The acute effect of exercise on the endothelial glycocalyx in healthy adults: A systematic review and meta-analysis.

BACKGROUND: In recent years, it has been demonstrated that when the endothelial glycocalyx, composed of proteoglycans, glycosaminoglycans and glycoproteins, is altered or modified, this property is lost, playing a fundamental role in cardiovascular pathologies. Cardiovascular risk factors can destroy the endothelial glycocalyx layer. Exercise has a positive effect on cardiovascular risk factors, but little is known about its direct effect on the integrity of the endothelial layer. METHODS: The Cochrane Library, PubMed, Web of Science and Scopus databases were searched from their inception to June 30, 2022. The DerSimonian and Laird method was used to compute pooled effect size estimates and their respective 95% confidence intervals for the acute effect of exercise (within 24 h) on the endothelial glycocalyx and its components in healthy adults. RESULTS: Ten studies were included in the meta-analysis, with a total of 252 healthy subjects. The types of exercise included were resistance training, interval training, resistance training and maximal incremental exercise, with a duration range of 30-60 min. Glycocalyx assessment times included ranged from 0 to 90 min post-exercise. Our findings showed that endothelial glycocalyx increases after acute effect of exercise in healthy population (.56, 95% CI: .38, .74). The acute effect of exercise on endothelial glycocalyx components were .47 (95% CIs: .27, .67) for glycosaminoglycans, .67 (95% CIs: .08, 1.26) for proteoglycans and .61 (95% CIs: .35, .86) for glycoproteins. CONCLUSIONS: In a healthy population, various types of exercise showed an acute improvement of the endothelial glycocalyx and its individual components.

Prevalence and genotypic associations of epilepsy in Prader-Willi Syndrome: A systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of epilepsy and febrile seizures and their association with genotype, i.e., 15q11-q13 deletions, uniparental chromosome 15 disomy (UPD) and other mutations, in the population with Prader-Willi syndrome (PWS). METHODS: A systematic search of Medline, Scopus, Web of Science and the Cochrane Library was conducted. Studies estimating the prevalence of seizures, epilepsy and febrile seizures in the PWS population were included. Meta-analyses of the prevalence of epilepsy and febrile seizures and their association with genotype using the prevalence ratio (PR) were performed. RESULTS: Fifteen studies were included. The prevalence of epilepsy was 0.11 (0.07, 0.15), similar to the prevalence of febrile seizures, with a prevalence of 0.09 (0.05, 0.13). The comparison "deletion vs. UPD" had a PR of 2.03 (0.90, 4.57) and 3.76 (1.54, 9.18) for epilepsy and febrile seizures. CONCLUSIONS: The prevalence of seizure disorders in PWS is higher than in the general population. In addition, deletions in 15q11-q13 may be associated with a higher risk of seizure disorders. Therefore, active screening for seizure disorders in PWS should improve the lives of these people. In addition, genotype could be used to stratify risk, even for epilepsy, although more studies or larger sample sizes are needed.

Dietary plant microRNAs as potential regulators of cellular cholesterol efflux.

AIM: Epidemiological evidence suggests adherence to vegetable-rich diets is associated to atheroprotective effects and bioactive components are most likely to play a relevant role. The notion of inter-kingdom regulation has opened a new research paradigm and perhaps microRNAs (miRNAs) from edible vegetables could influence consumer gene expression and lead to biological effects. We aimed to investigate the potential impact of broccoli-derived miRNAs on cellular cholesterol efflux in vitro. METHODS: Four miRNAs (miR159a, miR159b, miR166a and miR403) from Brassica oleracea var. italica (broccoli), a widely consumed cruciferous vegetable, were selected for further investigation, based on their high abundancy in this vegetable and their presence in other plants. Selected miRNAs were synthesized with a 3'-terminal 2'-O-methylation and their cellular toxicity, in vitro gastrointestinal resistance and cellular uptake were evaluated. Potential target genes within the mammalian transcriptome were assessed in silico following pathway analysis. In vitro cholesterol efflux was assessed in human THP-1-derived macrophages. RESULTS: miRNAs survival to in vitro GI digestion was around 1%, although some variation was seen between the four candidates. Cellular uptake by mammalian cells was confirmed, and an increase in cholesterol efflux was observed. Pathway analysis suggested these miRNAs are involved in biological processes related to phosphorylation, phosphatidylinositol and Wnt signaling, and to the insulin/IGF pathway. CONCLUSIONS: Health-promoting properties attributed to cruciferous vegetables, might be mediated (at least in part) through miRNA-related mechanisms.

Correction: Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Correction for 'Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis' by Alicia Saz-Lara et al., Food Funct., 2024, https://doi.org/10.1039/D3FO05061K.

Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

SCOPE: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. METHODS AND RESULTS: Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. CONCLUSION: HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.

Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs.

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs. However, the biological functions of PDEVs are not fully understood, and standard isolation protocols are lacking. Here, PDEVs were isolated from four foods with a combination of ultracentrifugation and size exclusion chromatography, and evaluated as vehicles for enhanced transport of synthetic miRNAs. In addition, the role of food-derived EVs as carriers of dietary (poly)phenols and other secondary metabolites was investigated. EVs from broccoli, pomegranate, apple, and orange were efficiently isolated and characterized. In all four sources, 4 miRNA families were present in tissues and EVs. miRNAs present in broccoli and fruit-derived EVs showed a reduced RNase degradation and were ferried inside exposed cells. EVs transfected with a combination of ath-miR159a, ath-miR162a-3p, ath-miR166b-3p, and ath-miR396b-5p showed toxic effects on human cells, as did natural broccoli EVs alone. PDEVs transport trace amounts of phytochemicals, including flavonoids, anthocyanidins, phenolic acids, or glucosinolates. Thus, PDEVs can act as nanocarriers for functional miRNAs that could be used in RNA-based therapy.

Hydroxytyrosol decreases EDNRA expression through epigenetic modification in colorectal cancer cells.

The Mediterranean diet (MD) is one of the healthiest ones and is associated with a lower incidence of cardiovascular and cerebrovascular diseases as well as cancer. Extra virgin olive oil (EVOO) is probably the most idiosyncratic component of this diet. EVOO has been attributed with many healthful effects, which may be due to its phenolic components, e.g. including hydroxytyrosol (HT). Recent studies suggest that EVOO and HT have molecular targets in human tissues and modulate epigenetic mechanisms. DNA methylation is one of the most studied epigenetic mechanisms and consists of the addition of a methyl group to the cytosines of the DNA chain. Given the purported health effects of EVOO (poly)phenols, we analyzed the changes induced by HT in DNA methylation, in a colorectal cancer cell line. Caco-2 cells were treated with HT for one week or with the demethylating agent 5'-azacytidine for 48 h. Global DNA methylation was assessed by ELISA. DNA bisulfitation was performed and Infinium Methylation EPIC BeadChips were used to analyze the specific methylation of CpG sites. We show an increase in global DNA methylation in Caco-2 cells after HT treatment, with a total of 32,141 differentially methylated (CpGs DMCpGs). Interestingly, our analyses revealed the endothelin receptor type A gene (EDNRA) as a possible molecular target of HT. In summary, we demonstrate that cellular supplementation with HT results in a specific methylome map and propose a potential gene target for HT.

Therapeutic potential of broccoli-derived extracellular vesicles as nanocarriers of exogenous miRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The wide-ranging biological activities of microRNAs stimulated research on disease mechanisms and is suggesting appealing therapeutic applications. When unprotected, miRNAs suffer from rapid degradation and appropriate strategies need to be developed to improve their therapeutic potential. Since the first observation of miRNAs being naturally transported by extracellular vesicles (EVs), the latter have been proposed as specific transport means for drug delivery, conferring stability and increasing resistance against RNase degradation. However, a standard, reproducible, and cost-effective protocol for EV isolation is lacking. Here, the use of broccoli-derived EVs as a therapeutic vehicle for extracellular RNA drug delivery was assessed. EVs were isolated from broccoli, combining ultracentrifugation and size exclusion chromatography methodology. Caco-2 cells were exposed to isolated EVs loaded with exogenous miRNAs and cellular viability was tested. The miRNAs were taken up by this intestinal cell line. Our results show that broccoli EVs can be efficiently isolated, characterized, and loaded with exogenous miRNAs, leading to toxicity in caco-2 cells. Because the pharmaceutical industry is searching for novel drug delivery nanovesicles with intrinsic properties such as low immunogenicity, stability to the gastrointestinal tract, ability to overcome biological barriers, large-scale production, cost-effectiveness, etc., broccoli-isolated nanovesicles might be suitable candidates for future pharmacological applications. We propose broccoli as a natural source of EVs, which are capable of transporting exogenous miRNAs with potential therapeutic effects and suggest that appropriate toxicological and randomized controlled trials as well as patent applications are warranted.

Nutri-Epigenetic Effects of Phenolic Compounds from Extra Virgin Olive Oil: A Systematic Review.

Dietary components can induce epigenetic changes through DNA methylation, histone modification, and regulation of microRNAs (miRNAs). Studies of diet-induced epigenetic regulation can inform anticipatory trials and fine-tune public health guidelines. We systematically reviewed data on the effect of extra virgin olive oil (EVOO) and its phenolic compounds (OOPCs) on the epigenetic landscape. We conducted a literature search using PubMed, Scopus, and Web of Science databases and scrutinized published evidence. After applying selection criteria (e.g., inclusion of in vitro, animal, or human studies supplemented with EVOO or its OOPCs), we thoroughly reviewed 51 articles, and the quality assessment was performed using the revised Cochrane risk of bias tool. The results show that both EVOO and its OOPCs can promote epigenetic changes capable of regulating the expression of genes and molecular targets involved in different metabolic processes. For example, oleuropein (OL) may be an epigenetic regulator in cancer, and hydroxytyrosol (HT) modulates the expression of miRNAs involved in the development of cancer, cardiovascular, and neurodegenerative diseases. We conclude that EVOO and its OOPCs can regulate gene expression by modifying epigenetic mechanisms that impact human pathophysiology. A full elucidation of the epigenetic effects of EVOO and its OOPCs may contribute to developing different pharma-nutritional strategies that exploit them as epigenetic agents. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42022320316.