Down-regulation of survivin suppresses uro-plasminogen activator through transcription factor JunB

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin- shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.     

常规肺通气功能检测在儿童支气管哮喘规范化管理中的应用

目的 通过对比支气管哮喘患儿规范化治疗前后肺功能指标的变化,为本地区儿童哮喘规范化管理提供依据。方法 采用肺功能测定系统对33 例哮喘儿童在急性发作期、缓解期3、6 个月及1 年分别进行常规肺通气功能测定,比较各期实测值,以及异常比例的差异。结果 哮喘患儿急性发作期用力肺活量（FVC）、1 秒用力呼气量（FEV1）、最大呼气流量（PEF）及75%、50%、25%肺活量时用力呼气流速（FEF25~75）等实测值与预计值比较均下降,规范化治疗后3个月开始相关指标逐渐恢复,6个月后反映大气道功能相关指标（FVC、FEV1等）基本恢复。1年时反映小气道功能相关指标FEF25~75 恢复。结论 通过对支气管哮喘儿童肺功能的监测,可以动态观察患儿气道功能恢复情况,为儿童支气管哮喘规范化管理提供客观依据。     

Lentivirus-mediated RNA Interference and Over-expression of CDK2AP1 CDNA Regulate CDK2AP1 Expression in Human Lung Cancer A549 Cells

Cyclin-dependent kinase 2-associated protein 1(CDK2AP1), a cell growth inhibitory factor, is abnormally expressed in cancer cells, and might be implicated in the development of lung cancer. However, no studies on the function of CDK2AP1 in human lung cancer have been yet reported. In this study, overexpressing lentiviral vectors containing full-length CDK2AP1 cDNA and CDK2AP1 shRNA(short hairpin RNA) were constructed. Our results show that infecting A549 cells with lentivirus containing CDK2AP1 shRNA or ful...     

Gas diffusion in a pulmonary acinus model: experiments with hyperpolarized helium-3

Diffusion of hyperpolarized helium-3 in epoxy phantoms was experimentally studied by pulsed-gradient nuclear magnetic resonance (NMR). One phantom with a dichotomic branching structure densely filling a cubic volume was built using the Kitaoka algorithm to model a healthy human acinus. Two other phantoms, one with a different size and the other one with a partial destruction of the branched structure, were built to simulate changes occurring at the early stages of emphysema. Gas pressure and composition (mixture with nitrogen) were varied, thus exploring different diffusion regimes. Preliminary measurements in a cylindrical glass cell allowed us to calibrate the gradient intensity with 1% accuracy. Measurements of NMR signal attenuation due to gas diffusion were compared to a classical Gaussian model and to Monte Carlo simulations. In the slow diffusion regime, the Gaussian model was in reasonable agreement with experiments for low gradient intensity, but there was a significant systematic deviation at larger gradient intensity. An apparent diffusion coefficient Dapp was deduced, and in agreement with previous findings, a linear decrease of Dapp/D0 with D0(1/2) was observed, where D0 is the free diffusion coefficient. In the regime of intermediate diffusion, experimental data could be described by the Gaussian model for very small gradient intensities only. The corresponding Dapp/D0 values seemed to reach a constant value. Monte Carlo simulations were generally in fair agreement with the measurements in both regimes. Our results suggest that, for diffusion times typical of medical magnetic resonance imaging, an increase in alveolar size has more impact on signal attenuation than a partial destruction of the branched structure at equivalent surface-to-volume ratio.     

An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized ³He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B₀ coil design that produces an optimized 65 G (6.5 mT) magnetic field for ³He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D ³He images with up to 2.8 mm resolution, and present initial 2D and 3D ³He images of human lungs in both supine and upright orientations. ¹H MRI can also be performed for diagnostic and calibration reasons.     

Pulmonary surfactant-derived antiviral actions at the respiratory surface

Lung surfactant (LS) is a membrane-based lipid-protein complex that lines the alveoli, reducing the surface tension at the air-liquid interface and thus minimizing the work of breathing. Besides this function, LS is also the first physical barrier between the outside air and the systemic circulation, therefore playing a key role in the defense against harmful particles and microorganisms.Viral respiratory tract infections (RTIs), and especially acute lower RTIs, are one of the leading causes of morbidity and mortality worldwide. LS participates in the network of interactions between viruses and the immune system to prevent or lessen the effects of the infection, but it is also altered by these pathogens, which can potentially impair its function.The aim of this review is to provide an integrated multidisciplinary overview toward understanding the interplay between respiratory viruses and LS and its health impact on the respiratory system. The review is centered on the antiviral mechanisms of both LS proteins and lipids, and their different interactions that lead to varying outcomes. Finally, a summary of the clinical application of surfactant in the scene of lung viral infection is disclosed, including state-of-the-art approaches of the therapeutic use of surfactant components.