THE EXPERIENCE OF NETWORKING POSTGRADUATE TRAINING PROGRAMMES

Introduction. Present scientific and innovative education programmes focus on the development of applied research in priority areas of industry, cross-industry and regional development. Implementation of such programs is most effective along with the network organization of the process of training. In accordance with the Federal Law on Education in the Russian Federation, this model of networking as «educational institution – educational organization» is a very convenient form of academic mobility realisation.The aim of the present paper is to analyse the model of interaction of the networking postgraduate training programmes at Krasnoyarsk State Medical University named after Prof. V. F. Voino-Yasenetsky and Medical School of Niigata University (Japan).Methodology and research methods involve theoretical analysis of the scientific outcomes of implementing a networking postgraduate training programme, comparative-teaching method, generalization, and pedagogical modeling.Results. The mechanisms of developing the partnership between universities of different countries are detailed. The experience of network international education in a postgraduate study is presented. The presented experience allowed the authors to develop an integrated strategy of cooperation with foreign colleagues in this direction. The advantages and problems of use of a network form of training of academic and teaching staff in a postgraduate school are revealed. The proposals and recommendations on optimization and harmonization of the purposes, tasks and programs of network interaction of the educational organizations are formulated.Practical significance. The proposed materials of the publication can form the base for creation and designing of an effective system of postgraduate education and competitiveness growth of the Russian universities

THE EXPERIENCE OF NETWORKING POSTGRADUATE TRAINING PROGRAMMES

Introduction. Present scientific and innovative education programmes focus on the development of applied research in priority areas of industry, cross-industry and regional development. Implementation of such programs is most effective along with the network organization of the process of training. In accordance with the Federal Law on Education in the Russian Federation, this model of networking as «educational institution – educational organization» is a very convenient form of academic mobility realisation. The aim of the present paper is to analyse the model of interaction of the networking postgraduate training programmes at Krasnoyarsk State Medical University named after Prof. V. F. Voino-Yasenetsky and Medical School of Niigata University (Japan).Methodology and research methods involve theoretical analysis of the scientific outcomes of implementing a networking postgraduate training programme, comparative-teaching method, generalization, and pedagogical modeling. Results. The mechanisms of developing the partnership between universities of different countries are detailed. The experience of network international education in a postgraduate study is presented. The presented experience allowed the authors to develop an integrated strategy of cooperation with foreign colleagues in this direction. The advantages and problems of use of a network form of training of academic and teaching staff in a postgraduate school are revealed. The proposals and recommendations on optimization and harmonization of the purposes, tasks and programs of network interaction of the educational organizations are formulated. Practical significance. The proposed materials of the publication can form the base for creation and designing of an effective system of postgraduate education and competitiveness growth of the Russian universities. Введение. Современные научно-инновационные образовательные программы ориентированы на развитие прикладных исследований по приоритетным направлениям отраслевого, межотраслевого и регионального развития. Реализация таких программ наиболее эффективна при сетевой организации процесса обучения. Кроме прочего, модель сетевых отношений «образовательная организация – образовательная организация» является весьма удобной формой осуществления академической мобильности. Цель публикации – анализ практического воплощения модели сетевого обучения аспирантов в Красноярском государственном медицинском университете и Медицинской школе Университета Ниигаты (Япония). Методология и методики. В работе использовались теоретический анализ научных достижений сетевой образовательной программы аспирантуры, сравнительно-педагогический метод, обобщение и педагогическое моделирование.Результаты. Детализированы механизмы налаживания партнерских отношений между университетами разных стран. Представлен опыт сетевого международного образования в аспирантуре, позволивший выработать единую стратегию сотрудничества с зарубежными коллегами в этом направлении. Выявлены преимущества и проблемы использования сетевой формы подготовки научно-педагогических кадров в аспирантуре. Сформулированы предложения и рекомендации по оптимизации и гармонизации целей, задач и программ сетевого взаимодействия образовательных организаций. Практическая значимость. Материалы статьи могут служить базой для создания эффективной системы послевузовского образования и повышения конкурентоспособности российских университетов

Модели ГЭБ in vitro: преимущества и недостатки, текущее положение и перспективы развития

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.Все больше исследователей фокусируют внимание не на эндотелиальных клетках как отдельных единицах гематоэнцефалического барьера (ГЭБ), но на сложных взаимоотношениях различных типов клеток внутри нейроваскулярной единицы, для чего широко используют различные модели ГЭБ in vitro. Основной точкой приложения таких моделей являются исследования проницаемости ГЭБ для различных молекул, патологических и лекарственных, в рамках изучения заболеваний и создания способов таргетной доставки терапевтических веществ в центральную нервную систему. В данной статье на основании российской и зарубежной научной литературы проведен анализ существующих моделей ГЭБ in vitro, их преимуществ и недостатков; освещены ключевые параметры, согласно которым оценивают релевантность модели ГЭБ in vitro; предложена унифицированная классификация таких моделей. По результатам анализа можно заключить, что наблюдается тенденция к переходу от 2D-моделей на полупроницаемых вставках к 3D-моделям на основе клеточных сфероидов и микрофлюидных чипов. Кроме того, использование индуцированных плюрипотентных стволовых клеток человека вместо первичных клеток, выделенных от животных, позволит с большей достоверностью масштабировать результаты, полученные in vitro, на условия in vivo

Plasticity of Adipose Tissue-Derived Stem Cells and Regulation of Angiogenesis

Adipose tissue is recognized as an important organ with metabolic, regulatory, and plastic roles. Adipose tissue-derived stem cells (ASCs) with self-renewal properties localize in the stromal vascular fraction (SVF) being present in a vascular niche, thereby, contributing to local regulation of angiogenesis and vessel remodeling. In the past decades, ASCs have attracted much attention from biologists and bioengineers, particularly, because of their multilineage differentiation potential, strong proliferation, and migration abilities in vitro and high resistance to oxidative stress and senescence. Current data suggest that the SVF serves as an important source of endothelial progenitors, endothelial cells, and pericytes, thereby, contributing to vessel remodeling and growth. In addition, ASCs demonstrate intriguing metabolic and interlineage plasticity, which makes them good candidates for creating regenerative therapeutic protocols, in vitro tissue models and microphysiological systems, and tissue-on-chip devices for diagnostic and regeneration-supporting purposes. This review covers recent achievements in understanding the metabolic activity within the SVF niches (lactate and NAD+ metabolism), which is critical for maintaining the pool of ASCs, and discloses their pro-angiogenic potential, particularly, in the complex therapy of cardiovascular and cerebrovascular diseases

Designing in vitro Blood-Brain Barrier Models Reproducing Alterations in Brain Aging

Blood-brain barrier (BBB) modeling in vitro is a huge area of research covering study of intercellular communications and development of BBB, establishment of specific properties that provide controlled permeability of the barrier. Current approaches in designing new BBB models include development of new (bio) scaffolds supporting barriergenesis/angiogenesis and BBB integrity; use of methods enabling modulation of BBB permeability; application of modern analytical techniques for screening the transfer of metabolites, bio-macromolecules, selected drug candidates and drug delivery systems; establishment of 3D models; application of microfluidic technologies; reconstruction of microphysiological systems with the barrier constituents. Acceptance of idea that BBB in vitro models should resemble real functional activity of the barrier in different periods of ontogenesis and in different (patho) physiological conditions leads to proposal that establishment of BBB in vitro model with alterations specific for aging brain is one of current challenges in neurosciences and bioengineering. Vascular dysfunction in the aging brain often associates with leaky BBB, alterations in perivascular microenvironment, neuroinflammation, perturbed neuronal and astroglial activity within the neurovascular unit, impairments in neurogenic niches where microvascular scaffold plays a key regulatory role. The review article is focused on aging-related alterations in BBB and current approaches to development of “aging” BBB models in vitro

Differential Roles of Environmental Enrichment in Alzheimer’s Type of Neurodegeneration and Physiological Aging

Impairment of hippocampal adult neurogenesis in aging or degenerating brain is a well-known phenomenon caused by the shortage of brain stem cell pool, alterations in the local microenvironment within the neurogenic niches, or deregulation of stem cell development. Environmental enrichment (EE) has been proposed as a potent tool to restore brain functions, to prevent aging-associated neurodegeneration, and to cure neuronal deficits seen in neurodevelopmental and neurodegenerative disorders. Here, we report our data on the effects of environmental enrichment on hippocampal neurogenesis in vivo and neurosphere-forming capacity of hippocampal stem/progenitor cells in vitro. Two models – Alzheimer’s type of neurodegeneration and physiological brain aging – were chosen for the comparative analysis of EE effects. We found that environmental enrichment greatly affects the expression of markers specific for stem cells, progenitor cells and differentiated neurons (Pax6, Ngn2, NeuroD1, NeuN) in the hippocampus of young adult rats or rats with Alzheimer’s disease (AD) model but less efficiently in aged animals. Application of time-lag mathematical model for the analysis of impedance traces obtained in real-time monitoring of cell proliferation in vitro revealed that EE could restore neurosphere-forming capacity of hippocampal stem/progenitor cells more efficiently in young adult animals (fourfold greater in the control group comparing to the AD model group) but not in the aged rats (no positive effect of environmental enrichment at all). In accordance with the results obtained in vivo, EE was almost ineffective in the recovery of hippocampal neurogenic reserve in vitro in aged, but not in amyloid-treated or young adult, rats. Therefore, EE-based neuroprotective strategies effective in Aβ-affected brain could not be directly extrapolated to aged brain

Аберрантный ангиогенез в ткани головного мозга при экспериментальной болезни Альцгеймера

The aim was to study the molecular mechanisms of the violation of the structural and functional integrity ofthe blood-brain barrier in chronic neurodegeneration of the Alzheimer’s type associated with the development of cerebral angiopathy.Materials and methods. The transgenic model of Alzheimer’s disease is the B6SLJ-Tg line mice (APPSwFlLon,PSEN1 * M146L * L286V) 6799Vas group which includes 9 months aged males. The control group included C57BL / 6 x SJL mice, males aged 9 months.Results. The total length of the vessels in the area of the dentate gyrus is 2.5 times greater in transgenic animal models of Alzheimer’s disease than in animals of the control group (p < 0.01). The average diameter of blood vessels in all areas of the hippocampus is smaller compared with the control (p < 0.05). Transgenic modeling of neurodegeneration in the CA2 zone of the hippocampus increases the relative area of tissue with increased permeability of blood-brain barrier (BBB) (17.80 [9.15; 36.75]) compared to control (1.38 [0.04; 7.60]) at p < 0.05. A similar difference (p < 0.05) is also observed in the hippocampal area CA1. A tendency (p > 0.05) to decrease the number of CD31+ endothelial cells in the dentate gyrus of the hippocampus (21.52 [17.56; 24.50]) in animals of the experimental group compared with the control group (23.08[21.18; 29.84]) was detected. A similar situation is observed in the CA2 and CA3 areas of the hippocampus.Conclusion. Neurodegenerative changes in the hippocampus of animals with a transgenic AD model are associated with impaired microcirculation in the brain tissue as a result of a reduction in the diameter and branching of blood vessels, and damage and increased permeability of BBB.Цель – изучение молекулярных механизмов нарушения структурно-функциональной целостности гематоэнцефалического барьера (ГЭБ) при хронической нейродегенерации  альцгеймеровского типа, ассоциированной с развитием церебральной ангипопатии. Материалы и методы. Опытная группа – генетическая модель болезни Альцгеймера (БА) – мыши линии B6SLJ -Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas, самцы в возрасте 9 мес. Контрольная группа – мыши линии C57BL/6 x SJL, самцы в возрасте 9 мес.Результаты. У животных с генетической моделью БА в зубчатой извилине гиппокампа  общая длина сосудов в 2,5 раза больше, чем у контрольной группы (p < 0,01), при этом  средний диаметр сосудов во всех областях гиппокампа меньше по сравнению с контролем (p < 0,05). Выявлено, что при генетическом моделировании  нейродегенерации в СА2 зоне гиппокампа наблюдается увеличение относительной  площади ткани с повышенной проницаемостью ГЭБ (17,80 [9,15;36,75]) по сравнению с контролем (1,38 [0,04;7,60]) при p < 0,05. Подобное различие (p < 0,05) наблюдается и в зоне СА1 гиппокампа. У животных опытной группы выявлена тенденция (p > 0,05) к снижению количества CD31+ эндотелиальных клеток в зубчатой извилине гиппокампа (21,52 [17,56; 24,50]) по сравнению с контролем (23,08 [21,18; 29,84]). Аналогичная ситуация наблюдается в зонах СА2 и СА3 гиппокампа.Заключение. Нейродегенеративные изменения в гиппокампе животных с генетической  моделью БА ассоциированы с нарушением микроциркуляции в ткани головного мозга в  результате сокращения диаметра и разветвленности сосудов, повреждения и повышения проницаемости ГЭБ

Экспрессия P-гликопротеина на лимфоцитах периферической крови при тяжелых формах бронхиальной астмы и его роль в определении чувствительности к терапии глюкокортикостероидами

P-glycoprotein (Pgp) is a membrane transporter of hydrophobic molecules providing efflux of xenobiotics from the cytosole outside the cell. In epithelial cells, Pgp is thought to be responsible for resistance to steroids. Severe bronchial asthma (SBA) is a heterogenous disease characterized by resistance to and dependence on steroids. The goal of this study was to assess expression of Pgp on peripheral blood lymphocytes in severe bronchial asthma and to evaluate the role of Pgp in developing the resistance to glucocorticoid therapy (GC). Assessment of Pgp expression revealed difference in response to GC treatment. All the patients were susceptible to GC, however, the time of therapeutic effect appearance and the number of Pgp-immunopositive cells differed significantly. Thus, more prolonged application of GC for reducing clinical manifestations was required in patients with aspirin induced or fatal bronchial asthma. The number of Pgp-immunopositive lymphocytes per one patients was significantly higher in patients with fatal bronchial asthma and in patients with steroid dependent bronchial asthma (6.8 ± 0.1 and 7.2 ± 0.2, respectively) comparing with patients with non stable bronchial asthma being therapeutically resistant (3.2±0.2 and 3.5±0.1, respectively). Thus, our findings suggest possible pathogenic role of Pgp in development of resistance to GC therapy in patients with bronchial asthma. Detection of Pgp expression on peripheral blood lymphocytes would allow optimizing the volume and duration of intensive anti inflammatory therapy and predicting the doses of basic drugs.P-гликопротеин (Pgp) — мембранный транспортер гидрофобных молекул, обеспечивающий выброс ксенобиотиков из цитоплазмы во внеклеточное пространство. В клетках эпителиальной природы Pgp отвечает за стероидорезистентность. Тяжелая БА (ТБА) — гетерогенное заболевание, характеризующееся формированием стероидозависимости или стероидорезистентности. Цель исследования изучить экспрессию Pgp на лимфоцитах периферической крови при тяжелых формах бронхиальной астмы (БА) и его роль в развитии резистентности к глюкокортикостероидной (ГКС) терапии. Изучение экспрессии Pgp выявило различие в ответе на лечение ГКС. Все пациенты были чувствительны к ГКС, но время наступления терапевтического эффекта и количество клеток Pgp+ в исследуемых группах достоверно отличались. Так, у пациентов с аспириновой и фатальной БА (ФБА) потребовалось более продолжительное назначение ГКС для купирования обострения. Количество Pgp+ лимфоцитов на одного больного также достоверно оказалось выше и составило 6,8 ± 0,1 в группе ФБА и 7,2 ± 0,2 у пациентов со стероидозависимой БА, в сравнении с больными с терапевтически резистентной (ТРБА) и нестабильной (НБА) — 3,2 ± 0,2 и 3,5 ± 0,1 соответственно. Таким образом, проведенное нами исследование подтверждает возможную патогенетическую роль Pgp в развитии резистентности пациентов БА к терапии ГКС. Определение уровня экспрессии Pgp+ на лимфоцитах периферической крови поможет оптимизировать объем и продолжительность интенсивной противовоспалительной терапии и прогнозировать дозы базисных препаратов

Oxytocin signal and social behaviour: comparison among adult and infant oxytocin, oxytocin receptor and CD38 gene knockout mice.

金沢大学医薬保健研究域医学系Oxytocin in the hypothalamus is the biological basis of social recognition, trust, love and bonding. Previously, we showed that CD38, a proliferation marker in leukaemia cells, plays an important role in the hypothalamus in the process of oxytocin release in adult mice. Disruption of Cd38 (Cd38 (-/-)) elicited impairment of maternal behaviour and male social recognition in adult mice, similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene knockout (Oxt (-/-) and Oxtr (-/-), respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalisation calls was lower in Cd38 (-/-) than Cd38( +/+) pups. However, these behavioural changes were much milder than those observed in Oxt (-/-) and Oxtr (-/-) mice, indicating less impairment of social behaviour in Cd38 (-/-) pups. These phenotypes appeared to be caused by the high plasma oxytocin levels during development from the neonatal period to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of plasma oxytocin differentiation. Breastfeeding was an important exogenous source of plasma oxytocin regulation before weaning as a result of the presence of oxytocin in milk and the dam\u27s mammary glands. The dissimilarity between Cd38 (-/-) infant behaviour and those of Oxt (-/-) or Oxtr (-/-) mice can be explained partly by this exogenous source of oxytocin. These results suggest that secretion of oxytocin into the brain in a CD38-dependent manner may play an important role in the development of social behaviour