We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of internal organs, liver morphology, adipokines, cytokines, and biochemical indices of animals were assessed. The Tyr supplementation potentiated increased anxiety in EPM and contributed to a muscle tone increase, a decrease in the AST/ALT ratio, and an increase in protein anabolism in both mice strains. Tyr contributed to a decrease in liver fatty degeneration and ALT reduction only in DBCB that were sensitive to the development of obesity. The addition of Trp caused an increase in muscle tone and potentiated an increase in anxiety with age in animals of both genotypes. Trp had toxic effects on the livers of mice, which was manifested in increased fatty degeneration in DBCB, edema, and the appearance of micronuclei in DBA/2J. The main identified effects of Tyr on mice are considered in the light of its modulating effect on the dopamine neurotransmitter metabolism, while for the Trp supplement, effects were presumably associated with the synthesis of its toxic metabolites by representatives of the intestinal microflora.

Влияние микро- и нанопластиков - контаминантов пищевой продукции на иммунную систему

Патогенетические механизмы развития гематологических нарушений при индуцированной жировой дистрофии печени у крыс линии Wistar и оценка регуляторного

BACKGROUND:The model of obesity under experimental conditions is reproduced by using high-calorie diets in animals. It has been established that metabolic disorders cause meta-inflammation not only in peripheral organs and tissues, but also in brain structures. The search for effective neuroprotective antioxidants to suppress inflammatory processes in the cerebral cortex in obesity is an urgent task due to the widespread prevalence of this disease.AIM: to evaluate the effect of minor biologically active substances — carnosine (CAR) and α-lipoic acid (ALA) on the cytokine profile of the frontal cortex of the left hemisphere of the brain in Wistar male rats with obesity induced by a high-calorie choline-deficient diet.MATERIALS AND METHODS:The studies were carried out on male Wistar rats with an initial body weight of 150±10 g. The animals were randomized by body weight into 5 groups. For 8 weeks, rats of the 1st (control) group received a complete modified diet of AIN93M; rats of the 2nd group consumed a high-calorie choline-deficient diet (HCHDR), the fat content of which was 45%, fructose — 20% of the energy value of the diet; rats of the 3rd group received HCHDR with the addition of CAR at a dose of 75 mg per 1 kg of body weight; rats of the 4th group received HCHDR with the addition of ALA at a dose of 75 mg per 1 kg of body weight; rats of the 5th group received HCHDR with the addition of the CAR + ALA complex in a total dose of 150 mg per 1 kg of body weight. Animals were removed from the experiment by decapitation under ether anesthesia. The levels of triglycerides (Tg) and free fatty acids (FFA) in blood plasma (mmol) were determined on a biochemical analyzer (Konelab 20i, Thermo Clinical Labsystems Oy, Finland). Content of cytokines and chemokines (pg/ml): GM-CSF, IL-10, IL-17A, IL-12p40, IL-12p70, IL-1α, IL-2, IL-4, IL-5, IFN-γ, MCP-1, M-CSF, MIP-1α, MIP-2, MIP-3α, RANTES, and TNF-α in cerebral cortex lysates were determined by multiplex immunoassay using a Luminex 200 analyzer (Luminex Corporation, USA). To assess the relationship between the level of cytokines in blood plasma and changes in their concentrations under the influence of HCCDR in lysates of the cortex of the frontal lobe of the left hemisphere of the brain, the ratio was calculated: the level of cytokines pg/ml in blood plasma [1]/the content of cytokines pg/ml in lysates (pl/ lys) for each sample.RESULTS: On the model of obesity in rats, the presence of an inflammatory process in the cerebral cortex was established, as evidenced by an increase in the content of pro-inflammatory factors: IL-2, M-CSF, MIP-1α and RANTES and a decrease in the content of immunoregulatory cytokines of varying severity: IL-10, IL17A, IL-12p40, IL-12p70, TNF-a, MIP-2 and MIP-3α in group 2 rats. (HCHDR) compared with the control group. Enrichment of HCHDR with biologically active substances: CAR, ALA or their complex, ensured the normalization of lipid metabolism, as evidenced by the decrease in the ratio of circulating Tg to FFA in the blood serum of rats to control values: 1st gr. (control) — 1,04±0.23; 2nd gr. (HCHDR) — 1,64±0.63; 3rd gr. (CAR) — 0,98±0.31; 4th gr. (ALA) — 0,86±0.31; 5th gr. (CAR+ALA) — 1,02±0.38. Enrichment of HCHDR with CAR, ALA or their complex led to a decrease in the content of pro-inflammatory and apoptosis-regulating cytokines and chemokines in the cortex of the frontal lobe of the rat brain: IL-1α, IL-2, IL-17A, M-CSF, MCP-1, MIP3α and RANTES, along with an increase in the level of the anti-inflammatory cytokine IL-10, which indicates the suppression of the inflammatory process induced by the consumption of HCHDR in rats.CONCLUSION:The data obtained indicate the prospect of using CAR and ALA or their complex as neuroprotective antioxidants to reduce the inflammatory process in brain structures in obesity.

Specialized food products and biologically active food supplements enriched with minor biologically active substances are considered as a useful supplement in the treatment of obesity and other nutrition-dependent diseases. Biologically active substances of food can have a complex effect on the expression of a large number of genes, which can affect the results of a therapy. The aim of the study was to analyze the nutrigenomic mechanisms of the effect of biologically active substances - l-carnitine and resveratrol on the expression of liver genes of DBA/2J mice and DBCB tetrahybrid, differing in genotype and sensitivity to the development of diet-induced obesity, using the method of full transcriptomic profiling of liver tissue. We carried out the experiment on male DBA/2J mice and the hybrid of the 2nd generation DBCB, obtained by crossing 4 lines of mice (DBA/2J, BALB/c, CBA/ lac and С57Black/6J). Mice for the experiment were obtained from Stolbovaya nursery, Federal State Budgetory Scientific Institution Scientific Center of Biomedical Technologies of the Federal Medical-Biological Agency (Moscow region, Russia). We worked with animals in accordance with international recommendations (Directive 2010/63/EU on the protection of animals used for scientific purposes adopted on September 22, 2010; Guide for the care and use of laboratory animals. Eighth Edition / Committee for the Update of the Guide for the Care and Use of Laboratory Animals; Institute for Laboratory Animal Research (ILAR); Division on Earth and Life Studies (DELS); National Research Council of the National Academies. Washington: The National Academies Press. 2011).The mice were divided into four groups with an equal number of 8 individuals. During 65 days, animals of the 1st (control) groups received a balanced semi-synthetic diet and purified drinking water, the 2nd groups received a high-carbohydrate and high-fat diet with a high fat content (30% by of dry matter of the diet) and replacing drinking water by 20% fructose solution, 3rd groups - high-carbohydrate and high-fat diet with the addition of resveratrol at a dose of 25 mg/kg body weight, 4th groups - high-carbohydrate and high-fat diet with the addition of l-carnitine at a dose of 300 mg/kg body weight. Full transcriptome analysis was performed using the Gene Expression Hybridization Kit (Agilent Technologies, USA) on SurePrint G3 Mouse GE 8×60K Microarray Kit microarrays. Differential gene expression was expressed as base 2 logarithm of increasing or decreasing fluorescence (log2 FC) compared to control groups, separately for DBA/2J and DBCB mice. Chip scan data and calculation of differential expression values were exported to the “R” IDE and bioinformatics analysis was performed with quantile normalization and further analysis in the limma package. The packages AnnotationDbi, org.Rn.eg.db, pathview, gage, gageData were used to identify metabolic pathways among the genes, metabolic pathways and functions of biological systems presented in the international database Kyoto Encyclopedia of Genes and Genomes and to visualize them. To visualize the results at all stages, the standard “R” graphics and additional packages ggplot2, ggrepel, and gplots were used. Liver morphology was studied by light microscopy after staining with hematoxyline-eosine (See Fig. 1). We revealed differential expression for at least one of the intergroup comparisons in the amount of │log2FC│≥0.5 (towards both enhancement and attenuation) and at a p-value ≤ 0.05 for 415 transcripts, of which 311 were identified with proteins or RNA with a known function (See Tables 1-3). Consumption of a high-carbohydrate and high-fat diet was reflected in differential expression of 62 genes in DBA/2J mice and 97 in DBCB mice. In DBA/2J mice fed on a high-carbohydrate and high-fat diet, supplementation with resveratrol and l-carnitine caused a differential expression of 26 genes each. At the same time, only 2 genes (Pklr, Tkfc) responded to resveratrol and l-carnitine in mice of this strain. In DBCB tetrahybrid mice, resveratrol consumption corresponded to differential expression of 147 genes, and l-carnitine consumption corresponded to 221 genes. 61 genes from DBCB mice responded to both supplements, and the number of genes simultaneously targeted by high-carbohydrate and high-fat diets, resveratrol and l-carnitine was 10 (See Fig. 2). The gene expression profiles in DBA/2J and DBCB mice formed two separate clusters, the differences within which, determined by the composition of the diets, were less significant than the interstrain differences (See Fig. 3). Differential expression values in DBCB and DBA mice responding to HFCD and both supplements correlated negatively (See Fig. 4). The consumption of a high-carbohydrate and high-fat diet in DBA/2J mice resulted in significant changes in 4 metabolic pathways, and in DBCB mice, in addition, in 5 more metabolic pathways. Resveratrol consumption did not cause significant changes in DBA/2J mice, and in tetrahybrid mice it affected mmu04512 ECM-receptor interaction. L-carnitine supplementation caused significant changes in mmu00830 Retinol metabolism only in DBCB mice (See Table 4). Consumption of a high-carbohydrate and high-fat diet produced similar changes in the mmu00830 Retinol metabolism pathway in both mice (See Fig. 5). In metabolic pathway mmu03320 PPAR signaling pathway DBA/2J and DBCB mice showed positive differential expression of the PPARγ gene and negative Scd1. At the same time, only DBCB mice in this metabolic pathway are characterized by activation of the RXR gene expression and suppression of FABP, and the direction in changing Cyp4a1 in both mice is opposite (See Fig. 6). Changes in the metabolic pathway mmu00590 Arachidonic acid metabolism characterized by the imbalance in the expression of Cyp4a and Cyp2 isoforms, which are responsible for the synthesis of various hydroxy and epoxy derivatives of arachidonic acid, is...

Objectives: To identify typical patterns of abdominal wall muscle activation in patients with diastasis recti and inguinal hernias compared to controls during the Valsalva maneuver, voluntary coughing, and physical activity. Methods: The study included 15 subjects: 5 with diastasis recti, 4 with inguinal hernias, and 6 healthy controls. The functions of rectus abdominis (RA) and external oblique (OE) muscles were measured by surface electromyography (sEMG). Using ultrasound, the thicknesses of the RA, OE, internal oblique (IO), and transversus abdominis (TA) muscles were assessed as well as the echo intensity (EI) of RA and OE. Results: We found a significant effect of the type of abdominal wall pathology on the maximum sEMG amplitude (p = 0.005). There was a reliable trend in maximum sEMG amplitude, with the highest one in diastasis recti and a significantly lower one in inguinal hernias. Duncan’s test showed a significant difference in muscle thickness, both on the right and left sides, between patients with diastasis and controls, but only on the left side between patients with diastasis and those with inguinal hernia (p < 0.05). Conclusions: The abdominal wall pathology results in a change in the function and structure of the abdominal muscles, which can be detected using electromyography and ultrasound examination. The presence of diastasis recti is accompanied by an increase in bioelectrical activity and a decrease in thickness.