P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development

Vascular dysfunction in cardiovascular diseases includes vasomotor response impairments, endothelial cells (ECs) activation, and smooth muscle cells (SMCs) proliferation and migration to the intima. This results in intimal hyperplasia and vessel failure. We previously reported that activation of the P2Y11 receptor (P2Y11R) in human dendritic cells, cardiofibroblasts and cardiomyocytes was protective against hypoxia/reoxygenation (HR) lesions. In this study, we investigated the role of P2Y11R signaling in vascular dysfunction. P2Y11R activity was modulated using its pharmacological agonist NF546 and antagonist NF340. Rat aortic rings were exposed to angiotensin II (AngII) and evaluated for their vasomotor response. The P2Y11R agonist NF546 reduced AngII-induced vascular dysfunction by promoting EC-dependent vasorelaxation, through an increased nitric oxide (NO) bioavailability and reduced AngII-induced H₂O₂ release; these effects were prevented by the use of the P2Y11R antagonist NF340. Human vascular SMCs and ECs were subjected to AngII or H/R simulation in vitro. P2Y11R agonist modulated vasoactive factors in human ECs, that is, endothelial nitric oxide synthase (eNOS) and endothelin-1, reduced SMC proliferation and prevented the switch towards a synthetic phenotype. H/R and AngII increased ECs secretome-induced SMC proliferation, an effect prevented by P2Y11R activation. Thus, our data suggest that P2Y11R activation may protect blood vessels from HR-/AngII-induced injury and reduce vascular dysfunctions. These results open the way for new vasculoprotective interventions.     

Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks

Nano Research - New strategies for spatially controlled growth of human neurons may provide viable solutions to treat and recover peripheral or spinal cord injuries. While topography cues are known...     

Structure and composition of model cheeses influence sodium NMR mobility,kinetics of sodium release and sodium partition coefficients

The mobility and release of sodium ions were assessed in model cheeses with three different lipid/protein ratios, with or without added NaCl. The rheological properties of the cheeses were analysed using uniaxial compression tests. Microstructure was characterised by confocal laser scanning microscopy. ²³Na nuclear magnetic resonance (NMR) spectroscopy was used to study the molecular mobility of sodium ions in model cheeses through measurements of the relaxation and creation times. Greater mobility was observed in cheeses containing a lower protein content and with added NaCl. The kinetics of sodium release from the cheese to an aqueous phase was correlated with the mobility of sodium ions. The highest rates of sodium release were observed with a lower protein content and with added NaCl. The water/cheese partition coefficients of sodium increased when NaCl was added or the protein content was higher. The study highlighted the effect of model cheese characteristics on molecular and macroscopic behaviours of sodium.     

Protein NMR Spectroscopy at 150 kHz Magic-Angle Spinning Continues To Improve Resolution and Mass Sensitivity

Spectral resolution is the key to unleashing the structural and dynamic information contained in NMR spectra. Fast magic-angle spinning (MAS) has recently revolutionized the spectroscopy of biomolecular solids. Herein, we report a further remarkable improvement in the resolution of the spectra of four fully protonated proteins and a small drug molecule by pushing the MAS rotation frequency higher (150 kHz) than the more routinely used 100 kHz. We observed a reduction in the average homogeneous linewidth by a factor of 1.5 and a decrease in the observed linewidth by a factor 1.25. We conclude that even faster MAS is highly attractive and increases mass sensitivity at a moderate price in overall sensitivity.     

Anti-AGE activity of poplar-type propolis: mechanism of action of main phenolic compounds

This study aimed to compare the protective effect of two geographically distinct propolis against the formation of advanced glycation end products (AGEs). The polyphenol content of propolis extracts (EEPs) was analysed using HPLC-DAD-MS profiling and evaluated for their protective effects against pentosidine-like AGEs. Dicarbonyl trapping capacities of major EEP compounds were determined using a methylglyoxal scavenging in vitro assay. Both propolis samples were characterised with high levels of pinobanksin derivatives exhibiting strong anti-AGE properties. EEPs reduced AGE formation more effectively than well-known natural AGE inhibitors such as quercetin or chlorogenic acid. Individual evaluations of the five major compounds in EEPs showed that flavonoids strongly inhibit the formation of AGEs by trapping dicarbonyl intermediates, whereas compounds such as caffeic acid derivatives only act as antioxidant agents. Propolis is thus a promising candidate for the prevention and control of AGE-related chronic diseases.