RESUMO
Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are stromal cells, capable of proliferating and differentiating into different types of tissues. This aims of this study is to investigate the role of BMSCs transfected with angiopoietin-1 (Ang-1) in optic nerve injury induced by hyperoxia in a neonatal mice model. Ang-1 overexpression vector was constructed and used to transfect BMSCs. Reverse transcription-quantitative polymerase chain reaction was performed to detect Ang-1 expression in BMSCs. The hyperoxia-induced optic nerve injury model was established. The optic nerves at 6-7 mm posterior to the eyeball were extracted, and were treated with luxol fast blue staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy to examine the effects of Ang-1-modified BMSCs on optic nerve injury induced by hyperoxia. The mice in the Ang-1 + BMSCs and BMSCs groups showed remarkably improved myelin sheaths of nerve fibers compared to the hyperoxia saline group. The positive expression and integrated optic density of Ang-1 in the Ang-1 + BMSCs group were significantly higher compared to the air control, hyperoxia saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the diameter of axons and the thickness of myelin sheath in the air control and Ang-1 + BMSCs groups were higher compared to the hyperoxia saline group. Our study provides evidence supporting that Ang-1-modified BMSCs may have preventive and therapeutic effects on hyperoxia-induced optic nerve injury in neonatal mice.
Assuntos
Angiopoietina-1/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Traumatismos do Nervo Óptico/terapia , Angiopoietina-1/uso terapêutico , Animais , Animais Recém-Nascidos , Axônios/efeitos dos fármacos , Axônios/metabolismo , Modelos Animais de Doenças , Humanos , Hiperóxia/complicações , Camundongos , Traumatismos do Nervo Óptico/etiologia , Traumatismos do Nervo Óptico/genética , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , TransfecçãoRESUMO
To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.
Assuntos
Proteínas de Fusão bcr-abl/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Desenho de Fármacos , Modelos Moleculares , Relação Quantitativa Estrutura-AtividadeRESUMO
BACKGROUND: Wnt proteins as growth factor have multiple functions in neural development, and especially serve key roles in differentiation and development. Wnt-3a is an intercellular signaling molecule that is involved in a variety of morphogenetic events. The purpose of this study was to investigate the effects of Wnt-3a signal protein on proliferation and differentiation of neural stem cells derived from adult mouse spinal cord. METHODS: Adult mouse neural stem cells were cultured with serum free incubation. The recombined plasmid pSecTag2/Hygro B-Wnt3a for eukaryotic expression transfected adult neural stem cell, then the expression protein was detected by Western blot. The differentiation of adult neural stem cells was identified by the immunocytochemical technique. RESULTS: The inducing differentiated rates of neurons were improved greatly by Wnt-3a protein compared with control (p<0.05). CONCLUSION: Wnt-3a has obvious influence on the neuronal differentiation of adult neural stem cell.
Assuntos
Células-Tronco Adultas/fisiologia , Diferenciação Celular/fisiologia , Neurônios/fisiologia , Medula Espinal/citologia , Proteínas Wnt/fisiologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Feminino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/efeitos dos fármacos , Transfecção , Regulação para Cima/fisiologia , Proteínas Wnt/farmacologia , Proteína Wnt3 , Proteína Wnt3ARESUMO
OBJECTIVE: To research the protective effect of pueraria flavonoid on the cerebral ischemic reperfusion injury. METHOD: Using the middle cerebral artery occlusion model (MCAO) in rats, we investigated the influence of pueraria flavonoid on the brain water content, the infarct volume, the activities of SOD, and the content of MDA. RESULT: Pueraria Flavonoid could obviously reduce the brain water content and the infract volume in MCAO, increase the activities of SOD, and decrease the content of MDA in the cerebral ischemia- reinfusion model of rats. CONCLUSION: Pueraria has the function of scavenging free radicals and the protective effect on ischemic brain tissue.
Assuntos
Encéfalo/patologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Pueraria , Traumatismo por Reperfusão , Animais , Encéfalo/metabolismo , Feminino , Flavonoides/isolamento & purificação , Infarto da Artéria Cerebral Média/complicações , Masculino , Malondialdeído/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Plantas Medicinais/química , Pueraria/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismoRESUMO
These active components and monomes inhibit thrombosis aimed directly at activation, adhesiveness and aggregation of platelet, thus preventing and curing ischemic cardiovascular and cerebrovascular diseases. Here we summarized the effect of active components and monomes of the traditional Chinese medicine targeted platelet on ischemic cardiovascular and cerebrovascular diseases, to provide references for drug investigation and clinical application.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Plantas Medicinais , Ativação Plaquetária/efeitos dos fármacos , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonas/isolamento & purificação , Flavonas/farmacologia , Humanos , Plantas Medicinais/química , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by selective neuron loss, amyloid plaques, and neurofibrillary tangles. Oxidative stress plays an essential role in the progression of AD. As the carotenoid crocetin has been shown to possess anti-oxidative effects in previous studies, now we have investigated the neuroprotective effects and potential molecular mechanism of crocetin action against Aß1â42 induced toxicity in mouse hippocampal-derived Ht22 cells. Our results showed that there was a significant reduction in Ht22 cell viability when exposed to Aß1â42 (0.5 µM) for 24 hours. Furthermore, increased reactive oxygen species production, reduced mitochondrial membrane potential and phosphorylation of extracellular signal-regulated kinase were observed in the cells. However, when pre-incubated with crocetin (1 and 5 µM) for 24 hours followed by Aß1â42 (0.5 µM) challenge, there was a marked increase in cell viability, reduced in reactive oxygen species formation, and increased mitochondrial membrane potential. Pre-treatment with crocetin (5 µM) also activated extracellular signal-regulated kinase 1/2 phosphorylation. These data demonstrate that crocetin has neuroprotective effects on Aß1â42-induced Ht22 cell injury which may result from its anti-oxidative role. This finding may provide a potential therapeutic candidate for the treatment of AD.