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Estimation of wine components' intake (polyphenols, alcohol, etc.) through Food Frequency Questionnaires (FFQs) may be particularly inaccurate. This paper reports the development of a deep learning (DL) method to determine red wine volume from single-view images, along with its application in a consumer study developed via a web service. The DL model demonstrated satisfactory performance not only in a daily lifelike images dataset (mean absolute error = 10 mL), but also in a real images dataset that was generated through the consumer study (mean absolute error = 26 mL). Based on the data reported by the participants in the consumer study (n = 38), average red wine volume in a glass was 114 ± 33 mL, which represents an intake of 137-342 mg of total polyphenols, 11.2 g of alcohol, 0.342 g of sugars, among other components. Therefore, the proposed method constitutes a diet-monitoring tool of substantial utility in the accurate assessment of wine components' intake., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The study determines the sustained and acute effects of a red-fleshed apple (RFA), rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an infusion from Aronia melanocarpa (AI) with an equivalent content of ACNs as RFA, on different cardiometabolic risk biomarkers in hypercholesterolemic subjects. A randomized, parallel study was performed for 6 weeks and two dose-response studies were performed at the baseline and after intervention. At 6 weeks, RFA consumption improved ischemic reactive hyperemia and decreased C-reactive protein and interleukine-6 compared to WFA consumption. Moreover, at 6 weeks, AI decreased P-selectin compared to WFA and improved the lipid profile. Three products reduced C1q, C4 and Factor B, and RFA and AI reduced C3. Although both RFA and AI have a similar ACN content, RFA, by a matrix effect, induced more improvements in inflammation, whereas AI improved the lipid profile. Anti-inflammatory protein modulation by proteomic reduction of the complement system and immunoglobulins were verified after WFA, AI and RFA consumption.

The recovery of raw materials offers an opportunity for applying the principles of circular bioeconomy. The phenolic composition of three underused wine byproducts (skin, seed, and bunch stem) was analyzed through UHPLC-QqQ-MS/MS to evaluate the intercultivar variability comparing red and white grape cultivars from La Rioja (Spain) and the influence of the winemaking, comparing conventional fermentation and carbonic maceration. We observed that the red skin, especially from Graciano, is rich in anthocyanins, whereas the white skin contains mainly phenolic acids, flavonols, and flavan-3-ols, with Maturana Blanca being the richest variety. Seeds are rich in flavan-3-ols and lignans with Maturana Blanca and Viura, respectively, the richest cultivars. Stems contain high amounts of flavan-3-ols, lignans, and stilbenes, with the red cultivars of Garnacha and Tempranillo being the richest samples. Carbonic maceration has a negative effect on the phenolic amount compared to conventional fermentation. In synthesis, we observed that each type of byproduct from red or white grape cultivars has a particular phenolic composition that can result in obtaining different ingredients with particular phenolic composition for target applications.

Onion ( Allium cepa L.) and its newly derived product "black onion" are characterised by the presence of compounds with potential bioactivity, particularly organosulfur compounds (OSCs). However, little is known about the metabolism, distribution, and excretion of these compounds as they pass through the gastrointestinal tract. This study monitored healthy subjects after an acute intake of black onion and analysed the excretion of OSCs using UHPLC-HRMS. A total of 31 OSCs were detected in urine after the acute ingestion of black onion, the main components being S -methyl-L-cysteine sulfoxide (methiin) (13.6 ± 3.9 μmol), isoalliin (12.4 ± 4.7 μmol) and S -propyl-L-cysteine (deoxypropiin) (3.1 ± 0.7 μmol). Moreover, N -acetylated metabolites of the major OSCs detected in black onion, namely, N -acetyl- S -(1-propenyl)-L-cysteine sulfoxide (NAS1PCS) and N -acetyl- S -(1-propenyl)-L-cysteine (NAS1PC), were found in urine after black onion consumption. The N -acetylation reaction takes place in the kidneys and liver, and metabolism pathways are proposed to explain the excretion of OSCs in urine. The basis of the identification of OSCs as urinary metabolites after black onion consumption is described for the first time and provides the basis for further research.

The consumption of black garlic has been related to a decreased risk of many human diseases due to the presence of phytochemicals such as organosulfur compounds (OSCs). However, information on the metabolization of these compounds in humans is limited. By means of ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), this study aims to determine the OSCs and their metabolites excreted in urine 24 h after an acute intake of 20 g of black garlic by healthy humans. Thirty-three OSCs were identified and quantified, methiin (17,954 ± 6040 nmol), isoalliin (15,001 ± 9241 nmol), S -(2-carboxypropyl)-L-cysteine (8804 ± 7220 nmol) and S-propyl-L-cysteine (deoxypropiin) (7035 ± 1392 nmol) being the main ones. Also detected were the metabolites N -acetyl- S -allyl-L-cysteine (NASAC), N -acetyl- S -allyl-L-cysteine sulfoxide (NASACS) and N -acetyl- S -(2-carboxypropyl)-L-cysteine (NACPC), derived from S -allyl-L-cysteine (SAC), alliin and S -(2-carboxypropyl)-L-cysteine, respectively. These compounds are potentially N -acetylated in the liver and kidney. The total excretion of OSCs 24 h after the ingestion of black garlic was 64,312 ± 26,584 nmol. A tentative metabolic pathway has been proposed for OSCs in humans.

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1 H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases.

In this paper, we present a method to determine the volume of wine in different types of glass liquid containers from a single-view image. The proposed model predicts red wine volume from a photograph of the glass containing the wine. Experimental results demonstrated satisfactory performance of our image-based wine measurement system, with a Mean Absolute Error lower than 10 mL . To train and evaluate our system, we introduced the WineGut_BrainUp dataset, a new dataset of glasses of wine that contains 24305 laboratory images, including a wide range of containers, volumes of wine, backgrounds, object distances, angles and lightning, with or without calibration object. The proposed methodology is a suitable analytical tool for automate measurement of red wine volume. Indeed, it has potential real life applications in diet monitoring and wine consumption studies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

The present review has analyzed the scientific literature, available in the PubMed and Scopus databases, in order to summarize the current state of diet anthocyanin research in breast cancer (BC) and colorectal cancer (CRC) animal models but also for up-to-date human studies. For CRC, 28 preclinical and 9 clinical studies were selected in line with our search query in science databases. In relation to BC, 14 preclinical and 5 clinical studies were selected. Remarkably, all the preclinical studies, to a greater or lesser degree, suggested a chemoprevention effect of anthocyanin in BC/CRC rodent models. These encouraging results from animal models are not extrapolated to the same degree to human studies where, from the similar theoretical daily doses of anthocyanins in these studies, the opposite results were reported. Nevertheless, it is worth mentioning that the anthocyanin doses in the human studies carried out recently are low if we consider the estimated exposure to anthocyanins issued by the European Food Safety Agency (EFSA) or extremely low if we consider with caution the human equivalent dose based on body surface area from the preclinical dosage regimes used. Therefore, although some clinical data has demonstrated an inverse relation between anthocyanin consumption and BC/CRC, this could, in fact, be more relevant if we increase the daily human anthocyanin dose (as observed in animal model dose-effect studies) while new toxicological data for this flavonoid subtype are brought to light., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Red-fleshed apple cultivars with an enhanced content of anthocyanins have recently attracted the interest of apple producers and consumers due to their attractive color and promising added health benefits. In this paper, we provide the first comprehensive overview of new hybrid red-fleshed apples, mainly focusing on their (poly)phenolic composition, the effect of processing, the (poly)phenolic bioavailability and the biological effects. Evidence so far from in vitro and in vivo studies supports their added beneficial effects compared to common apples on health outcomes such as cancer, cardiovascular disease, inflammation and immune function, which are mainly related to their specific (poly)phenol composition.

Sizeable scientific evidence indicates the health benefits related to phenolic compounds and dietary fiber. Various phenolic compounds-rich foods or ingredients are also rich in dietary fiber, and these two health components may interrelate via noncovalent (reversible) and covalent (mostly irreversible) interactions. Notwithstanding, these interactions are responsible for the carrier effect ascribed to fiber toward the digestive system and can modulate the bioaccessibility of phenolics, thus shaping health-promoting effects in vivo. On this basis, the present review focuses on the nature, occurrence, and implications of the interactions between phenolics and food components. Covalent and noncovalent interactions are presented, their occurrence discussed, and the effect of food processing introduced. Once reaching the large intestine, fiber-bound phenolics undergo an intense transformation by the microbial community therein, encompassing reactions such as deglycosylation, dehydroxylation, α- and β-oxidation, dehydrogenation, demethylation, decarboxylation, C-ring fission, and cleavage to lower molecular weight phenolics. Comparatively less information is still available on the consequences on gut microbiota. So far, the very most of the information on the ability of bound phenolics to modulate gut microbiota relates to in vitro models and single strains in culture medium. Despite offering promising information, such models provide limited information about the effect on gut microbes, and future research is deemed in this field., (© 2022 The Authors. Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups ( n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observed that involved different bioactive components, and inflammatory proteins were reduced.

Grapevine cultivar and clone genotype is an important factor in the phenolic composition of wine. In this study, a new intense dark black berry color variant of Tempranillo, known as Tempranillo negro or VN21, is described. A targeted chromatographic approach based on UHPLC-QqQ-MS/MS was used to study the anthocyanins and non-colored phenols of the grape berry (skin and seeds) and wine. RJ43, one of the most cultivated clones in D.O.Ca. Rioja (Spain), was analyzed for comparison. Results suggest that the unique color of the grape skin in Tempranillo negro could be explained by higher concentrations of peonidin and cyanidin derivatives. This genotype accumulated anthocyanins in the seeds. Those differences in the berry were enhanced in the VN21 wines, which displayed notably higher concentrations of anthocyanins, and significantly increased contents of proanthocyanidins and stilbenes. This study exemplifies the application of phenol chromatographic analyses of spontaneous somatic variants to grapevine clonal selection., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: It has been reported that the phenolic metabolite 3'-methoxycinnamic acid-4'-sulfate generated from 5-O-caffeoylquinic acid may have potential benefits in human health. However, the variation in 3'- and 4'-methylation of 3',4'-dihydroxycinnamic acid and its impact on the yield of this sulfate metabolite is unclear and has been poorly studied., Methods and Results: To address this aim, the excreted 3'-methoxy and 4'-methoxy metabolites in urine samples (24-h) are determined in 14 volunteers after an acute intake of 80 g of red-fleshed apple (RFA) or white-fleshed apple (WFA). These methoxy metabolites are also determined in the same volunteers in a second acute intake after a 6-week sustained consumption of the same products., Conclusion: Seven 3'-methoxy and seven 4'-methoxy metabolites are determined, i.e., the free cinnamic and corresponding phenylpropanoic acid, plus their sulfate, glucuronide, and glycine conjugates. In only six volunteers, five females and one male, is 4'-methylation preferred over 3'-methylation, but it is observed that an individual's 3'- : 4'-methylation ratio can change over time, and that the yield of 3'-methoxycinnamic acid-4'-sulfate is extremely variable, ranging from undetectable to 71% of the total C 6 -C 3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

The Mediterranean diet (MD) has become a dietary pattern of reference due to its preventive effects against chronic diseases, especially relevant in cardiovascular diseases (CVD). Establishing an objective tool to determine the degree of adherence to the MD is a pending task and deserves consideration. The central axis that distinguishes the MD from other dietary patterns is the choice and modality of food consumption. Identification of intake biomarkers of commonly consumed foods is a key strategy for estimating the degree of adherence to the MD and understanding the protective mechanisms that lead to a positive impact on health. Throughout this review we propose potential candidates to be validated as MD adherence biomarkers, with particular focus on the metabolites derived from the phenolic compounds that are associated with the consumption of typical Mediterranean plant foods. Certain phenolic metabolites are good indicators of the intake of specific foods, but others denote the intake of a wide-range of foods. For this, it is important to emphasise the need to increase the number of dietary interventions with specific foods in order to validate the biomarkers of MD adherence. Moreover, the identification and quantification of food phenolic intake biomarkers encouraging scientific research focuses on the study of the biological mechanisms in which polyphenols are involved.

Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function., Methods and Results: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity., Conclusion: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats., (© 2021 Wiley-VCH GmbH.)

Background & Aims: The integrity of the intestinal barrier in the diseased is key to prevent further complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals., Methods: The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools., Results: From 1241 articles, 14 studies were included. In animals, oral resveratrol (n = 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n = 2), curcumin (n = 1), genistein (n = 1), chlorogenic acid (n = 1), grape pomace (n = 1), olive leaf (n = 1) or cranberry extract (n = 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-α, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia., Conclusions: The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC., Competing Interests: Conflict of interest The authors have declared no conflicts of interest. Complete Declaration of Interest forms for each author has been uploaded at the time of manuscript submission., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Protein functional interactions could explain the biological response of secoiridoids (SECs), main phenolic compounds in virgin olive oil (VOO). The aim was to assess protein-protein interactions (PPIs) of the aorta gap junction alpha-1 (GJA1) and the heart peptidyl-prolyl cis-trans isomerase (FKBP1A), plus the phosphorylated heart proteome, to describe new molecular pathways in the cardiovascular system in rats using nanoliquid chromatography coupled with mass spectrometry. PPIs modified by SECs and associated with GJA1 in aorta rat tissue were calpain, TUBA1A, and HSPB1. Those associated with FKBP1A in rat heart tissue included SUCLG1, HSPE1, and TNNI3. In the heart, SECs modulated the phosphoproteome through the main canonical pathways PI3K/mTOR signaling (AKT1S1 and GAB2) and gap junction signaling (GAB2 and GJA1). PPIs associated with GJA1 and with FKBP1A, the phosphorylation of GAB2, and the dephosphorylation of GJA1 and AKT1S1 in rat tissues are promising protein targets promoting cardiovascular protection to explain the health benefits of VOO.

The present study evaluated the impact of different thermal (infrared-drying, hot air-drying and purée pasteurization) and non-thermal (freeze-drying) processing technologies on red-fleshed apple (poly)phenolic compounds. We further investigated the processing effect on the (poly)phenol bioavailability in a crossover postprandial study where three subjects consumed three apple products (freeze-dried snack, hot air-dried snack and pasteurized purée). (Poly)phenolic compounds present in the apple products and their biological metabolites in urine were analyzed using liquid chromatography coupled to mass spectrometry (UPLC-MS/MS). When comparing different processes, infrared-drying caused important losses in most of the apple (poly)phenolics, while hot air-drying and purée pasteurization maintained approximately 83% and 65% of total (poly)phenols compared with the freeze-dried snack, respectively. Anthocyanins in particular were degraded to a higher extent, and hot air-dried apple and pasteurized purée maintained respectively 26% and 9% compared with freeze-dried apple snack. The acute intake showed that pasteurized purée exhibited the highest (poly)phenol bioavailability, followed by hot air-drying and freeze-dried snack, highlighting the impact of processing on (poly)phenols absorption. In conclusion, for obtaining affordable new red-fleshed apple products with enhanced (poly)phenol bioavailability, purée pasteurization and hot air-drying represent viable techniques. However, to obtain a red-fleshed apple snack with high anthocyanin content, freeze-drying is the technique that best preserves them.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual's oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described., Competing Interests: The authors declare no conflict of interest

Colorectal cancer (CRC) is the fourth cancer with the most new cases reported in 2018 worldwide. Consumption of fruit and vegetables is a protective factor against the risk of CRC. Beyond this, flavonoids could orchestrate these healthy effects. Apart from containing the typical apple flavonoids, red-fleshed apples also contain anthocyanins, mainly cyanidin-3-O-galactoside (Cy3Gal). Through an azoxymethane rat carcinogenesis model, a study was carried out in order to assess the possible protective effects of apple polyphenols, with special attention to anthocyanins. In addition, apart from negative and positive controls, a group with chemotherapy with 5-fluorouracil (5FU) was included to compare their performance against the output collected from the animal treatments with white-fleshed apple (WF), red-fleshed apple (RF) and Cy3Gal (AE). Although the 5FU group presented the best performance towards aberrant crypt foci (ACF) inhibition (70.1%), rats fed with white-fleshed apples ('Golden Smoothee') were able to achieve 41.3% ACF inhibition, while none of the challenged treatments (WF, RF and AE) suffered mucin depletion in their colonocytes. Expression changes of 17 genes related to CRC were assessed. In detail, the ACF inhibition phenotype detected in 5FU and WF groups could be explained through the expression changes detected in the apoptosis-related genes of Aurka, p53 and Cox2. Moreover, in the apple consumption groups (WF and RF), a reduced protein expression of matrix metalloproteinases with gelatinase activity (MMP-2 and 9) was detected. Overall, our study suggests an effect of apple polyphenols and apple anthocyanin Cy3Gal against colon carcinogenesis, retarding/diminishing the appearance of the precancerous markers studied., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The analysis of the fat-soluble vitamins A and E and lipid micronutrients in blood, such as carotenoids, is an important parameter to monitor the micronutrient status in humans. Although the potential of dried blood spot (DBS) cards, the use of this technique for blood sampling and subsequent analysis of these fat-soluble micronutrients has been poorly or not studied. An analytical method based on DBS cards (FTA® DMPK-A) combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been developed and validated for the determination of carotenoids (lutein, zeaxanthin, β-cryptoxanthin and β-carotene), tocopherols (α-tocopherol, γ-tocopherol and δ-tocopherol) and all-trans-retinol in human blood. Under optimum DBS card extraction conditions, the extraction recoveries of the studied compounds were higher than 72%, the sample matrix effect lower than 17%, and the detection limits at hundred nM concentration levels. The developed method was applied to the analysis of human blood, and the concentration ranges obtained fell within the expected ranges previously reported in healthy adults. Moreover, the influence of hematocrit effect was investigated in a range of 25-55% in order to compare the obtained results to those reported in the literature for the analysis of plasma samples. This method represents an improvement over current techniques reported in the literature due to the use of a non-invasive blood collection method, and moreover, this methodology was for the first time 1) validated for the analysis of all-trans-retinol, tocopherols and carotenoids, and 2) applied for the determination of tocopherols in human blood samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [ 3 H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassette a1 . Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.

Scope: We investigate the postprandial modulation of cardiovascular-related microRNAs elicited by extra virgin olive oil (EVOOs) containing different levels of their own polyphenols., Methods and Results: It is randomized, postprandial, parallel, double-blind study. Twelve healthy participants consumed 30 mL of EVOO containing low (L-EVOO; 250 mg total phenols kg -1 of oil), medium (M-EVOO; 500 mg total phenols kg -1 of oil), and high (H-EVOO; 750 mg total phenols kg -1 of oil) enriched EVOOs. Postprandial plasma microRNAs levels are analyzed by real-time quantitative PCR. The results show that L-EVOO intake is associated with decreased let-7e-5p and miR-328a-3p levels and increased miR-17-5p and miR-20a-5p, concentrations. M-EVOO decreases plasma let-7e-5p and increases miR-17-5p, miR-20a-5p, and miR-192-5p levels. Finally, H-EVOO decreases let-7e-5p, miR-10a-5p, miR-21-5p, and miR-26b-5p levels., Conclusion: During the postprandial state, the levels of let-7e-5p decrease with EVOO regardless of polyphenol content suggesting a general response to the fatty acid composition of EVOO or/and the presence of at least 250 mg polyphenol kg -1 olive oil. Moreover, the miR-17-92 cluster increases by low and medium polyphenol content suggesting a role in fatty acid metabolism and nutrient sensing. Thus, postprandial modulation of circulating microRNAs levels could be a potential mechanism for the cardiovascular benefits associated with EVOO intake., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Berries are rich sources of (poly)phenols which have been associated with the prevention of cardiovascular diseases in animal models and in human clinical trials. Recently, a berry enriched diet was reported to decrease blood pressure and attenuate kidney disease progression on Dahl salt-sensitive rats. However, the relationship between kidney function, metabolism and (poly)phenols was not evaluated. We hypothesize that berries promote metabolic alterations concomitantly with an attenuation of the progression of renal disease. For that, kidney and urinary metabolomic changes induced by the berry enriched diet in hypertensive rats (Dahl salt-sensitive) were analyzed using liquid chromatography (UPLC-MS/MS) and 1 H NMR techniques. Moreover, physiological and metabolic parameters, and kidney histopathological data were also collected. The severity of the kidney lesions promoted in Dahl rats by a high salt diet was significantly reduced by berries, namely a decrease in sclerotic glomeruli. In addition, was observed a high urinary excretion of metabolites that are indicators of alterations in glycolysis/gluconeogenesis, citrate cycle, and pyruvate metabolism in the salt induced-hypertensive rats, a metabolic profile counteracted by berries consumption. We also provide novel insights that relates (poly)phenols consumption with alterations in cysteine redox pools. Cysteine contribute to the redox signaling that is normally disrupted during kidney disease onset and progression. Our findings provide a vision about the metabolic responses of hypertensive rats to a (poly)phenol enriched diet, which may contribute to the understanding of the beneficial effects of (poly)phenols in salt-induced hypertension., Competing Interests: Declaration of competing interest The authors have declared no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.

Diets rich in (poly)phenols are associated with a reduced reduction in the incidence of cardiovascular disorders. While the absorption and metabolism of (poly)phenols has been described, it is not clear how their metabolic fate is affected under pathological conditions. This study evaluated the metabolic fate of berry (poly)phenols in an in vivo model of hypertension as well as the associated microbiota response. Dahl salt-sensitive rats were fed either a low-salt diet (0.26% NaCl) or a high-salt diet (8% NaCl), with or without a berry mixture (blueberries, blackberries, raspberries, Portuguese crowberry and strawberry tree fruit) for 9 weeks. The salt-enriched diet promoted an increase in the urinary excretion of berry (poly)phenol metabolites, while the abundance of these metabolites decreased in faeces, as revealed by UPLC-MS/MS. Moreover, salt and berries modulated gut microbiota composition as demonstrated by 16S rRNA analysis. Some changes in the microbiota composition were associated with the high-salt diet and revealed an expansion of the families Proteobacteria and Erysipelotrichaceae . However, this effect was mitigated by the dietary supplementation with berries. Alterations in the metabolic fate of (poly)phenols occur in parallel with the modulation of gut microbiota in hypertensive rats. Thus, beneficial effects of (poly)phenols could be related with these interlinked modifications, between metabolites and microbiota environments., Competing Interests: The authors declare no conflict of interest.

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues. Following the bioinformatic analyses of publicly available data from a selection of in vivo studies involving HT-supplementation, we selected differentially expressed lipid metabolism-related genes and proteins common to more than one study, for validation in rodent liver samples from the entire selection. Four miRNAs (miR-802-5p, miR-423-3p, miR-30a-5p, and miR-146b-5p) responded to HT supplementation. Of note, miR-802-5p was commonly regulated in the liver and intestine. Our premise was that, in an organ crucial for lipid metabolism such as the liver, consistent modulation should be found for a specific target of HT even if different doses and duration of HT supplementation were used in vivo. Even though our results show inconsistency regarding differentially expressed lipid metabolism-related genes and proteins across studies, we found Fgf21 and Rora as potential novel targets of HT. Omics approaches should be fine-tuned to better exploit the available databases.

The consumption of antioxidant-rich foods such as virgin olive oil (VOO) promotes high-density lipoprotein (HDL) anti-atherogenic capacities. Intake of functional VOOs (enriched with olive/thyme phenolic compounds (PCs)) also improves HDL functions, but the gene expression changes behind these benefits are not fully understood. Our aim was to determine whether these functional VOOs could enhance the expression of cholesterol efflux-related genes. In a randomized, double-blind, crossover, controlled trial, 22 hypercholesterolemic subjects ingested for three weeks 25 mL/day of: (1) a functional VOO enriched with olive oil PCs (500 mg/kg); (2) a functional VOO enriched with olive oil (250 mg/kg) and thyme PCs (250 mg/kg; FVOOT), and; (3) a natural VOO (olive oil PCs: 80 mg/kg, control intervention). We assessed whether these interventions improved the expression of cholesterol efflux-related genes in peripheral blood mononuclear cells by quantitative reverse-transcription polymerase chain reactions. The FVOOT intervention upregulated the expression of CYP27A1 ( P = 0.041 and P = 0.053, versus baseline and the control intervention, respectively), CAV1 ( P = 0.070, versus the control intervention), and LXRβ, RXRα, and PPARβ/δ ( P = 0.005, P = 0.005, and P = 0.038, respectively, relative to the baseline). The consumption of a functional VOO enriched with olive oil and thyme PCs enhanced the expression of key cholesterol efflux regulators, such as CYP27A1 and nuclear receptor-related genes., Competing Interests: The authors declare no conflict of interest.

Scope: The antithrombotic effects of resveratrol (RV) and its derivatives remain unknown. The objective is to evaluate the modulatory effects of RV, its glucoside form, piceid, and its biological metabolites (RV-3-O-β-d-glucuronide, RV-4'-O-d-glucuronide, and RV-3-O-sulfate) on tissue factor (TF). Moreover, the endothelial metabolism of RV is assessed., Methods and Results: Human aortic endothelial cells (HAECs) are incubated with trans-piceid, trans-RV, or their biological metabolites and stimulated with tumor necrosis factor-α (TNF-α). TF activity, protein levels, and mRNA expression are determined in cell lysates. Moreover, RV conjugation (phase-II-metabolism) to its sulfated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) are also assessed in cell lysates and culture media. RV decreased TF activity, protein levels, and mRNA expression, whereas piceid and RV metabolites (RVmet) had no effects. RV-3-O-sulfate was the main metabolite generated in the endothelium, while RVmet are deconjugated to free RV. Isomerization of trans-RV and its trans-metabolites to their cis-forms is observed., Conclusions: RV exerts antithrombotic effects by modulating TF. RVmet and piceid does not exert this effect. However, the capacity of endothelial cells to deconjugate RVmet to free RV indicates that RVmet function as an endothelial reservoir for RV regeneration, thus, contributing to the antithrombotic effects of RV., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Colorectal cancer (CRC), also known as colon cancer, is the third most common form of cancer worldwide in men and the second in women and is characterized by several genetic alterations, among them the expression of several genes. 1,2-dimethylhydrazine (DMH) and its metabolite azoxymethane (AOM) are procarcinogens commonly used to induce colon cancer in rats (DMH/AOM rat model). This rat model has been used to study changes in mRNA expression in genes involved in this pathological condition. However, a lack of proper detailed PCR primer design in the literature limits the reproducibility of the published data. The present study aims to design, optimize and validate the qPCR, in accordance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines, for seventeen genes commonly used in the DMH/AOM rat model of CRC ( Apc, Aurka, Bax, Bcl2, β -catenin, Ccnd1, Cdkn1a, Cox2, Gsk3beta, IL-33, iNOs, Nrf2, p53, RelA, Smad4, Tnfα and Vegfa ) and two reference genes ( Actb or β - actin and B2m ). The specificity of all primer pairs was empirically validated on agarose gel, and furthermore, the melting curve inspection was checked as was their efficiency (%) ranging from 90 to 110 with a correlation coefficient of r 2  > 0.980. Finally, a pilot study was performed to compare the robustness of two candidate reference genes., Competing Interests: The authors declare there are no competing interests.

Scope: The application of dried blood spot (DBS) cards for the study in human blood of dietary polyphenol bioavailability has been poorly studied., Methods and Results: An analytical method based on blood sampling with DBS cards combined with LC-MS/MS has been developed and validated. To test the method validation, the phenolic metabolites are determined in human blood and plasma obtained after an acute intake of a red-fleshed apple snack in ten volunteers. Capillary blood by finger prick is compared to venous blood by venipuncture and whole blood is also compared to their corresponding venous plasma samples. Moreover, the venous plasma results using DBS cards are compared to those obtained by microElution solid phase extraction (µSPE). The main phenolic metabolites detected in blood and plasma samples are phloretin glucuronide, dihydroxyphenylpropionic acid sulphate, (methyl) catechol sulphate, catechol glucuronide, and hydroxyphenyl-γ-valerolactone glucuronide. No significant differences are observed between capillary blood, venous blood, and plasma samples using DBS, and neither between plasma samples analyzed by DBS or µSPE., Conclusions: Finger-prick blood sampling based on DBS appears to be a suitable alternative to the classic invasive venipuncture for the determination of circulating phenolic metabolites in nutritional postprandial studies., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The main objective of this study was to evaluate the impact of the season on the apple phytochemical composition (phenolic compounds, triterpenes, and organic and ascorbic acids). For this proposal, four red-fleshed and five white-fleshed apple varieties from two consecutive seasons (2015 and 2016) were studied. A significant interaction with the season in some compounds was observed. The total phenolic content in the apple flesh from 2015 was higher than that from 2016 probably related with the lower rainfall during the harvest period in 2015 that could have favored hydric stress in the apple trees. The impact of the season on the apple skin was different. The 2016 season was characterized by higher maximum and minimum temperatures resulting in a higher content of flavonols, triterpenes, and organic acids. Anthocyanin concentration in both the flesh and skin of the red-fleshed apples showed no clear relationship to the season, and each variety showed an individual pattern.

Among cereals, barley ( Hordeum vulgare L.) is notable for its high content of bioactives such as β-glucan and phenolic compounds, but it is not used as widely in human nutrition as wheat. To compare the impact of food formulation and processing on barley bioactives, crackers, cookies, and fresh pasta were prepared combining wheat and barley flour. After quantification of β-glucan and PCs in the barley flour and barley-based products, their behavior during in vitro gastrointestinal digestion and colonic fermentation was studied. The β-glucan and PCs were not drastically affected by processing. The amount of bioaccessible compounds after gastrointestinal digestion was lower than the amount retained in the undigested fraction. After in vitro colonic fermentation, β-glucan was mainly metabolized to acetic and propionic acids and PCs to phenylpropionic and phenylacetic acids. Based on the results of the study, the daily ingestion of barley-based foods may contribute to the intake of beneficial bioactive compounds.

Scope: The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work., Methods and Results: VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg -1 ), FVOO (500 mg kg -1 ), and FVOOT (500 mg kg -1 ; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources., Conclusion: Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the present study, 27 barley genotypes (Hordeum vulgare L.) grown in two geographic origins (Czech Republic and Spain) were analysed for their contents of β-glucan, tocols and phenolic compounds (free and bound). The samples included hulled, hull-less and coloured genotypes. The results showed that concentrations of β-glucan range from 2.40 to 7.42g/100g. Total tocol content of the barley samples ranged between 39.9 and 81.6μg/g. A total of 64 compounds were identified in the barley samples. These included 19 phenolic acids and aldehydes, 9 flavan 3-ols, 9 flavone glycosides, and 27 anthocyanins. The results showed a wide range of phenolic concentrations in the barley samples, highlighting the presence of considerable amounts of anthocyanins in purple barley genotypes. In synthesis, barley should be considered a good source of bioactive components, especially because of the broad spectrum of phytochemicals with potential health benefits besides the soluble fibre (β-glucan)., (Copyright © 2017. Published by Elsevier Ltd.)

A preliminary study to evaluate the effect of dietary supplementation with olive phenols (oleuropein, hydroxytyrosol and secoiridoids), thyme phenols and a combination of these (5 mg per kg rat weight per day) on the α-tocopherol concentrations in the muscle and liver of healthy adult Wistar rats over 21 days was conducted. In addition, the excretion of α-tocopherol through the faeces was examined. The results demonstrated that the diet supplemented with some phenolic compounds of olive and thyme increased α-tocopherol (P < 0.05) in the liver of female rats, although the α-tocopherol content in the diet of all groups was identical. In addition, a synergic effect between the olive phenols and thyme was observed. Therefore, our study indicates a protective effect of olive and thyme phenols supplemented in the diet on α-tocopherol, resulting in a higher concentration of endogenous α-tocopherol in the rat liver.

Hydroxytyrosol (HT) and its derivatives represent the minor components of Virgin Olive Oil (VOO) that are of great interest for their pharmacological properties and among the most widely researched natural antioxidant compounds. In this review, the occurrence and metabolic fate of HT and its precursors are presented prior to discussing its beneficial effects on health. Bioavailability studies show that the metabolites detected in plasma depend on the model used (animal or human), the HT source (simple molecule or complex precursors) and the dose administered. However, in all cases HT sulphate appears to be the most ubiquitous metabolite in biofluids and it seems probable that it is responsible to a great extent for HT biological effects. Epidemiological evidence of HT and its derivatives against such lifestyle-associated pathologies as cancer, cardiovascular and neurodegenerative diseases is reviewed together with the newest perspectives on the mechanisms of action based on in-vitro and animal studies. According to the reviewed data, HT and its precursors could have the potential clinical use in cardiovascular diseases; more epidemiological data is needed to demonstrate their neurodegenerative diseases and cancer prevention., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

At present, high-density lipoprotein (HDL) function is thought to be more relevant than HDL cholesterol quantity. Consumption of olive oil phenolic compounds (PCs) has beneficial effects on HDL-related markers. Enriched food with complementary antioxidants could be a suitable option to obtain additional protective effects. Our aim was to ascertain whether virgin olive oils (VOOs) enriched with (a) their own PC (FVOO) and (b) their own PC plus complementary ones from thyme (FVOOT) could improve HDL status and function. Thirty-three hypercholesterolemic individuals ingested (25 ml/day, 3 weeks) (a) VOO (80 ppm), (b) FVOO (500 ppm) and (c) FVOOT (500 ppm) in a randomized, double-blind, controlled, crossover trial. A rise in HDL antioxidant compounds was observed after both functional olive oil interventions. Nevertheless, α-tocopherol, the main HDL antioxidant, was only augmented after FVOOT versus its baseline. In conclusion, long-term consumption of phenol-enriched olive oils induced a better HDL antioxidant content, the complementary phenol-enriched olive oil being the one which increased the main HDL antioxidant, α-tocopherol. Complementary phenol-enriched olive oil could be a useful dietary tool for improving HDL richness in antioxidants., (Copyright © 2017. Published by Elsevier Inc.)

Scope: Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion., Methods and Results: Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity., Conclusions: HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)