Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.

Coronaviruses (CoVs) are single-stranded RNA viruses which following virus attachment and entry into the host cell, particularly type 2 pneumocytes but also endothelial cells, release RNA into cytosol where it serves as a matrix for the host translation machinery to produce viral proteins. The viral RNA in cytoplasm can interact with host cell microRNAs which can degrade viral RNA and/or prevent viral replication. As such host cellular miRNAs represent key cellular mediators of antiviral defense. Polyphenols, plant food bioactives, exert antiviral properties, which is partially due to their capacity to modulate the expression of miRNAs. The objective of this work was to assess if polyphenols can play a role in prevention of SARS-CoV-2 associated complications by modulating the expression of host miRNAs. To test this hypothesis, we performed literature search to identify miRNAs that could bind SARS-CoV-2 RNA as well as miRNAs which expression can be modulated by polyphenols in lung, type 2 pneumocytes or endothelial cells. We identified over 600 miRNAs that have capacity to bind viral RNA and 125 miRNAs which expression can be modulated by polyphenols in the cells of interest. We identified that there are 17 miRNAs with both the capacity to bind viral RNA and which expression can be modulated by polyphenols. Some of these miRNAs have been identified as having antiviral properties or can target genes involved in regulation of processes of viral replication, apoptosis or viral infection. Taken together this analysis suggests that polyphenols could modulate expression of miRNAs in alveolar and endothelial cells and exert antiviral capacity.

PURPOSE:Evidence exists regarding the beneficial effects of diets rich in plant-based foods regarding the prevention of cardiometabolic diseases. These plant-based foods are an exclusive and abundant source of a variety of biologically active phytochemicals, including polyphenols, carotenoids, glucosinolates and phytosterols, with known health-promoting effects through a wide range of biological activities, such as improvements in endothelial function, platelet function, blood pressure, blood lipid profile and insulin sensitivity. We know that an individual's physical/genetic makeup may influence their response to a dietary intervention, and thereby may influence the benefit/risk associated with consumption of a particular dietary constituent. This inter-individual variation in responsiveness has also been described for dietary plant bioactives but has not been explored in depth. To address this issue, the European scientific experts involved in the COST Action POSITIVe systematically analyzed data from published studies to assess the inter-individual variation in selected clinical biomarkers associated with cardiometabolic risk, in response to the consumption of plant-based bioactives (poly)phenols and phytosterols. The present review summarizes the main findings resulting from the meta-analyses already completed. RESULTS:Meta-analyses of randomized controlled trials conducted within POSITIVe suggest that age, sex, ethnicity, pathophysiological status and medication may be responsible for the heterogeneity in the biological responsiveness to (poly)phenol and phytosterol consumption and could lead to inconclusive results in some clinical trials aiming to demonstrate the health effects of specific dietary bioactive compounds. However, the contribution of these factors is not yet demonstrated consistently across all polyphenolic groups and cardiometabolic outcomes, partly due to the heterogeneity in trial designs, low granularity of data reporting, variety of food vectors and target populations, suggesting the need to implement more stringent reporting practices in the future studies. Studies investigating the effects of genetic background or gut microbiome on variability were limited and should be considered in future studies. CONCLUSION:Understanding why some bioactive plant compounds work effectively in some individuals but not, or less, in others is crucial for a full consideration of these compounds in future strategies of personalized nutrition for a better prevention of cardiometabolic disease. However, there is also still a need for the development of a substantial evidence-base to develop health strategies, food products or lifestyle solutions that embrace this variability.

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.

Several  epidemiological  studies  have  linked  flavonols  with  decreased  risk  of  cardiovascular  disease  (CVD).  However,  some  heterogeneity  in  the  individual  physiological  responses to the consumption of these compounds has been identified. This meta-analysis aimed to  study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood  pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from  18 human randomized controlled trials were pooled and the effect was estimated using fixed or  random effects meta-analysis model and reported as difference in means (DM). Variability in the  response of blood lipids to supplementation with flavonols was assessed by stratifying various  population subgroups: age, sex, country, and health status. Results showed significant reductions  in total cholesterol (DM = -0.10 mmol/L; 95% CI: -0.20, -0.01), LDL cholesterol (DM = -0.14 mmol/L;  Nutrients 2017, 9, 117  2 of 21  95% CI: -0.21, 0.07), and triacylglycerol (DM = -0.10 mmol/L; 95% CI: -0.18, 0.03), and a significant  increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also  observed in fasting plasma glucose (DM = -0.18 mmol/L; 95%CI: -0.29, -0.08), and in blood pressure  (SBP: DM = -4.84 mmHg; 95% CI: -5.64, -4.04; DBP: DM = -3.32 mmHg; 95% CI: -4.09, -2.55).  Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian  countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and  normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk,  however, country of origin and health status may influence the effect of flavonol intake on blood  lipid levels.