There are organized forms of cellular infiltrate observed in immune-inflammatory rheumatic diseases, i.e., ectopic follicle-like lymphoid structures and delayed-type response granulomas, whereas diffuse cellular inflammatory infiltrates represent non-organized forms. In these types of cellular infiltration, an integral pathogenetic link includes programmable cell death variants, with autophagy, apoptosis, necroptosis, pyroptosis and netosis being the most significant. There is a close relationship between these forms of cell death. This relationship occured in the process of biological evolution, being characterized by pronounced conservatism, and it follows general biological laws of molecular cellular processes. The “danger signals” (DAMPs) released during cell death induce a state of autoreactivity caused, e.g., by modulation of cell death processes using cellular PRR receptors of the innate immune system. When analyzing the processes of endocytosis, signaling pathways, adaptive molecules, transcription factors involved into these modes of cell death, we discuss pathogenetic role of changing membrane structures and molecular pathways of programmed cell death in immune-inflammatory rheumatic diseases. In this regard, there are fundamental membrane-associated cellular processes, genesis of various types of intracellular inflammasomes, cross-presentation of MHC-restricted products of disorganized loose fibrous connective tissue, and induction of innate and adaptive immune autoreactivity. Causal relationships of the molecular pathways for initiation of these forms of cell death, thus enabling identification of the molecular targets, in order to modulate productive inflammation.

Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered.

Background: The global pandemic of coronavirus disease is a societal, economic, and publichealth crisis that is still underway. The spike glycoprotein of SARS-CoV-2 is one of the primary ingredients for virulence, tissue tropism, and host areas. Aim: This study aimed to determine mutations in the S protein of the Iraqi COVID-19 isolates.

Full genome sequences of Iraqi strains were obtained from GISAID. Using statistical saturation mutagenesis and other informatics methods, we investigated 20 sequences of SARS-CoV-2 S protein missense mutation isolates in Iraq selected from NCBI.

The following mutations were detected for all the strains under study compared to the wild type: L452R, A522V, E583D and D614G. The number of mutations in the strains was different depending on the location of the state from which the sample was collected The D614G mutation was found in 19 strains. One strain had three mutations, while the other was a wild form strain. The structure of the mutant protein changes dramatically, as does the energy of the atoms concerning the docking position, affecting the protein's stability.

The mutation sites would improve the S protein's stability. Molecular docking of RBD-ACE2 is affected differently by residues L452R and A522V.

Complexity and multifactorial nature of potential pathogenic consequences of SARS-CoV-2 infection in human body, discovery of new virus-induced mechanisms triggering a cascade of pathological responses in the cells of host organism leading to development of multiple organ failure elicited increasing interest in morpho-functional state of blood cells in reconvalescent persons after COVID-19 infection. The aim of the present work is to characterize morphofunctional pattern of blood cells at different periods of recovery, depending on the severity of COVID-19. We examined 55 convalescents after bearing COVID-19 infection: Group I included the convalescents 30 days after the disease (n = 39); Group II consisted of the persons 60 days after recovery (n = 16); Group III included clinically healthy volunteers with no history of clinical SARS-CoV-2 infection (n = 11). The cells were examined by means of Olympus CX41 microscope (Olympus, Japan), and VZ-C31S digital videocamera (VideoZavr, Russia) using the VideoZavr software (version 1.5). Assessment of neutrophil populations in the whole blood samples was performed with BD Accuri C6 Plus flow cytometer (USA) with automatic differentiation of cells between lymphocytes and monocytes, according to the degree of granularity. Cytokine production was determined using commercial kits for detection of IFNγ, TNFα, IL-4, IL-8, IL-10 (JSC Vector-Best, Russia), IL-17A (eBioscience, Austria) was assayed with automatic enzyme immunoassay analyzer “LAZURIT” (Dynex Technologies, USA). Among the convalescents who suffered the moderate-degree COVID-19 (45.5% and 50% of cases, respectively) on days +30 and +60 after clinical recovery, a significantly increased ratio of morphologically altered forms of erythrocytes (echinocytes, ovalocytes, dacryocytes, codocytes) was noted as compared with group III (p = 0.00001 and p = 0.001, respectively). Regardless of clinical severity of the disease; a mean of 40.6% convalescents from groups I and II had moderate disturbances in the neutrophil morphology (cytoplasmic vacuolization, chromatin decondensation at the pre-netosis stage, transformation of cells by the netosis type), and, in 27.4% of cases, the areas of neutrophilplatelet aggregation were seen. In blood supernates from recovered patients, we have revealed a significantly decreased content of IFNγ (P = 0.02), TNFα (p = 0.03), IL-10 (p = 0.04) and IL-17A (p = 0.02). The revealed morphological and functional changes in blood cells in the persons who underwent COVID-19 infection suggest long-term maintenance of toxic damage to erythrocytes, neutrophils and lymphocytes over the recovery period. The effects of the detected morphological and functional disorders of blood cells following COVID-19 recovery leading to increase in blood viscosity and microcirculation, formation of neutrophil-platelet aggregates, may cause higher risks of thrombotic complications at the long-range period as well as decreased levels of regulatory cytokines, thus confirming slow recovery of the lymphocyte populations (Th1, Th2, Th17) of the immune system.

Allele typing of single-nucleotide polymorphisms (SNPs) may be used in predictive medicine and to determine targets for the most effective treatment strategies for various diseases. The purpose of the present work was to investigate the association between the SNPs of inflammatory genes, e.g., IL10 (C819T; rs1800871; C592A; rs1800872); IL4 (C589T; rs2243250); fibrosis-related factors - TGFβ1 (G915C; rs1800471); MMP1 (1607insG; rs1799750); apoptosis-regulators (TNFRSF11B G1181C; rs2073618); vasoconstricting factors (CRP C3872T; rs1205); CYP1A1 (A2454G; rs1048943), endothelial dysfunction (EDN1 G925T; rs5370); (NOS3 C786T; rs2070744) and development of coronary heart disorders, breast cancer, bronchial asthma (BA) and threatened miscarriage in early pregnancy among population of the Republic of Adygea.

DNA samples of unrelated donors and patients (n = 74) with verified diagnoses of bronchial asthma (n = 13), coronary heart disease (n = 10), breast cancer (n = 10) and threatened miscarriage in the first trimester of pregnancy (n = 8) were isolated from peripheral blood leukocytes and typed by allele-specific polymerase chain reaction with electrophoretic detection of results using commercial tests-systems of NPF “Litech”, Moscow.

The study in a group of Adygea residents has revealed the statistical significance for the “normal” Arg25-allelic variant of the TGFβ1 gene (p < 0.05; F = 0.038; OR = 3.231; 95% CI = 1.081-9.656) in the development of bronchial asthma. There were no significant differences in SNP rs1800471 of the TGFβ1 gene in the groups with cardiovascular, oncological diseases and gestational disorders (p > 0.05). The frequency distribution of allelic variants NOS3 C786T; TNFRSF11B G1181C; 1607insG of the MMP1 gene; G925T of the EDN1 gene, and CYP1A1 2454G in the examined patients with cardiovascular disease and breast cancer did not significantly differ from the control group (p > 0.05). The statistical significance for the frequency of allelic variants rs1799750 (MMP1 gene) in cases of threatened early miscarriage and in women with a physiological course of pregnancy (F = 0.096; p < 0.05%: OR = 6.0) was close to reliable, but with a confidence interval > 1.0 (95% CI = 0,98036,716), thus requiring further research.

The obtained data could be sufficient in order to suggest predisposition for bronchial asthma, as well as to develop a set of preventive measures taking into account the individual characteristics of each patient.

It is well known that results of breast cancer (BC) hormonal therapy depend on expression of tumor estradiol and progesterone receptors (ER and PR) in tumor tissue. Mechanisms of ER⁺/PR⁺ tumors conversion to ER⁺/PR^- and ER^-/PR^- tumors remain scarcely studied. The decrease of steroid receptors expression seems to depend on action of genotoxic metabolites of environmental carcinogens (particularly, benzo[a]pyrene, BP) and endogenous steroids (in particular, estradiol, E2). The formation of these metabolites is regulated by the biotransformation enzymes. On the other hand, the formation of DNA-adducts with genotoxic metabolites may induce the synthesis of specific antibodies. Previously, it was shown that increase of the serum IgA-antibodies levels against Bp and E2 over the levels of IgA-antibodies against progesterone (IgA-Bp/IgA-Pg > 1 and IgA-E2/IgA-Pg), could be interpreted as immunological imbalance associated with high BC risk in healthy women. The purpose of this study was to detect the suggested associations between ER⁺/PR⁺ tumors conversion to ER⁺/PR⁺ and ER^-/PR^- tumors and immunological imbalance in the BC patients with distinct gene variants of biotransformation enzymes: CYP1A1*2A (rs 4646903), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTT1 (del), GSTP1 (rs1695). The IgA-Bp, IgA-E2 and IgA-Pg were studied in 1321 non-smoking BC patients by non-competitive solid phase immunoassay. The conjugates of Bp, E2 and Pg with bovine serum albumin were adsorbed as target antibodies. The goat antibodies against human IgA conjugated with horseradish peroxidase were used for detection of the studied specific antibodies. Gene polymorphisms of biotransformation enzymes were analyzed by the real-time PCR. Tumor ER and PR were detected by the standard immunohistochemical methods.

ER⁺/PR⁺ tumors in BC patients at the stage I (N = 534) were found in 68.7%, ER⁺/PR^- in 15.6%, ER^-/ PR^- in 15.7%. In BC patients at the II-IV stage (N = 787), frequency of ER⁺/PR⁺ tumors decreased to 60.2%, ER⁺/PR^- was similar (15.8%), and ER^-/PR^- increased to 24.0% (p < 0.0001). These alterations were revealed in BC patients at the IgA-Bp/IgA-Pg ratios > 1, and IgA-E2/IgA-Pg > 1 only. There were no differences found between BC patients at stage I and II-IV at the ER⁺/PR⁺, ER⁺/PR^-, ER^-/PR^- frequencies when these ratios were low.

The frequency of ER⁺/PR⁺ tumors in homozygotes TT of CYP19A1 was 77.1% at the I stage and 60.1% at the II-IV stages. Respectively the frequencies of ER^-/PR^- tumors were 11.8% and 26.1% (p < 0.001). ER⁺/ PR⁺ tumors were revealed in GSTT1 “+” BC patients at the I stage in 68.7% and at the II-IV stages in 58.0%. Respectively ER^-/PR^- tumors were found in 16.6% and 24.5% (p < 0.0004). The frequency of ER⁺/PR⁺ tumors was 57.1% in homozygotes GG of GSTP1 at the I stage and 60.7% at the II-IV stages. Respectively the frequencies of ER⁺/PR^- were 14.3% and 22.2% and ER^-/PR^- were 28.6% and 19.0% (p < 0.001). Proportions of low and high IgA-Bp/IgA-Pg and IgA-E2/IgA-Pg ratios were the same at the any enzyme genotype of studied CYP or GST variants. In conclusion, we have revealed a sufficient contribution of immunological imbalance to the conversion of steroid receptors in breast cancer growth, being independent of several CYP and GST gene polymorphisms.

The aim of present study was to investigate the hBD-3 gene expression in the surface epithelium of mucosa in ORL organs. We have studied a total of 210 mucosal samples, obtained at the most frequent surgical intervantions from 5 different anatomical functional areas: nose and paranasal sinuses, middle ear, nasopharynx, oropharynx, larynx. The inferior turbinate mucosa (1) and the normal middle nasal passage mucosa (2) served as controls. Estimation of hBD-3 and β-actin gene expression was performed by reverse transcription and realtime PCR. In the nasal and sino-nasal mucosa, only negligible expression levels were detected in 14.29-33.33% of samples, most often in the specimens from the middle nasal passage and ethmoid labyrinth polyps (53.84%), being absent in hypertrophic inferior turbinate. In the middle ear cavity, the frequency detection of the hBD-3 gene expression varied from 7.69% in the stapes superstructures mucosa to 53.85% of the mucosal samples in the presence of cholesteatoma. hBD-3 gene expression was detected in most tissue samples with high microbial contamination: palatine tonsils (100%); adenoid hypertrophy (84.62%); adenoids in hypertrophic states of adenoids and palatine tonsils (87.5%); laryngeal fibrous-vascular polyps (87.5%); other laryngeal pathology (77.78% of the samples). The highest levels of hBD-3 gene expression were found in laryngeal fibrous-vascular polyps. The findings presumed two functionally different types of immune response in mucosa of the ORL organs. In the anatomical-functional areas lined with ciliated epithelium (middle and inferior nasal passages, maxillary and ethmoid sinuses, middle ear), significantly lower frequencies (Fisher's exact test, p < 0.05 to p < 0.001) and levels (Mann-Whitney test, p < 0.05 to p < 0.001) of hBD-3 gene expression were detected, except of polyps of the middle nasal passage and ethmoid labyrinth, and mucosa of the tympanic cavity in cholesteatoma, which may be related to the nature of the pathological process. In the areas lined with squamous epithelium or a combination of squamous and ciliated epithelium, hBD-3 gene expression was detected almost everywhere and at significantly higher levels. In the context of chronic inflammation and infection-related diseases of the ORL organs, in addition to the direct microbicidal activity of hBD-3 as the first line of immune response, one may suggest peptide dysregulation and, even, pathogenetic effects of hBD-3, e.g., increased sensitivity to infections, pathological changes in the composition of the commensal bacteria, fibrous remodeling.

The leading role of diabetic retinopathy is considered the main causal factor of decreased visual acuity in the able-bodied and elderly ages determines its clinical relevance, including immunological aspects of pathogenesis to improve the diagnosis and treatment of this ophthalmic pathology. Currently, changes in lacrimal fluid interleukins in elderly patients suffering from diabetic retinopathy have not been sufficiently studied. The aim of our work was to study the content of pro-inflammatory and anti-inflammatory interleukins in lacrimal fluid in elderly patients with diabetic retinopathy.

The lacrimal fluid interleukins were analyzed in two clinical groups: the main group was represented by 72 elderly patients with diabetic retinopathy, and the control group included 64 patients of the same age with type 2 diabetes mellitus without diabetic retinopathy. The diagnosis of diabetic retinopathy was assessed from the criteria of Clinical Recommendations “Diabetes mellitus, diabetic retinopathy, diabetic macular edema” issued by the All-Russian Association of Ophthalmologists based on the results of a comprehensive ophthalmological examination. In the lacrimal fluid taken from all patients, the content of various pro- and anti-inflammatory interleukins was studied by solid-phase enzyme immunoassay using R&D Diagnostic Inc. (USA) test systems. Arithmetic average values, their errors, relative risk factors and confidence intervals were calculated, and their significance was evaluated. We have obtained following results: a statistically significant increase of most proinflammatory interleukins was detected in the lacrimal fluid of patients with diabetic retinopathy. In particular, expression of IL-6 was increased to 142.9±7.8 pg/ml among the patients with diabetic retinopathy versus 6.8±0.7 pg/ml in the comparison group, IL-3 was increased to 2.4±0.3 pg/ml versus 0.3±0.05 pg/ml, respectively (p < 0.001). The production of other pro-inflammatory interleukins at the local site has also increased, except of IL-7. However, the concentration of IL-4 and IL-10 was significantly decreased in the patients with diabetic retinopathy, with even higher increase of IL-10 (4.3±0.5 pg/ml versus 11.7±2.3 pg/ml, p < 0.001). The relative risk values were the highest for IL-6 (7.824), at the reliable confidence interval of 7.5388.261; for IL-3 these values comprised 3.269 (CI 3.084-3.721). High relative risk values were also established for IL-8, IL-5 and IL-1α₂. The relative risk of developing diabetic retinopathy by almost 2 times was associated with higher contents of IL-8 in the lacrimal fluid (statistically significant confidence interval of 1.728-2.432 (p < 0.01); for IL-5 it was 1.748 (confidence interval of 1.462-2.194 (p < 0.01); for IL-1α₂ it comprised 1.718 (confidence interval of 1.524-2.137, p < 0.001). These findings suggest an association of the abovementioned interleukins and development of diabetic retinopathy. The established patterns expand modern views concerning immunopathogenesis of diabetic retinopathy, involving the interleukins of lacrimal fluid.

Alopecia areata is an autoimmune disease characterized by non-scarring hair loss with preservation of the hair follicle. Hair loss in alopecia areata can be either focal with the appearance of clearly defined foci of alopecia, or diffuse or complete hair loss in any area of the skin where hair follicles are present. Data on the role of food allergy in the development of alopecia areata and the nature of the sensitization spectrum are extremely scarce. Objective: to study the features of the spectrum of sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata.

The study involved patients with alopecia areata (n = 17), who were divided into groups according to age: group 1 — children (n = 9) and group 2 — adults (n = 8). All patients underwent a specific allergological examination: collection of an allergic history, skin prick testing with food and pollen allergens (Allergopharma, Germany).

Analysis of the spectrum of sensitization to food allergens in patients with alopecia areata revealed features depending on their age. Thus, in the group of sick children, the highest frequency of sensitization to whole chicken eggs, food cereals, yeast, soybeans and cow's milk proteins was noted. In the group of sick adults, the most significant food allergens were: egg protein, rye flour, oats. Among the pollen allergens in the first group of patients, the most common allergens were a mixture of weed and grass pollen, in the second group, a mixture of meadow grass pollen. All patients, taking into account allergological testing, were administered an individual elimination diet with the exclusion of causally significant allergens, taking into account crossreacting allergens. The elimination effect was assessed 2 months after the start of the elimination diet. 70% of patients showed a clinical improvement, i.e., the growth of vellus was noted (vellus depigmented hair) in the foci of alopecia, as well as terminal pigmented hair. Complete regression of alopecia foci occurred on average within 3-6 months from the start of therapy.

The sensitization to food and pollen (cross-reacting) allergens in patients with alopecia areata and the positive effect of the elimination diet revealed in our study well supports the role of food allergy in the development of this disorder. Therefore, the study of the causal relationship between food allergy and alopecia areata is of particular relevance and creates prerequisites for the discovery of new diagnostic and therapeutic options.

Chronic non-infectious inflammation of low intensity is the most important mechanism of development and progression in atherosclerosis. Under the conditions of persistent non-resolving inflammation observed in the vascular wall and atherosclerotic plaque (ASB), permanent tissue damage occurs, thus leading to increased formation of endogenous danger-associated molecular patterns (DAMPs). The non-histone chromosomal protein HMGB1 may be regarded as a prototypical DAMPs. HMGB1 acts as a DAMP if entering the extracellular space, causing inflammation by its binding to pattern-recognizing receptors (TLR2, TLR4, RAGE, CD36, etc.). A number of clinical studies have revealed higher HMGB1 levels in the blood of patients with coronary heart disease and atherosclerotic disease of the lower limb arteries, as well as its interrelations with the burden of coronary artery atherosclerosis. Currently, the mechanisms of HMGB1-mediated atherosclerosis progression are studied only fragmentary. The aim of our study was to investigate relationships between the serum HMGB1 level and subsets of circulating monocyte subpopulations in patients with subclinical atherosclerosis.

The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Serum HMGB1 concentration was determined using enzyme immunoassay kits (Human HMGB1/HMG-1 ELISA Kit, NBP2-62766, Novus Biologicals, USA). The serum HMGB1 threshold was 18.75 pg/ml, whereas the measurement range was 31.25 to 2000 pg/ml. Phenotyping of the blood monocyte subpopulations was performed by flow cytometry using Navios 6/2 device (Beckman Coulter, USA).

An increase in serum HMGB1 concentration was associated with decreased number of classical M2 monocytes, and an increase in intermediate and M1 monocytes. Moreover, an increase in HMGB1 concentration was associated with higher numbers of classical, intermediate, and non-classical monocytes expressing CD36 and TLR2. Increased HMGB1 concentration (from Q1 to Q4) correlated with higher numbers of classical (p = 0.001) and intermediate monocytes (p = 0.006) but not with non-classical phenotypes (p = 0.147). Upon increase of HMGB1 concentration (Q1 to Q4), we have found an increase in the number of classical (p < 0.0001), intermediate (p < 0.0001), and non-classical (p < 0.0001), CD36-expressing monocytes. An increased number of intermediate (p = 0.022; p_{1, 4} = 0.034) and non-classical, TLR2-expressing monocytes was also revealed (p = 0.002; p_{1, 4} = 0.035). By mean of correlation analysis, IL-1β concentrations showed direct correlation with the number of M1 monocytes (r = 0.268; p = 0.035) and inverse relation with the number of M2 monocytes (r = -0.376; p = 0.003).

Increased serum HMGB1 concentration in patients with subclinical atherosclerosis was associated with decreased numbers of classical and M2 monocytes, as well as higher numbers of intermediate and M1 monocytes, like as with increased contents of intermediate and non-classical monocytes expressing CD36 and TLR2. IL-1β levels directly correlated with HMGB1 concentration and the number of Mi-monocytes.

Metabolic syndrome (MS) is a serious medical and social problem due to its high prevalence, lack of common approaches to diagnosis and treatment. Prevention of food dysadaptation reactions and the studies of control mechanisms of immune tolerance to food antigens is of special scientific interest, thus providing available anti-inflammatory tools for correcting increased permeability of the intestinal epithelium and vascular endothelium associated with development of MS. Nutritional dysadaptation occurs due to inappropriate diet being mediated by the geno-phenotypic characteristics of digestive enzymes and immune system which control the efficiency of food digestion.

Immunological control of digestion, including dynamic maintenance of tolerance to food antigens, is carried out at two levels of immune system: innate response with functional involvement of microbiota, and adaptive response, represented by cellular and humoral mechanisms associated with molecular epitopes and critical mass of persistent food antigens which are present in immunologically competent areas of small intestine, due to changing permeability of intestinal barrier and transcytosis processes. Patients and methods: aiming for assessment of the diet contribution to the immuno-biochemical and rheological imbalance in people with increased body weight, 170 volunteers of both sexes aged 20-55 years were examined, depending on the body mass index: > 27.0 kg/m² (clinical group, n = 120), and those with BMI of < 25.0 kg/m² (control group, n = 50). We have revealed statistically significant increase of multiple parameters in the clinical group, i.e., concentration of IL-6, IL-17, cholesterol, glucose, glycosylated hemoglobin, insulin, indices of insulin resistance and atherogenicity. Increased levels of specific IgG antibodies to a number of food antigens were found in the subjects in the clinical group. In the course of our study, a statistically significant relationships was found between total numbers of platelets (p < 0.05; r = 0.213), erythrocytes (p < 0.05; r = -0.211), mean erythrocyte volume (MCV) (p < 0, 05; r = 0.339), and the concentration of IgG to casein in the blood, as well as a correlation between the levels of sIgG to soybeans and the number of platelets (p < 0.05; r = 0.231). At the same time, some associations were found between the established values of IgG to casein pAG, and the risk of developing atherogenic changes (atherogenicity index > 3) being significant at OR = 2.68 (1.33-5.42), as well as between IgG values to casein pAG (OR = 8.9 (2.6-30.5)), to soybean pAG (OR = 5.6 (1.8-16.7)), to gluten pAG ((F = 0.00359. p < 0.05), and increased body mass index.

The results obtained were interpreted as a possible impairment of food tolerance for a number of food antigens in individuals with high body mass index, due to the revealed correlations between concentrations of IgG to food antigens, imbalance of pro-inflammatory cytokines, rheological and metabolic parameters. These data may be used as biomarkers suggesting higher risk of evolving metabolic syndrome.

Arterial hypertension (AH) is among the life-threatening diseases and requires permanent antihypertensive therapy, including telmisartan. However, the effect of telmisartan upon systemic interleukin profile in elderly hypertensive patients requires further study, due to the limited data on previously analyzed interleukins. The aim of our study was to evaluate the immune pleiotropic effect of telmisartan upon miultiple pro- and anti-inflammatory blood interleukins in the patients with hypertension. The study included examination of 74 patients aged 60-74 years suffering from hypertension treated with telmisartan (80 mg/day in the morning time). The immune response to telmisartan assessed by the blood contents of different interleukins was evaluated following 6 months of treatment. These markers were determined by flow cytometry using “Becton Dickinson FACS Canto 2” device (USA). The pleiotropic immune effect of telmisartan upon the interleukin profile in hypertensive patients aged 60-74 was established by statistically significant changes in multiple pro-inflammatory and anti-inflammatory interleukins. Following 6 months of telmisartan therapy, the patients with arterial hypertension have shown a statistically significant decrease in blood cytokines, i.e., IL-1 в was reduced to 8.1±0.6 pg/ml vs initial 10.5±0.8 pg/ml; IL-2, to 8.6±0.8 pg/ml vs initial 11.8±1.1 pg/ml; IL-6, to 18.4±0.5 pg/ml vs initial 21.2±0.7 pg/ml; IL-8, to 3.5±0.6 pg/ml vs 5.4±0.5 pg/ml. We have also revealed a statistically significant decrease of blood TNFα levels to 5.3±0.5 pg/ml versus initial 6.8±0.4 pg/ml in the elderly patients with hypertension after 6 months of antihypertensive therapy with telmisartan. Moreover, the levels of pro-inflammatory systemic interleukins and, especially, IL-4 showed an increase from 4.6±0.5 pg/ml to 7.0±0.6 pg/ml in the course of telmisartan therapy in these patients. In summary, one may suggest that telmisartan exerts a significant immune pleiotropic effect in the patients with hypertension, confirmed by the systemic changes of interleukin contents. The pleiotropic effects of telmisartan have been established in patients with arterial hypertension, expressed as a significant decrease in IL-1, IL-2, IL-6, IL-8, TNFα levels, along with increased IL-4 and IL-10 contents. The results obtained showed a significant pleiotropic effect of telmisartan in the patients with arterial hypertension upon several interleukins, thus expanding the role of immune inflammation in this disorder, as well as its reversal with telmisartan therapy.

Polymethyl methacrylate-based acrylic resin is commonly used in current dental practice as an underlying material for fabrication of overdenture restorations. To increase service life of laminar overdentures, we have developed a technique to fabricate a novel combined base for a full overdenture using a fiberglass-based composite. It makes sense to evaluate probable hazards of inflammatory process which could be activated when using structural polymer materials and composites in dental practice. Our study aimed for assessment of changes in production of key cytokines (interferon-y and interleukin-4) by ex vivo incubated human mononuclear leukocytes in the presence of acrylic resin and fiberglass-based composite.

The experiments dealt with peripheral venous blood leukocytes obtained from 13 apparently healthy male volunteers (mean age = 24 years). The leukocytes were isolated from heparinized blood by gradient centrifugation. The cells were cultured in plastic round-bottom 96-well plates, in moist atmosphere with 5% CO2 at 37 °C for 72 h. Following the incubation, the culture supernates were collected and frozen for further determination of cytokine concentration using ELISA reagent kits for interferon-y and interleukin-4 measurement (Vector-Best, Russia). The samples of two structural materials were tested in the bioassays: the specimens of acrylic resin, Ftorax were compression-moulded by hot polymerization in prefabricated casts; the specimens of a composite, Trinia, were computer-milled. Glass specimens of similar shape and size were used as references. The statistical analysis used a software package, Statistica 7.0. Significance of the differences was evaluated using the Student's test and the Mann-Whitney test. When testing the statistical hypotheses, the significance level (p) was taken to be 0.05.

Significant decrease of IFNγ production was revealed in presence of Trinia than in the samples with glass and with the acrylic specimens, whereas cell viability counts did not differ from the blank values. There was no statistical differences in IL-4 production between the samples with the polymer materials and the glass. When estimating individual stimulation indexes, the materials used in this research were found to showed a pronounced stimulatory effect with peripheral blood lymphocytes from only one volunteer. These findings indicate that Trinia triggers anti-inflammatory activity of leukocytes, whereas IFNγ production level is somewhat decreased, and IL-4 production remains unchanged.

Thus, the research assessed the method for personalized evaluation of reactivity of prosthodontic structural polymer materials. Absence of increase in lymphocytic production of key cytokines can be regarded as a hopeful sign which indicates that inflammatory process is not activated when Trinia is used in overdenture bases.

Current literature contains a large amount of data on the modifying effect of cold stress on the functions of immune cell system, in particular, on the secretion of cytokines by the cells of innate and adaptive immunity, mRNA expression. However, the modulatory mechanisms of cold stress effects upon immune response are still not studied in details. We have previously shown that cold stress strongly modulates innate immunity reactions, in particular, leads to increased macrophage secretion of reactive oxygen species, IL-10, but does not affect production of pro-inflammatory cytokines (IL-1β and TNFα. In this work, we aimed for evaluation of effects exerted by acute cold stress upon some adaptive immunity indices, i.e., antibody synthesis, production of IL-2, IL-4, IFNγ by murine splenocytes as well as production of IL-12 and oxygen radicals, taking into account appropriate time-dependent changes. Materials and methods. White male mice were the object of the present study. The animals were divided into the following groups: 1^st (control), 2^nd (cold stress exposure, at -20 °С for 10 min), 3^rd (cold stress at -20 °С for 60 min). Subgroups of the animals were intraperitoneally sensitized with sheep erythrocytes (10⁸ cells in 0.2 ml in 0.9% NaCl) one hour after ending of the cold exposure. On the day 5, the number of antibody-forming cells in the spleen was assessed by the method of local hemolysis in agarose gel. The other subgroup of animals was removed from the experiment 1 and 6 hours after the end of stress exposure, the spleen and cells were isolated from peritoneal cavity. The cytokine concentrations in supernatants were determined by means of enzyme-linked immunosorbent assay systems; production of reactive oxygen species in peritoneal cells was assessed using a luminol-dependent chemiluminescence reaction. It was established that 10- and 60-min cold stress did not have a statistically significant effect on the antibody production, spontaneous and stimulated production of IL-4 by splenocytes. However, inhibition of IL-2 production was observed 60 min following cold stress of either type. At the same time, inhibited IFNγ production was revealed after the both stress regimens. In the animals subjected to cooling for 60 min, a decrease in IL-12 production was also detected. In addition, the 60-min stress led to a pronounced and persistently increased production of oxygen radicals, which may exert negative effects on the development of immune responses. Hence, the acute cold stress led to inhibition of the production of cytokines related to the T cell immune response.

Genetic factors play an important role in the development and progression of many disorders including lung sarcoidosis which is a systemic inflammatory granulomatous disease of unknown etiology, characterized by the formation of epithelioid cell granules in affected tissues. Intensity of the developing inflammation may partially depend on genetic factors which may influence both susceptibility to lung sarcoidosis, and also clinical course of the disease and the degree of inflammatory response from the immune system. Allelic polymorphism of distinct genes is therefore worth of study. In the carriers of certain allele variants, one may observe either increase, or a decreased production of pro-inflammatory factors. Among the candidate factors involved in higher susceptibility of humans, one may consider Toll-like receptors (TLRS) which may contribute to formation of granulomas. Relevant data concerning association between the allele variants of these genes and susceptibility to lung sarcoidosis, and its clinical course are still quite limited and contradictory. The aim of the present study was to analyze the association between the Arg753Gln (rs574308) polymorphism of the Toll-like receptor 2 (TLR2) gene and the risk of developing pulmonary sarcoidosis.

A total of 253 persons were under study including 122 patients diagnosed with morphologically verified sarcoidosis with lung involvement (average age, 41.00±12.56 years), and 131 healthy donors comprising a control group (average age, 44.00±14.23 years). The distribution of alleles and genotypes for the Arg753Gln (rs574308) polymorphic TLR2 gene marker was studied in the groups of patients with pulmonary sarcoidosis and healthy donors. The test alleles of this polymorphic marker were typed by means of PCR technique followed by length analysis restriction fragments (PCR-RFLP method).

There were no statistically significant differences in the distribution of allele and genotype frequencies for the polymorphic marker Arg753Gln (rs574308) of the TLR2 gene between the control group and the group of patients with pulmonary sarcoidosis: χ² = 2.0, df = 1, p = 0.158 and χ² = 2.19, df = 2, p = 0.140, respectively.

The polymorphic marker Arg753Gln (rs574308) of Toll-like receptor 2 gene is not associated with the risk of developing pulmonary sarcoidosis among ethnic Russians of the Republic of Karelia.

Increased concentration of cell-free DNA (cfDNA) in the circulating blood of humans and animals is a sign of inflammatory conditions and a distinctive characteristic of various pathophysiological processes in the body. The aim of the present study was to investigate the possible role of tumor necrosis factor (TNFα) in changes of cfDNA contents in peripheral blood as a response to experimentally induced systemic inflammation.

We used 40 female hybrid mice (C57Bl/6xDBA/2) F1 at the age of 6-8 weeks. The concentration of cfDNA and its individual fractions was determined using a PicoGreen fluorescent dye. The dynamics of inflammatory process was evaluated after 4, 8, 11 and 24 hours following LPS injection. A significant increase in the blood plasma cfDNA levels was shown under the action of E. coli lipopolysaccharide (LPS), along with simultaneous decreased levels of cfDNA, associated with cell surface. The ratio of cell surface-bound cfDNA to the total cfDNA contents was reduced in dose-dependent manner as early as 4 hours after LPS injection to the animals, thus allowing us to consider this ratio a characteristic sign of netosis of neutrophilic granulocytes during the development of acute inflammation. The described effects are significantly suppressed with co-injection of recombinant TNFα neutralizing protein along with LPS, whereas increased intake of neutrophils in the tissues is determined by some other factors which are not directly related to the production of this cytokine.

Based on the obtained data, we proposed a following hypothesis: induction of netosis by inflammatory stimuli causes an increase in the concentration of cfDNA in blood plasma not only due to de novo emerging extracellular DNA by neutrophil netosis, but also by the release of distinct cfDNA fraction that was previously firmly bound to cell membranes in multiple body tissues under the action of proteases released during netosis.