Effect of ceria on the organization and bio-ability of anatase fullerene-like crystals

The nanostructure and the oxygen storage capacity against reactive oxygen species (ROS) are essential features to take into account during the design of a new material that will be used as the basis of novel therapeutic technologies. Here we evaluate the incorporation of nano-ceria, which has a demonstrated ability to scavenge free radicals under physiological conditions comparable to those observed for superoxide dismutase and catalase, to TiO2 crystalline assemblies. The material was planned to merge the scavenging properties of CeO2 on a specifically designed structured TiO2 substrate. The presence of Ce atoms has a clear influence in the materials' morphologies, distorting anatase crystal lattice and inducing the formation of fullerene-like structures. The cytotoxicity of the materials against L929 fibroblasts after 24 hours of cell culture was evaluated. Both structural and oxidative properties of the materials have a clear effect on fibroblast viability; in fact it was demonstrated that cellular proliferation can be modulated varying the Ce3+/Ti4+ molar ratio.Fil: Gravina, Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Ruso, Juan Manuel. Universidad de Santiago de Compostela; EspañaFil: Mbeh, Doris Antoinette. École Polytechnique De Montréal; CanadáFil: Yahia, L'Hocine. École Polytechnique De Montréal; CanadáFil: Merhi Yahye. University Of Montreal; CanadáFil: Sartuqui, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; ArgentinaFil: Messina, Paula Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Universidad Nacional del Sur; Argentin

Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets.

P-selectin is rapidly translocated from platelet alpha-granules following activation. Intracellular cyclic AMP (cAMP) is a potent inhibitory pathway that results in global downregulation of platelet activation. While cAMP-dependent protein kinase (PKA) has long been considered as the main mediator of cAMP-dependent effects, no study has yet evaluated its effect on P-selectin expression in human platelets. Pretreatment of thrombin-stimulated platelets with forskolin resulted in a concentration- dependent inhibition of P-selectin expression that correlated with adenylyl cyclase activity. Inhibition of PKA with H-89 reversed cAMP-induced inhibition of P-selectin while cGMP-dependent protein kinase (PKG) inhibition with KT5823 significantly potentiated cAMP-dependent inhibition of P-selectin. Similar results were also observed in a platelet/neutrophil binding assay. In conclusion, cAMP-induced inhibition of P-selectin expression is, in large part, mediated through activation of PKA. PKG appears to be solicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation

The Role of the Proteasome in Platelet Function

Platelets are megakaryocyte-derived acellular fragments prepped to maintain primary hemostasis and thrombosis by preserving vascular integrity. Although they lack nuclei, platelets harbor functional genomic mediators that bolster platelet activity in a signal-specific manner by performing limited de novo protein synthesis. Furthermore, despite their limited protein synthesis, platelets are equipped with multiple protein degradation mechanisms, such as the proteasome. In nucleated cells, the functions of the proteasome are well established and primarily include proteostasis among a myriad of other signaling processes. However, the role of proteasome-mediated protein degradation in platelets remains elusive. In this review article, we recapitulate the developing literature on the functions of the proteasome in platelets, discussing its emerging regulatory role in platelet viability and function and highlighting how its functional coupling with the transcription factor NF-κB constitutes a novel potential therapeutic target in atherothrombotic diseases

Modulating the Release Kinetics of Paclitaxel from Membrane-Covered Stents Using Different Loading Strategies

Membrane-covered Express2TM Monorail® stents composed of chitosan (CH) blended with polyethylene oxide (PEO) in 70:30% wt (CH-PEO) were coated with a monolayer of hyaluronic acid (HA). This significantly improved the resistance to platelet adhesion and demonstrated excellent mechanical properties, resisting the harsh conditions during stent crimping and subsequent inflation. CH-PEO/HA membrane was then combined with a paclitaxel (Pac) delivery system via three different approaches for comparison of release profiles of Pac. The activity of Pac in these systems was confirmed since its presence in the membrane significantly decreased cell viability of U937 macrophages. Presented results are promising for applications requiring different release patterns of hydrophobic drugs