Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

OBJECTIVE Epithelial-mesenchymal transition(EMT)is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis(PF).It is known that a transcription factor snail could regulate the progression of EMT.Nuclear factor erythroid 2 related factor 2(Nrf2),a key regulator of antioxidant defense system,protects cells and tissues against oxidative stress.However,it is not known whether Nrf2 regulates snail thereby modulating the development of PF.MEHODS Bleomycin(BLM)was intratracheally injected into both Nrf2-knockout(Nrf2-/-)and wild-type mice to compare the development of PF.Rat type II alveolar epithelial cells(AECs)RLE-6TN were treated with a specific Nrf2activator sulforaphane,or transfected with Nrf2 and snail si RNAs to determine their effects on transforming growth factorβ1(TGF-β1)-induced EMT.RESULTS BLM-induced EMT and lung fibrosis were more severe in Nrf2-/-mice compared to wild-type mice.In vitro,sulforaphane treatment attenuated TGF-β1-induced EMT,accompanied by the down-regulation of snail.Inversely,silencing Nrf2 by si RNA enhanced TGF-β1-induced EMT along with the expression of snail.Interestingly,silencing snail by si RNA reduced TGF-β1-induced EMT even in the presence of sulforaphane in RLE-6TN cells.CONCLUSION These findings suggested that Nrf2 may attenuate EMT and fibrosis process through regulating the expression of snail in PF.

法庭科学STR检验的标准物质体系

在法庭科学领域推进相关有证标准物质的研制和应用,对建设DNA分析的标准化体系具有重要意义。当前不断涌现新的DNA检验方法,并迅速应用于刑事案件调查,现行方法的有效性和准确性需要标准物质开展认证与验证。DNA STR(short tandem repeat)分型检验是当前法庭科学进行个体身份识别和亲缘关系判断的主要依据,有证DNA标准物质是实现不同实验室间信息资源共享,保障STR分型结果准确可比的标尺。概述了STR检验技术及其过程中使用的国内外标准品和标准物质,并对我国构建STR检验的标准物质体系提出了建议和展望。

Interaction of Wnt/β-catenin and Nrf2 pathways in cigarette smoke-induced inflammation and emphysema

OBJECTIVE The present study aimed to investigate the relationship between Wnt/β-catenin and Nrf2 signaling pathways,and understanding the mechanisms underlying the process of inflammatory in chronic obstructive pulmonary disease(COPD),which was a serious disease of respiratory system.METHODS We duplicate the emphysema model with porcine pancreatic elastase(PPE)in Nrf2-/-and WT mouse for 21d,and intraperitoneal injection of Li Cl,the activator of Wnt/β-catenin signaling pathway from 14 d to the end.Hematoxylin and eosin(H&E)staining was performed to assess the histopathologic level,and immunohistochemistry(IHC)for Mac-3(the marker of macrophagocyte)and Ly6G(the marker of neutrophil)was used to observe the inflammatory infiltrate,while the levels of Wnt/β-catenin and Nrf2 signaling pathways related proteins heme oxygenase-1(HO-1),NAD(P)H:quinone oxidoreductase 1(NQO1),and the expression of inflammatory cytokine interleukin-6(IL-6)were detected by Western blotting of lung tissues.In vitro,cigarette smoke extract(CSE)-treated normal human bronchial epithelial(NHBE)cells,cell viability was examined by MTT assay,and then we treated recombinant human Wnt3a,si Nrf2 and si Wnt3a to measure the expression of Wnt3a,β-catenin,Nrf2,HO-1,NQO-1,and IL-6.Cellular immunofluorescence staining was employed to identify the nuclear translocation of Nrf2.RESULTS We found that the Li Cl-treated group has markedly decreased the damage of alveolar structure and inflammatory signs than the model group of WT mice rather than Nrf2-/-group.It also seen that Li Cl not only increasedβ-catenin,but it also led to a comparable increase in Nrf2,HO-1,NQO1,and decrease of IL-6 compared with WT model groups but except to Nrf2-/-group in vivo.And it showed that Wnt3atreatment has significantly increased the nuclear translocation of Nrf2 and the expression of HO-1 and NQO1,reduced the IL-6 release,while there has no significance when Nrf2 was blocked in CSE-induced NHBE cells.CONCLUSION Our results demonstrated that Wnt3a/β-catenin significantly balanced oxidative stress and attenuated inflammation reaction by promoting Nrf2 nuclear translocation and activity.

基于单神经元的高速列车速度跟踪控制

列车自动驾驶成为近年来的研究热点,其中的速度精准控制与跟踪性能仍需进一步研究与改善,为此采用单神经元对列车速度实施控制。首先阐述单质点列车模型,研究单神经元控制算法。然后设计列车速度跟踪控制系统,该系统采用非线性反馈闭环控制结构,它能实时产生列车所需的牵引力和制动力。最后在计算机上进行仿真研究,并比较三种方法的仿真结果。仿真实验表明,单神经元控制具有跟踪误差小、响应时间短、结构简单等优势。