Structural, transport and microwave properties of 123/sapphire films: Thickness effect

The effect of thickness and growth conditions on the structure and microwave properties has been investigated for the 123/sapphire films. It has been shown that in the conditions of epitaxial growth the Al atoms do not diffuse from substrate into the film and the films with thickness up to 100 nm exhibit the excellent direct current (DC) properties. The increase of thickness of GdBaCuO films causes the formation of extended line-mesh defects and the increase of the surface resistance (R(sub S)). The low value of surface resistance R(sub S)(75 GHz, 77K) = 20 mOhm has been obtained for the two layer YBaCuO/CdBaCuO/sapphire films

Роль галектина-1, -3 в механизмах дисрегуляции Т-клеточного звена иммунного ответа при раке толстого кишечника

The aim of the study was to characterize the features of the subpopulation composition and cytokine-secretory activity of T lymphocytes (Th1, Th17 and Treg) in relation to the concentration of galectin-1 and galectin-3 in the blood of patients with colon cancer.Materials and methods. A total of 26 patients diagnosed with colon cancer were examined. The study material included whole peripheral blood, blood plasma, and supernatants of suspension cultures of mononuclear leukocytes. Lymphocytes isolated from blood were typed by flow cytometry using monoclonal  antibodies. The content of galectin-1 and galectin-3 (in blood plasma) and IFNγ, IL-17A, and TGFβ (in supernatants of mononuclear leukocyte culture in vitro) were determined by enzyme-linked immunosorbent assay. The results obtained were analyzed by statistical methods.Results. In patients with colon cancer, a significant increase in the concentration of galectin-1 and galectin-3 in the blood plasma was found, which was associated with a decrease in the content of CD4+T-bet+ Th1 lymphocytes, CD4+RORC2+ Th17 lymphocytes in the blood and in vitro hyposecretion of IL-17. At the same time, positive correlations were revealed between the concentration of galectin-1 and galectin-3, the content of CD4+FoxP3+ Treg cells in the blood, and the secretion of TGFβ by mononuclear leukocytes in vitro.Conclusion. In colon cancer, increased levels of galectin-1 and galectin-3 in the blood are associated with quantitative deficiency and inhibited secretory activity of effector T lymphocytes and activation of the immunosuppressive functions of regulatory T cells. These results suggest a negative role of galectin 1 and galectin 3 in the mechanisms of regulation of the T cell immune response in colon cancer.Цель исследования – охарактеризовать особенности субпопуляционного состава и цитокин-секреторной активности Т-лимфоцитов (Th1, Th17 и Treg) во взаимосвязи с концентрацией галектина-1 и галектина-3 в крови у больных раком толстого кишечника.Материалы и методы. Обследованы 26 пациентов (14 мужчин и 12 женщин, средний возраст (62,9 ± 6,7) лет) с диагнозом рака толстого кишечника. В группу контроля вошли 17 здоровых доноров (11 мужчин и 6 женщин, средний возраст (58,2 ± 3,1) лет). Материалом исследования служила цельная периферическая кровь, плазма крови и супернатанты суспензионной культуры мононуклеарных лейкоцитов. Выделенные из крови лимфоциты типировали методом проточной лазерной цитофлуориметрии с использованием моноклональных антител. Методом иммуноферментного анализа определяли содержание галектина-1 и галектина-3 (в плазме крови) и IFNγ, IL-17A и TGFβ (в супернатантах культуры мононуклеарных лейкоцитов in vitro). Полученные результаты анализировали статистическими методами.Результаты. У больных раком толстого кишечника установлено значимое увеличение концентрации галектина-1 и галектина-3 в плазме крови, ассоциированное со снижением содержания CD4+T-bet+ Th1- лимфоцитов, CD4+RORC2+ Th17-лимфоцитов в крови и гипосекрецией IL-17 лимфоцитами in vitro. Напротив, выявлена положительная корреляция между концентрацией галектинов 1 и 3, содержанием CD4+FoxP3+Treg клеток в крови и секрецией TGFβ мононуклеарными лейкоцитами in vitro.Заключение. При раке толстого кишечника повышенный уровень галектинов 1 и 3 в крови сопряжен с количественным дефицитом и угнетением секреторной активности эффекторных Т-лимфоцитов, и, напротив, активацией иммуносупрессорных функций  регуляторных Т-клеток. Полученные результаты указывают на негативную роль галектина-1 и галектина-3 в механизмах регуляции Т-клеточного звена иммунного ответа при раке толстого кишечника

RESEARCH ON NEW BISMUTH-SUBSTITUTED APATITES

The work was carried out within the framework of the Strategic Academic Leadership Program “Priority 2030” (internal project number N-413-99_2023-2024)

High-temperature superconductive magnets for suspension levitation transport system

JSC NIIEFA has been developed combine electromagnetic suspension for magnet levitation transport system with permanent and normal conducting electromagnets, which operate with reduced electricity consumption [1]

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Human EHMT2/G9a activates p53 through methylation-independent mechanism

p53 is a critical tumor suppressor in humans. It functions mostly as a transcriptional factor and its activity is regulated by numerous post-translational modifications. Among different covalent modifications found on p53 the most controversial one is lysine methylation. We found that human G9a (hG9a) unlike its mouse orthologue (mG9a) potently stimulated p53 transcriptional activity. Both ectopic and endogenous hG9a augmented p53-dependent transcription of pro-apoptotic genes, including Bax and Puma, resulting in enhanced apoptosis and reduced colony formation. Significantly, shRNA-mediated knockdown of hG9a attenuated p53-dependent activation of Puma. On the molecular level, hG9a interacted with histone acetyltransferase, p300/CBP, resulting in increased histone acetylation at the promoter of Puma. The bioinformatics data substantiated our findings showing that positive correlation between G9a and p53 expression is associated with better survival of lung cancer patients. Collectively, this study demonstrates that depending on the cellular and organismal context, orthologous proteins may exert both overlapping and opposing functions. Furthermore, this finding has important ramifications on the use of G9a inhibitors in combination with genotoxic drugs to treat p53-positive tumors.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.258

CHEMICAL STUDY OF FLAVONS AND FLAVONOLS COMPOSITION IN PROPOLIS

The aim of the study. This article is dedicated to the comparative assessment of flavones and flavonols composition in various samples of propolis for providing the possibility of its standardization. Materials and methods. To carry out the research, 6 experimental samples of propolis were taken from different regions of Russia. Using those samples, we prepared the extracts with 80% ethanol according to traditional scheme of making tinctures in the ratio of 1:10. After that our extracts were filtered and used directly in the assessment. Chromatographic separation of spirit extracts of propolis was carried out on a liquid chromatograph of “Agilent Technologies 1200 Infinity”, USA. The detection was carried out on the basis of the diode array detector “Agilent 1200”. Results and discussion. Using the reversed-phase HPLC in gradient elution regime we managed to identify flavonols and flavones. It was found out that the composition of propolis has a stable composition of flavones and flavonols including quercetin, isoramnetin, 3,4’-dimethoxycempferol, ramnetin, penduletin, kaempferol, ramnocitrin, galangin, kaempherid, chrysin and methoxyhalangin. Among the identified components, the highest content is in flavonols, methoxyl derivatives ramnocitrin (22,0%), and kaempherid (12,0%); in flavones it is chrysin(16,0%). The specific gravity of each component within the specified group was calculated by the internal normalization method. It was established that about 84% of all flavonols are in kaempferol and its methoxyl derivatives. The composition of flavones and flavonols can vary depending on the sample. Hereby, kempferol was identified in all the studied samples, whereas some of the identified components were absent from separate propolis samples. Propolis standardization by method of high-performance liquid chromatography in respect of the content of flavonoids in terms of kaempferol as a stable, commercially most available component of propolis was suggested. With the use of absolute calibration, the quantitative content of kaempferol in propolis samples wasdetermined in the range of 0.0141-0.0159%. Conclusion. The results of the carried out experiments made it possible to recommend the quality assessment of propolis according to the content of kaempferol in the experimental samples