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Vol 17, No 1 (2022)

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Telocytes: localization, structure, functions and significance in pathology

Odintsova I.A., Slutskaya D.R., Berezovskaya T.I.


The review article presents the material analyzing and summarizing the information about the localization, ultramicroscopic structure, functions and significance in pathological processes of newly discovered cells - telocytes. The information about molecular markers of telocytes are considered. The questions about the tissue belonging of these cells are discussed, the relevance of studying their role in the development of pathological processes in different organs is emphasized. The analysis of literature data was carried out taking into account the fundamental provisions of the doctrine of the cell-differon organization of tissues.
Genes & Cells. 2022;17(1):6-12
pages 6-12 views

Multiomics approaches to search for molecular-genetic predictors of osteoporosis

Yalaev B.I., Tyurin A.V., Khusainova R.I.


The identification of genetic loci and biochemical markers associated with the risk of fractures and the level of bone mineral density (BMD) did not give an unambiguous answer about the molecular pathogenesis of osteoporosis (OP). There are still unresolved questions about the possibility of early diagnosis and prognosis of the course of the disease. The molecular effects of genetic variants located in the coding regions of the human genome are easy to study. However, most of the single nucleotide polymorphic loci that are associated with osteoporosis susceptibility are located in non-coding or intergenic regions. Their role in the pathogenesis of this disease is not fully understood. The use of biochemical markers in the diagnosis and monitoring of osteoporosis therapy does not allow developing approaches to early diagnosis of the disease before a fracture occurs. Significant problems arise in the interpretation of research results for use in clinical medicine. But the combination of multidisciplinary data, such as genome-wide association study (GWAS), changes in the patterns of biogenic elements of bone remodeling, catalytic activity of a number of enzymes, and protein expression has significantly expanded the understanding of the key links in the pathogenesis of the disease. The article reviews and summarizes the latest advances in multiomics studies of osteoporosis, including bionformatic analysis to find key risk factors for the development of OP, as well as pharmacogenetic aspects of modern therapy of the disease.
Genes & Cells. 2022;17(1):13-18
pages 13-18 views

Safety and efficiency of inhalation method for administration of small extracellular vesicles derived from multipotent mesenchymal stromal cells of human umbilical cord in SARS- CoV-2 associated pneumonia

Tiumina O.V., Davydkin I.L., Volchkov S.E., Ovchinnikov P.A., Bugakov A.I., Sharonova D.U., Konstantinov D.U., Zolotovskaya I.A.


The coronavirus infection (COVID-19), an acute viral disease with predominant affection of the upper respiratory tract, is a challenge for modern medicine. Considering the fact that in the pathogenesis of coronavirus pneumonia there is violation of the immune response (hyper-response, cytokine storm) the drugs that locally regulate it may be promising in the pneumonia treatment. Biological activity of exosomes is widely investigated in the world. Small extracellular vesicles of mesenchymal cells have the following effects: anti-apoptotic, proliferation stimulation, anti-inflammatory and immunomodulatory. Objective: to evaluate the safety and efficacy of the method of inhalation administration of small extracellular vesicles in bilateral pneumonia caused by a new SARS-CoV-2 coronavirus infection. To study these effects an interventional, prospective, randomized, double-blind, placebo-controlled study has been conducted to evaluate the safety and efficacy of inhaled small extracellular vesicles administration to the patients with bilateral pneumonia caused by the new coronavirus infection SARS-CoV-2. Altogether 36 patients with confirmed new coronavirus infection COVID-19, complicated by bilateral pneumonia of moderate severity (12 patients each in study groups 1 and 2, depending on the type of given small extracellular vesicles, and the control group) participated in the study. Small extracellular vesicles were inhaled twice a day in the dose of 2-10х1010 particles. The efficacy and safety of the method were assessed judging by the patients' general state, assessment of the disease severity, general and biochemical blood tests, coagulogram, saturation, CT scan of the lungs before and after 1 0 days of treatment. The observation period was 30 days after hospitalization. During the study the safety of the method was proved, all the patients recovered. Reliable differences of the blood CRP index, which normalized by day 10 of treatment in groups 1 and 2, but remained elevated in the control group. No significant differences were found in other assessed parameters.
Genes & Cells. 2022;17(1):19-25
pages 19-25 views

Structural and functional transformations of the brain in experimental mild traumatic brain injury

Plekhova N.G., Radkov I.V., Zinoviev S.V., Shumatov V.B.


In mild traumatic brain injury, it is of interest to study neurode-generative conditions resulting from inflammatory changes in the nervous tissue. Purpose of the study: in the acute period in case of mild experimental traumatic brain injury, to reveal structural transformations of the nervous tissue of the brain. A modified model of a falling weight was used to reproduce of these trauma in adult rats. An immunohistochemical study of the brain with using rat-specific monoclonal antibodies to endothelin-1, glial fibrillar acidic protein, vimentin, and blood-brain barrier endothelial protein (SMI 71) was performed. It has been established that on the first day after injury in the cerebral cortex of animals, the spasm of blood vessels with capillary ischemia predominates. On day 8, there is an increase in the number of hyper- and hypochromic neurons, and after 14 days, restoration of the tone of the microcircu-latory bed is detected with signs of a violation of the permeability of the blood-brain barrier. A significant redistribution in the tissues of the cerebral hemispheres of glial elements containing acid glial protein and vimentin, as well as neurons producing endothelin-1, was noted. In the delayed post-traumatic period, compensatory reactions of the nervous tissue were revealed, which are characterized by the presence of morphological changes in neurons (an increase in the diameter and number of nucleoli in size) associated with intracellular regeneration, as well as the synthesis of various protein factors in them. Thus, the pathogenesis of mild experimental craniocerebral injury in the ischemic (1 day) and intermediate (8 days) periods is characterized by the presence of mild violations of the structural integrity of the nervous tissue of the brain. In the late post-traumatic period (14 days), neurons and astrocytes exhibit compensatory reactions.
Genes & Cells. 2022;17(1):26-30
pages 26-30 views

Expression profile of the microenvironment of morphological structures in luminal breast cancer

Tashireva L.A., Gerashchenko T.S., Zolotareva S.Y., Perelmuter V.M.


In breast cancer, the predictive value of tumor microenvironment parameters differs depending on the molecular subtype. Multidirectional significance may be reflection of heterogeneity of invasive breast carcinoma and requires further study. Significance of the tumor microenvironment in the formation and determination of the properties of various morphological structures is still not fully understood. The aim of the study is to determine the differences in the expression profile of the microenvironment of various morphological structures of breast cancer. 84 patients with breast cancer (T1-3N0-3M0) were included in the study of tumor-infiltrating lymphocytes level in microenvironment of different morphological structures. Microdissected samples of the microenvironment of different morphological structures sequenced using NextSeq500 (Illumina). CIBERSORT analysis was performed to deciphered the cellular composition of the microenvironment of each type of the structures. The microenvironment of all morphological structures was quite diverse in terms of cellular composition. The microenvironment of the single tumor cells exhibits pronounced pro-tumor properties, including expression of the IL1B gene, activation of inflammatory signaling pathways, increased signature of M2 macrophages. The results shown the role of the microenvironment of single tumor cells in breast cancer distant metastasis.
Genes & Cells. 2022;17(1):31-37
pages 31-37 views

Cells corresponding to telocites have been detected in pathologically altered skeletal muscle

Chekmareva I.A., Deev R.V., Chernova O.N., Bikhteev I.U., Emelin A.M.


A relatively recently described population of cells, apparently belonging to the tissue system of the internal environment, are the telocytes. Their peculiarities are not only the co-expression of CD117- and CD34-molecules, but also thin, indistinguishable processes at the light-optical level, whose length can be many times greater than the diameter of the cell body. In this regard, transmission electron microscopy remains the method of choice for their detection in tissues. Telocytes were found in the myocardium, connective tissue of the gallbladder, in gastrointestinal tract, in the stroma of the exocrine glands, the placenta, some vessels. However, data on the detection of telocytes in striated skeletal muscle tissue are either absent or still rare. This brief report demonstrates cells that, by their ultrastructural characteristics, can be identified as telocytes in the endomysium of gastrocnemius muscle in Bla/J mice (mutation in the dysferlin gene, DYSF).
Genes & Cells. 2022;17(1):38-41
pages 38-41 views

Elastic ear cartilage of Acomys mice is recovering after injury

Bilyalov A.I., Filimoshina D.D., Filatov N.S., Bilyalova A.A., Titova A.A., Gataullina L.R., Plushkina A.S., Shagimardanova E.I., Deev R.V., Kiyasov A.P., Kozlova O.S., Nesmelov A.A., Gusev O.A.


The article presents data on the regeneration of the auricle tissues of Acomys cahirinus mice (n=12) and Balb/c mice (n=12). Two experimental models were used: a full-thickness perforated defect with a diameter of 3 mm and subtotal removal of the auricle. Macrophotography and histological examination using general histological stains and detection of elastic fibers were performed after 2, 5, 15, 21, 30, 60, 90, and 120 days. It was found that regeneration in Acomys is more pronounced, which manifested itself in the complete elimination of the defect by 30-60 days in contrast to the control (Balb/c). A feature of this was less pronounced post-traumatic inflammation in Acomys mice. It was established the growth of a full-fledged auricle in case of its surgical removal. An important feature of regeneration in this case is the development of new cartilage tissue both from the edges of the original cartilage and developed in the form of separate islands of cartilage tissue. The newly formed cartilage was characterized by high cel-lularity, a smaller volume of the matrix, in the structure of which elastic fibers were formed. However, it should be noted that within 30-60 days. the recovery process, apparently, is not completed, the formed tissue regenerate enters the remodeling phase.
Genes & Cells. 2022;17(1):42-47
pages 42-47 views

The origin of menopause

Boyarsky K.Y., Skobeeva V.A., Chekhonina O.B., Kahiani E.I.


The origin of menopause is mysterious and difficult to explain in terms of evolutionary theory. Menopause is described in humans and in four cetacean species. Natural selection cannot act on a trait that appears after the end of reproduction; therefore, it cannot be formed by the classical selection mechanism. All the proposed theories of the onset of menopause, adaptive and non-adaptive, can explain the benefits of menopause, but are completely untenable from the point of view of the theory of evolution and do not answer the main question - how did it arise. We propose a hypothesis based on the assertion that menopause is a byproduct of the rapid increase in the size of the cerebral cortex during the formation of Homo sapiens. Genes associated with the development of congenital microcephaly, which are responsible for the development of the cerebral cortex, were identified, and clear traces of natural selection were found in them, and a powerful evolutionary process continues up to the present. Most products of these genes are associated with the process of formation of the cell division spindle, both in the process of mitosis and meiosis. We hypothesize that the rapid evolutionary process that led to the growth of the cerebral cortex in humans, as a side effect, led to the formation of a high frequency of aneuploidy in oocytes. A similar process has also led to the formation of menopause in cetaceans.
Genes & Cells. 2022;17(1):48-54
pages 48-54 views

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Genes & Cells. 2022;17(1):55-57
pages 55-57 views

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