Alzheimer’s disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of β-amyloid peptide 25–35 (Aβ25–35) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ25–35, and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca2+ homeostasis and attenuated Aβ25–35 neurotoxicity. Additionally, Aβ25–35-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the β-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.
The analgesic effects of the rat in response to electroacupuncture (EA) or low-dose morphine (3 mg/kg) show marked individual variations. In the midbrain periaqueductal gray (PAG) of the rat, the content of the neuropeptide cholecystokinin octapeptide (CCK-8) was found to be significantly higher in the low responder (LR) rats as compared to that in the high responders (HR). Since PAG has been shown to be a strategic site for CCK-8 to exert an anti-opioid action, a high CCK content in PAG may account for the low analgesic responsiveness to EA and morphine. In order to block the expression of the gene encoding preproCCK in the brain, antisense CCK expression vector pSV2-CCKAS was microinjected into the lateral cerebral ventricle of the rat, leading to a decrease of the CCK-mRNA as well as the CCK-8 content in rat brain. This effect started 4 days after the intracerebroventricular (i.c.v.) injection of the antisense expression vector, and lasted no more than 1 week. This procedure was shown to be very effective in converting LR rats into HR for EA analgesia and morphine analgesia, and also delayed the development of tolerance elicited by prolonged EA stimulation or repeated morphine administration. The time course of the augmentation of opioid analgesia (4-6 days after the i.c.v. injection of the expression vector) paralleled the decrease of the brain CCK-8 content. The results argue that blocking the CCK gene expression in the brain may tilt the balance between opioid and anti-opioid peptides in favor of the former, thus strengthening the EA analgesia and morphine analgesia, and delaying the development of opioid tolerance.
BackgroundPrevious studies have provided inconsistent findings on smoking among migrants, and very limited data exist on their second-hand smoke exposure. This study aims to investigate internal migrants’ smoking prevalence, second-hand smoke exposure among non-smokers, and knowledge of the health hazards of smoking in 12 major migrant provinces in China in 2013.MethodsData from the 2013 Migrant Dynamics Monitoring Survey in China published by the National Commission of Health and Family Planning was used in this study. Descriptive analysis, Chi-square analysis, and sex-stratified multivariate logistic regression analysis were used to explore the determinants of current smoking and second-hand smoke exposure.ResultsAmong 7200 migrants, 34.1% (55% male, 4% female) were current smokers. For males, factors associated with current smoking were education year (aOR = 0.95, 95% CI: 0.93–0.98), duration of stay (aOR = 1.01, 95% CI: 1.00–1.03) and occupation (aOR = 1.25, 95% CI: 1.03–1.53). For females, household registration status (aOR = 1.70, 95% CI: 1.04–2.80) was the most important factor associated with current smoking. Sixty five percent of non-smokers were exposed to second-hand smoke. Factors associated with exposure to second-hand smoke were duration of stay (aOR = 1.01, 95% CI: 1.00–1.02), divorced/widowed marital status (aOR = 0.48, 95% CI: 0.25–0.91), occupation (aOR = 1.29, 95% CI: 1.05–1.58) and the nature of employer (aOR = 0.77, 95% CI: 0.60–0.97). About 95% of participants were aware that lung cancer is one of the hazards of smoking. Non-current smokers had a better knowledge of fertility reduction and accelerated aging as hazards of smoking than current smokers (p < 0.01). Knowledge of the impact of smoking on cardiovascular diseases was relatively low compared with knowledge of other smoking-related hazards (26.1–44.3%).ConclusionsCurrent smoking and exposure to second-hand smoke among internal migrants in China is high. Socio-demographic characteristics and migration status were strongly associated with current smoking and second-hand smoke exposure. We recommend specifically targeted tobacco control interventions to help to address these risk factors, such as focusing on divorced/widowed women.
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