Репозиторий Университета

Репликативный полипротеин 1а вируса желтухи свеклы (ВЖС) содержит консервативные домены лидерной папаин-подобной протеиназы (РСР), метилтрансферазы (MTR) и РНК хеликазы (HEL). Центральный район (central region, CR) между MTR и HEL ранее считали «вариабельным». Нами проведен компьютерный анализ CR, который позволил выявить новый консервативный домен между позициями 1287-1390 (здесь и далее приводится нумерация аминокислотных остатков белка 1а вируса желтухи свеклы, BYV), сохраняющийся у всех представителей рода Closterovirus. Этот домен содержит 4 предсказанных альфа-спиральных участка (альфа А – D) и три строго консервативные позиции – глютамат-1291, пролин-1380 и аргинин-1384. Кроме того, биоинформатический анализ позволил предсказать амфипатическую спираль в позициях 1368-1380 (входящую в состав участка альфа D). Гидрофобный домен CR-2 (позиции 1305-1494 белка 1а), вызывающий при экспрессии в растениях реструктуризацию эндоплазматического ретикулюма и образование подвижных глобул диаметром ~1 мкм, включает участки альфа В, С и D. Установлено, что экспрессия в растениях слитных белков CR-2:GFP и GFP:CR-2 вызывает сходный «глобулообразующий» фенотип, т.е. N-концевое или C-концевое положение маркера GFP в слитном белке не влияет на переформатирование мембран эндоплазматического ретикулюма. Проведен делеционный анализ CR-2 BYV. Показано, что делеционные варианты 1355-1494 и 1325-1484 сохраняют фенотип дикого типа (образование глобул и реструктуризация ЭР вокруг ядра клетки). Варианты 1375-1484, 1368-1484 и 1368-1432 индуцировали образование глобул, но утрачивали способность к реструктуризации ЭР. Внесение замен гидрофобных аминокислотных остатков на остатки серина и глицина в «минимальном» делеционном мутанте 1368-1432 блокировало образование глобул. Предложена рабочая гипотеза о влиянии консервативной амфипатической спирали 1368-1385 в белке 1а BYV на ремоделирование мембран ЭР растительной клетки и создание репликативных платформ при клостеровирусной инфекции.

Autophagy is an evolutionary conserved intracellular catabolic process of vital importance to cell and tissue homeostasis. Autophagy is implicated in the pathogenesis of atherosclerosis but participating cells, molecular mechanisms and functional outcomes have not been fully elucidated. T-cadherin, an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily of adhesion molecules, is upregulated on smooth muscle cells (SMCs)¹ in atherosclerotic lesions. Here, using rat and murine aortic SMCs as experimental models, we surveyed the ability of T-cadherin to regulate autophagy in SMCs during serum-starvation stress. Ectopic upregulation of T-cadherin in SMCs resulted in augmented autophagy characterized by increased autophagic flux, LC3-II abundance and autophagosome formation. Analysis of signal transduction pathway effectors and use of specific pharmacological inhibitors demonstrated that T-cadherin-associated enhancement of the autophagic response to serum-deprivation was dependent on MEK1/2/Erk1/2 activation and independent of PI3K/Akt/mTORC1, reactive oxygen species or endoplasmic reticulum stress. T-cadherin upregulation on SMCs conferred a survival advantage during prolonged serum-starvation which was sensitive to inhibition of MEK1/2/Erk1/2 by PD98059 or UO126 and to blockade of autophagy by chloroquine. Loss of T-cadherin expression in SMCs diminished autophagy responsiveness and compromised survival under conditions of serum-starvation. Overall our findings have identified T-cadherin as a novel positive regulator of autophagy and survival in SMCs.

Objective. To assess antioxidant therapy (ascorbic acid (AA), Cytoflavin) prescribed as part of the standard treatment scheme based on clinical and morphological data in cerebral infarct. Materials and methods. The study was performed from 2010 to 2014 in eight vascular centers in the Russian Federation. A total of 373 patients with acute ischemic stroke in the carotid basin were studied. Group 1 consisted of 132 patients who received 5% AA solution at a daily dose of 20 ml; group 2 consisted of 113 patients receiving the antioxidant Cytoflavin at a daily dose of 20 ml for 10 days; group 3 consisted of 108 patients receiving Cytoflavin for 20 days, the dose being decreased to 10 ml from day 11 to day 20. Patients’ status was evaluated using a set of clinical, laboratory, and instrumented methods. Results and conclusions. Analysis of CT scan results obtained on treatment days 1 and 21 showed that Cytoflavin led to significant regression of the volume of cerebral ischemia, by an average factor of 1.5–1.7. No significant morphological changes were seen in the AA-treated group; among Cytoflavin-treated patients there was a two-fold reduction in the proportion of patients in which the volume of cerebral ischemia increased during the period 1–21 days. In patients with initial assessments of at least 14 points on the NIH scale, Cytoflavin treatment for 20 days promoted more marked improvements in neurological, functional, and cognitive status than seen in patients given infusions for 10 days.

Objectives: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia.

Methods: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated.

Results: In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age.

Conclusions: Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.

Проведен анализ научной литературы за период с 1991 по 2016 г., посвященной хирургической подготовке костной ткани челюстей к дентальной имплантации путем применения синтетических остеопластических материалов. Подбор научной литературы проводился в Центральной научной медицинской библиотеке, электронной медицинской библиотеке eLIBRARY.RU, а также по базе данных медицинских публикаций PubMed. В обзоре проанализированы результаты экспериментальных и клинических исследований особенностей и эффективности применения таких материалов, сроки их замещения на новообразованную костную ткань, а также эффективность применения синтетических заменителей и других видов остеопластических материалов.

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.