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Background/objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue., Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort., Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA)., Conclusions: The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.

The paper presents an analysis of the proteomic composition in relation to both the risk of thrombosis and changes in the state of cardiomyocytes associated with the risk of cardiac fibrosis and heart failure. We examined 12 practically healthy male volunteers exposed to head-down -6° tilt bed rest (HDBR) for 21 days. The revealed decrease in the level of stimulating growth factor 2 (ST2) on days 10 and 21 relative to the initial values (background; 5 days before HDBR) indicated a decrease in the myocardial load and cardiomyocyte extensibility. The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increased on day 2, decreased on days 10 and 21 of HDBR relative to the background levels, and returned to baseline values after the recovery period (5 days after HDBR). The revealed changes in the level of NT-proBNP reflected the increase in circulating blood volume corresponding to HDBR duration and the role of the gravity component in increasing the functional load on the myocardium. Unchanged blood level of D-dimer at all points of the study indicates that there is no risk of thrombosis under the conditions of this study., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kashirina, Pastushkova, Goncharova and Larina.)

In order to identify changes in the blood proteome of healthy volunteers after passive tilt test carried out on day 19 of head-down bed rest, a chromato-mass-spectrometric analysis of samples of dried blood spots was carried out. It was revealed that the body's response to the tilt test was characterized by a decrease in the level of HDL and kininogen-1. After the tilt test, we observed an increase in the level of vimentin, vitamin K-dependent protein C, Wnt signaling pathway proteins, proteins involved in autophagy and adaptive immune response, focal adhesion proteins, vascular damage marker S100A8, PEDF regulator, and some proteins of the heart: cardiac actin ACTC1 and transcription factor GATA4. The obtained results lay the foundation for future research in the framework of identifying the risks of developing cardiovascular changes in astronauts after space flights., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The interest in the role of the gravitational factor during landing after long-term space flights (SF) leads to the search for various innovative approaches to assessing the compliance of external changes observed by clinicians. The results of special research methods such as Omics technologies that may reflect physiological responses to the conditions created during landing are of great interest. Our purpose is to compare the blood plasma proteome changes associated with the trauma and endothelial dysfunction processes prior to launch and on the day of landing, as well as the groups of cosmonauts with and without the secondary hemorrhagic purpura. In our study, the concentrations of 125 plasma proteins in 18 Russian cosmonauts, measured using targeted proteomic analysis based on liquid chromatography and tandem mass spectrometry were analyzed. The results reveal the trends of 12 proteins participating in the processes that trigger hemorrhagic purpura under the effect of re-entry g-forces. Exposure to intense g-forces and return to the gravity are the key factors for external manifestations of changes in the body systems induced by a long-term stay in space microgravity. Our results may be useful for further research to experts in gravitational physiology, aviation and space medicine., (Copyright © 2022 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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., (Copyright © 2021 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

As the life of the International Space Station (ISS) is lengthening, Russian crews are dominated by cosmonauts over 40 years of age who have repeatedly made a space flight (SF) and have a long stay on the ISS. In order to study the age-related features of the regulation of heart rate variability (HRV) in cosmonauts, based on proteomics data, we analyzed simultaneously the obtained data on the proteomic composition of urine samples and electrocardiogram (ECG) parameters, followed by an analysis of heart rate variability (HRV) in cosmonauts in the age group of 46,5±3,4 (n=12). The survey was carried out in the period of preparation for the next flight. The urine proteome was studied by mass spectrometry and analyzed by bioinformatic methods. Heart rate variability was assessed by software methods for analyzing ECG fragments. For the first time, data based on proteomics on the age-related features of the regulation of heart rate variability in cosmonauts are presented. According to age periodization, cosmonauts are in the middle age of the second period. The concentrations of mucin 1, type VI collagen, and cadherin 13 were shown to change with age. A decrease in HRV was also observed with increasing age. There was an increase in sympathetic influence and a progressive decrease in parasympathetic influence.

The study presents the results of evaluating the changes in the concentrations of blood plasma proteins associated with heart rate variability (HRV) in cosmonauts who have completed space missions lasting about 6months. The concentrations of 125 proteins were quantified in biological samples of the cosmonauts' blood plasma. The subgroups of proteins associated with the physiological processes of the HRV autonomic regulation were identified using bioinformatic resources (Immunoglobulin heavy constant mu, Complement C1q subcomponent subunit C, Plasma serine protease inhibitor, Protein-72kDa 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pastushkova, Rusanov, Goncharova, Nosovskiy, Luchitskaya, Kashirina, Kononikhin, Kussmaul, Yakhya, Larina and Nikolaev.)

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., (Copyright © 2020 Rusanov, Pastushkova, Larina, Chernikova, Goncharova, Nosovsky, Kashirina, Brzhozovsky, Navasiolava, Kononikhin, Kussmaul, Custaud and Nikolaev.)

Comprehensive studies of the effects of prolonged exposure to space conditions and the overload experienced during landing on physiological and biochemical changes in the human body are extremely important in the context of planning long-distance space flights, which can be associated with constant overloads and various risk factors for significant physiological changes. Exhaled breath condensate (EBC) can be considered as a valuable subject for monitoring physiological changes and is more suitable for long-term storage than traditional monitoring subjects such as blood and urine. Herein, the EBC proteome changes due to the effects of spaceflight factors are analyzed. Thirteen EBC samples were collected from five Russian cosmonauts (i) one month before flight (background), (ii) immediately upon landing modules in the field (R0) after 169-199 days spaceflights, and (iii) on the seventh day after landing (R+7). Semi-quantitative label-free EBC proteomic analysis resulted in 164 proteins, the highest number of which was detected in EBC after landing (R0). Pathways enrichment analysis using the GO database reveals a large group of proteins which take part in keratinization processes ( CASP14 , DSG1 , DSP , JUP , and so on). Nine proteins (including KRT2 , KRT9 , KRT1 , KRT10 , KRT14 , DCD , KRT6C , KRT6A , and KRT5 ) were detected in all three groups. A two-sample Welch's t -test identified a significant change in KRT2 and KRT9 levels after landing. Enrichment analysis using the KEGG database revealed the significant participation of detected proteins in pathogenic E. coli infection ( ACTG1 , TUBA1C , TUBA4A , TUBB , TUBB8 , and YWHAZ ), which may indicate microbiota changes associated with being in space. This assumption is confirmed by microbial composition analysis. In general, the results suggest that EBC can be used for noninvasive monitoring of health status and respiratory tract pathologies during spaceflights, and that the obtained data are important for the development of medicine for use in extreme situations. Data are available from ProteomeXchange using the identifier PXD014191.

Background: The conditions of space flight have a significant effect on the physiological processes in the human body, yet the molecular mechanisms driving physiological changes remain unknown., Methods: Blood samples of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station were collected 30 days before launch and on the first and seventh days after landing., Results: A panel of 125 proteins in the blood plasma was quantitated by a well-established and highly regarded targeted mass spectrometry approach. This method involves the monitoring of multiple reactions in conjunction with stable isotope-labeled standards at the University of Victoria - Genome BC Proteomics Centre., Conclusions: Reduction of circulating plasma volume during space flight and activation of fluid retention at the final stage of the flight affect the changes in plasma protein concentrations present in the first days after landing. Using an ANOVA approach, it was revealed that only 1 protein (S100A9) reliably responded to space flight conditions. This protein plays an important role in the functioning of the endothelium and can serve as a marker for activation of inflammatory reactions. Concentrations of the proteins of complement, coagulation cascades, and acute phase reactants increase in the blood of cosmonauts as measured the first day after landing. Most of these proteins' concentrations continue to increase by the 7th day after space flight. Similar dynamics are observed for proteases and their inhibitors. Thus, there is a shift in proteolytic blood systems, which is necessary for the restoration of muscle tissue and maintenance of oncotic homeostasis.

In our study urine protein composition of 18 healthy volunteers was compared with that of 18 patients with ischemic heart disease and concomitant hypertension. Liquid chromatography-mass-spectrometry (LC-MS) analysis of the second fraction of morning urine was carried out using nano-line high performance liquid chromatograph and hybrid mass spectrometer. The analysis revealed 23 proteins expressed in the endothelium, according to the information contained in the database Bgee, and 49 proteins, with direct functional link with the processes in the endothelium in the reconstruction of associative networks using ANDSystem program. Comparison of urine proteome of healthy people and patients with postinfarction cardiosclerosis revealed proteins specific for patients with cardiovascular disease. Thus, proteins vitronectin, syndecan-4, a histidine rich glycoprotein, endothelial protein C receptor, colony stimulating factor, cathepsin D and sekretogranin-1 may be considered as potential markers for cardiovascular diseases. Further research in this area should be conducted for clinical and experimental verification of these hypotheses.

Introduction: Spaceflight is one of the most extreme conditions encountered by humans: Individuals are exposed to radiation, microgravity, hypodynamia, and will experience isolation. A better understanding of the molecular processes induced by these factors may allow us to develop personalized countermeasures to minimize risks to astronauts. Areas covered: This review is a summary of literature searches from PubMed, NASA, Roskosmos and the authors' research experiences and opinions. The review covers the available proteomic data on the effects of spaceflight factors on the human body, including both real space missions and ground-based model experiments. Expert commentary: Overall, the authors believe that the present background, methodology and equipment improvements will enhance spaceflight safety and support accumulation of new knowledge on how organisms adapt to extreme conditions.

Specifics of urine proteome is sensitive to a multitude of factors. One is nutrition or entrance in organism of main nutrients including salt (NaCI). Purpose of the investigation was to study the proteomic composition of healthy human urine in the controlled environment of a 105-day isolation experiment (project <>) with various levels of salt intake. Analysis was performed using the present-day proteomics techniques based on chromatography-mass spectrometry and bio-informatics options. An attempt was made to correlate changes in processes and physiological systems with the controlled salt intake. As a result, a list of proteins directly responsible for different salt intake during the experiment and then a list of tissues where these proteins express predominantly were compiled; besides, analysis of the processes these proteins are involved in was performed.

We investigated the age dynamics of proteomic profile of urine in 52 healthy men aged 18 to 51 years. A special sample preparation was performed, followed by liquid chromatography-mass spectrometry. Liquid chromatography-mass spectrometry of the minor proteins was performed on a nano-HPLC Agilent 1100 system («Agilent Technologies Inc.», USA) in combination with a LTQ-FT Ultra mass spectrometer («Thermo Electron», Germany). A total of 259 proteins were identified. According to the TiGER database, a tissue origin was established for 141 proteins and identified 715 processes in which they participate. We found a significant positive correlation with age, the number of proteins (R=0,566; p-value=1,24E-05) and the weight of proteins (R=0,45; p value=8,17E-04). Identified 23 proteins were significantly more frequent in the urine of subjects with increasing age (p<0,05), and only one protein - RGSL, Regulator of G protein signaling protein-like (MW 125.69) - less frequently.

Original data on the peculiarities of adaptation to and functional status of the reproductive system in long-term antiorthostatic hypokinesia (AOH) have been obtained. The studies involved eight healthy female volunteers aged 26-37 years who were exposed to the head-down tilt (-6 degrees) for 120 days. The test subjects were divided into 2 groups of 4 persons each. In Group A, the countermeasures, i.e. physical exercise and pharmacological means, were used. In Group B, at no time did the test subjects use the countermeasures throughout the 120-day AOH. With and without the countermeasures, hypokinesia was found to impact the female reproductive system developing clinical symptoms of deficiency of the menstrual lutein phase and giving rise to small inclusions of functional fluids in the ovaries. Within 6 months after AOH, the ovarial function of the test subjects was fully recovered which may be indicative of the functional character of changes. These changes can be explained by dissociation of the functional relations in the hypothalamo-hypophyseal-ovarial system manifested by increases in the plasmic concentrations of luteinizing hormone (LH) against normal levels of follicle-stimulating hormone (FSH) and prolactin, and moderately increased levels of testosterone, relative hyperestrogenemia and hypoprogesteronemia. These clinical and hormonal developments are contrary to the observations usually made in various models of stress. Similarity of the hormonal profiles under hypokinesia and long-term immersion of female swimmers may be ascribed to common mechanisms underlying the disturbance of the reproductive function.