Genome-Wide Expression Analysis Reveals Diverse Effects of Acute Nicotine Exposure on Neuronal Function-Related Genes and Pathways

Previous human and animal studies demonstrate that acute nicotine exposure has complicated influences on the function of the nervous system, which may lead to long-lasting effects on the behavior and physiology of the subject. To determine the genes and pathways that might account for long-term changes after acute nicotine exposure, a pathway-focused oligoarray specifically designed for drug addiction research was used to assess acute nicotine effect on gene expression in the neuron-like SH-SY5Y cells. Our results showed that 295 genes involved in various biological functions were differentially regulated by 1 h of nicotine treatment. Among these genes, the expression changes of 221 were blocked by mecamylamine, indicating that the majority of nicotine-modulated genes were altered through the nicotinic acetylcholine receptors (nAChRs)-mediated signaling process. We further identified 14 biochemical pathways enriched among the nicotine-modulated genes, among which were those involved in neural development/synaptic plasticity, neuronal survival/death, immune response, or cellular metabolism. In the genes significantly regulated by nicotine but blocked by mecamylamine, 13 enriched pathways were detected. Nine of these pathways were shared with those enriched in the genes regulated by nicotine, including neuronal function-related pathways such as glucocorticoid receptor signaling, p38 MAPK signaling, PI3K/AKT signaling, and PTEN signaling, implying that nAChRs play important roles in the regulation of these biological processes. Together, our results not only provide insights into the mechanism underlying the acute response of neuronal cells to nicotine but also provide clues to how acute nicotine exposure exerts long-term effects on the nervous system

Long-term Outcomes after Stroke in Elderly Patients with Atrial Fibrillation: A Hospital-based Follow-up Study in China

Background: Atrial fibrillation (AF) significantly increases the risk of stroke and disease burden; it is an established predictor of poor outcomes after stroke. However, reported differences in outcomes after stroke among elderly patients between AF and non-AF group are conflicting. We aimed to compare differences in outcomes at 1 year and 3 years after stroke among elderly patients (aged≥75 years old) between AF group and non-AF group. Methods: We recruited 1070 consecutive elderly patients who experienced acute ischemic stroke between January 2008 and December 2013 in Jiamusi University First Hospital, China in this study. Information regarding stroke subtype, severity, risk factors, and outcome (mortality, dependency, and recurrence) at 3 and 12 months after stroke were recorded and assessed between AF group and non-AF group.Results: The prevalence of AF was 16.1% overall, with a similar trend in the prevalence of AF between men and women. The AF group were more likely to experience severe stroke compared to the non-AF group (32.0% vs. 11.9%, respectively; P<0.001). There were no obvious differences between groups regarding the prevalence of hypertension, dyslipidemia, obesity, current smoking, and alcohol drinking but there was a higher prevalence of diabetes in the non-AF group (20.3% vs 30.1%, P=0.010). Mortality and dependency rates were significantly higher in the AF group than in the non-AF group at 1 year after stroke (29.6% vs 17.8%, P=0.001 for mortality; and 59.5% vs 36.1%, P=0.010 for dependency) and 3 years after stroke (46.1% vs 33.2%, P=0.032 for mortality; and 70.7% vs 49.2%, P=0.010 for dependency); however, there was no significant between-groups differences in rates of recurrence across the follow-up periods. The results for dependency remained stable after adjustment for sex, stroke severity, and stroke risk factors at 3 years after stroke (OR, 2.26; 95% CI, 1.06–4.81; P = 0.034); however, the relationship between AF and mortality and recurrence disappeared after adjusting for these covariatesConclusion: These findings suggest that it is crucial to highlight the treatment of elderly stroke patients with AF in order to reduce poor outcomes among the elderly and to reduce the burden of AF in China

Dissociation between conceptual and perceptual implicit memory：Evidence from patients with frontal and occipital lobe lesions

The latest neuroimaging studies about implicit memory have revealed that different implicit memory types may be processed by different parts of the brain. However, studies have rarely examined what subtypes of implicit memory processes are affected in patients with various brain-injuries. Twenty patients with frontal lobe injury, 25 patients with occipital lobe injury, and 29 healthy controls were recruited for the study. Two subtypes of implicit memory were investigated by using structurally parallel perceptual (picture identification task) and conceptual (category exemplar generation task) implicit memory tests in the three groups, as well as explicit memory tests. The results indicated that the priming of conceptual implicit memory and explicit memory tasks in patients with frontal lobe injury was poorer than that observed in healthy controls, while perceptual implicit memory was identical between the two groups. In contrast, the priming of perceptual implicit memory in patients with occipital lobe injury was poorer than that in healthy controls, while the priming of conceptual implicit memory and explicit memory was similar to that in healthy controls. This double dissociation between perceptual and conceptual implicit memory across the brain areas implies that occipital lobes may participate in perceptual implicit memory, while frontal lobes may be involved in processing conceptual memory

Heroin Inhibits HIV-Restriction miRNAs and Enhances HIV Infection of Macrophages

Although opioids have been extensively studied for their impact on the immune system, limited information is available about the specific actions of opioids on intracellular antiviral innate immunity against HIV infection. Thus, we investigated whether heroin, one of the most abused drugs, inhibits the expression of intracellular HIV restriction microRNA (miRNA) and facilitates HIV replication in macrophages. Heroin treatment of macrophages enhanced HIV replication, which was associated with the downregulation of several HIV restriction miRNAs. These heroin-mediated actions on the miRNAs and HIV could be antagonized by naltrexone, an opioid receptor antagonist. Furthermore, the in vitro negative impact of heroin on HIV-associated miRNAs was confirmed by the in vivo observation that heroin addicts had significantly lower levels of macrophage-derived HIV restriction miRNAs than those in the control subjects. These in vitro and in vivo findings indicate that heroin use compromises intracellular anti-HIV innate immunity, providing a favorable microenvironment for HIV survival in the target cells