Vol 24, No 2 (2021)

The article is devoted to studying the role of mesenchymal stromal cells in formation of microenvironment for hematopoietic stem cells under the conditions mimicking physiological bone remodeling in presence of artificial three-dimensional matrices (Ra = 2-3 μm). The study was carried out using experimental samples of artificial implants obtained in electrolyte from hydroxyapatite nanoparticles (HAP) produced at the Institute of Strength Physics and Materials Science (Siberian Branch of the Russian Academy of Sciences). The work included cultural and instrumental research techniques. Phenotypic profile of cells was assessed by flow cytometry. Determination of cytokine/chemokine levels from cell culture supernatants was assessed by flow fluorimetry. Detection of hematopoietic cells in the vision fields, as well as areas of extracellular matrix mineralization was carried out by means of cytomorphometry.

It was revealed that the 3D matrices with a calcium phosphate coating initiate the in vitro formation of specific microenvironment of MSCs, resulting in the increased numbers of HSCs with the CD45⁺CD34⁺ phenotype (at 14 days), an increased number of cells with hematopoietic morphology and evolving foci of extracellular matrix mineralization of the (at 21 days). Changed numbers of hematopoietic cells per vision field occurred, mainly, due to indirect effect of hematopoietic factors (SCF and G-CSF), along with decrease of proapoptotic factor TRAIL. It was also found that MSCs reduce the level of proinflammatory cytokines (IFNγ, TNFα, IP-10, IL-2, IL-6) in culture medium in the presence of artificial 3D calcium-phosphate-coated matrices. The revealed features of MSC functioning under the conditions simulating physiological bone remodeling, upon co-cultures with three-dimensional matrices (Ra = 2-3 μm), have shown a significant effect of MSCs upon regulation of HSCs by local microenvironment, through distinct modulating effects of cytokines, chemokines, and growth factors that provide intercellular interactions. Development of extracellular matrix mineralization areas during MSC cultivation in the presence of 3D matrices imitating mineral substance of bone tissue also indicates the formation of osteoblastic niches under the in vitro cultivation conditions.

The results obtained are important in order to assess functions of hematopoietic niches and the role of MSCs in their development and maintenance of the microenvironment.

The results obtained may find practical application in development of new classes of medical devices able to provide effective osseointegration.

The present work concerns a study of cytoprotective effect of biologically active substances (BAS) produced by probiotic microorganisms from the Bacillus genus. These substances were obtained from a sterile fugate of probiotic Bacillus subtilis VKPM B-3679 culture (a biosporicin-producing strain) and added to the culture of isolated hepatocytes, when modeling their in vitro toxic damage. Sterile buffered culture of Bacillus subtilis B-3679 was prepared by sterilizing filtration of the culture supernatant of this strain. The work was carried out using a passageable L-41 cell culture strain, which allows to assess toxicity of various substrates upon cell cultures and protection against toxic effects at different concentrations. At the first stage of study, the maximal non-toxic dose of sterile fugate and the minimal toxic dose of CCl4 established for the cultured L-41 cells. At the next stage, cytoprotective effect of BAS originating from the of B. subtilis B-3679 strain fugate, was studied and tested with L-41 cell line. Cytoprotective and regenerative effects of BAS containing in the fugate of B. subtilis B-3679 strain were demonstrated in the model of toxic damage using the culture of isolated hepatocytes. In preclinical studies, to assess the toxicity and safety of the experimental sample of a new biohepatoprotector for experimental animals, we have found that the complex of biologically active substances (metabolites) is non-toxic and safe for laboratory animals when administered intragastrically and intraperitoneally, and it does not cause any pathological changes in their internal organs and tissues. The basis of the new biohepatoprotection effect, which may provide a multifunctional action, allowing to effectively restore depressed liver functions, with simultaneous normalization of immunological parameters, is its active biocomponent, i.e., metabolites of probiotic spore-forming bacteria, which, when if brought to the body, produce a complex of biologically active metabolites (antibiotics, proteolytic, amylolytic, and other enzymes, immunoglobulins, as well as interleukins, vitamins, proteins, amino acids, and others bioactive substances). Due to experimentally established cytoprotective effect of the complex of BAS, the components of fugate culture of B. subtilis strain B-3679, will allow us to develop new promising medical immunobiological drugs that may provide a protective effect on human organs and tissues. As a result it was found that BAS, as components of fugate from B. subtilis B-3679 strain show both a pronounced cytoprotective effect, and a positive action upon regenerative abilities of liver cells, which is a significant factor for the future use of this strain as a biocomponent of a new immunotropic biohepatoprotector.

Adaptive immunity changes in thermal trauma (TT) increase the risk of infectious complications and limit repair of the lesion. Hence, search and preclinical testing of effective and safe means to locally manage TT, containing bioregulators, is an urgent task of modern medicine. Dermal films (DF) are an innovative and popular variant of wound coatings for small-area burns, and pleiotropic properties of melatonin (MT) suggest its effectiveness in TT. The aim of the work is to investigate the effect of MT, as a component of original DF, upon the indexes of adaptive immunity in experimental TT. The experiment was performed on 115 male Wistar rats. Grade IIIA TT with area of 3.5% were produced by contact with boiling water for 12 s. DF with an area of 12 cm² based on sodium carboxymethylcellulose contatning MT (5 mg/g) was applied daily for 5 days. Similar DF matrix, but without MT, was used in the control group, Amounts of CD3⁺ and CD45RA⁺ cells in blood, and lymphocyte subpolulations with early and late signs of apoptosis and partially necrotic cells were evaluated with flow cytofluorometer, as well as IgG and IgM concentrations were measured in blood serum using rat test systems. With TT, the amount of CD3⁺ in the blood decreases on days +5 and +10, CD45RA⁺, on days +5, +10 and +20, and the concentration of IgG in the serum, on days +5 and +10 of observation. On days +5 and +10 after TT, a relationship was established between CD3⁺ and the number of lymphocytes with signs of early apoptosis (R = -0.47; p < 0.05; R = -0.51; p < 0.05, respectively), and signs of late apoptosis and necrosis (R = -0.64; p < 0.05; R = -0.42; p < 0.05, respectively), between CD45RA⁺ and the number of lymphocytes with signs of early apoptosis (R = -0.47; p < 0.05; R = -0.49; p < 0.05, respectively), and signs of late apoptosis and necrosis (R = -0.57; p < 0.05; R = -0.49; p < 0.05, respectively). Usage of MT in DF composition leads to increase in blood CD3⁺ on the 5^th and 20^th days, CD45RA⁺, on the 5^th day, and an increase in serum IgG concentration was observed on the 5^th and 10^th days following TT. Restriction of necrotic and apoptotic death of blood lymphocyte may be among the mechanisms of the immunotropic effect produced by MT which is, probably, due to its local antioxidant and anti-inflammatory action in the TT area.

Microenvironment of sperm and its precursors includes various immune cell populations. This indicates not only their importance for immune privileged state within testes, but it concerns a regulatory role of these structures in performance of the most important physiological functions. Despite sufficient knowledge on the immune privileged state in the organ, the regulatory function are scarcely studied, and existing literature virtually does not cover the issues of local spermatogenesis regulation by various components of testicular microenvironment in the course of their regeneration. Purpose of the present study was to define the reactions of connective tissue in rat testis following traumatic lesion. Materials and methods: the study was carried out in mature male Wistar rats. Experimental animals were divided into 2 groups: intact animals and animals with blunt trauma to the left testicle. The animals were removed from the experiment on the 7^th and 30^th days. Blunt trauma was simulated by squeezing the organ with forceps with a force of 15 N for 3 seconds. For histological examination, the testes were excised, preparations were made by the standard scheme, stained with hematoxylin/ eosin, toluidine blue (to identify mast cells), and according to Van Gieson (to detect collagen fibers). Distinct components of connective tissue and spermatogenesis were evaluated in testicular preparations. Quantitative indexes were calculated using the ImageJ program. Total testosterone levels in the blood were determined by chemiluminescence technique. Statistical evaluation was performed with Statistica 8.0 software. Comparison of groups was performed using Mann-Whitney test. We have found that restoration of spermatogenesis in the damaged testis did not occur within 30 days after the injury. While the reaction of connective tissue was noted in the both testes, it was more pronounced in the damaged organ, and manifests as changes in testicular microvasculature, stimulation of fibroblastic response, multidirectional effects of mast cells and Leydig cells, depending on the duration of exposure. Changes in various components of microenvironment in the damaged testis led to similar changes in the intact organ. The mechanism of this change is usually associated with effect of antisperm antibodies and development of autoimmune processes, but another possible mechanism for impairment of spermatogenesis in the second paired intact organ may include effects of connective tissue microenvironment upon the spermatogenic epithelial cells.

Worldwide incidence of digestive system disorders doubles each decade, thus representing a significant medical and social problem. Despite lacking knowledge in pathogenesis of inflammatory bowel diseases, it is clear that serum cytokine imbalance, and lesions in the walls of gastrointestinal tract are observed in experimental colitis. Pathogenesis of UC remains controversial due to a large set of etiological factors that initiate activation of cellular and humoral mechanisms of the immune response upon development of inflammatory changes in the large intestine. At the same time, cytokine secretion and expression have not been studied in details. The aim of the work was to study the cytokine profile of blood in rats using the experimental oxazolone model of ulcerative colitis. The work was performed in 40 white Wistar rats; ulcerative colitis was induced by rectal administration of a 3% alcohol solution of oxazolone. For anesthesia, Zoletil-100 (INN: tiletamine hydrochloride, VirbacSanteAnimale; France) was used at a dose of 20 mg/kg. The studies were carried out on the 2^nd, 4^th and 6^th days. Serum concentration of IL-6, IL-8, IL-17 and IL-23 was determined by means of automatic ELISA analyzer “Personal LAB” using a specific test system for rats. For immunohistochemistry of Treg cells, we used anti-FoxP3 antibody (Arigo Biolaboratories, Тайвань) followed by immunhistostaining in VENTANA BenchMark XT (USA). Statistical evaluation was performed by non-parametric Mann-Whitney and Wald-Wolfowitz criteria. The difference was considered significant at р ≤ 0.05. In rats with experimental colitis, an increase of proinflammatory IL-17 which acts by attraction of neutrophils and other cells of innate immunity, supporting chronic inflammation and autoimmune reactions. We have found an increase of serum IL-23 concentration in rats with experimental ulcerative colitis on days 2, 4 and 6 of the experiment. This cytokine induces and maintains the inflammatory process in the wall of the large intestine. Significant decrease of FoxP3⁺Т-lymphocytes was revealed in colonic tissues, thus suggesting appropriate local autoimmune disorders.

Objective of this study was to carry out comparative analysis of bactericidal activity of synthetic peptide ZP2 (SP ZP2) against museum strains and clinical isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Materials and methods. We used museum strains of E. coli (ATCC 25922) and P. aeruginosa ATCC 27853, as well as 104 clinical isolates of Enterobacteriaceae, including E. coli (n = 22) and K. pneumoniae (n = 82), and 98 clinical isolates of non-fermenting Gramnegative bacteria, including P. aeruginosa (n = 43) and A. baumannii (n = 55), isolated from patients with various gynecological and surgical infections. Bactericidal activity of SP ZP2 (final concentration 10 μg/ml) against the microorganisms was assessed by difference in optical density (OD) for experimental and control broth cultures after 20 min of contact of bacterial suspensions (5 x 10⁸ CFU/ml) with SP ZP2 (in control — with distilled water), adding meat-peptone broth and 4-hour incubation at 37 °C. The effect of SP ZP2 was expressed by the Bactericidal Activity Index (BAI, %). Results. Using the in vitro assays, we have found that SP ZP2 had a pronounced bactericidal effect on both the reference strains of E. coli and P. aeruginosa, and majority (95.5-98.2%) of the studied clinical isolates of Gram-negative bacteria, regardless of their species. With regard of the average BAI values, the tested bacterial species may be ranked by increasing their sensitivity to the synthetic ZP2 peptide as follows: P. aeruginosa (74.0±2.3%) — E. coli (77.6±3.5%) — K. pneumoniae (82.8±1.6%) — A. baumannii (84.3±1.7%). In addition, significant intraspecific variability of clinical isolates of Gram-negative bacteria was revealed for their sensitivity to bactericidal effect of SP ZP2. Conclusion. The synthetic ZP2 peptide is able to inhibit growth of Gram-negative bacteria, as well as exerts a bactericidal effect, thus considering it as a promising candidate for development of new effective drugs with combined immunobiological properties for combatting infectious and inflammatory conditions caused by the indicated microorganisms which show common resistance to a wide range of antimicrobial drugs used in clinical practice.

Post-operation cognitive dysfunctions, related to mild manifestations of neurological pathology occuring after surgery, represent an important challenge for both fundamental and clinical medicine. The underlying phenomena of neuroinflammation are still poorly understood and discutable. The studies in immunopathogenesis of neuroinflammation may help in understanding the development of pathology and suggest ways to solve this problem. A special role for implementation of this process belongs to neuropeptides. Objective: to characterize immunopathogenesis of neuroinflammation in the individuals with immunocompromised state induced during aorto-coronary bypass surgery. A total of 110 patients with ischemic heart disease who underwent myocardial revascularization under extracorporeal circulation conditions were examined. Pathological neuroinflammation was recognized by development of postoperative cognitive dysfunction based on changing results of the cognitive examination (Montreal scale, MoCa test). The patients were tested before intervention, and on day 7 after surgery. According to the test results, all the patients were divided into 2 groups: (1) without signs of postoperative cognitive dysfunction and (2) with the mentioned signs. Venous blood was collected four times, on the day of surgery before the intervention, immediately after the surgery, 24 hours later, and on the 7^th day after surgery. S100b and BDNF contents were determined in the venous blood serum. The baseline level of the S100b protein in the study groups did not differ from the reference values. After surgery, an increase in S100b was observed in both groups, but in patients with emerging postoperative cognitive dysfunction, these indexes were significantly higher. Despite a tendency for stabilization, the increased level of neuropeptides persisted 24 hours after the surgery; on the 7^th day, the index was within the reference values, but in the 1^st group it was lower than in the 2^nd group. Prior to the operation, the BDNF level was significantly higher in the patients from group 1, compared with group 2. In the second group, the index was lower than the values obtained from the control group volunteers. After surgery, the values of BDNF in blood serum showed some differences: immediately after surgery, the level of neuropeptide was higher in patients without cognitive dysfunction. On day 7, the level of BDNF was within reference values, but in patients from group 2, the values were higher than in group 1.

Currently, differentiation between autism spectrum disorders and schizophrenia spectrum disorders in children is a difficult task, because it relies mainly on behavioral and symptomatic characteristics, since these disorders are highly similar. We have previously demonstrated that peripheral indexes of immune and neuroendocrine systems, which we combined into cytokine-neuroendocrine signature, may reflect distinct clinical phenotypes of autism and schizophrenia spectrum disorders. Moreover, a number of researchers discovered the “accelerated ageing” phenomenon in the persons with schizophrenia, which includes deficiencies of cognitive functions and performance as the main symptoms. Here we carried out a search for biological markers of the “accelerated ageing” phenomenon in children with autistic conditions and schizophrenia spectrum disorders. Our aim was to assess the opportunity of applying the cytokine-neuroendocrine signature as biological evidence of “accelerated ageing” phenomenon in children with autism and schizophrenia spectrum disorders, which could be potentially useful for differential diagnosis of these disorders.

Thirteen parameters of the cytokine-neuroendocrine signature were assessed in blood plasma using ELISA method in 82 children with autism, 9 children with schizophrenia, 45 normally developing children, 25 subjects in their reproductive age, and 39 elderly persons: cytokines (IL-6, IL- 1β, IFNγ, TNFα, IL-10, IL-4) and neurohormones (oxytocin, dopamine, adrenaline, noradrenaline, adrenocorticotropic hormone, cortisol, and serotonin). The nonlinear principal component analysis (CATPCA algorithm) was used to assess the variants of cytokine-neuroendocrine signature for different diagnostic categories, i.e., “autism spectrum disorders”, “schizophrenia spectrum disorders”, and “healthy ageing”.

The “healthy ageing” variant of cytokine-neuroendocrine signature presented a classic phenomenon, referred to as immune senescence presented by pro-inflammatory age-related cytokines — IL-6, IL- 1β, IFNγ. Only the “schizophrenia spectrum disorders” variant of the cytokine-neuroendocrine signature, unlike all the other signature variants, demonstrated high-level similarity with the “healthy ageing” variant (differing in 2 out of 13 indexes): lower levels of IL- 1β and IFNγ, at the same level of IL-6 “gerontological cytokine” index.

Evaluation of the cytokine-neuroendocrine signature can be used for differentiation between autistic disorders and schizophrenia spectrum disorders, including predictive diagnostics in children with autism, thus enabling group selection of children at risk for later conversion to schizophrenia.

Dysfunction of colonization resistance factors at the mucous membranes of genitourinary system during adhesion of Candida fungi is a common pathogenic situation leading to impairment of the mucous membrane regeneration, unsuccessful attempts at in vitro fertilization (IVF), increased risk of complications during gestation. The aim of present study was to substantiate the opportunity of complex therapy for chronic vulvovaginal candidiasis using cavitated saline and usage suppositories with alpha-2b human recombinant interferon a (Viferon LLC, Russia). The study involved 90 women at the age of25.45±7.16 years, with clinically and laboratory confirmed recurrencies of chronic vulvovaginal candidiasis observed, on average, 5.55±0.45 times. Group 1 consisted of 30 women with C. albicans infection of urogenital tract, at the mean age of 27.11±1.52 years, who received therapy with fluconazole (150 mg once every 7 days). Group 2 consisted of 30 women with C. albicans infection of mucous membranes, mean age 27.31±1.99 years, treated with Fluconazole (150 mg 1 time in 7 days, and 5-min. irrigation of vagina with ultrasonicated saline solution, 7 days; Low-intensity ultrasound exposure was performed using the Fotek AK100-25 hardware complex, ultrasonic vibration frequency of 25 kHz (Yekaterinburg, Russia). Group 3 consisted of 30 women whose treatment included Fluconazole (150 mg once every 6 days), irrigation of mucous membranes with ultrasonicated cavitated solution and subsequent administration of suppositories containing Viferon® 500,000 IU (1 suppository daily for 7 days). Biochemical studies included determination of isopropanol- and heptane-soluble primary, secondary end products of lipid peroxidation. Activity of the antioxidant system was studied by determination of superoxide dismutase, glutathione peroxidase, ceruloplasmin, vitamin C. Qualitative and quantitative characteristics of neutrophilic granulocytes from vaginal secretions were evaluated by testing phagocytic activity, reduction of nitroblue tetrazolium compound to diformazan. The studies of IL-8, TNFα, IL-2, and IL-10 cytokines were carried out in cell-free supernates of vaginal secretions by ELISA test systems (LLC “Vector Best”, Novosibirsk). Results: upon therapeutic exposure to low-frequency ultrasonic cavitation combined with antioxidant drug, we have observed a decreased local concentration of pro-inflammatory cytokines, the balance of lipid peroxidationantioxidant defense system was restored, and functional metabolic status of the phagocytes in vaginal secretions was normalized.

Persons exposed to ionizing radiation in utero and in early childhood constitute a risk group for the development of long-term stochastic consequences of irradiation. The imbalance of cytokines at the long terms after irradiation could be considered a carcinogenic triggering factor in subjects previously irradiated in utero and in early childhood, thus determining relevance of the study. The aim of the present study was to assess the levels of serum cytokines in native residents of coastal villages at the Techa River, whose chronic irradiation had been begun antenatally and to study probable interrelatirons between the detected changes, radiation and non-radiation factors at long terms after the exposure was begun. The main group included 61 persons from the Techa River Cohort who were born in 1950-1960, whose irradiation was begun in utero, being continued over the early postnatal period. For patients from the main group, the mean dose of antenatal radiation was calculated 74.7 mGy for red bone marrow as of, the mean dose of postnatal irradiation was calculated for red bone marrow as 537.5 mGy, and the median age of patients was 64.0 years. The comparison group (90 nonirradiated persons) was comparable to the main group in terms of age, gender, ethnicity and socio-economic status. The median levels for IL-2 in the main group were 1.37 pg/ml; in the comparison group, 2.70 pg/ml, p = 0.020; for IL-10, 4.53 pg/ml versus 7.58 pg/ml, p = 0.030 respectively; for GM-CSF, 0.39 pg/ml in the subjects who were irradiated in utero and in the early postnatal period versus 0.86 pg/ml in non-irradiated persons, p = 0.040. The median serum concentrations of IL-1β, IL-1α, IL-1(ra), IL-4, IL-6, IL-8, G-CSF, TNFα, IFNα, IFNγ in the study group did not show differences from the values in a group of non-irradiated persons. The decrease of the serum IL-2, IL-10 and GM-CSF levels in the persons of the main group did not depend on the dose of antenatal irradiation to red bone marrow, and on the radiation dose to red bone marrow received during the postnatal period of ontogenesis. In the main group, there was a moderate inverse relationship between the serum IL-10 level and age at the time of examination (SR = -0.53, p < 0.001). Serum concentrations of IL-2 and IL-10 in the people from comparison group showed a moderate positive correlation with their present age (SR = 0.47, p < 0.001 and SR = 0.42, p < 0.001 respectively).

Sperm quality can be directly or indirectly affected in chronic bacterial prostatitis, due to protein components of mucosal immunity, including lactoferrin, secretory immunoglobulin A, and lysozyme. Therefore, a search for relationships between spermogram indices and levels of antimicrobial factors in sperm plasma presents an urgent task in healthy men and patients with chronic bacterial prostatitis. The present paper contains the results of a study of sperm samples from 72 men aged 20 to 45 years. Samples were collected in sterile containers by masturbation after a minimum abstinence period of 3-5 days. None of the patients had previously taken antibiotics. Patients with sexually transmitted infections were excluded from the study. The patients were divided into two groups — conditionally healthy males (n = 30) and patients with chronic bacterial prostatitis (n = 42). Seminal plasma was obtained by two-stage centrifugation of ejaculate samples (1000-3000 rpm) for 30 minutes. Evaluation of lactoferrin and secretory immunoglobulin A levels in seminal plasma was carried out by ELISA technique (Vector-Best, Novosibirsk), lysozyme — by turbidimetric method. The results were recorded with Multiscan Labsystems photometer (Finland) at 492-nm wavelength. Statistical evaluation of the obtained data was carried out using Statistica 10 package (StatSoft, USA). To assess the kind of relationships between the studied parameters, the Spearman's rank correlation quotient was applied. When using the Spearman rankcorrelation approach, the strength of the relationships between the features was assessed, considering the values of < 0.3 as a weak connection; quotient levels of 0.4 to 0.7 as indexes of moderate relationships, and values of 0.7 and more, as high connection indexes.

We have found that an increased level of lactoferrin in some cases of leukocytospermia, oligospermia, and asthenospermia is accompanied by decreased number of leukocytes, increased sperm motility, preservation of sperm morphology, thus suggesting improvement of the sperm quality. Considering universal biological properties of lactoferrin and its receptors, an increased number of positive correlations between level lactoferrin level and spermogram parameters was shown in the patients with chronic bacterial prostatitis, as compared with healthy males, thus presuming high diagnostic value of this marker. Hence, diagnostic value of spermogram parameters is determined not only by their quantitative values, but also by the types of correlations with antimicrobial factor levels, in particular, with those of lactoferrin, secretory immunoglobulin A and lysozyme.

Curcumin is a polyphenolic compound, the main component of the Curcuma longa rhizome. Recently, there is growing interest to studies of this new, inexpensive and safe substance that may be used to treat various diseases. Curcumin is widely used in medicine due to its therapeutic efficacy and safety. Its usage in therapeutic practice as a dietary supplement has shown that curcumin exhibits antioxidant and immunomodulatory effects. Data from clinical studies have shown its pharmacokinetic, pharmacodynamic profile and potential use of curcumin in humans for treatment of various diseases, even at the early stages of treatment. Purpose of the study: analysis of immunomodulatory and microbiological properties when using the original grained preparation containing curcumin and methionine. It is suggested to have a regulatory effect by modulating microbial richness, diversity and composition of intestinal microflora. Analysis of immunomodulatory and microbiological activity of the components in the developed dosage form of the capsules with curcumin and methionine was carried out in vitro and in vivo. Functional and metabolic properties of neutrophils were determined with addition of its components, i.e., curcumin and methionine. The analysis of intensity and activity of neutrophils was carried out using the NBT-test. The analysis showed that simultaneous incubation of peripheral blood neutrophils from ICR (CD-1) mice with curcumin and methionine leads to an increase in spontaneous and induced NBT-reducing activity, an increase in the functional reserve and phagocytic activity of peripheral blood neutrophils in mice. A study of the modulating effects of oral intake of curcumin and methionine, which are part of the dosage form, on the intestinal microbiota of ICR (CD-1) mice was carried out. It was found that curcumin, together with methionine, affects the number of some representative families of intestinal microbial communities: in total, there were 640 common operating taxonomic units. between the curcumin-methionine and control groups, 65 were unique in the curcumin-methionine group and 93 in the control group. Given the direct link between gut microbiota and certain diseases, these results may help to interpret therapeutic benefits of curcumin with methionine. The results of the study showed that the developed dosage form, which contains curcumin and methionine, shows antioxidant and immunomodulatory effects, which can be potentially used to treat diseases associated with the effects of oxidative stress on the organism.

In this article, a comparative analysis of two experimental methods for treatment of chronic parodontitis was carried out, using a locally applied composition of silicon glycerohydrogel — peptide, and local injections of “Polyoxidonium” drug. The aim of this study was to compare efficiency of the two experimental methods for treatment of chronic periodontitis. Materials and methods: Using the facilities at the Institute of Immunology and Physiology (Yekaterinburg), a model of chronic inflammation of periodontal tissues was developed in Wistar rats, further treated by two experimental methods, i.e., (1) applying a composition containing organosilicon glycerohydrogel and a synthetic peptide, or (2) injections of “Polyoxidonium” drug directly into the foci of inflammation. Subsequently, a comparative evaluation of their efficiency was performed, including comparisons with control groups. The latters were treated by topical use of organosilicon glycerohydrogel (Group 1), and the local application of “Metrogyl Denta” gel (Group 2). Upon completion of the treatment, clinical and histological data were evaluated and compared. As based on the data obtained, we have found that all these drugs exerted favorable effect on the tissue regeneration, and led to reduced intensity of inflammatory processes. We have revealed also that the organosilicon glycerohydrogel — peptide composition provided a faster effect, due to the special characteristics of its components. The hydrogel, which has transcutaneous activity and plays a role of conductor substance, promotes faster penetration of the peptide into the tissues, thus allowing the peptide substance for more pronounced, complex antimicrobial and regenerative effect upon various pathogenetic components of chronic perirodontitis. If compared with the groups treated by glycerohydrogel silicon and “Polyoxidonium”, the terms of clinical improvement in the glycerohydrogel-peptide group were found to be increased by 57%, and appropriate indexes in the group treated with “Metrogyl Denta” improved by about 15%. The results of histological examination have confirmed normalization of the local tissue structure, as well as decreased inflammatory response observed for all the groups. Of particular interest, regeneration terms in the glycerohydrogel-peptide group were shorter (16 to 20 days) than in other groups (from 20 days), thus suggesting a more pronounced effect of this composition when compared to other treatments. Due to the presence of antimicrobial peptides in formulation of the glycerohydrogel-peptide composition, both pathogenetic and etiological links of the disease are affected, thus being important for development of integral approach to the treatment of chronic periodontitis.

Increasing use of raw materials from medicinal plant is due to the fact that the natural compounds may be preferred to synthetic ones by, generally, low toxicity, absence of side effects and addiction. Over recent decades, much attention has been paid to the study of immunotropic and antioxidant effect of medicinal plants, as well as to analysis of their trace element composition, since the action of the main biologically active substances is often manifested in combination with the natural mineral composition of the plant. The aim of the present work was to assess immunotropic effect of aqueous extracts of officinal medicinal raw materials and to analyze their trace element composition. The objects of the study were water extracts (1:10) from industrial samples of 11 types of raw materials (black currant leaves (Ribes nigrum L.), yarrow herb (Achillea millefolium L.), licorice roots (Glycyrrhiza uralensis Fisch.), Flowers of the sand immortelle (Helichrysum arenarium (L.) Moench), St. John's wort (Nurericum perforatum), wild strawberry leaves (Fragaria vesca L.), wild bird cherry (Padus avium Mill.), blood-red hawthorn (Crataegus sangunea Mill.) (Tanacetum flowers) vulgare L.), common chicory root (Cich rium ntybus Fisch.) and oat grass (Avena sativa L.) supplied to the network of pharmacies in Orenburg. Immunotropic effects of raw plant materials were evaluated in a model of adaptive immunity cells, by their ability to induce production of cytokines: IL-1β, TNFα and IL-10. The level of cytokines (IL-1β, TNFα, and IL-10) were assessed using ELISA (Cytokin, St. Petersburg, Russia). Elemental composition of raw material samples was determined by mass spectrometry with inductively coupled plasma using the ELAN-DRC-e device (PerkinElmer SCIEX, USA). Analysis of immunotropic activity of aqueous extracts from officinal medicinal plants showed that the majority of plant raw materials are characterized by a suppressive effect both upon pro-inflammatory mediators (TNFα, IL-1β), and the main anti-inflammatory cytokine (IL-10). In contrast, aqueous extracts of yarrow, oats and chicory were characterized by a selective immunomodulatory effect aimed at suppressing only inflammatory mediators. A tendency has been established for a significant accumulation of such biologically important trace elements as Zn, Mn, Fe and Cu in medicinal plants, which can determine their biological activity, and allows them to be considered as promising components at the stage of developing drugs that both exert immunotropic effect, and are a source of microelements.

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