BackgroundAdvanced glycation end products (AGEs), senescent macroprotein derivatives formed during a normal aging process and acceleratedly under diabetic conditions, play a role in atherosclerotic cardiovascular disease. AGEs cause endothelial cell (EC) damage, an initial trigger for atherosclerosis through the interaction with a receptor for AGEs (RAGE). We have previously shown that n-butanol extracts of Morinda citrifolia (noni), a plant belonging to the family Rubiaceae, block the binding of AGEs to RAGE in vitro. In this study, we examined the effects of n-butanol extracts of noni on reactive oxygen species (ROS) generation and inflammatory reactions on AGE-exposed human umbilical vein ECs (HUVECs).MethodsHUVECs were treated with 100 μg/ml AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni for 4 h. Then ROS generation and inflammatory and gene expression in HUVECs were evaluated by dihydroethidium staining and real-time reverse transcription-polymerase chain reaction analyses, respectively. THP-1 cell adhesion to HUVECs was measured after 2-day incubation of AGE-BSA or BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni.ResultsN-butanol extracts of noni at 670 ng/ml significantly inhibited the AGE-induced ROS generation and RAGE, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 gene expressions in HUVECs. AGEs significantly increased monocytic THP-1 cell adhesion to HUVECs, which was also prevented by 670 ng/ml n-butanol extracts of noni.ConclusionsThe present study demonstrated for the first time that N-butanol extracts of noni could suppress the AGE-induced inflammatory reactions in HUVECs through its anti-oxidative properties via blocking of the interaction of AGEs with RAGE. Inhibition of the AGE-RAGE axis by n-butanol extracts of noni may be a novel nutraceutical strategy for the treatment of cardiovascular disease.

Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and function, contributing to aging-related organ damage and diabetes-associated complications, such as cardiovascular disease (CVD). Moreover, engagement of receptor for AGEs, RAGE with the ligands evoke oxidative stress generation and inflammatory, thrombotic and fibrotic reactions in various kinds of tissues, further exacerbating the deleterious effects of AGEs on multiple organ systems. So the AGE-RAGE axis is a novel therapeutic target for numerous devastating disorders. Several observational studies have shown the association of dietary consumption of fruits and vegetables with the reduced risk of CVD in a general population. Although beneficial effects of fruits and vegetables against CVD could mainly be ascribed to its anti-oxidative properties, blockade of the AGERAGE axis by phytochemicals may also contribute to cardiovascular event protection. Therefore, in this review, we focus on 4 phytochemicals (quercetin, sulforaphane, iridoids, and curcumin) and summarize their effects on AGE formation as well as RAGE-mediated signaling pathway in various cell types and organs, including endothelial cells, vessels, and heart.

Highly branched, coral-like Pd nanostructures were formed using a biomineralization peptide conjugated to an oligomeric peptide that simultaneously controls the spatial orientation, arrangement and valency. The Pd nanocoral showed very high catalytic activity in the reduction of nitrophenol. The results highlight the importance of topological arrangement in nanostructure formation and catalytic activity.

Aim: Several studies have shown an association between fluid overload (FO) and mortality or duration of mechanical ventilation in critically ill patients. However, the association between FO and delirium duration remains unclear. Methods: This retrospective observational cohort study was undertaken at University of Tsukuba Hospital (Tsukuba, Japan) from April 2015 to March 2017. Mechanically ventilated patients who stayed in the intensive care unit for more than 7 days were eligible for inclusion. Univariate analysis was carried out with the Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. A multivariate proportional odds logistic regression model was used to evaluate the association between FO and delirium/coma days (DCDs) during the 7-day study period. Results: A total of 118 patients were included and divided into FO and non-FO groups. Fluid overload occurred in 40% of patients. The FO group had a higher APACHE II score than the non-FO group (19 [16-26] versus 23 [20-29], P = 0.017). Cumulative fluid balance at day 3 was higher in the FO group (3,238 [281-6,530] versus 7,886 [4,106-10,631], P < 0.001). Delirium days within 7 days was longer in the FO group (1 [0-3] versus 2 [1-3], P = 0.048) and DCDs was longer in the FO group (4 [1-5] versus 6 [3-7], P = 0.002). After adjusting for covariates, there were significant associations between FO and DCDs (odds ratio, 2.16; 95% confidence interval, 1.05-4.47). Conclusions: Our findings suggest that FO is associated with increased DCDs in mechanically ventilated patients.