The configuration,solvatochromism and metallo‐responses of two novel cyano‐containing oligo(phenylene‐vinylene) derivatives

Two novel cyano‐containing oligo(phenylenevinylene) (OPV) derivatives have been designed and synthesized. Photophysical and sensing properties of the two compounds were studied. Such studies reveal the intramolecular charge transfer process between cyano groups and OPV core. The results showed that the alkyl difference of substituted OPV leads to the changes of molecular configuration and metallo‐response of two compounds. Copyright © 2010 John Wiley & Sons, Ltd.     

TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL-treated vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) are an important origin of foam cells besides macrophages. The mechanisms underlying VSMC foam cell formation are relatively little known. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1) and autophagy have a potential role in regulating foam cell formation. Our study demonstrated that autophagy protected against foam cell formation in oxidized low-density lipoprotein (oxLDL)-treated VSMCs; activation of TRPV1 by capsaicin rescued the autophagy impaired by oxLDL and activated autophagy–lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded foam cell formation of VSMCs through autophagy induction; activation of TRPV1 by capsaicin induced autophagy through AMP-activated protein kinase (AMPK) signaling pathway. This study provides evidence that autophagy plays an important role in VSMC foam cell formation and highlights TRPV1 as a promising therapeutic target in atherosclerosis.     

A novel and highly efficient production system for recombinant adeno-associated virus vector

Recombinant adeno-associated virus (rAAV) has proven to be a promising gene delivery vector for human gene therapy. However, its application has been limited by difficulty in obtaining enough quantities of high-titer vector stocks. In this paper, a novel and highly efficient production system for rAAV is described. A recombinant herpes simplex virus type 1 (rHSV-1) designated HSV1-rc/AUL2, which expressed adeno-associated virus type2 (AAV-2) Rep and Cap proteins, was constructed previously. The data confirmed that its functions were to support rAAV replication and packaging, and the generated rAAV was infectious. Meanwhile, an rAAV proviral cell line designated BHK/SG2, which carried the green fluorescent protein (GFP) gene expression cassette, was established by transfecting BHK-21 cells with rAAV vector plasmid pSNAV-2-GFP. Infecting BHK/SG2 with HSV1-rc/AUL2 at an MOI of 0.1 resulted in the optimal yields of rAAV, reaching 250 transducing unit (TU) or 4.28×104 particles per cell. Therefore, compared     

Angiogenic synergism,vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2

The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-alpha and PDGFR-beta by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.     

Involvement of ZEB1 and E-cadherin in the invasion of lung squamous cell carcinoma

This study intended to investigate the expression of the ZEB1 and E-cadherin proteins in lung squamous cell carcinoma (LSCC) tissues and to examine the clinicopathological correlation between protein levels and LSCC. RT-PCR and Western blot were used to examine the expression of ZEB1 and E-cadherin mRNAs and proteins in LSCC tissues as well as in adjacent normal tissues, and then analyze the relationship between the clinicopathological characteristics and the expression changes of ZEB1 and E-cadherin mRNAs in LSCC. In addition, RNAi was used to knockdown the expression of the ZEB1 gene in Human HCC827 cells; subsequently, changes in the invasive ability of the resultant cells were studied. The positive rates of ZEB1 and E-cadherin mRNAs in LSCC tissues were 69.2 and 38.5 %, respectively. They differed significantly from the corresponding positive rates in the adjacent normal lung tissues (15.4 and 80.8 %, p < 0.05). There was a negative correlation between the protein levels of ZEB1 and E-cadherin in LSCC tissues (r = -0.714, p < 0.001); in addition, it was found that ZEB1 protein expression in LSCC tissues was significantly higher than that in the neighboring normal lung tissues (p < 0.05), and its expression was also significantly higher in patients with lymph node metastases and distant metastases compared to those patients without metastatic disease (p < 0.05). On the contrary, E-cadherin expression was significantly lower in LSCC tissues than that in the neighboring normal tissue (p < 0.05). It was lower in patients with lymph node metastasis and distant metastasis compared to patients without metastatic disease (p < 0.05). However, the expression of ZEB1 and E-cadherin was independent of gender, age, tumor size, or tumor differentiation level (p > 0.05). Transfection of ZEB1 siRNA into HCC827 cells significantly reduced the ZEB1 protein level (p < 0.01) and significantly elevated E-cadherin levels (p < 0.01). Moreover, significantly less ZEB1 siRNA-transfected cells migrated through Transwell chambers in the LSCC tissue than that in the control groups (untransfected or transfected with control siRNA, p < 0.01). The expression of the ZEB1 gene in LSCC tissues is downregulated with the expression of E-cadherin. On the other hand, the expression of siRNA against ZEB1 promotes E-cadherin expression and suppresses the invasive ability conferred by E-cadherin. In conclusion, our data suggested that overexpression of the ZEB1 gene is possibly associated with the occurrence, development, invasion of LSCC.