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1.  Damage Detection on Sudden Stiffness Reduction Based on Discrete Wavelet Transform 
The Scientific World Journal  2014;2014:807620.
The sudden stiffness reduction in a structure may cause the signal discontinuity in the acceleration responses close to the damage location at the damage time instant. To this end, the damage detection on sudden stiffness reduction of building structures has been actively investigated in this study. The signal discontinuity of the structural acceleration responses of an example building is extracted based on the discrete wavelet transform. It is proved that the variation of the first level detail coefficients of the wavelet transform at damage instant is linearly proportional to the magnitude of the stiffness reduction. A new damage index is proposed and implemented to detect the damage time instant, location, and severity of a structure due to a sudden change of structural stiffness. Numerical simulation using a five-story shear building under different types of excitation is carried out to assess the effectiveness and reliability of the proposed damage index for the building at different damage levels. The sensitivity of the damage index to the intensity and frequency range of measurement noise is also investigated. The made observations demonstrate that the proposed damage index can accurately identify the sudden damage events if the noise intensity is limited.
doi:10.1155/2014/807620
PMCID: PMC4058814  PMID: 24991647
2.  Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression 
BMC Cancer  2013;13:461.
Background
Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression.
Methods
Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).
Results
MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro.
Conclusions
Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
doi:10.1186/1471-2407-13-461
PMCID: PMC3851462  PMID: 24098911
Long non-coding RNA; MEG3; NSCLC; Proliferation; p53
3.  Nicorandil Prevents Right Ventricular Remodeling by Inhibiting Apoptosis and Lowering Pressure Overload in Rats with Pulmonary Arterial Hypertension 
PLoS ONE  2012;7(9):e44485.
Background
Most of the deaths among patients with severe pulmonary arterial hypertension (PAH) are caused by progressive right ventricular (RV) pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear.
Methodology/Principal Findings
RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats.
Conclusions/Significance
Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels. The use of a mitoKATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV remodeling during the early stages of PAH.
doi:10.1371/journal.pone.0044485
PMCID: PMC3436887  PMID: 22970229
4.  Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction 
The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 μM iptakalim or the combination of 10 μM iptakalim and 1, 10 and 100 μM glibenclamide for 24 h, and the eNOS activity and NO levels were measured in the conditioned medium from the HPAEC cultures. The eNOS activity and NO levels were reduced significantly in the conditioned medium from HPAEC cultures under hypoxic conditions. Pre-treatment with 10 μM iptakalim normalized the reduction of the eNOS activity and NO levels caused by hypoxia in the conditioned medium from HPAEC cultures. Iptakalim raised the eNOS activity and NO levels under hypoxic conditions, but was blocked by the KATP channel blocker, glibenclamide. Our results indicate that hypoxia impairs NO system function, whereas the ATP-sensitive K+ channel opener, iptakalim, may rescue HPAECs from hypoxia-induced NO system dysfunction.
doi:10.3892/etm.2011.414
PMCID: PMC3438542  PMID: 22969925
iptakalim; human pulmonary artery endothelial cells; endothelial nitric oxide synthase; nitric oxide
5.  Proteomic analysis of the effect of iptakalim on human pulmonary arterial smooth muscle cell proliferation 
Acta Pharmacologica Sinica  2009;30(2):175-183.
Aim:
To investigate the anti-proliferative effect of iptakalim (Ipt), a newly selective KATP channel opener, in endothelin-1 (ET-1)-induced human pulmonary arterial smooth muscle cells (PASMCs) using proteomic analysis.
Methods:
Human PASMCs were incubated with ET-1 (10−8 mol/L) and ET-1 (10−8 mol/L) plus iptaklim (10−5 mol/L) for 24 h. Analysis via 2-DE gel electrophoresis and MALDI-TOF-MS was employed to display the different protein profiles of whole-cell protein from cultures of control, ET-1 treatment alone, and treatment with ET-1 and iptaklim combined. Real time RT-PCR and Western blot analysis were used to confirm the proteomic analysis.
Results:
When iptakalim inhibited the proliferative effect of ET-1 in human PASMCs by opening the KATP channels, the expression of different groups of cellular proteins was changed, including cytoskeleton-associated proteins, plasma membrane proteins and receptors, chaperone proteins, ion transport–associated proteins, and glycolytic and metabolism-associated proteins. We found that iptakalim could inhibit the proliferation of human PASMCs partly by affecting the expression of Hsp60, vimentin, nucleoporin P54 (NUP54) and Bcl-XL by opening the KATP channel.
Conclusion:
The data suggest that a wide range of signaling pathways may be involved in abolishing ET-1-induced proliferation of human PASMCs following iptakalim treatment.
doi:10.1038/aps.2008.30
PMCID: PMC4002473  PMID: 19169269
pulmonary arterial smooth muscle cells; KATP channel opener; iptakalim; proteomics; proliferation
6.  Arsenic trioxide, a potent inhibitor of NF-κB, abrogates allergen-induced airway hyperresponsiveness and inflammation 
Respiratory Research  2006;7(1):146.
Background
Overactivation of nuclear factor κB (NF-κB) orchestrates airway eosinophilia, but does not dampen airway hyperresponsiveness in asthma. NF-κB repression by arsenic trioxide (As2O3) contributes to apoptosis of eosinophils (EOS) in airways. Here we provide evidence that As2O3 abrogates allergen (OVA)-induced airway eosinophilia by modulating the expression of IκBα, an NF-κB inhibitory protein, and decreases the airway hyperresponsiveness.
Methods
Using a murine model of asthma, the airway hyperresponsiveness was conducted by barometric whole-body plethysmography. Airway eosinophilia, OVA-specific IgE in serum, and chemokine eotaxin and RANTES (regulated upon activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid were measured by lung histology, Diff-Quick staining, and ELISA. Chemokine-induced EOS chemotactic activity was evaluated using EOS chemotaxis assay. Electrophoretic mobility shift assay and Western blot analysis were performed to assess pulmonary NF-κB activation and IκBα expression, respectively.
Results
As2O3 attenuated the allergen-induced serum IgE, chemokine expression of eotaxin and RANTES, and the EOS recruitment in bronchoalveolar lavage fluid, which is associated with an increased IκBα expression as well as a decreased NF-κB activation. Also, As2O3 suppressed the chemotaxis of EOS dose-dependently in vitro. Additionally, As2O3 significantly ameliorated the allergen-driven airway hyperresponsiveness, the cardinal feature underlying asthma.
Conclusion
These findings demonstrate an essential role of NF-κB in airway eosinophilia, and illustrate a potential dissociation between airway inflammation and hyperresponsiveness. As2O3 likely exerts its broad anti-inflammatory effects by suppression of NF-κB activation through augmentation of IκBα expression in asthma.
doi:10.1186/1465-9921-7-146
PMCID: PMC1769498  PMID: 17178007

Results 1-6 (6)