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One of the most recently proposed candidates as a potential trigger for cardiovascular diseases is trimethylamine-N-oxide (TMAO). Possible direct effects of TMAO on myocardial tissue, independent of vascular damage, have been only partially explored so far. In the present study, we assessed the detrimental direct effects of TMAO on cardiomyocyte contractility and intracellular calcium dynamics, and the ability of urolithin B-glucuronide (Uro B-gluc) in counteracting TMAO-induced cell damage. Cell mechanics and calcium transients were measured, and ultrastructural analysis was performed in ventricular cardiomyocytes isolated from the heart of normal adult rats. Cells were either untreated, exposed to TMAO, or to TMAO and Uro B-gluc. TMAO exposure worsened cardiomyocyte mechanics and intracellular calcium handling, as documented by the decrease in the fraction of shortening (FS) and the maximal rate of shortening and re-lengthening, associated with reduced efficiency in the intracellular calcium removal. Ultrastructurally, TMAO-treated cardiomyocytes also exhibited glycogen accumulation, a higher number of mitochondria and lipofuscin-like pigment deposition, suggesting an altered cellular energetic metabolism and a higher rate of protein oxidative damage, respectively. Uro B-gluc led to a complete recovery of cellular contractility and calcium dynamics, and morphologically to a reduced glycogen accumulation. We demonstrated for the first time a direct negative role of TMAO on cardiomyocyte functional properties and the ability of Uro B-gluc in counteracting these detrimental effects. [ABSTRACT FROM AUTHOR]

Myeloid angiogenic cells (MACs) play a key role in endothelial repairing processes and functionality but their activity may be impaired by the lipotoxic effects of some molecules like stearic acid (SA). Among the dietary components potentially able to modulate endothelial function in vivo, (poly)phenolic compounds represent serious candidates. Here, we apply a comprehensive multidisciplinary approach to shed light on the prospects of Bergamot (Citrus bergamia), a citrus fruit rich in flavanones and other phenolic compounds, in the framework of lipotoxicity-induced MACs impairment. The flavanone profile of bergamot juice was characterized and 16 compounds were identified, with a new 3-hydroxy-3-methylglutaryl (HMG) flavanone, isosakuranetin-7-Oneohesperidoside- 6"-O-HMG, described for the first time. Then, a pilot bioavailability study was conducted in healthy volunteers to assess the circulating flavanone metabolites in plasma and urine after consumption of bergamot juice. Up to 12 flavanone phase II conjugates (sulfates and glucuronides of hesperetin, naringenin and eriodyctiol) were detected and quantified. Finally, the effect of some of the metabolites identified in vivo, namely hesperetin-7-O-glucuronide, hesperetin-3'-O-glucuronide, naringenin-7-O-glucuronide and naringenin-4'-O-glucuronide, was tested, at physiological concentrations, on gene expression of inflammatory markers and apoptosis in MACs exposed to SA. Under these conditions, naringenin-4'0-O-glucuronide and hesperetin-7-O-glucuronide were able to modulate inflammation, while no flavanone glucuronide was effective in curbing stearate-induced lipoapoptosis. These results demonstrate that some flavanone metabolites, derived from the in vivo transformation of bergamot juice phenolics in humans, may mitigate stearate-induced inflammation in MACs. [ABSTRACT FROM AUTHOR]

Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer's disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity in children has risen greatly worldwide. Diet and poor physical activity are the two risk factors usually examined, but epidemiological evidence exists suggesting a link between sleep duration and overweight/obesity in children. The aim of this study was to describe the relationship among body mass index (BMI), diet quality, physical activity level, and sleep duration in 690 children attending the 5th grade in primary schools (9-11 years old) in the city of Parma (Italy) involved in the Giocampus educational program. This was achieved through (i) measuring anthropometric data to compute body mass index; (ii) administering a food questionnaire to evaluate adherence to the Mediterranean Diet (KIDMED score); and (iii) administering a lifestyle questionnaire to classify children physical activity level (PAL), sleep duration, and school achievement. A highly significant negative association was found between BMI and sleep hours. Moreover, there was a significant positive association between PAL and KIDMED scores. No evidence was found of association between BMI and PAL, nor between BMI and KIDMED score. Data from this study established that BMI is correlated to gender and sleep duration, defining sleep habits as one of the factors linked to overweight and obesity. [ABSTRACT FROM AUTHOR]

The market of plant-based nutraceuticals and food supplements is continuously growing due to the increased consumer demand. The introduction of new products with relevant nutritional characteristics represents a new way of providing bioactive compounds and (poly)phenols to consumers, becoming a strategy to ideally guarantee the health benefits attributed to plant foodstuffs and allowing the increase of daily bioactive compound intake. A paramount step in the study of nutraceuticals is the evaluation of the bioavailability and metabolism of their putatively active components. Therefore, the aim of the present study was to investigate the absorption profile of the (poly)phenolic compounds contained in three different plant-based food supplements, made of 36 different plant matrices, which were consumed by 20 subjects in an open one-arm study design. Blood samples were collected at baseline and 1, 2, 5, and 10 h after capsule intake. Twenty quantifiable metabolites deriving from different (poly)phenolic compounds were identified. Results showed that the consumption of the three capsules allowed the effective absorption of several (poly)phenolic compounds and metabolites appearing at different times in plasma, thereby indicating different absorption profiles. The capsules thus ensured potential health-promoting molecules to be potentially available to target tissues and organs. [ABSTRACT FROM AUTHOR]

Urinary biomarkers of mycotoxin exposure were evaluated in a group of celiac patients (n = 55) and in a control group of healthy subjects (n = 50) following their habitual diet. Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) were monitored in 105 urinary samples collected from the two groups. Dietary habits were also recorded through compilation of a seven-day weighed dietary diary. Biomarkers of mycotoxin exposure were detected in 21 celiac patients and in 15 control subjects, corresponding to about 34% of total participants. In particular, ZEN was the most detected mycotoxin among all the studied subjects with a total of 19 positive cases. Results did not show a statistically significant difference in mycotoxin exposure between the two groups, and the presence of specific mycotoxins was not related to the intake of any particular food category. Our findings suggest little urgency of specific regulation for gluten free products, although the prevalence of exposure observed in free-living diets of both celiac and healthy subjects underlines the need of a constant surveillance on mycotoxins occurrence at large. [ABSTRACT FROM AUTHOR]

The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism. [ABSTRACT FROM AUTHOR]

Research on the potential protective effects of coffee and its bioactives (caffeine, chlorogenic acids and diterpenes) against oxidative stress and related chronic disease risk has been increasing in the last years. The present review summarizes the main findings on the effect of coffee consumption on protection against lipid, protein and DNA damage, as well as on the modulation of antioxidant capacity and antioxidant enzymes in human studies. Twenty-six dietary intervention studies (involving acute and chronic coffee intake) have been considered. Overall, the results suggest that coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake. On the contrary, the effects of coffee on plasma antioxidant capacity and antioxidant enzymes, as well as on protein and lipid damage, are unclear following both acute and chronic exposure. The high heterogeneity in terms of type of coffee, doses and duration of the studies, the lack of information on coffee and/or brew bioactive composition, as well as the choice of biomarkers and the methods used for their evaluation, may partially explain the variability observed among findings. More robust and well-controlled intervention studies are necessary for a thorough understanding of the effect of coffee on oxidative stress markers in humans. [ABSTRACT FROM AUTHOR]

Wheat aleurone, due to its potentially higher bioaccessibility and bioavailability of micronutrients and phenolic acids, could represent a useful ingredient in the production of commonly consumed cereal-based food. The aim of the present study was to investigate the in vitro bioaccessibility of phenolic acids both from an aleurone-enriched bread and from a whole grain bread. The two bread samples were firstly characterized for the phenolic acid content. An in vitro digestion was then performed in order to evaluate the release of phenolic acids. The results obtained suggest that the bioaccessibility of the phenolic acids in the aleurone-enriched bread is higher than in the whole grain bread. These in vitro results suggest the potential use of aleurone in the production of foods, and this may represent an attractive possibility to vehicle nutritionally interesting components to consumers. [ABSTRACT FROM AUTHOR]

Gnagnan (Solanum indicum L.) is a spontaneous plant widely distributed in Ivory Coast. During ripening stages, Solanum indicum L. presents different colours (green, yellow and red) and is reported to contain several albeit poorly characterized antioxidant compounds. This paper describes in detail the antioxidant profile (ascorbic acid, carotenoids and polyphenols), antioxidant capacity (FRAP test and Folin-Ciocalteau assay) and the colour changes of Gnagnan berries at different ripening levels. Ascorbic acid content was similar in green and yellow berries, but significantly lower in red ones. Red berries showed a higher content of carotenoids compared to green and yellow ones. Regarding polyphenols, several phenolic acids and flavonoids were found in all berries. The content of caffeoylquinic acids, caffeic acid, flavonol glycosides and naringenin was higher in red berries, while the content of p-coumaric acid and feruloylquinic acids was similar among the three colours. The FRAP assay increased with the ripening process, whereas total polyphenols were similar among berries. Significant differences were found for the colorimetric indexes among products of different degrees of ripening. The present results show the important role of the ripening stage in increasing the antioxidant content of Gnagnan berries. [ABSTRACT FROM AUTHOR]

Durum wheat pasta is considered a low-glycemic index (GI) food. In recent years, the interest in developing enriched pasta has increased. Since both the formulation and processing technologies may affect the GI, this study aimed to investigate the GI values of pasta products (pp) reported in the literature until 2020. GI values of pp analyzed following the ISO guidelines were included in this survey. A total of 95 pp were identified and, according to their formulation, classified into 10 categories (n, mean GI): category n 1: 100% refined wheat (35, 55); category n 2: 100% whole wheat (6, 52); category n 3: other cereal-based products (8, 52); category n 4: containing egg (5, 52); category n 5: gluten free (11, 60); category n 6: containing legumes (9, 46); category n 7: noodles and vermicelli (9, 56); category n 8: containing vegetable or algae (6, 51); category n 9: containing other ingredients (5, 37); category n 10: stuffed (1, 58). Overall, pasta is confirmed to be a medium–low-GI food, even if a high variability among or within each category emerged. The formulation of enriched pp able to elicit a controlled glycemic response could represent a strategy to improve the nutritional value of pasta. [ABSTRACT FROM AUTHOR]

The glycaemic index (GI) is a food metric that ranks the acute impact of available (digestible) carbohydrates on blood glucose. At present, few countries regulate the inclusion of GI on food labels even though the information may assist consumers to manage blood glucose levels. Australia and New Zealand regulate GI claims as nutrition content claims and also recognize the GI Foundation's certified Low GI trademark as an endorsement. The GI Foundation of South Africa endorses foods with low, medium and high GI symbols. In Asia, Singapore's Healthier Choice Symbol has specific provisions for low GI claims. Low GI claims are also permitted on food labels in India. In China, there are no national regulations specific to GI; however, voluntary claims are permitted. In the USA, GI claims are not specifically regulated but are permitted, as they are deemed to fall under general food-labelling provisions. In Canada and the European Union, GI claims are not legal under current food law. Inconsistences in food regulation around the world undermine consumer and health professional confidence and call for harmonization. Global provisions for GI claims/endorsements in food standard codes would be in the best interests of people with diabetes and those at risk. [ABSTRACT FROM AUTHOR]

Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the "gut-brain axis". [ABSTRACT FROM AUTHOR]

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level. [ABSTRACT FROM AUTHOR]

While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost–benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations. [ABSTRACT FROM AUTHOR]

Published meta-analyses indicate significant but inconsistent incident type-2 diabetes (T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is now over a decade ago that a published meta-analysis used a predefined standard to identify valid studies. Considering valid studies only, and using random effects dose–response meta-analysis (DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relations would support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit >1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). The combined T2D–GI RR was 1.27 (1.15–1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that for the T2D–GL RR was 1.26 (1.15–1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet. The corresponding global DRM using restricted cubic splines were 1.87 (1.56–2.25) (p < 0.001, n = 10) and 1.89 (1.66–2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000 kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GL were robustly associated with incident T2D. Together with mechanistic and other data, this supports that consideration should be given to these dietary risk factors in nutrition advice. Concerning the public health relevance at the global level, our evidence indicates that GI and GL are substantial food markers predicting the development of T2D worldwide, for persons of European ancestry and of East Asian ancestry. [ABSTRACT FROM AUTHOR]