Protective effects of blocking PD-1 pathway on retinal ganglion cells in a mouse model of chronic ocular hypertension

PurposeIn this study, we aimed to investigate whether Programmed cell death 1 ligand 1/programmed cell death 1 ligand 2 (PD-L1/PD-L2) double knockout (dKO) has a protective effect on RGCs in a mouse model of chronic ocular hypertension (COHT).MethodsWe used superparamagnetic iron oxide to induce COHT in mice. Apoptosis of retinal ganglion cells (RGCs) and activation of microglia were evaluated using western blotting (WB) and immunofluorescence staining of the mouse retina. In addition, we also conducted transcriptome sequencing and further gene expression analyses using the gene ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) database.ResultsIn the mouse model of COHT, PD-L1/PD-L2 prevented the apoptosis of RGCs to some extent. Blocking the programmed cell death 1 (PD-1) pathway also increased the number of anti-inflammatory M2-activated microglia and enhanced the phosphorylation of its related pathway signal transducer and activator of transcription (STAT)6. Sequencing results showed that this protective effect may have been achieved by regulating the NF−B, tumour necrosis factor (TNF), PI3K/Akt and toll-like receptor signaling pathway etc.ConclusionBlocking the PD-1 pathway has a protective effect on RGCs in the mouse model of COHT induced by superparamagnetic iron oxide

Creación y Simulación de Metodologías de Análisis, Clasificación e Integración de Nuevos Requerimientos a Software Propietario

La priorización de nuevos requerimientos a implementar en un software propietario es un punto fundamental para su mantenimiento, la conservación de la calidad, observación de las reglas de negocio y los estándares de la empresa. Aunque existen herramientas de priorización basadas en técnicas probadas y reconocidas, las mismas requieren una calificación previa de cada requerimiento. Si la empresa cuenta con solicitudes provenientes de varios clientes de un mismo producto, aumentan los factores que afectan a la empresa, las herramientas disponibles no contemplan estos aspectos y hacen mucho más compleja la tarea de calificación. Este trabajo de investigación abarca la realización de un relevamiento de los métodos de priorización y selección de nuevos requerimientos utilizados por empresas de la zona de Rosario, y la definición de una metodología para la selección un nuevo requerimiento, que implica el análisis y evaluación de todas las implicaciones sobre el producto de software y la empresa, respetando sus reglas de negocio. La metodología creada conduce a la definición de los procesos para la construcción de una herramienta de calificación y priorización de nuevos requerimientos en software propietario que tiene solicitudes de varios clientes al mismo tiempo, con instrumentos de calificación que consideran todos los aspectos relacionados, proveerá técnicas de priorización actuales y emitirá informes personalizados según diferentes perspectivas de la empresa.Eje: Ingeniería de SoftwareRed de Universidades con Carreras en Informática (RedUNCI

A New Approach to Integrated Multi-Trophic Aquaculture System of the Sea Cucumber Apostichopus japonicus and the Sea Urchin Strongylocentrotus intermedius

The sea cucumber Apostichopus japonicus and the sea urchin Strongylocentrotus intermedius are two commercially important species and are widely cultured in China. Here, a laboratory experiment was conducted for 34 days to assess whether the survival, growth and behavior performances are better in the new commercially valuable integrated multi-trophic aquaculture (IMTA) system (group M, 90 S. intermedius and 37 A. japonicus/10,638 cm3 of stocking density) than those in the control group for sea urchins (group U, 90 S. intermedius/10,638 cm3 of stocking density) and the control group for sea cucumbers (group C, 37 A. japonicus/10,638 cm3 of stocking density). We found that feeding behavior, crawling behavior, body length and body weight of sea cucumbers were significantly greater in group M than those in group C. These results suggest that the new IMTA system improves fitness-related behaviors and consequently leads to a better growth in A. japonicus while maintaining a high biomass. We further found that group M showed significantly larger body size and Aristotle’s lantern reflex as well as significantly lower mortality and morbidity in sea urchins, compared to those in group U. This suggests that the new IMTA system greatly improves feeding behavior and body growth, and survival of cultured S. intermedius. This IMTA system is a promising candidate to promote the production efficiency of juvenile A. japonicus (as primary species) and S. intermedius (as subsidiary species) in China

Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance. Keywords: Cannabidiol, Ischemia/reperfusion, Mitochondrial bioenergetics, Pentose-phosphate pathway, Neuroprotectio

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB