Modern forms of interaction of the technical college with the interprises of the real sector of economics and the society of the Kurgan region

В статье раскрываются аспекты социального партнерства, реализуемого «Курганским промышленным техникумом», рассматриваются современные формы взаимодействия с предприятиями реального сектора экономики, способы формирования профессиональных компетенций обучающихся.This article deals with the aspects of social partnership, actualized by «The Kurgan industrial college»; the modern forms of interaction with enterprises of the real sector of economics and the methods of students’ professional competence formation are also considered

INTERLEUKIN 33 AND FIBROSIS: PATHOGENESIS UPDATED

Interleukin 33 (IL-33) is a member of the IL-1 family, which is widely expressed on all types of cells. IL-33 was identified as a functional ligand for the plasma membrane receptor complex, which is a heterodimer consisting of a membrane bound ST2 receptor (growth stimulating factor). IL-33 is involved in the development of immune response with predominant release of pro-inflammatory T helper type 2 cytokines. IL-33 is widely expressed on various structure-forming cells, such as epithelial, endothelial and smooth muscle cells. Increased expression of IL-33 is observed during necrosis of these cells (after tissue or cell damage), and it is released into extracellular space, and acts as an endogenous danger signal, sending a sort of warnings to neighboring cells and tissues. Recently, many studies have shown that IL-33 can participate in development and progression of fibrosis in various organs. However, it exerts anti-inflammatory effects upon development of other diseases. This review will discuss biological characteristics of IL-33 and a role of the IL-33/ST2 signaling pathway in the development of fibrosis

CYTOKINE PROFILE IN VISCERAL OBESITY AND ADVERSE CARDIOVASCULAR PROGNOSIS OF MYOCARDIAL INFARCTION

Presence of myocardial infarction in patients with obesity can lead to an uncontrolled increase in proinflammatory cytokines and unfavorable course of the pathological process. Objective: to study the relationship of key inflammatory factors and the development of complications at different terms after myocardial infarction in patients with visceral obesity. The study involved 94 men with myocardial infarction. Visceral obesity was diagnosed by multi-slice computed tomography (LightspeedVCT 64 ,General Electric,USA). On the 1st and 12th day of hospitalization, we determined serum concentrations of interleukins (TNFα, IL-1β, IL-6, IL-8 IL-10 and IL-12), and C-reactive protein. Adverse cardiovascular events were documented during the next year. The most informative indicators were identified by a stepwise logistic regression analysis. In patients with myocardial infarction an imbalance of cytokine profile revealed, i.e., an increase in proinflammatory markers (TNFα, IL-1β, IL-6, IL-8, IL-12, CRP), along with decrease in IL-10, being more pronounced in cases of visceral obesity. Among the studied markers, closest relationship was observed between visceral obesity and serum concentrations of IL-6 and CRP. Over the year, adverse cardiovascular events proved to be more frequent in patients with visceral obesity. Post-infarction complication risk was associated with higher concentrations of IL-6, IL-12 and IL-10 deficiency. Hence, development of adverse cardiovascular events within a year after myocardial infarction is more typical to the patients with visceral obesity, and is accompanied by activation of proinflammatory cytokines and IL-10 deficiency

Pharmacogenetic Aspects of Type 2 Diabetes Treatment

In this article, we analyze the role of different variants of the KCNJ11, TCF7L2, SLC22A1, SLC22A3, CYP2C9, CYP2C8, PPARγ genes polymorphisms in efficacy of diabetes mellitus pharmacotherapy. T allele of the KCNJ11 rs2285676 gene polymorphism and G allele of KCNJ11 rs5218 gene polymorphism are associated with the response to IDPP-4 therapy; the presence of KCNJ11 gene rs5210 polymorphism A allele is a predictor of poor response. The effect of rs7903146 polymorphism of TCF7L2 gene was evaluated on the response to treatment of patients taking linagliptin. Linagliptin significantly reduced HbA1c levels for all three rs7903146 genotypes (CC: –0.82 %; CT: –0.77 %; TT: –0.57 %). A significantly smaller effect of therapy was observed with the genotype with ТТ. The rs622342 polymorphism of SLC22A1 gene was studied in effectiveness of metformin. The researches demonstrated that carriers of variant AA had an average decrease of HbA1c of 0.53 %, heterozygous – decrease of 0.32 %, and carriers of a minor variant of SS had an increase of 0.2 % in the level of HbA1c. A significant effect of CYP2C9 polymorphisms on the pharmacokinetic parameters of PSM was noted. When studying the kinetics of glibenclamide, it was found that carriage of the allele *2 significantly reduces glibenclamide metabolism: homozygous carriers had clearance 90 % lower than homozygous carriers of the wild variant. The studies confirmed the association of the allelic variants of Thr394Thr and Gly482Ser of PPARγ gene with higher efficacy of the rosiglitazone. The data obtained from the analysis of the association of the Pro12Ala polymorphism of PPARγ gene and the response to therapy is contradictory. Thus the personalized approach, based on the knowledge of polymorphism options, will allow choosing the most effective drug with transparent kinetics for each individual patient

Comparative evaluation of the expression of enzymes of the ceramide <i>de novo</i> synthesis pathway in cardiac adipose tissue and blood vessels of cardiovascular patients

Aim. To compare the expression of enzymes of the ceramide de novo synthesis pathway in cardiac adipose tissue (AT) and blood vessels of patients with coronary artery disease (CAD) and acquired heart defects.Material and methods. The study included 20 patients with CAD and 18 patients with aortic stenosis/regurgitation. Biopsies of subcutaneous, epicardial, perivascular AT (SCAT, EAT, PVAT, respectively) were obtained during surgery. Quantitative PCR test was used to evaluate the gene expression of de novo ceramide synthesis enzymes (serine palmitoyltransferase C1 and C2: SPTLC1, SPTLC2; ceramide synthase 1-6: CERS1-6; dihydroceramide desaturase: DEGS1). Statistical analysis was performed using GraphPad Prism 8 (GraphPad Software).Results. Patients with CAD were characterized by a higher level of mRNA SPTLC1 in SCAT and EAT, SPTLC2, CERS1, producing C18 ceramides, CERS5 and CERS6, generating C14-C16 ceramides in EAT, CERS2 — in SCAT, producing long-chain ceramides C20-C24, CERS4, synthesizing very long-chain ceamides C18-C20. In PVAT, a high expression of CERS4 and CERS3, which synthesizes very long-chain ceramides C26 and higher, was revealed. DEGS1 expression was highest in SCAT and EAT. In patients with heart defects, there was a high expression of CERS3 in PVAT, CERS4 in EAT and PVAT, DEGS1 in EAT. The mRNA level of SPTLC1 in SCAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and 5 in EAT, DEGS1 in SCAT and EAT among patients with CAD was higher than in the comparison group.Conclusion. Regional fat depots of the heart differed in the level of expression of enzymes of the ceramide de novo synthesis pathway. The results obtained indicate the activation of ceramide synthesis along this pathway in predominantly epicardial adipocytes in coronary pathology, which may contribute to the accumulation of long-chain ceramides in the AT of this localization

Initiator Elements Function to Determine the Activity State of BX-C Enhancers

A >300 kb cis-regulatory region is required for the proper expression of the three bithorax complex (BX-C) homeotic genes. Based on genetic and transgenic analysis, a model has been proposed in which the numerous BX-C cis-regulatory elements are spatially restricted through the activation or repression of parasegment-specific chromatin domains. Particular early embryonic enhancers, called initiators, have been proposed to control this complex process. Here, in order to better understand the process of domain activation, we have undertaken a systematic in situ dissection of the iab-6 cis-regulatory domain using a new method, called InSIRT. Using this method, we create and genetically characterize mutations affecting iab-6 function, including mutations specifically modifying the iab-6 initiator. Through our mutagenesis of the iab-6 initiator, we provide strong evidence that initiators function not to directly control homeotic gene expression but rather as domain control centers to determine the activity state of the enhancers and silencers within a cis-regulatory domain

Оценка биосовместимости и антимикробных свойств биодеградируемых сосудистых протезов различного полимерного состава с атромбогенным и противомикробным лекарственным покрытием

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p &lt; 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p &lt; 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p &lt; 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.Создание сосудистых протезов с атромбогенным и противомикробным покрытием является очень актуальным направлением.Цель. Оценить биосовместимость и антимикробные свойства биодеградируемых сосудистых протезов различного полимерного состава с атромбогенным и противомикробным лекарственным покрытием.Материалы и методы. Модифицирование поверхности биодеградируемых сосудистых протезов проведено через комплексообразование с поливинилпирролидоном, который был полимеризован с поверхностью полимерных каркасов посредством ионизирующего излучения в 10 и 15 кГр. Оценены физико-механические свойства и гемосовместимость. Проведены бактериологические исследования с использованием тест-штаммов грамотрицательных и грамположительных микроорганизмов: Klebsiella pneumoniae spp. ozaena № 5055, Escherichia coli ATCC 25922, Staphylococcus aureus АTCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa ATCC27853.Результаты. Отмечено отсутствие влияния модифицирующих манипуляций с участием ионизирующего излучения на физико-механические характеристики биодеградируемых протезов. Сосудистые протезы с атромбогенным и противомикробным покрытием проявляли атромбогенные свойства при контакте с кровью, в 5–7 раз снижая агрегацию тромбоцитов (p &lt; 0,05). Также на поверхности матриксов с лекарственным покрытием выявлено снижение адгезии и индекса деформации тромбоцитов (для протезов на основе PCL последний уменьшился в 1,9 раза относительно немодифицированных аналогов (p &lt; 0,05), на основе PHBV/PCL – в 1,3 раза относительно немодифицированных аналогов и в 1,5 раза относительно матриксов с поливинилпирролидоном (p &lt; 0,05). При проведении бактериологических исследований обнаружено местное ингибирующее действие в месте наложения на агар матриксов с катионным амфифилом. Зон задержки роста не выявлено. Полимерный состав матриксов и использованная доза ионизирующего излучения не привели к разнице в бактериостатических свойствах матриксов с амфифилом.Заключение. Проведение полного цикла модифицирования поверхности полимерных биодеградируемых протезов на основе как PCL, так и композиции РHBV/PCL, привело к значимому повышению атромбогенных и противомикробных свойств протезов и не ухудшило физико-механические и биосовместимые свойства разрабатываемых конструкций

Взаимосвязь кальциноза коронарных артерий и локальных жировых депо у пациентов с ишемической болезнью сердца

Highlights. Taking into account the connection between the increase in the volume of myocardial adipose tissue and vessels with massive calcification of the coronary arteries in coronary heart disease, morphometry of epicardial and perivascular adipose tissue during routine tomographic examinations can be considered as a non-invasive technique for determining a surrogate marker of severe coronary lesion.Aim. To evaluate the relationship of coronary artery calcification (CA) and morphometric parameters of local fat depots in patients with coronary heart disease (CHD).Methods. 125 patients with stable coronary artery disease aged 59±8.9 years were examined. Visualization of local fat depots, abdominal fat depots, and coronary calcification (CC) was performed using multislice computed tomography with subsequent post-processing of images on the Siemens Leonardo workstation (Germany). Non-contrast magnetic resonance imaging of the heart was used to determine the EAT thickness.Results. Coronary calcification was detected in 95.2% of the examined patients with coronary artery disease (n = 119). There were higher indices of the EAT thickness of the right and left ventricles in case of massive CC, the thickness of the pericardial adipose tissue at the level of the trunk of the left coronary, anterior descending, circumflex arteries, and increased morphometry indices of the abdominal fat depot in comparison with the patients who had moderate and medium CC.Conclusion. An increase in the volume of adipose tissue of the myocardium and vessels in CAD is associated with massive calcification, which is reflected in the pathogenetic “adipovascular” continuum, characterized by the stimulation of adipogenesis against the background of atherocalcinosis of the coronary arteries. Morphometry of epicardial and perivascular adipose tissue during routine tomographic studies is a non-invasive technique for determining a surrogate marker of severe coronary lesions.Основные положения. С учетом обнаруженной ассоциации увеличения объема жировой ткани миокарда и сосудов с массивным кальцинозом коронарных артерий при ишемической болезни сердца морфометрия эпикардиальной и периваскулярной жировой ткани при рутинных томографических исследованиях может быть рассмотрена в качестве неинвазивной методики определения суррогатного маркера тяжелого поражения коронарного русла.Цель. Оценить взаимосвязь кальциноза коронарных артерий (КА) и морфометрических показателей локальных жировых депо у пациентов с ишемической болезнью сердца (ИБС).Материалы и методы. Обследовано 125 больных стабильной ИБС в возрасте 59 (53,0; 66,0) лет. Визуализация локальных жировых депо сосудов, абдоминального жирового депо и кальциноза КА выполнена методом мультиспиральной компьютерной томографии с последующей постпроцессинговой обработкой изображений на мультимодальной рабочей станции Leonardo (Siemens, ФРГ). Толщина эпикардиальной жировой ткани определена методом бесконтрастной магнитно-резонансной томографии сердца.Результаты. Кальциноз КА выявлен у 95,2% обследованных пациентов с ИБС (n = 119). При массивном кальцинозе отмечены более высокие показатели толщины эпикардиальной жировой ткани правого и левого желудочков, толщины перикардиальной жировой ткани на уровне ствола левой коронарной, передней нисходящей, огибающей артерий и повышенные показатели морфометрии абдоминального жирового депо в сравнении с пациентами с умеренным и средним кальцинозом КА.Заключение. При ИБС увеличение объема жировой ткани миокарда и сосудов ассоциировано с массивным кальцинозом, что находит отражение в патогенетическом адиповаскулярном континууме, характеризующимся стимулированием адипогенеза на фоне атерокальциноза КА. Морфометрия эпикардиальной и периваскулярной жировой ткани при рутинных томографических исследованиях является неинвазивной методикой определения суррогатного маркера тяжелого поражения коронарного русла

Chromosomal organization at the level of gene complexes

Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development. Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex. The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within gene complexes and how they can be characterized

Impact of recipient-related factors on structural dysfunction of xenoaortic bioprosthetic heart&nbsp;valves

Olga Barbarash, Natalya Rutkovskaya, Oksana Hryachkova, Olga Gruzdeva, Evgenya Uchasova, Anastasia Ponasenko, Natalya Kondyukova, Yuri Odarenko, Leonid Barbarash Federal State Budgetary Scientific Institution Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia Objective: To analyze the influence of recipient-related metabolic factors on the rate of structural dysfunction caused by the calcification of xenoaortic bioprostheses. Materials and methods: We retrospectively analyzed clinical status, calcium&ndash;phosphorus metabolism, and nonspecific markers of inflammatory response in bioprosthetic mitral valve recipients with calcific degeneration confirmed by histological and electron microscopic studies (group 1, n=22), and in those without degeneration (group 2, n=48). Results: Patients with confirmed calcification of bioprostheses were more likely to have a severe clinical state (functional class IV in 36% in group 1 versus 15% in group 2, P=0.03) and a longer cardiopulmonary bypass period (112.8&plusmn;18.8 minutes in group 1 versus 97.2&plusmn;23.6 minutes in group 2, P=0.02) during primary surgery. Patients in group 1 demonstrated moderate hypovitaminosis D (median 34.0, interquartile range [21.0; 49.4] vs 40 [27.2; 54.0] pmol/L, P&gt;0.05), osteoprotegerin deficiency (82.5 [44.2; 115.4] vs 113.5 [65.7; 191.3] pg/mL, P&gt;0.05) and osteopontin deficiency (4.5 [3.3; 7.7] vs 5.2 [4.1; 7.2] ng/mL, P&gt;0.05), and significantly reduced bone-specific alkaline phosphatase isoenzyme (17.1 [12.2; 21.4] vs 22.3 [15.5; 30.5] U/L, P=0.01) and interleukin-8 levels (9.74 [9.19; 10.09] pg/mL vs 13.17 [9.72; 23.1] pg/mL, P=0.045) compared with group 2, with an overall increase in serum levels of proinflammatory markers. Conclusion: Possible predictors of the rate of calcific degeneration of bioprostheses include the degree of decompensated heart failure, the duration and invasiveness of surgery, and the characteristics of calcium&ndash;phosphorus homeostasis in the recipient, defined by bone resorption and local and systemic inflammation. The results confirm the hypothesis that cell-mediated regulation of pathological calcification is caused by dysregulation of metabolic processes, which are in turn controlled by proinflammatory signals. Keywords: bioprostheses, calcium&ndash;phosphorus metabolism, inflammation, calcificatio