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A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as a complementary tool to identify high-risk individuals. The T2D polygenic score maintained predictive utility after adjusting for family history and combining genetics with family history led to even more improved disease risk prediction. We observed that the PGS was meaningfully related to age of onset with implications for screening practices: there was a linear and statistically significant relationship between the PGS and T2D onset (-1.3 years per standard deviation of the PGS). Evaluation of U.S. Preventive Task Force and a simplified version of American Diabetes Association screening guidelines showed that addition of a screening criterion for those above the 90th percentile of the PGS provided a small increase the sensitivity of the screening algorithm. Among T2D-negative individuals, the T2D PGS was associated with prediabetes, where each standard deviation increase of the PGS was associated with a 23% increase in the odds of prediabetes diagnosis. Additionally, each standard deviation increase in the PGS corresponded to a 43% increase in the odds of incident T2D at one-year follow-up. Using complications and forms of clinical intervention (i.e., lifestyle modification, metformin treatment, or insulin treatment) as proxies for advanced illness we also found statistically significant associations between the T2D PGS and insulin treatment and diabetic neuropathy. Importantly, we were able to replicate many findings in a Hispanic/Latino cohort from our database, highlighting the value of the T2D PGS as a clinical tool for individuals with ancestry other than European. In this group, the T2D PGS provided additional disease risk information beyond that offered by traditional screening methodologies. The T2D PGS also had predictive value for the age of onset and for prediabetes among T2D-negative Hispanic/Latino participants. These findings strengthen the notion that a T2D PGS could play a role in the clinical setting across multiple ancestries, potentially improving T2D screening practices, risk stratification, and disease management., Competing Interests: JA, OSa, OSv, SD, RK, LB, MM, SA, PF, SS, JP and BK are current or former employees of 23andMe, Inc. with financial interest in the company., (Copyright © 2022 Ashenhurst, Sazonova, Svrchek, Detweiler, Kita, Babalola, McIntyre, Aslibekyan, Fontanillas, Shringarpure, Pollard and Koelsch.)

The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45-69 years old) was examined at baseline in 2003-2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006-2008 and 2015-2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m 2 ; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM.

Currently, there is a decrease in the total number of organizations for summer recreation of children in the country while the share of organizations of group II of sanitary and epidemiological well-being among them remains at a consistently high level that determines the potential risk of harm to the health of the child population. At the same time, there is an increase in the number of children with a pronounced health-improving effect. So, it becomes necessary to analyze the information content of modern criteria for assessing the effectiveness of health improvement and to search for ways to resolve the noted contradictions., Objective: Analysis and scientific and methodological substantiation of modern criteria for assessing the effectiveness of children's health improvement in recreation organizations (camps)., Material and Methods: An analysis of the literature data, our own research results' systematization and effectiveness assessment of the health improvement of 195 children aged 10 to 15 years (112 girls and 83 boys) belonging to I and II health groups and vacationers in the inpatient organization of the Samara region in the 2019 summer campaign were carried out. Anthropometric, physio-metric, and bio-impedance metrics were studied in two stages (on the 1st or 2nd day of arrival and 1 day before the camp leaving). In a comparative analysis the differences were considered significant when p <0.05., Results: Stationary rest and recreation organizations in the all-Russian structure of recreation organizations for children account for 5.8%. During staying in the camp, there was a significant decrease in the proportion of girls with underweight ( p =0.039); among boys no significant changes were found. The general trend towards a change in the level of physical development is not statistically significant. Bio-impedance analysis revealed only 51.3% of children with changes in indicators characterizing the health-improving effect. The tendencies to change in the proportion of children with different levels of arm muscle strength and lung capacity during the staying in then camp are statistically significant. Correlations were established between muscle strength with basal metabolism ( r =0.86) and muscle mass ( r =0.86), as well as negative links between average strength and the percentage of adipose tissue ( r = -0.52). During the staying in the camp, the 4 cases of acute respiratory infections were registered that did not affect the assessment of the recovery effectiveness., Conclusion: In order to assess the health-improving effect among children during one trial in the camp, the leading functional signs are muscle strength of the arms and vital capacity of the lungs. Additional criteria can be the morbidity during the staying in the camp, and in terms of the nutritional status analysis - the results of bio-impedance analysis. To assess the physical development at the beginning of the camp trial, the use of regional regression scales is informative that requires a corresponding explanation in the documents. In turn, the data from the baseline measurements should be used to build individual health measures during the staying in the camp.

Fumarase (EC 4.2.1.2) is encoded in sunflower (Helianthus annuus L.) by two genes (FUM1 and FUM2) expressing correspondingly the mitochondrial and the cytosolic form. Both forms have been purified from sunflower cotyledons and characterized. Three quarters of fumarase activity is located in the mitochondrial and one quarter in the cytosolic fraction. The cytosolic form has lower pH optimum than the mitochondrial form, it possesses higher affinity to malate, activated by Mn 2+ and less efficiently by Mg 2+ while the mitochondrial form is activated only by Mg 2+ . It is proposed that the mitochondrial form is involved in the respiratory processes linked to the tricarboxylic acid cycle and the cytosolic form participates in the utilization of succinate produced in the glyoxylate cycle providing the flux to gluconeogenesis in germinating sunflower seeds., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10 -8 ) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

The article presents the data of a retrospective analysis of the average per capita consumption of food by the population of the Samara region in comparison with the all-Russian indicators and recommended values of consumption in the period from 2010 to 2015, as well as the analysis of the actual nutrition of different groups of the working-age population of the Samara region in 2015 (2154 people aged 18 up to 62 years of age, 1179 of them women, 975 men) using the method of 24-hour reproduction of food and the frequency method with quantitative assessment of consumed products, in comparison with the dynamics of the prevalence of alimentary-dependent diseases. Estimation of parameters of nutritional status was also conducted on blood level of cholesterol and glucose, bioelectrical impedance analysis of body composition (n=514). It was found that 48.2% of the subjects had normal body weight, 38.1% -overweight, 13.7% - obesity. The analysis of actual consumption revealed an unfavorable trend of increasing consumption of fats, as well as sugar from 2010 to 2015, while the consumption of vegetables, fruits and berries was lowed compared to the national indicators and recommended consumption values. The analysis of actual nutrition allowed to make a conclusion about severe violations of the relationships between nutrients in the diet of all surveyed populations, characterized by the excess intake of fat (45% of the energy diet value), including saturated fatty acids, and added sugar (13% calories). In the diet of 82% of the respondents the content of vitamins B1 and B2 did not reach the recommended level, niacin - 37%, vitamin A - 47%, vitamin C - 68%, calcium and iron - 14%. With an increase in BMI, there was an increase in blood level of cholesterol and glucose (r=0.24 and r=0.26, respectively, p<0.05), both in men and women. In individuals with excess fat and added sugar in the diet, increased fat body component (r=0.17, p<0.05) and lowered content of skeletal muscle mass (r=0.25, p<0.05) were observed. The revealed unfavorable trend of nutritional and metabolic disorders, against the background of increased consumption of fats, added sugar, indicates the need for an integrated approach to the correction of diet at both individual and population levels., (Copyright© GEOTAR-Media Publishing Group.)

Vitamin status of 77 employees of oil refineries (39 men and 38 women aged 22 to 62 years, body mass index - 25.0±4.7 kg/m 2 ) has been assessed in autumn. The sufficiency with vitamins A, E, D, B 2 , B 12 , folate and beta-carotene was evaluated by determination in blood plasma, daily intake of vitamins B1, B2, niacin, C, A and betacarotene was calculated by frequency of food consumption during previous month. All surveyed were sufficiently supplied with vitamins A, B12 and folate (reduced level was detected in 0-2.6%). The content of tocopherols referred to triglycerides was reduced in 33% of the workers, in men it was 2 fold more likely (p<0.05) than in women (43.6 vs 21.1%). Vitamin D insufficiency took place in 23.4% of individuals, vitamin B 2 and beta-carotene - in 44.2%. A reduced blood plasma content of one vitamin was detected in 39.0% of the surveyed, while two vitamins - in 24.7% persons, 2.2 fold more often (p<0.05) in men than in women. Multivitamin insufficiency was detected in 10.4% of workers. Reduced blood plasma level of at least one vitamin-antioxidant was detected in 46.8% (in 61.5% of men and 31.6% of women, p<0.05). 26.0% of surveyed were provided with all 6 vitamins and beta-carotene. Reduced relative to RDA daily intake of antioxidant vitamins (ascorbic acid and beta-carotene) was observed in 64.9 and 100% of individuals, B group vitamins (niacin, B 2 and B 1 ) - in 48.1-64.9%, vitamin A - in 42.9%., (Copyright© GEOTAR-Media Publishing Group.)

Objective - to assess the changes and the relationship of inflammation markers, adipokine levels and lipid metabolism in overweight and obesity, with signs of the metabolic syndrome. The study involved 62 women aged from 25 to 50 years. Group 1 included women (n=20) with a BMI<27.0, with no signs of metabolic syndrome, group 2 (n=20) - with a BMI>27.0, who were overweight or obese, with no signs of metabolic syndrome, 3 group (n=22) with a BMI>27.0, having overweight or obesity and the presence of any signs of metabolic syndrome. We determined relative and absolute lymphocyte counts and neutrophil granulocytes in the blood, lipid spectrum, blood serum levels of apolipoprotein A-1 (ApoA-1), and apolipoprotein B (apoB), leptin, adiponectin, interleukin-1β (IL-1β), interleukin 6 (IL-6), C-reactive protein (CRP). It was noted (p≤0.001) an increase of CRP in the blood of obese women, regardless of the presence of the metabolic syndrome: its concentration in groups 2 and 3 reached 6.69±3.03 and 7.30±3.08 mg/l, respectively, against 2.39±1.66 mg/l in group 1. Increasing BMI was accompanied by (p≤0.01) increase in erythrocyte sedimentation rate (8.1±5.0; 14.3±8.7; 13.9±8.5 mm per hour, respectively, in groups 1, 2 and 3). In women from groups 1 and 3 an increase in triglycerides, accompanied by a decrease in HDL (r=-0.44; p<0.025 and r=-0,57; p<0.001, respectively), and increase of LDL cholesterol (r=1.0; p<0.001) has been shown. The maximum number of positive correlations between indicators of lipid profile and inflammation markers was found in group 1, the minimum in group 3. This analysis showed the presence of chronic inflammation, which was accompanied by various disorders of lipid metabolism, even in the absence of clinical signs of pathology, the severity of which increased with increasing BMI and the development of metabolic syndrome., (Copyright© GEOTAR-Media Publishing Group.)

Inhibition of fumarase activity in the light has been studied in Arabidopsis in relation to the involvement of phytochrome. Using knockout phytochrome mutants, we observed that the main regulator of FUM1 gene transcription, encoding the mitochondrial form of fumarase, is phytochrome A. The active form of phytochrome A suppressed FUM1 expression, while the expression of the FUM2 gene encoding the cytosolic form of fumarase was unaffected both in darkness and in light. The nuclear concentration of Ca(2+) was modulated by red and far-red light. We suggest that the signal transduction mechanism operates via Ca(2+) activation of expression of the gene encoding the transcription factor PIF3, which binds to promoters of phytochrome-regulated genes and inhibits FUM1 expression., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The Purpose of the Study: To determine the prognostic significance of the expression of molecules of PCNA, Bcl-2, NF-Kb and tachykinins (substance P, neurokinin A) in patients with gastric ulcer (CU) receiving cytotoxic therapy., Materials and Methods: Total surveyed 90 patients divided into 3. equal groups. The first comparison group consisted of patients with chronic atrophic H. pylori-associated gastritis (CAG) (30 pers.). A second control group consisted of patients with gastric ulcer (30 pers.). Third, the study group consisted of 30 people. with CU suffering from hematological malignancies, in a period of complete clinical remission of the disease and receiving supportive polychemotherapy (PCT). Patients underwent endoscopy, morphological and immunohistochemical study of the mucous membrane of the antrum and body of the stomach to detect the expression of molecules of PCNA, Bcl-2, neurokinin A, substance P and factor Nf-Kb., Results: The total level of dyspeptic syndrome on visual scale analogue in patients receiving chemotherapy and GU (GUpct) was significantly higher (p < 0.05) compared with patients with GU. It should be noted that patients with GUpct reducing clinical symptoms is much slower (p < 0.05). At the same time in 13 (43.3%) patients with GUpct determines the duration of ulcer healing, whereas in patients with GU in only 4 (13.3%) patients. Patients with GUpct more frequently (p < 0.05) were verified II and stage Ill chronic gastritis (CG), while Stage I--less (p < 0.05). Patients with GUpct significantly more often (p<0.05) was determined by the II degree of CG and significantly less (p < 0.05)--IV degree. Patients with GUpct determined significantly lower (p < 0.05), the expression performance PCNA, substance P and neurokinin A and higher (p < 0.05)--Bcl-2 and factor Nf-kB., Conclusion: GU in patients receiving chemotherapy, dyspeptic syndrome is characterized by severe, advanced stage of CG on the background of relatively low severity of CG in accordance with the classification of OLGA (2008). Patients with GUpht have a significant level of violation of regeneration changes how is this atrophy, intestinal metaplasia, dysplasia of gastric mucosa association with gross violations of the processes of epithelial cell homeostasis of epithelial cells regulation after molecules PCNA, Bcl-2, NF-kB and tachykinins (substation P, neurokinin A).

Sufficiency of 58 employees of a thermal power plant (47 men and 11 women aged 21 to 64 years, body mass index - 27.0±5.8 kg/m 2 ), with vitamins A, E, D, B 6 , B 12 , folic acid and carotenoids (content in the blood plasma) and vitamin C (urinary excretion) was conducted in winter (February 2015). All surveyed workers were sufficiently supplied with vitamins A, B 6 , B 12 and folic acid (a reduced level was detected in 0-9%). Insufficient supplying with vitamin E had 19% of the workers (and only men), vitamin C - 44%, vitamin D - 61%, carotenoids - 93%. Only 5% persons were sufficiently provided with all 6 vitamins. A combined deficiency of two vitamins had 38% of them, three - 22%, four - 16%. Simultaneously reduced plasma level of two antioxidants was observed in 36% of subjects, three - in 12%. Significant positive correlation (p <0.05) was detected between plasma levels: total cholesterol and retinol and β-carotene; tocopherol and total cholesterol, triglycerides, low density lipoprotein cholesterol; between the concentration of vitamin D, and high density lipoproteins; levels of retinol and tocopherol and β-carotene. In parallel intake of vitamins C, A, B 1 , B 2 and niacin has been assessed by calculation of the frequency of food consumption during the previous month. Reduced relatively recommended daily intake of vitamins A, C has been found in approximately half of the surveyed, niacin, vitamin B1 and B 2 - in 70-80%. Comparison of the data on the availability of vitamins C and A, obtained by calculation of vitamin intake and biochemical methods gave identical results in 55 and 60% of cases, correspondingly. The lack of vitamins has been detected more frequently by assessing dietary intake., (Copyright© GEOTAR-Media Publishing Group.)

When planning your diet regime is desirable to focus on the natural feeding behavior of the person. However, many aspects of eating behavior are not studied. The aim of this work was to study the changes of diet calorie and nutrient composition depending on the body mass index (BMI), time of day, week cycle phase: weekends/weekdays, and the availability of rational installation in nutrition. The study involved 67 women aged 29 to 49 years with a BMI of 18.3 to 34.2 kg/m2. Macronutrient composition and energy value of the diet were evaluated by analyzing the food diaries, which were filled by all respondents continuously for 8 workdays and 4 weekends. The results of this study showed no significant correlation between BMI and calorie intake, while a positive correlation was observed between BMI and fat component of the diet (r=0.362, p≤0.05). It was also found that the restriction of food intake in the evening (after 8 pm) did not lead to a decrease in total daily energy value of the diet, and was characterized by the consumption in the evening about 31% of the total fat intake. Diet energy value was significantly higher on weekends than during the week and was 2376±394 against 1940±402 kcal (p<0.05). According to the data obtained, compliance «restriction of supply in the evening» does not lead to a significant reduction in daily caloric intake.

The development of atherosclerosis involves phenotypic changes among vascular smooth muscle cells (VSMCs) that correlate with stiffening and remodeling of the extracellular matrix (ECM). VSMCs are highly sensitive to the composition and mechanical state of the surrounding ECM, and ECM remodeling during atherosclerosis likely contributes to pathology. We hypothesized that ECM mechanics and biochemistry are interdependent in their regulation of VSMC behavior and investigated the effect of ligand presentation on certain stiffness-mediated processes. Our findings demonstrate that substrate stiffening is not a unidirectional stimulus-instead, the influence of mechanics on cell behavior is highly conditioned on ligand biochemistry. This "stiffness-by-ligand" effect was evident for VSMC adhesion, spreading, cytoskeletal polymerization, and focal adhesion assembly, where VSMCs cultured on fibronectin (Fn)-modified substrates showed an augmented response to increasing stiffness, whereas cells on laminin (Ln) substrates showed a dampened response. By contrast, cells on Fn substrates showed a decrease in myosin light chain (MLC) phosphorylation and elongation with increasing stiffness, whereas Ln supported an increase in MLC phosphorylation and no change in cell shape with increasing stiffness. Taken together, these findings show that identical cell populations exhibit opposing responses to substrate stiffening depending on ECM presentation. Our results also suggest that the shift in VSMC phenotype in a developing atherosclerotic lesion is jointly regulated by stromal mechanics and biochemistry. This study highlights the complex influence of the blood vessel wall microenvironment on VSMC phenotype and provides insight into how cells may integrate ECM biochemistry and mechanics during normal and pathological tissue function., (Copyright © 2014. Published by Elsevier B.V.)

There was performed the assessment of habitat quality for Samara population. Risk factors for prevalence of respiratory diseases (pneumonia, allergic rhinitis, asthma) in children, teenagers and adults were revealed to be formaldehyde, phenol, hydrogen sulfide in the ambient, cadmium and copper in the soil.

The diabetes mellitus is a real threat to population health in all countries. In international practice studying and successful solutions of problems conditioned by this disease are related to development of registries. The Novosibirsk municipal registry of diabetes mellitus is an integral part of the Public registry. The data of municipal registry and analysis of conditions of environment were used to detect characteristics of morbidity of diabetes mellitus in population residing in the territories with different level of anthropogenic pollution by aero-pollutants. The technique of mapping was applied to develop thematic clinical hygienic map. The technique of the thematic clinical hygienic mapping broaden functional possibilities and sphere of application of territorial registry of diabetes mellitus. This technique opens new possibilities and perspectives in development of complex programs of prevention in the territories with anthropogenic pollution.

Poly(N-isopropylacrylamide) (PNIPAAm)-grafted poly(dimethylsiloxane) (PDMS) offers an inexpensive, biocompatible, oxygen permeable, and easily microtextured thermo-responsive substrate for producing cell sheets. This study introduces a method of grafting PNIPAAm onto microtextured PDMS that is suitable for generating aligned vascular smooth muscle cell (VSMC) sheets. We examined a wide range of processing parameters in order to identify the conditions that led to acceptable sheet growth and detachment behavior. Substrates grafted under these conditions produced confluent cell sheets that fully detached in less than 10 min after lowering the culture temperature from 37 °C to 20 °C. The grafted layer thickness was determined to be 496±8 nm by atomic force microscopy. Surface characterization by Fourier transform infrared spectroscopy showed a relative grafting yield of 0.488±0.10, defined as the ratio of the PNIPAAm 1647 cm(-1) to the PDMS 2962 cm(-1) absorbance peaks. The water contact angle of the substrates was shown to change from 89.6° to 101.0° at 20 °C and 37 °C, respectively. We also found that cell behavior on PNIPAAm-grafted PDMS was not directly related to surface wettability or relative grafting densities., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Experimental conditions shown that formaldehyde decreased course of diabetes. Adding to meal the powder of plant's rhizome Curcuma longa contributes to the restoration of the morphological structure of the liver, kidney, the normalization of water-salt and carbohydrate metabolism, this can be used in programs for integrated prevention of diabetes in areas of technological risk.

The stroma plays an important role in the development and progression of human diseases. Pulmonary diseases such as asthma, fibrosis and cancer are thought to be the result of altered communications between the epithelial and stromal tissue compartments. In order to study these epithelial-mesenchymal interactions, we developed a three dimensional (3D) in vitro model of the human airway that mimics bronchial morphology and function. This model consists of a type-I collagen matrix, normal human fetal lung fibroblasts (IMR-90) or primary human adult lung cancer-associated fibroblasts (LuCAFs), and a surface epithelium of normal human bronchial epithelial cells (HBECs). When cultured at an air-liquid interface (ALI), the epithelial component generated a well-differentiated pseudo-stratified bronchial epithelium that contained basal, ciliated, and non-ciliated (secretory) epithelial cells. IMR-90 and LuCAFs differentially altered the phenotype of HBECs in distinct ways. While IMR-90 permitted HBECs to form a typical respiratory surface epithelium, LuCAFs promoted HBECs to invade the collagen gel forming both epithelial nodules and cysts, suggesting that LuCAFs may alter the HBEC phenotype by modifying biomechanical signals conveyed through the extracellular matrix (ECM). Furthermore, LuCAFs secreted soluble factors that induced HBECs to express genes associated with immune responses, apoptosis, mitosis, cell survival, differentiation and cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The vessel wall experiences progressive stiffening with age and the development of cardiovascular disease, which alters the micromechanical environment experienced by resident vascular smooth muscle cells (VSMCs). In vitro studies have shown that VSMCs are sensitive to substrate stiffness, but the exact molecular mechanisms of their response to stiffness remains unknown. Studies have also shown that cell-cell interactions can affect mechanotransduction at the cell-substrate interface. Using flexible substrates, we show that the expression of proteins associated with cell-matrix adhesion and cytoskeletal tension is regulated by substrate stiffness, and that an increase in cell density selectively attenuates some of these effects. We also show that cell-cell interactions exert a strong effect on cell morphology in a substrate-stiffness dependent manner. Collectively, the data suggest that as VSMCs form cell-cell contacts, substrate stiffness becomes a less potent regulator of focal adhesion signaling. This study provides insight into the mechanisms by which VSMCs respond to the mechanical environment of the blood vessel wall, and point to cell-cell interactions as critical mediators of VSMC response to vascular injury., (Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Survey of the brainwork workers with low physical activity has revealed the risks of inadequate consumption of fiber, calcium, iron, vitamins B1, B2, C, A, due to mismanagement of their consumption.

The diagnostic findings sick of a hemophilia with recurring hemarthrosis are presented. At studying of componential structure of a body by a method of bioimpedansometriya considerable fluctuations of an index of weight of a body, a poor development of a muscular fabric, increase in percentage of a fatty fabric that is connected with low, physical activity and increase in the contribution of fat in power value of a food ration have been found out in patients. Results of research of an actual food by a frequency method with a quantitative estimation at sick of hemophilia and healthy students testify to probable risk of insufficient consumption of vitamins B1, B2 and calcium, magnesium that demands individual correction.

Substantiate the need for long-term program of sanitation the diet of the population of the Samara Region. A systemic analysis of actual nutrition of different population groups in the region showed an excessive consumption of fats and added sugar--the main risk factors of obesity, cardiovascular diseases and diabetes mellitus. The risks of inadequate consumption of vitamins B, calcium, iron, caused by the irrational combination of the foodstuff use, are revealed.

The data of the investigation of 340 average income men and women ages 18-60 whose labour is characterized by low power expenditure, are represented in this article. Their food ration contains about 13% of protein and more than 40% of fat, the most part of it contains the saturated fatty acids. 55% of men and 50% of women have got body mass index (BMI) more than 25; obesity is revealed with 7% of men and 18% of women. Glucose blood level is raised at 30% of the surveyed and is correlated with the consumption of the added sugar (r = 0.44; p < 0.05). The cholesterol maintenance in blood is above normal with 60% of the surveyed, cholesterol connection with the cholesterol food maintenance is not revealed.

Nutrition is one of the most important determinants of human health. The investigation has determined the pattern of actual nutrition of the Samara Region, its influence on the occurrence of cardiovascular, endocrine, urogenital, and musculoskeletal, and digestive diseases. Emphasis is placed on unbalanced diets excluding meat, by increasing the consumption of bread and cereals, which is a universal factor for the development of visceral diseases. Balanced nutrition using full-value natural products in the optimum ratio is a major condition for health preservation and a means for prevention of the development of various diseases.

In work the data are presented, which characterize the connection of a diet with disease of illnesses of digestive organs which rises in process of increase of products that contain gluten and meat reduction in diet. Immune reaction is found out, that shows the appearance of antibodies. A gladin and fabric transglutaminaze. Reaction characteristics are different in people with different blood groups.

Twenty-two fragments of beta-actin and beta-actin-related protein were isolated from the acidic extracts of rat spleen tissue. beta-Actin fragments (75-90), (78-89), and (78-88), 0.01-1 microM, decreased live cell number of L929 murine tumor fibroblasts by 80-90%, with maximal cytotoxic effect of 30-40%. The fragments of (78-90) segment and the fragment of beta-actin-related protein (69-77) were less active (inhibitory effect up to 55%, cytotoxic-up to 25%)., (Copyright (c) 2008 European Peptide Society and John Wiley & Sons, Ltd.)

According to previously reported data, the supernatant of a primary culture of human erythrocytes contains 33 hemoglobin fragments. An analysis of the supernatant of a 20% (v/v) suspension of human erythrocytes allowed us to identify additionally four peptides whose precursors are cytoplasmic beta-actin (two fragments), fructose diphosphate aldolase B, and an unknown protein, as well as the amino acids tyrosine and tryptophan. The composition and the content of the components of the supernatant did not depend on the age or blood group of donors. The dynamics of accumulation in the supernatant (20-80 min of incubation) of the 14 hemoglobin fragments with the most reliably reproducible contents was obtained. The content of six peptides increased more than twofold between 20 and 40 min of incubation: the maximum increase in concentration was observed between 40 and 80 min (140%). The level of peptides that had the maximum concentration at the end of incubation was about 1000 pmol/ml of sedimented erythrocytes. The biological effects of the peptides identified in the supernatant of erythrocytes involve the stimulation of proliferation and hemopoiesis, suppression of proliferation, a bactericide effect, etc. These effects indicate the physiological importance of peptide release by erythrocytes. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

Neokyotorphin [TSKYR, hemoglobin alpha-chain fragment (137-141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8-Br-cAMP, but not the PKC activator 4beta-phorbol 12-myristate, 13-acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca2+ L-type channel inhibitors verapamil or nifedipine, the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, kinase inhibitors H-89 (PKA), KN-62 (Ca2+/calmodulin-dependent kinase II) and PD98059 (mitogen-activated protein kinase). The proliferative effect of 8-Br-cAMP was also suppressed by KN-62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP-like action for neokyotorphin.

The action of the cytostatic drugs (epirubicin and vincristine) in combination with the endogenous antiproliferative beta-hemoglobin fragment (33-39), valorphin, was studied in tumor (L929 and A549) cell cultures, primary culture of murine bone marrow cells and in murine model of breast carcinoma in vivo. Simultaneous application of 1 microM valorphin and 1 microM epirubicin, in vitro, did not result in an additive suppressive effect on cell culture growth. Additive effects were achieved with alternating applications of the peptide and the drugs, namely, 0.5 microM (but not 1 microM) epirubicin added 24 h prior to 1 microM valorphin; 1 microM valorphin added 48 h prior to 0.1 microM epirubicin, or 0.1 microM vincristine, or 0.05 microM vincristine, which resulted in 100% cell death in the both series with vincristine and up to 78% cell biomass reduction in the experiments with epirubicin. In the in vivo model (female BLRB mice with subcutaneously inoculated syngeneic mammary carcinoma), simultaneous treatment with 25 mg/m(2) epirubicin and 1 mg/kg valorphin resulted in 42% of tumor growth inhibition, as compared with the negative control group and 22% inhibition as compared with the epirubcin-treated group (at 20th day of treatment). Survival was significantly improved (69% compared to 39% in the group treated with epirubicin only) at day 26 after the treatment beginning.

The driving forces, incentives and strategic targets of peptide synthesis have undergone considerable evolution during the centenary following the pioneer work of Emil Fischer. In those days peptide synthesis was considered as a way of confirming the polypeptide theory of protein structure. The scientific community also expected (naively) that the synthesis would eventually lead to the creation of artificial living organisms. Only in the 1950s, when the first exact amino acid sequences were established did peptide chemistry obtain firmer ground and clearly defined targets. The total synthesis of peptide hormones and antibiotics became possible, providing valuable material for elucidating structure-functional relationships and the mechanisms of biological action. In the following years the number of peptides isolated from various biological sources grew with impressive speed and peptides became known as the most abundant, ubiquitous group of low molecular bioregulators. The design and synthesis of novel peptide based pharmaceuticals became an important area of peptide chemistry. At present we are facing the challenge of analysing the structures and bioactivities of total sets of peptides, i.e. peptidoms, present in concrete tissues or groups of cells. The results obtained along these lines at the IBCH RAS Institute of Bioorganic Chemistry are briefly considered in the review.

alpha-Hemoglobin fragments alpha-(133-141), alpha-(134-141), alpha-(135-141), alpha-(137-141), alpha-(134-140), alpha-(133-138), alpha-(134-140) and alpha-(137-138) stimulate L929 tumor cell proliferation, alpha-(134-141) being the most active. alpha-(134-141) stimulates proliferation of M3 melanoma cells, murine embryonic fibroblasts, primary cultures of red bone marrow and spleen cells. In L929 cells the effect of alpha-(134-141) is cell density independent; in M3 cells alpha-(137-141) and alpha-(134-141) are most active at density 10,000 cells/well (96 well plate) independently on FBS content.

Hemorphins, i.e. endogenous fragments of beta-globin chain segment (32-41) LVVYPWTQRY(F) suppress the growth of transformed murine fibroblasts L929 cell culture, the effect is due to cytotoxicity and inhibition of cell proliferation. The contribution of cytotoxicity depends on the presence of Leu(32): VV-hemorphins, except VV-hemorphin-4, exhibit cytotoxicity significantly higher than respective LVV-hemorphins. Decrease of cell number induced by hemorphins depend on the extent of N- and C-terminal degradation of hemorphins: VV-hemorphins in most cases are more active than LVV-, V-hemorphins, and hemorphins. In the group of VV-hemorphins the activity of VV-hemorphin-5 (valorphin) is significantly higher than of VV-hemorphin-7, VV-hemorphin-6, and VV-hemorphin-4, meaning that the presence of C-terminal Gln is important for suppressing of cell number. The amino acid sequence VVYPWTQ corresponding to valorphin was identified as important for manifestation of the both cytotoxic and antiproliferative effects.

It is shown that neokyotorphin (the alpha-globin fragment 137-141) stimulates proliferation of normal cells (murine embryonic fibroblasts, red bone marrow and spleen cells) and tumor cells (murine melanoma and transformed fibroblasts L929) in the absence or in the presence of fetal bovine serum. In contrast to serum deprivation conditions, the ability to potentiate L929 cell growth in the presence of fetal serum is strongly cell density dependent. The peptide also enhances the viability of L929 cells, murine embryonic fibroblasts and of the primary cultures of murine red bone marrow cells and splenocytes under serum-deprivation conditions for at least 72 h. The results of flow cytometry analysis suggest that the effect of neokyotorphin on survival of L929 cells in serum-free culture medium is due to maintenance of cell proliferation in the absence of growth factors. Along with cell cycle progression the peptide induces reversible reduction of L929 cell size.

171 iron-deficient painters and 20 subjects with chronic intoxication with aromatic hydrocarbons were studied in a large aircraft construction factory. After correlative analysis of iron metabolism, ferritin, erythrocytes, diameter and perimeter of reticulocytes, length of service three types of iron-deficiency were identified: typical, with evident toxicity, with a high risk of toxic damage. An important role of lipid peroxidation activity and toxic erythrocyto-membranopathy for pathomorphosis of iron deficiency anemia and progress of toxic anemia is demonstrated. A differential approach to treatment of different anemia variants was used. The treatment included membranoprotectors (alpha-tocopherol, essential, lypostabil) and unspecific detoxication (SUMS-enterosorbent, unitiol).

Spectrographic studies of fat acids in erythrocytic membranes and lipid peroxidation (LPO) contributed to the identification of different phases in the formation of damage effects. Exposition to toxic complexes (mostly solvents) in the first year caused a predominant growth of the antioxidant systems' activity characteristic of the processes of adaptation. In case with the work duration from one to five years, the u saturated fat acid content growth was accompanied by both pro- and antioxidative processes, which was indicative of the compensatory nature of the revealed changes. The most vivid shifts in the LPO reactions and the fat acids' content in erythrocytic membranes were found in the occupational group of patients engaged in the profession for more than 5 years. Those included major changes in the spectrum of both saturated and unsaturated acids, LPO activation with concomitant depression of the antioxidative systems.