OBJECTIVE: To test if artemisinin, an anti-Malarial drug, can slow down the amyloidogenesis and neuroinflammation in APPswe/PS1dE9 transgenic mice and the mechamism will be investigated further. BACKGROUND: Neuroinflammation is thought to be the key mechanism linked to Alzheimer9s disease (AD) pathogenesis, which is deeply invovled in amyloid plaques, neurofibrillary tangles and microglia activation. Artemisinin has been reported to exert anti-inflammatory effects but the exact machanism need to clarified, and the effect of downregulation of amyloid deposition indicates the new direction for AD secondary prevention strategies. DESIGN/METHODS: 5-month-old APPswe/PS1dE9 transgenic mice were used to evaluate the effects of artemisinin on AD pathogenesis, Five mice were injected with 40 mg/kg artemisinin in DMSO at the same time once daily, for continuous 30 days. The other five mice were injected with DMSO as control. Immunohistochemical staining, Western Blotting, ELISA were combined to evaluate the expression or levels of soluble and insoluble Aβ42, IL-6, TNF-α, IL-1β,LRP1, RAGE, APP carboxyl terminal, BACE1, PS1, Aph-1a, serine 536 phosphorylated NF-κB p65, NF-κB p65, IκB-α, serine 32 phosphorylated IκB-α, NALP3, Cleaved Caspase-1 (Asp297). RESULTS: We found that artemisinin treatment can (1) decreased neuritic plaque burden; (2) didn9t alter Aβ transport across the blood–brain barrier; (3) regulated APP processing via inhibiting β-secretase activity; (4) inhibited NF-κB activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice. The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathlogy due to its effects on suppressing NF-κB activity and NALP3 inflammasome activation. CONCLUSIONS: The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathlogy due to its effects on suppressing NF-κB activity and NALP3 inflammasome activation. Furthermore, Our study suggests that artemisinin could be potent candidate in the secondary prevention drugs for AD. Supported by: National Natural Science Foundation of China grant (30700248; 81271211), and Jiangsu Provincial Natural Science Foundation of Basic Research Plan (BK2009049). We thank Laboratory Animal Center of Nanjing First Hospital for breeding the animals and providing animal experimental facility. Disclosure: Dr. Shi has nothing to disclose. Dr. Xu has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Sun has nothing to disclose.
Abstract IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.
We conducted a meta-analysis of positron emission tomography (PET) findings in Alzheimer's disease and MCI, to help clarify the changes underpinning this condition. All studies using the PET tracers PiB (measuring density of Aβ plaques) or FDG (measuring cerebral metabolic rates of glucose) to investigate patients with MCI or AD were considered for the meta-analysis. Authors were contacted to obtain additional data. Meta-analyses of PiB-PET and FDG-PET changes between patients and controls were undertaken using with the effect-size signed differential mapping (ES-SDM) voxel-based meta-analytic method. A total of 24 studies were included involving 728 AD patients, 211 MCI patients and 658 healthy controls. Individuals with AD showed a significant PiB retention in bilateral precuneus, inferior, middle and superior temporal gyrus, supramarginal gyrus, cingulate gyrus and fusiform gyrus, as well as right insula and putamen. Also, AD patients showed a significant glucose hypometabolism in bilateral precuneus, inferior, middle and superior temporal gyrus, supramarginal gyrus, cingulate gyrus, fusiform gyrus, angular gyrus, inferior parietal lobule and middle frontal gyrus, as well as left precentral and parahippocampal gyrus and right superior frontal gyrus and thalamus. An exploratory meta-analysis of the few studies on MCI showed decreased glucose metabolism in smaller regions than in patients with AD. This meta-analysis characterizes the prototypical Aβ deposits and cerebral metabolic rates of glucose changes in Alzheimer's disease and MCI. It supports the notion that Aβ accumulation biomarkers become abnormal first and biomarkers of synaptic dysfunction demonstrate abnormalities after the Aβ accumulation biomarkers. Summary of the meta-analysis flow Regional differences of Aβ deposit in AD patients compared with controls Regional differences of glucose metabolism in AD patients compared with controls Regional differences of glucose metabolism in MCI patients compared to controls
OBJECTIVE: To investigate the prevalence of cerebral amyloid angiopathy (CAA) in the patients with spontaneous intracerebral hemorrhage (ICH) . To exlpore the connection between LRP1 and RAGE, the main receptors for Abeta clearance.
Abstract Background Invasive and non-invasive mechanical ventilation (MV) have been combined as sequential MV in the treatment of respiratory failure. However, the effectiveness remains unclear. Here, we performed a randomized controlled study to assess the efficacy and safety of sequential MV in the treatment of tuberculosis with respiratory failure. Methods Forty-four tuberculosis patients diagnosed with respiratory failure were randomly divided into sequential MV group (n = 24) and conventional MV group (n = 20). Initially, the patients in both groups received invasive positive pressure ventilation. When the patients' conditions were relieved, the ventilation modality in sequential MV group was switched to oronasal face mask continuous positive airway pressure until weaning. Results After treatment, the patients in sequential MV group had similar respiratory rate, heart rate, oxygenation index, alveolo-arterial oxygen partial pressure difference (A-aDO 2 ), blood pH, PaCO 2 to those in conventional MV group (all P value > 0.05). There was no significant difference in ventilation time and ICU stay between the two groups ( P > 0.05), but sequential MV group significantly reduced the time of invasive ventilation (mean difference (MD): − 36.2 h, 95% confidence interval (CI) − 53.6, − 18.8 h, P < 0.001). Sequential MV group also reduced the incidence of ventilator-associated pneumonia (VAP; relative risk (RR): 0.44, 95% CI 0.24, 0.83, P = 0.006) and atelectasis (RR:0.49, 95% CI 0.24,1.00, P = 0.040). Conclusions Sequential MV was effective in treating tuberculosis with respiratory failure. It showed advantages in reducing invasive ventilation time and ventilator-associated adverse events. Registration number for clinical trial Chinese Clinical Trial Registry ChiCTR2000032311, April 21st, 2020
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