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Uncovering the main determinants of diet quality is one of the greatest challenges for Public Health, since it could guide future strategies and interventions against cardiovascular diseases (CVDs). The present cross-sectional analysis of the Kardiovize cohort evaluates the prevalence of dietary risk factors for CVDs and their association with social and behavioural characteristics in a random sample of 1536 adults (aged 25-64 years) from Brno, Czech Republic.A face-to-face health interview guided by structured questionnaires was carried out on socio-demographic characteristics (age, sex, educational level, employment, marital status, income, and household size) and behaviours (smoking status, physical activity, and sleep habits). Twelve dietary risk factors covered by the Global Burden of Diseases comparative risk assessment framework were assessed using a Food Frequency Questionnaire. In general, we observed that the consumption of nearly all healthy foods and nutrients was suboptimal, and that it was also aggravated by high intake of foods and nutrients that constituted dietary risk factors. Moreover, we found several associations of social and behavioural characteristics with specific dietary risk factors. Particularly, being male (β = 0.466; SE = 0.079; p 0.001), increasing household size (β = 0.130; SE = 0.047; p = 0.006), low income (β = 0.192; SE = 0.091; p = 0.035), and decreasing physical activity level (β = 0.172; SE = 0.054; p = 0.002) were associated with increasing number of dietary risk factors.Thus, our study raises an urgent need for Public Health strategies promoting healthy eating in adulthood, which should be based on traditional and novel determinants of dietary risk.

A recent work by Nishina et al. provides new evidence that DPP4 inhibitors exert antitumor effects against hepatocellular carcinoma (HCC) by orchestrating immune responses.

Objective To investigate the association of pet ownership, and specifically dog ownership, with cardiovascular diseases (CVD) risk factors and cardiovascular health (CVH) in the Kardiovize Brno 2030 study, a randomly selected prospective cohort in Central Europe. Patients and Methods We included 1769 subjects (aged from 25 to 64 years; 44.3% males) with no history of CVD who were recruited from January 1, 2013, to December 19, 2014. We compared sociodemographic characteristics, CVD risk factors, CVH metrics (ie, body mass index, healthy diet, physical activity level, smoking status, blood pressure, fasting glucose, and total cholesterol), and score between pet owners and non-pet owners or dog owners and several other subgroups. Results Approximately 42% of subjects owned any type of pet: 24.3% owned a dog and 17.9% owned another animal. Pet owners, and specifically dog owners, were more likely to report physical activity, diet, and blood glucose at ideal level, and smoking at poor level, which resulted in higher CVH score than non-pet owners (median, 10; interquartile range = 3 vs median, 9; interquartile range = 3; P=0.006). Compared with owners of other pets, dog owners were more likely to report physical activity and diet at ideal level. The comparison of dog owners with non-dog owners yielded similar results. After adjustment for covariates, dog owners exhibited higher CVH scores than non-pet owners (β=0.342; SE=0.122; P=0.005), other pet-owners (β=0.309; SE=0.151; P=0.041), and non-dog owners (β=0.341; SE=0.117; P=0.004). Conclusion Except for smoking, dog owners were more likely to achieve recommended level of behavioral CVH metrics (physical activity and diet) than non-dog owners, which translated into better CVH.

Objective Atherosclerosis is a major contributor to cardiovascular disease, with a higher burden on men than women during the occupational age. Intake of individual dietary antioxidants is inversely associated with risk of atherosclerosis development. We aimed to understand the relationship between dietary composite antioxidant intake and the carotid intima media thickness (cIMT), which is a proxy of atherosclerosis progression. Approach and results We performed a cross-sectional analysis that included 894 members of the Kardiovize cohort, a random urban sample population. Nutrient intakes were derived by 24-h recall. We constructed a composite dietary antioxidant index (CDAI), based on zinc, selenium, vitamin A, vitamin C, vitamin E and carotenoids. We considered the CDAI as the exposure variable and primary outcomes were the following cardio-metabolic parameters: body mass index (BMI), waist-to-hip ratio (WHR), body fat mass (BFM), systolic and diastolic blood pressure, triglycerides, HDL and LDL cholesterol, and cIMT. Associations and interactions between variables were evaluated using linear regression analyses. In women, a 1 mg increase in dietary intake of zinc or vitamin E decreased the cIMT by 3.36 and 1.48 µm, respectively, after adjusting for covariates. Similarly, the cIMT decreased by 4.72 µm for each one-unit increase in CDAI (p = 0.018). Beyond CDAI, age (β = 3.61; SE=0.89; p = 0.001), systolic blood pressure (β = 1.30; SE=0.59; p = 0.029) and triglycerides (β = 22.94; SE=10.09; p = 0.024) were significant predictors of cIMT in women. By contrast, we found no association between CDAI and cIMT in men. Conclusions CDAI negatively associates with cIMT in women. These findings indicate that combined intake of nutrients with anti-oxidant properties might prevent the initiation and progression of arterial lesions in a sex-specific manner.

Human behavior is influenced by both genetic and environmental factors. Monoamine oxidase A (MAOA) is among the most investigated genetic determinants of violent behaviors, while the monoamine oxidase B (MAOB) is explored in Parkinson's disease. We collected twenty-four post-mortem brain tissue datasets of 3871 and 1820 non-demented males and females, respectively, who died from causes not attributable to neurodegenerative diseases. The gene expressions of MAOA and MAOB (MAO genes) were analyzed in these subjects, who were further stratified according to age into eleven groups ranging from late Infancy (5-9 months) to centenarians (>100 years). MAO genes were differently expressed in brains during the entire life span. In particular, maximal and minimal expression levels were found in early life and around the teen years. Females tended to have higher MAO gene levels throughout their lives than those found in age-matched males, even when expressions were separately measured in different brain regions. We demonstrated the existence of age- and sex- related variations in the MAO transcript levels in defined brain regions. More in-depth protein studies are needed to confirm our preliminary results obtained only on messenger RNAs in order to establish the role played by MAO genes in human development.

Hepatocellular carcinoma (HCC) is one of the fastest-growing causes of cancer-related mortalities worldwide and this trend is mimicked by the surge of non-alcoholic fatty liver disease (NAFLD). Altered hepatic lipid metabolism promotes HCC development through inflammation and activation of oncogenes. GDF11 is a member of the TGF-β superfamily and recent data have implicated GDF11 as an anti-aging factor that can alleviate high-fat diet induced obesity, hyperglycemia, insulin resistance and NAFLD. However, its role in hepatic lipid metabolism is still not fully delineated. The aim of the present study was to characterize the role of GDF11 in hepatic and HCC cells lipid accumulation. To achieve this, we performed imaging, biochemical, lipidomic, and transcriptomic analyses in primary hepatocytes and in HCC cells treated with GDF11 to study the GDF11-activated signaling pathways. GDF11 treatment rapidly triggered ALK5-dependent SMAD2/3 nuclear translocation and elevated lipid droplets in HCC cells, but not in primary hepatocytes. In HCC cells, ALK5 inhibition hampered GDF11-mediated SMAD2/3 signaling and attenuated lipid accumulation. Using ultra-high-performance liquid chromatography/mass spectrometry, we detected increased accumulation of longer acyl-chain di/tri-acylglycerols and glycerophospholipids. Unbiased transcriptomic analysis identified TGF-β and PI3K-AKT signaling among the top pathways/cellular processes activated in GDF11 treated HCC cells. In summary, GDF11 supplementation promotes pro-lipogenic gene expression and lipid accumulation in HCC cells. Integration of our “omics” data pointed to a GDF11-induced upregulation of de novo lipogenesis through activation of ALK5/SMAD2/3/PI3K-AKT pathways. Thus, GDF11 could contribute to metabolic reprogramming and dysregulation of lipid metabolism in HCC cells, without effects on healthy hepatocytes.

The Timeless (Tim) gene, originally identified in Drosophila melanogaster and subsequently in mammals, is involved in the molecular clockwork that drives 24h periodicity in physiology and behavior. The Tim protein is involved not only in circadian rhythmicity but also in embryonic development, cell cycle progression, DNA replication, and the DNA damage response (DDR). It is thus a multifaceted factor implicated in the maintenance of many cellular processes, tissue functions, and ultimately homeostasis of various organisms, from insects to humans. This review highlights the current knowledge of Tim functions, especially the most recent achievements, and illustrates the possible roles that this factor plays in the physiological preservation of health, as well as in the pathogenic mechanisms of related diseases.

The circadian system controls the behavior and multiple physiological functions. In mammals, the suprachiasmatic nucleus (SCN) acts as the master pacemaker and regulates the circadian clocks of peripheral tissues. The SCN receives information regarding the light-dark cycle and is thus synchronized to the external 24-hour environment. In contrast, peripheral clocks, such as the liver clock, receive information from the SCN and other factors; in particular, food intake which leads to insulin secretion induces strong entrainment of the liver clock. On the other hand, the liver clock of insulin-depleted mice treated with streptozotocin (STZ) has been shown to be entrained by scheduled feeding, suggesting that insulin is not necessary for entrainment of the liver clock by feeding. In this study, we aimed to elucidate additional mechanism on entraining liver clock by feeding a protein-only diet and/or amino-acid administration which does not increase insulin levels. We demonstrated that protein-only diet and cysteine administration elicit entrainment of the liver clock via glucagon secretion and/or insulin-like growth factors (IGF-1) production. Our findings suggest that glucagon and/or IGF-1 production are additional key factors in food-induced entrainment., Highlights • Dietary protein or cysteine increase serum glucagon and hepatic IGF-1 levels, and entrain liver circadian rhythm. • Increasing IGF-1 levels is an additional entrainment factor of liver circadian rhythm. • Hepatic IGF-1 production is found to be a key factor in the entrainment of liver circadian rhythm in STZ-treated mice. Disruption of the circadian rhythm leads to multiple disorders; thus the maintenance of circadian oscillation is necessary for maintaining normalized physiological functions. Postprandial insulin secretion is known as an entraining factor of peripheral circadian rhythm; however, this pathway is not appropriate for diabetes patients in whom insulin signaling is disrupted. Here we report that both dietary protein and cysteine alone entrain liver circadian rhythm by increasing glucagon and/or IGF-1 levels independently of insulin. Findings indicate an additional entrainment factor that can be applied to chronotherapy by controlling food content or by supplementation in peoples with diabetes, circadian rhythm disorders.

Chronic hepatitis C patients display many genotype-specific clinical features of HCV infection. The core proteins encoded by different genotypes dysregulate numerous sets of distinct host genes. In this study we tested the hypothesis that HCV core proteins 1b and 3a would actually act on a limited number of independent cellular players, as well as on several functionally linked gene products. Structural and functional tests identified a core set of host genes dysregulated by HCV core genotypes 1b and 3a. The core proteins of HCV genotypes 1b and 3a target specifically limited sets of functionally related gene products, which may be responsible for the variations in the clinical spectra associated with HCV infection.

The circadian clock machinery orchestrates organism metabolism in order to ensure that development, survival and reproduction are attuned to diurnal environmental variations. For unknown reasons, there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissues homeostasis and changes in the feeding behavior of aged organisms. This disruption of the relationship between the clock and the nutrient sensing networks might underlie age-related diseases; overall, greater knowledge of the molecular mediators of and variations in clock networks during lifespan may shed light on the aging process and how it may be delayed. In this review we address the complex links between the circadian clock, metabolic (dys)functions and aging in different model organisms.

BACKGROUND/AIMS: The impact of dietary fatty acids on the development of cancers is highly controversial. We recently demonstrated that unsaturated fatty acids trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-kappaB-dependent mechanism in hepatocytes. In this study, we investigated whether unsaturated fatty acids promote hepatoma progression by downregulating PTEN expression. METHODS: The effects of fatty acids and PTEN-specific siRNAs on proliferation, invasiveness and gene expression were assessed using HepG2 hepatoma cells. The tumor promoting activity of unsaturated fatty acids was evaluated in vivo using HepG2 xenografts in nude mice. RESULTS: Incubation of HepG2 cells with unsaturated fatty acids, or PTEN-specific siRNAs, increased cell proliferation, cell migration and invasiveness, and altered the expression of genes involved in inflammation, epithelial-to-mesenchymal transition and carcinogenesis. These effects were dependent on PTEN expression levels and were prevented by mTOR and NF-kappaB inhibitors. Consistent with these data, the development and size of subcutaneous HepG2-derived tumors in nude mice xenografts were dramatically increased when mice were fed with an oleic acid-enriched diet, even in the absence of weight gain. CONCLUSIONS: These data demonstrate that dietary unsaturated fatty acids promote hepatoma progression by reducing the expression of the tumor suppressor PTEN.

kcal/100 g) for 12 weeks. Control mice consumed normal laboratory chaw (360 kcal/100 g). Anti-HBs production due to immunization with HBsAg-based vaccine was evaluated in vivo. HBsAg-specific T cell proliferation and functional capacities of MDSC and DC were evaluated in vitro. Results: In spite of exhibiting an inflammatory hepatic mucosa (increased serum ALT and hepatic inflammation) and fatty acids were compared to control mice (P < 0.05). the levels of anti-HBs and HBsAg-specific T lymphocyte proliferation were significantly lower in NAFLD mice compared to control mice (p < 0.01). The proliferation of T and B lymphocytes was increased in NAFLD mice due to stimulation with polyclonal immune modulators (concanavalin A and lipopolysaccharides). However, the capacity of DC of NAFLD mice to process and present HBsAg were significantly lower than those of control mice (p < 0.05). In addition, impaired DC functions of NAFLD mice were further exacerbated in presence of MDSC of NAFDL mice. Conclusions: Impaired antigen-specific immunity of NAFLD subjects to vaccine in spite of inflammatory mucosal milieu seems to be related to distorted antigen presenting capacity of DC and suppressor capacity of MDSC.

Methods: To avoid contamination, viral RNA was extracted in different places (Lyon versus Bobigny and Bangui) for ancient and recent samples, respectively. Manual or automated (Siemens Process Versant kPCR) extractions led to available nucleic acids extracts. Viral RNA presence was based on the RT-PCR of a 400 bp HDV genome fragment (R0 region). Four to six clones were characterized for positive samples. Furthermore we aimed to amplify and clone the full length of HDV coding sequences from R0-positive samples. HD-positive contemporary samples were obtained from a wide serological survey among school and medical students (n = 1335). Results: FH-associated HDV sequences were obtained from 6 patients and indicated that different African HDV1 strains were responsible for the FH outbreak. In one case quasispecies analysis indicated a punctual deletion in the HD coding gene that could lead to a frame shift in the 3′terminal region of the large delta protein gene, changing the carboxy terminal end of the Large HD protein. HBV genotype E (n =8) and A (n =1) corresponded to the circulating HBV strains during this outbreak. Conclusion: HDV viral RNA could be retrieved from ancient serum samples kept at −20°C for 25 years confirming the strengthness of the viral pseudo double stranded RNA. FH delta in Bangui was linked to different HDV strains. However, all corresponded to HDV genotype 1. HBV Genotype E was the main associated HBV genotype already present in RCA in the mid eighties.