RESUMO
The aim of this study was to elucidate the neuronal protection effect of sodium butyrate (NaB) on neuronal apoptosis in rats with cerebral infarction (CI), and the involvement of the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways. MI model in rats was performed by middle cerebral artery occlusion (MCAO). Three hours after reperfusion, gastric administration of 5 or 10 mg/kg NaB was performed. Neurological deficit score, infarct size and brain edema were evaluated in rats after 24 h of reperfusion. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine contents of oxidative stress factors. Lactate dehydrogenase (LDH) activity, cell viability and apoptosis in extracted neurons were determined. Moreover, expression levels of Bcl-2, Bax, Akt and ERK1/2 were examined. NaB treatment markedly reduced infarct size and brain edema content in CI rats, and NaB treatment improved viability, decreased LDH activity and reversed contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in a dose-dependent manner. In addition, NaB treatment dose-dependently reduced apoptotic rate and Bax level, as well as enhanced Bcl-2 level. Protein levels of Akt and ERK1/2 were markedly upregulated in NaB-treated neurons. NaB treatment alleviates neuronal apoptosis via the PI3K/Akt and ERK1/2 pathways in CI rats, thus protecting the deterioration of CI.
Assuntos
Apoptose , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Traumatismo por Reperfusão , Transdução de Sinais/efeitos dos fármacos , SódioRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that contributes to dementia in the elderly population. Genome-wide linkage analysis has identified chromosome 12p as the AD-susceptible region, which includes lectin-like oxidized low-density lipoprotein receptor 1 (OLR1). The OLR1 +1073 C/T single-nucleotide polymorphism is located in the 3'-untranslated region of the gene and may influence the binding of regulatory microRNAs (miRNAs) and OLR1 protein homeostasis. A number of studies have reported an association between this variant and AD. However, the results are controversial. A meta-analysis of case-control studies examining the relationship between the OLR1 +1073 C/T single-nucleotide polymorphism and AD risk was performed. Five studies were selected that included 2419 cases and 2381 controls. The results revealed a significantly decreased AD risk in the recessive model (TT vs TC + CC: odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.65-0.96). The control group in one of the studies was in Hardy-Weinberg disequilibrium, so we performed additional meta-analysis excluding this study. The significance was much more pronounced in the recessive model (TT vs TC + CC: OR = 0.72, 95%CI = 0.62-0.85). Using miRanda and RNA hybrid methods, the polymorphic allele was shown to influence the binding of various miRNAs. Our results suggested that the +1073 C/T polymorphism decreased the risk of AD. The polymorphic allele was also predicted to affect the binding site of many miRNAs, which may explain the relationship between the +1073 C/T variant and AD.
Assuntos
Doença de Alzheimer/genética , Receptores Depuradores Classe E/genética , Regiões 3' não Traduzidas , Sítios de Ligação , Estudos de Casos e Controles , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Depuradores Classe E/química , Receptores Depuradores Classe E/metabolismoRESUMO
Objective: The auditory deficits of single-sided deafness (SSD) can be treated with a novel intra-oral device, SoundBite, which delivers sound by applying vibratory signal to the teeth. The purpose of this study was to evaluate the efficacy and benefit of the bone conduction device for Chinese adults with SSD. Methods: Eighteen patients aged 19-66 yrs with acquired, permanent sensorineural SSD and no current treatment by any other devices for SSD, were recruited in a prospective controlled, nonrandomized, unblinded study. They were requested the continually daily wear of the new device over a 30-day free trial period. The intra-oral hearing device was placed around two maxillary teeth and was similar to a small partial denture or retainer. The audiological tests included pure tone air conduction thresholds, monosyllable word recognition score (WRS) in quiet and sentence reception thresholds in noise (via CMNmatrix test). The benefit was determined with the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Speech, Spatial and Qualities of Hearing Scale (SSQ) questionnaire. Results: The monosyllable WRS and the 50% threshold of signal-to-noise ratio (SNR50) were significantly better in all aided conditions. The head shadow effect, assessed by the SNR50 via CMNmatrix test improved an average of 2.6 dB after 30 days' wearing compared with unaided condition (P<0.001). The APHAB scores improved (P<0.05) for all subjects for the Global and Ease of Communication, Reverberation, Background Noise subscales. The SSQ scores improved (P<0.05) for all subjects for Speech, Spatial and Qualities of Hearing subscales. Conclusion: The SoundBite is a good alternative to the well-established implantable bone conduction devices in patients with SSD. An improvement in listening ability in noise and quiet as well as a decrease of the head shadow effect is validated as the expected.
Assuntos
Surdez , Auxiliares de Audição , Perda Auditiva Unilateral , Percepção da Fala , Adulto , Idoso , Condução Óssea , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PCR method was used to introduce the code sequence of Factor Xa cleavage site to the 5' end of cecropin CMIV mutant gene X, then the gene was cloned into the expression vector pGEX-KG, and was highly expressed in E. coli BL21 by IPTG induction. The fusion protein was purified by affinity-chromatography and was cleaved by Factor Xa. Cecropin X with antibacterial activity was obtained after purified by ion-exchange chromatography.