A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial

Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (?\u274.4 ? 0.8% blueberry treatment vs. ?\u2722.0 ? 1.1% smoking treatment, p < 0.01) and Framingham reactive hyperemia (+28.3 ? 19.2% blueberry treatment vs. ?\u2742.8 ? 20.0% smoking treatment, p < 0.0001), and the increase of systolic blood pressure (+8.4 ? 0.02% blueberry treatment vs. +13.1 ? 0.02% smoking treatment, mmHg, p < 0.05) after cigarette smoking. No effect was observed for arterial stiffness and other vital signs. In conclusion, data obtained suggest a protective role of blueberry on reactive hyperemia, Framingham reactive hyperemia, and systolic blood pressure in subjects exposed to smoke of one cigarette. Future studies are necessary to elucidate the mechanisms involved

An in vitro approach to study the absorption of a new oral formulation of berberine

Background Berberine (BBR) possesses several biological activities in humans, but the poor water solubility and low oral bioavailability preclude its pharmacological use. To overcome these limitations, several formulations have been prepared including encapsulation, micro- and nano-emulsion. The aim of this study was to develop a nanoemulsion delivery system of BBR and to evaluate its membrane permeability using Caco-2 cell model. Methods Nanoemulsions containing different ratios BBR:Compritol ATO 888 (a lipid excipient) were formulated at 25 and 80 °C. The controls consisted of BBR and carboxymethylcellulose. Absorption of BBR nanoemulsions delivery systems was evaluatedin vitro by using human colon adenocarcinoma cells (Caco-2) Transwell model. The amount of permeated BBR was determined by LC-HR-MS at time zero and every 30 min for 180 min. Results Nanoemulsions significantly improved apical-to-basal transport of BBR compared to the control formulation. Kinetics of BBR uptake showed that the maximum amount absorbed was reached after 90-120 min and the percentage of BBR absorbed by Caco-2 cells increased with increasing BBR-to-Compritol ratio (1:20 &gt; 1:10 &gt; 1:5 &gt; 1:1). Moreover, the formulation prepared at 80 °C showed a higher absorption rate (6-fold increment compared to control) than that developed at 25 °C (4.5-fold increment compared to control). Furthermore, demethyl-BBR was detected after 120 min of incubation as partial metabolism of berberine in the intestine. Conclusions Overall, in ourin vitro model, these new nanoemulsions seem to potentially improve the absorption of BBR. However, in vivo studies are required in order to demonstrate the bioavailability of BBR from this new formulation

Impact of Substituting Meats with Plant-Based Analogues on Health-Related Markers: A Systematic Review of Human Intervention Studies

The growing drive towards more sustainable dietary patterns has led to an increased demand for and availability of plant-based meat analogues (PBMAs). This systematic review aims to summarize the currently available evidence from human intervention studies investigating the impact of substituting animal meat (AM) with PBMAs in adults. A total of 19 studies were included. Overall, an increase in satiety following PBMA intake was reported, albeit to different extents and not always accompanied by changes in leptin and ghrelin. PBMAs generally resulted in lower protein bioavailability and a smaller increase in plasma essential amino acids in comparison to AM. However, muscle protein synthesis and physical performance were not affected. Finally, conflicting results have been reported for other outcomes, such as pancreatic and gastrointestinal hormones, oxidative stress and inflammation, vascular function, and microbiota composition. In conclusion, we documented that the impact of substituting AM with PBMA products has been scarcely investigated. In addition, the heterogeneity found in terms of study design, population, outcomes, and findings suggests the need for additional high-quality intervention trials, particularly long-term ones, to better clarify the advantages and potential critical issues of such substitutions within sustainable healthy diets

Plant-Based Foods and Vascular Function: A Systematic Review of Dietary Intervention Trials in Older Subjects and Hypothesized Mechanisms of Action

Cardiovascular diseases, still the leading cause of mortality in the world, are closely related to vascular function. Older subjects are more susceptible to endothelial dysfunction and therefore it is important to define possible preventive or support strategies, such as consumption of foods with health-promoting effects. This systematic review aims to summarize the currently available evidence on acute or chronic trials testing the effect of selected plant-based foods on vascular function parameters in older subjects, and consider plausible mechanisms that may support the main findings. A total of 15 trials were included and analyzed, testing the effects of beetroot, plum, blueberry, and vegetable oils. We found some interesting results regarding markers of vascular reactivity, in particular for beetroot, while no effects were found for markers of arterial stiffness. The amelioration of vascular function seems to be more related to the restoration of a condition of nitric oxide impairment, exacerbated by diseases or hypoxic condition, rather than the enhancement of a physiological situation, as indicated by the limited effects on healthy older subjects or in control groups with young subjects. However, the overall set of selected studies is, in any case, rather limited and heterogeneous in terms of characteristics of the studies, indicating the need for additional highquality intervention trials to better clarify the role of vegetable foods in restoring and/or improving vascular function in order to better elucidate the mechanisms through which these foods may exert their vascular health benefits in older subjects

Differential effects of wild blueberry (poly)phenol metabolites in modulating lipid metabolism and oxidative stress in 3T3‐L1 adipocytes

Adipocyte hypertrophy, driven by lipid accumulation, is crucial in the development of obesity. Wild blueberry (WB; Vaccinium angustifolium) (poly)phenols (PPs) metabolites may modulate adipogenesis and the development of obesity. This study examines WB PP metabolites’ effects on lipid accumulation, lipid metabolism, and oxidative stress in mature 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated for 48 h with free fatty acids (FFAs; oleic/palmitic acid 750 μM, 2:1 ratio) and WB-derived PPs, including ferulic acid (FA), isoferulic acid (IA), vanillic acid (VA), and syringic acid (SA) at physiological and supra-physiological concentrations. Assessments included lipid accumulation, glycerol release, and markers of lipid metabolism (sterol regulatory element-binding protein 1c [SREBP-1], fatty acid synthase [FASN], FAB4) and oxidative stress (DNA damage, 8-hydroxy 2-deoxyguanosine [8OHdG], nuclear erythroid factor 2-related factors 2 (NRF2), heme oxygenase 1 [HO-1]). FFAs significantly increased lipid accumulation, glycerol release, and FASN levels, while reducing HO-1 levels, without affecting other markers. WB PP metabolites did not reduce lipid accumulation, but IA and VA reduced FASN levels (−25% and −26%; p &lt; 0.05), and SA improved HO-1 levels (+150%; p &lt; 0.05). Despite the different effects observed, the findings obtained under our experimental conditions seem to suggest that IA, VA, and SA may modulate lipid metabolism and oxidative stress markers. However, further studies are fundamental to corroborate the findings obtained and support the contribution of these BB PPs metabolites and other compounds in the prevention and management of obesity

An overview of registered clinical trials on glucosinolates and human health : the current situation

Epidemiological studies suggest a potential role of glucosinolates (GSLs) and isothiocyanates on human health. However, evidence from intervention studies, due to heterogeneity in features of study design, duration, participants, food or food components administered, and outcomes analyzed, is still insufficient. The current review aims to provide an overview of the trials on GSLs and GSL-rich foods registered over the last 20 years with the intention to summarize the main topics and results, but also the existing gaps that still need to be covered. Studies were collected by using ClinicalTrials.gov and the International Standard Randomized Controlled Trial Number (ISRCTN) registry. A total of 87 registered trials were identified with which most of them were performed by using extracts or pure compounds (n = 60) while few were conducted with GSL-rich foods (n = 27). In detail, sulforaphane was the most investigated compound, while broccoli was the most frequent food tested in the trials. The majority of the studies assessed the health effects of GSLs focusing on outcomes related to cancer and cognitive function, even if the current findings are not univocal. Emerging topics also included the study of GSLs and gut microbiota interaction and impact on skin health. Further attention was also drawn to the bioavailability of GSLs and/or derivatives from foods, extracts, and single compounds by also considering the contribution of the different genetic polymorphisms. In conclusion, although considerable efforts have been made to study GSLs and GSL-rich foods, further studies are necessary to provide evidence-based research and to corroborate the findings obtained. The interindividual response due to genetic polymorphisms should be further investigated in order to explore the contribution to the overall beneficial effect

Acute effect of blueberry intake on vascular function in older subjects: Study protocol for a randomized, controlled, crossover trial

Aging is associated with an increased risk of developing cardiovascular disease which is often accompanied by a decline in vascular health and function. Current evidence suggests that berries may have a potential role in the modulation of vascular function, but dietary interventions are still needed to confirm findings, especially in older subjects. In the context of the MIND FoodS HUB project, this study aims to investigate the effect of a single serving of blueberry (250 g of blueberry versus a control product) in a group of older subjects (≥ 60y) through a randomized, controlled, cross-over dietary intervention trial. Specifically, the study evaluates the absorption kinetics of bioactives following the blueberries intake and the effects on markers related to oxidative stress, inflammation, and vascular function analyzed at different time points. By considering a drop-out rate estimate of 25%, at least 20 subjects will be recruited in the study. The study will provide evidence to support the potential beneficial effects of blueberry and its bioactive compounds on vascular function in a group of population more susceptible to vascular dysfunction and to the development of cardiovascular diseases. Moreover, the study will contribute the analysis of several metabolic and functional markers that can support the biological plausibility of the results obtained. Finally, the trial will provide data on the absorption and metabolism of blueberry bioactives which will be used to study their association with the different markers under study

Effects of Quercetin Metabolites on Glucose‐Dependent Lipid Accumulation in 3T3‐L1 Adipocytes

The aim of the study was to assess the effects of quercetin metabolites (QMs) on lipid accumulation in adipocytes under high-glucose and physiological-glucose concentrations and to elucidate the mechanisms involved. 3T3-L1 mature adipocytes were exposed to a physiological glucose concentration, as a model of caloric restriction (CR), or high glucose (control), with and without QMs (quercetin-3-glucuronide [Q3G] and isorhamnetin [ISOR]). Cells were treated with Q3G (0.3 and 0.6 mu mol/L) and ISOR (0.2 and 0.4 mu mol/L) for 48 h. Lipid accumulation (Oil Red O staining) and Delta glucose level (HPLC) were assessed. Under high glucose, Q3G and ISOR reduced lipid accumulation (-10.8% and -10.4%; p &lt; 0.01) and Delta glucose level (-13.6% and -14.2%; p &lt; 0.05). Under CR, QMs increased Delta glucose level (+21.6% for Q3G and +21% for ISOR; p &lt; 0.05). ISOR increased pAMPK levels under high glucose (+1.4-fold; p &lt; 0.05). Under CR, Q3G and ISOR increased pAMPK (+1.4- and +1.5-fold; p &lt; 0.05), while ISOR upregulated SIRT1 and PGC-1 alpha (+2.3- and +1.5-fold; p &lt; 0.05). Findings support, for the first time, the potential contribution of QMs, especially ISOR, in the regulation of lipid metabolism in vitro, possibly via AMPK activation. Further studies, including in vivo, are encouraged to strengthen evidence of the mechanisms observed

Wild blueberry (V. angustifolium) improves TNFα-induced cell barrier permeability through claudin-1 and oxidative stress modulation in Caco-2 cells

Increasing evidence links the impairment of intestinal permeability (IP), a feature of the intestinal barrier, to numerous dysmetabolic and dysfunctional conditions. Several host and environmental factors, including dietary factors, can negatively and/or positively affect IP. In this regard, polyphenol-rich foods including berries have been proposed as potential IP modulators. However, the exact mechanisms involved are not yet fully elucidated. The aim of the present study was to evaluate the effect of a wild blueberry (WB; V. angustifolium) powder, naturally rich in polyphenols, to affect Caco-2 cell monolayer permeability and to identify the potential mechanisms in modulating the IP process. Caco-2 cells were incubated with TNF-α (10 ng mL-1), as a pro-inflammatory stimulus, and supplemented for 24 hours with different concentrations (1 and 5 mg mL-1) of WB powder. The integrity of the intestinal cell monolayer was evaluated by measuring the transepithelial electrical resistance (TEER) and the paracellular transport of FITC-dextran. In addition, the production of the tight junction proteins, such as claudin-1 and occludin, as well as protein carbonyl and 8-hydroxy 2 deoxyguanosine, as oxidative stress markers, were quantified in the supernatant by ELISA kits. Overall, the treatment with WB powder (5 mg mL-1) mitigated the loss of Caco-2 cell barrier integrity, as documented by an increase in TEER and a reduction in FITC values. This modulation was accompanied by an upregulation of claudin-1 and a reduction of 8-OHdG. Conversely, no effect was documented for the lower concentration (1 mg mL-1) and the other IP markers, as well as oxidative stress markers analysed. In conclusion, our findings suggest a potential role of WB in the modulation of cell barrier integrity. This modulation process could be attributed to an increase in claudin-1 expression and a reduction in 8-OHdG. Further studies should be performed to corroborate the results obtained. In addition, since the effects were observed at doses of WB achievable with the diet, these findings should be substantiated also through in vivo approaches

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio