The effects of spaceflight on human physiology is an increasingly studied field, yet the molecular mechanisms driving physiological changes remain unknown. With that in mind, this study was performed to obtain a deeper understanding of changes to the human proteome during space travel, by quantitating a panel of 125 proteins in the blood plasma of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station. The panel of labeled prototypic tryptic peptides from these proteins covered a concentration range of more than 5 orders of magnitude in human plasma. Quantitation was achieved by a well-established and highly-regarded targeted mass spectrometry approach involving multiple reaction monitoring in conjunction with stable isotope-labeled standards. Linear discriminant function analysis of the quantitative results revealed three distinct groups of proteins: 1) proteins with post-flight protein concentrations remaining stable, 2) proteins whose concentrations recovered slowly, or 3) proteins whose concentrations recovered rapidly to their pre-flight levels. Using a systems biology approach, nearly all of the reacting proteins could be linked to pathways that regulate the activities of proteases, natural immunity, lipid metabolism, coagulation cascades, or extracellular matrix metabolism.
Background The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system. Results The proteins cadherin-13, mucin-1, alpha-1 of collagen subunit type VI (COL6A1), hemisentin-1, semenogelin-2, SH3 domain-binding protein, transthyretin and serine proteases inhibitors realize a homeostatic role in individuals with different initial type of the cardiovascular system regulation. The role of significantly changed urine proteins in the cardiovascular homeostasis maintenance is associated with complex processes of atherogenesis, neoangiogenesis, activation of calcium channels, changes in cell adhesion and transmembrane properties, changes in extracellular matrix, participation in protection from oxidative stress and leveling the effects of hypoxia. Therefore, the concentrations of these proteins significantly differ between groups with dominant parasympathetic and sympathetic influences. Conclusion The space flight induced urine proteome changes are significantly different in the groups identified by heart rate autonomic regulation peculiarities before space flight. All these proteins regulate the associated biological processes which affect the stiffness of the vascular wall, blood pressure level, the severity of atherosclerotic changes, the rate and degree of age-related involution of elastin and fibulin, age-related increase in collagen stiffness, genetically determined features of elastin fibers. The increased vascular rigidity (including the aorta) and of myocardium may be regarded as a universal response to various extreme factors. Significant differences in the semi-quantitative analysis of signal proteins between groups with different types of autonomic regulation are explained by a common goal: to ensure optimal adaptation regardless of age and of the genetically determined type of responses to the extreme environmental factors effects. Electronic supplementary material The online version of this article (10.1186/s12918-019-0688-9) contains supplementary material, which is available to authorized users.
Хроническая неспецифическая боль в нижней части (БНЧС)-самая частая причина нарушения трудоспособности и снижения качества жизни в современном обществе. Цель исследования-обсуждение целесообразности выявления причин хронической неспецифической БНЧС и в случае обнаружения поражения фасеточного сустава (ФС) или крестцово-подвздошного сочленения (КПС) применения нестероидных противовоспалительных препаратов (НПВП) и введения анестетиков и глюкокортикоидов в область ФС или КПС. Пациенты и методы. Под наблюдением находилась 121 пациентка с хронической неспецифической БНЧС в возрасте от 22 до 59 лет. Поражение ФС выявлено у 53 (43,8%) больных. Пациентки были информированы о благоприятном прогнозе заболевания, получили рекомендации по двигательной активности, им также были назначены НПВП и миорелаксанты. У 28 (23%) пациенток клинически значимый обезболивающий эффект был достигнут в течение 2 нед; у остальных 93 (77%) проведена комплексная терапия с введением анестетиков в область ФС и КПС. Результаты и обсуждение. Показано, что основой успешной персонифицированной терапии у таких больных является адекватная диагностика с выявлением преобладающих источников болевой импульсации (триггеров), в том числе с использованием малоинвазивных методов диагностики-локального введения раствора местного анестетика в предполагаемый триггер боли. Высокая эффективность включения в комплексную терапию хронической неспецифической БНЧС введения анестетиков в область ФС и КПС во многом связана с быстрым устранением боли, что имеет большое психологическое значение. Обсуждаются центральные механизмы действия НПВП, в частности эторикоксиба. Заключение. Таким образом, выяснение причин хронической неспецифической БНЧС у пациента позволяет рекомендовать персонифицированную терапию, направленную на устранение не только симптомов, но и первопричины заболевания. Применение при поражении ФС эторикоксиба, отличающегося максимальной анальгетической эффективностью у больных остеоартритом, патогенетически оправдано и должно сочетаться с нелекарственными методами лечения.
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The purpose of the study was to investigate the regulatory and metabolic changes in the circulatory system when simulating microgravity conditions in a five-day dry immersion. These changes reflect the adaptation processes characteristic for the initial stages of a space flight or a short-duration space flight. Studies were conducted with 13 healthy male volunteers aged 21 to 29 years. The assessment of regulatory and metabolic processes in the circulatory system was based on the heart rate variability (HRV) and urine proteomic profile analysis. It was found that the restructuring of hemodynamics during 5 days hypogravity begins with the inclusion of the nervous circuit of regulation, and for manifestations at the body fluids protein composition level and activation of the metabolic regulation, these periods are apparently insufficient. Perhaps this is due to the fact that the metabolic regulation, being evolutionarily ancient and genetically determined, is more stable and requires more time for its pronounced activation when stimulated by extreme life conditions.
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