Association between Arg753Gln (rs574308) polymorphism of the Toll-like receptor 2 (TLR2) gene and the risk of pulmonary sarcoidosis among the residents of Karelia”

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

Design of Pre-Dumping Ring Spin Rotator with a Possibility of Helicity Switching for Polarized Positrons at the ILC

The use of polarized beams enhance the possibility of the precision measurements at the International Linear Collider (ILC). In order to preserve the degree of polarization during beam transport spin rotators are included in the current TDR ILC Lattice. In this report some advantages of using a combined spin rotator/spin flipper are discussed. A few possible lattice designs of spin flipper developed at DESY in 2012 are presented.Comment: Talk presented at the International Workshop on Future Linear Colliders (LCWS15), Whistler, Canada, 2-6 November 201

FOXP3, IL2R, CD8A and RORγ gene expression in peripheral blood leukocytes of healthy people and patients with arterial hypertension

Impaired balance of T regulatory and T effector lymphocytes has recently been considered as an important pathogenetic link in arterial hypertension (AH). There are, however, contradictory literature data about contents of these cells in the patients with hypertension, or obtained in experimental animal models of induced hypertension. Most results about changed patterns of immune cells in cardiovascular diseases were obtained by means of flow cytometry. There are also some works on expression of genes encoding surface and cytoplasmic differentiation antigens of immune cells in the patients with cardiovascular pathologies. These results coincide with the data obtained with flow cytometric techniques. Purpose of the present study was to analyze of the levels of gene transcripts encoding differentiation markers of regulatory (FOXP3, IL2R) T cells, effector T subpopulations (T helpers 17 (RORγ), and CD8 lymphocytes (CD8A) in healthy subjects and the patients with arterial hypertension (stages I-II). We examined healthy individuals (40 people, 20 men and 20 women), 27 patients with hypertension who did not receive antihypertensive therapy (14 men and 13 women), 26 hypertensive patients taking β-adrenergic receptor blockers (metoprolol or bisoprolol), including 12 men and 14 women. The relative levels of transcripts in peripheral blood leukocytes were assessed by real-time RT-PCR. It was shown that the transcriptional activity of FOXP3, IL2R, RORγ, and CD8A genes in peripheral blood leukocytes of the diseased people was significantly higher than in healthy individuals (p < 0.01). This finding may indicate an increased number of circulating T regulatory lymphocytes, CD8+ cells and T helpers 17 in hypertensive patients, and activation of T cell immunity in these patients. There were no statistically significant gender differences in FOXP3, IL2R, RORγ and CD8A gene expression in leukocytes, both in the group of healthy people and in hypertensive patients. The patients receiving cardioselective β-adrenergic receptor blockers (metoprolol and bisoprolol) exhibited lower expression of these genes, thus, probably, indicating antiinflammatory and immunomodulatory properties of these drugs

THE RESULTS OF THE STUDY OF VARIETIES OF ALFALFA IN THE CENTRAL-CHERNOZEM ZONE

Three-year study of one hundred world collection of alfalfa was conducted in Central Black-Earth zone of Russia. The varieties of Medicago × varia ‘Zheltogibridnaya 99’, ‘Flora 2’, ‘Karlygash’ and ‘№ 152’ (hybrid ‘Severnaya hybridnaya’ בAugune II’) were recommended for breeding programs. The most variable were character of seed production, productivity of green mass and hay yield productivity; character of foliage and the intensity of regrowth of plants on the 20-th day after spring regrowth had medium variability. The height before the first mowing and height in the phase of full flowering had low variability. There was a significant correlation between the yield of green mass and hay, the yield of green mass and intensity of regrowth and a weak negative correlation between the yield of green mass and seed yield

Expression of DROSHA and DICER genes in peripheral blood leukocytes in lung sarcoidosis

Aim. To study the expression level of the genes DROSHA and DICER in peripheral blood leukocytes (PBL) of patients with sarcoidosis of the lungs Materials and methods. The study included 32 patients diagnosed with persistent lung sarcoidosis (mean age 41.56±1.27 years) and 36 healthy donors (control; mean age 42.79±1.95 years). The level of expression of messenger RNA (mRNA) of the genes DROSHA and DICER were determined in PBL of healthy donors and patients with sarcoidosis of the lung by polymerase chain reaction in real time. Results. As a result of the conducted researches it is established that the level of drosha gene expression in PBL patients with sarcoidosis of lungs is significantly reduced in comparison with the control (

DICER and DROSHA gene expression in peripheral mononuclear blood cells from rheumatoid arthritis patients under methotrexate therapy

The aim of this research was studying the level of DROSHA and DICER genes expression in peripheral mononuclear blood cells (PBMC) in rheumatoid arthritis (RA) patients under methotrexate therapy. Materials and methods. 82 people (from 45 to 70 years) enrolled in this study were divided into 3 groups (the first one - healthy donors (n=33 median age 49.93±1.87); the second group - rheumatoid arthritis patients without any therapy (n=15; median age 57.28±15.18) and the third group (n=34; median age 60.88±9.02) - rheumatoid arthritis patients who treated at least 4 weeks with methotrexate therapy (10-20 mg/week). The DICER and DROSHA genes expression level was determined by real-time PCR. Results. The number of DICER gene transcripts in PBMC in rheumatoid arthritis patients without therapy as in RA patients treated with methotrexate was reduced in comparison with the healthy donors (p0.05 respectively). The level of DROSHA gene expression in PBMC was not significantly different in all groups enrolled in this study (p>0.05). Conclusion. Our findings suggest that that the DICER gene expression level in perifheral mononuclear blood cells decreased with the development of rheumatoid arthritis. Methotrexate doesn’t influence on the mRNA level of this gene

Macrophage polarization in sarcoidosis

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the formation of epithelioid cell granulomas, multisystem lesions with a certain frequency of involvement of various organs, mainly the lungs (up to 90% of cases). Over the past decade, significant progress has been made in understanding the pathogenesis of sarcoidosis, the important role of immunological, genetic and environmental factors in the development of this pathology has been established. It is believed that the leading mechanism in the pathogenesis of sarcoidosis is the aberrant activation of the innate and adaptive immune response to unidentified antigen(s), which leads to the development of granulomatous inflammation and the formation of granulomas. However, despite the huge number of studies that has been carried out, the mechanisms and signaling pathways that control the development of the inflammatory process during the formation of granulomas and the progression of pathology have not been fully determined.This literature review examines the important role of various cytokines and T helper subpopulations in sarcoidosis. Particular attention is paid to the cells of innate immunity – macrophages in the pathogenesis of this disease. These cells play a key role in the formation of sarcoid granulomas and in the pathogenesis of sarcoidosis. The macrophage population is characterized by plasticity and functional heterogeneity. In response to various signals from the microenvironment, macrophages are able to acquire certain phenotypes. The review considers the issues of polarization of macrophages, changes in the phenotype of these cells to subpopulations M1 (M1 phenotype; classically activated; pro-inflammatory) and M2 (M2 phenotype; alternatively activated, anti-inflammatory). These two cell populations are characterized by the expression of different markers on their surface, which allow these cells to differentiate from each other. The analysis of literature data on the levels of key polarizing cytokines for macrophages and cells-producers of these cytokines that patients with sarcoidosis have, in acute and chronic course of the disease, was carried out.Important aspects of the alternative activation of macrophages of the M2 phenotype and their division into subtypes: M2a, M2b, M2c, M2d are noted. The features of various subtypes’ activation of macrophages in this granulomatosis and their importance in the development and progression of pathology are considered. Studying the role of macrophages’ phenotypes, understanding the mechanisms by which the phenotypes of these cells are activated and modulated in various microenvironmental conditions, can contribute to the development and implementation into clinical practice of new therapeutic approaches for the treatment of sarcoidosis and many other forms of pathologies

Clinical and immunological features of chronic odontogenic maxillary sinusitis, depending on the length of the flow

The study involved 29 patients with an established diagnosis of chronic odontogenic maxillary sinusitis, oro-antral fistula: an assessment of clinical and immunological parameters and identified a number of features, depending on the duration of the disease.Обследовано 29 пациентов с установленным диагнозом хронический одонтогенный верхнечелюстной синусит, оро-антральное соустье: проведена оценка клинико-иммунологических показателей и выявлены ряд особенностей, в зависимости от длительности заболевания

Роль полиморфизма генов в чувствительности к саркоидозу легких

Authors of this review described gene polymorphism  involved in the development  of the immune  response in sarcoidosis. Gene background could determine not only the subject’s susceptibility to sarcoidosis, but also a clinical course of the disease. Currently,  allele variants that could be used as prognostic markers to reveal subjects susceptible to sarcoidosis and to predict a clinical course of sarcoidosis are investigated. Published data on a relationship between the carriage of certain allele variants and the subject’s susceptibility to sarcoidosis are scarce and controversial. Nevertheless, those data could be used to detect potential goals for targeted therapy of sarcoidosis and to develop measures to prevent this disease.В обзоре обобщены  сведения  о роли полиморфных вариантов  генов в формировании иммунного  ответа при саркоидозе.  Обозначены основные  гены-кандидаты, однонуклеотидные замены,  которые могут оказывать  модулирующее действие на развитие иммунных реакций при данной патологии, а также определять не только восприимчивость людей к возникновению саркоидоза  легких, но и оказывать влияние  на клинические характеристики течения заболевания

Анализ ассоциации полиморфизма Asp299Gln (rs 4986790) и Thr399Ile (rs 4986791) гена TLR4 с риском развития саркоидоза легких (на примере жителей Карелии)

The objective: to analyze the association of the Asp299Gln (rs 4986790) and Thr399Ile(rs 4986791) polymorphisms of the TLR4 gene with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.Subjects and Methods. 253 people were examined: 122 patients diagnosed with morphologically verified sarcoidosis with lung involvement (average age – 41.00 ± 12.56 years) (Sarcoidosis Group) and 131 healthy donors (Control Group) (average age – 44.00 ± 14.23 years). All subjects in both groups considered themselves Russians by ethnicity, as reported in the survey. The distribution of alleles and genotypes by the polymorphic markers Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene was studied in the group of patients with pulmonary sarcoidosis and the group of healthy individuals. Genotyping was carried out by PCR-RFLP.Results. There were no statistically significant differences in the distribution of allele and genotype frequencies for the Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) polymorphic markers of the TLR4 gene between the group of patients with pulmonary sarcoidosis and the control group: (χ2 = 0, df = 1, p = 0.997 и χ2 = 1.0, df = 2, p = 0.606; χ2 = 0.785, df = 1, p = 0.376 и χ2 = 0, df = 2, p = 1.0).Conclusion. The polymorphic marker Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene is not associated with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.Цель исследования: изучить связи полиморфизма Asp299Gln (rs 4986790) и Thr399Ile (rs 4986791) гена TLR4 с риском развития саркоидоза легких у русского населения Республики Карелия.Материалы и методы. Обследовано 253 человека: 122 больных с диагнозом морфологически верифицированного саркоидоза с поражением легких (средний возраст 41,00 ± 12,56 года) (группа саркоидоз) и 131 здоровый донор (группа сравнения) (средний возраст 44,00 ± 14,23 года). Все обследованные обеих групп считали себя по национальности русскими, о чем сообщили в проведенном анкетировании. Исследовано распределение аллелей и генотипов по полиморфным маркерам Asp299Gln (rs 4986790) и Thr399Ile (rs 4986791) гена TLR4 в группе больных саркоидозом легких и в группе сравнения. Генотипирование проводилось методом ПЦР-ПДРФ.Результаты. Статистически значимых различий в распределении частот аллелей и генотипов по полиморфным маркерам Asp299Gln (rs 4986790) и Thr399Ile (rs 4986791) гена TLR4 между группой саркоидоз и группой сравнения не выявлено (χ2 = 0, df = 1, p = 0,997 и χ2 = 1,0, df = 2, p = 0,606; χ2 = 0,785, df = 1, p = 0,376 и χ2 = 0, df = 2, p = 1,0).Заключение. Полиморфные маркеры Asp299Gln (rs 4986790) и Thr399Ile (rs 4986791) гена TLR4 не связаны с риском развития саркоидоза легких у русского населения Республики Карелия