Regulation of the biosynthesis of acyl analogs of platelet-activating factor by purinergic agonist in endothelial cells

AbstractWe have previously shown that platelet-activating factor (PAF)-dependent transacetylase (TA) contains three catalytic activities, namely PAF: lysophospholipid TA (TAL), PAF: sphingosine TA (TAS) and PAF acetylhydrolase. It serves as a modifier of PAF actions by producing different lipid signal molecules. The TAL activity is involved in the biosynthesis of acyl analogs of PAF (acyl-PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine, acylacetyl-GPC) in agonist-stimulated endothelial cells. In the present investigation, we have studied the mechanism(s) by which the TA activity is regulated in ATP-treated endothelial cells. We have demonstrated that ATP, and thiol-modifying agents with ATP, specifically regulate only the TAL part of the TA activities

Bergamot essential oil nanoemulsions: antimicrobial and cytotoxic activity.

Abstract Bergamot essential oil (BEO) is well-known for its food preservation activity, as well as anticancer efficacy. However, the poor BEO water solubility and deriving low bioaccessibility have limited its wider applications. The incorporation in nanoemulsions of BEO and its refined fractions was investigated to enhance its dispersibility in water to promote its antimicrobial activity, tested against Escherichia coli, Lactobacillus delbrueckii, and Saccharomyces cerevisiae, and its cytotoxicity already at low concentrations. Different nanoemulsion formulations were tested based on food-grade ingredients, which were characterized in terms of hydrodynamic diameter and polydispersity index, and physical stability. The antimicrobial activity against all the tested micro-organisms was observed to be higher for BEO in its initial composition, than the light fraction, richer in d-limonene, ß-pinene, and γ-terpinene, or the heavy fraction, richer in linalyl acetate and linalool. Remarkably, the use of BEO nanoemulsions notably enhanced the antimicrobial activity for all the tested oils. BEO exhibited also a measurable cytotoxic activity against Caco-2 cells, which was also enhanced by the use of the different nanoemulsions tested, in comparison with free oil, which discourages the direct use of BEO nanoemulsions as a food preservative. Conversely, BEO nanoemulsions might find use in therapeutic applications as anticarcinogenic agents

Potential impact of functional biomolecules-enriched foods on human health: A randomized controlled clinical trial

Naturally occurring milk compounds have recently been investigated for their health-promoting properties; in fact, their anti-microbial, immuno-modulatory, antioxidant and anti-thrombotic activities, have increasingly gained interest within the scientific community. We have reported a translational, randomized, controlled clinical trial (RCT) on human subjects with a moderate to high cardiovascular risk, and a body mass index (BMI) >25.1 kg/m2, to evaluate the clinical impact of biomolecules-enriched Mediterranean Buffalo (Bubalus bubalis) milk and its derived dairy foods, produced with innovative breeding techniques. The experimental arm involved patients that followed a diet including the above-described products (treated group; n= 11); the control arm was based on a diet including cow milk and its dairy products (control group; n= 9). The results of this study have been statistically evaluated, pointing out a specific significance related to the comparative analysis of the blood pressure among the 2 arms; in fact, this value showed a significant improvement in an extremely short experimental time. Nevertheless, this study also reported not-significant results that were indicative of an interesting and promising tendency in modulating specific diet-depending haematological and biomedical values. In conclusion, this RCT has assessed that the foods derived from buffalo milk naturally enriched with biomolecules, was able to improve the overall blood glucose levels, the BMI and the body weight. These preliminary results are suitable for the design of future strategies in the prevention of cardiometabolic diseases, thus improving the overall quality of life and the policies of healthcare management

Phenolic Profiles of Red Wine Relate to Vascular Endothelial Benefits Mediated by SIRT1 and SIRT6

Dietary phenolic compounds possess potent bioactivity against inflammatory pathways of chronic inflammatory conditions, such as type 2 diabetes. Here, the phenolic profile and bioac-tivity of Italian red wines Gaglioppo, Magliocco, and Nerello Mascalese were characterized. NMR, HPLC/UV-Vis and spectrophotometric characterization showed that Magliocco was the richest wine in monomeric anthocyanins (two-fold), catechins, and low molecular weight phenolics (LMWP). A positive correlation was observed between the polyphenolic content and antioxidant capacity (p < 0.05), with Magliocco displaying the highest antioxidant capacity (p < 0.01). In vitro evidence on the endothelial cell models of insulin resistance and hyperglycemia showed the ability of Magliocco to reduce reactive oxygen species (ROS) (p < 0.01) and cytokine release (p < 0.01) and to upregulate SIRT1 and SIRT6 (p < 0.01). On the whole, the results indicated that the quantitative and qualitative phenolic profiles of red wines influence their in vitro beneficial effects on oxidative and proinflammatory milieu in endothelial cells, showing a positive modulation of SIRT1 and SIRT6, both implied in vascular aging

Breed and Feeding System Impact the Bioactive Anti-Inflammatory Properties of Bovine Milk

In the present study, we aimed at assessing the influence of breed and feeding system on the bovine milk profile of betaines and carnitines and milk capacity in counteracting the inflammatory endothelial cell (EC) damage induced by interleukin (IL)-6. In the first experimental design, two breeds were chosen (Holstein vs. Modicana) to investigate the biomolecule content and antioxidant capacity in milk and dairy products. In the second experimental design, two feeding systems (pasture vs. total mixed ratio) were tested only in Holstein to evaluate the possible effect on the functional profile of milk and dairy products. Finally, the bulk milk from the two experimental designs was used to evaluate the efficacy of preventing IL-6-induced endothelial inflammatory damage. Results showed that Modicana milk and whey had higher biomolecule content and antioxidant activity compared to Holstein milk (p < 0.01). Milk from Holstein fed TMR showed higher concentration of γ-butyrobetaine, δ-valerobetaine (p < 0.01), and l-carnitine (p < 0.05). Similarly, whey from Holstein fed TMR also showed higher content of δ-valerobetaine, glycine betaine, l-carnitine, and acetyl-l-carnitine (p < 0.01) compared to the Holstein fed pasture. Conversely, the antioxidant activity of milk and dairy products was not affected by the feeding system. In ECs, all milk samples reduced the IL-6-induced cytokine release, as well as the accumulation of reactive oxygen species (ROS) and the induction of cell death, with the most robust effect elicited by Modicana milk (p < 0.01). Overall, Modicana milk showed a higher content of biomolecules and antioxidant activity compared to Holstein, suggesting that the breed, more than the feeding system, can positively affect the health-promoting profile of dairy cattle milk

Metformin therapy effects on the expression of sodium-glucose cotransporter 2, leptin, and sirt6 levels in pericoronary fat excised from pre-diabetic patients with acute myocardial infarction

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG

Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside

We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts

High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control