[Global demographic problem and active aging (literature review)].

The article presents an overview of foreign sources devoted to the problems of population aging as a significant phenomenon that has become the most important medical and socio-demographic challenge in the world. The review provides global data on this problem and shows the need for elaborating and implementing active aging strategies, optimizing opportunities for health, participation and safety in order to improve the life quality as people age. The paper employs the method of content analysis of scientific publications retrieved in PubMed database by keywords - «aging¼, «population aging¼, «demographic trend¼, «longevity¼, and «life expectancy¼. Scientific publications for the period 2018-2023, WHO and UN materials, statistical data, and popular scientific publications have been studied. The purpose of the review was to analyze trends and global nature of aging based on scientific publications and open sources, and to highlight the most promising areas of the demographic policy on the older adults. In the time of rapid demographic changes, it is extremely important to use all available opportunities that maximize healthy aging with the participation of the older adults. We should remember that aging is a natural process and it is better to accept it, both psychologically and physically, rather than ignore. Healthy aging should become and has become the main principle of life, suggesting a longer healthy life of the older adults, who, in turn, should understand how to accept and implement this principle in their lives.

The adjuvant effect of polymuramil, a NOD1 and NOD2 agonist, differs when immunizing mice of different inbred lines with nonstructural hepatitis C virus (Flaviviridae: Hepacivirus)proteins and is synergistically enhanced in combination with pyrogenalum, a TLR4 agonist.

INTRODUCTION: Hepatitis C is a liver disease with high chronicity, the cause of cirrhosis and hepatocarcinoma. The main obstacle to controlling hepatitis C is the lack of vaccines. The aim of the work was to compare the immunogenic activity of nonstructural recombinant proteins NS3, NS4 and NS5B of hepatitis C virus (HCV) as components of a subunit candidate vaccine and to analyze the adjuvant properties of two available commercial drugs, polymuramil and pyrogenalum. MATERIALS AND METHODS: BALB/c, DBA/2J and C57BL/6 mice were immunized with nonstructural proteins without adjuvants or with polymuramyl (NOD1 and NOD2 agonist) and pyrogenalum (TLR-4 agonist). The activity of antibodies was determined in ELISA, the cellular response - by antigen-specific lymphocyte proliferation and by production of IFN-γ in vitro. RESULTS: Recombinant proteins showed different immunogenicity. NS4 induced antibodies more efficiently than NS3 and NS5B. Significant differences were found in the immune response of three inbred lines mice: the level of IFN-γ in BALB/c and DBA/2J mice induced by NS5B protein was 30 times higher than in C57Bl/6 mice. In contrast, the induction of antibodies in BALB/c mice was lower than in C57Bl/6 and DBA/2J. Polymuramil did not increase the humoral response to NS5B and enhanced the cellular response only in C57BL/6 mice. The combined use of polymuramil with pyrogenalum significantly increased both the humoral and cellular response of mice to all recombinant HCV proteins. CONCLUSION: Different immunogenic properties and different functions of recombinant non-structural HCV proteins indicate the feasibility of their combined inclusion in subunit vaccines. It was established for the first time that immunization with HCV proteins with a complex adjuvant (polymuramyl + pyrogenalum) has a synergistic effect, significantly exceeding the effect of each of them separately.

[Lyudmila Antoninovna Shangina as the scientist and pedagogue].

The article is devoted to scientific biography of the prominent neuroanatomist, Doctor of Medical Sciences, Professor L. A. Shangina, representative of the scientific school of Tonkov-Bushmakin. Her input into becoming of the chairs of normal anatomy of medical institutes in Irkutsk, Moscow, Kursk, Dushanbe (Tajikistan) and Smolensk and in organization of scientific community of neuromorphologists in the USSR in the middle and second half of the twentieth century is demonstrated. The special attention is paid to the results of scientific studies of L. A. Shangina and her post-graduate students of topography of nerves innervating human heart, of topography of accessory nerve (XI pair of cranial nerves), of structure of receptors of autonomic nervous system in walls of alimentary tract and urinary system.

Period-doubling bifurcation in surface radio-frequency trap: Transition to chaos through Feigenbaum scenario.

We have numerically investigated the dynamics of charged microparticles in a "five-wire" surface radio-frequency trap. The period-doubling bifurcation conditions have been shown to depend on the particle, the trap, and the alternating voltage parameters. For a comprehensive study of the dynamics chaotization through a cascade of period doubling, we have used Fourier analysis of a particle trajectory as well as the calculations of a non-trivial Lyapunov exponent map. We have demonstrated that the period-doubling bifurcation is consistent with a Feigenbaum scenario. A new approach to particle property determination can, thus, be based on observing a period-doubling bifurcation.

[Exosomes in the life cycle of viruses and the pathogenesis of viral infections].

Exosomes are extracellular vesicles of endosomal origin, with a bilayer membrane, 30160 nm in diameter. Exosomes are released from cells of different origins and are detected in various body fluids. They contain nucleic acids, proteins, lipids, metabolites and can transfer the contents to recipient cells. Exosome biogenesis involves cellular proteins of the Rab GTPase family and the ESCRT system, which regulate budding, vesicle transport, molecule sorting, membrane fusion, formation of multivesicular bodies and exosome secretion. Exosomes are released from cells infected with viruses and may contain viral DNA and RNA, as well as mRNA, microRNA, other types of RNA, proteins and virions. Exosomes are capable of transferring viral components into uninfected cells of various organs and tissues. This review analyzes the impact of exosomes on the life cycle of widespread viruses that cause serious human diseases: human immunodeficiency virus (HIV-1), hepatitis B virus, hepatitis C virus, SARS-CoV-2. Viruses are able to enter cells by endocytosis, use molecular and cellular pathways involving Rab and ESCRT proteins to release exosomes and spread viral infections. It has been shown that exosomes can have multidirectional effects on the pathogenesis of viral infections, suppressing or enhancing the course of diseases. Exosomes can potentially be used in noninvasive diagnostics as biomarkers of the stage of infection, and exosomes loaded with biomolecules and drugs - as therapeutic agents. Genetically modified exosomes are promising candidates for new antiviral vaccines.

[Adjuvant effect of dispersed fullerene C60 on the immune response to constructs harboring amino acid and nucleotide sequences of hepatitis C virus nonstructural NS5B protein].

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.

[ANALYSIS OF THE STAFFING OF MEDICAL ORGANIZATIONS SUBORDINATE TO THE DEPARTMENT OF HEALTH OF THE CITY OF MOSCOW IN 2021].

An analysis was made of the structure and number of medical workers (doctors and paramedical personnel) of the Moscow healthcare system for the period 2017-2021. The analysis showed that the number of medical full-time positions over the same period increased by 13.6%, and regular positions of nursing staff by 8.9%. The provision of the population (per 10 thousand population) with doctors increased by 13.0% from 35.6 in 2017 to 40.2 in 2021. The provision of the population with nurses decreased by 2.4% from 58.4 in 2017 to 57.0 in 2021. Among medical workers, the number of individual doctors, over the same period, increased by 15.5%, and the number of individuals of paramedical personnel decreased by 3.4%. The staffing of medical rates (by positions), in general, decreased by 2.4% from 82.5 in 2017 to 80.5 in 2021, and the rates of nursing staff decreased by 9.7% from 87.4% in 2017 to 79.0% in 2021. The part-time ratio was 1.1 for medical positions and for positions of paramedical personnel. Issues related to low staffing and the coefficient of part-time employment for individual medical positions and positions of paramedical personnel require further resolution.

Physiological Media in Studies of Cell Metabolism.

Changes in cell metabolism accompany the development of a wide spectrum of pathologies including cancer, autoimmune, and inflammatory diseases. Therefore, usage of inhibitors of metabolic enzymes are considered a promising strategy for the development of therapeutic agents. However, the investigation of cellular metabolism is hampered by the significant impact of culture media, which interfere with many cellular processes, thus making cellular models irrelevant. There are numerous reports that show that the results from in vitro systems are not reproduced in in vivo models and patients. Over the last decade a novel approach has emerged, which consists of adaptation of the culture medium composition to that closer to the composition of blood plasma. In 2017‒2019, two plasma-like media were proposed, Plasmax and HPLM. In the review, we have summarized the drawbacks of common media and have analyzed changes in the metabolism of cells cultivated in common and plasma-like media in normal and pathological conditions.

Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells.

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

[Physiological Media in Studies of Cell Metabolism].

Changes in cell metabolism accompany the development of a wide spectrum of pathologies including cancer, autoimmune, and inflammatory diseases. Therefore, usage of inhibitors of metabolic enzymes are considered a promising strategy for the development of therapeutic agents. However, the investigation of cellular metabolism is hampered by the significant impact of culture media, which interfere with many cellular processes, thus making cellular models irrelevant. There are numerous reports that show that the results from in vitro systems are not reproduced in in vivo models and patients. Over the last decade a novel approach has emerged, which consists of adaptation of the culture medium composition to that closer to the composition of blood plasma. In 2017-2019, two plasma-like media were proposed, Plasmax and HPLM. In the review, we have summarized the drawbacks of common media and have analyzed changes in the metabolism of cells cultivated in common and plasma-like media in normal and pathological conditions.

[Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells].

Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a "protective" autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

[Expression of HIV-1 Reverse Transcriptase in Murine Cancer Cells Increases Mitochondrial Respiration].

Changes in metabolic pathways are often associated with the development of a wide range of pathologies. Increased glycolysis under conditions of sufficient tissue oxygen supply and its dissociation from the Krebs cycle, known as aerobic glycolysis or the Warburg effect, is a hallmark of many malignant neoplasms. Identification of specific metabolic shifts can characterize the metabolic programming of individual types of tumor cells, the stage of their transformation, and predict their metastatic potential. Viral infection can also alter the metabolism of cells to support the process of viral replication. Infection with human immunodeficiency virus type 1 (HIV-1) is associated with an increased incidence of various cancers, and for some viral proteins a direct oncogenic effect was demonstrated. In particular, we showed that the expression of HIV-1 reverse transcriptase (RT) in 4T1 breast adenocarcinoma cells increases the tumorigenic and metastatic potential of cells in vitro and in vivo by a mechanism associated with the ability of RT to induce reactive oxygen species in cells (ROS). The aim of this work was to study the molecular mechanism of this process, namely the effect of HIV-1 RT on the key metabolic pathways associated with tumor progression: glycolysis and mitochondrial respiration. Expression of HIV-1 RT had no effect on the glycolysis process. At the same time, it led to an increase in mitochondrial respiration and the level of ATP synthesis in the cell, while not affecting the availability of the substrates, carbon donors for the Krebs cycle, which excludes the effect of RT on the metabolic enzymes of cells. Increased mitochondrial respiration was associated with restoration of the mitochondrial network despite the RT-induced reduction in mitochondrial mass. Increased mitochondrial respiration may increase cell motility, which explains their increased tumorigenicity and metastatic potential. These data are important for understanding the pathogenesis of HIV-1 infection, including the stimulation of the formation and spread of HIV-1 associated malignancies.

Acute coronary syndrome in patients with cancer: features of the course and the possibility of predicting hospital and long-term (6 months) periods using GDF-15, NT-proBNP, hs-CRP biomarkers.

Aim    To evaluate clinical features of the course of acute coronary syndrome (ACS) in patients with oncological diseases (OD) and to determine the role of biomarkers GDF-15, NT-proBNP, and hs-CRP in short-term and long-term prognoses.Material and methods    In 88 patients (34 patients with ACS and OD and 54 patients with ACS without OD), complaints and historical, objective, and laboratory and instrumental data were evaluated and blood concentrations of GDF-15, NT-proBNP, and hs-CRP biomarkers were measured on the first day of hospitalization. Incidence of cardiovascular complications (CVC) and outcomes of hospital and long-term (6 months) periods were analyzed. Statistical analysis of results was performed with the Statistica 12.0, MedCalc 19.1.7 software. The level of statistical significance was р<0.05.Results    In the ACS+OD group as compared to the ACS without OD group, the onset of disease was mostly atypical, with shortness of breath and/or general weakness; the ACS+OD patients more frequently had III-IV Killip class acute heart failure (29 and 7 %, р=0.01); mean hemoglobin concentration (125.6±27.9 and 141±16.6 g/l, р=0.003), prothrombin index (76.4±15.2 and 84.9±17.6 %, р=0.003), and left ventricular ejection fraction (47.7±6.1 and 50.7±7.2 %, р=0.02) were lower; and median concentrations of GDF-15 (1.95 [1.3; 2.8] and 1.45 [1.2; 2.0] ng/ml, р=0.03), NT-proBNP (947.3 [517.8; 1598.2], and 491.1 [85.1; 1069.1] pg/ml, р=0.006), and hs-CRP (14.1 [8.15; 36.75] and 7.8 [4.4; 16.2] mg/l, р=0.01) were higher. The presence of OD was associated with development of CVC, including urgent endpoints in the long-term and also increased the probability of fatal outcome within 6 months after discharge from the hospital. To predict the risk of CVC in patients with ACS and OD, two models with high prognostic values (AUC>0.9) were proposed. In the long-term, the value of NT-proBNP (cut-off point >524.5 pg/ml) was a statistically significant predictor for development of endpoints with a high predictive value (AUC>0.8).Conclusion    The features of the clinical course of ACS in patients with OD indicate the importance of isolating such patients into a separate group. Additional use of the developed models, along with a standard risk assessment by the GRACE scale, will allow individualized management of patients with ACS and OD during the hospital and long-term (6 months) periods.

[Aminothiols in blood plasma at different subtypes of ischemic stroke]. / Aminotioly plazmy krovi pri razlichnykh podtipakh ishemicheskogo insul'ta.

OBJECTIVE: To evaluate the hemostasis of plasma aminothiols in different subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 177 patients, aged 62 (55-68) years, admitted in the first 8-24 hours since IS onset. The pathogenetic subtype of IS was clarified according to the results of clinical and instrumental examination by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Determination of the total plasma aminothiols levels, their reduced forms and redox status was performed using the ultra-efficient Acquity H-Class UPLC liquid chromatograph (Waters, CSHA). RESULTS: Large-artery atherosclerosis was diagnosed in 24.3% patients, cardioembolic stroke in 20.3%, lacunar stroke in 55.4%. Significant differences in total levels of cysteine (Cys), glutathione (Gsh) and homocysteine (Hcy) were identified in patients with different IS subtypes. Patients with large-artery atherosclerosis and lacunar stroke showed the highest level of Hcy, patients with cardioembolic stroke had the lowest levels of Cys and Gsh. CONCLUSION: Total levels of plasma aminothiols are associated with different subtypes of IS.

Efficient optimization method for finding minimum energy paths of magnetic transitions.

Efficient algorithms for the calculation of minimum energy paths of magnetic transitions are implemented within the geodesic nudged elastic band (GNEB) approach. While an objective function is not available for GNEB and a traditional line search can, therefore, not be performed, the use of limited memory Broyden-Fletcher-Goldfarb-Shanno (LBFGS) and conjugate gradient algorithms in conjunction with orthogonal spin optimization (OSO) approach is shown to greatly outperform the previously used velocity projection and dissipative Landau-Lifschitz dynamics optimization methods. The implementation makes use of energy weighted springs for the distribution of the discretization points along the path and this is found to improve performance significantly. The various methods are applied to several test problems using a Heisenberg-type Hamiltonian, extended in some cases to include Dzyaloshinskii-Moriya and exchange interactions beyond nearest neighbours. Minimum energy paths are found for magnetization reversals in a nano-island, collapse of skyrmions in two-dimensional layers and annihilation of a chiral bobber near the surface of a three-dimensional magnet. The LBFGS-OSO method is found to outperform the dynamics based approaches by up to a factor of 8 in some cases.

[Hyperhomocysteinemia and endothelial dysfunction in patients with cerebral vascular and autoimmune diseases]. / Gipergomotsisteinemiia i éndotelial'naia disfunktsiia pri sosudistykh i autoimmunnykh zabolevaniiakh golovnogo mozga.

Endothelial dysfunction today is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and induction of apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in the pathogenesis of MS.

A Novel Sulfonated Derivative of ß-Cyclodextrin Effectively Inhibits Influenza A Virus Infection in vitro and in vivo.

The development of novel drugs against the influenza virus with high efficiency and low toxicity is an urgent and important task. Previous reports have demonstrated that compounds based on sulfo derivatives of oligo- and polysaccharides possess high antiviral activity. In this study, we have examined the ability of a novel sulfonated derivative of ß-cyclodextrin (KS-6469) to inhibit the influenza virus A/WSN/33 (H1N1) infection in vitro and in vivo. The antiviral potential of KS-6469 against the influenza virus was evaluated in Madin-Darby Canine Kidney epithelial cells treated with serially diluted KS-6469. We found out that KS-6469 completely inhibited viral reproduction after treatment of the infected cells with the compound for 48 h. Our data show that double intranasal treatment of mice with KS-6469 fully protected the animals from a lethal infection and significantly decreased the viral titers in the lungs of the infected animals. Thus, the novel sulfonated ß-cyclodextrin derivative KS-6469 is a promising candidate for the development of antiviral drugs for preventing and treating the influenza infection.

[Evaluation of the efficiency of magnetophoresis transdermal diclofenac delivery in patients with knee osteoarthritis]. / Otsenka éffektivnosti primeneniia magnitoforeza transdermal'noi formy diklofenaka u patsientov s osteoartritom kolennogo sustava.

Osteoarthritis (OA) is a serious sociomedical problem, one of the leading causes of persistent disability and reduced quality of life. Modern publications on the use of transdermal drug formulations for OA evaluate the efficiency and safety of isolated drug administration. Pulse magnetotherapy is a modern method for potentiating the therapeutic effects of both the drug and the magnetic field (MF) in the single magnetophoretic technique. AIM: to determine the effect of pulsed MF on the clinical efficacy and tolerability of magnetophoretic transdermal diclofenac delivery in patients with gonarthrosis. SUBJECTS AND METHODS: A clinical randomized placebo-controlled study was conducted in 65 patients with Kellgren-Lawrence grade 2-3 knee OA, who were divided into 3 groups. Group 1 including 25 patients received magnetophoretic diclofenac gel delivery using a traveling MF (intensity, 20 mT; frequency, 6.25 Hz; exposure. 20 min, 12 sessions); Group 2 consisting of 20 patients used placebo magnetotherapy with diclofenac without MF; Group 3 comprising 20 patients had low-frequency pulse magnetotherapy with traveling MF without topical diclofenac therapy. VAS and WOMAC and the EQ-5D questionnaire were used during the examination. The results of treatment were analyzed according to the OMERACT-OARSI criterion. RESULTS: According to VAS and WOMAC scores, combination therapy showed a marked analgesic effect in the patients who had received magnetotherapy (p<0.01), as well as a significant reduction in stiffness and an improvement in functional characteristics, which were more pronounced in those who had magnetophoresis (p<0.001). According to the EQ-5D questionnaire, magnetotherapy was noted to have a positive impact on quality-of-life indicators. Analysis according the OMERACT-OARSI criterion demonstrated a high rate (67.8%) of response to magnetophoretic sis using diclofenac application formulations. CONCLUSION: Magnetophoretic transdermal diclofenac delivery using low-frequency pulsed MF is effective and safe for patients with knee OA and causes no serious adverse events.

[Efficiency of magnetic therapy techniques in the treatment and rehabilitation of patients with joint diseases from the standpoint of evidence-based medicine]. / Éffektivnost' metodov magnitoterapii v lechenii i reabilitatsii patsientov s zabolevaniiami sustavov s pozitsii dokazatel'noi meditsiny.

This article provides information on currently proven effective treatment methods for patients with joint diseases, by using magnetic fields with various physical characteristics. A wide range of biotropic parameters allows obtaining various primary physicochemical changes in biological tissues, which was a rationale for including magnetic therapy (MT) in the combination treatment of degenerative-dystrophic and inflammatory diseases. Analysis of scientific publications suggests that there are a large number of randomized, placebo-controlled studies providing evidence for reduced pain, improved joint functional activity and quality of life in patients with knee osteoarthritis under magnetic fields with varying inductions, frequencies, and exposures. There are few randomized clinical trials identifying the efficiency of MT for a number of other joint diseases and after arthroplasty. Despite the fact that there are differences in methodological approaches, it is possible to draw a general conclusion on the scientific validity of using MT in the complex treatment and rehabilitation programs for patients with joint diseases and on the prospects of further developments in this area.

Effect of Selank on Morphological Parameters of Rat Liver in Chronic Foot-Shock Stress.

We studied the effects of Selank on morphological parameters of the liver in Wistar male rats subjected to chronic foot-shock stress. Selank was injected intraperitoneally in doses of 100, 300 and 1000 µg/kg 15 min before each stress session. Morphological and morphometrical analysis showed that chronic foot-shock stress induced hydropic degeneration of hepatocytes, an increase of the nucleus/cytoplasm ratio due to an increase in the area of nuclei and reduction of the cytoplasm area, the appearance of focal necroses, and lymphohistiocyte infiltration. Injection of Selank in all doses reduced the intensity of stress-induced degenerative changes. Administration of Selank in doses of 300 and 1000 µg/kg restored the nucleus/cytoplasm ratio in hepatocytes. The maximum stress-limiting effect was attained after administration of 300 µg/kg Selank.