No abstract

Non-thermal plasma (NTP) consists of a huge amount of biologically active particles, whereas its temperature is close to ambient. This combination allows one to use NTP as a perspective tool for solving different biomedical tasks, including antitumor therapy. The treatment of tumor cells with NTP caused dose-dependent effects, such as growth arrest and apoptosis. However, while the outcome of NTP treatment has been established, the molecular mechanisms of the interaction between NTP and eukaryotic cells have not been thoroughly studied thus far. In this work, the mechanisms and the type of death of human colon carcinoma HCT 116 cells upon application of non-thermal argon plasma were studied. The effect of NTP on the major stress-activated protein p53 was investigated. The results demonstrate that the viability of HCT116 cells upon plasma treatment is dependent on the functional p53 protein. NTP treatment caused an increase in the intracellular concentration of p53 and the induction of the p53-controlled regulon. The p53-dependent accumulation of active proapoptotic caspase-3 was shown in NTP-treated cells. The study was the first to demonstrate that treatment of human colon carcinoma cells with NTP results in p53-dependent apoptosis. The results obtained contribute to our understanding of the applicability of NTP in antitumor therapy.

This contribution summarizes the results of investigations of water-electrolyte metabolism and its hormonal regulation conducted in cosmonauts who performed long-term space flights (from 18 to 366 days) aboard the space stations Salyut and Mir and compares them with the results obtained during various NASA flights. The role of the kidneys in ion metabolism regulation was assessed by various water-salt load tests before and after flights. In addition, the results of a year-long space flight and of medical experiments performed during the 237- and 241-day missions by the physicians and cosmonaut-researchers Atkov and Polyakov are reviewed in detail. In spite of interindividual variations, metabolic, and endocrine studies during prolonged space flights showed a reduction in body mass, usually with a reduction in body water and electrolytes and considerable changes in blood hormone concentrations and urinary hormone excretion. These changes reflect the processes of extended adaptation to a new environment. It is likely that shifts in electrolyte metabolism in weightlessness are primarily due to metabolic changes that diminish the tissue ability for ion retention and to concomitant changes in the endocrine status. The postflight examinations revealed changes in fluid-electrolyte metabolism and in the function of the kidneys which indicated a hypohydration status and a stimulation of hormonal systems responsible for fluid-electrolyte homeostasis in order to readapt to the normal gravitation. Postflight decline in osmotic concentration of urine in cosmonauts was accompanied by an altered response to antidiuretic hormone and was probably caused by changes in the functional state of the kidneys. We conclude that detailed knowledge of the alterations in water-electrolyte metabolism and its hormonal regulation on different stages of space flight are important prerequisites for the development of countermeasures to space deconditioning and thus for increased human efficiency in space. In addition, these data contribute to an increase in our general knowledge on the regulation of kidney function.

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.