A (poly)phenol-rich diet reduces serum and faecal calprotectin in older adults with increased intestinal permeability: the MaPLE randomised controlled trial.

BACKGROUND: Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses. METHODS: A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline. RESULTS: Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction. CONCLUSIONS: Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation. TRIAL REGISTRATION: 28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981 .

Berry Dietary Interventions in Metabolic Syndrome: New Insights.

Metabolic Syndrome (MetS) is characterized by a group of dysmetabolic conditions, including abdominal obesity, dyslipidemia, glucose intolerance and/or insulin resistance, and hypertension. Generally, MetS is accompanied by an exacerbation of oxidative stress, inflammation, and vascular dysfunction. Increasing evidence suggests that berries and berry bioactives could play a potential role in the prevention and mitigation of the risk factors associated with MetS. The present systematic review summarizes the more recently available evidence deriving from human intervention studies investigating the effect of berries in subjects with at least three out of five MetS parameters. The PubMed, Scopus, and Embase databases were systematically searched from January 2010 until December 2022. A total of 17 human intervention trials met the inclusion criteria. Most of them were focused on blueberry (n = 6), cranberry (n = 3), and chokeberry (n = 3), while very few or none were available for the other berries. If considering MetS features, the main positive effects were related to lipid profile (low and high-density lipoproteins, cholesterol, and triglycerides) following blueberries and chokeberries, while conflicting results were documented for anthropometric parameters, blood pressure, and fasting blood glucose levels. Other markers analyzed within the studies included vascular function, oxidative stress, and inflammation. Here, the main positive effects were related to inflammation with a reduction in interleukin 6 and tumor necrosis factor-alpha following the intake of different berries. In conclusion, although limited, the evidence seems to support a potential role for berries in the modulation of lipid profile and inflammation in subjects with MetS. Furthermore, high-quality intervention trials are mandatory to demonstrate the role of berries in reducing risk factors for MetS and related conditions. In the future, such a demonstration could bring the adoption of berries as a potential dietary strategy to prevent/counteract MetS and related risk factors.

Processing and Nutritional Quality of Breakfast Cereals Sold in Italy: Results from the Food Labelling of Italian Products (FLIP) Study.

This study aimed to compare the level of processing (as assessed by the NOVA classification) and the nutritional quality (as assessed by nutrition values, Nutri-Score and NutrInform battery) of breakfast cereals currently on the Italian market. A total of 349 items were found, mostly belonging to the NOVA 4 group (66.5%) and to Nutri-Score C and A (40% and 30%, respectively). The NOVA 4 products showed the highest energy, total fat, saturates, and sugar content per 100 g and had the highest number of items with Nutri-Score C (49%) and D (22%). Conversely, NOVA 1 products had the highest content of fibre and protein, the lowest amounts of sugars and salt, and 82% of them were Nutri-Score A, while few Nutri-Score B and C were found. Differences were attenuated when products were compared for their NutrInform battery, with NOVA 4 items showing only slightly fuller batteries for saturated fats, sugar, and salt than NOVA 1 and NOVA 3 products. Overall, these results suggest that the NOVA classification partially overlaps with systems based on the nutritional quality of foods. The lower nutritional quality of NOVA 4 foods may at least partially explain the association found between the consumption of ultra-processed foods and the risk of chronic diseases.

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.

Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects.

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies.

Nut and legume consumption and human health: an umbrella review of observational studies.

Consumption of nuts and legumes has been associated with several health benefits. The aim of this study was to systematically review existing meta-analyses of observational studies on nut and legume intake and non-communicable diseases, and assess the level of evidence. Out of the six meta-analyses focussed on legume and 15 on nut intake, a possible association with decreased risk of colorectal adenoma and coronary heart disease was found for higher legume consumption, and a decreased risk of cardiovascular and cancer mortality, colon cancer, hypertension and ischaemic stroke for higher nut consumption. The association between legume consumption and cardiovascular diseases (CVDs), as well as nut consumption and risk of cancer, CVD incidence and all-cause mortality, was deemed as "limited" due to heterogeneity between results and/or potential confounding factors. General benefit towards better health can be observed for nut and legume consumption. Further studies are needed to better elucidate potential confounding factors.

A Review of Registered Clinical Trials on Dietary (Poly)Phenols: Past Efforts and Possible Future Directions.

In recent years, the increasing number of studies on polyphenol demonstrates the efforts in elucidating the potential role of these bioactives on human health. This study reviews the main topics and characteristics of clinical trials on polyphenols registered over the last 20 years, in order to track past and current efforts as well as to highlight the main research gaps in this field. The review was conducted by collecting trials registered in ClinicalTrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) registry. Overall, 750 clinical trials were selected and included in the final evaluation. Most of the trials were performed on extracts or pure compounds followed by studies conducted on polyphenol-rich foods, in particular berries. A total of 520 clinical trials focused on health effects, 55 on bioavailability, and 175 on both. Regarding outcomes, 139 registered intervention studies had the lipid profile and blood pressure as primary outcomes. The overview provided by this analysis also emphasizes the emerging interest in new outcomes related to polyphenols intervention such as microbiota composition and the evaluation of inter-individual variability in response to the intake of polyphenols. Our review underlines the need of further trials covering unexplored or debated research aspects and provides insights for the design and development of future intervention studies and related research areas.

Absorption, Pharmacokinetics, and Urinary Excretion of Pyridines After Consumption of Coffee and Cocoa-Based Products Containing Coffee in a Repeated Dose, Crossover Human Intervention Study.

SCOPE: The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa-based products containing coffee (CBPCC), considering different patterns of consumption. METHODS AND RESULTS: In a three-arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one-month treatment, blood and urine samples are collected for 24 h. Trigonelline, N-methylpyridinium, N-methylnicotinamide, and N-methyl-4-pyridone-5-carboxamide are quantified. Trigonelline and N-methylpyridinium absorption curves and 24-h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter-subject variability due to sex and smoking is assessed, showing sex-related differences in the metabolism of trigonelline and smoking-related ones for N-methylpyridinium. CONCLUSION: The daily exposure to coffee pyridines after consumption of different coffee dosages in a real-life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee-derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions.

Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects.

The evaluation of food intake in older subjects is crucial in order to be able to verify adherence to nutritional recommendations. In this context, estimation of the intake of specific dietary bioactives, such as polyphenols, although particularly challenging, is necessary to plan possible intervention strategies to increase their intake. The aims of the present study were to: (i) evaluate the nutritional composition of dietary menus provided in a residential care setting; (ii) estimate the actual intake of nutrients and polyphenols in a group of older subjects participating in the MaPLE study; and (iii) investigate the impact of an eight-week polyphenol-rich dietary pattern, compared to an eight-week control diet, on overall nutrient and polyphenol intake in older participants. The menus served to the participants provided ~770 mg per day of total polyphenols on average with small variations between seasons. The analysis of real consumption, measured using weighed food diaries, demonstrated a lower nutrient (~20%) and polyphenol intake (~15%) compared to that provided by the menus. The feasibility of dietary patterns that enable an increase in polyphenol intake with putative health benefits for age-related conditions is discussed, with a perspective to developing dietary guidelines for this target population.

Programa de educação em saúde melhora indicadores de autocuidado em diabetes e hipertensão / El programa de educación en salud mejora los indicadores de autocuidado en diabetes e hipertensión / Health education program improves self-care indicators in diabetes and hypertension

Dentre as doenças crônicas não transmissíveis, a hipertensão arterial sistêmica (HAS) e o diabetes mellitus (DM) são as mais frequentes e constituem um problema de saúde mundial. Diante da necessidade de implantação de programas de autocuidado voltados para essas doenças, o trabalho tem como objetivo validar um programa de autocuidado para pacientes diabéticos e hipertensos. Trata-se de um estudo de coorte prospectivo de uma população de 100 indivíduos que estavam em sala de espera. A coleta dos dados foi realizada por meio de questionários sobre diferentes temas, aplicados nos encontros, para avaliar o conhecimento dos pacientes no pré e no pós-teste. Somente algumas questões específicas de cada tema não apresentaram diferença significativa entre o pré e o pós-teste. No entanto, todos os temas abordados apresentaram incremento de conhecimento no pós-teste. Sendo assim, pode-se validar este programa de cuidado para pacientes diabéticos e hipertensos, pois promove incremento de conhecimento para os pacientes.

Among chronic non-transmissible diseases, systemic arterial hypertension (SAH) and diabetes mellitus (DM) are the most frequent and constitute a global health problem. In view of the need to implement self-care programs about these diseases, the objective of this study is to validate a self-care program for diabetic and hypertensive patients. It is a prospective cohort study of a population of 100 individuals who were in the waiting room. The data collection was done through questionnaires about different topics, that were applied in the meetings, to evaluate the knowledge of patients in the pretest and posttest. Only a few specific questions of each theme did not present a significant difference between the pretest and posttest. However, all the themes addressed presented posttest knowledge increment. Therefore, this self-care program can be validated for diabetic and hypertensive patients, because it promotes an increase of knowledge for these patients.

Entre las enfermedades crónicas no transmisibles, hipertensión arterial sistémica (HAS) y la diabetes mellitus (DM) son las más frecuentes y constituyen un problema de salud mundial. Ante la necesidad de implantación de programas de autocuidado orientados a estas enfermedades, el trabajo tiene como objetivo validar un programa de autocuidado para pacientes diabéticos e hipertensos. Se trata de un estudio de cohorte prospectiva de una población de 100 individuos que estaban en la sala de espera. La recolección de los datos se realizó a través de cuestionarios sobre diferentes temas, aplicados en los encuentros, para evaluar el conocimiento de los pacientes en el pre-teste y en el post-test. Sólo algunas cuestiones específicas de cada tema no presentaron diferencia significativa entre el pre-test y el post-test. Sin embargo, todos los temas abordados presentaron incremento de conocimiento en el post-test. Por lo tanto, se puede validar este programa de autocuidado para pacientes diabéticos e hipertensos, pues promueve incremento de conocimiento para los pacientes.

Role of berries in vascular function: a systematic review of human intervention studies.

CONTEXT: Berries are a source of polyphenols with recognized health-promoting activities. Several studies suggest that consumption of berries may improve vascular function. OBJECTIVE: The aim of this systematic review is to provide evidence of short- and long-term benefits of berries on outcomes of vascular function. DATA SOURCES: Human intervention studies were collected from PubMed and Scopus databases. STUDY SELECTION: Studies were eligible if they investigated the effects of acute or chronic berry consumption on one or more markers of vascular function in humans and provided a characterization of the berry polyphenolic content. Only randomized controlled trials were included, and studies were excluded if berries were combined with other foods. DATA EXTRACTION: After selection, 22 randomized controlled trials were included and analyzed, most of which were performed in healthy individuals or patients with cardiovascular risk factors. RESULTS: The overall results seem to suggest a protective role of berries in vascular function, likely dependent on the time of exposure, the type and dose of berry, and the biomarkers analyzed. Flow-mediated dilation and reactive hyperemia index (markers of vascular reactivity) improved following short-term interventions, while pulse wave velocity and augmentation index (markers of arterial stiffness) improved only after medium- to long-term intervention. CONCLUSIONS: Current evidence suggests that berries, at physiological relevant doses, may have a role in the modulation of vascular function and stiffness. High-quality human intervention trials are encouraged in order to strengthen these findings and to better elucidate the mechanisms involved in such modulation.

Acute Intake of a Grape and Blueberry Polyphenol-Rich Extract Ameliorates Cognitive Performance in Healthy Young Adults During a Sustained Cognitive Effort.

Despite an increasing level of evidence supporting the individual beneficial effect of polyphenols on cognitive performance, information related to the potential synergistic action of these phytonutrients on cognitive performance during a prolonged cognitive effort is currently lacking. This study investigated the acute and sustained action of a polyphenols-rich extract from grape and blueberry (PEGB), on working memory and attention in healthy students during a prolonged and intensive cognitive effort. In this randomised, cross-over, double blind study, 30 healthy students consumed 600 mg of PEGB or a placebo. Ninety minutes after product intake, cognitive functions were assessed for one hour using a cognitive demand battery including serial subtraction tasks, a rapid visual information processing (RVIP) task and a visual analogical scale. Flow-mediated dilation (FMD) and plasma flavan-3-ols metabolites quantification were also performed. A 2.5-fold increase in serial three subtraction variation net scores was observed following PEGB consumption versus placebo (p < 0.001). A trend towards significance was also observed with RVIP percentage of correct answers (p = 0.058). No treatment effect was observed on FMD. Our findings suggest that consumption of PEGB coupled with a healthy lifestyle may be a safe alternative to acutely improve working memory and attention during a sustained cognitive effort.

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790.

Dietary Polyphenol Intake, Blood Pressure, and Hypertension: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Dietary polyphenols, including flavonoids, have been the focus of major recent attentions due to their wide content in a variety of foods commonly consumed and the findings from numerous studies showing evidence of an association with positive outcomes on human health. METHODS: A systematic search using electronic databases PubMed and EMBASE was performed to retrieve English language studies published from the earliest indexing year of each database to April 2019, reporting on the association between dietary flavonoids intake and hypertension. RESULTS: The search strategy resulted in the final selection of 20 studies including 15 cross-sectional investigations and 7 prospective cohorts (1 study reported on 3 prospective cohorts). 5 prospective cohorts, comprising 200,256 individuals and 45,732 cases of hypertension were included in the quantitative analysis. Analysis by extreme quantiles of intake of flavonoid showed a non-significant association with decreased risk of hypertension (RR (risk ratio): 0.96, 95% CI (confidence interval): 0.89, 1.03). Taking into consideration individual flavonoid subclasses, dietary anthocyanins intake was associated with 8% reduction in risk of hypertension, when comparing highest vs. lowest exposure (RR: 0.92, 95% CI: 0.88, 0.97). CONCLUSIONS: Further studies are needed to strengthen the retrieved association between anthocyanins consumption and decreased risk of hypertension and clarify whether total flavonoids or rather individual subclasses may exert beneficial effects on blood pressure.

Second edition of SIMPAR's "Feed Your Destiny" workshop: the role of lifestyle in improving pain management.

This review is aimed to summarize the latest data regarding pain and nutrition, which have emerged during the second edition of Feed Your Destiny (FYD). Theme presentations and interactive discussions were held at a workshop on March 30, 2017, in Florence, Italy, during the 9th Annual Meeting of Study in Multidisciplinary Pain Research, where an international faculty, including recognized experts in nutrition and pain, reported the scientific evidence on this topic from various perspectives. Presentations were divided into two sections. In the initial sessions, we analyzed the outcome variables and methods of measurement for health claims pertaining to pain proposed under Regulation EC No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Moreover, we evaluated how the Mediterranean diet can have a potential impact on pain, gastrointestinal disorders, obesity, cancer, and aging. Second, we discussed the evidence regarding vitamin D as a nutraceutical that may contribute to pain control, evaluating the interindividual variability of pain nature and nurture, and the role of micro-RNAs (miRNAs), polyunsaturated omega 3 fatty acids, and phenolic compounds, with a final revision of the clinical role of nutrition in tailoring pain therapy. The key take-home message provided by the FYD workshop was that a balanced, personalized nutritional regimen might play a role as a synergic strategy that can improve management of chronic pain through a precision medicine approach.

From seed to cooked pasta: influence of traditional and non-conventional transformation processes on total antioxidant capacity and phenolic acid content.

The aim of this work was to compare the traditional with a non-conventional (i.e. kernel micronisation) durum wheat milling process by monitoring the content of bound, conjugated and free phenolic acids (PAs) and the level of the total antioxidant capacity (TAC) occurring in the durum wheat pasta production chain, from seed to cooked pasta. The traditional transformation processes negatively influenced TAC and PA content (40% and 89% decrease from seed to cooked pasta, respectively), mainly during the milling process (25% and 84% decrease of TAC and PA, respectively), which has been related to the removal of external layers of kernels. Conversely, the micronisation applied on durum wheat kernels allowed to obtain whole-wheat pasta that preserved the seed endowment of antioxidant compounds even in cooked pasta. These results indicate the micronisation as a valuable approach to produce pasta with improved nutritional value and potential health-promoting effects compared to the traditional pasta.

Bioaccessibility and bioavailability of phenolic compounds in bread: a review.

Cereal-based products, like breads, are a vehicle for bioactive compounds, including polyphenols. The health effects of polyphenols like phenolic acids (PAs) are dependent on their bioaccessibility and bioavailability. The present review summarizes the current understanding of potential strategies to improve phenolic bioaccessibility and bioavailability and the main findings of in vitro and in vivo studies investigating these strategies applied to breads, including the use of raw ingredients with greater phenolic content and different pre-processing technologies, such as fermentation and enzymatic treatment of ingredients. There is considerable variability between in vitro studies, mainly resulting from the use of different methodologies, highlighting the need for standardization. Of the few in vivo bioavailability studies identified, acute, single-dose studies demonstrate that modifications to selected raw materials and bioprocessing of bran could increase the bioavailability, but not necessarily the net content, of bread phenolics. The two medium-term identified dietary interventions also demonstrated greater phenolic content, resulting from the modification of the raw materials used. Overall, the findings suggest that several strategies can be used to develop new bread products with greater phenolic bioaccessibility and bioavailability. However, due to the large variability and the few studies available, further investigations are required to determine better the usefulness of these innovative processes.

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

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

Cystatin S-a candidate biomarker for severity of submandibular gland involvement in Sjögren's syndrome.

Objectives: Salivary cystatin S is a defence protein mainly produced by submandibular glands and involved in innate oral immunity. This study aimed to verify whether cystatin S was diversely expressed in different disease subsets of primary Sjogren's syndrome (pSS) patients, defined on the basis of salivary flow [unstimulated salivary flow rate (USFR)], minor salivary gland (MSG) focus score and submandibular gland ultrasonography abnormalities. We also evaluated miR-126 and miR-335-5p expression in MSG biopsies to verify whether an aberrant regulation of cystatin S at the glandular level may influence its salivary expression. Methods: Forty pSS patients and 20 sex- and age-matched healthy volunteers were included. Salivary cystatin S levels were assessed by western blot analysis using a stain-free technology. The expression of miR-126, miR-335-5p and cystatin S was assessed by quantitative PCR in 15 MSG biopsies differing for USFR and MSG focus score. Results: We found that salivary cystatin S was significantly decreased in pSS patients vs healthy volunteers ( P = 0.000), especially in those with hyposalivation. A positive correlation was observed between cystatin S and USFR ( r = 0.75, P = 0.01). Salivary cystatin S was also significantly reduced in patients with a submandibular gland ultrasonography score ⩾2. The expression levels of miR-126 and miR-335-5P increased in inverse proportion with USFR. The mRNA of cystatin S did not change significantly, suggesting post-transcriptional regulation. Conclusion: Cystatin S emerged as a promising biomarker for pSS, strongly correlated with glandular dysfunction. An upregulation of miR-126 and miR-335-5P might be implicated in its expression.

Absorption Profile of (Poly)Phenolic Compounds after Consumption of Three Food Supplements Containing 36 Different Fruits, Vegetables, and Berries.

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.