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Previous studies have failed to draw a consistent conclusion over the effect of vitamin D administration on asthma. We hypothesized that vitamin D supplementation could improve the clinical efficacy of corticosteroids in patients with asthma as measured by exacerbations, Asthma Control Test (ACT) score, and lung function in order to maintain asthma control. We searched Web of Science, PubMed, the Cochrane Library, and ScienceDirect up through January 20, 2021 for randomized controlled trials analyzing the effect of vitamin D supplementation on asthma exacerbation. Studies were limited to patients with moderate to severe asthma who were treated with corticosteroids. We identified 12 studies involving 1,543 participants in this meta-analysis. Vitamin D supplementation significantly reduced the risk of asthma exacerbation (pooled risk ratio (RR) 0.70, 95% confidence interval (CI), 0.59, 0.83; P.05). The pooled RR of the ACT score was 0.04 (95% CI, -0.19, 0.27; P.05). The pooled standardized mean difference in vitamin D levels was 1.07 (95% CI, 0.77, 1.38; P.05), and in the percentage of forced expiratory volume in one second was -0.02 (95% CI, -0.13, 0.09; P.05). The pooled RR of adverse events was 1.06 (95% CI, 0.89, 1.25; P.05). We performed subgroup analysis and meta-regression of serum vitamin D levels but found no source of heterogeneity. Vitamin D supplementation safely reduced the rate of asthma exacerbation but did not improve ACT score or lung function among patients with asthma treated with corticosteroids.

Alzheimer's disease (AD) is a neurodegenerative disorder, which has become the leading cause of dementia cases globally. Synaptic failure is an early pathological feature of AD. However, the cause of synaptic failure in AD, especially the GABAergic synaptic activity remains unclear. Extensive evidence indicates that the presence of soluble amyloid-β is an early pathological feature in AD, which triggers synaptic dysfunction and cognitive decline. Our recent study explored the relation of GABAergic transmission and soluble Aβ in early APP/PS1 mice. Firstly, we found soluble Aβ42 levels were significantly increased in serum, hippocampus and prefrontal cortex in 3-4 months APP/PS1 mice, which was much earlier than Aβ plagues formation. In addition, we found TNF-α and BDNF expression levels were increased, while KCC2 and GABAAR expression were decreased in 3-4 months APP/PS1 hippocampus. When we treated 3-4 months APP/PS1 mice with a potent γ-secretase inhibitor, LY411575, which can reduce the soluble Aβ42 levels, the TNF-α and BDNF protein levels were decreased, while KCC2 and GABAAR levels were increased. In conclusion, our study suggested soluble Aβ may impaired the GABA inhibition by mediating KCC2 levels in early APP/PS1 mice. KCC2 may be served as a potential biomarker for AD.

Shufengjiedu capsules (SFJDCs), a traditional Chinese medicine, have been widely used as an antiviral, antibacterial, antitumor, and anti-inflammatory drug. However, the roles of SFJDCs in allergic rhinitis remain unclear. The purpose of this study was to investigate the effects of SFJDCs in olfaction and lung injury in rats with allergic rhinitis. An animal model of allergic rhinitis was created by intraperitoneal injection and intranasal administration of ovalbumin to rats. All rats were divided into seven groups: a model group, a low-dose SFJDC group, a medium-dose SFJDC group, a high-dose SFJDC group, a cetirizine group, and a control group. Hematoxylin and eosin (HE) staining was used to observe pathological changes in rat lung and olfactory epithelium (OE) tissue, and peripheral blood was collected and subjected to an enzyme-linked immunosorbent assay (ELISA) to detect IgE, tumor necrosis factor alpha (TNF-α), and IL-1ꞵ levels. Western blotting, immunohistochemistry staining, and immunofluorescence staining were performed to detect inflammatory cytokines and levels of the autophagy biomarker beclin1 and the apoptosis biomarker cleaeved-caspased3 in lung and OE tissue. ELISA indicated that SFJDCs significantly decreased IgE, TNF-α, and IL-1ꞵ levels in peripheral blood, the lungs, and OE tissue. In addition, Western blotting and staining indicated that SFJDCs repair lung injury, protect against neuronal apoptosis in OE, and rescue impaired autophagy in the lungs and OE tissue. In conclusion, results indicated that SFJDCs might protect against neuronal loss in the OE and lung injury by enhancing autophagy and decreasing apoptosis in rats with allergic rhinitis. Therefore, SFJDCs might serve as an alternative treatment for allergic rhinitis.

Aim This work was to investigate the relationship between ApoE and autophagy regulated by AMPK/mTOR pathway in the pathological process of NAFLD. Main methods Both WT and ApoE−/− mice were divided into two groups and allocated into either a normal chow (ND) or a high-fat diet (HFD) for 8 weeks. After that, we detected the indicators of lipid accumulation, hepatic injury, mitochondrial function hallmark, autophagy, apoptosis, inflammation, and oxidative stress by commercially available kits, immunohistochemistry, immunofluorescent staining, and western blot. Key finding We found the lipid levels of serum and liver, and hepatic injury were significantly increased in the ApoE−/−-HFD group compared to other groups. ApoE−/− mice exhibited increased deposition of fat in liver tissue. The PGC1α, NRF1, ATP, p-AMPK, AMPK, Beclin1, and LC3 levels were downregulated and ROS, p-mTOR, and mTOR were increased in the ApoE−/−-HFD group compared to WT-HFD group. When treated with AMPK and autophagy activators, AICAR and rapamycin, these pathologies and protein levels can be rescued. The expression levels of apoptosis-related proteins, inflammation, and oxidative stress were increased in the ApoE−/−-HFD group compared to the WT-HFD group. Significance Our results indicated that ApoE deficiency can regulate AMPK/mTOR pathway, which leads to NAFLD most likely by modulating hepatic mitochondrial function.