Vol 86, No 3 (2016)

A real revolution is under way in the development of medicinal preparations. New-generation medicines are able to change the course of oncological and cardiovascular diseases, as well as type one and type two diabetes mellitus. So-called “small molecules” are used to affect biological processes and monoclonal antibodies, which are valuable tools to control cells that cause pathological processes. Target preparations are able to identify damaged cells and destroy exclusively malignant neoplasms, not affecting healthy organs and tissues. Individually selected drug-induced therapy contributes to quick improvement in the patient’s condition and reduces considerably the risk of lethal outcome.

The results of studies of the molecular action mechanism of the peptides Semax and Selank—simple glyprolines that are used to prepare peptide-based drugs—are presented. A concept of creating an amino acid sequence of peptides is given; their interaction with receptor systems of the cell and their influence on the cell’s transcriptome, which forms the cell-mediated response, are considered. On the basis of the findings, pharmaceutical compositions of peptide drugs have been developed and their production and introduction into clinical practice have been organized.

Traditional approaches to chemotherapy remain ineffective in the case of aggressive tumors of the central nervous system. In this context, new strategies of the targeted delivery of antitumor preparations are actively being studied. This work presents the research results for vector nanocontainer systems based on anti-Cx43 and anti-GFAP monoclonal antibodies for the therapy of experimental C6 glioma. The focus has been on the creation of a C6 glioma model in rats, the synthesis of vector immunoliposome preparations, and the study of the binding of C6 glioma cells with monoclonal anti-Cx43 and anti-GFAP antibodies in vivo after intravenous infusion. Studies using the immunofluorescence method and intravital MRI have demonstrated the possibility to visualize the periglioma space with the obtained nanocontainer systems, which makes it possible to employ such systems for the targeted delivery of diagnostic and therapeutic agents to the periglioma zone of high-grade gliomas.

According to the concept of the young scientific discipline of epigenetics, the level of gene expression in various cells and tissues of the organism changes during the life of an individual under the influence of external and internal factors. The essence of reversible epigenetic modifications is enzymatic covalent association/dissociation of functional chemical groups to certain DNA nucleotides, as well as to amino-acid residues of histone proteins of chromatin. The two main epigenetic modifications are DNA methylation and histone deacetylation—the mechanisms that inhibit gene expression.

Active studies on the role of epigenetics in the initiation and progression of malignant tumors have led to the formation of an independent scientific trend, cancer epigenetics. The number of publications that prove the epigenetic nature of proliferative diseases of organs of the reproductive system, particularly nonmalignant and precancerous pathologies of the cervix, as well as endometrium pathologies accompanied by infertility, is rapidly growing.

The reversibility of anomalous epigenetic modifications makes its mediating enzymes extremely attractive medicinal targets in developing targeted epigenetic preparations. DNA methyltransferase and histone deacetylase enzymes are assumed to be the key targets. Recently, scientists have been paying increasingly more attention to nontoxic substances of natural origin with antitumor epigenetic activity.

The clinical studies conducted by the authors of this paper have shown that the preparations Indinol^® Forto (the active agent is indole-3-carbinol) and Epigallate^® (the active agent is epigallocatechin-3-gallate) (MiraksBioFarma, Ilmix Group, Moscow), which were usually prescribed within combination therapy of nonmalignant (HPV infections) and precancerous (CIN 1–2) diseases of the cervix and pathologies of the endometrium, are effective epigenetic means that significantly demethylate and restore the activity of tumor suppressor genes, normalize the clinical picture, and ensure the absence of relapses of the above diseases a year after combination therapy. It has also been established that these preparations reverse the anomalous DNA methylation of the genes HOXA10 and HOXA11 and restore the synthesis of these genes–coded proteins, which mediate the receptivity of the endometrium in patients with infertility against the background of chronic endometritis.

The proposed state-of-the-art schemes of combination therapy with the use of effective and safe epigenetically active preparations that restore the activity of tumor protection genes will become a powerful new tool for the treatment and prevention of widespread gynecological diseases, including those accompanied by infertility, and will favor qualitative improvement of the nation’s reproductive health.

Achievements in genomics and proteomics, as well as the exponential growth of computing power, ensure qualitatively new opportunities in understanding the molecular nature of “living matter” and, as a consequence, the extension of the capabilities of medicine. This paper considers two scientific fields in which high-throughput computing is especially effective. The first is computer-aided design of drugs, and the second is analysis of human molecular polymorphism and individual sensitivity to drugs. General provisions are illustrated with specific examples, including the development of a new class of antimyasthenic drugs—cholinesterase inhibitors, research in the molecular polymorphism of brain aspartoacylase, the clarification of the nature of Canavan disease, and the study of individual sensitivity to drugs—cholinesterase inhibitors.

The changeability of viruses largely depends on adaptation to the conditions of reproduction and mechanisms of the antiviral protection of host cells. Within populations, adaptation is associated with HLA specifics of identifying viral antigens. A population’s genetic profile and the diversity of HLA haplotypes affect not only the morbidity rate but also the destiny of entire ethnic groups, their size, and premature mortality indicators. Therefore, the solution to the problem of protecting a population against mass viral infections is impossible without taking into account the HLA interethnic polymorphism, which specifies sensitivity to infections and response to mass vaccination. Recent achievements in human genetics allow the system of preventive medicine to upgrade to the level of genetic personalization. In a multinational country like Russia, this approach should become the basis for the preventive trend in practical medicine.

As is known, the creation of effective and safe drugs rests on priority trends of scientific and technological advance, based on new knowledge in the field of life sciences and living-system technologies. Essentially, the entire diversity of biotechnologies is primarily targeted at using biological objects as a means for the production of effective and safe drugs, among which the share of phytopreparations and biologically active substances from plants amounts to 60–65%.

Ever since the end of WWII and the Great Patriotic War 70 years ago, debates on this epoch-making event in world history have never ceased. They became particularly acute after the disintegration of the Soviet Union and the Warsaw Pact. Last year, a new burst of discussions was caused by the 70th anniversary of the Victory. The author of this scientific paper, which was heard at a meeting of the RAS Presidium, highlights important points of the discussions and the shift of the focus of historical studies from military actions toward a wide panorama of life activities of society and individuals in the conditions of the war and its reflection in mass consciousness.

Substantial changes in the global and domestic wine market have made it necessity to modify the technologies of producing high-quality wines, to decrease production costs, and to ensure food safety. Proceeding from the long-standing analysis of the industry’s economy, climatic and agrocenotic changes, and topical research and practice tasks, a number of fundamental scientific problems are formulated that should be solved to obtain new knowledge in order to increase the efficiency and competitiveness of the sector’s production. The dynamics and development of cenotic interconnections and physiological–biochemical processes in the components of agroecosystems, which are predetermined by the significant edaphoclimatic differentiation of viticulture zones and microzones, as well as by a number of other factors, require continuous research and development of preventive measures to maintain agrocoenoses in highly productive conditions, the creation and adaptation of assortments, epiphytotic prevention, and bringing the technologies into accordance with the level of production development.

This article is a continuation of the work published in the journal Vestnik RAN (no. 3, 2016). The previous article described the international experience in preparing and using agent-oriented models and technical groundwork for their implementation on supercomputers. This article describes two multiagent demographic models built at the RAS Central Economics and Mathematics Institute. The models differ in the level of detailization when simulating human reproductive behavior. The stages and methods of the efficient reflection of the computing core of a multiagent system on the architecture of a state-of-the-art supercomputer using the supercomputer technology for agent-oriented simulation (STARS) developed by the authors are analyzed.

The first hotspots of WWII sprang up in the Far Eastern region of Asia because of the aggressive actions of Japan, the intent of which was directed at China. In the summer of 1937, upon occupying China’s northeastern provinces and creating there the puppet state of Manchukuo, Japan, under the slogan Pan-Asianism ideas, the seizure of China at large started. Under this threat, the leadership of the Republic of China announced its readiness to fight against the aggressor and to carry on a long war with Japan. The Soviet Union began to provide serious support for China’s military by supplying weapons and sending military advisers, specialists, and volunteer pilots. In fact, during the war between China and Japan, the Soviet Union and the Republic of China formed a strategic partnership. Therefore, the Soviet support of China’s integrity helped its people to preserve the country in the general front of the Allied Powers in WWII.