Vol 4, No 3 (2012)


Immunology in the XXI Century — Progress and Achievements

Khaitov R.M.


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.

Acta Naturae. 2012;4(3):6-10
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The Chemistry of Life

Trofimov B.A.


Boris Aleksandrovich Trofimov, laureate of the Russian Federation National Award for substantial contribution to the development of new methods fine organic synthesis in order to design innovative drugs and modern materials, including specialpurpose ones, tells us about his discoveries and further research plans.

Acta Naturae. 2012;4(3):11-15
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The Use of Cellular Technologies in Treatment of Liver Pathologies

Petrakova O.S., Chernioglo E.S., Terskikh V.V., Kalistratova E.N., Vasiliev A.V.


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.

Acta Naturae. 2012;4(3):16-30
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Receptor Properties and Features of Cytokinin Signaling

Lomin S.N., Krivosheev D.M., Steklov M.Y., Osolodkin D.I., Romanov G.A.


Cytokinins belong to one of the most important and well-known classes of plant hormones. Discovered over half a century ago, cytokinins have retained the attention of researchers due to the variety of the effects they have on the growth and development of vegetable organisms, their participation in a plant adaptation to external conditions, and the potential to be used in biotechnology, agriculture, medicine and even cosmetics. The molecular mechanism by which cytokinins function remained unknown for a long time. Things started to change only in the 21 st century, after the discovery of the receptors for these phytohormones. It appeared that plants found ways to adapt a two-component signal transduction system borrowed from prokaryotic organisms for cytokinin signalling. This review covers the recent advances in research of the molecular basis for the perception and transduction of the cytokinin signal. Emphasis is placed on cytokinin receptors, their domain and three-dimensional structures, subcellular localization, signalling activity, effect of mutations, ligand-binding properties, and phylogeny.

Acta Naturae. 2012;4(3):31-45
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Lipopolysaccharide of Yersinia Pestis, the Cause of Plague: Structure, Genetics, Biological Properties

Knirel Y.A., Anisimov A.P.


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.

Acta Naturae. 2012;4(3):46-58
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A Polygenic Approach to the Study of Polygenic Diseases

Lvovs D., Favorova O.O., Favorov A.V.


Polygenic diseases are caused by the joint contribution of a number of independently acting or interacting polymorphic genes; the individual contribution of each gene may be small or even unnoticeable. The carriage of certain combinations of genes can determine the occurrence of clinically heterogeneous forms of the disease and treatment efficacy. This review describes the approaches used in a polygenic analysis of data in medical genomics, in particular, pharmacogenomics, aimed at identifying the cumulative effect of genes. This effect may result from the summation of gains of different genes or be caused by the epistatic interaction between the genes. Both cases are undoubtedly of great interest in investigating the nature of polygenic diseases. The means that allow one to discriminate between these two possibilities are discussed. The methods for searching for combinations of alleles of different genes associated with the polygenic phenotypic traits of the disease, as well as the methods for presenting and validating the results, are described and compared. An attempt is made to evaluate the applicability of the existing methods to an epistasis analysis. The results obtained by the authors using the APSampler software are described and summarized.

Acta Naturae. 2012;4(3):59-71
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Cardiological Biopharmaceuticals in the Conception of Drug Targeting Delivery: Practical Results and Research Perspectives

Maksimenko A.V.


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.

Acta Naturae. 2012;4(3):72-81
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Research Articles

Non-Thermal Plasma Causes P53-Dependent Apoptosis in Human Colon Carcinoma Cells

Tuhvatulin A.I., Sysolyatina E.V., Scheblyakov D.V., Logunov D.Y., Vasiliev M.M., Yurova M.A., Danilova M.A., Petrov O.F., Naroditsky B.S., Morfill G.E., Grigoriev A.I., Fortov V.E., Gintsburg A.L., Ermolaeva S.A.


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.

Acta Naturae. 2012;4(3):82-87
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Mitochondrial Pathway of α-Tocopheryl Succinate-Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells

Savitskaya M.A., Vildanova M.S., Kisurina-Evgenieva O.P., Smirnova E.A., Onischenko G.E.


Vitamin E derivatives are known to act as agents exhibiting cytotoxity against tumor cells. The effect of vitamin E succinate on human epidermoid carcinoma cell line A431 was investigated in this study using live imaging, immunocytochemistry, and transmission electron microscopy. α-Tocopheryl succinate-induced apoptotic cell death in A431 cells was shown to be both dose- and time-dependent. The hyperproduction of reactive oxygen species, changes in size, shape and ultrastructural characteristics of mitochondria followed by the release of cytochrome c from mitochondria to cytosol were observed. These results suggest that α-tocopheryl succinate induces apoptosis that occurs via the mitochondrial pathway. Mitochondria are shown to be crucial targets in α-tocopheryl succinate-induced caspase-dependent cell death in human carcinoma A431 cells.

Acta Naturae. 2012;4(3):88-94
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Gene Expression upon Proliferation and Differentiation of Hematopoietic Cells with PH Chromosome ex vivo

Grineva N.I., Duchovenskay E.A., Timofeev A.M., Akhlynina T.V., Gerasimova L.P., Manakova T.E., Borovkova T.V., Schmarov D.A., Sarycheva N.G., Naydenova N.M., Gavrichkova A.R., Kolosova L.Y., Kolosheynova T.I., Kovaleva L.G.


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.

Acta Naturae. 2012;4(3):95-114
pages 95-114 views

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