Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) with a presumed autoimmune etiology. Approved treatments for MS are immunoregulatory and are able to reduce the inflammatory components of the disease. However, these treatments do not suppress progressive clinical disability. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination are likely to improve long-term outcomes and reduce the rate of axonal damage. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system and has diverse neuromodulatory effects. In this study, using the cuprizone (CPZ) demyelination model of MS, we demonstrate that GAL has pronounced neuroprotective effects with respect to demyelination and remyelination. Using our GAL transgenic mouse (GAL-Tg), we identified a novel attenuation of OLs against CPZ induced demyelination, which was exerted independently of progenitor cells. Alleviation of myelin breakdown in the GAL-Tg mice was observed to be significant. Furthermore, we observed changes in the expression of the GAL receptor GalR1 during the demyelination and remyelination processes. Our data strongly indicate that GAL has the capacity to influence the outcome of primary insults that directly target OLs, as opposed to cases where immune activation is the primary pathogenic event. Taken together, these results suggest that GAL is a promising next-generation target for the treatment of MS.
Both of gp91(phox) (an isoform of nicotinamide adenine dinucleotide phosphate reduced oxidases) and Src (a nonreceptor protein tyrosine kinase) are abundantly expressed in the brain and play a prominent role in mediating ischemic alteration in neurons. The inhibitory strategy of them is believed to be the promising treatment of stroke. The present study was designed to investigate the effect of equol (0.625-2.5 mg·kg(-1), i.g. for 3 days), a predominant active metabolite of daidzein, on neuroprotection against cerebral ischemia/reperfusion injury in rats and the underlying mechanisms. We found that equol decreased the mortality, neurological deficit, brain histological damage, infarct volume, serum lactate dehydrogenase activity and malondialdehyde content in a dose-dependent manner in rats with 2-h middle cerebral artery occlusion, followed by 22-h reperfusion. Western blot analysis revealed that protein levels of gp91(phox) and phosphorylated Src-Tyr416 (p-Src) in ischemic cerebral cortex were increased in rats treated with vehicle, which was reversed in animals treated with equol. In rat pheochromocytoma cell line (PC12) with hypoxia/reoxygenation injury, silencing of gp91(phox) with specific siRNA did not affect the increase of p-Src level by hypoxia/reoxygenation injury and the inhibition of p-Src level by equol, while silencing of Src suppressed the upregulation of gp91(phox) by hypoxia/reoxygenation injury and enhanced the inhibitory effect of equol on gp91(phox) expression. These results demonstrate that equol confers a neuroprotection in rats via inhibiting the activation of Src and upregulation of gp91(phox) induced by focal cerebral ischemia/reperfusion, and Src may play a partial role in regulating gp91(phox) expression of neurons.
This study evaluated the relationship between cross-cultural social adaptation and overseas life satisfaction among Chinese medical aid team members (CMATMs) in Africa. A revised Chinese version of the Sociocultural Adaptation Scale (CSCAS) was used to measure participants’ cross-cultural social adaptation. The self-designed survey of the CMATMs’ overseas life satisfaction includes the following five aspects: food, housing, transportation, entertainment, and security. Electronic questionnaires were distributed non-randomly. Linear regression models were established to explore the association between cross-cultural social adaptation and all dimensions of overseas life satisfaction. After adjusting all the confounders, compared with moderate adaptation, poor adaptation was negatively correlated with all dimensions of overseas life satisfaction (B for food = −0.71, B for housing = −0.76, B for transportation = −0.70, B for entertainment = −0.53, B for security = −0.81, B for overall satisfaction = −0.71, all p < 0.001), whereas good adaptation was positively associated with all dimensions of overseas life satisfaction (B for food = 1.23, B for housing = 1.00, B for transportation = 0.84, B for entertainment = 0.84, B for security = 0.76, B for overall life satisfaction = 0.94, all p < 0.001). This study shows that a better cross-cultural social adaptation was positively connected to a higher level of overseas life satisfaction in general, and more specifically to higher levels of satisfaction with food, housing, transportation, entertainment, and security. This knowledge can be utilized in promoting cross-cultural social adaptation and overseas life satisfaction among CMATMs in Africa.
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