Immunomodulatory properties of recombinant human granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a myelopoietic growth factor that exerts pleiotropic effect not only on the differentiation of immature progenitor cells into polymorphonuclear neutrophils, monocytes/macrophages and dendritic cells, but also controls the functioning of differentiated cells. GM-CSF is currently being investigated in clinical trials as an immunomodulator and adjuvant. However, a wide range of biological activities and, sometimes, paradoxical effects of this cytokine require more thorough studies of its action, in order to predict its efficacy under different conditions of immunotherapy. In this work, we have studied the effect of recombinant human GM-CSF on metabolic activity of mouse peritoneal exudate cells in primary cell cultures. Metabolic (redox) activity of the cells was assessed by their ability to reduce nitroblue tetrazolium (NBT) in the course of MF- and Fc-dependent phagocytosis triggered by addition of opsonized zymosan, or sheep erythrocytes to the culture medium. We have shown the dose-dependent stimulatory effect of GM-CSF on the oxidative metabolism of phagocytic peritoneal macrophages and neutrophils. Upon culturing the pepton-elicited cells at wide range of GM-CSF concentrations (5 to 40,000 ng/mL) for 2 and 24 hours, a more pronounced effect of the substance was observed for neutrophils. The GM-CSF preparation caused a significant increase (by 13-17%) in the redox activity of neutrophils induced by opsonized zymosan that persisted at a low dose range, and was retained after 24 hours. The stimulatory effect of GM-CSF on macrophages with NBT index increase by 16% was observed in the short-term cultures. In general, the elicited cells of both types showed a more pronounced response to lower concentrations of GM-CSF (5-125 ng/mL), and weaker effect at higher doses of the preparation. A similar dependence was found when studying the resident macrophages. Culturing of resident cells with GM-CSF at the doses of 5,000 to 40,000 ng/mL for 24 hours caused a significantly increased redox activity of the cells induced by zymosan, or sheep erythrocytes (by 33-52%). In both cases, the maximal response was detected at a dose of 5,000 ng/mL and decreased with increasing dose. The stimulatory effect of GM-CSF upon resident macrophages was more pronounced as compared to elicited cells, which was characterized by the prolonged period of cell activation (up to 24 hours of culture). The data obtained are of interest, in view of prospective usage of GM-CSF as a component of immunomodulatory and adjuvant therapy for various infectious diseases

Study of the adjuvant properties of preparations containing recombinant human granulocyte-macrophage colony stimulating factor

The relevance of the search for new vaccine adjuvants is growing along with the increase in the number of current vaccine preparations, especially those developed on the basis of proteins. Some cytokines are known to exert adjuvant properties. The present work is devoted to the study of adjuvant activity of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and constructs based on it. Earlier, we developed a technology for isolation and purification of GM-CSF from the E. coli SG20050/p280_2GM producer strain, as well as a technology for conjugating polyglucin:spermidine complexes with rhGM-CSF. Double-stranded RNA was used to obtain molecular constructs on the basis of rhGM-CSF conjugate. To assemble constructs, the ratio of the components was calculated for one dose of the preparation to contain 5-40 mg of rhGM-CSF and 100 mg of double-stranded RNA. The effectiveness of the formation of molecular constructs was evaluated by dsRNA electrophoretic mobility shift in a 1% agarose gel. The effectiveness of the resulting adjuvants was determined in ELISA assays by measuring the titers of specific antibodies in mouse sera against ovalbumin or recombinant receptor-binding domain of the surface S protein of the severe acute respiratory syndrome coronavirus 2 (Delta variant (B.1.617.2). The experiments were carried out in 100 male BALB/c mice weighing 16-18 g. Mice were immunized twice, with a 14-day interval, by intramuscular injection of 200 mL per animal. Recombinant receptor-binding domain of the surface protein of SARS-CoV-2 was administered at a dose of 50 mg/animal, ovalbumin – at two doses – 1 mg or 5 mg/animal. Corresponding antigen was used as a positive control, a saline solution – as a negative control. It was shown that the maximum effect was achieved by immunization with a construct based on double-stranded RNA and rhGM-CSF conjugated to polyglucin-spermidine. The use of a conjugate without double-stranded RNA as an adjuvant also improved humoral response. The use of native rhGM-CSF did not increase the titers of specific antibodies. Thus, it was found that rhGM-CSF being a part of a polysaccharide conjugate or a molecular construct exerted an ability to enhance the humoral immune response to protein antigens

FEATURES OF SAFE DEVELOPMENT ENSURE OF HAZARDOUS GAS-DYNAMIC PHENOMENA DEPOSITS

Geomechanical methods to control the deposits of dangerous gases are developed. Conditions for the formation of through and closed local gaz channels are established. It allows choosing efficient positioning of degasification wells, to find and apply the optimal settings. A correlation between residual pressure of methane after degassing events and horizontal deformations of the dangerous layer is holding. Using the results of researches will allow to prevent accidents or to reduce their negative impacts and to increase the efficiency of methane utilization

INTEGRATION OF THE BUSINESS COMMUNITY AND EDUCATION AS A FACTOR OF INNOVATION DEVELOPMENT OF THE REGION'S ECONOMY (ON THE EXAMPLE OF THE LIPETSK REGION)

Summary. Modern global processes identified human capital, education and science as determinants of innovation development. In order to achieve economic growth the government should create the necessary conditions for effective interaction of business, scientific and educational processes at the level of each region. Most of the subjects of the Russian Federation tend to the mono-production of individual industries. The basic industry of the Lipetsk region is metallurgy. The policy of modernization and differentiation of economy allowed to reduce the share of this sector to 55% and led to the rapid development of other industries, agriculture, food and processing industry and construction. Innovations are widely supported and new types of production are created in the region. High rates of economic development have affected the regional labor market, changed the structure of labor demand and increased employers’ requirements to the quality of educational programs. The system of vocational education of the Lipetsk region is represented by the institutions of different levels. It offers a wide range of educational programs for traditional sectors of the regional economy. New and high-tech industries have a shortage of personnel. Employers demand engineering and technical professions and highly skilled workers. It is necessary to organize continuous improvement of qualification and create a system of continuous and advanced vocational education. To solve the problem of the shortage of labour in the region the Concept of "Human resource development of the Lipetsk region” was developed and approved. There is a Coordinating Council on staffing and vocational education. The road map for the creation of manufacturing and educational clusters was approved. Manufacturing and educational cluster of metallurgical profile proved to be effective. Three more manufacturing and educational clusters of machine-building, agriculture and construction profiles are created and developing. It is necessary to strengthen the integration of the business community and education, to form professional competence, to extend forms of interaction between the real sector of economy and professional educational institutions

The features of calculation movements and deformations of the surface at borehole to hydromining operations

The new calculation method of the surface movements and deformations in which for the first time prominent features of the developed space at borehole hydromining operations are considered is developed

Russian Students’ Social Representations of Higher Education

The ideas of the theory social representations proposed by Moscovici and developed in the structural approach by Abric were used in the research in order to reveal the structure and content of students’ social representations of higher education in a modern society. The total sample size was 572 students: of which 197 were secondary school students (average age of 16.7), 189 were undergraduate students (average age of 20.8) and 186 were master students (average age of 29.3). The methodology of Vergès for the analysis of the structure of social representations was used. We tested the hypothesis that the structure of social representations of higher education has general and specific features correlated to the age and educational level of students. It was found that the social representations of schoolchildren, undergraduate students and master’s students differ in a number of elements and content characteristics. Generally social representations of students with different education levels had similar characteristics. Students of secondary schools expanded the core performance, in contrast to students of universities, presumably because of their fewer social experiences, providing large “distance” to higher education as an “object”

CARDIOLOGICAL ASPECTS OF THE JOINT HYPERMOBILITY SYNDROME

Objective: to identify the capacities of a Cardiovisor-06C device in the diagnosis of the cardiological aspects of the joint hypermobility syndrome (JHMS). Subjects and methods. The study covered 12 students with JHMS. All the respondents were examined using a Cardiovisor-06C device. Results. All the students were found to have deviations from the normal integral indicators: Myocardium, Rhythm, Pulse, Specification code, as well as some electrocardiogram indicators: the durations of P-Q and Q-T intervals and P wave. Conclusion. The early and preclinical manifestations of possible heart abnormalities in the JHMS can be detected by a Cardiovisor-06C device

CARDIOVASCULAR RISK FACTORS AND SELECTED PARAMETERS OF ECG DISPERSION MAPPING IN MEDICAL STUDENTS

Aim. To investigate the association between the risk factors (RFs) of cardiovascular disease (CVD) and selected parameters of ECG dispersion mapping in medical students, in order to facilitate preclinical diagnostics and timely risk management.Material and methods. The study included 72 students of the Internal Disease and Paediatrics Faculties of the N. N. Burdenko Voronezh State Medical Academy, aged 21–26 years (mean age 21,9±0,1 years; 18 men and 54 women). The examination included a questionnaire survey on CVD RFs, a clinical assessment, and the measurement of hemodynamic parameters. ECG parameters, including such integral characteristics as “Myocardium”, “Rhythm”, and “Detail Code”, were assessed both at rest and during the physical stress test, using the Cardiovisor 6C device.Results. All participants were divided into two groups. In the group with multiple CVD RFs, the distribution of these factors was as follows: 40% smoked (n=6), 53% consumed 2–3 drinks of alcohol per occasion (n=8), 40% had high normal blood pressure (BP) or Stage 1 elevation of BP, based on the office measurement data (n=6). Three (20%) and 4 (27%) students were overweight (OW) and obese (O; Stage I), respectively. Low physical activity (PA) was reported by 14 students (93%), and moderate to high levels of stress by 67% (n=10) and 33% (n=5), respectively. Immediately after the physical stress test and 2 minutes later, the “Myocardium” parameter was ≥17%, being significantly different from the values observed in students without multiple RFs. Abnormal values of the integral parameters of ventricular depolarisation and left ventricular repolarisation suggest the myocardial electrical heterogeneity among students with multiple CVD RFs.Conclusion. Students with multiple CVD RFs, such as smoking, alcohol, elevated BP, OW, Stage I O, moderate to high stress levels, and low PA, also demonstrated the myocardial electrical heterogeneity during the physical stress test

Structural test of anatomy of pancreas in pathological process

Topografo-anatomic features of a pancreas of dogs from a position of ultrasonic diagnostics are established and the algorithm of her research is developed for a pathology (detailed survey Para pancreatic fabrics and itself glandule; survey of all departments of a belly cavity for a free liquid; survey of pleural cavities and cavities of a pericardium on presence liquor; detailed survey of bilious channels; aim survey of vessels of system vein Porte, research retroperitoneal spaces)

The clinical morphology of a pancreas of dogs by ultrasonic diagnostics

In article are defined anatomic and ultrasonic reference points of a pancreas at dogs from the point of view of topographical anatomy and its standard morphological indicators are established. It is thus shown that they completely correspond to ultrasonic data and are defined somatotypes animals. On the basis of the analysis of data of a morphometry and ultrasonic research compliance of structural characteristics of a pancreas to its ultrasonic indicators, both in norm is revealed, and at pathology. Scientific justification of application of a method of an ultrasonographic at diagnostics of pathologies of a pancreas at the dogs, based on results of studying of topography-anatomic and ultrasonic parameters of this body is presented. Advantage of application of an ultrasonic method of research as the main diagnostic indication is shown at identification and treatment of animals with pancreas pathology