bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the level of antiglycan antibodies in the blood and clinical and laboratory parameters of patients with normal pregnancy and pregnancy complicated by moderate preeclampsia
Authors: Ziganshina M. M. , Shilova N. V. , Khasbiullina N. R. , Tyutyunnik N. V. , Kan N. E. , Naumov V. A. , Tyutyunnik V. L.
Published: April 2022

One of the new trends in the study of the pathogenesis of preeclampsia (PE) is the study of the development of glycopathology in the functional mother-placenta-fetus system. Given the importance of carbohydrate-protein interactions for the morphogenesis of the placenta, interactions in the immune system, and the formation of tolerance to fetal alloantigens, anti-glycan antibodies (AgAbs), which can interfere with these interactions, changing them, may play a special role in the pathogenesis of PE. Since the production of antibodies occurs against the background of existing natural antibodies, as well as adaptive ones acquired during life, it is obvious that there are a significant number of factors that are interrelated with AgAbs, which is important for the pathogenesis and identification of risk factors for the disease. Objective: to determine the relationship between the content of AgAbs in the blood and clinical and laboratory parameters in patients with physiological pregnancy and PE.The study includes 146 pregnant women: the main group I consisted of 51 patients with moderate PE, the comparison group – 95 conditionally healthy pregnant women. Clinical and anamnestic data, peculiarities of the course of pregnancy, data of laboratory examinations, data of a representative spectrum of AgAbs were studied. AgAbs (IgG and IgM) were studied in serum using a glycoarray containing 473 glycans and 216 polysaccharides. To determine the relationship between the variables, the nonparametric Spearman rank correlation method was used for the analysis of quantitative data, and the Wilcoxon T-test for the analysis of qualitative data.It was found that in the main group there were more correlations between the level of AgAbs of various specificities and clinical and laboratory parameters than in the comparison group. A burdened gynecological and infectious history, complications during pregnancy are associated with changes in the profile of AgAbs of both classes in patients whose pregnancy is complicated by moderate PE, which indicates the pathogenetic significance of these antibodies. In healthy pregnant women, the level of antibodies to a number of glycans is reciprocally related to the number of lymphocytes, platelets, and ALT, which may indicate the regulatory role of these antibodies, since lymphocytosis, thrombocytopenia, and increased transaminases in the blood are pathological conditions.The revealed relationships between the AgAbs level and clinical-anamnestic and laboratory parameters indicate different patterns of correlation relationships in health and disease, which apparently indicates the pathogenetic
Role of apoptosis disturbances in external genital endometriosis
Authors: Avanesova T. G. , Levkovich M. A. , Ermolova N. V. , Krukier I. I. , Dudareva M. V.
Published: April 2022

External genital endometriosis (EGE) is currently considered one of the most common disorders in women at their reproductive age. EGE is a chronic disease that affects about 10% of women of reproductive age, leading to functional and structural changes in reproductive system, infertility, pelvic pain, and affects their quality of life. Moreover, the patients with endometriosis often suffer from depression, especially, due to pain syndrome. Endometriosis is associated with dysregulation of T-cell immune response, which presents as altered interactions between T-cells, macrophages, NK (natural killer cells), B-cells, thus allowing ectopic implantation of endometrial cells. The pronounced negative effect of EGE on the quality of life of patients, their reproductive function, impaired adaptation of the patients in community, and growing costs of treatment determine social significance of the disease and importance of appropriate studies. It is obvious that disorders of the immune system play a significant role in IGE development. However, despite extensive research in this area, the processes of apoptosis in IGE have not been sufficiently studied. Therefore, the aim of our study was to assess the origin of apoptosis disorders in women with stage I-II and III-IV of external genital endometriosis. We examined 71 patients with EGE which were divided into 2 groups: group 1 included the patients with EGE stage I-II (n = 31), and group 2, the patients with stage III-IV EGE (n = 40). The control group included 24 patients without EGE. The population profile of peripheral blood lymphocytes was determined by laser flow cytometry using Immunotex reagents, i.e., FITC-labeled CD8+, CD16+, and PE-labeled CD95+ antibodies. The number of lymphocytes entering apoptosis was detected using a diagnostic kit for AnnexinV+ (FITC) and PI+ from Caltag. The results were read on a BECKMAN COULTER EPICS XL-II flow cytometer using standard protocols.An imbalance between activation and apoptosis of immunocompetent cells may be a significant cause of EGE. Induction of apoptosis by the Fas-FasL pathway in patients with external genital endometriosis leads to decreased cytotoxicity mediated by T-lymphocytes and NK-cells. A statistically significant decrease in the content of AnnexinV+ presenting lymphocytes suggests impairment of their receptor-dependent apoptosis.Altered apoptosis processes may be responsible for the development of IGE by promotion of proliferation and growth of endometrioid implants.
Detection of immunoregulatory rheumatoid factor
Authors: Beduleva L. М. , Sidorov A. Yu. , Abisheva N. N. , Gilmanova L. U. , Gorbushina A. N.
Published: April 2022

Regulatory rheumatoid factor (regRF) represents a separate rheumatoid factor population that might be potentially used for clinical diagnostics, whereas regRF-producing lymphocytes serve as a promising therapeutic target for autoimmune diseases. Hence, it is worth outlining conditions allowing to reliably detect regRF in humans and laboratory animals. The method of agglutination with tanned IgG-loaded red blood cells was used to measure level of regulatory rheumatoid factor, because it allows to identify solely regRF as compared to the latex fixation method detecting both the regulatory rheumatoid factor as well as the rheumatoid factor associated with rheumatic diseases. It was found that fresh or frozen serum should be used to detect regRF in rats. Freshly purified rat blood plasma stabilized with heparin, sodium citrate or EDTA did not allow to detect regRF, potentially being linked to the presence of fibrinogen known to demonstrate IgG binding activity. In addition, heparin itself also complicates regRF detection in rats. In humans, regRF was reliably detected in pre-frozen plasma stabilized with sodium citrate. Finally, false-negative results were obtained in a small number of cases while using blood serum for detecting regRF in humans.
Evaluation of triterpenoid miliacin-related anti-mutagenic effect in mice exposed to ionising radiation
Authors: Sarycheva Yu. A. , Tokareva A. A. , Shtil A. A. , Kolyvanova M. A. , Morozov V. N. , Panfilova T. V. , Frolov B. A.
Published: April 2022

Triterpenoid miliacin-related anti-mutagenic effect aftert exposure to isonizing radiation was studied to assess its protective properties against radiation-induced immunosuppression. (CBAxC57Bl6)F1 mice were subdivided into four groups: 1) intact mice; 2) irradiated mice; 3) miliacin-pretreated irradiated mice; and 4) miliacin-solvent-pretreated irradiated mice. Irradiation of animals was performed on the X-ray device “RUST-M1” (4 Gy; exposure time 288 sec.). Twenty four hours post irradiation myelokaryocytes were isolated for analysis. Chromosome preparations were examined by light microscopy. Injections of miliacin (4 mg/kg daily for 3 consecutive days) attenuated the irradiation-triggered mutagenic effect assessed by counting cells with chromosomal aberrations as well as number of aberrations per 100 metaphase plates. Miliacin exerted a protective effect on radiation-induced chromosomal aberrations, although degree of protection was less pronounced compared to chemically induced mutagenesis. These data indicate about limited potential for miliacin to protect central immune organs such as red bone marrow upon radiation exposure.
IL-1β and TNFα measured in supernatants of peripheral blood cell cultures from children with autoimmune and infectious pathology
Authors: Pashnina I. A. , Krivolapova I. M. , Chereshneva M. V.
Published: April 2022

Cytokines are small-molecular weight proteins involved in regulating inflammation, proliferation and differentiation of immunocompetent cells, as well as effector functions. IL-1β and TNFα are among the most powerful inducers of the inflammatory response. Production of proinflammatory cytokines comprises normal response to infection and represents an arm of various autoimmune disease pathogenesis. It is worth comparing cytokine production in autoimmune and infectious diseases to determine features of cytokine profile. The aim of the study was to evaluate proinflammatory cytokines IL-1β and TNFα produced by blood cells in children with autoimmune and infectious diseases. 194 children, aged 2-17 years, were examined: 99 patients with juvenile idiopathic arthritis; 26 patients with unspecified reactive arthropathy; 14 children with systemic lupus erythematosus; 24 children with chronic viral hepatitis C; 33 healthy children. Heparinized blood samples were diluted with a glutamine-containing culture medium RPMI-1640, samples with/without phytohemagglutinin stimulation were prepared as well. Samples of diluted blood were incubated for 24 hours (37 °C, 5% CO2). The concentrations of IL-1β and TNFα in the cell culture supernatants were determined by ELISA. It was found that groups of patients with rheumatic diseases (systemic lupus erythematosus, juvenile idiopathic arthritis and unspecified reactive arthropathy) were featured with spontaneous production of IL-1β and TNFα at higher level than in control, and the stimulated synthesis of IL-1β was lower. In patients with chronic viral hepatitis C, the spontaneous concentration IL-1β and TNFα and the stimulated concentration of IL-1β did not differ those ones found in healthy children. Stimulated TNFα production in patients with juvenile idiopathic arthritis, unspecified reactive arthropathy, and hepatitis C was significantly higher than in control group. More intensive spontaneous production IL-1β and TNFα in groups of patients with rheumatic diseases indicates previous activation of immunocompetent cells. Decreased stimulated IL-1β production in groups with various diseases points at exhaustion of immunocompetent cell functional reserve due to chronic activation.
Analyzing IL6 gene polymorphism in patients with various clinical forms of pulmonary tuberculosis
Authors: Belyaeva S. V.
Published: April 2022

Throughout the world, tuberculosis still remains one of the most important public health problems. According to numerous publications, TB infectrion is considered as a genetically determined disease, and host genetical polymorphism underlies a mechanism resulting in disease progression from primary infection to clinical manifestations. Currently, an association between TB infection and IL6 gene polymorphism at position -174 responsible for low cytokine production has been extensively investigated. Previously, we evaluated the association between IL6 gene alleles and genotypes and predisposition/resistance to tuberculosis in Russian descendants residing in the Chelyabinsk Region. Here, we conducted a comparative analysis for prevalence of IL6 gene alleles and genotypes in patients differed in lung damage degree such as infiltrative, focal, and fibrous-cavernous forms of pulmonary tuberculosis by isolating whole blood DNA samples and subsequent genotyping of IL6 gene polymorphisms with polymerase chain reaction and agarose gel electrophoresis. We found that patients with a focal TB form were characterized by prevalence of IL6(-174)*C/C genotype associated with low cytokine production, whereas patients with severe fibrous-cavernous carried IL6(-174)*G/C genotype accounting for modedrated IL-6 production.
Examining sIgE-profile in patients with ambrosia allergy in Samara
Authors: Zhukova N. N. , Manzhos M. V. , Seleznev A. V.
Published: April 2022

It is considered that Ambrosia trifida is not widespread in Russia, thereby avoiding its threatening effects to populational health. However, there are some areas in Russia where more than half of land area is covered by Ambrosia trifida. Many such foci are found in the Samara, Orenburg regions, Tatarstan and Bashkiria. Ambrosia trifida is distributed in Central Russia, the North Caucasus region and Siberia. The objective of the study was to examine specific IgE-profile in ragweed sensitized patients in the Samara region. A clinical and allergy examination of 969 patients with allergic rhinitis was performed. Allergic diagnostics was performed by using skin testing (prick-test) with standard set of pollen, household, and epidermal allergens. The data of skin tests in patients co-sensitized with ragweed and Artemisia allowed to analyze IgE-antibodies specific to the major Ambrosia (Amb a 1, Аmb. trifida) and Artemisia (Art v 1) allergens. Patients with negative skin test for the Amdrosia artemisiifolia and clinical manifestations of seasonal allergy were assessed for level of sIgE-antibodies nAmb a 1 and Amb trif. Skin test data demonstrated that seasonal and combined forms of allergic rhinitis dominated in patients examined. In particular, positive skin test data for pollen allergens dominated (50.6%) among all allergen groups so that more than half of them belonged to weed pollen allergens. Patients challenged with skin tests for Artemisia and ragweed allergens more likely displayed positive reaction to the Artemisia allergen (71.27%) and Ambrosia artemisiifolia (50.88%). Co-sensitization (to Artemisia and ragweed) prevailed in this geographic region featured with equal rate of simultaneously detected sIgE specific to the two types of ragweed and artemisia (nAmb a 1 + nArt v 1 + Amb trif) as well as Ambrosia trifida and Artemisia (Amb trif + nArt v 1). Almost half of the patients with negative Ambrosia art. prick-test were found to bear sIgE specific to Amb trif. Further investigation will help to better understand this phenomenon and take a fresh look at diagnostics and treatment of ragweed allergy in relevant geographic area.
Serum macrophage colony-stimulating factor levels in patients with essential hypertension after SARS-CoV-2 infection
Authors: Radaeva O. A. , Simbirtsev A. S. , Selezneva N. M. , Iskandyarova M. S.
Published: April 2022

Understanding changes in the cytokine-mediated mechanisms in immunopathogenesis of essential hypertension (EH) after COVID-19 poses a pressing scientific issue. SARS-CoV-2 exerts direct effects on macrophages with high probability altering regulatory M-CSF-VEGF-A-IL-34 axis, thereby accounting for change in cytokine-mediated patterns of hypertension progression. Immunopathogenesis of complications after SARS-CoV-2 infection and a role of M-CSF in EH pathogenesis justify study objective – to compare the serum M-CSF and VEGF-A, IL-34 levels in stage II EH patients prior to COVID-19 and one month after recovery to assess modality of altered M-CSF-mediated mechanisms behind hypertension progression. Four groups of patients were stratified depending on EH and clinical characteristics of COVID-19 (without/with pneumonia). Blood sampling was performed one month after COVID-19. The serum M-CSF and VEGF-A, IL-34 level was measured by using enzyme-linked immunosorbent assay. The data were statistically processed by using Stat Soft Statistica 13.5. Comparative analysis of serum M-CSF level in patients with stage II EH prior and after COVID-19 revealed that regardless of clinical course (with/without pneumonia) they were featured with higher levels of M-CSF one month after recovery (p 0.001) vs baseline level. The serum VEGF-A level in patients with stage II EH did not change in papallel with increased M-CSF (458 pg/ml or more) one month after SARS CoV 2 infection. However, M-CSF stimulated rise in serum VEGF-A level and accounted for formation of marked coronary collateral network prior to infection. A relationship between the increased serum M-CSF level (higher than 392 pg/ml) and elevated percentage of COVID-19 with pneumonia in patients with stage II EH prior to the infection might be related to the hypothesis about “a role of dysregulated activation of mononuclear phagocytes in development of lung tissue damage”. The data presented prove scientific and clinical value of assessing a role for M-CSF with respect to altered cytokine-mediated patterns of EH progression after COVID-19 recovery.
Examining effects of NS1 specific antibodies on sublethal influenza infection and secondary bacterial pneumonia in mice
Authors: Kartashova N. P. , Leneva I. A. , Falynskova I. N. , Poddubikov A. V.
Published: April 2022

Influenza is a highly contagious respiratory disease widespread throughout the world that causes disease in humans, birds and many mammalian species. Annually, around 20% of the global human gets sick with influenza so that more than 500,000 people die its various complications. Secondary bacterial pneumonia poses the peak threat during influenza infection, being most frequently caused by S. pneumoniae. Multiple studies in humans confirm the negative impact of influenza virus infection on subsequent outcome of bacterial pneumonia and provides insight into increased morbidity and mortality due to complicated influenza infection. In particular, the last 2009 influenza pandemic caused by H1N1 virus revealed that 25-56% cases of severe disease forms were associated with secondary pneumonia, among which 14-46% of them were fatal. Based on the aforementioned, it is of high priority to investigate a role of influenza virus proteins in developing of pathogen synergism in viral-bacterial pneumonia, particularly influenza virus non-structural protein NS1. The study objective was to examine effects of NS1-specific antibodies on course of influenza infection and secondary bacterial pneumonia in mice. For this, we used an experimental model of sublethal influenza infection followed by secondary Streptococcus pneumoniae bacterial pneumonia. Influenza A/Puerto Rico/8/34 (H1N1) virus and S. pneumoniae No. 3405 strain were used to simulate influenza infection. Rabbit serum containing antibodies against recombinant NS1 protein from A/Puerto Rico/8/34 virus and native rabbit serum (contain no specific antibodies) were used for vaccination. The study was carried out with female BALB/c mice, weighing 20-22 g. Protective activity of animal serum was assessed by using the three criteria: infection-related mortality, life expectancy and body weight change. The data obtained showed that passive transfer of antibodies specific to influenza virus NS1 protein did not lowered viral replication in sublethal murine model of influenza infection. Subsequent secondary bacterial pneumonia induced by S. pneumoniae revealed no protective effect of anti-NS1 protein antibodies assessed by measuring survival rate, lung viral and bacterial titers in treated vs. control mice.
Examining protective efficacy of influenza virus NA-containing virus-like particles (VLP) in mouse model of post-influenza bacterial pneumonia caused by Staphylococcus aureus
Authors: Glubokova E. A. , Leneva I. A. , Falinskova I. N. , Poddubikov A. V.
Published: April 2022

Currently, pneumonia resulting from post-influenza infection still remains a pressing issue. In particular, virtually no studies regarding a role of immune response against influenza virus neuraminidase in regulating host susceptibility to subsequent bacterial superinfection are now available. Virus-like particles represent one of the new and promising approaches in contemporary virology for developing influenza vaccines and studying influenza virus proteins. Upon that, it is possible to obtain virus-like particles carrying individual influenza virus-derived proteins such as neuraminidase and hemagglutinin. This allows to get closer insight into potential role of individual influenza virus proteins for host immune response as well as assess a risk of developing secondary bacterial pneumonia. In this study we examined an immune response against influenza virus NA protein and its impact in generating resistance to secondary bacterial pneumonia by using neuraminidase-bearing virus-like particles. We used an experimental model of secondary bacterial pneumonia induced by Staphylococcus aureus after influenza infection. Animals were preliminarily vaccinated with virus-like particles carrying neuraminidase, hemagglutinin, or both (a cocktail of virus-like particles). In this model vaccinated animals were infected 21 days later with influenza viruses A/Puerto Rico/8/34 (H1N1) and reassortant strain NIBRG-121xp (A/California/04/2009 (pndm H1N1 2009) X A/Puerto Rico/8/34 ( H1N1) bearing surface proteins hemagglutinin and neuraminidase derived from the A/California/04/2009 virus as well as the internal proteins derived from A/Puerto Rico/8/34. Next, 5 days after influenza infection mice were infected with Staphylococcus aureus. Moreover, animals in one group were simultaneously vaccinated and infected with A/Puerto Rico/8/34 (H1N1) followed by inoculation on day 21 with reassortant virus NIBRG- 121xp. The protective vaccine activity was assessed by measuring survival rate, life expectancy and decreased body weight loss. The data obtained showed that virus-like particles containing neuraminidase revealed no protective activity. However, a cocktail of virus-like particles, containing hemagglutinin and neuraminidase, protected animals from lethal outcome as well as body weight loss. Moreover, the increase virus-like particles containing neuraminidase in the cocktail of virus-like particles (virus-like particles containing neuraminidase + hemagglutinin) led to elevated protective effect after vaccination that was comparable or even superior to that one in mice with post-infectious immunity.
Changes in cytokines and urothelial factors of urine in interstitial cystitis/painful bladder syndrome
Authors: Sholan R. F.
Published: April 2022

Interstitial cystitis/bladder pain syndrome (IC/BPS) is thought to have an autoimmune component due to increased prevalence of certain autoimmune conditions in the patients. Recent studies have revealed abnormalities in cytokine signaling in cultured urothelial cells of the urinary bladder. However, there is only scarce information on concentration of cytokines and some biomarkers, e.g., heparin-binding growth factor (HB-EGF) and epidermal growth factor (EGF), in the patients with IC/BPS. The purpose of present study was to determine concentrations of cytokines, HB-EGF and EGF in urine and their interrelations in patients with IC/BPS. 68 women with IC/BPS and 20 women without this disease (control group) were examined. The average age of women with IC/BPS was 54.2±12.4 years, the control group was 35.3±9.7 years. The morning urine samples were tested for interleukin contents (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), as well as HB-EGF and EGF concentrations measured by ELISA technique. Statistical analysis of the obtained results was performed using Statistica software in Microsoft Excel. A relationship between the indexes was calculated with Pearson correlation quotient. The ratios for Th1/Th2 cytokines were calculated. Urination frequency, clinical symptoms including pollakiuria, nocturia and its urgency, were significantly more often in patients with IC/BPS compared to the control group (p 0.05-0.001). In patients with IC/BPS, the average levels of IL-1β, IL-8, IL-6 and TNFα exhibited, respectively, 2.4-, 2.3- and 2.0-fold increase over control values (p 0.05). The HB-EGF and EGF excretion in the urine was 2.3 times (p 0.05) over control levels. The IL-1β/IL-6 ratio averaged 1.16 in the group of patients with IC/BPS versus 0.95 in the control group, and the TNFα/IL-6 ratio was 1.0, respectively. There was a positive correlation between the levels of IL-1β and IL-6, TNFα (p 0.05), HB-EGF and EGF, and a negative correlation with IL-8 (p 0.01). In women with IC/BPS, there was a weak multidirectional correlation between IL-6 and other cytokines, as well as with HB-EGF and EGF contents. IL-8 levels in both groups showed weak correlation with other indexes. The TNFα amount weakly correlated with HB-EGF and EGF in IC/BPS. Based on the results obtained, one may state that, in IC/BPS, the excretion of pro-inflammatory cytokines was significantly increased, the balance of Th1/Th2 cytokines and contents of growth factors are disturbed. Expression of cytokines in combination with growth factors (HB-EGF and EGF) can be used to explain the pathophysiology of the clinical features in IC/BPS. Analysis of cytokine profiles may be used for differential diagnosis of IC/BPS and other disorders of urinary bladder.
Features of sensitization to molds and its role in development of respiratory allergic diseases
Authors: Gervazieva V. B. , Samoylikov P. V. , Vasilyeva G. V.
Published: April 2022

Over recent decades, a steady increase in the number of allergic diseases has been shown. Current evidence demonstrate a close association between their emergence and exposure to fungal allergens. In this regard, the aim of the present study was to identify frequency and structure of sensitization to the most clinically significant molds in the patients with respiratory allergic diseases. In blood serum of 283 patients with allergic rhinitis and bronchial asthma, we determined total IgE and sIgE to the mold allergens: Penicillium notatum, Cladosporium herbarum, Aspergillus fumigatus and Alternaria alternata by the ImmunoCAP method (Phadia, Sweden). Statistical analysis was carried out by nonparametric methods. The total IgE levels (420 (225.5-641) kU/l) were higher (p 0.05) in patients with sensitization to fungal allergens than in general group (296 (129- 530) kU/l). Multiple sensitization to respiratory allergens was revealed in the patients with allergic rhinitis and bronchial asthma, and sensitization to fungal allergens was associated with increasingly severe manifestations of the disease. In the patients with fungal allergies, sIgE to Alternaria alternata was most often detected (92.5%), with average level of 3.52 (0.635-19.525) kUA/l. Sixteen patients (40%) were sensitized to Aspergillus fumigatus (0.14 (0.06-0.63) kUA/l). In 19 patients (47.5%), we found increased levels of sIgE to Cladosporium herbarum (0.29 (0.045-1.005) kUA/l). Sensitization to Penicillium notatum was detected in 12 patients (30%), the sIgE levels were 0.125 (0.01-0.5) kUA/l. Detection rates in the total group of fungus-allergic patients with respiratory allergies were as follows: Penicillium notatum, 4.2%; Cladosporium herbarum, 6.7%; Aspergillus fumigatus, 5.6%; Alternaria alternata, 13.07%. We found a significant correlation (p 0.05) between the sIgE contents to different fungal allergens. The levels of IgE antibodies to Alternaria alternata correlated with the levels of sIgE to other fungi (Aspergillus fumigates, r = 0.45; Cladosporium herbarum, r = 0.39; Penicillium notatum, r = 0.39). These findings allow us to suggest that sensitization to Alternaria alternata (13.07%) and Cladosporium herbarum (6.7%) is most common among the patients with allergic rhinitis and bronchial asthma, whereas fungal sensitization aggravates clinical course of these diseases. Determination of sIgE to Alternaria alternata can serve as a marker for the presence of potential cross-sensitization to other fungal allergens, i.e., Aspergillus fumigatus, Cladosporium herbarum, and Penicillium notatum.
Pathogenetic rationale for usage of recombinant interleukins in the patients with mandibular fractures to prevent post-traumatic osteomyelitis
Authors: Paskova E. V. , Markelova E. V. , Golitsyna A. A. , Rusakova E. Yu. , Romanchuk A. L. , Nevezhkin D. A. , Knysh S. V.
Published: April 2022

The paper presents the results on spontaneous and induced production of IFNγ, IL-4, IL-13 cytokines in blood cells of patients with mandibular fractures and post-traumatic osteomyelitis. Osteomyelitis of the jaw represents one of the urgent challenges in modern medicine. There are many reasons for development of purulent necrotic processes of the jaw bones, including disorders of innate and adaptive immune response. Currently, the immunological aspects of post-traumatic complications of maxillofacial region remain poorly understood. There are no unambiguous and systematic studies of immune mechanisms in pathogenesis of post-traumatic osteomyelitis of the lower jaw. The aim of our study was to theoretically confirm application of recombinant interleukins (IL-1β, IL-2, IFNγ) in the patients with jaw fractures, in order to prevent osteomyelitis, as based on the studies of spontaneous and induced cytokine production (IFNγ, IL-4, IL-13). Spontaneous and stimulated production of IFNγ, IL-4, and IL-13 cytokines by blood cells was determined using specific reagent kits from RD Diagnostic Inc. (USA). The results were recorded using an ELISA Multiscan analyzer (Finland). Statistical significance of intergroup differences was determined by the Mann–Whitney method. The level of statistical significance at which the null hypotheses were rejected was 0.05. To stratify the cases of post-traumatic osteomyelitis and uncomplicated mandibular fracture, the models were developed with a singlelayer neural network, using the nnet R-studio package. To assess quality of the models, the areas under the ROC curves (AUC), Akaike criterion (AIC), and the relative classification accuracy (OTC) were used, which was determined as the ratio of correctly established model diagnosis numbers to the total number of patients. The study results demonstrate that the patients with mandibular fractures exhibit a moderate impairment of LPS-induced IL-4 and IFNγ production by leukocytes with IL-13 activation. In presence of osteomyelitis, this imbalance is promoted, thus suggesting an impaired ability of the cells to produce IL-4 and IFNγ. An opportunity for usage immunomodulation when treating the patients with mandibular fractures is represented by P = 1/(1+e-z) where z is defined via IL-1β, IL-2 and IFNγ levels on the first day of observation. In vitro supplementation with recombinant IL-1β and IFNγ modulates cell function, improving the cytokine profile. The prognostic models, imitating binary logistic regression, were used to demonstrate that recombinant IL-1β could be used to prevent patients with mandibular fractures from developing post-traumatic osteomyelitis (AIC = 13.2, AUC = 0.96, р = 0.026).
Role of S100b protein and BDNF in immunopathogenesis of neuroinflammation in the patients with induced immunocompromised state
Authors: Knysh S. V. , Markelova E. V. , Zenina A. A. , Kostushko A. V. , Fedyanina L. N.
Published: April 2022

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 7th 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 7th day, the index was within the reference values, but in the 1st group it was lower than in the 2nd 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.
Altered expression of cell membrane HLA-G molecules in mothers of children with inborn heart defects upon exposure to plasma gamma-globulin from multiparous women
Authors: Shabaldin A. V. , Deeva N. S. , Sukhikh А. S. , Vavin G. V. , Kryukov P. M.
Published: April 2022

High incidence of newborns with inborn heart defects (HD) and sufficient contribution of this disorder into perinatal, infant and pediatric mortality, as well as disability levels, even after radical surgical treatment determine significance of search for novel methods of prediction and prevention of appropriate HD risks at the stage of pregnancy planning. HLA-G is among key molecules participating in immune interactions between maternal microenvironment and embryos. Maximal antibody titers for HLA antigens is detected in multiparous women. However, the question remains open, which HLA molecules participate in blockage of immune inflammation in the mother-embryo system: either by maternal antibodies, or by donor immune globulins. Hence, the aim of our study was to obtain enriched γ-globulin preparation from blood of multiparous women and evaluation of its activity towards female HLA-G molecules. The γ-globulin fraction (GGF) was obtained from blood plasma of muliparous women by means of affine chromatography using DEAE Affi-Gel Blue system (BioRad, USA). We have formed 2 groups: a control group (14 healthy males), and experimental group of 14 women who gave birth to the children with inborn heart defects.The changes of HLA-G expression on lymphocytes exposed to GGF were evaluated according to a flow cytometry protocol with calculation of percentage values using appropriate quotients. Evaluation of functional activity exerted by the GGF concentrate in control group showed inhibition of HLA-G expression on CD3+ and CD--lymphocytes against effects of autologous serum. GGF effects in experimental group upon HLA-G expression were differently directed, e.g., GGF sufficiently inhibited membrane HLA-G expression on the CD3-negative lymphocytes, compared to control group. Meanwhile, GGF showed stimulatory effect upon CD3+-lymphocytes, or it did not show any inhibitory action. The preparation obtained may serve as prototype for intravenous infusion. Moreover, in future one may use such immunoglobulin preparations, both for immune prophylaxis of non-syndromal sporadic HDs at the pregragravidary stage, as well as at early terms of pregnancy. The therapeutic effect will achieved due to blockage of embryoblast HLA molecules available to recognition.
Features of polymorphic site combinations of Toll-like receptor (TLR) genes in children with ventricular septal defects
Authors: Shabaldin A. V. , Tsepokina A. V. , Shmulevich S. A. , Ponasenko A. V.
Published: April 2022

Congenital heart disease is the leading cause of the childhood disability and mortality. The development of new technologies has made it possible to advance in diagnosis and treatment of congenital heart disease, but its etiology is poorly understood. Considering multifactorial origin of this disease, a search for biomarkers having fundamental and practical importance is of current interest. Study of the genetic component is one of the areas of research. E.g., Toll-like receptors (TLR) are important regulators of susceptibility to infectious and non-infectious diseases. Polymorphic variants with single nucleotide substitutions in these genes may be accompanied by changes in the structure and expression of the encoded proteins, thus affecting functional activity of these receptors. Our aim was to study some genetic predictors of congenital heart defects in children. Materials and methods. We examined 47 children (21 girls and 26 boys) with congenital heart defects: 23 children had a ventricular septal defect (VSD); 24 children, atrial septal defect (ASD). The patients in the main group were 1 to 9 years old. As a control group, 96 conditionally healthy age- and sex-matched children were examined. Real-time genotyping was carried out with Viia7 real-time PCR system (Applied Biosystems, USA) using TaqMan probes of four TLR genes (TLR1 rs5743611, rs5743551, TLR2 rs5743708, rs3804099, TLR4 rs4986791, rs4986790, TLR6 rs3775073, rs5743810). Results. The distribution of all studied polymorphic variants corresponded to the HardyWeinberg equilibrium. It was revealed that sporadic nonsydromal VSD are associated with G allele of the TLR2 gene (rs5743708) and T allele of the TLR6 gene (rs3775073). According to ROC analysis, the combination of these alleles is a significant parameter showing high degree of sensitivity (82.4%). Both TLR2 (rs5743708) and TLR6 (rs3775073) gene variants define amino acid substitutions (missense mutations) in TLR molecules. Thus, we concluded that genetic testing can be used to identify risk groups at the early stages.
Immunotropic effect of medicinal plants with different microelemental composition
Authors: Ivanova E. V. , Voronkova I. P. , Bondarenko A. I. , Tarenkova I. V.
Published: April 2022

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.
Anticytokine activity and the ability to produce cytokine-like substances of staphylococci isolated from the prostatic secretions in men with symptoms of urogenital infection
Authors: Kartashova O. L. , Pashkova T. M. , Pashinina O. A. , Morozova N. V.
Published: April 2022

To be causal agents for infectious and inflammatory diseases, the microorganisms should have a pathogenic potential, the framework of which is based on persistence factors that ensure their protection from various effectors of the host's immunity. There is evidence that some microorganisms can have anti-cytokine activity (ACA), and at the same time, many microorganisms many synthesize cytokine-like substances, thus, in fact, exhibit cytokine activity. The aim of the present study was to establish the presence of cytokine-like substances and anti-cytokine activity in Staphylococcus strains isolated from prostate secretions in men with symptoms of urogenital infection. This study involved 24 clinical isolates of different Staphylococci types isolated from the prostate gland secretions in men with symptoms of urogenital infection. Ability of staphylococci to cause changes in the IL-4, IL-6, IL-8, IL-10 and TNFα contents was carried out by co-incubating bacteria suspended in normal saline solution together with cytokine solutions, at a ratio of 1:1 (experimental samples). As a control, a solution of cytokines supplemented by normal saline was used. Concentration of cytokines in experimental and control samples was determined by enzyme immunoassay. Anti-cytokine activity (ACA) was expressed as a percentage (%) of cytokine inactivation in experimental mixtures compared to the controls, cytokine activity, as % of cytokine production in the experimental samples compared to the control.The studied staphylococci showed anti-cytokine activity against IL-4 and IL-10, and exhibited ability to produce IL-6 and TNF. At the same time, among staphylococci, there were strains both showing anti-cytokine activity against IL-8, and producing this cytokine.Among different staphylococcal species isolated from prostate secretions in men with symptoms of urogenital infection, the presence of anti-cytokine activity and the ability to produce cytokines was detected; their production (presence and level) was characterized by intraspecific variability. S. xylosus proved to be the most active cytokine producer, which also have the highest anti-cytokine activity against IL-4.
Local concentrations of secretory immunoglobulin a in patients with adenoiditis, rhinosinusitis and exacerbation of chronic purulent otitis media when using physiatric methods in complex therapy
Authors: Korkmazov M. Yu. , Dubinets I. D. , Lengina M. A. , Solodovnic A. V.
Published: April 2022

Improvement of therapeutic tools is one of topical issues in modern otorhinolaryngology. The article is devoted to the study of the stimulating effect of physical therapy on the concentrations of secretory IgA in nasal secretions, from the entries of auditory tubes and nasopharynx in the patients suffering from adenoiditis, rhinosinusitis, and exacerbation of chronic otitis media. The increase in clinical and immunological efficiency when using low-frequency ultrasonic cavitation therapy in combination with photochromotherapy in combined treatment of these conditions was evaluated in dynamics by measuring concentrations of secretory immunoglobulin levels in nasal secretions using enzyme immunoassay technique (Vector-Best, Russia). The purpose of this study was to improve clinical and immunological effectiveness of treatment of patients with chronic adenoiditis, sinusitis and exacerbation of chronic purulent otitis media when using low-frequency ultrasound cavitation and photochromotherapy in complex therapy. The study involved 54 patients. The control group consisted of 25 patients who received conventional treatment (topical and systemic antibacterial and anti-inflammatory drugs, unloading and elimination procedures, symptomatic and restorative therapy) and the main group of 29 people who, in addition to etiotropic therapy, received low-frequency ultrasound cavitation irrigation of the nasal cavity followed by a course of photochromotherapy. Evaluation of the effectiveness of treatment was carried out by studying the barrier state of the nasal mucosa by the levels of secretory IgA concentration by the method of enzyme immunoassay. The low-frequency ultrasound cavitation in combination with photochromotherapy as an adjunct to etiotropic treatment in patients with adenoiditis, rhinosinusitis and exacerbation of chronic otitis media promotes an earlier increase in secretory IgA concentration of nasal mucosa and entry of the auditory tube when compared to standard treatment methods. The trend to IgA increase by 14 days reached maximal values and was slightly decreased month later. An early increase in the concentration of secretory IgA in nasal secretions and the entry of auditory tube, and positive clinical results of treatment are observed when low-frequency ultrasound cavitation is used in etiotropic therapy in combination with photochromotherapy in patients with adenoiditis, rhinosinusitis and exacerbation of chronic otitis media. The results substantiate the opportunity of introducing these physical methods of physical therapy into complex etiotropic therapy, as a non-invasive and effective method.
Prospects for the government of Pedro Sanchez in the context of socio-political situation in Spain
Authors: Khenkin S. M.
Published: April 2022

The left and the right parties in modern Spain often approach many problems that the country faces very differently. In these conditions, the question of whether the left-wing coalition government led by Pedro Sánchez will remain in power until the end of 2023, when the next parliamentary elections are to take place, is of utmost importance. And if it does, will the Socialists win again, or will the initiative pass to the right forces? Government performance is assessed rather contradictory by the citizens of Spain and there are certain reasons for this. The country has embarked on the thorny path of overcoming the consequences of the pandemic. Many sectors of Spanish economy are recovering, the situation in the labour market has improved. But in general, the pace of economic recovery has not yet reached expected indicators and results. Inflation has risen because of rising electricity and gasoline prices, and the purchasing power of the population has declined. At the moment, the government’s prospects are largely determined by the relationship between the Spanish Socialist Workers’ Party and Unidas Podemos coalition. This relationship is very complex and contradictory, and as a result disagreements and conflicts arise quite often. An equally difficult question is whether the support of the separatist and nationalist parties of Catalonia and the Basque Country, without which the current government will lose its absolute majority in the lower house of parliament and cannot count on effective governance, will continue. The government’s choices are narrowed by the position of the right-wing parties that stand in stiff and uncompromising opposition and accuse it of complete irrelevancy. Tension reigns in public life with political situation remaining volatile and largely unpredictable.