Vol 22, No 2-2 (2019)

The tumor necrosis factor alpha (TNFα) play key role as the main pro-infl ammatory cytokine in immune processes in rheumatoid arthritis (RA). However, the activity and functions of TNFα can be regulated not only by soluble receptors (which act primarily as neutralizers of action), but also by the amount, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). Analysis of the co-expression parameters of TNFR1 and TNFR2 in RA patients compared with healthy donors showed that changes in the amount and co-expression of type 1 and type 2 receptors for TNF-alpha on the surface of immunocompetent cells are associated with indicators of disease activity.

Gut is inhabited by numerous of bacteria interacting with the immune system of the host. Disturbance of the gut homeostasis leads to various pathological states, which are to be treated by changing of microbiota. The study demonstrate the effects of microbiota alteration on viability of mice with deficient barrier function in the gut (Muc2-/-). The susceptibility of Muc2-/- mice to changing of microbiota suggesting the mice as an appropriate model for testing approaches to alter gut microbiota.

Neutrophils are the main eff ector cells that are mediated immune response to exogenous pathogens including opportunistic fungi Aspergillus fumigatus. Neutrophils infi ltrate infl amed tissues and massively die during the fi ght against pathogen. However, in some cases neutrophils survive and migrate to lymphatic vessels to neutralize residual pathogens and activate adaptive immune response. In the present study we characterized the ability of neutrophils to migrate via lymphatic vessels during A. fumigatus conidia-induced infl ammation. As a result, new data about neutrophils migration kinetics to lymphatic vessels and the role of neutrophils in control of fungal spore dissemination in the host organism were obtained.

The paper presents new data on T-lymphocyte expression of plexin B1, a high-affinity receptor for class IV semaphorin Sema4D, which expression was previously attributed exclusively to non-immune cells. The biological significance of this phenomenon, as well as its role in the regulation of T-lymphocyte functions are discussed, primarily of cell migration.

Cytokines are biological markers whose overproduction can lead to an inflammatory reaction and cause the development of pathological reactions. In the present work, the serum levels of IL-17A, IL-17F and IL-13 were studied in 36 patients with acquired angioedema during the period of clinical manifestations. The control group consisted of 10 practically healthy donors. This study showed a high level of IL-17A, IL-17F in patients with acquired angioedema during the period of clinical manifestations, while a comparative analysis showed no differences in the content of serum IL-13 in the control group and the control group. Thus, the determination of the level of IL-17A, IL-17 F in serum can be used as a laboratory diagnostic marker of acquired angioedema.

The study included 68 patients with arterial hypertension 1, 2 and 3 degrees, in whom the concentration of cytokines and components of the complement system was determined in the blood plasma before and after 4 weeks of systemic antihypertensive therapy. In patients with arterial hypertension prior to the onset of systemic antihypertensive therapy, changes in the level of pro-inflammatory and antiinflammatory cytokines and activation of the complement system were found in proportion to the level of blood pressure. In patients with arterial hypertension who have reached the target values of blood pressure against the background of ongoing pharmacotherapy, the severity of immune changes is significantly lower than in patients whose blood pressure has not reached the target level.

It was found that the 2-h immobilization stress reduced the secretion of reactive oxygen species (ROS) and IL-1β by cells of the peritoneal cavity of mice. The introduction to mice of β-endorphin at doses of 100 and 0.0005 μg / kg before immobilization modulated the eff ects of stress.

The interrelations of lymphocyte subpopulations pattern in peripheral blood and level of cartilage (Urine CartiLaps (CTX II) and bone (Serum CrossLaps) tissue metabolic markers in biological media exemplifi ed by 74 patients with incipient (0‒I) and late (III‒IV) stages of primary and post-traumatic osteoarthrosis as well as 20 healthy persons aged 45.9±11.4 have been studied. The activation of bone tissue destruction and cartilage extra-cellular matrix disorganization has been discovered at 0-I stages of primary OA, III‒IV stages of primary and post-traumatic osteoarthrosis. The evidences of immunodepression for T-cell immunity have been revealed represented by decrease of (CD3⁺CD4⁺) and (CD3⁺CD8⁺) lymphocytes. The presence (р<0.05) of mean strength (R = –0.66) negative interrelations between (CD3⁺CD4⁺) lymphocytes and Urine CartiLaps as well as (R = –0.70) between (CD3⁺CD8⁺) cells and (Serum CrossLaps) at late stages of primary and post-traumatic osteoarthrosis has been proven. In virtue of the obtained results the conclusion about incipient stages of primary osteoarthrosis being characterized with more signifi cant processes of cartilage extra-cellular matrix disorganization and bone tissue destruction has been drawn. III‒IV stages of both primary and post-traumatic osteoarthrosis are characterized with profound loss of type I and II collagen and accumulation of their degradation impurities in biological media accompanied by evidences of cell-immunity depression represented by decrease of T-lymphocytes count due to (CD3⁺CD4⁺) and (CD3⁺CD8⁺) pools. This proves the generality of pathogenetic remodelling regulatory mechanisms in bone and cartilage skeletal tissues at late presentations of the disease.

Two monoclonal antibodies were developed and were shown to block the complement system alternative pathway (AP) activation at the stage of assembly and activation of C3 convertase. The humanized antibody hC34 specific to a binding site on α’2 determinant of С3с fragment inhibited in vitro the human complement activation by 90% at a dose of 3 μg/ml of blood serum. The antibody 3А8 specific to rat complement C3 component and similar to antibody hC34 was demonstrated to be pharmacologically active in model of closed craniocerebral injury (data of functional and histological studies). The results of this study indicate the humanized antibody hc34 to be promising for treatment of central nervous system pathologies and of other diseases associated with complement hyperactivation.

The dynamics of the density of the spatial distribution of mast cells of the body of the womb and the content of catecholamines, serotonin and histamine during sexual cycle, pregnancy and postpartum period in rats were examined by fl uorescence-histochemical methods. The linear correlation of serotonin&catecholamines content in mast cells was kept at high level (during sexual cycle, pregnancy) or was quickly recovered (during postpartum involution) by changing of the uterus functional state. The participation of mast cells in the restoration of uterine sympathetic innervation after birth was considered. The leading role of mast cells in paracrine regulation of uterine tissue morphogenesis was assumed.

The injections of two compounds of the substituted 1, 3, 4-thiadiazines class (L-17 and L-14) were accompanied by normalization of the total number and fractions of peripheral blood leukocytes in rats with type 2 diabetes, obtained by administration of nicotinamide and streptozotocin. L-17 is more effective than L-14 in reducing hyperglycemia.

A morphological and cytochemical study of the oxidative metabolism of cells bronchoalveolar lavage (BAL) patients with varying degrees of severity chronic obstructive pulmonary disease (COPD) was studed. It was established that along with cell necrosis, enucleation of granulocytes and macrophages is determined, which refers to the morphological feature of programmed death by the formation of extracellular traps – NET-osis. Proven correlation between indicators of netosis, changes in the oxidative metabolism of cells and the degrees of severity of COPD.

It was shown that peptide of the GM-CSF active center is the pluripotent colony-stimulating factor possessing the expressed antibacterial, antiviral, immunostimulating, reparation, radio tire-tread action of in vitro and in vivo. Similar properties the cosmetic preparation ACEGRAM created on its basis possesses.

Despite well-studied role of the adapter STING in the cell response to cytosolic DNA, its contribution to the activation of programmed cell death was not considered at the proper level. In this study was shown that activation of STING in T cells leads to production of typeI interferons, upregulation expression levels of the interferon-stimulating gene group (ISG), as well as cell death. It is also shown that cell death is mediated by UPR (Unfolded Protein Response).

As it is known, serum creatinine and glomerular filtration rate are considered to be markers of kidney damage. In chronic kidney disease, these markers reveal a late stage of kidney damage, when drug therapy is not always effective and the process of kidney damage is irreversible. In recent years, special attention has been paid to the search for predictors of acute and relapses of chronic renal damage, which could lead to the detection of premorbid pathological changes in the kidneys, to determine the nature and differentiate the defeat of various parts of the nephron, to establish the stage of the process, to assess the severity of inflammation and the intensity of fi brogenesis. One of these early markers is NGAL are investigated.

Natural killer cells are attributed to lymphocytes of innate immunity for their ability of spontaneous antitumor activity without prior activation. However, recent studies have shown that some viral infections, such as human cytomegalovirus, can cause an increase in the number of NK cells with the phenotype CD57+NKG2C+ compared to healthy donors. It is assumed that cells of this subpopulation have some properties of adaptivity and immunological memory to HCMV infection. This paper is devoted to the study of properties of human NK-cell subpopulations selected for the markers CD57 and NKG2C, when stimulated with IL-2 and membrane-bound IL-21.

The study is devoted to determining the effect of magnetic iron-containing nanoparticles on the functional state of blood neutrophils. The object of the study was neutrophil granulocytes (n=34). 3 groups were formed: control (without incubation); in the second group – exposed to synthetic magnetic ironcontaining ferrihydrite nanoparticles; in the third group – synthetic magnetic iron-containing ferrihydrite nanoparticles, in the third group – synthetic magnetic iron-containing ferrihydrite nanoparticles coated with natural polysaccharide – arabinogalactane. The concentration of nanoparticles ferrihydrite was 5 mg/ml and 20 mg/ml. Explored the early and late chemiluminescent response. It was found that the functional activity of cells under the influence of different experimental types of iron-containing nanoparticles varies depending on the concentration, with an increase in the number of acting nanoparticles, a unidirectional reaction with a decrease in cell activity is observed.

We developed and characterized the model of psoriasiform dermatitis in mice induced by induced by intradermal administration of recombinant human IL-36γ. Induced skin lesions resemble human psoriasis in means of both macroscopic (PASI) and microscopic features (acanthosis, parakeratosis, dermal leucocyte infiltration). This model can be used for anti-psoriatic drugs efficiency research.

It has been established that during endometriosis, regardless of the severity of the disease, at the systemiс level IL-4 synthesis, intracellular expression of IL-4 and IL-6 were increased in the total lymphocyte and in the T-helper population, and in the peritoneal fluid the level of IL-6⁺ lymphocytes was increased. Changes in the synthesis, intracellular expression and the serum IL-4 content were proportional to the severity of endometriosis. In endometriosis stages I–II the intracellular production of IL-5 increased in the total lymphocyte population and in the T-helper pool. In endometriosis III–IV the IL-6 synthesis by peripheral lymphocytes increased, as well as the serum level of IL-4, the amount of IL-4⁺, CD4⁺IL-4⁺ lymphocytes and sCD30 in the peritoneal fluid. 

IL-4 and TNFα cytokines are involved in the pathogenesis of spontaneous urticaria and can be considered as potential biomarkers of the disease.

The purpose of this study is to study the effect of single and combined stress effects on the neutrophil function of the blood of rabbits in the experiment. For the experiment used 10 male rabbits, age ‒ 8 months, live weight 3,40±0,73 kg. In the first series of experiments, transport stress was modeled by transporting animals in a car. We caused immobilization stress in the second series of experiments by fixing the rabbit with its legs in the supine position. In the third series of experiments, a combination of effects was performed (immobilization, then, after three days, transportation). Phagocytic activity of blood neutrophils, phagocytic index, digestion index (killing) were determined. It was shown that the combination of stress effects negatively affects not only the phagocytic activity of neutrophils directly during their layering, but also the restoration of the functional systems of blood phagocytes in the post-stress period compared to single stresses.

The study involved healthy women, the average age of whom was 45.0±3.41. All patients received a single procedure for the biorevitalization of the facial skin. Some indicators of systemic and tissue immunity were evaluated. When analyzing the number of immune cells in the skin before and after the procedure, the amount of CD3⁺, CD4⁺, CD8⁺ was doubled. The amount of CD20+ remained practically unchanged. When assessing immunoglobulins M, G in the skin before and after the procedure, a decrease in these indicators was observed. IgA practically did not change. The amount of immunoglobulins in the skin changed as well as in the blood. It decreased. When assessing the parameters of cellular immunity of blood, it was found out that the cellular composition of the blood does not practically change. Significant changes occurred only in the absolute and relative amount of CD3^–CD56⁺. These indicators signifi cantly increased.  

Modern methods of multicolor flow cytometry in combination with MHC multimer technologies allow not only to identify and isolate cytotoxic T-lymphocyte (CTL) populations, but also to conduct phenotypic research on the level of differentiation, functional features of these cells, and even to investigate the distribution of memory T-cell subsets inside populations specific to particular epitopes of tumor antigens. In the present study, we assessed the level of differentiation and the content of memory T-cell subpopulations in cytotoxic T-lymphocyte populations specific for HER2/neu antigen epitopes (HER2) using the MHC-multimers antigen-specific CD8⁺ T-cell staining method and multicolor flow cytometry. The resulting HER2-specific T cells to a large extent (about 40‒50%) have the TSCM phenotype, a population capable of the most pronounced antitumor immune response due to a combination of effector properties with self-sustainability. 

Dendritic cells (DCs) regulate immune responses by modulating T and B cells in the direction of effector or tolerogenic responses. In this study, the effect of BAY 11-7082 on the formation of immunosuppressive DC of C57Bl/6 mice in vitro using recombinant IL-10 or TGF-β was evaluated. It was shown that the addition of BAY 11-7082 to the culture of immature DCs did not significantly affect the expression of the maturation molecules of dendritic cells (CD80, CD86). When using BAY 11-7082 in combination with IL-10 or TGF-β, reduced the expression of these molecules. The joint cultivation of DC with splenocytes in the presence of BAY 11-7082 and IL-10/TGF-β promoted the differentiation of regulatory T-cells (CD4+CD25hiFoxP3+) and did not contribute to the differentiation of CD4+ T-cells producing IL-10.

Allogeneic biomaterials (AB) after implantation in a defect in the calf muscles of rats and the uterine horn of the rat contribute to the regeneration of tissues due to migration of M1 macrophages expressing Pro-inflammatory factors, TNFα, IL-1. They inhibit the migration of M2 macrophages, fibrosis factors, promote migration and differentiation of myocytes. IN ischemic damaged myocardium after AB implantation, on the contrary, cd68 macrophage deficiency was found, but high expression by Timp2 cells compared to the control, which could contribute to the reduction of scar area. After the introduction of AB in muscle tissues revealed resident macrophages with phenotype IL-1⁺/CD68⁺/PCNA⁺/Hale⁺/ vimentin⁺/FGF1^- /TGF-β1^–. 

Using confocal fluorescence microscopy it was shown that stearylamine (SA) at concentration of 0.2 mg/ml causes the neutrophil extracellular traps formation. In comparison with classic NET activator, the phorbol ether of myristate acetate (PMA), SA activates this process much faster, in 30‒60 min, while under PMA stimulation it occurs in 2‒3 hours. Using luminol-dependent chemiluminescence, we showed that SA does not activate NADPH oxidase. SA dose-dependently suppresses the oxidative burst stimulated with PMA, zymosan, or latex. The direct evidence that NADPH oxidase is not activated under the SA action was obtained by using neutrophils isolated from the blood of patients with chronic granulomatous disease (CGD). It is obvious from our results, that SA-induced NET formation does not require the participation of reactive oxygen species and proceeds according to a nonclassical mechanism.

An experimental model of diffuse toxic rat liver damage with carbon tetrachloride (CCl4) and its correction by aminophthalhydrazide (APH) was used to evaluate the response of mast cells and the degree of fibrosis. Structural disorders and suppression of regenerative processes in the liver under conditions of chemical trauma were accompanied by increased migration of mast cells to the portal stroma and an increased content of secretory granules in them. The use of APH contributes to the normalization of the area, occupied by collagen in the liver tissue, and reduces the number of mast cells, but maintains a high content of secretory granules in them.

A model of the bacterial process under the influence of fMLP was reproduced in the in vitro system, which made it possible to reveal the features of the transformation of CD66b⁺CD33⁺CD16⁺CD11b⁺neutrofi l granulocytes (NG). Multidirectional effects of mono-effects of peptides and rIFNα2b on the expression of the studied markers of NG in healthy children were identified. The modulating effect of rIFNα2b on the transformed fMLP phenotype of NG is associated with polarization into an anti-inflammatory phenotype. 

Biomaterials have recently been recognized for their potential use in regenerative medicine and tissue engineering, since they not only represent a scaff old for cell populations, but also can infl uence functionality of diff erent cell types. In particular silk-based biomaterials (i. e. fibroin or spidroin) are of high interest, because they show prominent mechanistic features and have proregenerative potential. In our work we showed that composite fibroin/gelatin scaff olds induce moderate infl ammation both in vitro and in vivo and this eff ect depends on the configuration of the matrices. In particular, culturing of Mouse Embryonic Fibroblasts (MEF) on three-dimensional (3D), but not two-dimensional (2D) fibroin/gelatin scaff olds resulted in overexpression of adhesion molecules ICAM-1 and VCAM-1 as well as proinfl ammatory cytokines TNF and IL-6. Moreover subcutaneous injection of fibroin/gelatin microparticles in mice lead to accumulation of infl ammatory myeloid cells and acceleration of skin wound healing, while implantation of 3D fibroin/gelatin scaff olds under the kidney capsule promoted lymphocytes clusterization, resulting in generation of primitive lymphoid tissue. Altogether our data suggest immunomodulatory features of fibroin/gelatin scaff olds, which can be useful in tissue engineering and regenerative medicine.

The purpose of the study is to evaluate the eff ectiveness of purulent wounds treatment with the local combined use of Miliacile and EHF-therapy in patients with diabetes mellitus, based on determining the cytokine content. In 35 patients of the main group, Miliacile and EHF therapy were used in the local treatment of wounds, while in 35 patients of the control group, only Miliacile was used and the levels of TNFα, IFNγ, IL-4, IL-10 were determined in the blood serum of these patients upon admission to hospital, on the 7th day and at the end of treatment. As a result of treatment, there was observed a more pronounced increase in the level of cytokines (IFNγ, IL-4) and their decrease (IL-10, TNFα) in the patients of the main group as compared with patients of the control group. The eff ectiveness of purulent wounds treatment in patients with diabetes mellitus with the local use of Miliacile and EHF-therapy based on the determination of cytokine levels was determined.

The use of anti-inflammatory drugs for the basic therapy of ulcerative colitis (UC) (5-aminosalicylic acid (5-ASA), glucocorticoids) is limited to a wide range of side effects. The aim of the work is to study the effect of rectal suppositories of the original composition with vitamin D3 on the serum concentration of IgG, IgM and IL-8 in experimental UC. The work was performed on 70 white rats of the Wistar line, UC was modeled by two-stage administration of 3% oxazolone, vitamin D3 in the rectal suppositories of the original polyethylene glycol composition was used every 12 hours, in the comparison group rectal suppositories with 5-ASC were used. Serum concentrations of IL-8, IgG and IgM were determined using specific test systems for rats on an immunoassay analyzer on days 2, 4 and 6 of the experiment. It was established that in experimental oxazolone-induced ulcerative colitis in the serum of rats, the concentration of IL-8, IgG and IgM increases on days 2, 4 and 6 of the experiment. The use of vitamin D3 in the composition of rectal suppositories of the original composition daily with an interval of 12 hours with experimental UC leads to a decrease in the concentration of IL-8 for 6 days, and the concentration of IgG and IgM – on 4 and 6 days of observation.

We provide the fi rst characterization of glucose and energy metabolism rearrangements in human macrophages upon their activation with a NOD1 receptor agonist (N-acetyl-D-muramyl-L-alanylD-isoglutamyl-meso-diaminopimelic acid, or M-triDAP) in comparison with the eff ects of a TLR4 agonist, lipopolysaccharide (LPS). We demonstrate possibilities of modulation of cytokine production by macrophages using glycolysis inhibitors.

The content of endothelial progenitor cells in umbilical cord blood was determined in newborns born to mothers with preeclampsia and without preeclampsia. Phenotyping of umbilical cord blood endothelial cells was performed by flow cytometry, circulating endothelial cells (CES) were defined as: CD45^–, CD133⁺, VEGFR2⁺, CD34^–, endothelial progenitor cells (EPCS) were defined as: CD45^–, CD133⁺, VEGFR2⁺, CD34⁺. There was a decrease in both the total number of circulating endothelial cells and endothelial progenitor cells in premature infants compared to full-term ones. In newborns born to mothers with preeclampsia, only the number of ECP was significantly higher, compared with newborns from mothers without preeclampsia, and in the group of premature and full-term newborns. 

The study investigated the effect of conditioned media of M1 and M2 macrophages on the phenotype and proliferation of the human neuroblastoma cell line SH-SY5Y. It has been established that conditioned media of M2 macrophages, generated in the presence of GM-CSF under defi ciency of growth factors, have a pronounced stimulating effect on the SH-SY5Y cell proliferation. The expression of the low-affinity nerve growth factor receptor, CD271, correlates with cell morphology: in cultures with a predominance of N-type cells, the number of CD271+ cells is signifi cantly higher compared to cultures dominated by S-type cells.

Soybeans and peanuts are the strongest food allergens among all leguminous plants. Today, allergens of these legumes are not sufficiently accessible in clinical practice for a number of reasons. In this regard, the aim of the work was to obtain protein extracts from soybeans and peanuts and to evaluate their biochemicaland allergenic properties. The preparation of a solution of protein-polysaccharide complexes was performed by the method of water-salt extraction, the determination of the protein content was carried out by the method of Bradford, the study of the protein composition of the obtained extracts was carried out by the polyacrylamide gel electrophoresis. Allergenic properties were investigated by the method of inhibition of sIgE binding. Proteins were described in the obtained protein extracts. They belong to cupin, prolamin, profi lin protein fractions and Bet v 1-like proteins. A study of individual protein fractions and further comparison of their allergenic properties will significantly complement the component diagnostics, which is actively being introduced into clinical practice.

Neutrophils are the first line of defense against infectious diseases. The contribution of neutrophils to the pathogenesis of tuberculosis is controversial and not fully understood. In this study, we analyzed the heterogeneity of neutrophil populations in patients with tuberculosis and control subjects. In patients with tuberculosis, there is an increase in the number of low-density neutrophils compared with control subjects. We have found that the low-density neutrophil population is heterogeneous and contains a subpopulation of activated cells.

The work was aimed at determining the possibility of activation of lymphocytes and natural killer cells with the addition of various concentrations of IFN-γ in vitro. The results showed that IFN- γ promotes maturation of T eff ector cell-mediated immunity system.

Characterization of impaired JAK-STAT-signal transduction and SOCS regulation in cytokine-dependent activation in purulent-inflammatory diseases of soft tissues.

In the present work we demonstrated that IFNα-induced dendritic cells (IFN-DCs) loaded with a lysate of autologous tumor cells of high-grade glioma patients (DC_LYS) more eff ectively stimulated the proliferative response of autologous T-cells compared with unloaded IFN-DCs (DC_LPS) and did not induce apoptosis of CD4⁺ and CD8⁺ T cells. Moreover, DC_LYS activated cytotoxic CD8⁺ T cells (in the degranulation test) in cultures of autologous mononuclear cells of studied patients. 

It is established, that cultivation fibroblasts in conditions hypoxia leads to decrease in their morphological heterogeneity, increase proliferative to activity and viability of cells. Causes oppression of synthesis of components extracellular matrix (collagen and elastin) and decrease expression a receptor hyaluronic acids (CD44). Duration hypoxia causes a degree of decrease.

Dendritic cells (DC) are widely used to produce vaccines for the treatment of various types of diseases, such as malignant neoplasms, autoimmune disorders, rejection and GVHD. To control the functional properties of DCs, they are transfected with various immunoregulatory proteins, including IL-10. In this paper, the optimization of the method of electrical transfection (electroporation) of DCs with a DNA plasmid encoding IL-10 was performed. The effi ciency of DC electroporation (EP) reaches 45‒72% with cell death below 7%. The active expression of IL-10 in transfected DC was shown within 3 days after EP. According to the results of the work, EP was recognized as an eff ective method for obtaining transfected DCs for the production of cellular vaccines.

The levels of MMP-2, TIMP-2 and its ratio in blood serum were studied in order to identify predictors of severe AKI for initiating early renal replacement therapy after CABG. The study engaged 60 patients, from 45 to 74 years old, with CHD before and after CABG without diabetes mellitus. Statistically signifi cant differences of MMP-2, TIMP-2 and its ratio in the blood serum were revealed. Determining the ratio of two structural kidney damage markers (MMP-2, TIMP-2) in patients on the 2nd day after CABG allows to detect AKI. The dynamics of the MMP-2 / TIMP-2 ratio in the two compared groups with AKI was different. In the 1st group, the value of ratio signifi cantly decreased on the first day after CABG, significantly increased on the 2nd and reached high rates on the 7th day. In the 2nd group, there was a wave dynamics of MMP-2 / TIMP-2 ratio: increase on the first day, a signifi cant decrease on the 2nd and a twofold increase on the 7th day. Diagnostic and prognostic significance of the MMP-2 level was found in patients with CKD at all steps of monitoring.

MV has been shown to have a positive effect on the restoration of renal excretory function at a level comparable to the effect of MSCs. The use of MSC and MB in the treatment of acute renal failure resulted in almost the same result: on the 4th day the level of urea was 9.3 μg/ml and 9.37 μg/ml, respectively, which is 25% lower than in the glycerol control. By the 8th day, the level of urea was 7.9 μg/ ml after the introduction of MSC and 7.6 μg/ml after the introduction of MB, which is 21% lower than in the glycerol control. It has been shown that the MW produced by MSCs stimulate the proliferation of both splenocytes and cells of the kidney tissue in a dose-dependent manner. To study the resistance to apoptosis, splenocytes were used both from intact mice and from glycerol-induced ARF. The addition of MB causes a decrease in the level of apoptosis in both intact mice (21.73%) and mice with ARF (13.28%). Accordingly, inversely, the percentage of cells in the S / M phase of the cell cycle increased.

The study included children with chronic tonsillitis in the background cytomegalovirus or virus Epshtein-Barr infection. IL-1β, IL-6, TNF, IL-10 in blood serum and washes from tonsils were studied as laboratory parameters of local and general cytokine status. Imbalance of pro-inflammatory and antiinfl ammatory cytokines in the group of patients with chronic tonsillitis was revealed. Concomitant herpes virus infection exacerbates tendencies, leading to more meaningful local violation of the anti-microbial protection.

It was established that under conditions of chronic cold stress in mice, a decrease in the absolute and relative amount of antibody-forming cells in the spleen was observed. The blockade of opiate receptors led to the abolition of oppression.

The patients with a diagnosis of acute non-obstructive (ANOP) and obstructive pyelonephritis (AOP) (31 and 30 patients respectively) were under observation during treatment at the urological center of the National Healthcare Institution Scientifi c Clinical Center of Russian Railways. The levels of cytokines, complement components and their inhibitors in plasma and the first portion of morning urine, phagocytic and oxygen-dependent activity of circulating blood neutrophils were determined. At the systemic level, in patients with ANOP, to a greater extent in AOP, an increase in the concentration of pro-inflammatory cytokines (TNFα, IL-6, IL-8 and IFNγ), IFNα, IL-4 and IL-10, components of the C₃ and C_5a compliment was established, a decrease in the level of IL-1RA and a regulator of the complement factor H system, a decrease in the activity and intensity of phagocytosis of peripheral blood neutrophils with an increase in the activity of oxygen-dependent systems were also revealed. Before treatment at the local level (in the urine) in patients with ANOP, an increase in the concentration of all studied cytokines, except IL-4, components C₃ and C₅, and a decrease in IL-1RA was established. In AOP, changes were more pronounced, with the exception of a reduced level of factor H and sIgA. 

The production of reactive oxygen species by blood leukocytes and bone marrow cells in the reaction of luminol-dependent chemiluminescence under the action of non-opsonized zymosan and zymosan opsonized with fresh or inactivated autologous serum at 56 °C was investigated. It was established that an increase in the chemiluminescence levels takes place in all three variants of phagocyte activation, but it is most pronounced when using fresh serum.

The capacities of glycoarray – a unique method for investigation of carbohydrate-binding proteins including antibodies and lectins – are presented. It was shown that array is very flexi ble device and it can be directional changed for solution of a wide range of diff erent tasks of both fundamental and applied nature.

The study included 104 patients hospitalized in the neurological department of the Kursk Regional Clinical Hospital with chronic cerebral ischemia (CCI) against the background of hypertension of the II stage, equally divided by the I and II stages of the disease. In the blood (plasma, neutrophils and erythrocytes), the parameters of the immune and metabolic status were determined with an assessment of the relationship between the studied parameters. In patients with CCI stage I and stage II it is established that there are more reliable interrelations in patients with early stage of the disease compared with those in patients with stage II, and this probably indicates a greater disadaptation of the mechanisms for maintaining immune and metabolic homeostasis in patients with CCI stage II, compared with patients with stage I disease.

The lack of effective vaccines against Ebola virus initiates a search for new approaches to solving this problem. One of the promising directions in development of antiviral vaccines based on designing DNA-vaccines encoding artificial polyepitope immunogens. Previously, using the original software, we designed two polyepitopic T-cell immunogens containing cytotoxic and T-helper epitopes of Ebola virus and showed that DNA vaccines based on them provide synthesis of target mRNA and proteins in a culture of eukaryotic cells. As part of this work, we have shown that engineered DNA vaccine constructs induce virus-specific responses of CD4⁺ and CD8⁺ T-lymphocytes in immunized mice. 

World Health Organization (WHO) experts issue strain recommendations to ensure effective yearly influenza vaccination. Several important “firsts” had taken place in recent years. An up to a 1-month recommendation delay puts the whole system of timely procurement of enough doses of effective and safe influenza vaccines based on up-to-date strains at risk.

The obtained recombinant pneumolysin (rPLY) Streptococcus pneumoniae in atoxic form. The immunogenic and protective activity of rPLY was studied. It was shown that in the sera of mice after double injection of rPLY, the IgG titer increased by up to 32 times as compared with the sera of intact mice. After the third administration of rPLY, the IgG titer increased by up to 15 times compared with the initial IgG level after the second immunization. The protective activity of rPLY revealed in the experience of active protection in intraperitoneal infection of S. pneumoniae mice.

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract. It can cause HPV-related diseases that lead to serious health problems. Persistent high-risk (HR) human papillomavirus infection is necessary for development of cervical cancer. Vaccination is an eff ective method to prevent HPV-related diseases. The world experience in using of HPV vaccines has shown their safety and high eff ectiveness.

Development of a universal influenza vaccine is an important task. One of approaches for develop a universal influenza vaccine is design of artificial immunogens, which consist of fragments from proteins of diff erent subtypes of influenza virus. Candidate universal DNA-vaccine were design in the FBSI SRC VB «Vector» earlier. The vaccine encode artificial antigens designed on the basis of conservative fragments of the hemagglutinin stem from influenza A virus of two subtypes H1N1 and H3N2, and on the basis of conservative protein M2. The article presents results of a study of the T-cell immune response in mice that were immunized with DNA-vaccine constructs encoding the designed influenza virus antigens.

Domestic legislation is familiar with the concept of genodiagnostics, however, the most important issues related to its conduct (about permitted and prohibited to conduct varieties of genodiagnosis, guarantees of non-discrimination and confi dentiality following this procedure, about the fate of genetic samples remaining after it) remain unresolved. Within the framework of this article, the author examines examples of the normative regulation of the issues mentioned in foreign countries, suggesting that foreign experience should be used wisely.

Primary immunodeficiency (PID) is a diverse group of genetically determined diseases, including more than 330 diseases. Early detection of PID and selection of adequate therapy aff ects the prognosis of the disease, improves the quality of life and life expectancy of patients significantly. PID register is the main tool for solving the tasks. Registration of patients with PID in the Republic of Bashkortostan (RB) is carried out on the basis of the Republican Children Clinical Hospital (RCCH) of Ufa and at March 2019, the number of registered patients increased to 223 people. Currently, 126 children are observed in the RCCH of Ufa, 43 patients have been transferred to the adult network. Distinctive features of the regional register of the RB are the presence of patients for whom the diagnosis of PID was set at autopsy and the absence of patients with Nij megen syndrome. The solution of current problems related to the diagnosis and treatment of PID is possible only with state support and teamwork of doctors of various specialties.

Associations between polymorphic sites rs2239815 of gene MAPK8, rs1053023 of gene STAT3, rs4143094 of gene GATA3, rs28362491 of gene NF-kB1 with the absolute and relative number of CD19+ lymphocytes, CD3⁺CD4⁺ lymphocytes and with the absolute content of CD3⁺ and CD3⁺CD8⁺ lymphocytes were registeredin exposed persons. 

On 62 Wistar rats with a 30-day-long, to a greater extent with a 60-day-long ethanol introduction, the development of toxic liver damage has been established by biochemical and morphological methods. In presence of a 60-day-long chronic alcohol intoxication, compared with a 30-day-long ethanol introduction, a more pronounced suppression of adaptive cellular and humoral forms formation of the immune response to sheep erythrocytes, a decrease in the phagocytic capabilities of neutrophils with an increase in their oxygen-dependent activity have been determined.

Currently, Candida albicans is considered a predictor of chronic infl ammation and insulin resistance. The work investigated the contribution of fungal sensitization on the example of Candida albicans in the development of hypersensitivity to food antigens and manifestations of the metabolic syndrome.

This study represents one of the stages of the study of the antimicrobial action of trimethylammonium hexachloroplatinate on bacteria Escherichia coli.