Resveratrol and vascular health: evidence from clinical studies and mechanisms of actions related to its metabolites produced by gut microbiota.

Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.

Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal.

Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/ß-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects.

Prehospital qSOFA, mSOFA, and NEWS2 performance for sepsis prediction: A prospective, multi-center, cohort study.

Background: Nowadays, there is no gold standard score for prehospital sepsis and sepsis-related mortality identification. The aim of the present study was to analyze the performance of qSOFA, NEWS2 and mSOFA as sepsis predictors in patients with infection-suspected in prehospital care. The second objective is to study the predictive ability of the aforementioned scores in septic-shock and in-hospital mortality. Methods: Prospective, ambulance-based, and multicenter cohort study, developed by the emergency medical services, among patients (n = 535) with suspected infection transferred by ambulance with high-priority to the emergency department (ED). The study enrolled 40 ambulances and 4 ED in Spain between 1 January 2020, and 30 September 2021. All the variables used in the scores, in addition to socio-demographic data, standard vital signs, prehospital analytical parameters (glucose, lactate, and creatinine) were collected. For the evaluation of the scores, the discriminative power, calibration curve and decision curve analysis (DCA) were used. Results: The mSOFA outperformed the other two scores for mortality, presenting the following AUCs: 0.877 (95%CI 0.841-0.913), 0.761 (95%CI 0.706-0.816), 0.731 (95%CI 0.674-0.788), for mSOFA, NEWS, and qSOFA, respectively. No differences were found for sepsis nor septic shock, but mSOFA's AUCs was higher than the one of the other two scores. The calibration curve and DCA presented similar results. Conclusion: The use of mSOFA could provide and extra insight regarding the short-term mortality and sepsis diagnostic, backing its recommendation in the prehospital scenario.