Search

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We assess their adherence to four dietary patterns, namely, the Dietary Approach to Stop Hypertension (DASH) diet, the Mediterranean diet through the Greek and Italian Mediterranean Indices (GMI and IMI) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, using a validated semi-quantitative food frequency questionnaire (FFQ). We then assess their association with blood parameters and the 10-year risk of major CVD using a spline regression model. We found an inverse association between the DASH and MIND diets and total and LDL cholesterol, and triglyceride and HDL cholesterol values for the Mediterranean diets (IMI and GMI). Additionally, according to our sex-stratified analyses, men who have greater adherence to dietary patterns have a decreased risk of major CVD for all patterns. The results suggest that greater adherence to dietary patterns positively influences blood biochemical and metabolic parameters, thus reducing the risk of developing cardiovascular disease and delaying the use of drug treatments.

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30-60 years) in the 2017-2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 μg/L (interquartile range (IQR): 0.11-0.34 μg/L) and 3.21 μg/g creatinine (IQR: 2.21-4.80 μg/g creatinine), respectively, while median dietary cadmium intake was 6.16 μg/day (IQR: 5.22-7.93 μg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27-121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

Selenium is both an essential nutrient and a highly toxic element, depending on its dose and chemical forms. We aimed to quantify urinary selenium excretion and dietary selenium intake in 137 healthy non-smoking blood donors living in the northern Italian province of Reggio Emilia. We assessed selenium status by determining urinary selenium levels (mean 26.77 µg/L), and by estimating dietary selenium intake (mean 84.09 µg/day) using a validated semi-quantitative food frequency questionnaire. Fasting blood levels of glucose, lipids and thyroid-stimulating hormone were measured using automatized laboratory procedures. Dietary and urinary selenium were correlated (beta coefficient (β) = 0.19). Despite this, the association of the two indicators with health endpoints tended to diverge. Using linear regression analysis adjusted for age, sex, body mass index, cotinine levels and alcohol intake, we observed a positive association between urinary selenium and blood triglyceride (β = 0.14), LDL-cholesterol (β = 0.07) and glucose levels (β = 0.08), and an inverse one with HDL-cholesterol (β = −0.12). Concerning dietary selenium, a slightly positive association could be found with glycemic levels only (β = 0.02), while a negative one emerged for other endpoints. The two selenium indicators showed conflicting and statistically highly imprecise associations with circulating TSH levels. Our findings suggest that higher selenium exposure is adversely associated with blood glucose levels and lipid profile. This is the case even at selenium exposures not exceeding tolerable upper intake levels according to current guidelines.

BACKGROUND AND AIM: Cadmium is a toxic heavy metal exerting several adverse effects in humans, especially for kidney, bone, liver, and cardiovascular system. In particular, genotoxic effects may oc...

Introductory sentence. Demethylating drugs represent a powerful tool for epigenetic modulation of chromatin structure in cancer cells. 5-azacytidine (5-AZA) and 5-aza-2’-deoxycytidine (decitabine) are promising therapeutic solutions also in mature B-cell neoplasms, although the molecular mechanisms of action have yet to be elucidated. Here we describe their effects on non-Hodgkin lymphoma cells and demonstrate how hypomethylation is not homogeneous across the genome. Experimental procedures. Toledo (GC-derived) and NU-DUL-1 (ABC-like) diffuse large-B cell lymphoma (DLBCL; non-Hodgkin) cell lines. Peripheral blood mononuclear cells (PBMCs) isolation. Epitect methyl II methylation qPCR and global chromatin methylation quantitative assays. Immunoblottings. Proliferation assays. CpG islands bioinformatics analysis. Comet assay and phosphorylation of gamma-H2AX histone assay. Gene silencing through siRNAs. New data. A panel of 9 CpG islands within a set of genes that we previously identified has been investigated as a potential target for hypomethylating activity of 5AZA and decitabine. KLF4, DAPK1 and SPG20 promoters (located on chr. n°9 the first two and n°3 the latter) are not affected by a single dose of 5AZA after 48h or 7 days of incubation (the CpG islands within these promoters are fully unmethylated in healthy PBMCs). However, global chromatin demethylation is clearly visible either after 48h or 7 days in both cell lines. By comparison, decitabine demethylating effects return to the initial values after 7 days. MZB1 promoter results demethylated by both treatments, while MGMT is demethylated only in NU-DUL-1 by decitabine but not 5AZA. These data suggest that hypomethylating agents act selectively on discrete regions of the genome. 5AZA and decitabine markedly down-regulate DNMT1 in a dose-dependent fashion and activate PARP. Despite DNMT1 downregulation, KLF4, DAPK1 and SPG20 promoters result unaffected. DNMT1 silencing in our cells do not cause any change in the promoter methylation of the selected targets. The de novo methyltransferase DNMT3a is expressed only by NU-DUL-1 and its silencing leads to a partial MZB1 demethylation and to the significant decrease in global chromatin methylation whereas DNMT1 silencing does not. In order to assess an involvement of the genotoxic damage, Comet assays were performed up to 24 hours of incubation with the drugs. We demonstrate that 5AZA does not induce any significant genotoxic damage while decitabine causes a tail formation starting at 6h after drug administration. Conclusions. Our data show that 5AZA and decitabine exhibit different mechanisms of action on lymphoma cells. Different DLBCL-derived cell lines display different changes when exposed to single doses of hypomethylating drugs, underlying the fact that cell of origin may play a role during the response. DNMT3a contributes to chromatin methylation in lymphoma cells. Citation Format: Raffaele Frazzi, Tonia De Simone, Olga Serra, Annamaria Buschini, Laura Canovi, Tiziana De Luca, Francesco Merli. 5AZA and decitabine exhibit different molecular effects on non-Hodgkin lymphoma cells: Involvement of DNMT3a [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5198.