluble factors, receptors, transcription factors and microRNAs. The possible role of the pulmonary neuroendocrine system (apudocytes and neuroepithelial bodies) in the pathogenesis and pathobiology of childhood lung diseases, including congenital lung diseases, is discussed.
Genes & Cells. 2021;16(1):24-28
pages 24-28 views

Dynamic of tissue changes in oneand twostage treatment of chronic osteomyelytis using bioresorbable matirial impregnated with vancomicin (comparative experimental morphological study)

Konev V.A., Bozhkova S.A., Trushnikov V.V., Anisimova L.O., Netyl'ko G.I., Parfeev D.G.


The use of modern antibacterial agents and antiseptics in modern orthopedics does not always prevent infectious complications. Currently, two-stage surgical treatment with the implantation of an antimicrobial spacer is common. This method increases the duration of treatment, causing additional surgical trauma. The use of bioresorbable material with additional antibiotic impregnation simultaneously with the rehabilitation of the infectious focus can be considered a promising direction for improving the effectiveness of treatment of chronic osteomyelitis and reducing the treatment time of this group of patients. The main group consisted of rabbits with an experimental model of osteomyelitis followed by rehabilitation and one-stage replacement of the bone defect with bioresorbable material impregnated with vancomycin (n=12), and in animals of the comparison group (n=12) - two-stage surgical intervention with a similar material. Morphological studies were performed on animals of both groups on the 45th and 90th days after operations with replacement of a bone defect with a bioresorbable material with vancomycin. On the 45th day after the operation, the intensity of the processes of formation of newly formed bone tissue and restructuring of the osteoarthritis replacement material was more pronounced in the main group (28,2 vs 23,5%). Two-stage treatment is characterized by a more pronounced formation of fibrous tissue, the area of which in dynamics increased by 1,4 times (from 27,6 to 39,3%), with a single-stage method of treatment, this indicator increased only by 2% (from 22,9 to 24,9%). The infectious process was stopped in all experimental animals. The effectiveness of one-stage surgical treatment seems to be determined by a faster onset of osteohistogenesis in the area of a local osteomyelic defect when biocomposite is administered immediately after the purulent focus is sanitized. In addition, the absence of repeated surgical trauma with the loss of additional bone volume when removing the cement spacer during two-stage treatment is likely to play a significant role.
Genes & Cells. 2021;16(1):29-36
pages 29-36 views

Nuclear-nucleolar relationships and nucleolar stress in hepatocytes in hyperhomocysteinemia

Chuchkova N.N., Pazinenko K.A., Smetanina M.V., Kormilina N.V.


Hyperhomocysteinemia causes stress of the endoplasmic reticulum, which suggests the formation of nucleolar stress. The purpose of this work is to clarify the relationship between structural changes in the nucleus and the region of the nucleolar organizer in hyperhomocysteinemia to prove nucleolar stress in hyperhomo-cysteinemia, which can serve as an additional diagnostic marker of the disease. The object of the study was white mongrel rats with methionine-induced hyperhomocysteinemia. Histologic sections of the liver were stained with hematoxylin and eosin (to assess the histological structure of the organ, hepatocyte nuclei), ammonia silver (to analyze the areas of the nucleolar organizer - AgNORs). Morphometry has allowed to establish that hyperhomocysteinemia decreases the number of nuclei (1,86 times, p<0,05) and the total area occupied by nuclear material (1,69 times, p<0,05); decreases AgNORs (1,71 times, p<0,05) and the total area of the nucleolar organizer (2,31 times, p<0,05). In the hepatocytes of experimental animals, a class of nuclei with one nucleolus appears, but nuclei with 7 or more nucleoluses disappear, nucleolus of the inactive phenotype decreases (5,45 times, p<0,05), active (compact) AgNORs increases (2,15 times, p<0,05). The total number of argyrophilic granules, which characterize the number of RNA polymerases functioning in the cell, is also reduced, mainly due to silver granules localized extranuclearly. The detected changes in the AgNORs region can be characterized as nucleolar stress, the formation of which is caused by an increase in homocysteine levels and liver cell dysfunction. Thus, methionine-induced hyperhomocysteinemia leads to disorganization of nuclear-nucleolar relationships, is accompanied by nucleolar stress, and disrupts the nuclear stage of protein biosynthesis, which can exacerbate the existing pathology.
Genes & Cells. 2021;16(1):37-42
pages 37-42 views

Test-system in vitro for screening of therapeutic drugs with IL-17A inhibitory activity

Ossina N.K., Pugachev E.I., Kolyadenko I.A., Pryazhkina V.V., Shakurov E.G., Orlov E.V., Volova L.T.


To achieve greater clinical relevance of the newly discovered compounds, modern drug discovery requires disease-targeted assays based on human cells. The specific aim of this study was to design and develop a new cell-based assay for screening of compounds with IL-17A inhibitory activity. Human foreskin fibroblasts (HFF) were treated with IL-17A alone (experimental conditions I) or a mixture of IL-17A inhibitor netakimab and IL-17A (experimental conditions II). IL-17A - dependent production of inflammatory mediators IL-6, IL-8, MCP-1 was evaluated by ELISA (enzyme-linked immunosorbent assay). The study demonstrated the ability of HFF subcultured in vitro for a long time (>20 passages) to respond to IL-17A treatment by increased production of inflammatory cytokines IL-6, IL-8, MCP-1. Neutralization of IL-17A by netakimab (IL-17A inhibitor) resulted in a dose-dependent decrease of inflammatory cytokines production into cell growth medium. Thus, a new cell-based assay to evaluate the biological activity of Il-17A inhibitors has been developed and tested. The assay is based on the analysis of IL-17A-dependent production of inflammatory cytokines synthesized by human dermal fibroblasts. Netakimab has been shown to be a highly potent inhibitor of IL-17A.
Genes & Cells. 2021;16(1):43-48
pages 43-48 views

Diversity of haplogroup R1a-Z2122 in subpopulations of balkars and karachays according to microsatellite diversity

Dzhaubermezov M.A., Ekomasova N.V., Litvinov S.S., Tokareva E.A., Gabidullina L.R., Valiev R.R., Nurgalieva A.K., Khusnutdinova E.K.


Being one of the most mountainous Turkic peoples in the world, the genetic background of the Karachais and Balkars remains poorly understood. The aim of this study is to comprehensively study the haplogroup R1a-Z2122 of the Y-chromosome in the population of Karachais and in the sub-ethnic groups of Balkars. The material for the study was DNA samples from Karachais (n = 126) and Balkars (n = 235). The analysis of the genetic diversity of the population of Karachais and subpopulations of Balkars living in the central part of the North Caucasus region was carried out according to the data on the distribution of Y-SNP (Single nucleotide polymorphism) hap-logroups and Y-STR (Short tandem repeats) haplotypes. According to the results of genotyping of the R1a-Z2122 haplogroup in the Balkar subpopulations, the R1a-Z2122 haplogroup was detected with a frequency of 3.4%, and in the Karachai population - 2.4%. In the course of studying the distribution of this haplogroup in sub-ethnic groups of Balkars, its high content in the group of Chegemians was shown, where it is 6.8% of the diversity of haplogroups of the Y-chromosome. In the group of Baksans, the frequency of this haplogroup decreases to 4.8%, among Bezengievs it is found in 2.6% of the population, and among Malkars in 1.7%, while this haplogroup was not found in the Kholam population. For the analysis of STR-haplotypes of the Y-chromosome, we selected 11 samples belonging to the haplogroup R1a-Z2122. As a result of the construction of the median network and the circular dendrogram, significant variability was shown within the studied sample. The data obtained by us as a result of the research can be used in the development of courses for students of biological, historical and medical specialties. The created unique collection of DNA samples from Balkars and Karachais can subsequently be used for population, evolutionary, and medico-genetic studies.
Genes & Cells. 2021;16(1):49-52
pages 49-52 views

The effect of antihistamines drugs on the functional activity of neutrophils

Plekhova N.G., Dubnyak I.N., Eliseeva E.V.


Allergic inflammation is accompanied by stimulation of neutrophils with an increase in the formation of reactive oxygen species. The antioxidant effectiveness of some antihistamines is known, which reduces the risk of damage to surrounding tissues with the participation of these cells. Objective of the study: to determine the degree of various generations antihistamines influence on the death and enzymatic activity of neutrophils. The effect of the first antihistamines (diphenhydramine, clemastine) and second (lorata-dine, desloratadine) generations and the hormonal drug dexameth-asone on cell viability, the formation of active oxygen metabolites, enzyme activity, the amount of cationic proteins, and cytokine production by neutrophils was studied using the in vitro model. It was found that after exposure to loratadine at a dose of 2.5 |jg / ml, the number of viable cells was comparable (p = 0.001) with that in an intact culture. Found a stimulating effect of second generation antihistamines (loratadine, desloratadine) in low doses on the activity of NADPH-dependent oxide reductase. The form of neutrophil death depended on the type and dose of the drug; apoptosis was predominantly observed after cell contact with loratadine and desloratadine. Against the background of an increase in the activity of ATPase and myeloperoxidase after contact with diphenhydramine and clemastine (2.5 jg / ml), the largest number of neutrophils producing reactive oxygen species was revealed. Under the influence of desloratodine and clemastine, exocytosis of cationic proteins into the extracellular space and the lowest production of cytokines after contact with the latter were established. Thus, exposure to Hl-antihistamines, active both extra- and intracellular (diphenhydramine, loratadine), probably disrupted the metabolism of neutrophils, which led to an increase in their killer potential. Clemastine, acting mainly extracellularly, minimized the toxic effects of extracellular radicals, without affecting the production of intracellular oxidants involved in the regulation of neutrophil functions.
Genes & Cells. 2021;16(1):53-59
pages 53-59 views

Morphological and functional charakteristics of histogenetically related structures - producers of monoamines - in the local regulatory apparatus of the large duodenal papilla

Dekhkanov T.D., Oripov F.S.


Purpose of the study. Study of the morphology of open-type fluorescent cells and adrenergic nerve structures of the major duodenal papilla. Material and research methods. The material for the study was the area of the large duodenal papilla of 12 rabbits and 5 dogs. Fluorescent endocrine cells and adrenergic nerve structures were revealed by processing cryostat sections of the material with a gly-oxylic acid solution. Research results. It has been established that the fluorescent cells of the diffuse endocrine (APUD) system contain serotonin and catecholamines, the shade of their luminescence depends on the quantitative ratio of which. Where these two structures are located side by side, the shade of the glow is approximately the same. Discussion. It is assumed that the implementation of a complex response to the primary chemoreceptor information on the composition of the chyme, obtained by the fluorescent cells of the diffuse endocrine system of the major duodenal papilla, occurs through the exchange of biogenic amines between them and the adrenergic nerve structures of the duodenal papilla.
Genes & Cells. 2021;16(1):60-63
pages 60-63 views

Comparative analysis of the regeneratory potential of blood derivatives on a cell model of corneal epithelium damage

Subbot A.M., Trufanov S.V., Shakhbazyan N.P.


The problem of the restoration of the epithelial layer after various modifications of keratoplasty is of great fundamental interest. In this regard, new methods of induction of regeneration are being developed; one of the promising approaches in this area is the use of autologous blood derivatives with a high regenerative potential. Objective: to compare the effect of 3 blood derivatives serum, platelet-rich plasma and plasma rich growth factors on the culture of corneal epithelial cells. The study was carried out on cells of the epithelium of the human cornea of passage 3. To confirm corneal affiliation, cells were typed for characteristic cytokeratins. The dynamics of migration was assessed in the test for wound healing of the monolayer. Proliferation was assessed by the results of the formazan test. Plasma rich growth factors had the greatest stimulating effect on cell proliferation. There were no significant differences between groups in the rate of wound healing of the monolayer. It was found that, in comparison with the control, all stimulants shift the morphological phenotype of cells to a more mature side. As a result of the study, it was shown that all 3 types of tested blood derivatives are promoters of corneal re-epithelialization. The use of drugs obtained from blood can positively influence the processes of epithelialization in persistent epithelial corneal defects, which requires further study.
Genes & Cells. 2021;16(1):64-68
pages 64-68 views

Features of histotopography of skin mast cells when simulating a burn under conditions of using various methods of regional exposure

Soboleva M.Y., Nikityuk D.B., Alexeeva N.T., Klochkova S.V., Atyakshin D.A., Gerasimova O.A., Sokolov D.A., Kvaratskheliya A.G.


The issues of skin regeneration during thermal injury are an urgent problem of modern biomedicine. The quality and speed of restoration of the damaged epidermis largely ensures the quality of life of patients. The optimal method of wound treatment depends, inter alia, on knowledge of the structural and functional features of the extracellular matrix of the connective tissue of the dermis, including the amphora and fibrous components. Material and methods. In a study on adult Wistar rats, we modeled second degree burns of the posterior surface of the torso with an area of 1 0% of the body surface for the purpose of histological and immunohistochemical assessment of the involvement of mast cells in the wound process and their importance in the implementation of collagen fibrillogenesis in various protocols for the treatment of burn wounds. A planimetric analysis was carried out to obtain quantitative data on the content of mast cells per mm2 of the skin, their histotopography and morphofunctional typing were determined to assess the secretory activity. Results. The study revealed that the burn wound caused an increase in the population of skin mast cells with certain histotopo-graphic patterns, in particular, predominant accumulation in the peripheral region of the alteration zone. An increase in the secretory activity of mast cells led to a systemic reconstruction of the extracellular matrix, stimulating the healing processes by activating the formation of the fibrous component of the connective tissue. After thermal exposure, a significant increase in tryptase expression in the mast cell population was revealed when using water with an increased content of molecular hydrogen. Conclusion. The revealed features of various protocols of wound management in the efficiency of regenerative processes are due to the degree of involvement of mast cells in fibrillogenesis using direct and indirect pathways. Thus, the molecular mechanisms of extracellular matrix remodeling, induced by the secretory activity of mast cells, are promising targets for intensifying the regenerative effects of pharmacological agents.
Genes & Cells. 2021;16(1):69-74
pages 69-74 views

Umbilical cord blood cells in the treatment of patients with schizophrenia in remission

Morozova Y.V., Radaev S.M., Voronova E.I., Emelina D.A.


Schizophrenia is one of the most severe chronic relapsing mental diseases that significantly affect the level of social adaptation and quality of life of patients, often leads to their disability. Despite the success of modern psychopharmacology, achieving sustainable remission in schizophrenia remains a difficult task. The purpose of the study were the assessments of the safety and tolerability of intravenous administration of allogeneic AB0/ Rh-compatible mononuclear cord blood cells, as well as to study changes in cognitive performance in patients with schizophrenia in remission after treatment with umbilical cord blood cells. The study involved 30 patients with schizophrenia (men; average age 32,4 ± 9,7 years) in a state of hypochondria remission with a predominance of cognitive disorders against the background of prominent negative changes (F20.01-F20.04 according to ICD-1 0). Design is a prospective, placebo-controlled trial of efficiency and safety. The study consisted of 2 phases. In the pilot phase (3 months), the tolerability of a single cryopreserved concentrate of human cord blood injection containing mononuclear cells in a dose of 260± 20 million cells was estimated. The duration and severity of the effect was compared with placebo. In the clinical phase (48 months), patients received 4 injections of cord blood cell suspension in the same dose with intervals of 14 ± 3 days. The efficacy and safety of exposure were assessed using psychopathological, psychometric (scale of positive and negative symptoms of schizophrenia - PANSS) and psychological (The MATRIX Consensus Cognitive Battery) methods. The obtained results allow to conclude that the influence of human cord blood mononuclear cells on cognitive functions is realized due to the expressed metabolic (nootropic) and psychostimulating effects and restoration of normal neurotransmitters ratio. The effects are manifested in the form of activation of intellectual activity, acceleration of information processing, correction of memory functions, increase in the level of attention and vigilance, as well as a noticeable increase in "social intelligence” and, as a result, improvement in the quality of life. The effect of applying cord blood cells to enhance cognitive functions is characterized by resistance and duration of at least 4 years.
Genes & Cells. 2021;16(1):75-81
pages 75-81 views

The hipotises of the immune system's role in carcinogenesis

Slepov Y.K., Laushkin M.A., Deev R.V.


The presented controversial hypothesis is an attempt to reflect on the role of the adaptive immune response in carcinogenesis. It is a well-known fact that the most of the signaling pathways which are participating in embryogenesis and regeneration are also active in tumor growth. Considering their presence in different evolutionary groups, there's such a contradiction that with same mechanisms of proliferation, animals with high regenerative potential are less predisposed to malignancy than mammals. Comparing these two groups, it's being discovered that despite the importance of immune control as a factor impeding carcinogenesis, the animals' immune system with high regenerative potential is less developed. The above is a reading of the complete or partial absence of the adaptive link of immunity. These described distinctions have formed the basis of the hypothesis of the procarcino-genic role of the adaptive immune response.
Genes & Cells. 2021;16(1):82-91
pages 82-91 views
pages 92-93 views

Genome editing techniques: from yeast to human cells

Zhivotovsky B.D.
Genes & Cells. 2021;16(1):94-95
pages 94-95 views

Instructions for authors

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Genes & Cells. 2021;16(1):96-98
pages 96-98 views

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