Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

In vitro and in vivo evaluation of desmopressin-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles for its potential use in cancer treatment

Aim: To develop and characterize the antitumor activity of poly(D,L-lactic-co-glycolic acid) nanoparticles loaded with hemostatic and anticancer drug desmopressin (dDAVP). Materials & methods: After full physicochemical characterization, anticancer activity of dDAVP-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (NPdDAVP) was evaluated in vitro and in vivo on a highly aggressive breast cancer model. Results: After efficiently loading desmopressin in poly(D,L-lactic-co-glycolic acid) matrix, NPdDAVP exhibited suitable physicochemical characteristics for biomedical applications. NPdDAVP displayed a potent cytostatic effect in vitro, inhibiting tumor cell proliferation and colony forming ability. Moreover, intravenous treatment using nanoparticulated-dDAVP inhibited tumor progression and prolonged survival in animals bearing rapidly-growing mammary tumors. Conclusion: Within the framework of promising dDAVP repurposing studies, these findings support further preclinical development of the NPdDAVP for the management of highly aggressive cancer.Fil: Chevalier, Merari. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Farina, Hernán Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin