DIFFERENTIATION OF NK CELLS. A LOOK THROUGH THE PRISM OF TRANSCRIPTION FACTORS AND INTRACELLULAR MESSENGERS

All lymphoid cells are referred to as an innate or adaptive immunity unit in terms of the mechanisms of performing immune reactions. The functional activity of natural killer (NK) cells is not associated with pre-activation processes resulting from contact with antigen, rearrangement of antigen-recognition receptor genes, and clonal proliferation. In this regard, NK cells are traditionally referred to as cells of innate immunity. Previously, it was believed that NK cells represent the only population of innate immunity lymphoid cells, but, more recently, there has been increasing evidence in the literature concerning existence of different populations of these cells, thus serving a basis for isolating a common cluster called Innate Lymphoid Cells (ILC). According to the ILC classification, NK cells are classified as the first group of innate lymphoid cells according to their overall functional characteristics, as well as contribution of the T-bet transcription factor to their differentiation. Complexity, multistage and partially nonlinear character of NK cell differentiation are associated with influence of the cellular microenvironment, consistent expression of transcription factors and activation of various intracellular signaling pathways in NK cells. The review considers positioning of NK cells in the ILC classification, the main transcription factors involved in NK cell differentiation. The authors are seeking for generalization of the major routes of intracellular signal transmission in NK cells depending on their activation by cytokines located in the cellular microenvironment and affecting NK cells. The decidual NK cells during pregnancy represent a special object of NK cell differentiation. Stromal cells, trophoblast cells and macrophages are present in the decidua, in addition to NK cells. The review concerns a special case of microenvironmental effects upon expression of transcription factors and activation of NK intracellular messengers, while considering trophoblast cells an example of such influences. The recently discovered variety of NK cells, induced by the microenvironment in the course of their differentiation, requires further study

Usage of nutrient Medium Based on Dry Hydrolysate of Casein in Manufacturing Bivalent Chemical Cholera Vaccine

Objective of the study was to select the standardized substrate containing dry hydrolysate of casein for preparation of nutrient medium utilized for manufacturing bivalent chemical cholera vaccine under submerged cultivation of cholera vibrio strains in fermenters. Materials and methods. We used Vibrio cholerae O1 strains of classical biovar: strain 569B Inaba and strain M-41 Ogawa. Examined were two dry substrates of the medium: enzymatic hydrolysate of casein, Type I Himedia (India) and pancreatic hydrolysate of casein, produced by the State Scientific Center of Applied Microbiology and Biotechnology (Russian Federation). Produced under laboratory conditions at the premises of the RusRAPI “Microbe” medium was used as a control. Submerged cultivation was conducted in bioreactors during (9±1) h with aeration and automatic feeding of glucose and ammonia. Production of protective antigens was measured applying immunochemical and biological methods. Results and discussion. It is demonstrated that submerged cultivation of cholera vibrio production strains on nutrient media under study provides for synthesis of protective antigens the parameters of which comply with the requirements of normative documentation. More standardized and higher indicator values of the target product are ensured by cultivation of producer strains on nutrient medium with a substrate from dry enzymatic hydrolysate of casein, containing (1.5±0.1) g/l of amino nitrogen for the strain V. cholerae M-41 and (2±0.1) g/l – for V. cholerae 569 B. Transition to the use of standardized dry protein components of cultivation media does not lower the quality of the chemical cholera vaccine, but allows for the reduction of cost price and duration of technological process

The Chemical Composition of Two Supergiants in the Dwarf Irregular Galaxy WLM

[Abridged] The chemical composition of two stars in WLM has been determined from high quality UVES data obtained at the VLT UT2 (program 65.N-0375). The model atmospheres analysis shows that they have the same metallicity, [Fe/H] = -0.38 +/-0.20, and [Mg/Fe] = -0.24 +/-0.16. This result suggests that the [alpha(Mg)/Fe] ratio in WLM may be suppressed relative to solar abundances (also supported by differential abundances relative to similar stars in NGC6822 and the SMC). The absolute Mg abundance, [Mg/H] = -0.62 is high relative to what is expected from the nebulae though, where two independent spectroscopic analyses of the HII regions in WLM yield [O/H] = -0.89. Intriguingly, the oxygen abundance determined from the OI 6158 feature in one WLM star is [O/H] = -0.21 +/-0.10, corresponding to five times higher than the nebular oxygen abundance. This is the first time that a significant difference between young stellar and nebular oxygen abundances has been found, and presently, there is no simple explanation for this difference. If the stellar abundances reflect the true composition of WLM, then this galaxy lies well above the metallicity-luminosity relationship for dwarf irregular galaxies. It also suggests that WLM is more chemically evolved than currently interpreted from its color-magnitude diagram.Comment: 27 pages, 7 tables, 10 figures. accepted for publication in the Astronomical Journa

Assessment of Stability of Chemical Cholera Vaccine in a New Primary Packaging

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated

Локальная концентрация цитокинов у пациентов с немышечно-инвазивным раком мочевого пузыря с низким злокачественным потенциалом с учетом различной степени рецидивирования

Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence. Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were  echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.Цель исследования – изучить локальную концентрацию цитокинов и выявить особенности их распределения в тканях опухоли и перифокальной зоны при немышечно-инвазивном раке мочевого пузыря низкого злокачественного потенциала у пациентов с низкой и высокой вероятностью развития рецидива заболевания.Материалы и методы. Исследованы фрагменты опухоли и перифокальной зоны 31 пациента с впервые выявленным немышечно-инвазивным раком мочевого пузыря низкого злокачественного потенциала с различным уровнем вероятности развития рецидива. Рецидив заболевания у 15 пациентов был диагностирован через 6–9 мес после проведенного комплексного лечения. Фрагменты первичной и рецидивной опухолевой ткани механически дезагрегировали и центрифугировали при 1500 об/мин в течение 10 мин. В полученных образцах методом иммуноферментного анализа определяли уровень цитокинов: интерлейкинов (ИЛ) 1β, 6, 8, 10, 18, фактора некроза опухоли α (ФНО-α), интерферона γ (Вектор-Бест, Россия), эпителиального нейтрофил-активирующего пептида (ENA-78) (хемокин CXCL-5) (Cloud-Clone Corp., США). Статистическую обработку полученных результатов проводили с использованием пакета Statistica 13 (StatSoft Inc., США), результаты представлены в виде медианы и интерквартильного размаха – 25-го и 75-го процентилей (Ме [LQ; UQ]).Результаты. При сравнении концентрации цитокинов внутри групп установлено, что уровень воспалительных цитокинов (ФНО-α, ИЛ-1β, -8, -6, -18) в тканях опухоли был выше по сравнению с аналогичными показателями в тканях перифокальной зоны. Данная закономерность ожидаема, так как опухоль является очагом воспаления. При сравнении аналогичных показателей между группами в тканях опухоли при неблагоприятном течении заболевания, а именно при развитии рецидива, уровень практически всех воспалительных цитокинов (ФНО-α, ИЛ-1β, -8, -6) оказался выше. Аналогичная картина наблюдалась и в случае сравнения уровня цитокинов в тканях перифокальной зоны. Эти различия являются статистически достоверными. Значения показателя ENA-78 во всех случаях не определялись.Заключение. Полученные данные свидетельствует о том, что у пациентов с неблагоприятным течением заболевания (развитие рецидива) рост опухоли протекает на фоне высокой экспрессии провоспалительных цитокинов, которые в последующем могут привести к возникновению рецидива заболевания

Turkmen Students at Volgograd State Technical University

The attractiveness of the University in the world market of educational services is an indicator of its success, which is estimated by a set of criteria including the number of foreign students studying there. For Russian universities, the number of international students is one of the key indicators of internationalization. The authors pay special attention to the criterion of internationalization of higher education in the world ranking of universities. The article provides data related to measures to attract young foreigners to study in higher education institutions of the Russian Federation, including the Volgograd State Technical University. Today, an interest in engineering professions among foreign applicants has increased markedly. The effectiveness of the learning process among foreign students, their achievement levels strongly depend on the success of their adaptation to the new socio-cultural environment. The article addresses the problems of language adaptation of foreign students who came from the former Soviet republics, mainly on the example of students from Turkmenistan