[Key challenges in the dietary intake structure and cutting edge technologies for optimizing nutrition to protect the health of the Russian рopulation].

This article presents an analysis of some of the results of the work of the Federal Research Center for Nutrition and Biotechnology (Center) in recent years, highlighting the most important, promising areas of Nutrition Science and Food Hygiene that need further development. The priority area of Center functioning is scientific support for the implementation of the Doctrine of Food Security of the Russian Federation (Decree of the President of the Russian Federation dated January 21, 2020 No. 20), Decree of the President of the Russian Federation dated July 21, 2020 No. 474 «On the national development goals of the Russian Federation for the period until 2030 «in terms of ensuring an increase in life expectancy and improving the life quality of the population, the Strategy for Improving the Quality of Food Products in the Russian Federation until 2030 (Order of the Government of the Russian Federation dated June 29, 2016 No. 1364-r). The Center coordinates all research on medical nutrition problems in the Russian Federation within the framework of the work of the Problem Commission on Nutrition Hygiene of the Scientific Council of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, the Scientific Council of the Russian Academy of Sciences on Medical Nutrition Problems, the Scientific and Technical Committee of the Comprehensive Scientific Program «Priority Research in the Field of Nutrition of the Population¼, Profile Commission on Dietetics of the Expert Council in the Field of Health of the Ministry of Healthcare of Russian Federation, ensuring the implementation of their results with the participation of members of the Consortium "Healthcare, Nutrition, Demography". The most important area of the Center's work is scientific and expert support in the field of international and national technical regulation of the production and turnover of foods and raw materials, in particular, the work of the Russian national contact point of the Codex Alimentarius Commission (established by FAO and WHO), as well as the work of the Russian side in the Eurasian Economic Commission regarding the preparation of proposals for technical regulations of the Customs Union in the field of food safety, evaluation of draft technical regulations and amendments and additions to them.

[Alternaria toxins in tomato products marketed in the Russian Federation].

Tomatoes and tomato products are widely produced and consumed throughout the world. Alternaria spp. are the main cause of alternariosis (black mold disease) on fresh tomatoes, both in the field and after harvesting. Alternaria toxins are widespread contaminants of tomato products. The aim of the present study was to evaluate the contamination of tomato processing products from the domestic market with Alternaria toxins, as well as to assess their intake by humans through the consumption of tomato juices. Material and methods. The content of Alternaria toxins (alternatiol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid) was determined in 64 samples of tomato products (paste, ketchup, juice) by high-performance liquid chromatography coupled to tandem mass-spectrometric detection (HPLC-MS/MS). Results. The priority Alternaria toxins for tomato paste, ketchup and juice were tenuazonic acid (61% of 64 samples, in amounts from 20.0 to 1065.5 µg/kg), altenuene (52%, 8.9-200.1 µg/kg) and alternariol (27%, 12.2-561.6 µg/kg). Samples of tomato paste turned out to be the most contaminated with Alternaria toxins while tomato juice samples were the least contaminated. At the same time, several toxins were found in 91% of tomato paste samples, 35% of ketchups, and 23% of tomato juices. Conclusion. To the best of our knowledge, the present study is the first survey devoted to Alternaria toxins contamination of tomato paste, ketchup and tomato juice sold on the Russian market. The high frequency of their contamination with tenuazonic acid, altenuene and, to a lesser extent, alternariol has been established, which indicates a potential risk to human health when tomato processing products are consumed. This indicates the need for a hygienic assessment of contamination the above products with tenuazonic acid, altenuene and alternariol. When calculating the potential intake of Alternaria toxins for different age population groups, it was shown that high levels of alternariol (up to 56.77 ng/kg body weight per day) could be obtained under daily consumption of tomato juice by adults and children under three years of age, as well as tenuazonic acid when consuming tomato juice contaminated at the 95th percentile level as part of the diet in organized groups for orphans and children without parental care.

[International and Russian mechanisms for integrating innovations and experience to optimize the nutrition of the population].

The vigorous scientific and organizational activities of the Federal Research Center for Nutrition and Biotechnology, integration into the international scientific and technical space, the use of advanced innovative technologies, the best examples of world experience, cooperation with leading economic countries are the most important lever for optimizing the nutrition of the population of our country, which is essential for the preservation of the health of the nation and the implementation of the tasks of demographic policy in the Russian Federation.

[Mycotoxins in spices consumed in Russia].

Spices and herbs have been used since ancient times as flavor and aroma enhancers, colorants, preservatives and traditional medicines. As many other plant products, they can be exposed to contaminants, ones of which are mycotoxins, secondary metabolites of fungi. Such contamination can occur during harvesting, processing and storage, distribution, retailing and consumer use. Although they are used and consumed in small quantities, but added to a wide variety of products, especially ready-to-eat products. So the assessment of their contamination with mycotoxins is very important. The aim of the study was to investigate the contamination of spices and herbs with mycotoxins of fungi of the genera Aspergillus, Penicillium, Fusarium and Alternaria, as well as to assess the mycotoxins intake per person when consuming these food groups. Material and methods. Concentration of mycotoxins in 155 samples of spices and herbs was determined by ultra high-performance liquid chromatography coupled to tandem mass-spectrometric detection (UHPLC-MS/MS). The list of mycotoxins included deoxynivalenol, aflatoxins, ochratoxin A, zearalenone, T-2 toxin, fumonisins, sterigmatocistin, HT-2 toxin, diacetoxyscirpenol, enniatins, beauvericin, neosolaniol, citreoviridin, mycophenolic acid, citrinin, tentoxin, altenuene, alternariol and its monomethyl ether. Results. Among the regulated in plant products mycotoxins in the studied samples there were found aflatoxins (B1 - in 19% of samples, from 0.4 to 48.2 µg/kg, B2 - 8%, from < limit of quantitation (LOQ) to 3.2 µg/kg, G1 - 2%, 0.75-21 µg/kg, G2 - 5%, 0.5- 12.5 µg/kg), ochratoxin A (15% samples, 0.8-14 µg/kg), fumonisin B1 (8%, 16.1-722.6 µg/kg), and fumonisin B2 (14%, < LOQ - 79.6 µg/kg). T-2 toxin and deoxynivalenol were found in 10% of samples (< LOQ - 6.5 µg/kg and < LOQ - 65.5 µg/kg respectively), zearalenone - in 4 samples (1.7-106.2 µg/kg), HT-2 toxin - in 8 samples (5.4-19.8 µg/kg). Among little-studied (emergent) mycotoxins in the spices and herbs samples there were found tentoxin (in 36% of samples, in an amount from 0.7 to 10.9 µg/kg), altenuene (in 8%, 14.5-161.5 µg/kg). 10% of the samples were contaminated with alternariol and its methyl ether (from less than LOQ to 12.8 and < LOQ to 55.7 µg/kg, respectively), 4% - with sterigmatocystin (0.4-7.8 µg/kg), 5% - mycophenolic acid (13.1-297 µg/kg), 2% of the samples were contaminated with citrinin and enniatin B (< LOQ - 27.7 and 0.1-1 µg/kg), in 9 samples (6%) beauvericin was detected (< LOQ - 1.7 µg/kg). Over 60% of samples were contaminated with more than one mycotoxin. The content of aflatoxin B1 exceeded the maximum permissible level set in the EU (5 µg/kg) in nine samples. Conclusion. To the best of our knowledge, the present study is the first in the Russian Federation to report results indicating to the contamination of spices and herbs with mycotoxins. High occurrence of aflatoxins, tentoxin, ochratoxin A and fumonisin B2 has been observed. In calculating the potential exposure of mycotoxins, the possibility of high levels of aflatoxin B1 intake have been shown to be possible, which could lead to a public health risk when consuming contaminated spices, herbs and foods containing them.

[Bioactive compounds anthocyanins as a factor in the nutritional recovery of the body's adaptive potential after intense physical activity in the experiment: assessment of immunological and hematological indicators of adaptation].

Restoring the adaptive potential of an athlete is of paramount importance not only for the implementation of his training and competitive activities, but also for maintaining health. One of the leading place in complex recovery programs in sports is given to full-fledged optimal nutrition, which provides for meeting the body's requirements not only in energy, macro- and micronutrients, but also in minor bioactive compounds. The use of anthocyanin-containing products is a promising strategy for the normalization of metabolic and immune disorders that develop as a result of intense physical and neuro-emotional stress not only in athletes, but also in other groups of people exposed to these factors, including military personnel undergoing training in conditions close to combat. This determines the relevance of this study. The aim of the research was to study the effect of an anthocyanin-enriched diet on hematological profile and cellular immunity in rats after intense physical activity. Material and methods. The experiment was carried out for 4 weeks on 4 groups of male Wistar rats with an initial body weight of ~300 g. The motor activity of the animals of the 1st (control) and 2nd groups was limited by the standard keeping animals in the vivarium, while physically active rats of the 3rd and 4th groups received additional physical activity - training on a treadmill. Before the end of the experiment, the animals of 3rd and 4th groups were given debilitating physical activity on a treadmill (until the rats refused to continue the exercise). Rats of all 4 groups received a standard semi-synthetic diet, water ad libitum. Animals in 2nd and 4th groups were additionally fed blueberry and blackcurrant extract (30% anthocyanins) as part of the diet at a daily dose of 15 mg anthocyanins/kg body weight. Hematological parameters were determined on a Coulter ACT TM 5 diff OV hematological analyzer. Expression of CD45R, CD3, CD4, CD8a, CD161 receptors on rat peripheral blood lymphocytes was determined by direct immunofluorescent staining of whole blood cells using a panel of monoclonal antibodies conjugated with fluorescent dyes: APC, FITC, PE. The measurements were carried out on an FC-500 flow cytometer. Results. Intense physical activity in rats of the 3rd group did not lead to a significant change in erythrocyte parameters compared with the control group. Enrichment of the diet with blueberry and black currant extract (the 2nd and the 4th groups) provided a significant (p<0.05) increase in blood content of hemoglobin (Hb) (150.7±0.9 and 154.4±2.0 vs 145.4±0.9 g/l in control), hematocrit (44.95±0.21 and 46.18±0.64 vs 43.78±0.32%) and the average content of Hb in erythrocytes (18.00±0.20 and 18.03±0.24 vs 17.35±0.24 pg). The absolute content of leukocytes and other cellular elements of the leukocyte formula, as well as leukocyte indices in rats of the experimental groups didn't significantly differ from those of the control rats, which confirms the absence of an inflammatory process. Intense physical activity and anthocyanin enrichment of the diet didn't have a significant effect on rat platelet parameters. Enrichment of the diet of rats of the 4th group with blueberry and black currant extract led to the activation of cellular immunity, as evidenced by a significant (p<0.01) increase in the percentage (from the total content of T-lymphocytes) of T-helpers (70.13 ±1.34 vs 63.75±0.99%) and a decrease in the relative content of cytotoxic T-lymphocytes (28.65±1.38 vs 34.71±0.95%) in comparison with those in rats of the 3rd group and at the level of the trend (р<0.1) - from the 1st group indexes (66.87±1.20 and 31.87±1.26%, accordingly). Intense physical activity led to a decrease in immunoregulatory index in rats of the 3rd group (1.86±0.07) compared with the control (2.13±0.12) (p<0.1), and in animals of the 4th group this indicator was significantly higher (2.50±0.14, p<0.05). In animals of the 3rd group a statistically significant (p<0.05) decrease in the relative content of NK cells in peripheral blood was found compared to the control. Enrichment of the diet of physically active rats with blueberry and black currant extract led to a significant (p<0.05) increase in the percentage of NK cells compared to this indicator in rats of the 3rd group (4.87±0.75 vs 2.08±0.18%) and had no significant difference with the indicator in rats of the control group (4.32±0.98%). Conclusion. The enrichment of the rats' diet with blueberry and blackcurrant extract containing a daily dose of 15 mg of anthocyanins per kg of body weight provides an increase in blood Hb content, hematocrit and the average content Hb in erythrocytes. It has been established that intense physical activity induces the cellular immunity suppression. The activating effect of anthocyanins on adaptive cellular immunity and NK cells, which are lymphocytes of innate immunity, was revealed. The data obtained indicate the effectiveness of the use of bioactive compounds (anthocyanins) to increase the adaptive potential of the organism.

Systemic Biomarkers and Liver Morphology in Rats during Chronic Low-Dose Toxicant Administration against the Background of Vitamin Deficiency.

Liver morphology, intensity of apoptosis, and activity of xenobiotic metabolism enzymes were studied in a chronic model experiment in rats receiving a mixture of 6 pesticides against the background of life-long diets with adequate and insufficient supply of water-soluble vitamins. The dose of each pesticide in the mixture did not exceed the acceptable daily intake (1 ADI). It was found that chronic exposure to low doses of anthropogenic toxicants in combination with permanent vitamin deficiency provokes a number of liver changes, such as increased apoptosis activity, cytochrome P450 system depletion, steatosis, and inflammatory infiltration, which is a potential health risk factor.

[Effect of microand nanoplastics on the gastrointestinal mucosa and intestinal microbiome].

Worldwide production and use of the polymers has led to intensive environmental pollution with micro- and nanoplastics (MP and NP). Accumulating in ecosystems, MP are transmitted through food chains and enter the human body. The associated health risks are of grave concern and require assessment. The main entry gate for MP/NP supplied with food is the gastrointestinal tract (GIT). Despite the well-established concept of MP/NP toxicity, information about their actual effects on the GIT is contradictory. The aim of the research was to establish the nature and mechanisms of NPs and MPs action on the gastrointestinal mucosa and intestinal microbiome, basing on the literature data. Material and methods. The review was compiled after selecting of 90 documents from major databases including Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to March 2023). Results. In animal studies and in vitro models, it was shown that MP/NP affect mucus secretion, its rheological characteristics, and can cause an increase in the permeability of tight junctions of epithelial cells by reducing the expression of zonula occludens protein 1 (ZO-1), occludin and claudin-1, which promotes the penetration of MP through the intestinal wall. Various adsorption layers (coronas) formed on the surface of MPs both abiotically and during transit through the GIT can lead to both increased and reduced toxicity of MPs. Biofilms formed on MP/NP surface create favorable conditions for the activity of pathogenic bacteria and horizontal gene exchange between the components of the biofilm and the intestinal microbiome. Animal experiments have shown an unfavorable effect of MP/NP on the intestinal microbiota and its key metabolites, contributing to the development of dysbiosis. Conclusion. Most data on the effect of MP on the GIT have been obtained using a model object - polystyrene microspheres, which are rarely found in practice. A frequent limitation of the in vitro studies is the discrepancy between used doses (concentrations) of MP and those that may occur when MP are consumed with food. Data on the potential impact of MP/NP on the GIT protective barrier and intestinal microbiota obtained under various experimental conditions are contradictory. Thus, evidence of the impact of MP/NP on the GIT and intestinal microbiota of humans needs further confirmation, which will allow us to move on to the development of a set of measures that can reduce the risks of MP exposure to human health.

[Mycotoxins contamination of cocoa products and carob marketed in the Russian Federation].

Cocoa is a daily basic food for many people all over the world. Also, people engaged in healthy lifestyle often prefer carob. The aim of the present study was to evaluate occurrence of Aspergillus, Penicillium, Fusarium and Alternaria secondary metabolites in cocoa and carob available in the Russian Federation and assess mycotoxin's intake with these products. Material and methods. Concentration of 27 mycotoxins in 63 samples of cocoa and carob products was determined by ultra high-performance liquid chromatography coupled to tandem mass-spectrometric detection (UPLC-MS/MS). The list of mycotoxins included regulated ones (aflatoxins, ochratoxin A, deoxynivalenol, fumonisins, T-2 toxin, zearalenone), their derivatives and structural analogs (A and B trichothecenes), and emergent mycotoxins (alternariol, its monomethyl ether, altenuene, tentoxin, citrinin, sterigmatocistin, cyclopiazonic and mycophenolic acids, enniatins, beauvericin). Results. 29 of 41 cocoa samples were positive for beauvericin, contamination level was from 1.6 to 2184.8 µg/kg. Tentoxin, sterigmatocystin and alternatiol monomethyl ether were detected in 3 samples; their concentration varied in the ranges 0.7-1.2, 1.5-3.3 and 4.0-7.8 µg/kg correspondingly. Carob samples were positive for alternariol (14 of 22 samples, 1.5-43.1 µg/kg); tentoxin (13 samples, 0.5-8.7 µg/kg), mycophenolic acid (6 samples, 6.9-8.2 µg/kg) and for alternatiol monomethyl ether (3 samples, 1.0-1.2 µg/kg). Several samples of cocoa were contaminated with regulated mycotoxins: zearalenone (18 of 41 samples, 2.1-24.6 µg/kg), ochratoxin A (14 samples, 0.75-12.0 µg/kg) and aflatoxin B1 (2 samples, 0.59 and 0.86 µg/ kg). Several carob samples were contaminated with fumonisin B2 (7 of 22 samples, 4.2-5.2 µg/kg), ochratoxin A (5 samples, 0.5-1.4 µg/kg) and aflatoxin B1 (3 samples, 0.15-0.18 µg/kg). The ochratoxin A content in two instant cocoa beverages exceeded its maximum level (5 µg/kg) set for some plant products. Conclusion. To the best of our knowledge, the present study is the first survey devoted to emergent mycotoxin contamination of carob and cocoa alternative products marketed in the Russian Federation. The high occurrence of such mycotoxins as aflatoxins, beauvericin and ochratoxin A in these products indicates a potential health risk and the need for a hygienic assessment of cocoa and carob products' contamination not only with regulated in cocoa products aflatoxin B1, but with other mycotoxin including emergent ones. The risk of dietary intake of aflatoxins, beauvericin and ochratoxin A with cocoa products (especially with instant cocoa beverages) has been revealed for children over 7 years old in organized groups.

[The structure of blood gut microbiota markers in athletes and their relationship with the diet].

It is known that under conditions of ultra-high physical activity and a specific diet, the state of the microbiota plays a significant role in maintaining the health, metabolic and energy status of athletes. The purpose of the study was to evaluate the composition of blood microbial markers in professional football players and physically active people and their correlation with diets in order to substantiate recommendations for their optimization. Material and methods. In a cross-sectional study a group of football players (n=24, 28±3 years old, body mass index - 22.5±1.0 kg/m2) who received a diet according to the training regimen, and a comparison group of physically active individuals (n=25, 34±5 years old, body mass index - 21.8±2.8 kg/m2) have been examined. The method of gas chromatography-mass spectrometry was used to analyze microbial markers of microbiome, mycobiome, virome and blood metabolome populations. Data on actual dietary intake were collected using food diaries for 3 days, followed by data processing with the Nutrium 2.13.0 nutritional computer program. For analysis, individual daily requirements for energy and macronutrients have been calculated based on the basal metabolic rate (according to the Mifflin-San Geor formula, taking into account anthropometric data), the coefficient of physical activity (groups IV and II, respectively). Results. The analysis of the athletes' diet, compared with individual requirements and with the recommendations of the International Society for Sports Nutrition (ISSN), revealed a lack of complex carbohydrates (5±1 instead of 6.1±0.3 g/kg body weight day), an excess of sugars (23±4 instead of <10% of kcal). These figures are significantly higher than the intake of similar nutrients in physically active people in the comparison group. In football players, compared with the comparison group, significant changes in microbial markers were found for Alcaligenes spp., Clostridium ramosum, Coryneform CDC-group XX, Staphylococcus epidermidis (p<0.001), known for their pro-inflammatory activity in the intestine, as well as for Lactobacillus spp. (p<0.001) performing a protective function. In addition, mycobiome markers were increased in athletes: Candida spp. (p<0.001), Aspergillus spp. (p<0.001), among which there are potential pathogens of mycoses. This was not observed in the comparison group. At the same time, an increase in the microbial markers of Alcaligenes spp., Coryneform CDC-group XX, Lactobacillus spp., Streptomyces spp., Candida spp. Micromycetes spp., containing campesterol in the cell wall, in football players positively correlated with a high calorie diet (p<0.001). A similar correlation of mycobiome markers (Micromycetes spp., containing sitosterol in the cell wall, ρ=0.346, p=0.015) was observed with an excess of easily digestible carbohydrates. Taking into account the data obtained, a correction of the diet have been proposed: increasing the consumption of carbohydrates to 7.3-7.5 g/kg of body weight/day by including bakery products from whole grain flour and cereals in the diet (up to 300-370 g/day), limiting simple sugars (up to 90-95 g/day). Conclusion. High physical activity leads to changes in the structure of blood microbial markers, including a shift towards an increase in potentially pathogenic fungi. Wherein, a predictive role is played by an imbalance of macronutrients in terms of quantitative and qualitative composition, an excess of simple sugars, and a lack of slowly digestible carbohydrates. To correct the diet, an additional inclusion in the diet of their main sources - products from cereals (cereals and bakery products) is proposed.

[Specialized vitamin-mineral supplements for persons in extreme conditions].

Monitoring the actual nutrition of various groups of the population of the Russian Federation indicates the presence of pronounced deficiencies of essential micronutrients, and above all vitamins and biologically active compounds. Deficiency of many micronutrients is a risk factor for the development of a number of conditions (anxiety, depression, etc.) and non-communicable diseases (cardiovascular, cognitive and neuromuscular disorders). It reduces the effectiveness of the treatment of injuries and wounds, and also leads to a negative effect on the antioxidant protection of the body and a more pronounced response to stress. To prevent long-term consequences, the population is primarily provided with psychological assistance, not always paying due attention to healthy nutrition. The aim of the research was to substantiate and develop vitamin-mineral supplements (VMS) for special purposes to restore impaired functions in various population groups in extreme situations, including those located in the zones of a special military operation. Material and methods. A review of the literature on the problem in recent years was carried out using the databases of the RSCI, Google Scholar, ResearchGate, PubMed by the keywords "B vitamins", "vitamin-mineral supplement", "military personnel", "mood", "efficiency", "depression", "refugees", «multivitamin¼, «conflict¼, "efficiency". Results. In an emergency situation, under conditions of high physiological (physical and neuropsychiatric) stress, the requirements in micronutrients increase. An inverse association between micronutrient status and the development of symptoms of depression, sleep disturbance has been found. The analysis of the data on the administration of VMS with different composition in the nutrition of the population and law enforcement officers showed the effectiveness of its intake for all persons in the zone of military conflicts. At the same time, VMS should contain a complete set of vitamins, in doses for B vitamins 200-300% of the recommended daily intake (RDI), vitamin D and other vitamins in a dose of 100%, magnesium, zinc, iodine, iron - in doses up to 50% of RDI. The administration of such VMS for 1-6 months provides an increase in blood serum vitamin level and antioxidant activity, leads to an improvement in functional adaptation and military professional performance, increases self-esteem of health, reduces symptoms of stress and anxiety, improves the mood. Conclusion. The expediency of including VMS for special purposes in the nutrition of both military personnel and the entire population in the zone of military conflict has been proved. Enrichment of the diet with micronutrients is a reliable non-drug prevention of health disorders caused by stress in emergency.

[The global challenge of the XXI century - COVID-19: the answer of dietetics].

For the first time, the world is facing a global threat to humanity and unprecedented challenges associated with the spread of COVID-19. The fight against the new coronavirus infection requires the joint efforts of the entire world community and equal cooperation. The entire healthcare system is working today in a mobilization format. During the ongoing pandemic, the issue of nutrition of the population remains relevant. Increasing the adaptive potential of the body by optimizing nutrition is a necessity.

[On the new (2021) Norms of physiological requirements in energy and nutrients of various groups of the population of the Russian Federation].

The article presents the main provisions of the new "Norms of physiological requirements in energy and nutrients for various groups of the population of the Russian Federation" developed and approved in accordance with the established procedure, accumulating the latest fundamental knowledge and world and domestic experience, that determine the values of physiological requirements in nutrients and energy sources, adequate levels of consumption of micronutrients and biologically active substances with an established physiological effect. In the Norms the conceptual apparatus has been expanded and updated, several terms and definitions to them (nutriome, intestinal microbiome, trans-isomers of fatty acids, critical nutrients, edible salt, glycemic index of food products, etc.) have been introduced. Changes have been made to the age periodization of the child and adult population of the Russian Federation, as well as adjustments in the differentiation of the population by the level of physical activity (4 groups for men and women). Taking into account these data, the recommendations on the proportion of macronutrients in the calorie content of the daily diet have been adjusted. The levels of physiological requirements in energy and nutrients have been clarified, depending on the physical activity of the population, including vitamins and mineral substances for both men and women, including period of pregnancy and lactation, as well as for children of different ages. For the first time, recommendations are included to reduce the intake of critical nutrients for health (dietary salt, added sugars, trans-isomeric fatty acids), based on data from modern meta-analyzes on the negative health effects of their excessive intake. Recommendations on the consumption of ω-3 and ω-6 polyunsaturated fatty acids by children and adults, including pregnant and lactating women, have been significantly expanded; adequate dietary intake of plant sterols have been introduced for the first time; while adequate dietary intake of certain phenolic compounds (phenolic acids, flavonoids, polymeric phenolic compounds and stilbenes) were specified. For the first time, the Norms include recommended levels of water (drinks) consumption to maintain the body's water balance under optimal environmental conditions for adult men and women at different levels of physical activity, for children, as well as pregnant and lactating women. For the first time in world practice, a complex of qualitative and quantitative indicators of the reference intestinal microbiome is presented, including modern taxonomic and functional characteristics that give an conception of microbiota phenotype in adults with a normal body mass index.

[Pathogenetic mechanisms for the development of hematological disorders in induced fatty liver disease in Wistar rats and assessment of the regulatory effects of carnosine and α-lipoic acid].

The study of the relationship between hematopoiesis and metabolism is now particularly relevant in view of the high incidence of alimentary dependent diseases, including non-alcoholic fatty liver disease. In this regard, pathogenetic factors of this disease development are studied actively in order to choose adequate drug therapy and usage of bioactive substances with antioxidant properties. The aim of the study was to study the pathogenetic relationship of hematological disorders and imbalance of growth factors, leptin and ghrelin in male Wistar rats in the model of the initial stage of non-alcoholic fatty liver disease development and to assess the regulatory effect of minor bioactive substances - carnosine and α-lipoic acid. Material and methods. The studies were performed on male Wistar rats with initial body weight 150±10 g within 8 weeks. Animals were divided into 5 groups (n=8 in each). Rats of the control group received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the combined addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. Hematological values were determined on a hematological analyzer. The content of ghrelin and leptin, as well as growth factors GM-CSF and M-CSF in blood plasma and adipose tissue lysates, was determined by multiplex immunoassay using xMAP technology. Results. Rat intake of HCCDD resulted in decreased hemoglobin levels and red blood cell scores compared to controls. Diet enrichment with carnosine and α-lipoic acid did not have a reliable effect on these indicators. Carnosine intake had a protective effect on erythrocyte volume, a decrease of which was recorded in other experimental groups. HCCDD stimulated the growth of the absolute number of leukocytes in peripheral blood due to granulocytes and mononuclears. The enrichment of HCCDD with carnosine and α-lipoic acid led to a further increase in leukocytosis, the maximum level of which was observed in the group of rats fed HCCDD, simultaneously enriched with carnosine and α-lipoic acid (14.86±1.48×109/l compared to 8.67±1.23×109/l in control). All diets used in the research had no effect on the number of erythrocytes and platelets in the peripheral blood of rats. The use of both HCCDD alone and in combination with carnosine or α-lipoic acid intake had a negative effect on the level of growth factors GM-CSF and M-CSF in blood plasma and adipose tissue. The consumption of HCCDD caused an increase in leptin blood level (8.54±0.69 compared to 2.58±0.37 pg/ml in control, р<0.05), which was normalized by enriching the diet with carnosine and α-lipoic acid. Ghrelin blood level significantly decreased in all experimental groups compared to the control: by 30% in rats fed and by almost 50% when carnosine and α-lipoic acid were added to HCCDD. The intake of α-lipoic acid led to hormone level changes in adipose tissue lysates, leptin content decreased (2.31±0.11 vs 2.77±0.15 pg/ml), while ghrelin level significantly increased (0.35±0.14 vs 0.20±0.06 pg/ml), compared with the control group (р<0.05). Conclusion. The revealed interrelation of parameters of the cellular composition of peripheral blood and hemoglobin content with the changes in the content of GM-CSF, M-CSF, leptin and ghrelin in blood plasma and adipose tissue indicates the mutual influence of the studied CSF, leptin, ghrelin and added antioxidants (carnosine and α-lipoic acid) on the regulatory mechanisms of hematopoiesis in rats fed HCCDD.

[Effect of resveratrol, carnitin, quercetin and aromatic amino acids on the xenobiotic metabolising and antioxidant enzymes in the liver during obesity in rats with different genotypes].

The use of minor biologically active substances (BAS) in specialized products is one of the promising areas in the diet therapy for obesity and other alimentary-dependent diseases (metabolic syndrome, type 2 diabetes mellitus, etc.). The effects of the BAS in patients are often ambiguous, depending on a number of factors, one of which is the state of the organism enzyme systems (enzymes of xenobiotic metabolism and antioxidant defense), the patient's genotype, and many others. The aim was to study the effect of BAS [quercetin (Q), L-carnitine (L-Car), resveratrol (Res), aromatic amino acids tyrosine (Tyr) and tryptophan (Trp)] on the activities of phase I and II of xenobiotic-metabolising enzymes and antioxidant enzymes in rats using various in vivo models of obesity and with impaired dopamine transport. Material and methods. The activities of cytochrome P450 enzymes (CYP1A1 and CYP3A), glutathione transferase (GT), UDPglucuronosyltransferase (UDP-GT), hemoxygenase-1 (HO-1), and quinone reductase (QR) were determined by fluorimetric, spectrophotometric methods and HPLC in microsomes and cytosolic fraction of rat's liver. We used rats of outbred Wistar line, Zucker ZF line with hereditarily determined obesity and DAT-KO line with a knockout of the DAT dopamine transporter gene, which for 62 days were fed a standard balanced control or high-carbohydrate high-fat diet (30% fat by weight and 20% fructose solution instead of water) supplemented with BAS, such as Q, Res, L-Car, Tyr and Trp in doses 50, 25, 300, 1250 and 250 mg/kg of body weight respectively. Results and discussion. The presence of a DAT knockout led to a small but statistically significant decrease in the activity of GT in the liver in both homozygous and heterozygous animals. The CYP1A1 activity was significantly decreased in all carriers of the DAT knockout gene, while HO-1 activity, on the contrary, was increased, independently of the composition of the diet used. In Zucker ZF rats of all groups, in comparison with Wistar rats fed the corresponding diets, the activities of GT, UDP-GT, CYP1A1, CYP3A and QR were significantly reduced in terms of the total protein content. HO-1 activity was reduced in Zucker ZF rats in comparison with Wistar rats to a lesser extent, however, the addition of Q significantly influenced the difference between the two lines. Trp consumption led to a significant increase in GT activity in Wistar rats. In DAT-KO homozygotes this effect was insignificant, while in heterozygotes it was absent. Similarly, consumption of Trp resulted in a significant increase in CYP1A1 activity only in Wistar rats, but not in DAT-KO rats. The activity of UDP-GT under Trp intake increased only in DAT heterozygotes. The genotype significantly influenced the response of QR activity to Trp consumption, but in an ambiguous way - there was an increase in activity in heterozygotes and a decrease in homozygotes for DAT knockout. CYP1A1 activity was significantly increased in rats treated with Tyr. Conclusion. The data obtained indicate that the effect of various dietary supplements used in the treatment of obesity and metabolic syndrome on the xenobiotic-metabolising enzymes and antioxidant enzymes can have a different nature and direction depending on the genotype and the level of spontaneous physical activity and energy expenditure determined by it, which should be taken into account when approaches to personalized diet therapy of alimentary-dependent diseases are developing.

[Dried fruits marketed in Russia: multi-mycotoxin contamination].

Mycotoxins (MT) - secondary metabolites of micromycetes - are natural contaminants of plant products. Fruits are particularly susceptible to fungal contamination and MT accumulation due to high sugar content. It can occur at any production stage: during vegetation, drying and storage. The most hazardous MT - aflatoxins (AFLs) and ochratoxin A (OTA) - are regulated in dried fruits in some countries. However, their maximum levels (ML) were not set in Russia yet. The present research was aimed at the evaluation of MT contamination of dried fruits marketed in Russia. Material and methods. 54 samples of dried dates (n=11), apricots (n=9), raisins (n=9), prunes (n=7), figs (n=6), apples (n=3) and mixtures for compote (n=9) were analyzed for 32 MTs by HPLC-MS/MS with positive/negative ESI in the MRM mode. Results. OTA and fumonisins (FBs) were the major regulated contaminants, their occurrence proved to be 10 and 17% correspondingly. Emergent metabolites of Fusarium spp. enniatin A (ENN A, 22%) and beauvericin (BEA, 15%); Penicillium spp. mycophenolic and cyclopiazonic acids (MPA and CPA, about 19%); Alternaria spp. tentoxin (TE, 17%) were detected also. Two-thirds of positive samples were contaminated with two and more MTs. All studied samples could be referred as safe within the EU regulations. Conclusion. Some kinds of dry fruits proved to be susceptible to contamination with particular MTs. Characteristic pattern for raisin was the OTA and MPA combination, for figs - FBs and CPA. According to literature data concerning occurrence and safety of MTs and the results of our survey, the long-term monitoring of AFLs and OTA in dry fruits and AFLs, OTA, FBs and CPA in figs from different regions of Russia is necessary to assess the need for setting of MLs of these MTs.

[Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats].

Non-alcoholic fatty liver disease (NAFLD) is now a common liver disease affecting about a third of the world's population. In this regard, the issue of studying the pathogenetic factors of the development of this disease in order to select adequate drug therapy and biologically active substances with antioxidant properties regulating the balance of pro- and anti-inflammatory cytokines is of particular relevance. The aim of the study was to assess the effect of minor biologically active substances - carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in the experimental model of the initial stage of NAFLD. Material and methods. The studies were performed on male Wistar rats with initial body weight of 150±10 g. Animals were divided into 5 groups of 8 rats each. Within 8 weeks, rats of the 1st group (control) received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. The study of rat hepatocyte apoptosis was performed by flow cytometry. Hepatocytes were stained with annexin V and vital dye 7-aminoactinomycin, followed by detection on an flow cytometer. The content of cytokines and chemokines (IL-1α, IL-10, IL-17А, M-CSF, MIP-1α, MIP-3α, RANTES) in the cytoplasmic fraction of liver tissue was determined by multiplex immunoassay. Results and discussion. On the model of the initial stage of development of NAFLD in male Wistar rats the еnrichment of HCCDD with carnosine and α-lipoic acid had demonstrated a protective effect on hepatocytes with a decrease in apoptosis intensity to the level in control rats. Under the influence of HCCDD, an increase in the content of M-CSF and MIP-1α and a decrease in the levels of MIP-3α and RANTES, stimulating the migration and differentiation of various immunoregulatory populations to the parenchyma at an early stage of the formation of fatty hepatosis, in the cytoplasmic fraction of liver tissue were detected. Moreover, a decrease in the level of proinflammatory cytokines IL-17A and IL-1α and an increase in IL-10 produced mainly by Treg-populations indicate the absence of pronounced inflammatory changes in the liver of male Wistar rats at the initial stages of development of fatty dystrophy. Conclusion. Enrichment of HCCDD with both carnosine and α-lipoic acid in Wistar rats had a protective effect on hepatocytes with a decrease in apoptosis to a level in control rats. The increase in the IL-10/IL-17A ratio indicates the activation of anti-inflammatory mechanisms due to the functional predominance of Treg-cells over Th1/Th17 lymphocytes.

[To the 90th anniversary of the Institute of Nutrition: a look through the years].

Half of our health depends on the food quality. Federal Research Centre of Nutrition, Biotechnology and Food Safety has been dealing with this problem for 90 years. Core issues are medical enzymology, searching new food sources (protein problem), nutritional epidemiology, nutrition for professional athletes and cosmonauts, seeking new biologically active compounds, food toxicology and safety assessment of nanotechnologies, a study of the metabolism and mechanism of action of food contaminants, creation of a regulatory framework for chemical and microbiological safety, and much more. The infant and baby nutrition and nutrition of older people in recent years has developed rapidly.

[Nutriome as the direction of the "main blow": determination of physiological needs in macro- and micronutrients, minor biologically active substances].

One of the essential parts of fundamental research in Nutrition Science is the determination of the physiological requirements of humans for energy and food substances. Research that has been carried out in this area over the past 90 years, consistently develops and improves the norms of physiological requirements for energy and nutrients for various groups of the population of the Russian Federation. In the 50 years of the last century in this research field, determining the values of daily intake for macronutrients (proteins, lipids and carbohydrates), was in the first place. Then the Era of micronutrients (vitamins, minerals, trace elements) was started, and, finally, now there is the Era of minor food biologically active substances. More and more facts are accumulating about their leading role in regulating metabolism. They can be recognized as endogenous regulators, the primary vital components involved in the formation of human health. In recent years, the new definition of Nutriome is introduced into Nutrition Science. It is considered as a set of essential nutritional factors to maintain a dynamic equilibrium between human being and the environment, aimed to ensure viability, the preservation and reproduction of the species, keeping the adaptive capacity, the system of antioxidant defence, apoptosis, metabolism, and immune system function. The Nutriome is a formula for optimal nutrition, which is continually being improved and supplemented. Knowledge of this formula is the key to forming an optimal diet for a person, and, therefore, to save their health. It is evident that at the population level, the Nutriome has its characteristics, its structure for each age period of human life. The need to develop a formula for optimal nutrition and, consequently, updating nutrient-based dietary guidelines is induced by socio-economic and demographic changes in population, changes in anthropometric characteristics of children and adults, increasing prevalence of socially significant non-communicable diseases, developing studies of the significance of particular food substances and establishing the relationship between nutrition and health.

[Mass-spectrometric MRM analysis of FDA-verified proteins in the blood plasma of healthy volunteers]. / Mass-spektrometricheskii MRM analiz FDA-verifitsirovannykh belkov v plazme krovi zdorovykh dobrovol'tsev.

The proteomic composition of a biological sample serves as the most important feature of a biological object, and it allows discriminating normal and pathological conditions. Targeted mass spectrometric analysis, namely, multiple reaction monitoring (MRM) using synthetic isotopically-labeled internal standard (SIS), is the main alternative to the ELISA method for the analysis of diagnostically significant proteins. Based on the MRM results, a prototype test system has been developed; it employs the targeted mass spectrometric method for multiplex, quantitative analysis of FDA-verified proteins in whole blood plasma. Using this approach, it was possible to measure the content of 42 proteins in 31 samples in a concentration range spanning five orders of magnitude. The interindividual variability for 30 of the 42 registered proteins was less than 40%. The largest scatter was observed for haptoglobin (68%), immunoglobulin heavy constant delta IGHD (90%), angiotensin (72%), sex hormone-binding globulin SHBG (100%) and lipoprotein-(a) (136%). The obtained results on the concentration of proteins correlate with published data (Hortin et al., 2008, Clinical Chemistry, 54, 1608) with R2=0.84. The developed prototype test system based on targeted mass spectrometric analysis of proteins can be considered as an alternative to methods using monoclonal antibodies.

[COVID-19: new challenges for medical science and practical health].

Currently, due to the wide spread of the new coronavirus infection COVID-19 and the need for anti-epidemic measures, medical science should integrate all efforts to ensure, on the one hand, at the global level - the fight against the spread of infection, on the other hand, at the individual level - increasing the adaptive capacity and immune response of the organism to protect against COVID-19. Nutrition is the most important factor determining human health and the functioning of all mechanisms to protect a person from negative environmental factors. For the prevention and treatment of new coronavirus infection COVID-19, a significant role is played by the correction of eating disorders, including vitamin and micronutrient deficiency. Federal Research Centre of Nutrition and Biotechnology, together with Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), prepared Recommendations on nutrition for children and adults, requiring a self-isolation regime or quarantine at home in connection with COVID-19. In order to promptly inform and advise the population on nutrition optimization in the early days of anti-epidemic measures, an information reference Contact Center was created and is continuously functioning on the basis of the Federal Research Centre of Nutrition and Biotechnology. Equally important is the implementation of measures aimed at the prevention of food contamination with COVID-19 agent. In this regard, the Federal Research Centre of Nutrition and Biotechnology, together with Rospotrebnadzor prepared guidelines on measures to prevent the transmission of a new coronavirus infection through foods. Another aspect that the medical community has faced in connection with the pandemic is the need to reorient specialized medical organizations that have not previously worked with patients with infectious diseases in order to create Clinical centers for the treatment of the new coronavirus infection COVID-19. Thus, in the context of the spread of the new coronavirus infection COVID-19, many areas of medicine are involved in the process of providing anti-epidemic measures. Successful completion of the tasks will significantly reduce the negative consequences of the COVID-19 pandemic for the state and citizens.