[The study of interaction of different forms of human recombinant anti-mullerian hormone with a chimeric analogue of the AMH type II]. / Issledovanie vzaimodeistviia razlichnykh form rekombinantnogo antimiullerova gormona cheloveka s khimernym analogom ego retseptora II tipa.

The homodimeric glycoprotein, anti-mullerian hormone (AMH), described over 70 years ago by A. Jost, is the least studied member of the transforming growth factor beta superfamily. Despite the antitumor activity of AMH discovered at the end of the last century, the creation of effective drugs based on AMH is hindered primarily by the lack of information on the mechanism of various AMH forms interaction with a specific type II receptor (MISRII). Previously, we have shown that not only the full-length activated hormone but also its C-terminal fragment (C-rAMH) could bind to MISRII. In this work, using the surface plasmon resonance technique, we compared the interaction of three forms of recombinant AMH (rAMH) with the MISRII analogue - the chimeric protein MISRII-Fc containing AMH type II receptor and a Fc-fragment of the human IgG1 heavy chain. Comparison of the binding of MISRII-Fc, immobilized on a chip with group specificity for human immunoglobulins, to C-rAMH, to intact rAMH (pro-rAMH), and to rAMH containing one uncleaved monomer (hc-rAMH), showed that the KD of the complexes increased: 1.7 nM, 88 nM and 110 nM, respectively. Thus, we have shown that C-terminal fragment of AMH has the maximum affinity for the recombinant MISRII analogue, which indicates the prospects for the development of drugs based on this hormone derivative.

Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19.

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms - in gray, hydrogen atoms - in white, and phosphorus atoms - in yellow.

[Mullerian inhibiting substance type II receptor as a potential target for antineoplastic therapy]. / Retseptor antimiullerova gormona II tipa kak potentsial'naia mishen' dlia protivoopukholevoi terapii.

The review considers properties of the type II anti-Mullerian hormone receptor (mullerian inhibiting substance receptor type II, MISRII), a transmembrane sensor with its own serine/threonine protein kinase activity, triggering apoptosis of the Mullerian ducts in mammalian embryogenesis and providing formation of the male type reproductive system. According to recent data, MISRII overexpression in the postnatal period is found in cells of a number of ovarian, mammary gland, and prostate tumors, and anti-Mullerian hormone (AMH) has a pro-apoptotic effect on MISRII-positive tumor cells. This fact makes MISRII a potential target for targeted anti-cancer therapy. Treatment based on targeting MISRII seems to be a much more effective alternative to the traditional one and will significantly reduce the drug dose. However, the mechanism of MISRII-AMH interaction is still poorly understood, so the development of new anticancer drugs is complicated. The review analyzes MISRII molecular structure and expression levels in various tissues and cell lines, as well as current understanding of the AMH binding mechanisms and data on the possibility of using MISRII as a target for the action of AMH-based antineoplastic drugs.

[The dynamics of human total and activated anti-mullerian hormone serum levels in different life periods.]

Here, changes in the serum level of total anti-mullerian hormone (AMH) and its activated form in children of both sexes and women with different reproductive status are investigated. This TGFß superfamily cytokine is known to provide the formation of the male-type reproductive system in mammalian embryogenesis, and regulate folliculogenesis, spermatogenesis and the balance of sex hormones after birth. The biologically active form of the hormone (aAMH) is formed as a result of limited proteolysis of the AMH molecule; it is not reliably known in which tissues and under the action of which enzyme it occurs. The serum level of aAMH seems to be a more informative clinical indicator than the content of total AMH (tAMH), but there are no ELISA systems at the world market that provide direct quantitative detection of aAMH. In this work, quantitative detection of total hormone (tAMH) and its biologically active form (aAMH) in serum was performed using specially developed enzyme immunoassay systems. We showed that in girls, the total serum AMH level, as well as the concentration ratio aAMH / tAMH, practically does not change with age, whereas in boys, there is not only a significant decrease in the total serum AMH level previously described in the literature (Pearson correlation coefficient R = - 0.86, p <0.001), but also in the ratios of the aAMH / tAMH level (R = -0.531, p <0.001). It was also found that in pregnant women, the amount of total AMH and the proportion of aAMH in serum was significantly higher (p <0.01 and p <0.001, respectively) than in the control group women. The obtained results are in good agreement with the available data on the total and activated AMH content in the blood serum of people of different sex and age and indicate a change in the ratio of aAMH / tAMH serum levels in pregnancy. These data may be important both for deepening the understanding of AMH biology and for interpreting the results obtained using AMH detection based diagnostics.

[Tripeptide restorates structure of duodenum at accelerated aging].

Effect of tripeptide on the process of postradiational restoration of duodenum in rats has been studied in model of accelerated aging. Geroprotective effect of tripeptide was connected with reparation of bloodstream in duodenum and increase proliferative activity of duodenal epiteliocytes.

[Characteristics of the pineal gland and thymus relationship in aging].

The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

Peptides from the pituitary gland and cortex stimulate differentiation of polypotent embryonic tissue.

We studied the effects of synthetic peptides from the pituitary gland and brain cortex on differentiation of polypotent ectodermal tissue of the early gastrula of Xenopus laevis. It was shown that the pituitary gland peptide stimulates differentiation of polypotent tissue into epidermis and nerve tissue, while brain cortex peptide induces the development of mesenchyma and epidermis. Differentiation of polypotent tissue under the effect of the peptide is a mechanism of their geroprotective effect and suggests that they are promising as preparations for the treatment of neurodegenerative diseases.

Peptidergic regulation of thymocyte differentiation, proliferation, and apoptosis during aging of the thymus.

The effects of T-31, AB-17, and AB-9 peptides on old (passage 8) thymocyte culture were studied. Only AB-9 peptide exhibited a complex geroprotective effect on thymocytes during their aging. Peptide AB-9 stimulated proliferative activity and differentiation of thymocytes and inhibited their apoptosis.

Neuroendocrine and proliferative potential of human intestinal cells during aging.

A population of neuroendocrine cells secreting chromogranin A was verified in the intestine of subjects aged over 60 years. The count of intestinal cells expressing chromogranin A and Ki-67 proliferation protein increases with aging. More intensive expression of chromogranin A and Ki-67 protein in senile age and in long-livers is presumably a compensatory mechanism aimed at the gastrointestinal function maintenance during its age-associated involution.

[Influence of peptides from pineal gland on thymus function at aging].

The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

[Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

[Neuroimmunoendocrine mechanisms of aging].

The review discusses in detail the mechanisms of aging from the position of common signaling molecules produced in three regulatory systems: the nervous, endocrine and immune ones. It is shown that the neuroimmunoendocrine hormonal regulation of homeostasis plays the important role in the complex chain of processes that lead to aging of cells, tissues, organs and body as a whole. Particular attention is paid to morpho-functional involution of nervous, endocrine and immune systems, which is accompanied by a breach of elaborate signaling molecules. Detailed analysis and further development of integrated molecular commonality of views on the regulatory systems of both the central and especially local levels, opens vast new opportunities for deepening knowledge of the mechanisms of aging, as well as for the prevention, diagnosis and treatment of diseases associated with aging, in which pathogenesis the discoordination of neuro-immuno-endocrine signaling mechanisms plays an important role.

[Functional morphology of aging].

The review provides the analysis of the research results in the field of the study of the mechanisms of aging involution, which are connected with the peculiar properties of the expression of signaling molecules participating in intercellular communications in the different organs and tissues.

[Association of age-dependent magnetosensitivity dynamics with arterial hypertension].

The purpose of the research was to define magneto sensitivity degree in males depending on age and presence or absence of arterial hypertension. It has been shown, that at aging in the examined groups the number of males possessing high magneto sensitivity degree according to hypotensive type of cardiovascular reaction to magnetic test is decreasing (30,2% in children and up to 0% in males of senile age) and increasing (2,2 up to 36,0%, correspondingly) - according to hypertensive type. In the group of middle aged males with arterial hypertension the number of high magneto sensitive persons on hypertensive type was 5 times higher as compared to the group of practically healthy males of similar age. The results obtained demonstrate that at aging reactions of cardiovascular system on external physical impacts essentially change, dependence of an organism on changes of the geomagnetic field amplifies and probability of risk of hypertonic crisis development during the fluctuations of the Earth magnetic field increases.

Dynamics of blood values in experimental geomagnetic deprivation (in vitro) reflects biotropic effects of natural physical factors during early human ontogeny.

Heliogeophysical situation during prenatal development of humans is essential for blood rheology, hemostasis, and spectral and frequency parameters of the blood. The relationship between these parameters and natural physical factors is determined by the intensity of solar activity and geomagnetic induction during postnatal ontogeny. Analysis of changes in the functional relationship between hematological values and heliogeophysical factors under conditions of simulated hypogeomagnetic space included evaluation of possible consequences of distortions of the heliobiospheric relationships in large cities, particularly pronounced for cardiovascular patients.

[The specific features of the heliophysical situation in the period of preconceiving and early ontogenesis in patients with pulmonary tuberculosis].

The specific features of the heliophysical situation in preconceiving and early ontogenesis in patients with pulmonary tuberculosis were studied. There were significant differences in solar radioradiation intensity a week before the conception of an organism in healthy individuals and patients with tuberculosis.

Expression of argyrophilic proteins in the nucleolar organizer regions of human thymocytes and thymic epitheliocytes under conditions of coculturing with vilon and epithalon peptides.

Vilon stimulated and Epithalon suppressed the expression of argyrophilic proteins in nucleolar organizer regions of thymocytes and epithelial cells, stimulating or reducing, respectively, the formation, assembly, and transport of ribosomes into the cytoplasm and thus determining the intensity of protein synthesis in these cells. A direct mitogenic effect of Vilon was also revealed: this peptide promoted thymocyte transformation into proliferating blast cells.

Temperature and viscosity dependence in the stereoselective formation of the inverted housane for the photochemical nitrogen loss from the deuterium-stereolabeled parent diazabicyclo[2.2.1]hept-2-ene.

For the liquid-phase photolytic denitrogenation of the stereolabeled DBH derivative exo-d2-diazabicyclo[2.2.1]heptene (exo-d2-1), the k(inv)/k(ret) ratio of the inverted [2(inv)] and retained [2(ret)] housanes (bicyclo[2.1.0]pentanes) depends on the viscosity of the medium. For this purpose, the viscosity was varied by changing the solvent (various alcohols and diols, n-hexane, and acetonitrile) at constant temperature and by changing the temperature (-50 to +100 degrees C) in one single solvent, namely n-butanol. This viscosity effect is consistent with a stepwise denitrogenation mechanism in the liquid-phase photolysis of DBH, which proceeds through an unsymmetrical, nitrogen-containing transient, namely the singlet diazenyl diradical. The simple free-volume model adequately accounts for the observed viscosity behavior of the k(inv)/k(ret) ratio in terms of frictional effects. The temperature dependence discloses a small but measurable difference in the internal activation energies for the inversion and retention processes of the proposed diazenyl diradical.

Ultrastructure of the rat duodenal endocrine cells after prolonged irradiation.

We propose classification of duodenal endocrine cells of intact rats based on ultrastructural signs of secretory granules and subdivided these cells into 10 basic types. The effect of long-term irradiation in a total dose of 2.5 Gy on ultrastructural organization of duodenal apudocytes was studied. Irradiation induced nonspecific changes of cell organelles in apudocytes. Differences in the ultrastructural disorganization were detected between different types of apudocyte populations and between different types of endocrine cells. Under conditions of adaptation to radiation apudocytes released the secretory product not only through molecular extrusion and exocytosis, but also via degranulation.