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The purpose of this work was to reveal the intra- and inter-individual variability of the urine proteomic composition and of biochemical blood parameters in cosmonauts with different preflight autonomic status when they are back to Earth (on the 1st and 7th day after space flight). The objects of the study were 5-min samples of electrocardiogram (ECG) at rest and urine and venous blood samples, obtained in the same timeline from twelve male cosmonauts (age 46.5 ± 3.4 years), who performed space flights (SF) with duration 169–199 days onboard the Russian segment of the International Space Station (ISS). Two groups with different sympathetic-parasympathetic balance were identified (each consists of 6 cosmonauts) by the results of preflight heart rate variability (HRV) analysis. We have revealed in groups of cosmonauts with preflight predominance of sympathetic or parasympathetic tone the significant differences in the directionality of changes on days 1 and 7 after the SF as compared to the preflight values in three proteins (from total amount around 200): alpha-1 subunit of collagen type VI, Mucin 1, Cadherin-13. A set of biochemical parameters, unidirectionally changing with these proteins, was different in classified groups. Direct bilirubin, potassium and total calcium move unidirectionally with collagen, direct bilirubin, potassium – with mucin, and uric acid, ferrum, alpha-1, KFK, potassium - with cadherin in group with a sympathetic tone. Potassium, ferrum, alpha-1 move unidirectionally with collagen, amylase, KFK, AST, urea, inorganic phosphate, glucose, alkaline phosphatase, ionized calcium – with mucin, and total ferrum biding capacity, transferrin, glucose gamma globulin transferase - with cadherin in group with parasympathetic predominance. Probably, differences between groups in the concentration of these proteins and their different relationship with some biochemical parameters reflect different ways to achieve the same goal - adaptation to a complex of SF factors and re-adaptation after returning to Earth.

The study presents the results of evaluating the changes in the concentrations of blood plasma proteins associated with heart rate variability in cosmonauts who have completed space missions lasting about 6 months. The concentrations of 121 proteins were quantified in biological samples of the cosmonauts' blood plasma. The subgroups of proteins associated with the physiological processes of the heart rate variability autonomic regulation were identified using bioinformatic resources (Immunoglobulin heavy constant mu, Complement C1q subcomponent subunit C, Plasma serine protease inhibitor, Protein - 72 kDa type IV collagenase, Fibulin-1, Immunoglobulin lambda constant 3). The concentration of these proteins in the blood plasma before the flight, and the dynamics of concentration changes on the 1st and 7th days of the post-flight rehabilitation period differed in the groups of cosmonauts with a predominance of sympathetic or parasympathetic modulating autonomous influences. The dynamics of changes in the concentrations of the identified set of proteins reveal that in cosmonauts with a predominance of sympathetic modulating influences, the mechanisms of autonomic regulation are exposed to significant stress in the recovery period immediately after the completion of the space mission, compared with the cosmonauts with a predominance of parasympathetic modulating influences.

The study of proteins - potential markers, associated signal transduction pathways, and their targets - provides a new understanding of the fundamental mechanisms occurring at the level of regulatory processes in the cardiovascular system (CVS), especially in space flight, as well as in model experiments that reproduce its individual effects on the human body. The article presents the results of studies in an experiment with 120-day isolation within the framework of the SIRIUS project in which 6 volunteers aged 28 to 44 years (three men and three women) participated. SIRIUS (Scientific International Research in Unique Terrestrial Station) is the international research project, which studies the issues of biomedical and psychological support of long-term manned space flights. The possible involvement of collagen different types, an extracellular matrix protein, in the mechanisms of autonomic regulation of the CVS was studied. Using chromatic mass spectrometry in urine samples and analysis of heart rate variability, we have established that the extracellular matrix collagen, which is present, in particular, in the structure of the blood vessel wall, are markers associated with the modulating effect of the autonomic nervous system on the regulatory mechanisms of blood circulation. We hypothesized that these proteins may be a biomarker of the autonomic balance in the regulatory mechanisms of the circulatory system. In addition, these proteins can also be markers of the aging process, which increases the risks of developing autonomic dysfunction of the cardiovascular system (dominance of sympathicotonia) and changes in the quality of the tissue of the heart muscle and blood vessels, provoking the development of prenosological conditions and diseases of the cardiovascular system.

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.

The Institute of Biomedical Problems (IBMP) is the lead institution of the Russian Federation in the area of space biology and medicine. It has successfully implemented a set of innovation-based activities and projects to develop and introduce promising space products and technologies into the practices of Earth health care. To this end, various investigative methods developed for the medical selection of cosmonauts have been successfully applied in ophthalmology, gastroenterology, and cardiology. Axial loading “Regent” suits and soil simulators of bearing load have proved their efficiency in rehabilitating patients with motor disorders. Developmental prototypes of versatile training devices and technologies of their application are used for rehabilitation and purposeful development of physical status in people of various age groups. The application of telemedicine technologies allows one to diagnose and treat diseases in people who are in remote locations from medical centers or happen to be in extreme conditions. In cooperation with leading national medical institutions, other developments by the Institute have been also introduced into clinical practice: for example, the method of assessing the human functional state on the basis of computerized analysis of cardiac rhythm indices; methods of diagnosing, treating and preventing osteoporosis and metabolic osteopathias; methods of treating cardiorespiratory diseases using warmed-up heliox mixtures; methods of prophylactic examination and assessing the physical health status of the population; methods of monitoring the functional state and enhancing the physical capacity of athletes; developmental models of devices for simulating the effects of artificial gravity for refining methods of treatment and rehabilitation of patients; and systems of IV anesthesia with an option of a remote control. The effective management of innovation-based activities and the issues of commercialization of promising developments and objects of intellectual property are playing an ever-growing role in an effort to develop a scientific center in particular and a branch on the whole. The range and spectrum of applications of space medicine and biology achievements in sports, extreme, and rehabilitation medicine and preventive maintenance has expanded from year to year.