Vol 4, No 3 (2012)

The awarding ceremony for the laureates of the Russian Federation National Award 2011 in the field of science and engineering was held in Moscow this summer. Two interviews with the laureates are published in the popular science section of this issue of Acta Naturae. Rakhim Musaevich Khaitov, who has been awarded for outstanding achievements in the fundamental and practical development of Russian immunology, talks about the current state of biomedicine.

Cell techniques find increasing application in modern clinical practice. The II and III phases of clinical trials are already under way for various cellular products used for the restoration of the functions of the cornea, larynx, skin, etc. However, the obtainment of functional cell types specific to different organs and tissues still remains a subject of laboratory research. Liver is one of the most important organs; the problems and prospects of cellular therapy for liver pathologies are currently being actively studied. Cellular therapy of liver pathologies is a complex multistage process requiring a thorough understanding of the molecular mechanisms occurring in liver cells during differentiation and regeneration. An analysis of the current cellular therapy for liver pathologies is presented, the use of various cell types is described, the main molecular mechanisms of hepatocyte differentiation are analyzed, and the challenges and prospects of cell therapy for liver disorders are discussed in this review.

The present review summarizes data pertaining to the composition and structure of the carbohydrate moiety (core oligosaccharide) and lipid component (lipid A) of the various forms of lipopolysaccharide (LPS), one of the major pathogenicity factors of Yersinia pestis, the cause of plague. The review addresses the functions and the biological significance of genes for the biosynthesis of LPS, as well as the biological properties of LPS in strains from various intraspecies groups of Y. pestis and their mutants, including the contribution of LPS to the resistance of bacteria to factors of the innate immunity of both insect-vectors and mammal-hosts. Special attention is paid to temperature-dependent variations in the LPS structure, their genetic control and roles in the pathogenesis of plague. The evolutionary aspect is considered based on a comparison of the structure and genetics of the LPS of Y. pestis and other enteric bacteria, including other Yersinia species. The prospects of development of live plague vaccines created on the basis of Y. pestis strains with the genetically modified LPS are discussed.

The results of the clinical use of thrombolytic and antithrombotic preparations developed on the basis of protein conjugates obtained within the framework of the conception of drug targeting delivery in the organism are considered. A decrease has been noted in the number of biomedical projects focused on these derivatives as a result of various factors: the significant depletion of financial and organizational funds, the saturation of the pharmaceutical market with preparations of this kind, and the appearance of original means for interventional procedures. Factors that actively facilitate the conspicuous potentiation of the efficacy of bioconjugates were revealed: the biomedical testing of protein domains and their selected combinations, the optimization of molecular sizes for the bioconjugates obtained, the density of target localization, the application of cell adhesion molecules as targets, and the application of connected enzyme activities. Enzyme antioxidants and the opportunity for further elaboration of the drug delivery conception via the elucidation and formation of therapeutic targets for effective drug reactions by means of pharmacological pre- and postconditioning of myocardium arouse significant interest.

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.

The genes p53, mdm2, p21, c-myc, bcr/abl, bcr, bcl2, bax, and gapdh participate in the regulation of cell proliferation and differentiation, apoptosis and cell distribution for the cell cycle ex vivo in the Ph +cells of chronic myeloid leukemia containing the Ph chromosome and bcr/abl oncogene. Expression of these genes correlates with regulation of cell proliferation and differentiation by alternating proliferation and maturation stages for three main Ph +cell types that occur under chronic myeloid leukemia. The p53, p21, mdm2, and gapdh genes overexpress in active proliferating myeloid cells in the cell cycle S+G2/M phases and when the phases are coincident with the proliferation stage. Expression of these genes decreases to a considerable level under alternation of the Ph +cell proliferation and maturation stages and whenever the expression is greatly diminished under significant neutrophil accumulation and especially under repeated alternation of the stages. In the course of neutrophil maturation, gene expression levels decrease in the range of gapdh > actin > c-myc, bcr/abl,p21 > p53 > bcl2 > bax. The expression levels of these genes in neutrophils are lower than those in myelocytes and lower by an order of magnitude than that in the cells with a prolonged proliferation stage. The Bcr/abl expression gene under prolonged maturation and neutrophil accumulation is inhibited; however it is enhanced by 2-3 times for the proliferation stage with myelocyte accumulation. Minimal bcr/abl expression is observed under overexpression of p53, mdm2, p21, c-myc, as well as under cell maximum at the S and G2/M phases. Bcr/abl overexpression is observed under low expression of the p53, p21, mdm2 genes. In the Ph + cells with a high P/D efficiency index (5-20), overexpression of the genes in the range of bcr> gapdh>bcr/abl, as well as a decreased expression of the p53, bcl2, mdm2, p21<< gapdh genes is observed for Ph + cells from the CML blast crisis and CML acceleration phase. Low control of cell proliferation and cell cycle by gene-regulators presumably promotes bcr/abl overexpression and activates the production of bcr/abl + cells. Apoptosis in the Ph + cells is induced by expression of the bax > bcl2, p53, p21, c-myc and gapdh genes. The blocking of Ph + cell apoptosis, neutrophil accumulation, and decrease in the expression of the p53, mdm2 and p21, c-myc, bcr/abl genes occur at the maturation stage.