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Background：β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells.Isoprenaline （ISO,a β-adrenergic agonist） has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor （VEGF） expression;however,the underlying mechanism remains to be investigated.It is widely accepted that certain noncoding RNAs,including microRNAs （miRNAs） and long noncoding RNAs （lncRNAs）,can regulate endothelial cell behavior,including their involvement in angiogenesis.Therefore,we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells （HUVECs）.Methods：We evaluated VEGF-A messenger RNA （mRNA） and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay,respectively.To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis,we measured expression of the miRNAs miR-210,miR-21,and miR-l,as well as that of the lncRNAs growth arrest-specific transcript 5 （GAS5）,maternally expressed 3 （MEG3）,and metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） in HUVECs exposed to ISO.Furthermore,to ascertain its importance in ISO-mediated angiogenesis,we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs.All statistical analyses were performed using SPSS 16.0 software.Intergroup comparisons were carried out by one-way analysis of variance.Results：VEGF-A mRNA levels were elevated in the ISO group （1.57 ± 0.09） compared to those in the control group （P 〈 0.01）.Moreover,concentrations of VEGF-A in culture supernatants significantly differed between the control （113.00 ± 19.21 pg/ml） and ISO groups （287.00 ± 20.27 pg/ml;P 〈 0.01）.Expression of miR-1,miR-21,and miR-210 was higher （3.89 ± 0.44,2.87 ± 087,and 3.33 ± 1.31,respectively） in ISO-treated cells than that in controls （P 〈 0.01）,whereas that of GAS5 and MEG3 （0.22 ± 0.10 and 0.58 ± 0.16,respectively） was lower as a result of ISO administration （P 〈 0.05）.There was no significant difference in the expression of MALAT1 between the groups.Interestingly,miR-210 overexpression heightened the levels of VEGF-A and miR-21 （5.87 ± 1.24 and 2.74 ± 1.15,respectively;P 〈 0.01） and reduced those of GAS5 and MEG3 （0.19 ± 0.01 and 0.09 ± 0.05,respectively;P 〈 0.01）.Conclusions：ISO-mediated angiogenesis was associated with altered expression of miR-210,miR-21,and the lncRNAs GAS5 and MEG3.The effects ofmiR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO,indicating that it might play an important role in ISO-mediated angiogenesis.

Aim： To examine whether β-adrenoceptor （β-AR） agonists can induce hypoxia-inducible factor （HIF）-1α accumulation which then upregulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved. Methods： Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of β-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells. Results： Treatment of pancreatic cancer cell lines with β-AR agonists led to accumulation of HIF-1α and then up-regulated expression of its target genes independently of oxygen levels. The induction was partly or completely inhibited not only by β-AR antagonists but also by inhibitors of PKA transduction pathways and by siHIF-1α. Both β1-AR and β2-AR agonists produced the above-mentioned effects, but β2-AR agonist was more potent. Conclusion： Activation of β-AR receptor transactivates epidermal growth factor receptor （EGFR） and then elicites Akt and ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1α and downstream target genes independently of oxygen level. Our data suggest a novel mechanism in pancreatic cancer cells that links β-AR and HIF-1α signaling under normoxic conditions, with impli- cations for the control of glucose transport, angiogenesis and metastasis.

Using the high-resolution Terahertz Time-domain spectroscopy （THz-TDS） and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride （CH）, a 2 -adrenergic agonist for decreasing fat deposition and enhancing protein accretion, were measured in temperature range of 77–295 K. Between 0.2 and 3.6 THz （6.6–120.0 cm–1 ）, seven highly resolved spectral features, strong line-narrowing and a frequency blue-shift were observed with cooling. However, ractopamine hydrochloride, with some structural and pharmacological similarities to clenbuterol hydrochloride, showed no spectral features, indicating high sensitivity and strong specificity of THz-TDS. These results could be used for the rapid and nondestructive CH residual detection in food safety control.

Aim： To investigate the efficacy of glycyrrhizin （GL） combined with salbutamol （SA） as an anti-asthma therapy. Methods： Rat lung beta2-adrenergic receptor （β2-AR） mRNA level was measured by real-time RT PCR. Intracellular cAMP accumulation was evaluated with a reporter gene assay. An in vitro acetylcholine-induced guinea pig tracheal strip contraction model was used to test the relaxing effects of GL and SA. The anti-inflammatory effects of GL and SA were tested using tumor necrosis factor-α-induced NF-κB transcriptional activation reporter assay, I-κB Western blotting and interleukin-8 ELISA. An in vivo guinea pig asthma model was used to prove further the synergistic effect of GL and SA. Results： GL （0.3 μmol/L） increased mRNA levels of β2-AR in vivo and the accumulation of cAMP in vitro. The combination of GL and SA also resulted in significant complementary anti-inflammatory effects via inhibition of NF-κB activation, degradation of I-κB and production of interleukin-8. A significant synergistic effect of the combination was detected both in vitro and in vivo in a guinea pig mode. Conclusion： The results demonstrate that GL and SA have synergistic anti-asthmatic effects and offer the possibility of a therapeutic application of GL in combination with β2-AR agonists in the treatment of asthma.

In order to develop a model for screening the agonists of human β2-adrenoceptor from Chinese medicinal herbs extracts, we used a cell-based functional assay based on a common G protein-coupled receptor （GPCR） regulation mechanism and destabilized enhanced green fluorescent protein （d2EGFP） reporter gene technique. The positive cell clone was confirmed by real-time polymerase chain reaction （PCR） and imaging analysis. To assess the value of this model, we screened over 2000 high performance liquid chromatography （HPLC）-fractionated samples from the ethanol extracts of Chinese medicinal herbs. Six fractions （isolated from Panax japonicus, Veratrum nigrum, Phellodendron amurense, Fructus Aurantii lmmaturus, Chaenomeles speciosa, and Dictamnus dasycarpus） showed significant effects on active reporter gene expression, three of which （isolated from Phellodendron amurense, Fructus Aurantii lmmaturus, and Chaenomeles speciosa） were selected for further concentration response analysis and the half maximal effective concentration （EC1/2 max） values were 4.2, 2.7, and 4.8 μg/ml, respectively. Therefore, this reporter gene assay was suitable for screening β2-adrenoceptor agonists. The results suggest that the six herbal extracts are the possible agonists of β2-adrenoceptor.

目的 观察内生大麻素受体激动剂WIN 55,212-2对帕金森病左旋多巴相关异动症模型大鼠纹状体内单胺类神经递质释放的影响.方法 采用脑内微透析和高效液相色谱在线递质测量法观察WIN 55,212-2腹腔内注射对异动症模型大鼠左旋多巴相关异动症状和纹状体内单胺类神经递质释放的影响.结果 与溶剂注射相比,WIN 55,212-2注射显著抑制异动症模型大鼠左旋多巴皮下注射后的异动样症状（F1263=44.071,P＜0.001）,同时明显减少纹状体内多巴胺的释放（F1263=5.091,P＜0.05）.结论 纹状体内生大麻素受体可能通过抑制性的调节单胺类神经递质的释放来影响异动症模型大鼠的异动样症状.