740 Y-P

Ulcerative colitis is a common inflammatory bowel disease, and the activation of thePI3K/AKT and NF-κB signaling pathways plays a pivotal role in its pathogenesis. Dihydroartemisinin (DHA) is a widely used antimalarial drug and has shown anticancer effect partially through inhibiting the activation of PI3K/AKT and NF-κB. This study aimed to investigate the effect of dihydroartemisinin on ulcerative colitis and its mechanism. Adult male C57 mice were subjected to 3.0% dextran sulfate sodium (DSS) for seven days; simultaneously, dihydroartemisinin or control saline was administered by oral gavage once a day. In vitro, the intestinal epithelial cell-6 was treated with LPS for 24 hours with or without dihydroartemisinin combined with PI3K/Akt activator 740 Y-P or NF-κB activator phorbol myristate acetate. Western blotting was used to test the activation of PI3K/AKT and NF-κB. Dihydroartemisinin significantly ameliorated body weight loss, shortened colon length, and increased DAI in DSS-induced colitis. Meanwhile, histological damage was improved and was accompanied by decreased expression and secretion of proinflammatory cytokines. Moreover, DSS-induced elevation of phosphorylation of PI3K, AKT, IKKα, IκBα, and NF-κB (p65) was remarkably blunted by dihydroartemisinin both in vivo and in vitro, indicating an inhibitive property on the PI3K/AKT and NF-κB signaling pathways. Furthermore, administration of 740 Y-P or PMA significantly blocked protective activity of dihydroartemisinin against colitis in vitro. In conclusion, dihydroartemisinin can attenuate DSS-induced colitis, and its anticolitis effect might be mediated via the PI3K/AKT and NF-κB signaling pathways. DHA might serve as a promising drug for patients with ulcerative colitis.

Objective:To assess the effect of vitamin D and calcium supplementation in preventing recurrences of benign paroxysmal positional vertigo (BPPV).Methods:We performed an investigator-initiated, blinded-outcome assessor, parallel, multicenter, randomized controlled trial in 8 hospitals between December 2013 and May 2017. Patients with confirmed BPPV were randomly assigned to the intervention (n = 518) or the observation (n = 532) group after successful treatment with canalith repositioning maneuvers. The primary outcome was the annual recurrence rate (ARR). Patients in the intervention group had taken vitamin D 400 IU and 500 mg of calcium carbonate twice a day for 1 year when serum vitamin D level was lower than 20 ng/mL. Patients in the observation group were assigned to follow-ups without further vitamin D evaluation or supplementation.Results:The intervention group showed a reduction in the ARR (0.83 [95% confidence interval (CI), 0.74-0.92] vs 1.10 [95% CI, 1.00-1.19] recurrences per 1 person-year) with an incidence rate ratio of 0.76 (95% CI, 0.66-0.87,p< 0.001) and an absolute rate ratio of -0.27 (-0.40 to -0.14) from intention-to-treat analysis. The number needed to treat was 3.70 (95% CI, 2.50-7.14). The proportion of patients with recurrence was also lower in the intervention than in the observation group (37.8 vs 46.7%,p= 0.005).Conclusions:Supplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal.Classification of evidence:This study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV.

Background:Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions.Methods:All male Apolipoprotein E-deficient (ApoE-/-) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.Results:Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE-/-mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively.Conclusions:Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.