Postgenomic Properties of Natural Micronutrients.

Modern medical approaches to the therapy of various diseases, including cancer, are based on the use of toxic drugs. The unfavorable side effects of traditional medicine could be counterbalanced by addition of natural bioactive substances to conventional therapy due to their mild action on cells combined with the multitargeted effects. To elucidate the real mechanisms of their biological activity, versatile approaches including a number of "omics" such as genomics, transcriptomics, proteomics, and metabolomics are used. This review highlights inclusion of bioactive natural compounds into the therapy of chronic diseases from the viewpoint of modern omics-based nutritional biochemistry. The recently accumulated data argue for necessity to employ nutrigenetic and nutrimetabolomic analyses to prevent or diminish the risk of chronic diseases.

Activity of Cathepsin B and Proteome in the Serum and Brain of Rats with Different Behavioral Activity under Conditions of Metabolic Stress.

Study of the brain and serum of male Wistar rats with the metabolic stress model detected changed proteomic profiles of emotiogenic structures and an increase of cathepsin B activity. Antiapoptotic effect of coenzyme Q10, added to the ration, was detected. Differences in the adaptation response of animals with passive and active behavior under conditions of metabolic stress were detected.

Effect of Metabolic Stress on Lysosomal Proteolysis in the Liver and Brain of Rats Receiving Q10-Enriched Ration.

Activation of lysosomal proteolysis and increased coenzyme Q10 level were revealed in the liver and brain of rats with individual typological features under conditions of food deprivation. Changes in cathepsin B activity in these tissues were different in behaviorally active and passive animals. We observed indirect modulating effect of coenzyme Q10 in the regulation of activity of lysosomal endopeptidases in the brain of animals with different behavior during adaptation to metabolic stress.

[Analysis of the Specificity of IgA Antibodies Produced in the Mouse Small Intestine].

Intestinal microbiota controls multiple aspects of body homeostasis. The microbiota composition changes easily in response to internal or external factors, which may result in dysbiosis and associated inflammatory reactions. Thus, maintaining the microbiota composition by the host immune system is crucial, and one of the main mechanisms for microbiota control is production of immunoglobulin A (IgA) at mucosal surfaces. The molecular mechanisms regulating the interactions between the immune system and microbiota remain obscure. A panel of hybridoma cell lines was constructed to produce monoclonal IgA antibodies specific to various commensal bacteria present in intestinal microbiota. The panel can be used to further understand the mechanisms whereby the adaptive immune system controls the microbiota composition.

Proteomic Characteristics of Blood Serum in Rats with Different Behavioral Parameters after Acute Stress.

We studied proteome profile of blood serum of Wistar rats with different behavioral activity immediately and in 1 and 3 days after acute stress on the model of 12-h immobilization during the nighttime. Comparative analysis of 2D-electrophoretograms revealed differences in the expression of serum proteins in non-stressed (control) and stressed (experimental) rats. We found 22 protein spots that characterized the proteomic features of blood serum in rats with different prognostic resistance to stress. Mass-spectrometry of isolated spots identified 6 functional proteins. Persistent proteome changes in the blood of animals at different stages after acute stress were determined. The specificity of proteomic characteristics of blood serum was shown in behaviorally passive and active rats during the post-stress period. These data extend the concept on specific protein markers for the formation of a negative emotional state and adaptive-and-compensatory processes in mammals with different sensitivity to stressogenic factors.

Effect of Metabolic Stress on Coenzyme Q10 Content in Tissues of Active and Passive Rats.

The dynamics of coenzyme Q10 concentration in the blood plasma, liver, and brain of passive and active rats was studied on the model of metabolic stress. This parameter was shown to differ in rats with various patterns of behavior. Dietary consumption of coenzyme Q10 in doses of 10 and 100 mg/kg body weight was followed by changes in its content in experimental animals.

Effect of Coenzyme Q10 on Proteomic Profile of Rat Brain Amygdala during Acute Metabolic Stress.

Differences in the proteomic profiles of the brain amygdala in rats with different prognostic resistance to stress were found on the model of metabolic stress. Differential expression of tropomodulin-2, GTP-binding protein SAR1, peroxiredoxin-2, calcineurin B homologous protein 1, Ras-related protein Rab-14, glutathione S-transferase omega-1, Tcrb protein, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 8 (mitochondrial) was shown to depend on the behavioral pattern of animals and stage of the study. Specific features were observed in the involvement of the amygdala in the stress response of specimens with various behavioral characteristics.

Effect of Acute Emotional Stress on Proteomic Profile of Selected Brain Areas and Lysosomal Proteolysis in Rats with Different Behavioral Activity.

We compared proteome profiles of selected brain areas (cortex, amygdala, hippocampus, and reticular formation) and measured cathepsins B and D activity in liver lysosomal fraction in rats with different behavioral activity under conditions of emotional stress. In passive rats, the expression of some proteins in various brain regions was changed and baseline cathepsin B activity was higher than in active animals. Taken together, the results attest to differences in the adaptive response formation in rats, depending on behavioral features.

[DYNAMICS OF CYTOKINE CONCENTRATION IN THE BLOOD OF RATS WITH VARIOUS BEHAVIORAL CHARACTERISTICS AFTER ACUTE EMOTIONAL STRESS].

This work was designed to study a change in cytokine content in the peripheral blood of behaviorally passive and active Wistar rats at various time intervals after acute stress on the model of night-time immobilization. A decrease in the concentration of most pro- and anti-inflammatory cytokines in passive animals was most pronounced immediately and, particularly, 3 days after stress exposure. Variations in the blood cytokine profile after experimental stress were lower in behaviorally active specimens. A statistically significant decrease was observed only in the amount of a proinflammatory cytokine IL-1α and anti-inflammatory cytokines IL-4 and IL-13. As differentiated from passive rats, these changes in active specimens were most pronounced 1 day after negative emotiogenic exposure. Our results illustrate a specific involvement of immunoactive substances in the systemic regulation of physiological functions and development of individual resistance to the negative consequences of stress.

Biochemical changes in rats with different behavioral characteristics under conditions of metabolic stress.

Food deprivation is an extreme state of the functional feeding system, which is reflected in the character of changes in the activity of central and peripheral components selectively included in the system. We studied the dynamics of coenzyme Q10 levels and spectrum of omega-3 and omega-6 polyunsaturated fatty acids in the blood serum, liver, and brain as well as LPO intensity in the serum and liver in behaviorally passive and active rats under conditions of food deprivation. Our results indicate that adaptive and compensatory processes during acute metabolic stress depend on the initial behavioral characteristics of the animals.

Biochemical features in rats with different behavioral activity under conditions of emotional stress.

Adaptive capacities of the organism under conditions of emotional stress are determined by individual complex of anti-stress protective mechanisms. We studied the content of coenzyme Q10 and the spectrum of polyunsaturated fatty acids omega-3 and omega-6 in the serum, liver, and brain, and LPO intensity in the serum and liver of behaviorally active and passive rats under conditions of acute emotional stress. The differences in the formation of adaptive responses in animals with various behavioral activities were demonstrated.

[Toxicological assessment of nanostructured silica. III. Microecological, hematological indices, state of cellular immunity].

This paper is the third in a series of publications on the experimental study of subacute oral toxicity of nanostructured silicon dioxide (SiO2). We used commercial nanostructured SiO2, obtained by hydrolysis of tetrachlorosilane in the gaseous phase, with the size of the primary nanoparticles (NPs) of 5-30 nm. The aqueous dispersion of SiO2 after treatment with ultrasound was administered to rats with initial weight of 80 +/- 5 g for the first 30 days by intragastric gavage and further for 60 days with diets in doses of 0.1; 1.0; 10 and 100 mg/kg body weight per day. Animals of the control group were treated with deionized water. The amount of basic and transient populations of gut microbiocenosis, hematological indexes were measured using standard methods. Specific content of the B-lymphocytes (CD45RA+), total T-lymphocytes (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), NK-cells (CD161a+) in general population of lymphocytes was evaluated byflow cytometry; serum cytokine levels of TNF-alpha, IL-6, IL-10 were determined by ELISA. No significant changes in the qualitative and quantitative composition of the intestinal microbiota populations regardless of the dose of administered nanomaterial have been found. This gave reason to believe that the postulated mechanism of the toxic effects of the NPs of SiO2, mediated by modification of the composition of the intestinal microflora and the corresponding changes in its functional activity, apparently, is not realized. The main target of nanostructured SiO2 was the T-cellular system of the immune system of animals, that was manifested in the significant decrease of the number of leukocytes (33%), number of T-helper cells (13%), CD4/CD8 ratio (27%) and increasing the number of cytotoxic lymphocytes (19%) and the level of TNF-alpha (590%). The value of the maximum dose (NOAEL) of nanostructured SiO2, has no effect on T-cell immunity was not more than 100 mg/kg body weight per day.

[Nutrimetabolomics--the new stage of biochemistry of nutrition. The role of nutrilipidomic analysis].

In this review, in the light of current trends in the development of nutritional science and nutritional biochemistry the key directions associated with complex comprehensive study of metabolic processes in the body are discussed. We highlight the development of lipidomic researches and formation of nutrilipidomic analysis. We review the role of different lipids, including omega-3 and omega-6 PUFAs, in mechanism of protein expression, the nature of lipid-protein interactions, and the signaling function of lipids. Since PUFAs influence the increase of peroxide oxidation of lipids, this review summarizes current methodology used to estimate the oxidative stress.

[A review of current methods for nutrimetabolomic and proteomic research in biochemistry of nutrition].

At present biochemistry of nutrition involves the use of OMICs to investigate food quality, safety, bioactivity and nutrition mechanisms. In this context, nutrimetabolomics is one of the latest directions of nutrition development and provides a better understanding of the influence of nutritional factors on the metabolic pathways of the organism. Proteomic methods play an important role in nutrimetabolomics and allow to detect, identify and quantify proteins under different conditions. Variety of technical and methodological advances, improvements in bioinformatics and possibility of tandem use of different methods helps to solve a number of basic and applied science's problems. Currently huge amount of qualitative and quantitative data on the structure, functions and activities of proteins and their interactions is accumulated. Proteomics aims to establish and characterize a complete set of proteins of the organism. This review summarizes the basic applications of proteomics used in nutrimetabolomic researches. The advantages and disadvantages of the most common techniques of protein separation and sample ionization, types of mass analyzers, basic approaches to the identification of proteins and most widely used databases of known biological sequences are overviewed with a critical assessment of challenges and potential applications.

Dynamics of locomotor activity and heat production in rats after acute stress.

The dynamics of locomotor activity and heat production were studied in rats demonstrating passive and active behavior in the open field test at different time after exposure to acute emotional stress caused by 12-h immobilization during dark hours. The most pronounced changes in behavior and heat production followed by disturbances in circadian rhythms of these parameters were detected within the first 2 days after stress. In contrast to behaviorally active rats, the most significant decrease in locomotor activity and heat production of passive animals subjected to emotional stress was observed during dark hours. Circadian rhythms of behavior and heat production in rats tended to recover on day 3 after immobilization stress. These data illustrate the specificity of metabolic and behavioral changes reflecting the shift of endogenous biological rhythms in individuals with different prognostic resistance to stress at different terms after exposure to negative emotiogenic stimuli.

Proteomic study of rat hippocampus under conditions of emotional stress.

Proteomic differences in the hippocampus of stress-resistant and stress-sensitive rats were detected on the model of emotional stress. Differential expression of some proteins was detected in animals with different behavioral activity initially and after experimental stress exposure. Specific involvement of the hippocampus in the realization of stress response in animals with different sensitivity to emotional stress was demonstrated.

Biochemistry of blood plasma and some parameters of antioxidant status in rats with polyhypovitaminosis of varying severity.

In rats with profound vitamin deficiency, blood plasma level of triglycerides significantly decreased by 1.6 times, potassium ions by 5%, uric acid by 23%, ALT and AST by 1.4 times, while the levels of glucose increased by 32%, iron by 31%, urea by 58%, and alkaline phosphatase by 19%. Plasma level of phosphorus tended to decrease and ionized calcium concentration tended to increase. Severe deficiency of all vitamins is accompanied by pronounced accumulation of MDA in the plasma and liver together with simultaneous increase in the level of coenzyme Q10 by 4.6 times and decrease in vitamin C content by 21.4% in the rat liver compared to the control. It was found that severe combined deficiency of vitamins for 4 weeks produced considerable multidirectional alterations in diagnostically important metabolic parameters in rat plasma.

Effect of coenzyme Q10 on the proteomic profile of the cytosolic and microsomal fractions from rat hepatocytes upon dietary consumption of various lipid components during ontogeny.

We studied proteomic features of subcellular fractions from rat hepatocytes and intensity of enzymatic and non-enzymatic free radical oxidation depending on the type of dietary fat during adaptation of animals to modified nutrition. Our results illustrate the formation of specific nutriproteomes in the microsomal and cytosolic fractions of rat hepatocytes (measurement of the macro-component and micro-component composition of diet).

[Nutrimetabolomics--a new stage of biochemistry of nutrition. The role of nutriproteomic analysis].

Nutrition is one of the most critical aspects of human health and longevity. The idea of balanced nutrition supposes adequate supply of energy, macro- and micronutrients and furthermore normal functioning of specific mechanisms of nutrition. Contemporary biochemistry based on high performance methods, which assume increasing biological information. Developing of proteomic and metabolomic methods gives an opportunity to investigation macro- and micronutrients mechanisms of action. This was an incitement to formation new directions in biochemistry of nutrition: nutriproteomics and nutrimetabolomics.

Peculiarities of rat serum proteome profile in metabolic stress.

We identified individual proteins characterizing starvation-induced metabolic stress. Sustained changes at the level of proteome caused by metabolic stress were demonstrated. Intensified synthesis of S6 kinase ribosomal protein, immunoglobulin lambda light chains, and inter-alpha-trypsin inhibitor was observed in the experimental groups.