Ceria Nanoparticles Decrease UVA-Induced Fibroblast Death Through Cell Redox Regulation Leading to Cell Survival, Migration and Proliferation.

Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.

Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals.

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1-1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the plasma effect. Taken together, neutrophils cleared hemozoin crystals from the extracellular space via endocytosis into phagosomes and vesicles without inducing the release of neutrophil extracellular traps. However, human plasma components such as fibrinogen limited hemozoin clearance, whereas the presence of platelets augmented this process. These factors may influence the pro-inflammatory potential of hemozoin crystals in malaria.

Design of composite microparticle systems based on pectin and waste material of propolis for modified l-alanyl-l-glutamine release and with immunostimulant activity.

Catabolic conditions like acquired immunodeficiency syndrome, cancer, and burn can cause immunosuppression. Amino acids such as alanine and glutamine are essential for the activity of the immune system. Propolis is immunostimulant and the waste of propolis extraction has been reused with technological and therapeutic purposes. Therefore, this study describes the association of propolis byproduct extract (BPE) with pectin to prepare spray-dried microparticles containing the dipeptide l-alanyl-l-glutamine as stimulant systems of neutrophils. The use of a factorial design allowed selecting the best formulation, which was characterized by morphology, size, and entrapment efficiency analyses. In addition, the systems were characterized by thermal and X-ray diffraction analysis, Fourier-transform infrared spectroscopy, in vitro drug release, and in vitro cytotoxicity and stimulation test of neutrophils. Small well-structured microparticles with good entrapment efficiency values were achieved. Thermal stability of formulation was observed, and it was proved that pectin, BPE and l-alanyl-l-glutamine were dispersed throughout the matrix. The drug was released from the microparticles during 24 h governed by swelling and diffusion. The drug-loaded formulations showed a significant stimulating effect on neutrophils. These structures could increase the activity of immune cells, and other in vitro and in vivo studies should be performed in the future.