Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

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 Level of Markers Stimulating Growth Factor 2 (ST2), N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP), and D-Dimer in Healthy Volunteer Testers in 21-Day Head-Down -6° Tilt Bed Rest as a Model of Hypodynamia.

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.

Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells.

The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, the role of senescent cells in the tissue microenvironment is still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence.

Influence of a Passive Tilt Test on the Proteomic Composition of the Blood of Healthy Humans.

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.

Characteristics of blood plasma proteome changes associated with the hemorrhagic purpura of cosmonauts on the first day after long-term space missions.

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.

Relationship of collagen as the component of the extracellular matrix with the mechanisms of autonomic regulation of the cardiovascular system under simulated conditions of long-term isolation.

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.

[Age features of heart rate variability in cosmonauts according to urine proteomics data.].

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.

Blood Plasma Proteins Associated With Heart Rate Variability in Cosmonauts Who Have Completed Long-Duration Space Missions.

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).

[Characteristics of age-dependent changes in the urine´s proteom composition of the of the healthy persons (experimental and theoretical study).].

For the first time proteins are described, reliably increasing and decreasing in urine with age in the range of 20 to 60 years. The combinations of proteins associated with changes in immune processes, violation of blood reology, including the risk of coagulopathy, anticancer defense mechanisms, insulin signaling pathway, changes in cell characteristics are characterized division and quality of the newly formed fabric. Thus, the age dynamics of the main processes triggers a cascade of reactions manifested in the closure of «pathological biochemical circles» that form the prerequisites for the development of diseases and, over time, clinical manifestations.

[Chromato-mass spectrometric analysis of urine proteins associated with the functions of Toll-receptors in a healthy person under conditions of 17-day isolation.].

Under controlled conditions of 17-day isolation (Sirius-17 experiment), the protein composition of urine was studied in 6 healthy test volunteers-3 women and 3 men. Collection of samples in the form of a second freely separated morning urine fraction was carried out in the background (seven days before the experiment), as well as 1 day after the end of exposure. Chromatographic-mass-spectrometric semi-quantitative analysis of the protein composition of samples was performed on a system consisting of an Agilent 1100 chromatograph and an LTQ-FT Ultra hybrid mass spectrometer using bioinformatics resources UniProtKB, GeneOntology.

The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory 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.

Secretome of Cultured Human Endothelial Cells in Simulated Microgravity.

The secretome of human umbilical vein endothelial cells (HUVEC) cultured under static conditions and in modeled microgravity for 24 h was studied by chromatography-mass spectrometry. In the secretome of cells exposed to microgravity, we identified a group of microtubule proteins including many structural elements of microtubules and regulatory proteins interacting with Rho-GTPases. Hence, reorganization of actin cytoskeleton and microtubules induced by microgravity is under complex regulation mediated by Rho proteins.

Urine proteome changes associated with autonomic regulation of heart rate in cosmonauts.

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.

[Features of the proteome of the urine in chronic pyelonephritis.].

Clinical observation and examination of 12 patients with chronic pyelonephritis (CPN) were performed. The first group (GI) included patients with exacerbation of the disease. In the comparison group (GII)- the same patients after 1.

[Analysis of Urine Proteome in Patients With Postinfarction Cardiosclerosis Combined With Hypertensive Disease for Assessing Endothelial Dysfunction].

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.

Effect of Different Levels of Salt Consumption on Urine Protein Composition during 105-Day Isolation Analyzed with the Use of opoSOM Software.

We investigated changes in the urine protein composition of healthy volunteers in controlled conditions during 105-day isolation (Mars-500 program) at different levels of salt consumption. We used newest proteomic techniques based on chromatography-mass spectrometry and various methods of bioinformatics including opoSOM. The period of observation can be divided into three intervals with different dynamics of protein excretion: early (week 1-6), intermediate (week 7-11) and late interval (week 12-15).

Spaceflight induced changes in the human proteome.

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.