Vol 26, No 3 (2023)

Injury to the anterior cruciate ligament (ACL) of the knee joint is complicated by development of arthrogenic muscle inhibition due to disregulating afferent influences on the excitability of the spinal and supraspinal tracts. The aim of our work was to study electromyography parameters, and myokine levels in the course of myostimulation in traumatic ACL injury.

28 male athletes with traumatic ACL injuries participated in the study. On admission to the clinic, all patients underwent electromyographic examination of the injured limb by the means of Viking Quest EMG/ EP apparatus (Nicolet, USA). Some patients, 10 days before starting the surgical treatment, underwent passive electrical myostimulation (EMS) of the quadriceps femoris muscle using the INTELECT^® Advanced device (Chattanooga (DJO), USA). Further on, all patients underwent arthroplasty using a Karl Storz arthroscope (Germany). In the postoperative period, during immobilization for 2-weeks, the patients received EMS. After removing the orthosis, the patients switched to active training. The cytokine levels were studied using ELISA reagent kits from Vector-Best, Novosibirsk (IL-6), or from Cloud-Clone Corp. (China) for TGF–β1 assays. Statistical processing of the material was carried out using the Statistica package. vers.10.0 (StatSoft Inc., USA).

The highest average amplitude (μV) was recorded by electromyography in healthy individuals. In patients of the main group, significantly lower values of the average amplitude were recorded. After a 10-day EMS, a significant increase to the reference values of healthy individuals was noted. In the postsurgical dynamics, EMG indicators without EMS treatment remained at the same low levels. Meanwhile, the values following EMS treatment were comparable with those in healthy individuals, thus reflecting a faster and better muscle recovery after injury. The levels of IL-6 and TGF-β1 cytokines (myokines) significantly exceeded the initial levels in the course of EMS. The biological significance of increased IL-6 levels during the muscle exercise may consist the activation of AMP kinase and/or phosphatidylinositol-3-kinase at the level of skeletal muscles thus providing more efficient supply of energy substrate to the muscles. TGF-β1 promotes fibroblast proliferation, thus increasing collagen content.

Passive and active EMS leads to an improvement in electromyography parameters, along with increased concentration of myokines (IL-6 and TGF-β1) in peripheral blood, thus promoting improvement of energy balance, increasing the anti-inflammatory and repair potential of the damaged tissues.

Riamilovir, a drug registered in Russia (chemical formula: methylthionitrooxodihydrotriazolotriazinide sodium, trade name: Triazavirin) is a synthetic analogue of guanine and a drug of direct antiviral action. Currently, there are conflicting data regarding usage of riamilovir as a preventive and therapeutic agent in coronavirus infections. The purpose of this study was to analyze some results of riamilovir usage, both for prevention of the SARS-CoV-2 infection and for the treatment of COVID-19 during the first wave of the new coronavirus pandemic.

The analysis was based on a survey of 62 medical staff workers at a single medical institution in Ekaterinburg who was ill with COVID-19, being divided into 4 groups: (1) those who did not receive riamilovir (control), (2) persons who received riamilovir only as a disease prevention, (3) subjects who received the drug as a therapeutic agent, (4) those who received riamilovir before and during the disease.

The data concerning usage of riamilovir for the prevention of infection with the SARS-CoV-2 virus have shown the following consequences: increased duration of hospitalization, an increased incidence of COVID-19 complications, i.e., fever, shortness of breath, pulmonary insufficiency, pneumonia, higher frequency of neurological disorders, which were not reported elsewhere. Severe clinical course of the disease was observed much more often in cases of prophylactic riamilovir administration, and the rehabilitation period was incomplete 2 months after the disease. Clinical symptoms of muscle and joint pain were documented at later terms in all persons who received riamilovir to prevent a new coronavirus infection. Usage of riamilovir for therapeutic purposes made it possible to avoid the development of pulmonary insufficiency, severe course of the infectious disease, and entirely restore the state of health.

The study did not reveal the usefulness of riamilovir for prevention of COVID-19 complications when taking the drug before infection with the SARS-CoV-2 virus. However, the use of riamilovir for therapeutic purposes prevents development of severe clinical cases and is associated with 4-fold reduced risk of pain in muscles, joints, and spine among the COVID-19 patients.

There is only limited data on B-cell response in post-COVID patients despite its importance in studying the post-infection immunity. The present study aimed to investigate the features of the B-cell response in post-COVID patients, focusing on various B cell phenotypes. Along with the standard immunogram, the following cell phenotypes were examined: common B cells (CD45⁺, CD3^-, CD19⁺); common memory cells (CD45⁺, CD3^-, CD19⁺, CD27⁺); common non-memory cells (CD45⁺, CD3^-, CD19⁺, CD5⁺); B1 memory cells (CD45⁺, CD3^-, CD19⁺, CD5⁺, CD27⁺); B2 memory cells (CD45⁺, CD3^-, CD19⁺, CD5^-, CD27⁺); B1 non-memory cells (CD45⁺, CD3^-, CD19⁺, CD5⁺, CD27^-); and B2 non-memory cells (CD45⁺, CD3^-, CD19⁺, CD5^-, CD27^-). The study revealed a sharp increase in B1 memory cells in 15.3% of post-COVID patients with impaired levels of B1 memory cells. This increase was accompanied by elevated levels of total B memory cells, B1 total lymphocytes (mainly, B1 memory cells), total T lymphocytes, and total IgA. By contrast, the patients with impaired B1 memory cells exhibited a sharp decrease in plasma cells, B2 lymphocytes (both memory and non-memory cells), natural killer cells, T regulatory cells, early activation T cells (CD25⁺), and C3a complement fragment. These findings suggest a unique immune system disorder characterized by dysregulated B lymphocyte switching from IgM to IgG and IgA synthesis, thus resulting in marked decrease in B2 lymphocyte subpopulations. This disorder may be associated with reduced T regulatory lymphocytes and early activation of T lymphocytes responsible for regulating B lymphocyte differentiation. Furthermore, the patients also exhibited reduced hemoglobin and platelet parameters, thus, potentially, contributing to hypoxia and blood clotting abnormalities. Thus, the phenotype identification of these immune system disorders in post-COVID patients requires non-standard approaches to assessing immune status, thus compicating clinical examination, but highlighting the need for immunocorrective therapies. These findings contribute to better understanding of post-COVID immune system disorders and require further investigation into the underlying causal factors.

The article presents an experimental study of immunotropic activity of a new compound, a metabiotic, based on metabolites (biologically active substances) produced by a of saprophytic Bacillus subtilis B-9909 strain, being safe for health and standardized at Russian National Collection of Industrial Microorganisms (RNCIM). The aim of our study was to experimentally evaluate the immunotropic effects of metabolites produced by the probiotic Bacillus subtilis B-9909 upon the parameters of cellular immunity tested in the animal model of induced toxic liver damage. The metabolites were isolated from the cultural liquid of Bacillus subtilis culture (RNCIM strain B-9909) during its deep cultivation in a medium containing hydrochloric acid hydrolyzate of soy flour, or pancreatic hydrolyzate of casein. At 16-18 hours of cultivation, the cells were in the exponential growth phase. The indices of cellular status were studied in experimental groups of animals, when assessing therapeutic efficacy of an experimental metabiotic sample, as compared to a group of laboratory animals treated with the reference drug (ursosan). We assessed the quantitative indicators of blood as follows: determination of phagocytic activity (FA) of peripheral blood neutrophils; measurement of metabolic activity in peripheral blood neutrophils by means of NBT-test; quantitative determination of T and B lymphocytes; the number of antibody-forming cells (AFC). Liver damage was studied in a model of acute toxic hepatitis in albino rats. Experimental toxic hepatitis was induced by 40% solution of CCl₄ in vaseline oil injected intragastrically for 2 weeks at the dose of 0.2 g/kg. The results of experimental studies showed activation of phagocytic activity by peripheral blood neutrophils at the early terms of experiment, being also confirmed by the results of NBT-testing. Moreover, at the early observation terms, a significantly increased representation of T and B lymphocyte populations as well as AFC numbers, were revealed thus suggesting activation of all components of cellular immunity in response to the carbon tetrachloride toxicity. Thus, the reported studies on the cellular status of laboratory animals treated with metabolites produced by probiotic microorganisms of the genus Bacillus subtilis (B-9909) on laboratory animals with toxic liver damage allow us to conclude that the test sample of this metabiotic preparation exerts a significant immunomodulatory effect, when compared with ursosan. This evidence allows us to consider this compound a promising candidate drug for a new hepatoprotector with immunotropic effect.

Shocks of different origin (both septic and aseptic) be be considered clinical equivalents of systemic inflammation (SI) with following main manifestations : pronounced hypercytokinemia, other markers of systemic inflammatory response (SIR), coagulopathy, multiple organ failure (MOF), hypothalamic-pituitary-adrenal (HPA) distress, systemic tissue alteration. In general, these phenomena are directly and inversely related to systemic microcirculatory disturbances which determine the pathogenesis of distinct shock states. The aim of our study was to identify the features of SI phases in the development of two variants of septic shock, i.e., acute course (first week of the process) and prolonged/subacute sepsis (2 to 6 weeks from the onset of manifestations), as well as haemorrhagic shock studied 4-12 hours from the onset of massive blood loss. To verify the SI phases, we used the previously proposed SI scale, including the value of six SIR levels (RL-0-5), as well as additional criteria of SI, i.e., evaluation of clinical MOF grade (SOFA scale), plasma D-dimers (> 500 ng/mL), cortisol (> 1380 nmol/mL), tissue alteration markers, e.g., myoglobin (> 800 ng/mL) and/or troponin I (> 0.2 ng/mL). To calculate RL in SIR, plasma CRP and four cytokines (IL-6, IL-8, IL-10, TNFα) were determined. The presence of SI was established if the SI scale exceeded 5 points (numerical RL values + presence of additional criteria, each equal to 1 point). The time and severity of the developing critical state, as well as the RL scores, were taken into account when reviewing the phases.

There were three main SI phases: (1) evolving condition, (2) cytokine storm/phlogogenic hit (SD-4-5), and depressive (exhausting) phase. The latter was characterized by relatively low SIR values (RL-2-3). The lethality rate for shock in the presence of acute sepsis (n = 13) was 71.4%, reaching 94.1% in prolonged sepsis (n = 17). For haemorrhagic shock after massive blood loss, if not resolved within 24 hoursm the mortality rates was 53.8% (n = 13). Development of shock in acute sepsis, and haemorrhagic shock (within 4 to 12 hours after the onset of massive blood loss) is accompanied by the severity of critical-phase cytokine storm/PPS with a predominance of RL-5 in cases of lethal outcomes, and by a depression phase (RL-2-3) in prolonged sepsis. Overall mortality (for all groups) was 66.7% in the PS phase, 89.5% in the depressive phase and 15.4% in the evolvingl phase of haemorrhagic shock (with possible transition from this phase to the more critical SI phases until lethal outcome).

Shock states of both septic and aseptic origin are based on a typical pathological process of SI, which should be distinguished from the signs of SIR characteristic of high-intensity canonical inflammation. It is characterized by higher cytokinemia (cytokine storm phase) or by the presence of additional SI phenomena with relatively moderate SIR levels (depressive SI phase). Thus, the depressive phase of SI is more fatal for disease outcome compared to the cytokine storm phase with higher intensity of SIR.

Chronic inflammatory diseases of the pelvic organs (pelvic inflammatory disease, PID) in women is among the main understudied problems in gynecology worldwide with adverse medical and socio-economic consequences, thus justifying the need for further study of immunopathogenesis and development of new approaches to treatment. Our objective was to develop new immunotherapeutic approaches to correction of combined disorders of the immune system functioning in immunocompromised women with PID and to evaluate their clinical and immunological efficacy.

55 women aged 20-40 years were examined, i.e., 35 patients with exacerbation of sluggish or recurrent PID, resistant to conventional therapy. Testiung was performed before complex treatment (study group 1 – GI- 1) and after the course (study group 2 – GI-2). Contents of T and B lymphocytes, natural killer cells (NK) (CYTOMICS FC500, USA), phagocytic and microbicidal functions of neutrophilic granulocytes (NG) were assessed in SG-1 and SG-2 before and 2-3 days after complex treatment with addition of an immunotherapeutic drug based on hexapeptide (HP) at a daily dose of 45 mg/ml intramuscularly for 10 days.

In patients from SG-1, a decrease in T cells (CD3⁺CD19^- ) and B cells (CD3^-CD19⁺), a 2-fold increase in the content of NK CD3^-CD16⁺CD56⁺ was found, along with altered functioning of NG (deficiency of actively phagocytizing NG, a decrease in their digestive function and NADPH-oxidase activity). In SG-2 patients, the treatment was followed by restoration of the T (CD3⁺CD19^-) and B cells (CD3^-CD19⁺), NK cells (CD3^-CD16⁺CD56⁺), like as an increase in effector functions, i.e., microbial capture by NG and their killing ability due to activation of NADPH oxidases and normalization of microbicidal reserve capacity in the NG cell population. Positive clinical effect included reduction of clinical symptoms in acute period, absence of PID exacerbations over follow-up for 6 months (85.6% of cases). Occasional exacerbations of PID were associated with medical manipulations (5.7%) and unprotected sexual contacts (5.7%).

The immunopathogenetically proven approach to correction of combined functional impairment of immune system in the women with PID shows a positive clinical and immunological effect.

Over the past decade, targeted therapy with various monoclonal antibodies has become particularly relevant for the treatment of chronic polypous rhinosinusitis (PR). This is primarily due to the high incidence rate, polyetiological origin and pathogenetic features of polyposis development, low effectiveness of existing treatment approaches, the tendency for relapse, and comorbid conditions. The article provides a brief historical background concerning various predictors of the mucous membrane remodeling in the nasal cavity and paranasal sinuses at the stages of the polyposis formation thus justifying the need for implementation of monoclonal antibodies in the treatment schedules. Considering the leading role of Th2-inflammation in immunopathogenesis of developing polypous vegetations, the influence of targeted therapy upon treatment of chronic polypous rhinosinusitis is theoretically evaluated, and we highlight some important issues that should be further specified. Undoubtedly, inhibition of the synthesis of “necessary” interleukins leads to improvement in clinical symptoms and reduced size of polypous vegetations. At the same time, the real biochemical transformations of the nasal mucosa have been scarcely studied. E.g., an attempt to inhibit some cytokine may lead to indirect blockage of other pro-inflammatory cytokines. In future, it is necessary to study the pharmacodynamics of targeted drugs in order to clarify distinct contraindications to their use.

The aim of the study was to optimize the conditions for a model immunoassay in the immunofiltration format using diagnostic reagents based on horseradish peroxidase. Residual blood serum samples from patients in the “red” zone with a verified diagnosis of a new coronavirus infection were used as positive sera, and blood sera obtained before 2019 were used as negative samples. The procedure of immunofiltration analysis was carried out using a pool of negative and positive blood sera. Studies were carried out to optimize the analysis procedure and increase the significant characteristics of the test. Results. It has been shown that the addition of sodium dodecyl sulfate to a final concentration of 50 μM in the substrate buffer makes it possible to achieve a higher analytical signal and a stable result 10 minutes after the end of the analysis procedure. Such conditions of immunofiltration analysis as dilutions of the diagnostic reagent, the volume of the introduced sample and the amount of the S-protein of the coronavirus applied to the nitrocellulose membrane were optimized. It has been determined that using immunofiltration analysis it is possible to detect antibodies against the coronavirus S-protein in a dilution of a serum sample of more than 1/1000. The results of immunofiltration analysis reproduce the results of ELISA.

Psoriasis is a chronic inflammatory skin disease characterized by increased proliferation of epidermal cells, impaired keratinization, and an inflammatory reaction in the dermis due to activation of T-lymphocytes and synthesis of proinflammatory cytokines. Pathophysiology of psoriasis is associated not only with activation of proinflammatory reactions, but also with decreased anti-inflammatory functions of immunosuppressive cells. It is known that Treg, Breg and MDSCs do not perform their classical homeostatic functions in psoriasis. In recent years, there have been more and more cases of developing resistance to ongoing therapy with genetically engineered biological drugs (GEBD) in childhood, requiring replacement or discontinuation of the drug. The aim of our work was to estimate the content of MDSCs subpopulations and their functional activity in the peripheral blood of children with psoriasis at different effectiveness of biotherapeutic drugs. We examined 110 children with psoriasis vulgaris before the appointment of biologics, at 16 and 52 weeks of therapy with adalimumab, etanercept and ustikinumab, aged 6 to 18 years. Сomparison group consisted of 34 healthy children. The effectiveness of therapy was assessed by the achievement of PASI 75 by one year of therapy. Contents of myeloid-derived suppressor cells (MDSCs) and their subpopulations, and the activity of arginase-1 were assessed by multicolor flow cytometry. An increased content of MDSCs was found in children with psoriasis against the comparison group (p = 0.000). Analysis of the effectiveness of biologics in children with psoriasis, according to PASI, showed a significant reduction in disease severity in the group of patients with good effect, both at week 16 of therapy (p = 0.000) and by one year (p = 0.017). In the group of patients with good effect of biological therapy, percentage of total MDSCs population was higher, both before start of treatment and by 52^nd week of therapy (p < 0.01). Children with psoriasis showed increased immunosuppressive function of MDSCs by arginase-1 activity versus the comparison group (p = 0.000). The arginase-1 activity in patients with psoriasis at the stage of disease regression (PASI < 10) was significantly increased relative to children in progressive stage of psoriasis (PASI≥10; p = 0.001). Thus, the content of MDSCs and their suppressive activity in children with psoriasis is an informative efficiency predictor of the biological drugs. Fading of biotherapy effect after the induction course is accompanied by decreased number of MDSCs and their functional activity.

Odontogenic inflammatory diseases and injuries take a leading place in the structure of surgical dental pathology. They often proceed with inflammatory complications. The aim of the present work was to analyze the effector indexes of phagocytic cells at the local area of inflammation (secretions from purulent wounds, tooth socket and mixed saliva), and to evaluate the effect of topical cytokine therapy on the studied parameters in patients with inflammatory dental diseases (chronic periodontitis, odontogenic phlegmon) complicated by mandibular fractures. As a part of a two-stage research, 236 people were comprehensively examined, divided into groups depending on their clinical disease and method of treatment. This group included 74 patients (classified as K 04.5 – K 04.9), divided into subgroups by the types of periodontitis (chronic fibrous, granulating and granulomatous form); 102 patients with phlegmon (classified as L03.2, K12.2), who, at the second stage of basic therapy, received topical cytokine treatment with betaleukin (recombinant IL- 1β) and roncoleukin (recombinant IL-2). Fifty patients with fractures of the lower jaw (classified as S 02.6) underwent immunotherapy with betaleukin at the second stage of treatment. Examination of patients with inflammatory dental diseases at the first stage of study and analysis of the effector indexes of neutrophilic granulocytes and macrophages from the local inflammatory foci revealed some immunological predictive signs of lacking efficiency of the inflammatory response, manifesting as aberrant functional activity of phagocytes, e.g., inhibition of all studied parameters along with sufficiently reduced functional reserve of phagocytic cells in the patients with phlegmon; high ability to produce reactive oxygen species with a decreased functional reserve of neutrophils in the patients with fractures, and signs of activated chronic inflammation in the patients with periapical lesions. The second stage of our research associated with topical therapy with recombinant cytokines and analysis of the obtained data, ebabled us to detect different effects of drugs on the studied parameters and register the integral effect of immunotherapy, which represents normalization of altered functional indexes. Hence, the data obtained may indicate that, in patients with inflammatory processes in the maxillofacial region, a higher adaptive effector potential of phagocytes was formed at the affected focus following the topical cytokine therapy.

In patients who underwent COVID-19, various manifestations of post-COVID syndrome (PCS) are noted, causing the development of disorders accompanying severe viral infections, complicated by chronic fatigue syndrome (CFS) and severe cognitive disorders (CD). Studying the molecular mechanisms of these disorders in the system of neutrophilic granulocytes (NG) in patients with PCS associated with IFN production, receptor function of NG, in particular, their subsets expressing IFNα/βR, IFNγR(CD119), is relevant for the search for therapeutic strategies, restoration and enhancement of the innate immune response after COVID-19.

Our objective was to clarify the quantitative and phenotypic characteristics of certain subsets of neutrophil granulocytes, i.e., CD16⁺IFNα/βR1^-CD119⁺, CD16⁺IFNα/βR1⁺CD119^-, CD16⁺IFNα/βR1⁺CD119⁺, in peripheral blood of patients with post-COVID syndrome.

We have examined 39 patients (24-60 years old) with PCS 3 months after COVID-19 (study group 1, SG1). The comparison group (CG) included 30 volunteers examined over the pre-COVID period. Detection of herpesvirus infections (HSV1, EBV, HHV6, CMV) was carried out in scrapings from the tonsils and the posterior wall of the pharynx. To determine the severity of the clinical PCS symptoms, a questionnaire was used to assess its severity using a point scale. The content and phenotype of NG subsets CD16⁺IFNα/βR1^-CD119⁺, CD16⁺IFNα/βR1⁺CD119^-, CD16⁺IFNα/βR1⁺CD119⁺ were assessed by means of FC 500 (Beckman Coulter, USA).

In all patients of SG1, clinical manifestations of CFS and CD were revealed, at the average severity rates of 16.0 points (14.75-20.25). When detecting herpesvirus infections, 37.2% had only HSV1 infection; 62.8% of patients showed mixed infection (HSV1, EBV, HHV6), which exhibited more pronounced clinical symptoms. We have noted absence of CD16⁺IFNα/βR1⁺CD119⁺NG subset and phenotype transformation of CD16⁺IFNα/βR1^-CD119⁺NG, CD16⁺IFNα/βR1⁺CD119^-NG subsets. Increased density expression of CD16, IFNα/βR1, CD119 receptors was also found (p1-3 < 0.05) thus suggesting ability to accept the interferon signaling and response.

Reduced infectious burden in the post-COVID period and adequate functioning of the immune system, including the neuroimmunoendocrine regulation mechanisms, should contribute to the functional recovery of various organs, systems, thus neutralizing the PCS manifestations. Therefore, usage of recIFNα2b in combination with highly active antioxidants may contribute to development of protective immunity, prevention of acute respiratory viral infections, exacerbation of chronic infections, and restoration of the NG phenotypes followed by restoration of anti-infectious immune balance.

Immunological safety of nanoparticles is an urgent problem for development of drug delivery systems used as the basis for creating these systems. Cucurbit[n]urils (CB[n]) are molecular nanocontainers that can encapsulate various drugs and serve as the basis for delivery systems. Cucurbiturils are low-toxic compounds: under in vitro conditions, they exhibit weak immunomodulatory properties, without sufficient immunotoxicity. The aim of the present study was to evaluate the in vivo effects of cucurbiturils on the number and differential leukocyte counts in peripheral blood.

BALB/c mice aged 2-4 months were used in the work. For this study, cucurbiturils were diluted in phosphate-buffered saline and administered to laboratory animals intraperitoneally (three times a week).

When evaluating the effect of cucurbit[7]uril on blood parameters of the animals after three intraperitoneal injections weekly, no statistically significant changes were registered. However, at first administration, the animals showed a slight increase in relative number of lymphocytes after the first injection of CB[6], and an increased proportion of neutrophils after the first administration of CB[8]. Meanwhile, the proportions of lymphocytes and neutrophils were within normal ranges after the 2^nd and 3^rd injections of cucurbiturils, and did not show any significant differences against the controls. Moreover, the impact upon the subpopulation composition of peripheral blood lymphocytes in laboratory animals was assessed. After injection of CB[6], there was a decrease in T lymphocytes in the peripheral blood, along with increased proportion of CD19⁺B lymphocytes compared with the controls. CB[7] and CB[8] injections did not affect the subpopulation profile of peripheral blood lymphocytes.

We have found that intraperitoneal administration of CB[n] did not affect the blood parameters of laboratory animals, thus, probably suggesting the in vivo safety of these compounds. At the same time, CB[6] is able to exert a stimulating effect on humoral immunity by increasing relative contents of B lymphocytes.

We examined 65 men with unstable angina and acute myocardial infarction (acute coronary syndrome - ACS) from 40 to 65 years old who had previously had COVID-19 and 20 people with ACS who had not undergone COVID-19. All persons also had hypertension, and they required stenting of the coronary arteries within the next 3 days after admission to the hospital. From the immunological parameters by flow cytometry on the Navios cytofluorimeter (BeckmanCoulter, USA), according to the standardized technology for assessing the lymphocytic link of immunity [1], the following were determined: ), CD45+ CD3+ CD8+ (cytotoxic T-lymphocytes), CD45+CD3-CD19+ (B-lymphocytes), CD45+CD3+CD16+CD56+ (TNK cells), CD45+CD3-CD16+CD56+ (natural killer cells), CD45+ CD3+CD4+CD25+CD127- (T-regulatory cells), CD45+ CD3+CD4+CD25+ (T-lymphocytes - early activation), CD45+CD3+HLA-DR (T-lymphocytes - late activation). All patients were divided into groups depending on the content of NK cells (natural killer cells). Patients who have had COVID-19 have 3 phenotypes of disorders (decreased NK cell count, normal and increased), while non-survivors have 2 phenotypes (decreased NK cell count and normal). The most severe condition and severity of immune disorders were found in patients who had undergone COVID-19. In patients with acute coronary syndrome and COVID-19, predominantly with normal and elevated levels of NK cells, compared with ACS patients without COVID-19, a more severe course of the disease was observed - patients with acute myocardial infarction prevailed, they had a higher mortality rate, the duration of treatment was increased, and stent thrombosis was also more common. In persons with ACS and COVID-19 with elevated NK cells, the maximum decrease in the T-cell immunity was observed: T-lymphocytes of general, T-lymphocytes-helpers, T-cytotoxic lymphocytes, T-lymphocytes of early activation, T-regulatory cells in absolute numbers compared to other groups. The lowest immunoregulatory index and, at the same time, the maximum number of T-NK-lymphocytes were observed in persons who had undergone COVID-19 and had reduced NK cells. The minimum number of T-NK lymphocytes was recorded in patients with low NK cells who did not have COVID-19. Minimal T-lymphocytes (CD45+CD3+CD4+HLA-DR+) of late activation were found in people who recovered from COVID-19 with elevated and normal NK cells. The lowest number of late activation regulatory T cells was observed in patients who did not have COVID-19, but were vaccinated, and had a normal content of NK cells. The study also allows us to more clearly define the groups of patients with ACS who need additional immunocorrection.

Myeloid-derived suppressor cells (MDSC) - a population of immature cells of myeloid origin with inhibitory functions, mainly related to T lymphocytes. Normally, MDSC account for less than 1% of leukocytes in peripheral blood. The number of these cells increases during healthy pregnancy. However, MDSC have been shown to play a critical role in the maintenance of tumor growth and in autoimmune diseases.

Because MDSC are now considered important regulators of immunity, finding ways to manipulate their functions is important for the development of therapies for malignant and autoimmune diseases, as well as for pregnancy pathologies and post-transplant complications. The immunosuppressive mechanisms of these cells are mediated by their expression of the surface molecules CD73, ADAM17, PD -L1, the enzymes arginase 1 (Arg 1), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO), reactive oxygen species, and the production of the anti-inflammatory cytokines IL -10 and TGF-β1.

Pregnancy-specific β1-glycoprotein (PSG) is a pregnancy glycoprotein that has immunomodulatory effects on natural (dendritic cells and macrophages) and adaptive (T cells) immunity cells. At the same time, the effect of PSG on MDSC has not been investigated so far. Since this glycoprotein has promising pharmacological applications, it is necessary to study not only the native variant of PSG but also its recombinant form.

Since the main function of MDSC is immunosuppression, the aim of our work was to evaluate one of its mechanisms, namely the intracellular expression of amino acid degradation enzymes Arg1 and IDO under the influence of native and recombinant PSG in vitro.

MDSC differentiation was performed from CD11b+ cells isolated from peripheral blood of healthy volunteers. Cells were cultured for 7 days with stepwise addition of GM-CSF, IL -1β, and LPS. Native (n) (1, 10, and 100 μg/mL) and recombinant (r) (1 and 10 μg/mL) PSG was added to the cultures three days before the end of incubation. The percentage of MDSCs (Lin- HLA-DR -CD11b+CD33+) intracellularly expressing Arg1 and IDO was determined by flow cytometry.

It was found that nPSG and rPSG did not alter the amount of Arg1-expressing MDSCs at all concentrations examined. However, at a concentration of 10 μg/mL, both types of proteins caused a statistically significant increase in the percentage of cells expressing IDO.

We have already established that nPSG and rPSG affect MDSC differentiation by increasing the proportion of these cells belonging to the monocytic subpopulation. However, now we can say that PSG, in addition, enhances the suppressive function of the studied cells.

The obtained data are novel and open perspectives for targeting myeloid suppressor cells to improve cellular technologies in science and medicine.

Multiple studies are currently, aimed at studying the mechanisms of the development of basic age-related pathologies, e.g., arterial hypertension (AH). We found no literature sources concerning associations between the levels of matrix metalloproteinase type 7 (MMP-7), tissue inhibitor of matrix metalloproteinases type (TIMP-1) and anthropometric data which could be useful for diagnosing age-associated, socially dependent diseases and metabolic disorders. The article presents the data on the state of proteolysis system and anthropometric data of 45 almost healthy women and 45 women with arterial hypertension (AH) aged from 59 to 74 years old. The levels of MMP-7 and TIMP-1 in blood serum were studied by sandwich-variant of ELISA test. The waist and neck volume were measured three times with a centimeter tape at an accuracy of 1 cm. Statistical processing of the obtained data was performed using analytical software IBM SPSS Statistics, v. 22.0. The results show some correlations between the levels of MMP-7 and TIMP-1, and the waist and neck sizes (WC). Lower levels of MMP-7 and TIMP-1 were registered in the group of practically healthy women as compared to the second (AH) study group (p < 0.01). Anthropometric data were not markedly diverse: the waist size in the group of healthy women was less than in AH group (p < 0.05), and values of neck volume did not differ significantly between the groups. When assessing the relationships in the group of practically healthy women, we recorded a direct significant correlation between the waist size and neck volume (r = 0.754, p < 0.0001), while in the group of women with AH this relationship was weaker (r = 0.5782, p < 0.0001). In addition, a similar correlation was found between MMP-7 and TIMP-1 levels in the both groups studied. In the group of healthy women this relationship was of medium strength (r = 0.657, p < 0.0001), whereas in the group of women with AH it was stronger (r = 0.720, p < 0.0001). The data obtained suggest the presence of metabolic disorders in the women with arterial hypertension and signs of proteolytic enzyme system disorders.