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Vol 16, No 4 (2021)

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Restricted Access Access granted
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Modern concepts about genetic regulation of connective tissue gystophysiology and its relationship to the physical quality of "flexibility”

Zholinsky A.V., Kadykova A.I., Deev R.V.


"Flexibility” is a physical quality of a person, which is characterized by the ability to perform movements with a large amplitude. Flexibility is important for success in such activities as sports (artistic and rhythmic gymnastics, figure skating, etc.), as well in classical choreography, for example, ballet. Extracellular matrix producing cells and structural proteins of connective tissues take an active part in the formation of mobility of the elements of the musculoskeletal system. Connective tissues are a complex structural and functional system, the components of which are encoded by many genes. Mutations in them lead to various hereditary diseases that increase or decrease "flexibility”. The role of genes in the formation of conditions encoded in the ICD-11 LD28.Z remains unclear - "Syndromes involving connective tissue as the main feature, unspecified”, and their prognostic significance for people experiencing intense physical exertion. The purpose of this review is to generalize modern ideas about the role of genes, extracellular matrix and cells producing it in the formation of such a physical quality as flexibility.
Genes & Cells. 2021;16(4):6-13
pages 6-13 views

Mitochondrial genome and aging of cardiomyocytes

Kolyubaeva S.N., Sveklina T.S., Shustov S.B., Chirsky V.S., Ovchinnikov D.V., Eliseeva M.I.


The review presents data on the importance of mitochondrial DNA in aging of cardiomocytes. The mechanisms of accumulation of mutations in mtDNA and reduction of its content, as well as the consequences of these phenomena in cardiomyocytes are described. The similarity of the aging processes of cardiomyocytes and skeletal muscle cells and comparison with the aging processes occurring in mononuclear cells of peripheral blood is indicated. The death of cardiomyocytes and skeletal muscle cells leads to the destruction of mutant forms of mtDNA, as a result of which the content of mutant forms of mtDNA, constantly increasing with age, does not exceed 1-2% of the total number of mtDNA molecules. In addition, the death of cardiomyocytes and myocytes is accompanied by the release of CpG-motive cells mtDNA, which can cause local and general inflammation in old age. It is concluded, that in the treatment of elderly patients it is desirable to take into account the degree of aging ("biological age”) of their myocardial and their presence of chronic myocarditis, for which appropriate diagnostic methods should be developed.
Genes & Cells. 2021;16(4):14-21
pages 14-21 views

Analysis of approaches to increase the efficacy of cell therapy based on mesenchymal stromal cells

Potapnev M.P.


The review considers the main stages of isolating, processing and clinical use of human mesenchymal stromal cells (MSCs). They included: donor selection, selection of the source of MSCs, methods of isolation of cellular suspension from tissue, culturing in vitro for cell biomass propagation, priming of the resulting cell product, timing and ways of its clinical application, selection of the recipient of MSCs. The analysis of the stages of MSCs preparation and conditions for their use was carried out from the position of the influence on the final therapeutic effect of cell therapy in patients (or experimental animals - in preclinical studies). The optimal parameters of work with MSCs at each stage, the possibility to improve their quality / biological activity in order to increase their therapeutic efficacy were determined. The analysis and ways of avoiding the influence of adverse factors associated with the manufacturing and use of MSCs on the effectiveness of cell therapy in patients were given.
Genes & Cells. 2021;16(4):22-28
pages 22-28 views

Metaplasia: transformation of views

Deev R.V., Indeikin F.A.


"Metaplasia” is a concept of differentiated cells and tissues transformation that has been discussed since the second half of the19th century. The issues of the research were the essence, mechanisms and role in histogenetic and pathological process. The aim of this review is an attempt to trace and analyse the evolution of ideas about cells and tissues transformation possibilities beginning from the R. Virchow observations (1958). Also there is a need to correlate them with the modern understanding of the issues of the of opportunities in cell differentiation and the underlying pathological processes.
Genes & Cells. 2021;16(4):29-41
pages 29-41 views

Immunohistochemical detection of stem cell markers, transcription factors and PD-L1 in malignant gliomas in adults patients

Sulin K.A., Galkovsky B.E., Petrov A.A., Ryzhkova D.V., Krasnoshlyk P.V., Gulyaev D.A., Makarov I.A., Gaycova O.N., Sidorin V.S., Mitrofanova L.B.


The prognosis of glioblastoma (GLB) is poor: the 5-year survival rate is less than 10%. Almost all patients relapse after surgery according to the standard of treatment: resection, radiation therapy, and temozolomide. T reatment options today for relapse are limited, and no amount of therapy prolongs patients' lives. The development of resistance to therapy is associated with the microenvironment and tumor stem cells. Objective: to study the expression of stem cell markers, transcription factors and PD-L1 in malignant gliomas. A retrospective study included 17 patients with high-grade gliomas who underwent surgery. All patients underwent traditional histological examination, immunohistochemical analysis with antibodies to IDH1R132H, BRAF V600E, Ki-67, GFAP, NANOG, Nestin, CD133, SALL4, OCT4, SOX2, CD38, PD-L1, FOXM1, morphometric analysis with calculation of the average ratio cells with antigen expression to the number of all tumor cells. Expression of NANOG was observed in 47% of cases, Nestin - in 88%, CD133 - in 71%, SOX2 - in 100%, CD38 and FOXM1 - in 65%. None of the tumors expressed SALL4, only one OCT4. PD-L1 expression was detected only in 2 cases. Correlation analysis established the presence of significant associations between the expression of Nestin and CD133; FOXM1 and NANOG; Nestin and CD38; Ki-67 and SOX2. The presence of expression of stem cell markers and transcription factors NANOG, Nestin, CD133, CD38, SOX2, FOXM1 in malignant gliomas, in our opinion, dictates further targeted study of these markers on a larger sample and opens up new potential targets for targeted therapy.
Genes & Cells. 2021;16(4):42-50
pages 42-50 views

Norepinephrine regulates osteogenesis in the embryonic period of development

Pasatetckaia N.A., Lopatin A.I., Klimshin S.I., Lopatina E.V.


Sympathetic and sensory nerve fibers regulate osteosynthesis and osteoresorption processes throughout life. Fundamental research and clinical data confirm the existence of functional interactions between neurons and bone tissue cells and indicate the catabolic and anabolic effect of sympathetic nervous system mediators on bone tissue. There is practically no information about the regulation of osteoremodeling in embryogenesis. Objective: to study the effect of norepinephrine on the growth of bone tissue explants in the embryonic period of development. The studies were performed on the bone tissue explants of 12-day old chicken embryos. Norepinephrine (10-10 M - 10-4 M), propranolol (10-10 M), atenolol (10-4 M), urapidil (10-6 M) were added to the experimental Petri dishes. Norepinephrine (10-6 M) stimulates the growth of the bone tissue explants through α1-adrenoreceptors. The osteotoxic effect of high doses of the drug is realized through β2-adrenoreceptors. Embryonic osteogenesis is regulated by norepinephrine in dose-dependent manner. Physiological effect of the substance depends on the interaction with certain types of adrenoreceptors.
Genes & Cells. 2021;16(4):51-54
pages 51-54 views

The relationship between myeloid-derived supressor cells and clinico-laboratory parameters in patients with liver cyrrosis

Leplina O.Y., Tikhonova M.A., Tyrinova T.V., Meledina I.V., Zheltova O.I., Ostanin A.A., Chernykh E.R.


In the present study, we used multicolor flow cytometry assay to measure the numbers of various myeloid suppressor cell subpopulations (Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD14+HLA-DRlow/-) in peripheral blood of 51 participants, including 33 patients with viral- and 1 8 patients with «nonviral» (alcoholic or biliary/autoimmune) liver cirrhosis. Patients in both groups had increased proportions of Lin-HLA-DR-CD33+, Lin-HLA-DR-CD33+CD66b+, and CD 14+HLA-DRlow/-cells which levels did not depend on the type and replication of the virus in viral liver cirrhosis. In viral liver cirrhosis, the relative numbers of Lin-HLA-DR-CD33+cells directly correlated with the albumin levels (Rs=0.45; p=0.029). In «nonviral» group an inverse relationship was found between these indicators (Rs = -0.56; p=0.02), in addition the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells directly correlated with disease severity scores (Child-Pugh and MELD) direct correlation of the proportion of Lin-HLA-DR-CD33+and CD14+HLA-DRlow/-cells with the disease severity scores (Child-Pugh and MELD). Comparison of the initial content of myeloid suppressors with the response to complex therapy (that included autologous bone marrow-derived cell transplantation), showed that in viral liver cirrhosis, the proportion of Lin-HLA-DR-CD33+cells was characterized by a prognostic significance and, at values <1.9%, allowed to predict a decrease in the Child-Pugh score at 12 month follow-up with a sensitivity of 83.3% and a specificity of 71.4%. The data obtained indicate the relationship between myeloid-derived suppressor cells and albumin levels, disease severity and response to therapy, suggesting myeloid suppressors as a new therapeutic target in the liver cirrhosis.
Genes & Cells. 2021;16(4):55-62
pages 55-62 views

Reparative regeneration of histogenetically different bones

Podluzhnyi P.S., Presnyakov E.V., Jemkov N.I., Sorochanu I., Deev R.V.


The bone plates that forming the turtle shell differ in histogenesis. Thus, the costal and neural plates of the carapace (dorsal shield) have mesenchymal origin and develop by indirect perichondral osteogenesis from vertebrae and ribs. The bone plates of the plastron - abdominal shield, are known to be formed from neuroectodermal cells of the neural crest and develop by intramembrane osteogenesis in the dermis of the skin. The aim of the study was to compare the reparative regeneration of histogenetically different bone tissue of the carapace and plastron of freshwater red-eared turtles Trachemys scripta. The experiment was performed on freshwater red-eared turtles Trachemys scripta aged 3 months. 2 defects of carapace and plastron bone plates with a diameter of 5 mm and a depth of up to "soft tissues” were formed with further histological examination. It was found that the regeneration of the bone plates of the plastron is characterized by the formation of bone tissue in a larger volume and at an earlier date. After 30 days a layer of continuous newly formed bone tissue is formed. By 90 days the proportion of bone tissue in the carapace regenerate was 40,5% of the defect area, while in the plastron the regenerate occupied 47,4%. Thus, intramembranous formed bone tissue of neuroectodermal histogenesis has a more pronounced regenerative potential compared to perichondral formed bone of mesenchymal origin.
Genes & Cells. 2021;16(4):63-67
pages 63-67 views

Instructions for authors

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Genes & Cells. 2021;16(4):68-70
pages 68-70 views

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