RESUMO
OBJECTIVES: Both resveratrol (RV) and enriched environment (EE) exert beneficial effects on neurological functional recovery after an ischemic brain injury. METHODS: The neuroprotective effect of combined treatment of RV and EE was examined in a rat model of middle cerebral artery occlusion (MCAO), aiming to further promote neurological functional recovery. RESULTS: The combined therapy of RV and EE clearly improved locomotor activity and behaviour examination, compared to the monotherapy of RV or EE alone. Stroke severity was also markedly ameliorated by the co-treatment. Mechanistic study revealed that the combined treatment reduced oxidative stress. Moreover, the detrimental ERK1/2 signalling upregulated by MCAO injury was markedly suppressed by the co-treatment, compared to RV or EE monotherapy. DISCUSSION: Altogether, the combined therapy of RV and EE showed a clearly enhanced neuroprotective effect, compared to RV or EE monotherapy, which might be a new strategy for the treatment of ischemic brain injury.
Assuntos
Lesões Encefálicas , Meio Ambiente , Infarto da Artéria Cerebral Média/complicações , Fármacos Neuroprotetores/uso terapêutico , Estilbenos/uso terapêutico , Análise de Variância , Animais , Edema Encefálico/etiologia , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Infarto Encefálico/enfermagem , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/etiologia , Lesões Encefálicas/enfermagem , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Locomoção/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Exame Neurológico , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , ResveratrolRESUMO
MicroRNAs (miRNAs) function as negative regulators of gene expression involved in cancer metastasis. The aim of this study is to investigate the potential roles of miR-218 in non-small cell lung cancer and validate its regulation mechanism. Functional studies showed that miR-218 overexpression inhibited cell migration and invasion, but had no effect on cell viability. Enhanced green fluorescent protein reporter assay, real-time polymerase chain reaction and western blot analysis confirmed that miR-218 suppressed the expression of high mobility group box-1 (HMGB1) by directly targeting its 3'-untranslated region. Accordingly, silencing of HMGB1 accorded with the effects of miR-218 on cell migration and invasion, and overexpression of HMGB1 can restore cell migration and invasion which were reduced by miR-218. In conclusion, these findings demonstrate that miR-218 functions as a tumor suppressor in lung cancer. Furthermore, miR-218 may act as a potential therapeutic biomarker for metastatic lung cancer patients.