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The most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloid-beta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.To explore the underlying pathogenic mechanism of Parkinson's disease (PD) with concomitant postural abnormalities (PDPA) through the relationship between its gait and brain function characteristics. PD patients from the neurology outpatient clinic at Ruijin Hospital were recruited and grouped according to whether postural abnormalities (including camptocormia and Pisa syndrome) were present. PD-related scale assessments, three-dimensional gait tests and brain resting-state functional magnetic imaging were performed and analyzed. The gait characteristics independently associated with PDPA were decreased pelvic obliquity angle and progressive downward movement of the center of mass during walking. PDPA features included decreased functional connectivity between the left insula and bilateral supplementary motor area, which was significantly correlated with reduced Berg Balance Scale scores. Functional connectivity between the right insula and bilateral middle frontal gyrus was decreased and significantly correlated with a decreased pelvic obliquity angle and poor performance on the Timed Up and Go test. Moreover, through diffusion tensor imaging analysis, the average fractional anisotropy value of the fibers connecting the left insula and left supplementary motor area was shown to be decreased in PDPA. There is decreased functional connectivity among the insula, supplementary motor area and middle frontal gyrus with structural abnormalities between the left insula and the left supplementary motor area; these changes in brain connectivity are probably among the causes of gait dysfunction in PDPA and provide some clues regarding the pathogenic mechanisms of PDPA.Dietary interventions such as prolonged calorie restriction (CR) and intermittent fasting provide health benefits including a reduction in the inflammatory burden and regulation of energy metabolism. During CR, β-hydroxybutyrate (BHB) level is elevated in the serum. BHB is a ligand of GPR109A, which inhibits lipolysis and exerts anti-inflammatory effects on cells. During aging, comorbidities related to dyslipidemia are significantly associated with fatty liver. However, the underlying mechanisms of BHB in hepatic ER stress and dyslipidemia are unclear and remain to be elucidated. Here, we used aged rats that were administered with BHB and compared the modulatory effects of BHB through the GPR109A/AMPK pathway on the hepatic endoplasmic reticulum (ER) stress and lipid accumulation to CR rats. BHB caused suppression of hepatic ER stress and lipid accumulation through GPR109A/AMPK pathway in the aged rats. Aged rats of both treatment groups showed reduced cAMP level and PKA phosphorylation. Furthermore, AMPK-Ser173 phosphorylation via PKA was decreased, whereas AMPK-Thr172 phosphorylation was increased by BHB and CR. Further supporting evidence was provided in HepG2 cells that BHB inhibited ER stress and lipid accumulation induced by palmitate. These results suggest that BHB activates GPR109A and regulates the activation of AMPK. These findings were further confirmed by GPR109A-siRNA transfection in vitro. In addition, BHB treatment elevated the protein levels of AMPK leading to significant inhibition of hepatic steatosis, whereas AMPK-siRNA treatment abolished these effects. Taken together, these findings suggest that BHB could be a effective molecule that mimics CR in ameliorating age-related hepatic lipid accumulation via GPR109A signaling pathway.Pulsatile tinnitus, ear fullness, vertigo, hearing disorders, and vestibular dysfunction have been found to be related to high jugular bulb. Anatomical variation in this region also affects surgical planning and approaches. Therefore, knowledge on the detailed anatomy of the high jugular bulb is critical for middle ear and lateral skull base surgery. Prevalence of high jugular bulb is uncertain as data are usually derived from temporal bone specimens and patient reports from hospitals. Therefore, a community-based epidemiological study is necessary to understand the significance of high jugular bulb anatomy. RXC004 beta-catenin inhibitor Here, we report a cross-sectional study to characterize the prevalence of high jugular bulb and jugular bulb size using a 3.0 T magnetic resonance imaging. Furthermore, we studied the relationship between the prevalence of high jugular bulb and age-related changes. We enrolled 4539 permanent residents (9078 ears) from two communities in the Shanghai region who underwent magnetic resonance imaging between 2007 and 2011.
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