Role of polyphenols and polyphenol-rich foods in the modulation of PON1 activity and expression

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme involved in the protection of low-density lipoprotein and HDLs against lipid peroxidation. Several studies documented the capacity of polyphenols to stimulate PON1 transcription activation. The objective of the present review is to provide the main evidence about the role and the potential mechanism of action of polyphenols and polyphenol-rich foods in the modulation of PON1 gene expression and activity. A total of 76 in vitro and in vivo studies were included in the review. Overall, while evidence obtained in vitro is limited to quercetin and resveratrol, those deriving from animal models seem more convincing for a wide range of polyphenols but only at pharmacological doses. Evidence from human studies is promising but deserves more substantiation about the role of polyphenol-rich foods in the regulation of PON1 activity and expression. Research focused on the understanding of the structure\u2013activity relationship of polyphenols with PON1 and on the mechanisms at the base of PON1 modulation is warranted. Well-designed human intervention studies are encouraged to corroborate the findings of polyphenols also at physiological doses

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency : a randomized controlled trial

Background & Aims: Vegetarians and vegans are more vulnerable to vitamin B12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 \ub5g. However, single large oral doses of vitamin B12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B12 (350 \ub5g/week vs. 2000 \ub5g/week) in improving cyanocobalamin (vitamin B12) nutritional status in vegans and vegetarians with a marginal deficiency. Methods: A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 \ub5g/week) and control group Hd (high dose, 2000 \ub5g/week) vitamin B12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B12, related metabolic markers, and blood cell counts. Results: Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time x treatment interaction (P = 0.012) on serum concentration of vitamin B12. In particular, 90 days of supplementation increased the levels of cyanocobalamin (+81.8% in the Ld group and +144.0% in the Hd group) compared to baseline. A significant increase was observed for the levels of holotranscobalamin (+64.5% in the Ld group and +165.2% in the Hd group), while a decrease occurred for the levels of methylmalonic acid (-72.3% in the Ld group and -69.4% in the Hd group), homocysteine (-56.8% in the Ld group and -53.6% in the Hd group), and folate (-22.8% in the Ld group and -17.7% in the Hd group) compared to baseline (time effect, P < 0.0001). No difference was observed between groups (Ld vs. Hd). No effect was detected for the other variables under study. Conclusions: In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 \ub5g/day (350 \ub5g/week) of cobalamin, instead of 2000 \ub5g/week (provided as a single dose), to reach a state of nutritional adequacy of vitamin B12 in this target population

Effective single mode methodology for strongly coupled multimode molecular-plasmon nanosystems

Strong coupling between molecules and quantized fields has emerged as an effective methodology to engineer molecular properties. New hybrid states are formed when molecules interact with quantized fields. Since the properties of these states can be modulated by fine-tuning the field features, an exciting and new side of chemistry can be explored. In particular, significant modifications of the molecular properties can be achieved in plasmonic nanocavities, where the field quantization volume is reduced to sub-nanometric volumes. Intriguing applications of nanoplasmonics include the possibility of coupling the plasmons with a single molecule, instrumental for sensing, high-resolution spectroscopy, and single-molecule imaging. In this work, we focus on phenomena where the simultaneous effects of multiple plasmonic modes are critical. We propose a theoretical methodology to account for many plasmonic modes simultaneously while retaining computational feasibility. Our approach is conceptually simple and allows us to accurately account for the multimode effects and rationalize the nature of the interaction between multiple plasmonic excitations and molecules.Comment: 27 pages, 6 figure

Different effects of anthocyanins and phenolic acids from wild blueberry (Vaccinium angustifolium) on monocytes adhesion to endothelial cells in a TNF-alpha stimulated proinflammatory environment

SCOPE: Monocyte adhesion to the vascular endothelium is a crucial step in the early stages of atherogenesis. This study aims to investigate the capacity of an anthocyanin (ACN) and phenolic acid (PA)-rich fraction (RF) of a wild blueberry, single ACNs (cyanidin, malvidin, delphinidin) and related metabolites (protocatechuic, syringic and gallic acid) to counteract monocytes (THP-1) adhesion to endothelial cells (HUVECs) in a tumor necrosis \u3b1 (TNF-\u3b1) mediated pro-inflammatory environment. METHODS AND RESULTS: HUVECs were incubated with different concentrations (from 0.01 to 10 \u3bcg mL-1 ) of the compounds for 24 h. Labelled monocytic THP-1 cells were added to HUVECs and their adhesion was induced by TNF-\u3b1 (100 ng mL-1 ). ACN-RF reduced THP-1 adhesion to HUVECs with a maximum effect at 10 \u3bcg mL-1 (-33%). PA-RF counteracted THP-1 adhesion at 0.01, 0.1 and 1 \u3bcg mL-1 (-45%, -48.7% and -27.6%, respectively), but not at maximum concentration. Supplementation with gallic acid reduced THP-1 adhesion to HUVECs with a maximum effect at 1 \u3bcg mL-1 (-29.9%), while malvidin-3-glucoside and syringic acid increased the adhesion. No effect was observed for the other compounds. CONCLUSION: These results suggest that ACNs/PA-RF may prevent atherogenesis while the effects of the single ACNs and metabolites are controversial and merit further exploration

The central role of iron in human nutrition : from folk to contemporary medicine

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today\u2019s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal

Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake

Hyperlipidemia starts at a pediatric age and represents an unquestionable risk factor for cardiovascular disease. Modulation of the intestinal microbial ecosystem (IME), in principle, can ameliorate lipid profiles. In this study, we characterized the IME of children and adolescents with primary hyperlipidemia by analyzing fecal samples through 16S rRNA gene profiling (n\ua0=\ua015) and short chain fatty acid (SCFA) quantification (n\ua0=\ua032). The same analyses were also carried out on age-matched normolipidemic controls (n\ua0=\ua015). Moreover, we evaluated the modulatory effect of regular hazelnut intake (approximately 0.43 g of hazelnuts with skin per kg of body weight) on the IME of 15 children and adolescents with hyperlipidemia for eight weeks. We found alterations of numerous operational taxonomic units potentially associated with SCFA-producing bacteria and reductions in the fecal levels of acetate, butyrate and propionate in hyperlipidemic subjects. Furthermore, we observed that an eight-week hazelnut intervention may induce limited changes in fecal microbiota composition but can significantly modulate the fecal levels of predominant intestinal SCFAs, such as acetate. Finally, correlation analyses indicated that changes in lipidemic parameters are linked to modifications of the abundance of specific bacterial taxa, such as the families Lachnospiraceae and Ruminococcaceae and the genera Akkermansia, Bacteroides, Roseburia, and Faecalibacterium. This study suggests that children and adolescents with primary hyperlipidemia possess an altered IME. The promising results presented here support the need for future dietary interventions aimed at positively modulating the IME of hyperlipidemic subjects

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%\ub151.3% (P=.002) and 23.1%\ub147.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%\ub138.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900

Progress and status of APEmille

We report on the progress and status of the APEmille project: a SIMD parallel computer with a peak performance in the TeraFlops range which is now in an advanced development phase. We discuss the hardware and software architecture, and present some performance estimates for Lattice Gauge Theory (LGT) applications.Comment: Talk presented at LATTICE97, 3 pages, Late

Effect of hazelnut on serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Background & aim: Regular intake of nuts improves lipid profile and thus reduces the cardiovascular (CV) risk associated with hyperlipidemia. The aim of the study was to investigate the effect of a dietary intervention with hazelnuts (HZNs, 15-30 g/day, depending on patient weight) on serum lipid profile, anthropometric parameters and fatty acids (FAs) composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia. Methods: Eight-week randomized, single blind, controlled, three-arm, parallel-group study. Sixty-six subjects were enrolled and randomized in 3 groups receiving: 1) hazelnuts with skin (HZN+S); 2) hazelnuts without skin (HZN-S); 3) dietary advices for hyperlipidemia only (controls). Before and after intervention, clinical parameters were measured and blood samples were collected for the evaluation of serum lipid levels and phospholipid FA composition of erythrocytes. Results: Two-way ANOVA showed a significant effect of time on serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)/LDL-C ratio and non-HDL-C (p < 0.001), but not of treatment and time x treatment interaction. In particular, HZN+S and HZN-S significantly reduced the concentrations of LDL-C and increased HDL-C/LDL-C ratio. HZNs also had a favorable impact on FAs composition of erythrocyte phospholipids, as demonstrated by time x treatment interaction, with a significant increase of monounsaturated fatty acids (MUFAs) (p = 0.008) and MUFAs/saturated fatty acids (SFAs) ratio (p = 0.002) with respect to the control group. Conclusions: For the first time, we documented a positive effect of HZN consumption on lipid profile and FA composition of erythrocyte phospholipids in children with primary hyperlipidemia. Further studies are encouraged to better define HZN impact on the markers of CV risk in this population