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Vol 14, No 2 (2019)

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Open Access Open Access
Restricted Access Access granted
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Articles

PROFESSOR VLADIMIR TIMOFEYEVICH TALALAEV (TO THE 90TH DESCRIPTION OF HYSTOGENESIS OF RHEUMATIC GRANULOMAS)

Plaksa I.L., Deev R.V., Lobanov A.Y.

Abstract

The biographical article is dedicated to the memory of Vladimir Timofeevich Talalaev and is dedicated to the release of his main scientific work - the monograph «Acute Rheumatism», studied histogenesis of rheumatic granulomas (Aschoff body). The article presents the main periods of the life of V.T. Talalaeva and directions of work. The analysis of his contribution to the development of ideas about the pathomorphogenesis of acute rheumatism, as well as the formation of the modern look of the pathoanatomical service has been carried out. For the first time, previously unpublished materials from the archive of the MONIKI museum, where V.T. Talalaev spent most of his work and formed one of the most powerful centers for the development of pathomorphology at that time.
Genes & Cells. 2019;14(2):6-11
pages 6-11 views

CURRENT STATE OF TISSUE ENGINEERING FOR CARTILAGE REGENERATION

Beketov E.E., Isaeva E.V., Shegay P.V., Ivanov S.A., Kaprin A.D.

Abstract

The development of biomedical cell products for damaged cartilage recovery is an important direction of regenerative medicine. The review examines the main issues related to biodegradable tissue scaffold and hydrogel properties: selection of appropriate biomaterials, cells loaded and other supplements that could provide the best conditions for cartilage recovery. The results of in vitro and in vivo studies, as well as clinical trials registered at the National Institutes of Health database (ClinicalTrials.gov), are considered.
Genes & Cells. 2019;14(2):12-20
pages 12-20 views

SYSTEMIC MASTOCYTOSIS: CLINICAL AND MORPHOLOGICAL ANALYSIS FIVE PATIENTS WITH A RARE DISEASE

Plaksa I.L., Savin S.S., Charlanova E.M., Kravcova V.M., Afanasiev B.V.

Abstract

The central component of the diagnosis of systemic mastocytosis is a morphological study of the affected organ, which is aimed at assessing the volume of tumor infiltration and the pattern of damage, which may reflect the biological properties of the tumor and the prognosis of the disease. The material for the study was trephination biopsies and bone marrow smears of 5 patients with systemic mastocytosis, aged 17 to 68 years. Paraffin sections were stained with hematoxylin and eosin, azure by Romanovsky, and immunohistochemistry was performed with antibodies to CD25 (Interleukin-2 receptor alpha chain), CD2 (T-cell surface antigen T11/Leu-5), CD117 (Mast/ stem cell growth factor receptor) and tryptase. Bone marrow smears stained by Romanovsky-Giemsa. At the time of the diagnosis, the 2016 WHO revision classification was used. In all patients, a tumor was detected in SM. In the indolent form, the bone marrow diseases were located singly and discretely, and they also formed perisinusoidal and perivascular clusters up to 10-15 cells, the total number of which did not exceed 15% of all nucleated cells. On the contrary, in case of smouldering form (n=2), a nodular lesion pattern was revealed, in which mas-tocytes formed para- and intertrabecular foci of various shapes with sizes up to 200-300 cells, with a total volume of tumor infiltration of 36 and 43%. In two patients with an aggressive form of the disease, the infiltration volume of CM was 65 and 75%, while in both cases diffuse growth was observed, with a subtotal substitution of most of the bone marrow lacunae, with narrowing of hemopoiesis, as well as the appearance of secondary dysplasia features in erythroid and megakaryocytic lineages. Thus, the clinical manifestations of the disease correlate with the volume and pattern of CM damage in SM.
Genes & Cells. 2019;14(2):21-25
pages 21-25 views

CENTRAL NERVOUS SYSTEM ANTIGEN’S EPITOPES SELECTION, WHICH TAKE PART IN MULTIPLE SCLEROSIS PATIENTS AUTOIMMUNE REACTIONS, AS A WAY OF A SPECIFIC TOLEROGENITY CREATION

Bisaga G.N., Chirsky V.S., Baldueva I.A., Nechaeva T.L.

Abstract

To determine the central nervous system (CNS) peptide epitopes that take part in multiple sclerosis (MS) immune response, and taking into consideration the literature, we selected CNS peptides that most likely participated in MS immune response: MBP1 (83-99), MBP2 (111-129), MBP3 (146-170), PLP, and MOG. We estimated the specific activation of serum T-cells by the level of detected cytokines in 6 MS patients: 3 - with relapsing-remitting MS (RRMS), 2 - primary progressive MS (PPMS), 1 - secondary progressive MS (SPMS). As a result we revealed that all selected peptides took part in MS immunopathogenesis: in all patients MBP1 and PLP were involved; MBP2, MBP3, and MOG - in 5 of 6 patients. In response to CNS peptides T-cells most actively produced INFg, in a less degree - IL10 and IL4. In 5 of 6 cases we found negative correlation between levels of INFg and IL10. Cytokine levels did not differ between RRMS, PPMS and SPMS. Our results confirm the immunological phenomenon of epitope spreading that affects the efficacy of MS treatment, including immunological tolerance restoration.
Genes & Cells. 2019;14(2):26-31
pages 26-31 views

REPARATIVE RHABDOMYOGENESIS IN MICE WITH DYSF MUTATION

Chernova O.N., Mavlikeev M.O., Zeynalova A.K., Kiyasov A.P., Deev R.V.

Abstract

Dysferlinopathies are a group of muscular dystrophies with autosomal-recessive inheritance caused by mutations in DYSF gene. Dysferlin is a 237 kDa transmembrane protein responsible for reparation of the sarcolemma. It has calcium-sensitive C2 domains and after dysferlin binding with calcium ions the first one activates vesicles fusion and patch mechanism repair. There are number of knockout animal strains with dysferlin gene mutations. Bla/J mice have the ETn retrotransposon inserted in intron 4 of the DYSF gene of wild-type mice - C57Bl/6. The pathogenesis ascertainment of dysferlinopathies is important not only for revealing of physiological function of dysferlin, but its deficiency influence on reparative regeneration of skeletal muscles. In this paper the description of main pathohistological processes in skeletal muscle that take place in mice with dysferlinopathy after acute myotoxic injury is present. This article reviews quantitative evaluation of main pathomorphological processes in reparative regeneration: alteration (necrotized muscle fibers ratio), proliferation (Ki-67-positive myonuclei ratio), differentiation (mean cros-sectional area, percentage of centrinucleated muscle fibers, myo-genin-positive nuclei ratio, slow/fast muscle fibers ratio). It was identified that dysferlin-deficient mice have increased alteration level with more necrotized muscle fibers (35,1% (29,4%; 42,9%) in Bla/J vs. 25,8% (17,9%; 37,4%) in C57Bl/6 on 2 day after alteration, p<0,05) and decreased proliferation index and myogenic differentiation (3,2% (0,06%; 6,9% of myogenin-positive nuclei in Bla/J vs. 6,3% (1,3%; 15,3%) in C57Bl/6 on 4 day after injection) by contrast to control group.
Genes & Cells. 2019;14(2):32-39
pages 32-39 views

EVALUATION OF BIOCOMPATIBILITY AND EFFICIENCY OF PLASMID DNA DELIVERY BY GENE- ACTIVATED HYDROGELS IN VITRO

Bozo I.Y., Titova A.A., Zhuravleva M.N., Bilyalov A.I., Mavlikeev M.O., Yakovlev I.A., Eremin I.I., Pulin A.A., Komlev V.S., Deev R.V.

Abstract

Injectable forms of biomaterials have significant prospects for development of minimally invasive medical technologies in regenerative medicine. In this study, we evaluated the opportunities of using synthetic and natural hydrogels, including those containing calcium phosphates and hydroxyapatite, to deliver gene constructs, plasmid DNA molecules carrying some genes (encoding vascular endothelial growth factor, green fluorescent protein, or luciferase), to cells in vitro. The study of plasmid DNA delivery was performed in the line of mouse embryonic fibroblasts 3T3 using fluorescence and luminescent methods. Hydrogel biocompatibility was characterized in cultures of multipotent mesenchymal stromal cells. We found that the extracts of investigated hydrogels did not exert cytotoxic effects, however, with direct contact of materials containing either calcium phosphate particles or hydroxyapatite, a cytotoxic effect was observed. In the case of hydrogels based on collagen and hyaluronic acid that showed optimal biocompatibility, the transfection efficiency turned out to be low without using of a transfection agent and when used, it was 24 and 31%, respectively. Other variants of hydrogels did not provide plasmid DNA delivery, possibly due to cytotoxic effects. Further in vivo studies will clarify the features of plasmid DNA delivery with hydrogels, as well as evaluate the effectiveness of gene-activated hydrogels in tissue regeneration of the musculoskeletal system.
Genes & Cells. 2019;14(2):40-46
pages 40-46 views

STUDY OF BIOCOMPATIBILITY OF THE MATERIAL BASED ON SMALL INTESTINAL SUBMUCOSA IN TESTS IN VITRO AND IN VIVO

Dolgalev A.A., Venediktov A.A., Bobryshev D.V., Kruchinina A.D., Chagarov A.A., Evstratova Y.V., Zvyagina A.I., Krasnov K.S., Fadeeva I.S., Airapetov G.A.

Abstract

The development of barrier membranes for guided tissue regeneration remains an urgent task. A several authors proposed to use for this purpose xenomaterials from the small intestinal submucosa (SIS). The properties of such materials depend on the technology of donor cell removal (decellularization) and the condition of their extracellular matrix after processing (the presence or absence of proinflammatory damaged matrix components). The aim of this work was to study of biological properties of tissue-engineered xenogenic membranes made from porcine SIS by our patented technology (Cardioplant LLC, Russia) in experiments in vitro and in vivo. In vitro experiments was performed on cultures of multipotent mesenchymal stromal cells of the bone marrow and human skin fibroblasts, assessing viability, proliferative and mitotic activity of cells cultured on the surface of materials during 1 -7 days. The lyophilized barrier membrane bioPLATE MEMBRANE Barrier (Cardioplant LLC, Russia) used as control. To study of biocompatibility of experimental membranes in vivo, heterotopic implantation of materials to male Wistar rats was performed. The cell and tissue reactions and the degree of biointegration and the resorption of experimental materials were evaluated by rateover 14, 30, 60, and 90 days of implantation. The results indicate a higher biocompatibility of SIS-membrane compared with pericardial materials, and indicate the promise of using the porcine small intestinal submucosa to develop implants for guided tissue regeneration.
Genes & Cells. 2019;14(2):47-51
pages 47-51 views

IMPACT OF CANONICAL P-CATENIN/WNT SIGNALING IN NORMAL AND IMPAIRED BY ENDOCRINE DISRUPTOR DICHLORDIPHENYLTRICHLOROETHANE POSTNATAL DEVELOPMENT OF THE ADRENAL MEDULLA

Tsomartova D.A., Yaglova N.V., Nazimova S.V., Obernikhin S.S., Yaglov V.V.

Abstract

Exposure of developing organism to endocrine disrupting chemicals is an emerging scientific problem of wide concern. Dichlorodiphenyltrichloroethane (DDT) is considered to be one of the most wide-spread endocrine disruptors. Exposure of humans to low doses of DDT occurs around the globe. The present study was undertaken to elucidate the role of canonical Wnt-signaling in postnatal morphogenesis of the adrenal medulla in intact and developmentally exposed to DDT rats. The research was performed on male Wistar rats in pubertal (42nd day) and postpubertal (70th day) periods which were exposed to dDt during both prenatal and postnatal and only postnatal development. Adrenal histology showed enlargement of the adrenal medulla due to equal development of chromaffine cells and blood vessels from 42nd to 70th day in the intact rats and slower development of the adrenal medulla in the prenatally and postnatally exposed rats. Age-dependent changes in activation of canonical Wnt-signaling in the intact rats and altered Wnt-signaling along with impaired postnatal morphogenesis of the adrenal medulla in the DDT-exposed rats were found. The data obtained shows that prenatal exposure to DDT unlike postnatal exposure causes more profound decrease in activation of canonical Wnt-signaling in adrenal chromaffine cells and impairs development of adrenal medulla parenchyma.
Genes & Cells. 2019;14(2):52-57
pages 52-57 views

EFFECT OF ANGIOTENSIN II ON MATURATION OF OOCYTES OF COWS IN VITRO

Smetanina I.G., Tatarinova L.V.

Abstract

Physiological function of angiotensin II, in particular, the role of angiotensin II in the maturation of cows' eggs is not sufficiently evaluated. The purpose of this study was to evaluate the effect of different concentrations of angiotensin II on the maturation of the nuclei of cows' eggs in vitro in serum-free medium aMEM with hormonal additives or without them. In the first series of experiments, the cows' eggs matured in vitro in a medium containing hormonal additives with three different concentrations of angiotensin II (10-11, 10-9, 10-7 М). The criterion of successful maturation was the ability of the eggs to reach the stage of metaphase II. Our results demonstrate that angiotensin II in concentrations of 10-11, 10-9, 10-7 М does not affect the maturation of the egg nucleus in vitro if the maturation medium contained hormonal additives (57,1% eggs with the first polar body in the control vs 64,6% in the experiment; 60,8% vs 58,6%; 65,2% vs 66,7%, respectively). In the second series of experiments, the eggs were cultured in a medium without hormonal additives, where angiotensin II was added to a concentration of 10-7 М. Angiotensin II at a concentration of 10-7М significantly suppressed the release of the first polar body (43,6% in the control vs 29,3% in the experiment, P<0,05). This allows us to make a preliminary conclusion that the hormones cancel the inhibitory effect of angiotensin II on the maturation of the nucleus of cows' eggs in vitro. Further research is needed on the mechanisms by which angiotensin II regulates the maturation of cows' eggs. The question of angiotensin II as a possible component of culture media remains open.
Genes & Cells. 2019;14(2):58-61
pages 58-61 views

MORAL LIMITS OF GENOMIC RESEARCH AND BIOTECHNOLOGY AS THE BASIS TO FORME A LEGAL SPACE OF INNOVATIVE MEDICINE

Gerasimov A.M.

Abstract

Improving the human genome editing tools, scientists and medical practitioners are faced with the problem of deontological nature. The results of genetic research and experiments receive ambiguous ethical evaluation among representatives of scientific and medical community, the media and the public. Discusses issues of the moral component of intervention in human DNA. The purpose of the work is to substantiate the moral limits of genetic research and biotechnology. During the study, the dialectical method was used as a universal tool of cognition in combination with such general scientific and private scientific methods as formal-logical and systemic. In order to study public opinion on problem of moral conditionality of genetic science and biotechnology its own sociological research was conducted in the form of a survey of citizens. The study develops anthropological direction, which allows evaluating genetic science and innovative medical technologies from the position of natural freedom of individual. It is concluded that the scientific idea of modifying human genome in order to correct errors of nature meets the moral requirements. The set of people is indicated whose participation in genetic researches and experiments is not in a conflict to morality. The position of the Russian and foreign scientists on philosophical, ethical and legal problems of DNA editing in human cells is analyzed. A special attention is paid to the formation of the legal environment of innovative medicine.
Genes & Cells. 2019;14(2):62-67
pages 62-67 views

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