Immune cells, cytokines, and interferons are key mediators that ensure the gestational process from implantation to childbirth. The coordination of their signaling pathways determines molecular interactions between the mother and the fetus, the physiological course of pregnancy and its outcomes, particularly in the context of maternal respiratory viral infections. Here we analyze current information on physiological and pathological roles of cytokines and interferons during gestation in both uncomplicated and complicated pregnancies. Disrupted cytokine signaling might significantly alter fetal and placental development, leading to pregnancy complications and birth defects.
Background.Among all infectious diseases that occur in the human population, only acute respiratory viral infections, including influenza, lead to massive outbreaks, often taking on the character of epidemics and pandemics. Polymorphism of cytokine genes can be both a factor of predisposition and resistance to infection, the development of the disease, and a long, complicated course of influenza. Aim.Study of the genetic polymorphism of the genes of toll-like receptorsrs5743708 (Arg753Gln, G2258A),TLR3 rs3775291 (Phe412Leu, C1234T),TLR4 rs4986790 (Asp299Gly, A896G),TLR4 rs4986791 (Thr399Ile, C1196T)in healthy individuals and in patients with influenzaA(H3N2). Material and methods.The study, using the continuous sampling method, included patients with influenzaA (H3N2; 89people) who were treated at the Regional Clinical Infectious Diseases Hospital in Chita during the epidemic seasons of 20162017 and 20172018. The control group consisted of 96practically healthy donors. To analyze the polymorphism of theTLR2 rs5743708 (Arg753Gln, G2258A), TLR3 rs3775291 (Phe412Leu, C1234T), TLR4 rs4986790 (Asp299Gly, A896G),andTLR4 rs4986791 (Thr399Ile, C1196T)genes the method of polymerase chain reaction with electrophoretic detection using standard kits from Scientific and Production Company Litekh (Moscow) was applied.Statistical analysis was carried out in accordance with the principles of the International Committee of Medical Journal Editors and the Statistical Analysis and Methods in the Published Literature recommendations. Pearson's 2test was used for comparative evaluation of qualitative nominal data. Results.Patients with influenzaA (H3N2) more often had heterozygousTLR2 753Arg/Glnvariants [2=8.26, p=0.02; odds ratio (OR) 3.00; 95% confidence interval (CI) 1.336.73], homozygousTLR3 412Leu/Leuvariants (2=11.68, p=0.003; OR=2.39; 95% CI 1.043.61), heterozygous variants ofTLR4 299Asp/Gly(2=6.97; p=0.03; OR=2.15; 95% CI 1.024.70) and399Thr/Ile(2=8.39; p= 0.01; OR=2.30; 95% CI 1.064.88) compared with a group of healthy donors. Conclusion.The genotypes753Arg/Glnof theTLR2gene,412Leu/Leuof theTLR3gene,299Asp/Glyof theTLR4gene,Thr399Ileof theTLR4gene predispose to the development of influenzaA (H3N2); carriage of genotypes753Arg/Argof theTLR2gene,412Phe/Pheof theTLR3gene,299Asp/Aspof theTLR4gene,399Thr/Throf theTLR4gene reduces the likelihood of the influenzaA(H3N2) development.
Introduction. The biogeochemical environment of the territory of the Eastern Zabaikalye is characterized by excess, deficiency or unfavourable ratio of many macro- and microelements in soil, water and vegetation. This is due to the metallogenic characteristics of the region and industrial mining activities, carried out for more than three hundred years. The aim of the study was to investigate the accumulation of chemical elements in the hair in children and to identify specifics in their distribution depending on the naturally occurring and technogenic factors. Materials and method. Hair samples were taken from seventy nine 5-12 years children living in the areas of geochemical anomalies and in the administrative centre of the region, Chita. The elemental composition of the samples for 28 chemical elements was determined by multi-element instrumental neutron activation analysis (INAA). Statistical processing of the results was carried out using nonparametric methods, concentration coefficients were calculated relative to the regional background. Results. In settlements (V-Shakhtaminsky, Sherlovaya Gora, Kalga, Urulyungui) located in the zone of geochemical anomalies, which formation is associated with the presence of various and numerous deposits of lead-zinc, gold-polymetallic, tin, molybdenum ore and mining operations, the maximum amount of substances with content exceeding the regional background is observed in the biosubstrate. The values of concentration ratios above the background were established for antimony, gold, arsenic, europium, ytterbium, silver, rare-earth elements, cobalt, chromium, zinc and iron. Limitations. In studying the elemental homeostasis of children and adolescents living in natural and anthropogenic geochemical anomalies of Zabaikalsky Krai, the content of 28 chemical elements in hair was analyzed. Conclusion. The revealed characteristics of distribution and accumulation of certain spectrum of chemical substances in biosubstrate in children and adolescents reflect both metallogenic features of each territory and technogenic impact, which allows forming an idea of a unique regional component of the elemental homeostasis in the population.
The aim of the study was to evaluate the putative association of the rs11064153 variant of the SCNN1A sodium channel gene with arterial hypertension (AH) among patients suffering from AH and relatively healthy people in the Trans-Baikal Territory.Design and methods. The present study included 106 patients with a confirmed diagnosis of AH. All participants were included in the study after signing informed consent. The control group consisted of 98 practically healthy people. The groups were comparable in age: the average age in the group with primary AH was 45 ± 9,7 years, in the control group— 42,5 ± 5,8 years. The number of men in group 1 was 73,6% (78/106), in group 2–55,1% (54/98) of the total number of cases (Chi-square = 7,62, df = 1, p < 0,005). Molecular genetics typing of the studied genes was carried out. SNPs of the sodium channel genes SCNN1A (rs11064153) were determined by real-time polymerase chain reaction. We have evaluated the subordination of the distribution of genotypes of samples to the Hardy-Weinberg equilibrium, χ2 -test, and also estimated the odds ratio (OR).Results. Carriage of the T/T genotype in the group of patients with AH was more frequent than in the control group (97,4% and 86,6%, respectively; χ2 = 8,60, p = 0,01). Thus, carriage of the T/T genotype of the SCNN1A gene increased the likelihood of AH in patients (OR = 2,27, 95% confidence interval (CI) 1,29–4,01, p = 0,01). Among patients, the T allele was detected 1,5 times more often with a frequency of 0,78 compared with the group of healthy individuals — 0,22 (χ2 = 7,28; p = 0,007). The C/C genotype was detected only in three patients from the AH group (2,8%) and in seven patients from the control group (7,1%). It was found that the C allele of the SCNN1А gene (rs11064153) 5 times less often than in the control group, and its frequency was 0,22 versus 0,34, respectively (χ2 = 7,28, p = 0,007). The carriage of the C allele (C/C+T/C genotypes) is associated with a lower incidence in patients with AH (OR = 0.54; 95% CI 0,35–0,85, p = 0,007). In the samples examined by us, the carriage of the C allele reduced the likelihood of AH by 2,3 times.Conclusions. We have found that the T allele and the T/T genotype of the rs11064153 variant of the SCNN 1A gene increase the likelihood of developing hypertension. Carrying allele C and the C/C SCNN1A genotype (rs11064153) reduces the likelihood of developing AH.
Aim. To study lymphocytic-platelet adhesion, eosinophils and IgE concentration in children with acute obstructive bronchitis. Materials and methods. 70 children were examined, the first group consisted of children with acute bronchitis (n=38), the second group included healthy children (n=32). All children were examined for the concentration of IgE, the number of lymphocytes and eosinophils, and the count of lymphocyte-platelet aggregates. Results. In patients with obstructive bronchitis, there was no difference in the concentration of the relative and absolute number of lymphocytes compared with healthy children. High values of eosinophils were found in children with obstructive bronchitis (9.0 ± 0.7 %) while in children of the control group the same indicator was determined within the limits of normal values (0.9 ± 0.2 %). The level of IgE in children with obstructive bronchitis exceeded the concentration of this indicator in healthy children by 19 times. In children with obstructive bronchitis, the index and degree of lymphocyticplatelet adhesion were 20.0 ± 0.7 % and 10.5 ± 0.09, respectively, statistically significantly higher than similar indices in healthy children (14.0 ± 0.2 %, p = 0.0001 and 3.3 ± 0.1, p = 0.001, respectively). Conclusion. In the body of children with obstructive bronchitis, an immune response develops, which is involved in the pathogenesis of recurrence of the disease, the causes of which are infectious agents that stimulate innate immunity due to the presentation of PAMP molecules, as well as adaptive immunity, accompanied by killer reactions, the production of immunoglobulins, including IgE.
Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.
The paper presents data on the level of contamination of soil cover and technozems approximately the Khapcheranginsky mining and processing plant with 53 chemical elements. For more than 40 years, the enterprise has not been functioning, and processed rocks are stored on the surface, causing powerful technogenic pollution of the area. Reclamation measures have not been carried out, and tailings are not being properly operated. When analyzing the level of pollution in the settlement, it was found that in the technogenic zone the arsenic content exceeded the Threshold Limit Value (TLV) by 130 times (26 times the excess of the Approximate allowable concentrations (AAC), cadmium - 5,7 AAC, copper - 42 TLV, lead - 26,6 TLV (6,6 AAC), antimony - 1,7 TLV, zinc - 81,5 TLV (8,5 AAC). For the residential zone, excess of standard values was noted for the following elements: arsenic - 20-fold excess of TLV (4 AAC), copper - 17 TLV, lead - 3 TLV, antimony - 1.8 TLV, zinc - 14,5 TLV (1,5 AAC)) For the background territory, an excess of Threshold Limit Value (TLV) for arsenic (13-fold) and zinc (4 TLV) was noted, but this is probably due to the natural geochemical features of this region of southern Transbaikalia. The total pollution by the value of the Saeta index (Zc) in the tailings area was 269,6 units, which characterizes the technogenic zone as extremely polluted, the residential zone had a coefficient value of 75,6, and the background zone 27,7, which indicates a high level of soil contamination chemical elements, some of which are highly toxic. The main contribution to the total pollution index, according to the pollution index, belonged to the elements: As, Bi, Cd, Cu, In, Li, Pb, Sb, Sn, W, Zn, the contents of which in the conditions of the technogenic zone of the village of Khapcheranga are many times higher than the standard values. In terms of the geoaccumulation index (Igeo), the most significant toxic elements in the composition of technozems were arsenic and lead. The same elements together with tin had critical values in terms of the soil enrichment factor (EF (Pb) = 68,3, EF (As) = 61,6, EF (Sn) = 32,4), especially in the conditions of the technogenic zone. Thus, in the territory of the village of Khapcheranga and its environs, geochemical anomalies of natural and technogenic origin with an increased content of heavy metals (zinc, antimony, lead, cadmium) and arsenic, which have high carcinogenic activity, leading to teratogenic effects with immunosuppressive properties, were formed with complex exposureY
Background : Lymphocyte-platelet adhesion (LPA) is the ability of lymphocytes with CD3 + , CD4 + , CD16 + cell surface markers to form coaggregates with platelets using adhesion molecules, that allows lymphocytes to adhere to the damaged endothelium and migrate into the damaged surface of the vascular wall. Aims : Investigation of the amount of lymphocyte-platelet aggregates and lymphocyte-platelet clusters in patients with COVID-19. Methods : The research involved 168 patients with SARS-CoV-2 (COVID-19) and 100 healthy people of the same age and gender. Patient ' s blood samples were taken on the 1st-2d, 10th-12th, 21st-24th days. The participants of the study were Caucasian race and lived in the Trans-Baikal Territory. The examine of LPA was carried out by the method of Yuri Vitkovsky et al. (1999). The number of lymphocyte-platelet clusters (LPC) was estimated and expressed in rel. units per 100 free-standing cells. The results were expressed in averages and the standard deviation (M ± SD) was calculated. Significant differences were considered for P < 0.05. Results : The authors revealed that on the 1st-2d day of disease among patients the number of LPA increased to 28.9 ± 3.2%, LPC -to 5.0 ± 2.3% as compared with the control group ( P < 0.001). The average platelets volume LPA-rasio also increased by 2.9 times ( P < 0.05). Among patients during 10-12 days of the disease there was a notable increase of LPA and LPA-rasio up to 41.3 ± 1.9% and 5.8 ± 0.48 respectively (higher by 3 times as compared to the control group). On the 21-24th days of the disease with patients being in the hospital, there were no significant differences in the studied parameters among the patients and the control group. Conclusions : There is an increase in the ability of lymphocytes to adhere platelets to their surface and contact with other lymphocytes while forming clusters in the acute phase of COVID-19. Probably the process of clustering is mediated by platelet and leukocyte adhesive molecules.