Polymorphism of Transforming Growth Factor TGFB and Its Receptors TGFBRI, TGFBRII, TGFBRIIII Genes in Western Siberia Patients with Open-Angle Glaucoma.

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-ß is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention.

Diverse mantle components with invariant oxygen isotopes in the 2021 Fagradalsfjall eruption, Iceland.

The basalts of the 2021 Fagradalsfjall eruption were the first erupted on the Reykjanes Peninsula in 781 years and offer a unique opportunity to determine the composition of the mantle underlying Iceland, in particular its oxygen isotope composition (δ18O values). The basalts show compositional variations in Zr/Y, Nb/Zr and Nb/Y values that span roughly half of the previously described range for Icelandic basaltic magmas and signal involvement of Icelandic plume (OIB) and Enriched Mid-Ocean Ridge Basalt (EMORB) in magma genesis. Here we show that Fagradalsfjall δ18O values are invariable (mean δ18O = 5.4 ± 0.3‰ 2 SD, N = 47) and indistinguishable from "normal" upper mantle, in contrast to significantly lower δ18O values reported for erupted materials elsewhere in Iceland (e.g., the 2014-2015 eruption at Holuhraun, Central Iceland). Thus, despite differing trace element characteristics, the melts that supplied the Fagradalsfjall eruption show no evidence for 18O-depleted mantle or interaction with low-δ18O crust and may therefore represent a useful mantle reference value in this part of the Icelandic plume system.

Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress.

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 µg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 µg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.

State of Colon Microbiota in Rats during Chronic Restraint Stress and Selank Treatment.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 µg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

[Treatment of patients with multiple trauma in multi-field hospital]. / Rezul'taty lecheniia bol'nykh s politravmoi v mnogoprofil'noi klinike.

AIM: To analyze treatment of victims with multiple trauma in multi-field hospital. MATERIAL AND METHODS: Retrospective analysis of 2139 medical records of patients with multiple trauma (NISS score over 17) was performed. In-hospital mortality, patient transfer time, dominant injury, hospital-stay, gender and age of victims were assessed. RESULTS: New diagnostic and treatment options allowed achieving significant decrease of mortality from 39.7% (2004) to 10.8% (2016). CONCLUSION: Improved mortality was achieved due to organized work of the 'regional traumatological systems'. Mortality rate was below 10.7% if victims were transferred to the hospital within 6 hours after trauma. The highest mortality was observed in patients who were transferred to the hospital within 6-12 hours after injury (20.3%).

Blood Serum Levels of Proinflammatory Cytokines (IL-1ß, IL-6, TNFα, IL-8, IL-12p70, and IFNγ) in Patients with Uterine Myoma.

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1ß and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.

[Association of Serum Levels and Gene Polymorphism of Vascular Endothelium Growth Factor With Ischemic Heart Disease in Type 2 Diabetic Patients].

AIM: to study serum levels of vascular endothelium growth factor family peptides (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the presence of ischemic heart disease (IHD). MATERIALS AND METHODS: The study involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by Multiplex assay. Twenty-four persons without diabetes and IHD served as controls. The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039) was performed by TaqMan. RESULTS: Concentrations of VEGF-A and VEGF-C in patients with T2D were significantly lower than those in controls (p=0.03 and p=0.006, respectively). The level of VEGF-D showed a tendency to decrease (p=0.14). Patients with IHD, as compared to other patients, had higher levels of VEGF-A (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C was not different between groups. No relationships were found between VEGF-A, VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and CC-genotype at +936 position of VEGFA were more frequent among patients with IHD (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was not related to IHD and VEGF-A levels. CONCLUSION: Patients with T2D have decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039 polymorphism is associated with presence of IHD and levels of circulating VEGF-A in these patients.

[Polymorphism in the regulatory regions -С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis]. / Polimorfizm reguliatornykh regionov ­S2578A i +C936T gena faktora rosta sosudistogo éndoteliia (VEGF-A) u russkikh zhenshchin s revmatoidnym artritom.

AIM: To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. RESULTS: There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. CONCLUSION: The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

Individual Parameters of Cytokine Production in Healthy Siberian Caucasians.

The levels of spontaneous and concanavalin A-induced production of some key cytokines (TNF-α, IL-1ß, IL-4, Il-6, and IL-10) were assessed in the cultures of mononuclear cells derived from healthy volunteers examined for polymorphism of the promotor sites of the respective genes. The presence of certain allelic variants in the promoter regions of human cytokine genes mostly determines the rates of induced and spontaneous cytokine production. Allelic variant -31C of IL-1ß gene is associated with high production rate of the related cytokine. In addition, polymorphism of allelic variant C-590T of IL-4 gene significantly affects the production rates of IL-1ß, TNF-α, IL-6, and IL-10.

[Cytokine gene polymorphisms in patients with age-related macular degeneration].

AIM: To establish possible association between age-related macular degeneration (AMD) and cytokine genotype polymorphisms; for that promoter regions of a number of cytokine genes were studied, namely, TNF-A863C, TNF-A308G, TNF-A238G, IL1ß-C-31T, IL4-C590T, IL6-C174G, and IL10A-1082G. MATERIAL AND METHODS: A total of 102 AMD and 100 non-AMD participants in the same age range were examined at the Novosibirsk branch of the Academician S.N. Fyodorov IRTC «Eye Microsurgery¼. In all cases restriction fragment length polymorphism analysis was performed. RESULTS: The frequency of TNF-308 GA and IL10-1082 GG genotypes was higher in AMD patients than in the controls, while the TNF-308 АA minor genotype has proved protective against the disease. Moreover, AMD has been found to be positively related to 48 genotypic combinations and negatively - to 32 (with specificity as high as 98-99%). The odds ratio was also higher in combination analysis as compared to monogenotypes. CONCLUSION: Complex genetic analysis of cytokines gives an idea of the balance of proinflammatory and anti-inflammatory cytokines in AMD and, therefore, plays an important role in studying the disease pathogenesis and exploring therapeutic options.

[Association of Some Homozygous Genotypes of Genes Regulating Inflammation, Destruction and Angiogenesis With Laboratory Markers of Atherosclerosis Course in Men With Stable Effort Angina].

Great number of factors stimulating or inhibiting production of proteins in inflammatory process influence serum levels of markers of inflammation. A number of homozygous genotypes of inflammation, destruction, and angiogenesis genes have been found to be associated with basic clinical-laboratory indices of inflammation and atherosclerotic process. The revealed genetic markers can be used as complimentary markers of prognosis of the disease course.

[Effect of recultivated wastes of mining factories on children residing in the district of their location].

Wastes and tailing ponds of Tyrnyauz tungsten and molybdenum factory are the main sources of heavy metal incoming into environment in Kabardino-Balkarian Republic. The factory was closed more than 10 years ago and the recultivation of it's tailing ponds, where accumulated hundreds of millions tones of wastes, was completed. The aim of this investigation was an assessment of their possible influence on children residing in the vicinity of these tailing ponds (village Bylym). Village Verhny Baksan located about 30 km upstream of the valley of the Baksan River was chosen as reference (pure) locality. As a results of the performed investigations we revealed that in drinking water of Bylym and Verhny Baksan concentrations of molybdenum were 2.10±0.42 pg/l and 0.31±0.15 pg/l correspondingly, which is remarkably lower than maximum permitted concentrations. The concentrations of Mo, Cu and Pb in children's hair in both villages were practically the same, which indicates to the absence of their accumulation in human organism. But the quantity of cells with cytogenetic disorders in buccal epithelial cells in children from Bylym was 4.1 times higher in comparison with the corresponding index of uncontaminated area. The obtained data demonstrate that genotoxic effect of remedied tailing ponds retains.

[Matrix metalloproteinase 2, 3, and 9 gene polymorphisms in women with rheumatoid arthritis].

AIM: To study the promoter regions of the matrix metalloproteinase (MMP)2, MMP3, and MMP9 genes to assess their associations with the risk of rheumatoid arthritis (RA) and with the types of its clinical course in women. SUBJECTS AND METHODS: 162 female patients with RA and 329 women without this condition were examined. Polymorphisms in the gene promoter region for MMP2 (-1306 С→Т), MMP3 (-1171 5A→6А), and MMP9 (-1562 С→Т) were studied. Genotyping was carried out using the restriction fragment length polymorphism method. RESULTS: In the RA group, the -1306TT genotype of MMP2 was significantly more frequently encountered and the 6A6A genotype was less frequently seen. In the seropositive RA group, the frequency of the -1306ТТ genotype of MMP2 was significantly higher than that in the healthy individuals. The significant differences shown for the entire group of patients with RA were preserved when they were divided into groups according to the presence or absence of rheumatoid nodules. Furthermore, the frequency of the homozygous -1306 genotypes of MMP2 was higher in both groups than in the healthy individuals. CONCLUSION: The presence of the allelic variants of the MMP genes may be one of the genetic factors that predispose to RA in women.

[The lipid profile and psychometric assessments in patients with psychosomatic illnesses and chronic cerebral ischemia]. / Lipidnyi spektr krovi i psikhometricheskie pokazateli u patsientov s psikhosomaticheskoi patologiei i khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To explore the correlations between plasma cholesterol and triglyceride levels and psychometric assessments in patients with psychosomatic illnesses and chronic cerebral ischemia (CCI). MATERIAL AND METHODS: One hundred and ten patients (51% women, 49% men), aged from 46 to 76 years (mean 65.1 years) with CCI were examined. The study included cholesterol and triglyceride tests and a battery of tests for assessment of cognitive functions and neurotization level. RESULTS: Cholesterol levels were higher in patients with post-infarct cardiosclerosis (PICS) compared to the comparison group but did not differ from those of patients with peptic ulcer disease (PUD). Triglyceride levels were high in both psychosomatic groups, with higher levels in the patients with PICS compared to the patients with PUD. Plasma cholesterol and triglyceride levels were not correlated with assessments of cognitive functions in patients of different age. CONCLUSION: Cognitive impairment and higher level of neurotization were characteristic of patients with psychosomatic illnesses. Regression analysis has demonstrated that plasma cholesterol and triglyceride levels may be a prognostic factor for cognitive impairment.

[Analysis of genotype combinations at the polymorphic points of the promoter regions of the genes of three matrix metalloproteinases and the gene of vascular endothelial growth factor (VEGF) in patients with history of acute myocardial infarction].

AIM: To analyze the association of the promoter polymorphism of the genes of the matrix metalloproteinases (MMP) MMP2 (-1306), MMP3 (-1171), and MMP9 (-1562) and two vascular endothelial growth factor (VEGF) gene regulatory regions (-2578, +936) with the development of myocardial infarction (MI). MATERIALS AND METHODS: DNA was analyzed in 251 patients with a history of MI. Five polymorphic positions were genotyped by restrictase analysis of amplification products, by using specific primers. RESULTS: In addition to the MMP3 5A5A monogenotype, there were 4 complex genotypes that were significantly different between two analyzed groups and positively associated with acute coronary syndrome. Among them, each of two genotypes included 2 polymorphic positions; two genotypes did 3 analyzed polymorphic positions. Four complex (two-locus (n = 1), three-locus (n = 2), four-locus (n = 1) genotypes that were negatively associated with MI were also identified. CONCLUSION: These findings are evidence in favor of our assumption that the increasing number of genotypes as part of the analyzed combined genetic complexes detectable in one patient considerably enhances the clinical significance of the results of immunogenetic analysis.

[Associating of polymorphism in the promoter regions of genes of metalloproteinase (MMP2, MMP3, MMP9) with options of the clinical course of breast cancer in Russian women].

There were analyzed associating of functional polymorphism of the promoter regions of genes MMP2 C--1306T, MMP 9 C--1562 T, MMP3 5A--1171 6A in a group of healthy women and breast cancer patients in order to identify informative markers associated with the risk of developing the disease. The study included 395 DNA samples from women with breast cancer and 329 healthy women. Genotyping of polymorphisms was carried out by restriction analysis of amplification products (RFLP-analysis). Among female patients there was revealed significantly seldom a carrier of 6A6A MMP3-1117 and MMP 9-1562TT genotypes and also significantly increased the frequency of MMP3 5A6A genotype. The risk of lymph node metastasis reduced in patients with MMP9-1562CC genotype. Conversely heterozygosis at this position could be regarded as risk factor for metastasis. It was revealed associating of MMP3 5A6A genotype with the degree of malignancy.

[Genetic factors of angiogenic dysregulation in women with rheumatoid arthritis].

AIM: To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals. SUBJECTS AND METHODS: 509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C --> A, TNFA -308 G --> A, TNFA -238 G --> A; IL 1beta-31 C --> T, IL4 -590 C --> T, IL6 -174 G --> C, IL10 -1082 G --> A and IL10 -592 A --> C; VEGF -2578 C --> A, VEGF +936 C --> T; MMP 2 -1306 C --> T, MMP 9 -1562 C --> T were investigated by the restriction analysis of amplification products. RESULTS: The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1beta, IL4, IL10, IL6, and TNF-alpha genotypes. CONCLUSION: The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.

[Age and sexual changes structure of genes cytokines networks in Russian population].

OBJECTIVE: To study frequencies of occurrence of the combined genetic attributes including different variants of cytokines genotypes (TNFA, IL1B, IL4, IL6, IL10, VEGF), in different on sexual and age groups in population of Siberia Caucasoid. MATERIAL AND METHODS: Frequencies of distribution of variants of structure genes cytokines networks among 500 representatives of Siberia Caucasian population, men and women of two age groups--more younger than 35 years ("young") and 55 and more years ("elderly") are investigated. In structure of investigated genes cytokines net has come 10 variants of polymorphic sites of cytokines genes and vascular endothelial growth factor gene: TNFA-863 C --> A, TNFA-308 G --> A, TNFA-238 G --> A, IL1B-31 C --> T, IL4-590 C --> T, IL6-174 G --> C, IL10-1082 G --> A, IL10-592 A --> C, VEGF-2578 C --> A and VEGF+936 C --> T. Genotyping are carried out by restriction fragment length polymorphism method. Processing of results carried out on the basis of the original methodological approach including the complex connected computer analysis of genic circuits of various dimension. RESULTS AND CONCLUSIONS: It is shown, that the significant part of variants genes cytokines networks, which widely distributed among young people is completely absent in the "elderly" age group. Such variants disappearing with age separately for men and women are established. At the program mathematical analysis it is established, that parameters of the odds ratio achieve two-place sizes (OR = 27, p = 0,0004), that testifies to high specificity of complex genetic attributes. Presence in genome such variants of genes cytokines networks, found out in the childhood or young age, as supposed, is unfavorable personalized prognostic factors of life span of the individual.

[Cytokine gene polymorphism in type 2 diabetes mellitus in Russian women from eastern Europe].

AIM: To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women. SUBJECTS AND METHODS: 586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-alpha at positions C-863A, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA C-2578A were investigated. Restriction analysis of amplification products was applied. RESULTS: There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling. CONCLUSION: The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

[Complex of genotypes of cytokines as a genetic factor of risk of development of myocardial infarction of in Europien population of Russia men].

Cytokines as regulators of activity of inflammation play significant role in mechanisms of formation of atherosclerotic plaques and in processes of their destabilization. One of leading genetic factors determining level of their production appears to be polymorphism of cytokine genes structure at their promoter loci. We have conducted an analysis of distribution in groups of healthy male and female survivors of myocardial infarction (MI) of combined genetic signs represented as a complex of genotypes of a number of studied cytokine genes : TNF-A863C; TNF-A308G; TNF-A238G; IL1B-C511T; IL1B-C-31T; IL4-C590T; IL6-C174G; IL10A-1082G IL10-A592C. Among these homozygous combinations of cytokine genotypes characterizing a group of men who have lived up to middle and old age without development of MI there are widely represented genotypes associated with high levels of production of both cytokines with pronounced proinflammatory (IL-1) and antiinflammatory (IL-4, IL-10) activity. Absence of such multidirectional combinations in genome of patients with myocardial infarction can be considered one of genetic factors of risk of development of acute distirbances of coronary circulation.