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AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.
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Objective To compare the curative effect of conservative treatment and surgical treatment for bronchiectasis. Methods 60 patients with bronchiectasis were randomly divided into observation group and control group,30 cases in each group,they were treated with surgery and medical therapy respectively,the clinical efficacy,length of stay, costs, remission time of symptoms and signs, changes of blood gas index and ESR, CRP,TNF-α, WBC,NEUT of the two groups after treatment were compared. Results The curative rate of observation group was significandy higher than control group, while the length of stay, remission time of symptoms and signs and hospitalization costs were significantly lower than control group, the difference was statistically significant (all P ＜0.05) ;After treatmenit,the blood gas index of both groups improved significantly than before treatment(all P ＜ 0.05), and the blood gas index of observation group improved significantly than the control group (all P ＜ 0. 05); After treatment, ESR, CRP,TNF-α,WBC and NEUT of both groups were significantly decreased compared with those before treatment(all P ＜0. 05); Between the two groups, the index value of the observation group decreased significantly (all P ＜ 0.05).Conclusion Surgical treatment for bronchiectasis was superior to conservative treatment with better curative effect,lower cost, shorter hospital stay and faster relief of symptoms and signs, it had good prospects to be applied.