GENE POLYMORPHISM ANALYSIS OF CHEMOKINES, CHEMOKINE RECEPTORS, ACUTE PHASE PROTEINS, AND CD14 IN FEMALE OBESITY DEVELOPMENT

In the present study, we have investigated frequency of genotypes and functional alleles of genes encoding chemokines (CXCL12 rs1801157, CCL2 rs1024611), chemokine receptors (CCR5 del32, CX3CR1 rs3732378), acute phase proteins SAA rs1136743, and CD14 rs2569190 polymorphisms among Tatar obese or overweight women from the Republic of Bashkortostan.The group of patients comprised unrelated women with obesity (BMI ≥ 30 kg/m2, n = 225), females with overweight (BMI 25.0-29.9 kg/m2, n = 184), and control group of women (n = 327) BMI < 25.0 kg/m2. Genotyping was performed by PCR-RFLP analysis. Patients and controls differed in such parameters as body weight (p = 0.00001), BMI level (p = 0.001) and fasting glucose level (p = 0.0001).An association was revealed between obesity and AG-AA genotypes (p = 0.007) and A allele (p = 0.003) of polymorphic locus rs3732378 of CXCR1 gene, as well as TT genotype (p = 0.027) and T allele (p = 0.021) of polymorphic locus rs1136743 of SAA gene. It has been shown that the AA genotype of polymorphic locus rs3732378 of the CX3CR1 gene is associated with increased body weight (p = 0.002) and elevated BMI (p = 0.018); the GG genotype of polymorphic locus rs1024611 of the CCL2 gene is associated with elevated fasting glucose level (p = 0.001).As based on clinical and genetic data and using logistic regression, some statistically significant differences were revealed, which allow to predict development of obesity in Tatar women

Immunoglobulins and predicted mortality in clinical course of concomitant HIV and TB infection

A search for prognostic markers of HIV and tuberculosis coinfection (HIV/TB), especially in case of Mycobacterium tuberculosis multidrug resistance (MDR MBT) associated with low rates of TB eradication, is of relevance in connection with the problem of choosing adequate anti-TB therapy which is able to decrease mortality. 113 HIV/TB patients aged 24 to 58 years were examined: 70 males and 43 females hospitalized at the Novokuznetsk TB Clinic during the 2017—2019 period. MDR MBT (concomitant resistance to Isoniazid and Rifampicin) was found in 50 patients (12 patients with MDR MBT had additional resistance to Fluoroquinolones) aged 24 to 54 years — 31 males and 19 females. The control group consisted of 49 healthy individuals aged 27 to 72 years (26 females and 23 males) lacking focal and systemic infections with moderately pronounced age-related changes. In plasma samples, concentration of total (non-specific) immunoglobulins of classes E, M, G, A (including secretory immunoglobulin A, sIgA) were measured by using enzyme-linked immunosorbent assay. Data statistical processing was performed by using licensed software packages InStatII, Microsoft Excel, IBM SPSS Statistics 22. An extended range of individual variability in count of peripheral blood CD4 lymphocytes was revealed both among non-survivor and survivor patients with HIV/TB examined, being a drawback of using such parameter as lethality predictor. It was found that the serum level of total IgE, IgM, IgG, IgA and sIgA in patients with HIV/ TB was higher than that one in control group, whereas in non-survivor vs. survivor patients the concentration of IgE and sIgA was elevated. The coefficient of disease outcome prediction (CP) for patients with HIV/TB and MDR MBT was calculated being equal to the ratio of the multiplication of serum concentration of IgE, IgM, IgA and secretory IgA to CD4 lymphocyte count (CP = IgE x IgM x IgA x sIgA/CD4). CP higher than 200 was detected in 77% non-survivor and 6% of survivor patients. The relative risk of death with CP > 200 was very high (OR = 56.7, p < 0.0001) being 8.5 times higher than that one upon CD4 < 200 (OR = 6.7, p = 0.0237). A positive correlation between CP and lethal outcome was more valuable than that of CD4. The data presented allow us to propose CP for clinical use as an effective prognostic criterion for HIV/TB with MDR MBT

Анализ генетических факторов, вовлеченных в развитие хронической обструктивной болезни легких: оценка вклада генов биотрансформации ксенобиотиков и антиоксидантной защиты

Summary. The purpose of this study was to investigate a role of xenobiotic biotransformation and antioxidant defense gene polymorphism for development of chronic obstructive pulmonary disease (COPD). Polymorphism of these genes encoding 22 enzymes was investigated in 361 COPD patients and 585 healthy individuals at Republic of Bashkortostan. Our results indicate that CYP1А1 (2455A>G, 3801T>C), CYP1А2 (–163С>А), CYP2F1 (c.14_15insC), CYP2J2 (–76G>T), CYP2S1 (13106C>T, 13255A>G), GSTM1 (Del), GSTT1 (Del), CAT (–1167C>T), GPX1 (Pro197Leu), NQO1 (609C>T) genotypes and allele frequencies were similar in COPD and healthy control groups. A significant association have been determined between CYP1А2 (–2464delT), CYP1B1 (4326C>G), CYP2A6 (deletion), GSTP1 (Ile105Val, Ala114Val), CAT (–262 C>T), NQO1 (465C>T), SOD1 (c.239+34A>C), SOD3 (Arg213Gly), UGT2B7 (802C>T) gene loci and COPD.Oxidative stress is the crucial pathogenic factor of COPD. An increased risk of oxidative stress is associated with certain alleles of genes encoding cytochrome P450, glutathione S–transferase, superoxide dismutase, catalase, and others. We demonstrated that polymorphism of xenobiotic biotransformation and antioxidant defense genes significantly influences the individual response to toxic components of tobacco smoke and is associated with COPD in residents of Bashkortostan

Contribution of health care resources and socio-economic factors to the dynamics of the tuberculosis epidemic in Kuzbass

The interaction of a complex of socio-economic and medical resource-intensive factors that influence the formation of the situation with tuberculosis in the Kuzbass is considered. The preliminary, objectified selection of indicators from a large set of registered parameters in the epidemic monitoring system allows to prepare an objective description of the epidemic picture in the region for the subsequent in-depth multi-factor analysis of the situation. Determining the nature and power of the influence of social factors on the situation with tuberculosis and the types of health care costs can allow the creation of models for the regression of the epidemic and the management of this process.Рассмотрено взаимодействие комплекса социально-экономических и медицинских ресурсоемких факторов, оказывающих влияние на формирование ситуации с туберкулезом в Кузбассе. Предварительный объективизированный отбор показателей из большого набора регистрируемых параметров в системе эпидемического мониторинга позволяет подготовить объективное описание эпидемической картины в регионе для последующего углубленного многофакторного анализа ситуации. определение характера и силы влияния социальных факторов на ситуацию с туберкулезом и видов расходов на здравоохранение может позволить создать модели регресса эпидемии и управления этим процессом

Role of PI3K/AKT/mTOR signaling pathway and sirtuin genes in chronic obstructive pulmonary disease development

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system which develops as a result of a complex interaction of genetic and environmental factors closely related to lifestyle. We aimed to assess the combined effect of the PI3K/AKT/mTOR signaling pathway (PIK3R1, AKT1, MTOR, PTEN) and sirtuin (SIRT1, SIRT3, SIRT6) genes to COPD risk. SNPs of SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251), AKT1 (rs2494732), PIK3R1 (rs10515070, rs831125, rs3730089), MTOR (rs2295080, rs2536), PTEN (rs701848, rs2735343) genes were genotyped by real-time polymerase chain reaction (PCR) among 1245 case and control samples. Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and smoking pack-years. Significant associations with COPD were identified for SIRT1 (rs3818292) (P = 0.001, OR = 1.51 for AG), SIRT3 (rs3782116) (P = 0.0055, OR = 0.69) and SIRT3 (rs536715) (P = 0.00001, OR = 0.50) under the dominant model, SIRT6 (rs107251) (P = 0.00001, OR = 0.55 for СT), PIK3R1: (rs10515070 (P = 0.0023, OR = 1.47 for AT), rs831125 (P = 0.00001, OR = 2.28 for AG), rs3730089 (P = 0.0007, OR = 1.73 for GG)), PTEN: (rs701848 (P = 0.0015, OR = 1.35 under the log-additive model), and rs2735343 (P = 0.0001, OR = 1.64 for GC)). A significant genotype-dependent variation of lung function parameters was observed for SIRT1 (rs3818292), SIRT3 (rs3782116), PIK3R1 (rs3730089), and MTOR (rs2536). Gene-gene combinations that remained significantly associated with COPD were obtained; the highest risk of COPD was conferred by a combination of G allele of the PIK3R1 (rs831125) gene and GG of SIRT3 (rs536715) (OR = 3.45). The obtained results of polygenic analysis indicate the interaction of genes encoding sirtuins SIRT3, SIRT2, SIRT6 and PI3KR1, PTEN, MTOR and confirm the functional relationship between sirtuins and the PI3K/AKT/mTOR signaling pathway

МОЛЕКУЛЯРНЫЕ МАРКЕРЫ ПРОГНОЗА ПРИ РАКЕ МОЧЕВОГО ПУЗЫРЯ

Bladder cancer (BC) remains a current problem in oncourology. Despite that bladder cancer risk factors have been studied and described in the literature, new molecular and genetic mechanisms have been identified that predisposes to the disease development. There are numerous cellular processes involve in BC pathogenesis. The less-aggressive, non-invasive slow progressing bladder cancer types are defined by Ras-MAPK system activation. Tumors that are more aggressive and have low cancer-specific survival rate are characterized by changes in retinoblastoma genes and p53. Attempts are made to develop prognostic tests to predict tumor behavior, targeted treatment. perspectively, BC patients will be treated using molecular genetic markers allowing the accurate prediction of the patient’s tumor behavior and fitting the treatment tactics on the individual basis.Рак мочевого пузыря (РМП) остается актуальной проблемой онкоурологии. Несмотря на то, что факторы риска РМП изучены и описаны в литературе, выявляются новые молекулярно-генетические механизмы, предрасполагающие к развитию заболевания. В патогенез РМП вовлечено множество клеточных процессов. Менее агрессивные, неинвазивные, медленно прогрессирующие формы РМП характеризуются активацией системы Ras-mitogen-activated protein kinase (Ras-MAPK). Более агрессивные опухоли с низкой раковоспецифической выживаемостью, характеризуются изменениями в генах ретинобластомы и p53. Предпринимаются попытки разработать прогностические тесты, предсказывающие развитие опухоли, выбор тактики лечения. В перспективе в лечении пациентов РМП будут использоваться молекулярно-генетические маркеры, позволяющие достоверно предсказать поведение опухоли у пациента и выбрать индивидуальную тактику лечения

IL-8 CHEMOTACTIC FACTOR IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA AND FEATURES OF IL-8 GENE POLYMORPHISM (251 T/А)

Fifty-four patients with different clinical course (acute and protracted forms) of community-acquired pneumonia (CAP), were studied for interleukin-8 (IL-8) contents in blood serum and its production levels (spontaneous and PHA-stimulated), depending on the IL-8 gene polymorphism at the 251 T → A locus. Employing the data about immunogenetic differences, we have shown some associations between IL-8 production, depending on clinical outcome (adequate responders vs poor response to medication in acute pneumonia). Both in acute and chronic forms of pneumonia, poor response to therapy was associated with decreased reserve capacity of IL-8 production, and a downward trend of cytokine concentration in blood serum. It was revealed that the CAP patients with poor response to treatment exhibit deficient production of IL-8 associated with homozygous AA genotype at the -251 T/A locus of IL-8 gene

Application of liposomal systems derived from vegetable lecithins in food technologies

Liposomal systems are widely used in Medicine, Pharmacy and Cosmetology as delivery systems for transdermal, oral, parenteral administration of certain medicinal and biologically active substances into the body. This is due to unique properties of liposomes formed by natural phospholipids, amphiphilic molecules of which are able to form associates spontaneously in the aqueous medium, but also in the form of bilayers. The article deals with the classification of liposomes according to the structure; it has been also noted that the liposomes formed by natural phospholipids, are characterized by high biocompatibility, isotropy and thermoreversibility. An egg yolk is the richest source of natural phospholipids and it contains up to 78 % of phosphatidylcholines.However, isolation of phospholipids from plant sources such as soy, sunflower and rapeseed, is more profitable economically, and therefore more appropriate for the use in food technology. It has been shown that liposomal systems of plant origin have broad application in food technologies as food additives, enzyme encapsulators, bacteriocins and stabilizers of labile nutrients. However, poorly studied mechanism of liposomal formation and the problem of ensuring the stability of liposomal systems during storage are limiting factors of their wide use in food technologies, since under the influence of various factors their structure may be disrupted and, as a result, active substance can come out into the external environment.Thus, studies aimed at identifying regularities and mechanisms of formation of highly stable liposomal systems derived from phospholipids contained in plant lecithins are considered to be relevant

A COMPARATIVE EVALUATION OF THE STABILITY OF APPLE ACID COMPLEXES AND SOYA OIL PHOSPHOLIPIDS WITH IRON AND COPPER IONS

The effectiveness of hydration, which is the first stage of refining vegetable oils, depends primarily on the ability of the hydrating agent to convert nonhydratable phospholipids into their hydratable forms. The latter are complex compounds with polyvalent metal ions. Iron and copper ions have a negative effect on the quality of hydrated oils and the resulting lecithins, as their resistance to oxidation reduces. Malic acid solutions can be used as a hydrating agent.The complexation process of malic acid with iron and copper ions was studied by potentiometric titration. It was established that the introduction of iron and copper ions into the malic acid solution led to a decrease in pH values, which indicated the presence of complexation in these systems. It was established that malic acid with iron ions formed more stable complexes compared to copper ions. It was shown that the stability of complexes of malic acid with iron ions of [MeL2] type and copper ions of [MeL] type, formed in the system in the maximum amount, was significantly higher than the stability of the complex compounds of phosphatidylserines, phosphatidylinositols and phosphatidic acids with these ions. Comparison of the stability constants of complexes of iron and copper ions with succinic and malic acids showed that «Me – malic acid complexes» were more stable. Thus, the obtained results allow us to recommend aqueous solutions of malic acid as a hydrating agent for hydration of phospholipids from vegetable oils