Encapsulation of gold nanostructures and oil-in-water nanocarriers in microgels with biomedical potential

Indexación: Scopus.Funding: This research was funded by FONDECYT 1161450, 1150744, 11130494 and 1170929, FONDEQUIP EQM160157, EQM170111, CONICYT-FONDAP 15130011, and CONICYT PhD Scholarship 21141137.Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11–12 ◦ C) than nanospheres (1–2 ◦ C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications. © 2018 by the authors.https://www.mdpi.com/1420-3049/23/5/120

Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamine-induced locomotor conditioning

When psychostimulant drugs like amphetamine are administered repeatedly in the presence of a contextual stimulus complex, long-lasting associations form between the unconditioned effects of the drug and the contextual stimuli. Here we assessed the role played by the proline-directed serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) in the nucleus accumbens (NAcc) on the expression of the conditioned locomotion normally observed when rats are returned to a context previously paired with amphetamine. Infusing the Cdk5 inhibitor roscovitine (40 nmol/0.5µl/side) into the NAcc 30-min before the test for conditioning significantly enhanced the conditioned locomotor response observed in rats previously administered amphetamine in the test environment. This effect was specific to the expression of a conditioned response as inhibiting Cdk5 produced no effect in control rats previously administered saline or previously administered amphetamine elsewhere. As inhibiting Cdk5 during exposure to amphetamine has been found to block the accrual of locomotor conditioning, the present results suggest distinct roles for NAcc Cdk5 in the induction and expression of excitatory conditioning by amphetamine

Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca²⁺/P2X7 Receptor Signaling Axis.

Cancer cell adhesion to the vascular endothelium is an important step in tumor metastasis. Thy-1 (CD90), a cell adhesion molecule expressed in activated endothelial cells, has been implicated in melanoma metastasis by binding to integrins present in cancer cells. However, the signaling pathway(s) triggered by this Thy-1-Integrin interaction in cancer cells remains to be defined. Our previously reported data indicate that Ca <sup>2+</sup> -dependent hemichannel opening, as well as the P2X7 receptor, are key players in Thy-1-α <sub>V</sub> β <sub>3</sub> Integrin-induced migration of reactive astrocytes. Thus, we investigated whether this signaling pathway is activated in MDA-MB-231 breast cancer cells and in B16F10 melanoma cells when stimulated with Thy-1. In both cancer cell types, Thy-1 induced a rapid increase in intracellular Ca <sup>2+</sup> , ATP release, as well as cell migration and invasion. Connexin and Pannexin inhibitors decreased cell migration, implicating a requirement for hemichannel opening in Thy-1-induced cell migration. In addition, cell migration and invasion were precluded when the P2X7 receptor was pharmacologically blocked. Moreover, the ability of breast cancer and melanoma cells to transmigrate through an activated endothelial monolayer was significantly decreased when the β <sub>3</sub> Integrin was silenced in these cancer cells. Importantly, melanoma cells with silenced β <sub>3</sub> Integrin were unable to metastasize to the lung in a preclinical mouse model. Thus, our results suggest that the Ca <sup>2+</sup> /hemichannel/ATP/P2X7 receptor-signaling axis triggered by the Thy-1-α <sub>V</sub> β <sub>3</sub> Integrin interaction is important for cancer cell migration, invasion and transvasation. These findings open up the possibility of therapeutically targeting the Thy-1-Integrin signaling pathway to prevent metastasis

De la utopía en Psicología Social Murmullos políticos de una crisis.

Durante los años 60, 70 y 80 las ciencias sociales se ven impelidas por grandes movimientos sociales, pero sobretodo por una exigencia mayor que invitaba a revisar su propia configuración y planteamiento. Es en este marco que la Psicología Social entra en crisis, volcando la mirada hacia su interior, a las profundidades que le dieron existencia y desde donde le permiten reflexionar sobre dos aristas o conflictos importantes: uno relativo a la relevancia de los temas estudiados y otro referido al nivel epistemológico. En este marco de consideraciones el artículo replantea un foco importante que fue relegado al interior de la psicología social y que cobra absoluta relevancia en el contexto de las dinámicas sociales desiguales existentes en la región latinoamericana: se trata del ámbito de lo ético-político, dimensión necesaria de volver a repensar. Para tal efecto, en un primer momento, el artículo tensiona posturas sociopsicológica insertas en período de crisis, destacando sus conflictos, argumentos y posibilidades estratégicas de articulación, para luego dar cabida a una breve propuesta sobre condiciones mínimas para re-pensar lo sociopsicológico desde una postura política. Durante los años 60, 70 y 80 las ciencias sociales se ven impelidas por grandes movimientos sociales, pero sobretodo por una exigencia mayor que invitaba a revisar su propia configuración y planteamiento. Es en este marco que la Psicología Social entra en crisis, volcando la mirada hacia su interior, a las profundidades que le dieron existencia y desde donde le permiten reflexionar sobre dos aristas o conflictos importantes: uno relativo a la relevancia de los temas estudiados y otro referido al nivel epistemológico. En este marco de consideraciones el artículo replantea un foco importante que fue relegado al interior de la psicología social y que cobra absoluta relevancia en el contexto de las dinámicas sociales desiguales existentes en la región latinoamericana: se trata del ámbito de lo ético-político, dimensión necesaria de volver a repensar. Para tal efecto, en un primer momento, el artículo tensiona posturas sociopsicológica insertas en período de crisis, destacando sus conflictos, argumentos y posibil dades estratégicas de articulación, para luego dar cabida a una breve propuesta sobre condiciones mínimas para re-pensar lo sociopsicológico desde una postura política

Complete Genome Sequence and Comparative Metabolic Profiling of the Prototypical Enteroaggregative Escherichia coli Strain 042

Background \ud Escherichia coli can experience a multifaceted life, in some cases acting as a commensal while in other cases causing intestinal and/or extraintestinal disease. Several studies suggest enteroaggregative E. coli are the predominant cause of E. coli-mediated diarrhea in the developed world and are second only to Campylobacter sp. as a cause of bacterial-mediated diarrhea. Furthermore, enteroaggregative E. coli are a predominant cause of persistent diarrhea in the developing world where infection has been associated with malnourishment and growth retardation. \ud \ud Methods \ud In this study we determined the complete genomic sequence of E. coli 042, the prototypical member of the enteroaggregative E. coli, which has been shown to cause disease in volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains revealing previously uncharacterised virulence factors including a variety of secreted proteins and a capsular polysaccharide biosynthetic locus. In addition, by using Biolog™ Phenotype Microarrays we have provided a full metabolic profiling of E. coli 042 and the non-pathogenic lab strain E. coli K-12. We have highlighted the genetic basis for many of the metabolic differences between E. coli 042 and E. coli K-12. \ud \ud Conclusion \ud This study provides a genetic context for the vast amount of experimental and epidemiological data published thus far and provides a template for future diagnostic and intervention strategies

Increased acinar damage of salivary glands of patients with Sjögren's syndrome is paralleled by simultaneous imbalance of matrix metalloproteinase 3/tissue inhibitor of metalloproteinases 1 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 ratios

Indexación: Scopus.Objective. Previous findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproieinase 9 (MMP-9) and MMP-3 trigger the destruction of acinar structures in these glands. Tissue inhibitors of matrix metalloproteinases (TIMPs) tightly control MMP activity, and TIMP expression is an important modulator of effects attributed to MMPs. This study was undertaken to investigate the correlation between the balance of MMPs/TIMPs in the LSGs of SS patients and the degree of inflammatory infiltration and acinar structure integrity. Methods. Three groups of SS patients classified according to focus score and residual tissue were studied. The expression of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was examined at the messenger RNA and protein levels. The ratio of MMP/TIMP expression (R value) was calculated. Focus score and acinar structure were evaluated by histologic analysis. Results. In SS patients the MMP-3/TIMP-1 ratio was higher than 1 and the MMP-9/TIMP-1 ratio was much higher than 1 whereas the MMP-2/TIMP-2 ratio nearly equaled 1, suggesting elevated proteolytic activity due mainly to MMP-9. R values were independent of the focus score of inflammatory cells, but correlated well with the dramatic changes observed in morphologic integrity of acini, as revealed mainly by the lack of nuclear polarity. Acinar changes were more evident when R values for both MMP-9/TIMP-1 and MMP-3/TIMP-1 were higher. Conclusion. This study provides evidence that an altered balance between MMPs and their inhibitors is associated with acinar damage. Since salivary gland acinar cells express both MMPs and TIMPs, these cells may play an important role in extracellular matrix destruction and in the LSG pathophysiology in SS.https://onlinelibrary.wiley.com/doi/full/10.1002/art.2126