Search

Objectives. The aim of this study was to identify variation patterns of the in-series variation coefficient of adhesive strength to base and the dependency of the frost resistance coefficient on the criterion of adhesion on prescription factors of fine-grained concrete obtained from dry building mixtures based on various Portland cements containing various low-modulus inclusions and redispersible polymer powders from 0 to 3%. According to GOST 31357, the main quality indicators of the hardened mixture or fine-grained concrete, in addition to frost resistance, include the indicator of “frost resistance of the contact zone”, which characterises the ability of the hardened concrete to maintain adhesion to the base during normal separation following a certain number of freeze-thaw cycles.Method. The tests of the main samples were carried out after 75 freeze-thaw cycles in accordance with GOST 31356. The marks of the frost resistance of the contact zone are set from FKZ25 to FKZ100. The number of freeze-thaw cycles is taken as a mark, after which the adhesion strength to the base, determined according to GOST 31356, is at least 80% of the strength of the control samples. The arithmetical average is taken at between at least 5 values, while the variation coefficient measured across a series of adhesion strength values is not considered.Results. The average values of the variation coefficient of adhesion strength were: following 75 cycles of freezing-thawing – 0.224 (in a range from 0.058 to 0.616); following 25 cycles of freezing-thawing – an average of 0.129 (in a range from 0.016 to 0.352). The variation coefficient of adhesion strength can exceed the variation coefficient of compression strength by approximately 2.5 to 3 times. When introducing the redispersible powders into the structure of fine-grained concrete, there is no unambiguous pattern of change in the values of the variation coefficient of adhesion to base and it is possible to increase or decrease this value, while the values of the variation coefficient of adhesion can vary by an order of magnitude.Conclusion. For all concretes, there is a tendency of increase of the coefficient of frost resistance with a decrease in the adhesion variation coefficient both after hardening under normal conditions as well as during cyclic freezing and thawing. When conditions VF/V28A

Objectives This study was aimed at identifying the dependency of the frost resistance of the contact zone of fine-grained concretes (FGCs) obtained from dry building mixtures (DBMs) based on various Portland cements (PCs) with the content of various redispersable polymer powders (RPPs) from 0 to 3%.Method The research was based on 75 freeze-defrost cycles.Results Although the average dependency of adhesion with the base on additional porosity after 75 freeze-defrost cycles does not depend on the nature of NMV, adhesion is influenced by the cement type, the type and dosage of RPPs, as well as the nature of additional porosity. Since the content of organised volume of NMV in the form of VV has no effect on changes in adhesion with the concrete base following 75 freeze-defrost cycles, it is impractical to add more than 7% of NMV in the form of MS to the concrete mixture. The feasibility of using sulphate-resistant cement requires more research. The practical RPP dosage should be 1-2%. Some contradictions in conclusions on the volume of the introduced MS (by the strength criterion – at least 6%, by the criterion of frost resistance of the contact zone – no more than 7%) allows us to recommend the dosage of MS in RPP within 6-7% by volume for obtaining additional data on the MS effect on frost resistance.Conclusion The dependency of compressive strength on additional porosity for FGCs without NMV and with NMV in the VV form after hardening during 28 days under normal conditions almost coincides with the known dependency of strength on porosity for cement stone; the maximum divergence of the values ???????? ????0 in the investigated range does not exceed 5%. The dependency of compressive strength on additional porosity for FGCs without NMV and with NMV in the MS form is similar to the known dependency of strength from porosity for cement stone; however, with increasing porosity, there is a slight decrease in the effect of porosity on strength. The dependency of compressive strength after 75 freeze-defrost cycles on additional porosity for FGC without NMV practically coincides with the previously obtained dependency of strength on porosity for cement stone; the maximum divergence of the values ???????? ????0 in the investigated range does not exceed 9%. For FGCs with NMV in the MC form, increasing porosity causes a slight decrease in the porosity effect on strength, and for FGCs with NMV in the VV form, the dependency has a quantitative and qualitative difference. The value of NMV in the VV form recommended for improving the frost resistance of FGCs by the strength criterion is at least 3%, MS – at least 6%. According to the criterion of the frost resistance of the contact zone and the strength of MS, the recommended dosage is 6-7%. It was not possible to disclose the direct impact of the VV volume on the frost resistance of the contact zone.

Objectives Reliability and durability of structures using materials with various properties (plaster coatings, cement glue, new concrete during repair and restoration of structures, etc.) largely depends on the adhesion of the layers and the deformation properties of the coatings. To obtain the required properties of materials used for coatings, modifiers based on polymers and low-modulus inclusions are introduced into the composition of new concretes, for example, entrained air. The aim of the work is to identify some patterns of change in the properties of concrete with the joint introduction of these modifiers.Method Experimental determination of the tensile strength in bending, compression, E-modulus, adhesion to the concrete base by standard methods.Result The influence of separate and joint introduction of dispersible polymer powders and various low-modulus inclusions into the composition of fine-grained concrete has been established.Conclusion The joint introduction to the composition of fine-grained concrete of various low-modulus inclusions and redispersible polymer powders provides a reduction in the stress level during forced deformations due to the different effects additives on the strength and deformation properties and contributes to increased adhesion to the concrete.

Vitamin D3 transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α—M1 phenotype) or anti-inflammatory (TGF-β, IL-10—M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components.

Introduction. People in helping professions are more prone to emotional burnout and depression. Even at the university level, future physicians experience an increase in depressed mood. Despite the fact that this problem has been studied quite extensively, the role of socio-cognitive factors has not yet been studied enough. The purpose of this research is to fill this gap and explore the relationship between career anchors and the level of depressed mood among Russian medical students. Materials and Methods. The survey was conducted in 2020 and 2021. The sample of the survey included 864 students of the SSMU named after V. I. Razumovsky. Methods used in the survey: the Zung Self-Rating Depression Scale (SDS), adapted by T. I. Balashova and the diagnosis of career anchors, using Schein’s Career Orientations Inventory (COI) in the adaptation of V. A. Chiker. Data analysis methods: Shapiro‒Wilk and Fligner‒Killeen tests, Wilcoxon‒Mann‒Whitney and Nemenyi tests, and biweightmidcorrelation analysis. The search for predictors of depressed mood was carried out using the method of generalized additive models. Results. Career anchors are predictors of depressed mood. Service orientation and professional competence reduce the severity of depressed mood, while the relationship is non-linear. The desire of students to integrate different areas of their lives and organize the activities of other people is negatively associated with depressed mood, but the relationship is linear. The severity of depressed mood is exacerbated by career anchoring on autonomy. Discussion and Conclusion. The results of the study contribute to the understanding of the complex relationship between depressiveness and socio-cognitive factors. The results of this study can be instrumental in the development of a set of measures reducing the risk of depression in medical professionals by studying at a university.

Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.

Objective: Glioma is a highly invasive tumor, frequently disposed in essential areas of the brain, which makes its surgical excision extremely difficult; meanwhile adjuvant therapy remains quite ineffective. Methods: In the current report, a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model. This approach, termed “Karanahan”, is aimed at the eradication of cancer stem cells (CSCs), which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA. After being internalized, these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics, and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency. Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation. Results: U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice. In SCID mice with developed subcutaneous grafts, the treatment resulted in reliable slowing down of tumor growth rate (P < 0.05). In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment, the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control. Conclusions: The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.

The paper describes some biological features of the radioprotective effect of double-stranded RNA preparation. It was found that yeast RNA preparation has a prolonged radioprotective effect after irradiation by a lethal dose of 9.4 Gy. 100 % of animals survive on the 70th day of observation when irradiated 1 hour or 4 days after 7 mg RNA preparation injection, 60 % animals survive when irradiated on day 8 or 12. Time parameters of repair of double-stranded breaks induced by gamma rays were estimated. It was found that the injection of the RNA preparation at the time of maximum number of double-stranded breaks, 1 hour after irradiation, reduces the efficacy of radioprotective action compared with the injection 1 hour before irradiation and 4 hours after irradiation. A comparison of the radioprotective effect of the standard radioprotector B-190 and the RNA preparation was made in one experiment. It has been established that the total RNA preparation is more efficacious than B-190. Survival on the 40th day after irradiation was 78 % for the group of mice treated with the RNA preparation and 67 % for those treated with B-190. In the course of analytical studies of the total yeast RNA preparation, it was found that the preparation is a mixture of single-stranded and double-stranded RNA. It was shown that only double-stranded RNA has radioprotective properties. Injection of 160 μg double-stranded RNA protects 100 % of the experimental animals from an absolutely lethal dose of gamma radiation, 9.4 Gy. It was established that the radioprotective effect of double-stranded RNA does not depend on sequence, but depends on its double-stranded form and the presence of “open” ends of the molecule. It is supposed that the radioprotective effect of double-stranded RNA is associated with the participation of RNA molecules in the correct repair of radiation-damaged chromatin in blood stem cells. The hematopoietic pluripotent cells that have survived migrate to the periphery, reach the spleen and actively proliferate. The newly formed cell population restores the hematopoietic and immune systems, which determines the survival of lethally irradiated animals.

Substances for manufacture of parenteral drugs require control by the «Bacterial Endotoxin» (BE) Index with the LAL-test. The aim of the study was to show possible applicability of organic solvents in BE determination by the gel-thromb test in case of water-insoluble pharmaceutical substances. The results confirmed that ethyl alcohol practically had no effect on the endotoxin activity. In the routine assays it is advisable to test solutions of the substances at the alcohol concentration of 6% below.

The use of the LAL test as a method for determining bacterial endotoxins (BE) allows us to normalize the content of impurities causing a pyrogenic reaction in patients. Increasing the reliability and reproducibility of this method is promoted by validation procedures, which are an integral part of the methods for determining BE and are based on the construction of a «model experiment» where the test and control samples are compared. Depending on the test procedure (gel-clot or photometric tests) for determining the presence of BE, appropriate validation procedures are used to assess the necessary parameters. The purpose of the study: to prove the possibility of interchangeability of the methods for determining BE with the help of validation procedures on the example of the drug «Ceftriaxone powder for intramuscular injection 500 mg». Research techniques: Gel-clot and Kinetic Chromogenic tests. The results of the conducted tests confirm the reproducibility and specificity of the LAL test methods. The sensitivity of the LAL reagent used is confirmed. In the experiments of the gel-clot test for Ceftriaxone, a dilution of 1:160 of the base solution in the concentration of 100 mg/ml was validated. The parameters of the calibration curve in the Kinetic Chromogenic test corresponded to the validation requirements (CV0.98). Determination of the bacterial endotoxin content in Ceftriaxone by the photometric method is possible at the same 1:160 dilution, where the accuracy of determination of the BE in the test sample is

The article reports an original method for producing vitamin D3-binding protein (DBP) and its conversion into macrophage-activating factor GcMAF-RF. According to an original protocol, DBPs were obtained from human blood plasma using affinity chromatography, purified and modified to GcMAF-RF using cytoimmobilized glycosidases (beta-galactosidase and neuraminidase). The presence of the polypeptide obtained in the Gc group of blood plasma globulins was confirmed by Western blot using specific antibodies. The molecular properties of this polypeptide put it in correspondence with the GcMAF protein described in the literature, which is undergoing clinical trials in the USA, Britain, Israel and Japan (at Saisei Mirai; Reno Integrative Medical Center; Immuno Biotech Ltd; Efranat; and Catalytic Longevity). The biological activity of the GcMAF-RF preparation was detected by the induction of phagocytic activity of macrophages and their ability to produce nitrogen monoxide (NO) in vitro.The phagocytic activity of macrophages was evaluated by their ability to uptake magnetic beads. The degree of activation of macrophages was calculated by the ratio of trapped beads to the total number of macrophages. The level of NO production was estimated by the accumulation of nitrogen monoxide in the culture supernatants of peritoneal macrophages by the colorimetric method using the Griess reagent. It was shown that GcMAF-RF multiplies the phagocytic activity of macrophages and significantly increases their production of nitrogen monoxide. The macrophage activator GcMAF-RF, according to its characteristics, corresponds to similar preparations which are made available to the market by foreign companies, and can be considered as a new biologically active preparation with a wide spectrum of action. Of greatest interest is its ability - through the activation of macrophages - to enhance the adaptive immunity. In this regard, two areas of therapeutic use of the GcMAF-RF are proposed. The preparation will be in demand in the field of cancer treatment, and, in addition, it can be used in the treatment of a number of neurodegenerative pathologies.

Introduction: Karanahan , a cancer treatment technology aimed at eradicating tumor-initiating stem cells, has already proven effective in 7 tumor models. Karanahan comprises the following procedures: (1) collecting surgical specimens, (2) determining the duration of the DNA repair process in tumor cells exposed to a cross-linking cytostatic agent, and (3) determining the time point, when cells, including tumor-initiating stem cells, are synchronized in the certain phase of the cell cycle after triple exposure to the cytostatic, becoming vulnerable for the terminal treatment, which is supposed to completely eliminate the rest of survived tumor-initiating stem cells. Determining these basic tumor properties allows to design the schedule for the administration of a cross-linking cytostatic and a complex composite DNA preparation. Being conducted in accordance with the schedule designed, Karanahan results in the large-scale apoptosis of tumor cells with elimination of tumor-initiating stem cells. Methods: Breast tumor specimens were obtained from patients, and basic tumor properties essential for conducting Karanahan therapy were determined. Results: We report the first use of Karanahan in patients diagnosed with breast cancer. Technical details of handling surgical specimens for determining the essential Karanahan parameters (tumor volume, cell number, cell proliferation status, etc) have been worked out. The terminally ill patient, who was undergoing palliative treatment and whose tumor specimen matched the required criteria, received a complete course of Karanahan . Conclusions: The results of the treatment conducted indicate that Karanahan technology has a therapeutic potency and can be used as a breast cancer treatment option.

The control of transverse magneto-optical Kerr effect (TMOKE) enhancement is realized by balancing the radiative and absorption losses in one-dimensional all-nickel magnetoplasmonic crystals. The modulation of the surface shape tunes the plasmonic radiative losses and coupling of the incident light with surface plasmons. The maximal magneto-optical response corresponds to the optimal coupling implemented with the equality of radiative and absorption losses. A slight deviation from the optimal corrugation depth results in a significant reduction of the TMOKE value.

Vitamin D3 Binding Protein (DBP) is a multifunctional glycoprotein whose main role is to transport vitamin D3 and its metabolites, but it also is the precursor of the macrophage activating factor (GcMAF). DBP is converted to GcMAF as a result of site-specific selective deglycosylation under the action of β-galactosidase and sialidase, localized on activated B and T cells, respectively. GcMAF exerts its biological activity primarily as the capability of activating macrophages by enhancing their phagocytic function and producing ROS. Activation results in elevated expression of the specific macrophageal surface receptors involved in the recognition of tumor-associated antigens, as well as in the implementation of direct anticancer activity by inducing the apoptosis or necrosis of tumor cells. Increased interest in GcMAF is associated with its potential to be used in the clinic as a new antitumor drug. Besides its anti-tumor activity, GcMAF exerts a potential against a number of viral and neurodegenerative diseases associated with increased activity of N-acetylgalactosaminidase (nagalase) in the blood serum of patients. Nagalase is an enzyme that completely (rather than selectively) deglycosylates DBP so it cannot be converted to GcMAF, leading to immunodeficiency. Circulating DBP is composed of unmodified and O-glycosylated molecules with the glycosylation degree being dependent on the allelic variants of the gene encoding DBP. The role of DBP in the resistance of organism against a number of diseases is supported by the increased risk of a variety of severe illnesses (amyotrophic lateral sclerosis, colorectal cancer etc.) in patients deficient for GcMAF due to homozygosity for defective DBP alleles. In this review, we also will examine in detail the current data i) on the structure and functions of DBP, as the main precursor of GcMAF, ii) on the main mechanisms of GcMAF anticancer effect, iii) on the tumor strategy for neutralizing GcMAF activity, iv) on the results of GcMAF clinical trials in various cancers; and will discuss the available controversies regarding the positioning of GcMAF as an effective antitumor drug.

The article describes a method of comparative economic evaluation of technologies or options for the development of mineral deposits by underground mining, which, according to the mining and geological conditions, under these conditions may be alternative. It is shown that in modern conditions of changing technological structures, the hardening of the real economy involves the development of methods for evaluating the effectiveness of industrial technologies on a competitive basis. Definitions of terms and concepts in mining practice are given. As a criterion for evaluating the economic efficiency of the compared development systems, traditionally accepted is the magnitude of the conditional profit from mining and processing of ores in all areas of mining. The concepts of conditionally variable reduced costs are clarified. An algorithm for calculating the conditional profit for the technologies used for the extraction and processing of ores and the determination of them economically optimal is given. The technology indicators necessary for minimization of economic consequences from ore losses at the considered technology are determined. The approach to the definition of equivalent economic relations between indicators of the developed area is formulated. The conclusion is made about the feasibility of using the proposed methodology for the assessment of technology in order to optimize technological solutions at the design stage of a field for development with economic effect.

Abstract Background We have characterized the human cell line arised from the Epstein–Barr virus (EBV) positive multiple myeloma aspirate subjected to the long-term cultivation. This cell line has acquired the ability to form free-floating spheres and to produce a xenograft upon transplantation into NOD/SCID mice. Methods Cells from both in vitro culture and developed xenografts were investigated with a number of analytical approaches, including pathomorphological analysis, FISH analysis, and analysis of the surface antigens and of the VDJ locus rearrangement. Results The obtained results, as well as the confirmed presence of EBV, testify that both biological systems are derived from B-cells, which, in turn, is a progeny of the EBV-transformed B-cellular clone that supplanted the primordial multiple myeloma cells. Next we assessed whether cells that (i) were constantly present in vitro in the investigated cell line, (ii) were among the sphere-forming cells, and (iii) were capable of internalizing a fluorescent TAMRA-labeled DNA probe (TAMRA+ cells) belonged to one of the three types of undifferentiated bone marrow cells of a multiple myeloma patient: CD34+ hematopoietic stem cells, CD90+ mesenchymal stem cells, and clonotypic multiple myeloma cell. Conclusion TAMRA+ cells were shown to constitute the fourth independent subpopulation of undifferentiated bone marrow cells of the multiple myeloma patient. We have demonstrated the formation of ectopic contacts between TAMRA+ cells and cells of other types in culture, in particular with CD90+ mesenchymal stem cells, followed by the transfer of some TAMRA+ cell material into the contacted cell.

Primary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was evaluated on the primary cell lines of human glioblastoma culture by employing a new strategy of tumor-initiating stem cell synchronization and a domestic strategy of their eradication "3+1". The key elements of the strategy were the following indicator results: (1) evaluation of the presence of tumor-initiating stem cells in a population of cells from analyzed cultures by their ability to internalize double-stranded labeled DNA (TAMRA+ cells); (2) determination of the reference time points of the repair cycle of DNA interstrand cross-links induced by cross-linking cytostatic mitomycin C; (3) evaluation of cell cycle synchronization; (4) determination of the time (day after therapy initiation) when TAMRA+ cells were synchronously present in phase G1/S of the cell cycle, sensitive to the therapy; and (5) establishment of the TAMRA+ (tumor-initiating stem cells) eradication schedule. The cultures were treated with cross-linking cytostatic mitomycin C and a compositional DNA preparation. After the treatments, cell division slows down, and the cultures degrade. The K cell line completely degraded within 30 days of observation. The cell number of the Zh culture fell to nearly one-third of the starting value by day 15 of observation. On day 15, this indicator constituted 1/7.45 for mitomycin C and 1/10.28 for mitomycin C + DNA with reference to the control. The main target of the mitomycin C + DNA regimen was TAMRA+ tumor-initiating stem cells of the glioblastoma cell populations. The action of mitomycin C alone or in the combination with DNA demonstrated effective elimination of TAMRA+ tumor-initiating stem cells and the whole primary cultures of human glioblastomas.

One of the most important properties of extracellular double-stranded DNA related to the treatment of various diseases is its ability to activate effector cells of the immune system (anti-tumor and vaccinal immunity) through dendritic cells (DCs). The stimulatory effect of DNA on DCs is mediated by the TLR9 signaling pathway and/or through a system of cytosolic sensors and is manifested by increased expression of MHC class II antigens and costimulatory molecules and by increased synthesis of immunoregulatory cytokines. In this work, the expression of cytokines, differentiation antigens and transcription factor genes has been investigated in DCs activated by double-stranded human DNA (i) without any additional factors, (ii) using a lipophilic agent, and (iii) by blocking TLR9 with chloroquine. Evaluation of the DNA effect was carried out after the 6- and 24-hour exposure. It was found that the preparation of double-stranded DNA transfected by Lipofectamine 2000 boosts DCs at the same level as Poly(dA : dT), a synthetic equivalent of double-stranded DNA. It was discovered that combined application of DNA and chloroquine enhances expression of the IFN-α, IFN-β, IFN-γ, IL­8, МСР1, VEGF, CD25, and CD83 genes by hour 24 of incubation. It was for the first time shown that genomic “self” double-stranded DNA as a mono agent activates mRNA synthesis of cytokines IFN-α, IFN-β, IFN-γ, IL­8, IL­10, and VEGF in DCs at 6 hours of induction.

Metasurfaces are not adjustable after fabrication, and a critical challenge is to realise a technique of tuning their optical properties that is both fast and efficient. Here, Shcherbakov et al. realise an ultrafast tunable metasurface with picosecond-scale large absolute reflectance modulation at low pump fluences.

Previously, we reported on the development of a therapeutic regimen allowing eradication of primary murine Krebs-2 ascites transplants. This protocol involved multiple injections of dsDNA preparations administered during the NER and HR phases of repair of interstrand DNA cross-links induced by prior cyclophosphamide treatments. Mice treated under this protocol frequently developed secondary ascites, which indicated that some tumor-inducing cancer stem cells could survive the treatment and caused relapse. Further, we observed that animals receiving multiple dsDNA injections developed pronounced systemic inflammatory response. This prompted us to develop a more straightforward treatment regimen based on the synergistic activity of cyclophosphamide and dsDNA preparations, which would allow complete eradication of established primary Krebs-2 ascites and also be less toxic for the treated animals. This protocol relies on a precisely timed single injection of dsDNA during the NER/HR transition period of each repair cycle. Under this protocol, 8-day remission of Krebs-2 engrafted mice was achieved, which was similar to the results of the multiple-injection treatment schedule. We observed an increase in the average life span of Krebs-2- transplanted mice on a single-injection regimen, which was consistent with reduced toxicity of such treatment.

Cumulative evidence obtained in this series of studies has guided the logic behind the development of a novel composite dsDNA-based preparation whose therapeutic application according to the specific regimen completely cures the mice engrafted with otherwise lethal Krebs-2 ascites. The likely mechanism involves elimination of TAMRA+ tumor-inducing stem cells (TISCs) from Krebs-2 tumors. We performed quantitative analysis of TISC dynamics in Krebs-2 ascites following treatment with the cytostatic drug cyclophosphamide (CP) and untreated control cells. In intact ascites, TISC percentage oscillates around a certain value. Following CP treatment and massive apoptosis of committed cancer cell subpopulation, we observed relative increase in TISC percentage, which is consistent with reduced susceptibility of TISCs to CP. Nonetheless, this treatment apparently synchronizes TISCs in a cell cycle phase when they become sensitive to further drug treatments. We describe the regimen of synergistic DNA + CP activity against Krebs-2 ascites. This protocol results in a complete cure of 50 % of Krebs-2 engrafted mice and involves three metronomic injections of CP exactly at the timepoints when repair cycles are about to finish combined with dsDNA injections 18 hours following each CP injection. The “final shot” uses CP + DNA treatment, which targets the surviving yet highly synchronized and therefore treatmentsensitive cells. The first three CP/DNA injections appear to arrest Krebs-2 cells in late S-G2-M phase and result in their simultaneous progression into G1-S phase. The timing of the “final shot” is crucial for the successful treatment, which eradicates tumorigenic cell subpopulation from Krebs-2 ascites. Additionally, we quantified the changes in several biochemical, cellular and morphopathological parameters in mice throughout different treatment stages.

The purpose of the disclosure of the nature and role of economic efficiency and competitiveness in the process of analyzing activity in the manufacturing industry in this article identified the approaches to the specification of a data entity economic categories. In this regard, work on the basis of the review retrospective analysis of theoretical research existing definitions in this direction; it is revealed that in the modern economic literature single point of view chosen by the majority of scholars, the definition of these concepts at the present stage yet. The authors found that competitiveness as an integrated indicator of economic efficiency implies more complex relationships between economic entities in comparison with the efficiency, which in this context acts as an indicator of a degree of efficiency of use of available enterprises limited resources.

Aim: to evaluate features of the functional state of microvascular bed of the skin in patients with pulmonary arterial hypertension associated to congenital cardiac disease (PAH-CCD) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods. In study included 25 patients (41.6±15.8) with PAH-CCD, 25 patients (48.8±14.2) with CTEPH and 25 healthy volunteers (39.3±10.1 years). All the patients underwent a six-minute walking test (6-MWT), transthoracic echocardiography, thorax organs radiography, right heart catheterization (RHC) and Laser Doppler flowmetry (LDF) with amplitude and frequency wavelet analysis of blood flow oscillations and evaluation of constrictory and dilatatoryskin resistive microvesselsfunctions. Results. In the PAH-CCD in relation to the CTEPH groupaccording to the RHC were noted significantly higher values of systolic pressure in pulmonary artery (93.2 and 77.8 mm Hg respectively) and venous mixted blood saturation(63 and 57% Hg respectively). On this background 6- MWT distance was 356 and 325 m, the Borg dyspnea scale index was on average 3.12 and 3.76 respectively. According to the LDF pulseoximetry PAH-CCD and CTEPH patients had 90.1 and 94.7% respectively. According to the LDF with amplitude and frequency wavelet analysis the PAH-CCD patients had sig-nificantly higher values of the amplitude of myogenic, respiratory and pulse sectionof blood flow modulation, and also increased constrictory activity smooth muscle cells of skin precapillary arterioles in response to the stretching at venous occlusion and decreased dilatatory reserve at post-occlusi-ve reactive hyperemia. According to the LDF the CTEPH patients had elongationof time development of microvessel constriction in response to acti-vation of sympathetic nervous systemin respiratory and cold tests. Conclusion. According to the LDF functional state of skin microvessels in systemic circulation of the CTEPH patients was comparable with control groupexcept for elongation of time development of microvessel reactions for sympathetic vasoconstrictor stimulations. The PAH-CCD patients demonstrated basal tonus decreasing of smooth muscle cells of skin precapillary arterioles in systemic circulation, which can be regarded as a manifestation of autoregulatory response to systemic hypoxia.

Aim: To evaluate features of the functional state of microvascular bed of the skin in patients with idiopathic pulmonary arterial hypertension (IPAH) depending to acute vasoreactivity testing on inhaled nitric oxide. Methods: in study included 28 patients with IPAH (mean age 39,8±13,2 years) and 25 healthy volunteers (39,3±10,1 years). All the patients underwent 6-minuts walking test (6-MWT), transthoracic echocardiography, thorax organs radiography, right heart catheterization (RHC) with acute pharmacological test (APT), laser Doppler flowmetry (LDF) with functional tests. Patients were divided into 2 groups by results of APT. Results: according to the LDF the APT+ patients didn't differ from control group on any of the parameters. The APT-patients according to the basal perfusion also were comparable with control group, but had significantly higher constrictory reactions for all types vasoconstrictor stimulations (at activation of sympathetic nervous system in respiratory and cold tests, and in the development venule-arteriolar constrictory response on venous occlusion) and elongation of time development post-occlusive reactive hyperemia. We identified significant correlation of the amplitude of respiratory section of blood flow modulation, which reflected degree of venule plethora, with the RHC parameters and functional status of patients. Conclusion: In the APT-patients on against a background the of uncharged basal perfusion parameters noticed increased constrictory activity smooth muscle cells of resistive microvessels for all type vasoconstrictor stimulations, but expression of constrictory reactions correlated with indications of patients functional status.

Existence of a small subset of cancer cells referred to as tumor initiating stem cells (TISCs) largely responsible for tumor progression and resistance to chemotherapeutic cytostatic drugs reperesent an important recent paradigm shift. The present work is the first report in the series of papers from our group where we describe the development of anticancer therapy based on the selective targeting of TISCs. Here were characterize a cytoreductive activity of cyclophosphamide (CP), double-stranded DNA (dsDNA) and combinations thereof against the TISC population present in mouse Krebs-2 ascites. We evaluated engraftment potential of Krebs-2 cancer cells treated in ascites-bearing mice in vivo, followed by re-engraftment to congenic recipient mice in a form of a solid graft. These data indicate that with our approach TISCs can be completely eliminated even from a well-established ascites. We demonstrate that dsDNA-internalizing and CD34-positive cells are more sensitive to the synergistic effects of CP and dsDNA. When Krebs-2 ascites are treated with human DNA 1-12 hours post CP injection, this results in either elimination of cells that internalize TAMRA-labeled DNA (TISCs) or alters their phenotype, which is accompanied with the loss of surface expression of CD34. Next, we show that the timepoint 18 hrs post CP treatment is critical to the ongoing repair process in that it divides the repair into two phases: nucleotide excision repair + dsDNA break repair and homologous recombination. Importantly, both of these phases can be conveniently used for targeting the tumorigenic potential of the graft. In the context of monotherapy, CP is most effective against ascites grafts when administered as serial injections. To achieve maximum efficiency, the timing of consecutive injections must match the time when cancer cells found at G2/M during the first injection enter G1/S and/or the time of active repair via homologous recombination.

In the present paper, we report on the series of experiments where multiple regimens of CP and dsDNA injections were tested for targeting the ascites form of murine Krebs-2 cancer in situ. We show that combining CP with cross-linked human and salmon dsDNA results in a synergistic toxicity for ascites-bearing mice, an observation supported by the histopathology analysis of organs and tissues of experimental animals. In contrast, using a composite mixture of native and cross-linked human and salmon DNA after CP injections leads to a significant increase in average lifespan of the treated mice. Further, we demonstrate that repeated rounds of CP+dsDNA injections result in dramatic anticancer effect. The timing of injections is chosen so that they target the cells that were insensitive to the previous treatments as they were in the G2/M phase. 3-4 rounds of injections are needed to eliminate the subpopulation of tumor-initiating cancer stem cells. Our experiments identified the regimen when complete resorption of the primary Krebs-2 ascites occurs in all of the treated animals, followed by a remarkable remission period lasting 7-9 days. Yet, this regimen does not prevent secondary site metastases (either solid or ascites form) from developing, which is likely caused by the migration of ascites cells into adjacent tissues or by incomplete eradication of cancer stem cells. To address these and other questions, we expanded the study and performed histopathology analysis, which indicated that secondary metastases is not the only cause of death. In fact, many animals displayed unfolding systemic inflammatory reaction which was culminated by multiple organ failure. Thus, we developed the concept for treating ascites form of Krebs-2 cancer, which allows elimination of the primary ascites.

A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of “generalized cellular stress,” which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of “committed” tumor cells.

Injections ofexogenous DNAin combination witha cytostatic agent cyclophosphamide (CP) cause illness anddeathofexperimental mice. This phenomenon is referredto this as delayeddeath. It has been foundthat upon intraperitoneal injections fragments ofexogenous DNAreachthe bone marrowniche andenter the nuclei ofbone marrowcells (BMCs). Also, fragments ofexogenous DNAare capturedfrom culture medium byBMCs generatedex vivo. Upon suchtreatment, the fragments are incorporatedinto cells in a non-degradedform. We estimate that under suchconditions upto 1800 kb ofexogenous DNAcan be present in BMCs as fragments. After ex vivo incubation withBMCs, fragments ofexogenous DNAinternalizedin cells ofbothintact andCP pre-treatedmice become circularized. It has been shown that fragments ofexogenous DNAcan form high-molecular weight structures in vivo. Moreover, fragments localizedin BMCnuclei are suggestedto integrate into chromosome(s) ofrecipient mouse genomes when treatedwithCP andexogenous DNA.

Mice were observed to get sick and die upon administration of exogenous DNA in a specific period of time following their pretreatment with the cytostatic cyclophosphamide (CP) (Dolgova et al., 2011). It was established that exogenous DNA reaches internal compartments of bone marrow cells (BMCs) where it is processed (Dolgova et al., 2012a). Thus, BMCs appear to be the primary targets for the synergic action of these preparations (Dolgova et al., 2012b).In the present study, we show that the copy number for mouse interspersed genomic repeats decreases in the genome of mouse mononuclear cells as a result of interstrand cross-link (ICL) repair after pre-treatment with cytostatic CP. This phenomenon occurs within the time span from 18 to 24 h following CP injection, which corresponds to the final step in the repair of the majority of double-strand breaks (DSBs), as predominant intermediates in ICL repair. Injections of exogenous DNA in CP-pretreated mice preserve the copy number of interspersed repeats at the original level. Our results suggest that the fragments of exogenous DNA participate in ICL-induced DSB repair, thereby compromising the repair process.

The synergic action of the cytostatic drug cyclophosphamide (CP) and fragmented exogenous DNA causes illness and death in mice (Dolgova et al., 2011–2013). The observed «delayed death» effect was most clearly pronounced when the DNA preparation was administered 18 to 30 hours after CP treatment. This time span is designated as «death window».It was found that injections of exogenous DNA result in sustained increase in bone marrow cell (BMC) apoptosis, which occurs throughout the time of DNA administration (18–30 hours). Exogenous DNA, both allogeneic and belonging to various taxa induces BMCs apoptosis. Plasmid DNA has the greatest effect on apoptosis induction.The analysis of reduction and restoration of BMC subpopulations as the mice progressed to death revealed a virtually complete loss of the 12–20-mkm fraction of the cell population (about 3–4 % vs. 35–40 % in the control), which corresponds to the maximum leukopenia on day 3 after CP treatment. However, the relative amount of CD34+ hematopoietic stem cells (HSCs) from day 15 and till the end of the observation constituted 1,2–1,4 %, which corresponds to the wild-type range. Comparison of BMC smears from the sternal bone marrow of the CP and CP+DNA groups of mice indicates that the BMC populations isolated from CP+DNA animals lack young committed lymphopoiesis progenitor cells. Moreover, the affected mice had immature blast cell types in their blood, which was never observed in healthy or CP-treated mice. Pathological and morphological analyses show that starting from posttreatment day 9, mice that received CP+DNA preparations displayed pronounced morphological changes in their lungs, liver, pancreas, central and peripheral immune system organs, and brain. Most of the pathological changes observed are consistent with severe inflammatory response. This suggestion is proven by structural equivalents of functional involution of lymphoid organs, such as thymus, spleen, and lymph nodes.We speculate that the death of treated animals resulted from multiple organ dysfunctions caused by accidental involution of lymphoid organs and the systemic inflammatory response syndrome, both associated with injections of fragmented exogenous DNA into experimental animals within the «death window», which corresponds to the final step in the repair of the majority of CP-induced double-strand breaks.

The relevance of scientific research due to the fact that the study of the impact of the major issues of motivation on the formation and reproduction of the human capital in the social market economy, characterized by such elements on the basis of which the formation of human capital and its development.

The article deals with the concept of an innovative economy as the knowledge economy, reflecting the different theoretical approaches to the understanding of the nature and content of the category of “human capital." We consider the problems of reproduction of the human capital, the study of managing this process in terms of innovative development of territories. The article presents a systematization of approaches to the definition of “human capital".

Relevance of scientific research is caused by that efficiency of use and development of the human capital is the main priority for the majority of the leading countries of the world. Human capital promotes growth of quality of life of the population, and also increase in efficiency of national economy in general.

Relevance of the real research is caused by transition of Russia to information society. In such society new organizational forms - the virtual organizations representing networks of the economic agents cooperating in information space are of particular importance.

63 patients with parodontal diseases were divided into two groups. We used standard flap surgery in the first group (32 patients, 50,8%). Complex therapy of the second group (31 patients, 49,2%) were suppelmented with intraosseous infusion of natrium hypochlorite 0,03%. The results of our investigations allow us to speak about enhancement of efficiency in the complex treatment of parodontal disease.

45 patients with traumatic osteomyelitis of lower jaw were divided into two groups. We used standard surgical treatment in the first group (29 patients, 64,4%). Complex therapy of the second group (16 patients, 35,6%) were suppelmented with intraosseous infusion of natrium hypochlorite 0,03%. The results of our investigations allow us to speak about enhancement of efficiency in the treatment of chronoc traumatic osteomyelitis.

Wilson disease ATPase (ATP7B) has been implicated in the resistance of cancer cells to cisplatin. Using a simple in vivo assay in bacterial culture, in the present study we demonstrate that ATP7B can confer resistance to cisplatin by sequestering the drug in its N-terminal metal-binding domain without active drug extrusion from the cell. Expression of a protein fragment containing four N-terminal MBRs (metal-binding repeats) of ATP7B (MBR1–4) protects cells from the toxic effects of cisplatin. One MBR1–4 molecule binds up to three cisplatin molecules at the copper-binding sites in the MBRs. The findings of the present study suggest that suppressing enzymatic activity of ATP7B may not be an effective way of combating cisplatin resistance. Rather, the efforts should be directed at preventing cisplatin binding to the protein. [ABSTRACT FROM AUTHOR]

The Black Sea is one of the main recreational facilities in Russia subject to a high annual anthropogenic stress. Anthropogenic activity led to high coastal sea waters pollution, eutrophy, and endangered the sea’s self-purification capabilities. The total quarantine introduced on the Black Sea coast of the Krasnodar territory associated with the new coronavirus infection COVID-19 pandemic led to a decrease in anthropogenic pressure on coastal ecosystems and provided a unique opportunity to trace the dynamics of the most important hydrochemical indicators of coastal waters in the Tuapse district. The study aimed to characterize the impact of quarantine measures against the coronavirus on the state of coastal waters in the eastern part of the Russian Black Sea. For this, we identified and characterized the hydrochemical indicators and determined the effect of quarantine measures on their dynamics. The study used the standardized methods. The results obtained showed that a decrease in the recreational stress led to a proportional decrease in the pollutants supply to coastal sea waters; with the recreational stress resumption the concentrations of mobile pollutants tended to increase; a proportional relationship was established between biochemical oxygen demand (BOD5 ) and the ammonium nitrogen (NH4+) concentration; the nitrates’ (NO3–) concentration, in the seawater did not depend on the recreational stress degree. In particular, a proportional increase in NH4+ concentration and BOD5 in seawater was detected: in the third quarter of 2019 the concentration of NH4+ and BOD5 amounted to 3.0 mg/dm3 and 8.5 mg/dm3 , and 3.8 mg/dm3 and 7.5 mg/dm3 in the fourth quarter, respectively; in the 2020 samples, a decrease in the NH4+ concentration to 0.8 mg/dm3 in the third and to 1.2 mg/dm3 in the fourth quarter led to a proportional decrease in BOD5 4.5 mg/dm3 and 3.9 mg/dm3 , respectively. Thus, it was shown that the quarantine measures were shown to have a positive effect on the processes of self-purification of coastal sea waters in recreational zones.

Stem-like tumor cells of ascites carcinoma Krebs-2 and Epstein-Barr virus–induced B-lymphoma were shown to possess the innate capability of binding and internalizing the TAMRA-labeled double-stranded DNA (dsDNA) probe. The process of binding and internalizing is rather complicated and composed of the following successive stages: 1) initiating electrostatic interaction and contact of a negatively charged dsDNA molecule with a positively charged molecule(s) on the surface of a stem-like tumor cell; 2) binding of the dsDNA probe to a tumor stem cell surface protein(s) via the formation of a strong chemical/molecular bond; and 3) the very internalization of dsDNA into the cell. Binding of DNA to cell surface proteins is determined by the presence of heparin/polyanion-binding sites within the protein structure, which can be competitively blocked by heparin and/or dextran sulfate, wherein heparin blocks only the binding, while dextran sulfate abrogates both binding and internalization. The abrogation of internalization by dextran sulfate implies the role of scavenger receptors in this process. Cells were shown to uptake DNA in amounts constituting ∼0.008% of the haploid genome. Inhibitors of caveolae-dependent internalization abrogate the DNA uptake in Krebs-2 cells, and inhibitors of the clathrin/caveolar mechanism block the internalization in B-lymphoma cells. In the present report, it is shown for the first time that in contrast to the majority of committed tumor cells, stem-like tumor cells of Krebs-2 and B-lymphoma carry a general positive charge on their surface.

This article is the second communication in a series of articles devoted to the effects of a domestic preparation of macrophage-activating factor (GcMAF-RF) and assessment of its biological properties. The aim of this work was to study the effect of the GcMAF-RF upon M0 → M1 polarization of macrophages (Mph), and activation of the professional properties of ex vivo generated antigen-presenting dendritic cells (DC), as well as on ex vivo production of pro-inflammatory (TNFα, IL-1β, IL-6, IFNγ, IL-17, IL-18) and anti-inflammatory (TGF-β, IL-4, IL-10) cytokines, growth factors (IL-2, GM-CSF, G-CSF, VEGF) and chemokines (MCP, IL-8) by the whole blood cells from healthy donors. Mph and DC were generated from the monocytes (3 to 5×106 /ml) derived from adherent fraction of peripheral blood mononuclear cells (MNC) of healthy donors. Granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was used to obtain Mph, whereas DC production was induced by GM-CSF and interferon-α. To provide M1 polarizing signals, bacterial lipopolysaccharide (LPS from E. coli 0114:B4) was used in controls. In experimental series, GcMAF-RF was added 48 h before the end of culture. The stimulating effect of the obtained Mph and DC upon cell proliferation was assessed in allogeneic mixed culture of leukocytes (alloMLC) using radiometric technique, by 3 H-thymidine incorporation. The influence index (IR) of Mph or DC upon allo-SCL was calculated as the ratio of the proliferative response of MNCs in the presence of Mph, or DC to the level of spontaneous MNC proliferation. To determine the cytokine production by human whole blood cells ex vivo, peripheral blood samples from 3 donors with two replicate GcMAF-RF preparations were used, at a total of 6 points. All variants of the study were carried out with mitogen-activated and non-activated blood cells. The cytokine content was determined by the ELISA assays. The effects of GcMAF-RF were quantified as a fold increase (FI), i.e., the ratio of cytokine production in the presence of GcMAF-RF to the level of their spontaneous production. It was shown that the GcMAF-RF preparation was as effective, as lipopolysaccharide (LPS), the standard Mph and DC activator which induces polarization of differentiated M0-macrophages into M1 cells and final maturation of DCs, manifesting by a significant increase in their allo-stimulatory activity in a mixed leukocyte culture (allo-MLC). Moreover, GcMAF-RF stimulates production of numerous cytokines and chemokines (TNFα, IL-1β, IL-6, IL-18, IL-4, IL-10, GM-CSF, G-CSF, VEGF, IL-8), by blood cells (granulocytes, lymphocytes, monocytes), thus indicating direct participation of the macrophage activator GcMAF-RF in various immune processes. The domestic GcMAF-RF drug induces polarization of macrophages M0 → M1, final maturation of DCs and allostimulating activity of Mf and DCs, and is also able to effectively stimulate circulating blood cells to synthesize cytokines/chemokines with pro-inflammatory and immunoregulatory activities.

Price is the most important tool of company behavior on market, whose changes are caught immediately by customers, competitors and state structures. Adequate pricing can bring profit to the company and raise its competitiveness and stability on market. Unfortunately, rather often price decisions of home exporters working on non-raw material markets are only a response to competitors’ steps and they aim at reaching tactical, momentary but not strategic goals. Companies usually try to use the same price strategies on foreign markets as they use on national market. In conditions of the global crisis, uneven introduction of isolation regime and border closing by countries, breaking supply chains, bankruptcy or closure of national companies Russian exporters face the loss of distribution channels developed earlier. On the other hand, in these conditions they get an opportunity not only to settle on developed markets nut to penetrate new overseas markets in such segments, where the work of local companies was cut or shut down. In any case home exporters should think over their price strategy on foreign market and research changes in customer preferences, in their perception of company product value. The author gives recommendations aimed at improving exporters’ pricing in conditions of 2020 crisis on the basis of analyzing customers in view of their contribution to the company profit.

The solution copolymerization of styrene with vinylbenzyl trimethylammonium chloride (VBTMAC) was investigated. The solvents used in this study form homogeneous solutions with mixtures of monomers and possess different polarity, namely, isopropanol, DMSO, and their mixtures. Reactivity ratios of the copolymerization of these monomers in isopropanol were determined: rstyrene is 0.15 ± 0.01, rVBTMAC is 0.46 ± 0.004. Based on the values of the reactivity ratios authors conclude that the resulting copolymers have a tendency to alternate structural units. It was shown that the copolymerization of these monomers could not be described by means of Mayo-Lewis copolymerization model. The main reason for the deviation from the classical scheme of copolymerization is the bootstrap effect (the selective sorption of growing polymer radical by styrene). This effect increases with increasing polarity of the solvent as well as when the resulting copolymers are allocated in heterophase.

Abstract. There are some specific mechanisms in cell that detect the invasion into the cell of any foreign molecules, so-called pathogen-associated molecular patterns (PAMPs). The recognition of these PAMPs is realized by Toll-like receptors or is due to the cytosolic sensors action. In recent years much attention is directed to the investigation of foreign nucleic acids sensing and detection in cell. Nowadays some sensors of doublestranded DNA, such as STING, DAI, members of NOD-like protein family, RIG-like helicases, proteins of HIN-200 family are identified. Some of sensors interact with double-stranded DNA directly. The others are characterized as mediators of signal transduction from unknown DNA-sensor in the series of following molecular events. Induction of nuclear transcription factors NF-κB and IRF3/IRF7 to produce IFNβ or processing of proinflammatory cytokines IL-1β and IL-18 by means of inflammasome formation is a result of activation of cascade events induced by cytosolic DNA. In the review we combine information concerning signaling pathways characterized sensing of intracellular double-stranded DNA that results in the development of the cellular immune response.

Relevance of scientific research is caused by that efficiency of use and development of the human capital is the main priority for the majority of the leading countries of the world. Human capital promotes growth of quality of life of the population, and also increase in efficiency of national economy in general.