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Obtaining hydrological information in general, as well as determining the estimated water levels on water bodies, are mostly associated with the construction of hydraulic structures that allow the use of water for the needs of the national economy. The oil production industry is widely developed on the territory of the Khanty-Mansi Autonomous Okrug. Often oil and gas fields are located in sparsely populated areas where there is no information about the hydrological regime of watercourses. In order to ensure the safe operation of construction projects, there is a need to obtain hydrological information for crossed or nearby watercourses. Thus, this type of work is performed almost everywhere to solve similar problems. In this article, studies of the Iga River, located in the right bank of the Ob River, were carried out. To identify the degree of influence of the river level in different periods of the year, hydrological calculations of spring floods and rain floods were performed. Based on the calculations, a graph of the relationship between costs and levels was constructed. To determine the possible backup of the level of the Ob River to the level regime of the Iga River during periods of high waters, the levels of the Ob River were determined. Based on the analysis of joint levels, a conclusion was made about the influence of the Ob on the hydrological regime of the Iga River

The peculiarity of natural conditions of Yakutia plays an important role in the formation of economic activities of its population. A significant number of rivers and lakes are a favorable condition for the development and preservation of traditional fishing. Currently, more than 89% of the commercial fish catch is produced in the lower reaches of the large northern rivers and lakes in the Arctic and subarctic zones of Yakutia. The main part of this catch is whitefish species, which are valued for their fat content, protein content, culinary, and taste qualities. Fish is a valuable food product for the population of Yakutia. This article presents the results of the study on the nutritional value and the content of heavy metals in the Arctic cisco meat. The high content of fat and protein in the studied samples shows that the Arctic cisco meat belongs to high-protein and high-calorie products and has a high biological value. It was found that on average, the level of toxic metals in the Arctic cisco meat does not exceed the norms accepted in Russia for fish products. The data obtained suggest that the content of heavy metals in fish is due to the peculiarities of living conditions and environmental pollution. Over the past decades, the volume of fish production in Yakutia has been declining due to the socioeconomic and climatic factors. Due to the anthropogenic pollution of water in rivers and lakes by oil products and effluents and waste from various sectors of the economy, especially the mining industry, there is a reduction in the fish resources and there is a need to monitor the environmental condition of the fishing reservoirs and the fish food quality.

The development of functional products characterized by high biological efficiency is an urgent task. The article presents the results of the development of balanced-fatty acid terrins from poultry meat. To increase the biological effectiveness of chopped products, raw materials containing omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) were selected. Based on the analysis of the chemical composition of the raw material kit, the intervals for the Introduction of ingredients containing biologically effective components are calculated. Their optimum amount has been experimentally established. The resulting innovative products are characterized by a balanced composition in terms of content and ratio of omega-3 and omega-6 PUFAs. In addition, the value of the indicator of biological value has increased. Developed poultry terrins can be recommended both for a wide range of consumers, and for use in diet (including low-carb diets), baby food. The developed terrines will expand the range of chopped poultry products of functional orientation.

One of the priority areas of resource-saving technologies in the food industry and public catering is the development of functional products based on a balanced combination of protein-containing raw materials of animal origin and plant raw materials. In the work, for the production of chopped fish semi-finished products - cutlets (CFSFPc), based on the analysis of chemical composition data, the main raw materials and sources of polyunsaturated fatty acids (PFA) were selected; in accordance with the principles of creating functional products, the quantitative composition of the recipe components is optimized; the functional and technological properties (FTP) of model minced meat have been studied; an assessment of the organoleptic characteristics of finished products was carried out.

The article presents the socio-ecological practices of constructing a comfortable and safe urban environment on the example of the southern region of Russia and current trends in the scientific discussion affecting this topic. We considered expert assessments of the quality of training graduates of gardening and landscape construction programs based on the requirements of the Federal State Educational Standard. We presented the role of agrarian education in the promotion of environmentally friendly technologies in the preparation of graduates of gardening and landscape construction. Attention is paid to the modern skills of designing the urban environment based on the practice of involving the local community in this process and promoting transdisciplinary methods of researching the needs of the population. We proposed the areas of improving the process of training students under the program of garden and park and landscape construction, capable of contributing to the achievement of the strategic national goal of developing a comfortable and safe environment for the life of Russians.

One of the most important tasks of technical diagnostics and examination of industrial safety is the problem of assessing the residual life of long-running technical devices of hazardous production facilities. The paper presents the results of the study of the structural-phase state in a stable zone of localization of macrostrains, depending on the initial state of samples from steel 20. The samples were investigated without exploitation, after operation without destruction and with destruction. The samples were stretched at the same speed until a stable zone of strain localization appeared, after which the loading was stopped. The connection is established between the processes of localization of macrostrains and the evolution of the substructural state for steel 20. It has been established that the mechanism of localization of macrodeformations is the achievement of critical values of a fragmented substructure, in other words, according to the theory of evolution of substructural transformations, a bifurcation point occurs when the % fragmented substructure prevails. The critical values of dislocation density are established, which lead to a change in the type of dislocation substructure for equipment made of steel 20.

The article considers importance of formation of a transportation and logistics cluster of a region from the point of view of European integration movement of Ukraine. It analyses experience of different countries of the world in establishing and functioning of clusters, including transportation and logistics ones. It considers advantages of cluster strategies for organisation of a transportation and logistics system and factors that facilitate its development. It formulates the tasks that have to be solved for establishment of a regional transportation and logistics cluster. It offers a structural model of formation of a transportation and logistics cluster, which includes a main body consisting of not one cluster-forming enterprise but a number of enterprises that provide transportation and logistics services. It makes conclusions and identifies prospects of organisation a transportation and logistics cluster and requirements in improvement of assessment of its effectiveness.В статье рассмотрено значение формирования транспортно-логистического кластера региона с точки зрения включения Украины в евроинтеграцию. Проанализирован опыт различных стран мира в создании и функционировании кластеров, в том числе транспортно-логистических. Рассмотрены преимущества кластерных стратегий для организации транспортно-логистической системы и факторы, способствующие ее развитию. Сформулированы задачи, которые необходимо решить для создания регионального транспортно-логистического кластера. Предложена структурная модель формирования транспортно-логистического кластера, которая включает ядро, состоящее не из одного кластерообразующего предприятия, а из множества предприятий, предоставляющих транспортно-логистические услуги. Сделаны выводы и определены перспективы относительно организации транспортно-логистического кластера и потребности в совершенствовании оценки его эффективности.

The questions of forming of customer focus of the transport-logistic holding are considered on the basis of development of strategic directions of marketing activity and system of service of customers.В статье рассмотрены вопросы формирования клиентоориентированности транспортных холдингов на основе разработки стратегических направлений маркетинговой деятельности и системы обслуживания клиентов.

The paper describes results of studies of phase transitions in structural phase state occurring in the type 0.34C-1Cr-1Ni-1Mo-Fe steel under electrolytic plasma nitriding in nitrogen-containing water solution. The nitriding voltages considered in the given study were 550 and 600 V. The research was conducted by means of X-ray diffraction electron microscopy. The specimens were studied in two states : 1) before modification (original state) and 2) after nitriding in the surface layer of the specimen. The study was conducted on thin foils. It was found that nitriding lead to significant changes in the structure of steel, namely in its phase composition and in the number of existing phases. In the original state the structure of steel was given as lamellar pearlite, ferritic carbide mix and fragmented ferrite. After 550 V nitriding it was lath martensite, plates of α-phase, with colonies of thin parallel plates of γ-phase and coarse grains of α-phase, containing γ-phase grains which were different in size and shape and were various-directional. Increase in nitriding voltage up to 600 V lead to change in the structure given as a lamellar non-fragmented pearlite and fragmented ferrite. The original state was marked by presence of particles of M3C cementite, after nitriding irrespective of the voltage it had the particles of M3C alloyed cementite, Fe3Mo3N nitride and Cr2C0.61N0.39 carbonitride. The sizes, volume fractions and locations of particles were dependent on nitriding voltage.

The purpose of this paper is to define the role and place of the transportation component of the adjacent subjects of two countries in their economic potential for implementation of intergovernmental cooperation. The role and place of the transportation component in estimation of the benefits of the transportation and geographical position becomes evident only when the population, resources and economy of the border regions are jointly analyzed. The analysis of such parameters of the border regions of Russia (Western Siberia) and Kazakhstan performed by means of comparison and association of their economic and transportation potentials, showed that territorial production complexes in them have been developed, and the prospective development within the framework of the Eurasian Economic Union will be determined by the joint use of the benefits of the transportation and geographic position implemented with participation of railway transport.

The present paper investigates phase composition and fine structure of Ni-Al-Co-based alloy alloyed by Rhenium (Re) (~3 at.%), as well as studies preferred orientation of the given alloy primary phases by means of scanning electron microscopy and X-ray diffraction analysis. The original state was given as the alloy which underwent a complete cycle of heat treatment: stepwise homogenization, cooling, annealing, and cooling at 100°C/min back to room temperature. The alloy was further subject to annealing at 1000°C for 105 h and 968 h. It was also exposed to creep experiments at the same temperature for 105 h (loading 320 MPa), and for 968 h (220 MPa). γ- and γ′-phases were established to be the primary phases in both states of face-centered cubic crystal lattice. γ′-phase (phase with ordered atom arrangement having L12 superstructure) was the primary phase in all states of the alloy. Investigations showed that Re being able not to dissolve in the primary phases served as a phase-forming element. Phase composition and phase morphology were studied. The influence of high-temperature annealing and creep on superalloy structure and morphology of γ′-phase were defined. The influence of creep on the structure was proven to be different from the annealing effect. First, creep generated larger dissipation of orientations than annealing. Second, anisotropy of γ′-phase cuboids could be observed at meso-level. Cuboids partially joined together. Third, spheroidized cuboids could be often met after creep.

Three-layer materials consisting of the V-4.9Ti-4.8Cr/ferrite steel 17Cr-12Ni-Fe /V-4.9Ti-4.8Cr were obtained in the paper. Phase composition and microstructure of the transition zone of the three-layer material of vanadium alloy V-4.9Ti-4.8Cr and ferrite steel 17Cr-12Ni-Fe were considered. The use of the method of direct laser growing allowed obtaining a three-layer material with qualitative interconnection of layers, as well as decreasing a multistage nature of deformation and thermal operations used when obtaining a three-layer material in earlier works. Additional thermal treatment of a three-layer alloy led to growth of matrix grains up to 100 μm of the vanadium alloy. A uniform distribution of main elements V, Ti, Cr was observed in the transition zone both before and after annealing. A zone of interdiffusion of the metals amounted to 250-350 μm.

The border areas of countries are aimed at playing a special role in the development of general economic and social relations, enhancing the geopolitical significance of regional interstate relations. The purpose of the work is to study and show the modern economic complex of border regions on the example of Russia and Mongolia, in which railway transport plays a significant role. Statistical and analytical comparison as a method of scientific analysis allowed examining in detail the territorial production complex of a large region, its resource dependence, and the conditionality of the functioning by the configuration of transport routes and transport accessibility indicators, both in Russia and Mongolia. The Russian railways, which connect Siberia and the Far East with the European regions of the country, continue to provide interdistrict and interregional economic relations at the present time. The Mongolian railways, which have a smaller length, perform a linking role between the fields of raw materials and the points of its processing or further transportation. The study showed that railways continue to be the basis for interregional cross-border connections. However, as the shortest transport route between the countries of Western, Central, Eastern Europe, and the countries of Central, East, and South-East Asia, the railways of the region in question, uniting the border regions of Mongolia and Russia, can strengthen their role in interstate cooperation and become the most important part of the international Eurasian transport corridors - the Steppe Route and the Silk Road.

The paper describes the results of mathematical modelling of diesel fuel catalytic dewaxing process, performed taking into account the factors of process nonstationarity driven by changes in process technological parameters, feedstock composition and catalyst deactivation. The error of hydrocarbon contents calculation via the use of the developed model does not exceed 1.6 wt.%. This makes it possible to apply the model for solution to optimization and forecasting problems occurred in catalytic systems under industrial conditions. It was shown through the model calculation that temperature in the dewaxing reactor without catalyst deactivation is lower by 19 °C than actual and catalyst deactivation degree accounts for 32 %.

Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Lewis lung carcinoma. Mice of the C57BL/6 strain were fed with wheat of near-isogenic lines differing in the anthocyanin content for four months prior to tumor transplantation. Although a significant decrease in the size of the tumor and the number of metastases in the lungs was revealed in the groups with both types of grain diet, the highest percentage of animals without metastases and with attenuated cell proliferation in the primary tumor were observed in the mice with the anthocyanin-rich diet. Both grain diets reduced the body weight gain and spleen weight index. The antitumor effects of the grain diets were associated with the activation of different mechanisms: immune response of the allergic type with augmented interleukin(IL)-9 and eotaxin serum levels in mice fed with control grain vs. inhibition of the IL-6/LIF system accompanied by a decrease in the tumor-associated M2 macrophage marker arginase 1 gene mRNA levels and enhanced autophagy in the tumor evaluated by the mRNA levels of Beclin 1 gene. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition with confirmed in vivo antitumor activity.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan. Inhibitors of this Tdp1 in combination with topotecan may improve the effectiveness of therapy. In this work, we synthesized usnic acid derivatives, which are hybrids of its known derivatives: tumor sensitizers to topotecan. New compounds inhibit Tdp1 in the micromolar and submicromolar concentration range; some of them enhance the effect of topotecan on the metabolic activity of cells of various lines according to the MTT test. One of the new compounds (compound 7 ) not only sensitizes Krebs-2 and Lewis carcinomas of mice to the action of topotecan, but also normalizes the state of the peripheral blood of mice, which is disturbed in the presence of a tumor. Thus, the synthesized substances may be the prototype of a new class of additional therapy for cancer.

We have previously shown that the Tdp1 inhibitor, enamine derivative of usnic acid, the agent OL9-116, enhances the antitumor activity of topotecan. In the present study, we developed and validated LC-MS/MS method for the quantification of OL9-116 in mouse whole blood and studied pharmacokinetics of the agent. The substance OL9-116 was shown to be stable in the whole blood in vitro. Sample preparation included two steps: mixing 10 µL of a blood sample with 10 µL of 0.2 M ZnSO 4 aqueous solution, followed by protein precipitation with 100 µL of acetonitrile containing internal standard. Quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following chromatographic separation on a C8 reversed-phase column. The method was validated in terms of selectivity, linearity, accuracy, precision, recovery, and stability of the prepared sample. When the agent OL9-116 was administered intragastrically at a dose of 150 mg/kg, the maximum concentration in the blood (about 5000 ng/mL) was reached after 2-4 h followed by the distribution and elimination of the compound. A study of the antitumor activity of a combination of OL9-116 and topotecan against Lewis lung carcinoma revealed that administration of topotecan 3 h after OL9-116 resulted in the most pronounced antitumor effect compared to simultaneous or individual administration of both compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

It is well-established that double-stranded RNA (dsRNA) exhibits noticeable radioprotective and radiotherapeutic effects. The experiments conducted in this study directly demonstrated that dsRNA was delivered into the cell in its native form and that it induced hematopoietic progenitor proliferation. The 68 bp synthetic dsRNA labeled with 6-carboxyfluorescein (FAM) was internalized into mouse hematopoietic progenitors, c-Kit+ (a marker of long-term hematopoietic stem cells) cells and CD34+ (a marker of short-term hematopoietic stem cells and multipotent progenitors) cells. Treating bone marrow cells with dsRNA stimulated the growth of colonies, mainly cells of the granulocyte-macrophage lineage. A total of 0.8% of Krebs-2 cells internalized FAM-dsRNA and were simultaneously CD34+ cells. dsRNA in its native state was delivered into the cell, where it was present without any signs of processing. dsRNA binding to a cell was independent of cell charge. dsRNA internalization was related to the receptor-mediated process that requires energy from ATP. Synthetic dsRNA did not degrade in the bloodstream for at least 2 h. Hematopoietic precursors that had captured dsRNA reinfused into the bloodstream and populated the bone marrow and spleen. This study, for the first time, directly proved that synthetic dsRNA is internalized into a eukaryotic cell via a natural mechanism.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.

Nitric oxide (II) (NO) is the most important mediator of a wide range of physiological and pathophysiological processes. It is synthesized by NO synthases (NOSs), which have three main isoforms differing from each other in terms of activation and inhibition features, levels of NO production, subcellular localization, etc. At the same time, all isoforms are structurally very similar, and these differences are determined by NOS autoregulatory elements. The article presents an analysis of the autoregulatory and autoinhibitory mechanisms of the NOS reductase domain that determine differences in the productivity of isoforms, as well as their dependence on the concentration of Ca 2+ ions. The main regulatory elements in NOS that modulate the electron transfer from flavin to heme include calmodulin (CaM), an autoinhibitory insert (AI), and the C-terminal tail (C-tail). Hydrophobic interactions of CaM with the surface of the NOS oxidase domain are assumed to facilitate electron transfer from flavin mononucleotide (FMN). CaM binding causes a change in the inter-domain distances, a shift of AI and the C-tail, and, as a result, a decrease in their inhibitory effect. CaM also shifts the conformational equilibrium of the reductase domain towards more open conformations, reduces the lifetime of conformations, their stereometric distribution, and accelerates the flow of electrons through the reductase domain. The AI element, apparently, induces a conformational change that hinders electron transfer within the reductase domain, similar to the hinge domain in cytochrome P450. Together with CaM, the C-tail regulates the electron flow between flavins, the distance and relative orientation of isoalloxane rings, and also modulates the electron flow from FMN to the terminal acceptor. Together with the C-tail, AI also predetermines the dependence of neuronal and endothelial forms of NOS on the concentration of Ca 2+ ions, and the C-tail length affects differences in the productivity of NO synthesis. The inhibitory effect of the C-tail is likely to be reduced by CaM binding due to the C-tail shift due to the electrostatic repulsive forces of the negatively charged phosphate and aspartate residues. The autoregulatory elements of NOS require further study, since the mechanisms of their interaction are complex and multidirectional, and hence provide a wide range of characteristics of the observed isoforms.

The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug. We hypothesize that Tdp1 inhibition would sensitize cells towards the effect of Tpc. Herein, we report the synthesis and study of lipophilic derivatives of purine nucleosides that efficiently suppress Tdp1 activity, with IC 50 values in the 0.3-22.0 μM range. We also showed that this compound class can enhance DNA damage induced by topotecan in vitro by Comet assay on human cell lines HeLa and potentiate the antitumor effect of topotecan in vivo on a mice ascitic Krebs-2 carcinoma model. Thereby, this type of compound may be useful to develop drugs, that sensitize the effect of topotecan and reduce the required dose and, as a result, side effects.

The digital twin concept lays the foundation of the virtual vibrational analytics suggested in the current paper. The latter presents extended virtual experiments aimed at determining the specific features of the optical spectra of the studied molecules that provide reliable express analysis of the body spatial structure and chemical content. Reduced graphene oxide was selected as the virtual experiment goal. A set of nanosize necklaced graphene molecules, based on the same graphene domain but differing by the necklace contents, were selected as the relevant DTs. As shown, the Raman spectra signatures contained information concerning the spatial structure of the graphene domains, while the molecule necklaces were responsible for the IR spectra. Suggested sets of general frequency kits facilitate the detailed chemical analysis. Express analysis of a shungite carbon, composed of rGO basic structural units, revealed the high ability of the approach.

We studied the effect of a new targeted drug Pefagtal that represents a conjugate in which the MS2 phage filled with a substance toxic to cells (thallium salts) is covalently linked to peptides containing the RGD motif. The antitumor and pronounced antimetastatic effects of Pefagtal were demonstrated on transplanted mouse tumors differing in histological type and status of metastasis: Krebs-2 ascites adenocarcinoma of the mammary gland, Lewis lung adenocarcinoma, hepatoma-29, and lung adenocarcinoma. It is assumed that the RGD motif mediates primary binding of the construct to αvβ3 and αvβ5 integrins that are predominantly overexpressed in the endothelial cells of tumor blood vessels and in tumor and metastatic cells., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Currently, assessing exposure to toxic chemicals detected in foodstuffs is a vital issue, especially regarding foods for babies and toddlers. The research goal was to identify and quantify toxic chemicals (N-nitrosamines, phthalates) in baby foods. Material and methods . Our research objects were 21 samples of canned meat and vegetable purees; 30 samples of juices. All samples were bought in retail outlets. We applied solid phase extraction to prepare the samples for the chromatographic analysis. Chemicals were identified in samples by a hybrid technique, gas chromatography and quadrupole mass spectrometry (GC-MS). The components were classified by comparing the mass spectra we obtained with spectra of specific chemicals and data from the following libraries: NIST 08.L, WILEY275.L and PMW&#95;TOX2.L, AMDIS, USEPA (US Environmental Protection Agency) database with identification numbers of environmental pollutants; libraries containing mass spectra of narcotics, drugs, toxic pollutants and pesticides. Quantitative determination of phthalates in juice products by HPLC/MS was performed. Results . We identified three toxic chemicals in the analyzed canned meat and vegetable purees for babies. They belonged to the 1-3 hazard category and to different classes of organic compounds. Specifically, we identified nitrogen-containing chemicals (N-nitrosamines within a range of concentrations being 0.00077-0.0015 mg/kg with a 73% probability that a mass spectrum would match one taken from a library) in 52.9% of samples. These chemicals are not allowed in canned meat purees for babies by the Technical Regulations TR CU 021/2011 (<0.001 mg/kg). Next, we identified dibutyl phthalate and diethyl phthalate in 30.0% of samples; contents of these organic compounds in canned meat purees for babies are not stipulated by the TR CU 021/2011. We also identified an aromatic compound, namely furfural in 21.7% of samples, and a food additive, 2-butenoic acid (E570) in 5.3% of samples; their contents are regulated by the Technical Regulations TR CU 029/2012. Three toxic chemicals were identified in the analyzed juice samples. First, N-nitrosodiethylamine and N-nitrosodimethylamine were identified in 56.7% of samples (with a 73% probability that a mass spectrum would match one taken from a library, over a concentration range of 0.00045- 0.00077 mg/kg). Second, we identified phthalates (dibutyl phthalate, diethyl phthalate, and diisobutyl phthalate) in 30% of samples (in the concentration range from 0.4 to 59.26 mg/l). The contents of these compounds in juices for babies are not regulated by the TR CU 021/2011. We also detected furfural in 56.7% of samples (with a value of the coefficient of coincidence with library data of 90%), the use of which is regulated in TR CU 029/2012. Conclusion . We have developed and experimentally substantiated an algorithm of an analytical study with its focus on preparing food samples for further identification of chemicals in them. The algorithm involves using a complex technique that combines distillation, solid phase extraction, gas chromatography and mass spectrometry. This technique provides an opportunity to identify a component structure of complex chemical mixtures in food samples with high probability and reliability. It also provides solid evidence that organic compounds occur in food samples based on comparing analytical mass spectra with those taken from mass spectral libraries., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for 3'-end DNA lesions, predominantly stalled DNA-topoisomerase 1 (Top1) cleavage complexes. Tdp1 is a promising target for anticancer therapy based on DNA damage caused by Top1 poisoning. Earlier, we have reported about usnic acid enamine derivatives that are Tdp1 inhibitors sensitizing tumor cells to the action of Top1 poison (Zakharenko in J Nat Prod 79:2961-2967, 2016). In the present work, we showed a sensitizing effect of an enamine derivative of usnic acid (when administered intragastrically) on Lewis lung carcinoma in mice in combination with topotecan (TPT, Top1 poison used in the clinic). In the presence of the usnic acid derivative, both the volume of the primary tumor and the number of metastases significantly diminished. The absence of acute toxicity of this compound was demonstrated, as was the importance of the method of its administration for the manifestation of the sensitizing properties., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

In this study, we examined the in vivo toxicity of the liposomes F consisting of 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride, lipid-helper 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and folate lipoconjugate ( O -{2-[ rac -2,3-di(tetradecyloxy)prop-1-yloxycarbonyl]aminoethyl}- O '-[2-(pteroyl-L-glutam-5-yl)aminoethyl]octadecaethyleneglycol) and investigated the antitumor effect of combined antitumor therapy consisting of MDR1-targeted siMDR/F complexes and conventional polychemotherapy using tumor xenograft initiated in immunodeficient mice. Detailed analysis of acute and chronic toxicity of this liposomal formulation in healthy C57BL/6J mice demonstrated that formulation F and parent formulation L (without folate lipoconjugate) have no acute and chronic toxicity in mice. The study of the biodistribution of siMDR/F lipoplexes in SCID mice with xenograft tumors formed by tumor cells differing in the expression level of folate receptors showed that the accumulation in various types of tumors strongly depends on the abandons of folate receptors in tumor cells and effective accumulation occurs only in tumors formed by cells with the highest FR levels. Investigating the effects of combined therapy including anti-MDR1 siRNA/F complexes and polychemotherapy on a multidrug-resistant KB-8-5 tumor xenograft in SCID mice demonstrated that siMDR/F increases the efficiency of polychemotherapy: the treatment leads to pronounced inhibition of tumor growth, reduced necrosis and inflammation, and stimulates apoptosis in KB-8-5 tumor tissue. At the same time, it does not induce liver toxicity in tumor-bearing mice. These data confirm that folate-containing liposome F mediated the extremely efficient delivery of siRNA in FR-expressing tumors in vivo and ensured the safety and effectiveness of its action.

Background/aim: We compared the therapeutic efficacy of two recently developed experimental anticancer technologies: 1) in situ vaccination based on local immunotherapy with CpG oligonucleotides and anti-OX40 antibodies to activate antitumor immune response and 2) "Karanahan" technology [from the Sanskrit kāraṇa ('source') + han ('to kill')] based on the combined injection of cyclophosphamide and double-stranded DNA to eradicate cancer stem cells., Materials and Methods: The anticancer approaches were compared on three types of mouse malignant tumors with different grades of immunogenicity: weakly immunogenic carcinoma Krebs-2, moderately immunogenic Lewis carcinoma, and highly immunogenic A20 В-cellular lymphoma., Results: Our results indicated that in situ vaccination was the most effective against the highly immunogenic tumor А20. In addition, "Karanahan" demonstrated high efficiency in all types of tumors, regardless of their immunogenicity or size., Conclusion: "Karanahan" therapy showed higher efficacy relative to in situ vaccination with CpG oligonucleotides and anti-OX40 antibodies., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Topotecan is a cytostatic drug from the camptothecin group, it acts by inhibiting topoisomerase 1 (TOP1). Tyrosyl-DNA phosphodiesterase 1 (TDP1) is capable of interfering with the action of TOP1 inhibitors, reducing their therapeutic efficacy. Suppression of TDP1 activity may enhance the effects of topotecan. In this work, we investigated the effect of the antitumor drug topotecan alone and in combination with a TDP1 inhibitor, a hydrazinothiazole derivative of usnic acid, on Krebs-2 mouse ascites tumors. We have previously shown that this derivative efficiently inhibits TDP1. In the present work, we show that both topotecan and the TDP1 inhibitor have an antitumor effect when evaluated separately. The combination of topotecan and the TDP1 inhibitor additively reduces both the weight of the ascites tumor and the number of cells in ascites. In mice, the TDP1 inhibitor alone or in combination with topotecan eliminated the tumor cells. After the combined intraperitoneal administration of these two compounds, we observed cells in which lipid droplets occupied almost the entire cytoplasm and the accumulation of cell detritus, which was absent in the samples collected from mice treated with each compound separately.

We have previously shown that immunization of C57BL/6 mice, prone to spontaneous development of experimental autoimmune encephalomyelitis (EAE), with three antigens (MOG 35-55 , DNA-histone complex or DNA-methylated BSA complex), alters the differentiation profiles of bone marrow haematopoietic stem cells (HSCs). These are associated with the production of autoantibodies (auto-Abs) against these antigens and the formation of abzymes hydrolysing DNA, MOG, myelin basic protein (MBP) and histones. Immunization of mice with antigens accelerates the development of EAE. This work is the first to analyse the ratio of auto-Abs without and with catalytic activities at different stages of EAE development (onset, acute and remission phases) after immunization of mice with the three specific antigens. Prior to immunization and during spontaneous in-time development of EAE, the concentration of auto-Abs against MBP, MOG, histones and DNA and activities of IgG antibodies in the hydrolysis of substrates increased in parallel; correlation coefficients = +0.69-0.94. After immunization with MOG, DNA-histone complex or DNA-met-BSA complex, both positive (from +0.13 to +0.98) and negative correlations (from -0.09 to -0.69) were found between these values. Our study is the first showing that depending on the antigen, the relative amount of harmful auto-Abs without and abzymes with low or high catalytic activities may be produced only at onset and in acute or remission phases of EAE. The antigen governs the EAE development rate, whereby the ratio of auto-Abs without catalytic activity and with enzymatic activities of harmful abzymes hydrolysing MBP, MOG, histones and DNA varies strongly between different disease phases., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The standard D-G-2D pattern of Raman spectra of sp 2 amorphous carbons is considered from the viewpoint of graphene domains presenting their basic structure units (BSUs) in terms of molecular spectroscopy. The molecular approximation allows connecting the characteristic D-G doublet spectra image of one-phonon spectra with a considerable dispersion of the C=C bond lengths within graphene domains, governed by size, heteroatom necklace of BSUs as well as BSUs packing. The interpretation of 2D two-phonon spectra reveals a particular role of electrical anharmonicity in the spectra formation and attributes this effect to a high degree of the electron density delocalization in graphene domains. A size-stimulated transition from molecular to quasi-particle phonon consideration of Raman spectra was experimentally traced, which allowed evaluation of a free path of optical phonons in graphene crystal.

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., (Copyright © AUTHORS.)

The Purpose of the Article: Protection from ionizing radiation is the most important component in the curing malignant neoplasms, servicing atomic reactors, and resolving the situations associated with uncontrolled radioactive pollutions. In this regard, discovering new effective radioprotectors as well as novel principles of protecting living organisms from high-dose radiation is the most important factor, determining the new approaches in medical and technical usage of radiation., Materials and Methods: Experimental animals were irradiated on the γ-emitter (Cs 137 ) with a dose of 9.4 Gy. Radioprotective properties of several agents (total RNA, single-stranded RNA, double-stranded RNA and B-190) were estimated by the survival/death rates of experimental animals within 30-90 d. Pathomorphological examination of internal organs end electron microscope assay was done on days 9-12 after irradiation. Cloning and other molecular procedures were performed accordingly to commonly accepted protocols. For assessment of the internalization of labeled nucleic acid, bone marrow cells were incubated with double-stranded RNA labeled with 6-FAM fluorescent dye. Cells with internalized double-stranded RNA were assayed using Axio Imager M1 microscope. In the other experiment, bone marrow cells after incubation with double-stranded RNA were stained with Cy5-labeled anti-CD34 antibodies and assayed using Axioskop 2 microscope., Results: In this study, several biological features of the radioprotective action of double-stranded RNA are characterized. It was shown that 160 µg of the double-stranded RNA per mouse protect experimental animals from the absolutely lethal dose of γ-radiation of 9.4 Gy. In different experiments, 80-100% of irradiated animals survive and live until their natural death. Radioprotective properties of double-stranded RNA were found to be independent on its sequence, but strictly dependent on its double-stranded form. Moreover, double-stranded RNA must have 'open' ends of the molecule to exert its radioprotective activity., Conclusions: Experiments indicate that radioprotective effect of double-stranded RNA is tightly bound to its internalization into hematopoietic stem cells, which further repopulate the spleen parenchyma of irradiated mice. Actively proliferating progenitors form the splenic colonies, which further serve as the basis for restoration of hematopoiesis and immune function and determine the survival of animals received the lethal dose of radiation.

Till yet there is no data concerning mechanisms of autoimmune diseases development. Experimental autoimmune encephalomyelitis (EAE) prone C57BL/6 (T- and B-lymphocyte response), non-autoimmune CBA, and Th mice with T cell response were immunized with myelin oligodendrocyte glycoprotein (MOG 3 5-55 ) to compare different characteristics of autoimmune reaction development. Bone marrow differentiation profiles of hematopoietic stem cells (HSCs), lymphocyte proliferation in various organs associated with the production of antibodies against DNA, myelin basic protein (MBP), and MOG, as well as abzymes hydrolyzing these antigens, were analyzed before and after immunization. Profiles of HSC differentiation [BFU-E (erythroid burst-forming unit (early erythroid colonies), CFU-E (erythroid burst-forming unit (late erythroid colonies), CFU-GM (granulocytic-macrophagic colony-forming unit), and CFU-GEMM granulocytic-erythroid-megakaryocytic-macrophagic colony-forming unit] and patterns of lymphocyte proliferation in different organs (brain, spleen, thymus, and lymph nodes) were very different for C57BL/6, CBA, and Th mice. We conclude that only C57BL/6 mice were predisposed to spontaneous and MOG-induced acceleration of EAE development. CBA mice are not prone to the development of autoimmune reactions. After immunization, Th mice demonstrate changes in several parameters similar to C57BL/6 and other to CBA mice; Th mice are more prone to developing autoimmune reactions than CBA mice. Our data may be important for understanding the combined presence in mice lymphocytes with T and B cell responses for spontaneous and induced autoimmune diseases., Competing Interests: the authors declare the absence of competing financial interests.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC 50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC 50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The antimetastatic activity of combined or individual administration of topotecan and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitor was examined under various administration schedules in mice with Lewis lung carcinoma modeled by intravenous injection of 200,000 clone/mouse. The greatest antimetastatic effect was observed after combined use of topotecan and Tdp1 inhibitor as documented by macroscopic study of the lungs that revealed the decreased metastatic scores by 76, 91, or 74% at the respective inhibitor doses of 2, 4, or 6 mg/mouse, respectively, in parallel with inhibition of metastasis up to 98% (at inhibitor dose of 4 mg/mouse) and morphological and morphometric analyses of the lung sections, which revealed elevation of metastasis growth delay index to 86 and 63% at the respective inhibitor doses of 4 and 6 mg/mouse, respectively. The combined administration of topotecan and Tdp1 inhibitor is viewed as the most effective way to eliminate the metastatic formations with possible restitution of focal lesions.

The druggability of the tyrosyl-DNA phosphodiesterase 1 (Tdp1) enzyme was investigated in conjunction with topoisomerase 1 inhibition. A novel class of thiazole, aminothiazole and hydrazonothiazole usnic acid derivatives was synthesized and evaluated as Tdp1 inhibitors and their ability to sensitize tumors to topotecan, a topoisomerase inhibitor in clinical use. Of all the compounds tested, four hydrazinothiazole derivatives, 20c, 20d, 20h and 20i, inhibited the enzyme in the nanomolar range. The activity of the compounds was verified by affinity experiments as well as supported by molecular modelling. The most effective Tdp1 inhibitor, 20d, was ton-toxic and increased the effect of topotecan both in vitro and in vivo in the Lewis lung carcinoma model. Furthermore, 20d showed significant increase in the antitumor and antimetastatic effect of topotecan in mice. The results presented here justify compound 20d to be considered as a drug lead for antitumor therapy., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA-histone and DNA-methylated bovine serum albumin (met-BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG 35-55 results in the acceleration of EAE development. Anti-DNA antibodies are usually directed against DNA-histone complexes resulting from cell apoptosis. During the acute EAE phase (7-20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone-DNA results in a reduction of proteinuria, a significant increase in anti-DNA, anti-MBP and anti-MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA-histone and DNA-met-BSA only stimulated the formation of anti-DNA antibodies hydrolysing DNA with a long delay (15-20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA-met-BSA and DNA-histone complexes may have opposing effects compared to MOG. DNA-histone stimulates the appearance of histone-hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time-points. We conclude that MOG, DNA-histone and DNA-met-BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Krebs-2 solid carcinoma was cured using a new "3+1" strategy for eradication of Krebs-2 tumor-initiating stem cells. This strategy was based on synchronization of these cells in a treatment-sensitive phase of the cell cycle. The synchronization mechanism, subsequent destruction of Krebs-2 tumor-initiating stem cells, and cure of mice from a solid graft were found to depend on the temporal profile of the interstrand cross-link repair cycle. Also, the temporal profile of the Krebs-2 interstrand repair cycle was found to have a pronounced seasonal cyclicity at the place of experiments (Novosibirsk, Russia). As a result, the therapeutic effect that is based on application of the described strategy, originally developed for the "winter repair cycle" (November-April), is completely eliminated in the summer period (June-September). We conclude that оne of the possible and the likeliest reasons for our failure to observe the therapeutic effects was the seasonal cyclicity in the duration of the interstrand repair cycle, the parameter that is central to our strategy., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.

The author name M. V. Edeeva should read M. V. Edeleva.

Antimetastatic effect of the liposomal form of recombinant lactaptin RL2 (a proteolytic fragment of human breast milk κ-casein; 8.6 kDa) was studied in A/Sn mice after intravenous transplantation of GA-1 tumor with high rate of liver metastases. Tumor growth in the liver was found in all mice. In animals dying early, the tumors were presented by multiple nodes of about the same size; in mice dying later, the tumors in the liver were presented by just few large nodes formed by cells that survived chemotherapy. A single intravenous injection of RL2 lactaptin in liposomes prolonged lifespan of animals with liver metastases of GA-1 tumor by 1.5 times in comparison with that in untreated animals.

The article presents the results of experimental studies on the development of highly sensitive and selective chromatography-mass spectrometry technique for the determination of 9 N-nitrosamines in food samples (sausage products) using distillation and an automatic solid-phase extraction system on Coconut cartridges for sample preparation. In the elaborated conditions of sample preparation (distillation and solid-phase extraction) and chromatography-mass spectrometric analysis, we achieved a high recovery and efficiency of the separation of nine N-nitrosamines. The quantitation limit was at level of 0.0002 mg/kg with maximum error not exceeding 19%. The complex use of the distillation of N-nitrosamines with the addition of potassium hydroxide in combination with the optimal elution scheme for solid-phase extraction and concentrating the distillate into a Coconut carbon cartridge of 6 ml ensures the recovery of N-nitrosamines from the food product sample (sausage products) up to 93.2-100%. The process of approbation of the chromatography-mass spectrometric method in the samples of food products (sausage products) of various manufacturers revealed the content of N-nitrosamines in the concentration range 0.00029±0.000055÷0.350±0.05 mg/kg. The conducted studies of the content of the sum of highly toxic N-nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine) made it possible to disclose that in sample No. 5 the maximum allowable concentration was exceeded by 47 times, in samples No. 2 and 16, to 57.5 and 22.9 times and in sample No. 4 to 88 times, respectively., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Immunization of experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice with MOG 35-55 (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE-prone mice. In contrast to MOG, immunization with DNA leads to a suppression of proteinuria, a decrease in the concentrations of antibodies to MOG and DNA and a reduction in abzyme production. Immunization with DNA only resulted in a significant increase in DNase activity over 40 days where it became 122-fold higher than before immunization, and fivefold higher when comparing to the maximal activity obtained after MOG treatment. DNA and MOG immunization had different effects on the differentiation profiles of HSCs, lymphocyte proliferation, and the level of apoptosis in bone marrow and other organs of mice. The data indicate that for C57BL/6 mice, DNA may have antagonistic effects with respect to MOG immunization. The usually fast immune response following MOG injection in C57BL/6 mice is strongly delayed after immunization with DNA, which is probably due to a rearrangement of the immune system following the response to DNA., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Effect of alkoxyamines on normal and tumor cells was studied in vitro and in vivo. In vitro experiments showed that alkoxyamines produce a dose-dependent toxic effect on cells of human breast tumor MCF7 line. Transplantation of Krebs-2 ascites carcinoma cells preincubated with alkoxyamines to mice did not induce tumor growth. An opposite effect was observed in normal mouse cells: functional activity of peritoneal macrophages increased. The possibility of using alkoxyamines as theranostic agents is discussed.

We studied radioprotective effects of a preparation based on yeast RNA and its influence on therapeutic efficiency of ionizing radiation against transplanted tumors. Parenteral administration of yeast RNA preparation to mice in a dose of 10 mg 1 h prior to exposure to ionizing γ-radiation ( 137 Cs) in a lethal dose (LD 80/30 ) increased 30-day survival by 66%; by day 80, 80% of animals survived (vs. 2.5% in the control). Whole-body exposure to ionizing γ-radiation in a dose of 7 Gy significantly increased the mean lifespan of mice with experimental lung metastases or intraperitoneally transplanted leukemia L-1210 by 42 and 20.8%, respectively. RNA preparation injected to the mice with tumors 1 h before irradiation did not affect the therapeutic efficiency of ionizing radiation or significantly potentiated it (in mice with transplanted leukemia L-1210). These results suggest that yeast RNA preparation protects healthy tissues during radiotherapy of malignant tumors.

Antimetastatic activity of Platin in lyophilized liposomes stored for 7 years after fabrication was evaluated. The main flaw of liposomes as vehicles for drug delivery to the tumors is their high affinity for the liver, which accumulates a great amount thereof. This property of liposomes can be used for adjuvant therapy of operable primary tumors metastasizing to the liver. It is shown on the model of mouse GA-1 tumor metastases in the liver that platinum(II) complex compound Platin in phosphatidylcholine-cholesterol liposomes, stored for 7 years after lyophilization, causes complete cure of 40% animals, while free Platin prolongs the lifespan of mice with tumors by only 31.7% vs. control (no treatment).

Using the ability of poorly differentiated cells to natively internalize fragments of extracellular double-stranded DNA as a marker, we isolated a tumorigenic subpopulation present in Krebs-2 ascites that demonstrated the features of tumor-inducing cancer stem cells. Having combined TAMRA-labeled DNA probe and the power of RNA-seq technology, we identified a set of 168 genes specifically expressed in TAMRA-positive cells (tumor-initiating stem cells), these genes remaining silent in TAMRA-negative cancer cells. TAMRA+ cells displayed gene expression signatures characteristic of both stem cells and cancer cells. The observed expression differences between TAMRA+ and TAMRA- cells were validated by Real Time PCR. The results obtained corroborated the biological data that TAMRA+ murine Krebs-2 tumor cells are tumor-initiating stem cells. The approach developed can be applied to profile any poorly differentiated cell types that are capable of immanent internalization of double-stranded DNA.

This study demonstrates the results obtained from the GC/MS experimental determination of low concentrations of N-nitrosodiphenylamine in meat canned baby food in the concentration range of 0.027-3.89 mg/kg. The perfect conditions of sample preparation (extraction with organic solvent and solid phase extraction) as well as the application of the chromatography-mass spectrometry allowed us to detect N-nitrosodiphenylamine in samples of the meat canned baby food with high selectivity in concentrations ranged from 0.016 to 5 mg/kg when an error of 23% was assumed. The use of the reaction of transesterification of fatty acids by potassium methylate, the removal of the ester generated from the samples of canned meat by organic solvent (hexane), concentrating of N-nitrosodiphenylamine in the aqueous layer on the cartridges of an automatic solid-phase extraction system provided 99.94% extraction of N-nitrosodiphenylamine from the canned meat samples. The experiment has made evident the presence of N-nitrosodiphenylamine in the samples of canned meat (beef + chicken) with the help of mass-spectrometry method in the mode of full ion scanning using the AMDIS automatic mass-spectral identification system., (Copyright© GEOTAR-Media Publishing Group.)