RESUMO
Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. However, its pathogenetic mechanism is still poorly understood. An increasing number of studies have evidenced the important role of long noncoding RNAs (lncRNAs) in AD. The aim of the current study was to investigate the effect and molecular mechanism of the lncRNA X-inactive specific transcript (XIST) in AD. Bilateral common carotid artery occlusion (2VO) was used to induce an AD model in mice. Hydrogen peroxide (H2 O2 ) was used to induce an AD model in N2a cells. The lncRNA XIST, miR-124, and BACE1 messenger RNA expression levels were detected by a real-time polymerase chain reaction. The BACE1 protein expression level was detected by western blot and immunofluorescence assay. The Aß1-42 expression level was detected using an enzyme-linked immunosorbent assay kit. The expression level of lncRNA XIST was significantly upregulated in AD models, both in vivo and in vitro. Silencing of lncRNA XIST negatively regulated miR-124 and positively regulated BACE1 expression in N2a cells, which is attenuated by cotransfection of anti-miR-124 oligodeoxyribonucleotide (AMO-124). Silencing of lncRNA XIST reversed the effect of H2 O2 on miR-124, BACE1, and Aß1-42 expression in N2a cells, which was reversed by cotransfection of AMO-124. Silencing of lncRNA XIST attenuated AD-related BACE1 alteration through miR-124. LncRNA XIST may be a new potential target for the treatment of AD.
Assuntos
Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Regulação da Expressão Gênica , Inativação Gênica , MicroRNAs/genética , Neuroblastoma/prevenção & controle , RNA Longo não Codificante/antagonistas & inibidores , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Animais , Apoptose , Ácido Aspártico Endopeptidases/genética , Proliferação de Células , Modelos Animais de Doenças , Camundongos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , RNA Longo não Codificante/genética , Células Tumorais CultivadasRESUMO
BACKGROUND: A significant waning of enterovirus 71 (EV71) antibody titer after priming immunization with an inactivated EV71 vaccine implied the potential need for a booster dose. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, we recruited participants who had received at least 1 dose of priming EV71 vaccine in an early phase 2 clinical trial that was conducted in healthy infants and children aged 6-35 months. All participants were grouped according to the priming EV71 vaccine formulations (160 U, 320 U, and 640 U with adjuvant and 640 U without adjuvant) and then randomly assigned (ratio, 2:1) to receive a booster dose of vaccine or placebo within each formulation group. The primary end point was the geometric mean titer 28 days after the booster dose. RESULTS: A total of 773 participants were enrolled. Significantly greater immunological responses were induced by the booster shot of all 4 formulations of EV71 vaccine, compared with that induced by placebo (P < .0001). The frequencies of adverse reactions were similar between vaccine and placebo groups within each formulation group. CONCLUSIONS: A booster dose of EV71 vaccine 1 year after the priming EV71 immunization shows excellent immunogenicity and good safety profile. Clinical Trials Registration: NCT01734408.