92 research outputs found

    Global pharmaceutical innovation network.

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    <p>Note: AR Argentina, AT Austria, AU Australia, BE Belgium, CA Canada, CH Switzerland, CN China, CZ Czech Republic, DE Germany, DK Denmark, ES Spain, FI Finland, FR France, GB United Kingdom, IE Ireland, IL Israel, IN India, IT Italy, JP Japan, NL Netherlands, PL Poland, SE Sweden, US United States. Note: Vertex positions determined using spectral graph analytic methods according to the normalized Laplacian so that countries that are strongly interconnected positioned nearer to each other <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0077247#pone.0077247-Higham1" target="_blank">[27]</a>. Node size corresponds to the weighted degree centrality of a country that is defined as the sum of a countrýs co-intventorships, the strength of the lines correspond to total co-inventorships between two countries.</p

    Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment

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    Development of new, antimetastatic drugs from natural products has been substantially constrained by the lack of a reliable in vitro screening system. Such a system should ideally mimic the native, three-dimensional (3D) tumor microenvironment involving different cell types and allow quantitative analysis of cell behavior critical for metastasis. These requirements are largely unmet in the current model systems, leading to poor predictability of the in vitro collected data for in vivo trials, as well as prevailing inconsistency among different in vitro tests. In the present study, we report application of a 3D, microfluidic device for validation of the antimetastatic effects of 12 natural compounds. This system supports co-culture of endothelial and cancer cells in their native 3D morphology as in the tumor microenvironment and provides real-time monitoring of the cells treated with each compound. We found that three compounds, namely sanguinarine, nitidine, and resveratrol, exhibited significant antimetastatic or antiangiogenic effects. Each compound was further examined for its respective activity with separate conventional biological assays, and the outcomes were in agreement with the findings collected from the microfluidic system. In summary, we recommend use of this biomimetic model system as a new engineering tool for high-throughput evaluation of more diverse natural compounds with varying anticancer potentials

    The centrality share of the US in global drug innovation network.

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    <p>Note: The percentages in the cell refer to the share of the centrality of the US in total sum of relative centrality of all countries in global innovation network of specific drug coverage during specific time periods.</p

    Involvement of caspase activation in MCF-7 and MCF-7/ADR cells after treated with EVO for 48 h.

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    <p>EVO increase the activities of caspase 3/7 (<b>A</b>) and caspase 9 (<b>B</b>) in MCF-7 and MCF-7/ADR cells by a dose-dependent manner. Data were expressed as mean ± SE of two or three independent experiments. * P<0.05 vs. untreated MCF-7 cells, <sup>#</sup> P<0.05 vs. untreated MCF-7/ADR cells. (<b>C</b>) MCF-7 and MCF-7/ADR cells were treated with different concentrations of EVO for 48 h. The cells were used for Western blot analysis using antibodies against activated Caspase 7, 9 and GAPDH. Similar results were obtained in two or three separate experiments.</p

    Centrality percentage of countries in global drug innovation network: Total new drugs vs. NME drugs (2006–2010).

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    <p>Note: The percentages in the rows of Difference are equal to values of relative NME minus values of according total new drugs. The differences are used to measure changes of the centrality share of countries from innovation network based on total new drugs to the network constructed by NME. The percentages in the total new drugs and NME refer to the share of national or regional centrality in total sum of relative centrality.</p

    EVO induces apoptosis in MCF-7 and MCF-7/ADR cancer cells.

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    <p>(<b>A</b>) Hoechst 33342 fluorescent staining to detect apoptotic morphology of MCF-7 and MCF-7/ADR cells after treatment of different concentrations of EVO for 48 h. Apoptotic cells were recognized by condensed, fragmented and or degraded nuclei. Cells were observed of three experiments using Incell Analyzer 2000 (GE healthcare) (<b>B</b>) Quantitative apoptotic measurement by Annexin V/PI double staining in MCF-7 and MCF-7/ADR cells after treatment of different concentrations of EVO for 48 h. Data were expressed as mean ± SE of three independent experiments. * P<0.05 vs. untreated control (MCF-7), <sup>#</sup> P<0.05 vs. untreated control (MCF-7/ADR). (<b>C</b>) MCF-7 and MCF-7/ADR cells were plated on 100 mm-diameter dishes and treated with different concentrations of EVO for 48 h. The cells were used for Western blot analysis using antibodies against activated PARP and β-Actin.</p

    Kinetics Study of the Esterification Reaction of Diethylene Glycol Monobutyl Ether with Acetic Acid Catalyzed by Heteropolyanion-Based Ionic Liquids

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    Novel heteropolyanion-based ionic liquids (HPA-ILs) were obtained by combining Keggin heteropolyanions and organic cations and used as catalysts for an esterification reaction. The kinetic behaviors in the esterification of diethylene glycol monobutyl ether (DGBE) with acetic acid in the presence of HPA-ILs as catalysts were investigated systemically. Different types of HPA-ILs were used for the esterification of DGBE. Compared with H<sub>2</sub>SO<sub>4</sub>, H<sub>3</sub>PW<sub>12</sub>O<sub>40</sub>, and Amberlyst-15 resins, [BSEt<sub>3</sub>N]<sub>3</sub>PW<sub>12</sub>O<sub>40</sub> and [BSmim]<sub>3</sub>PW<sub>12</sub>O<sub>40</sub> exhibited excellent catalytic activities. The influences of reaction temperature, catalyst dosage, and reactant molar ratio on the conversion of DGBE were studied in detail. The kinetic data were successfully correlated by a pseudohomogeneous (PH) model in the temperature range of 343.15–363.15 K. The simulation values obtained by the kinetic model were in good agreement with the experimental data. Moreover, [BSEt<sub>3</sub>N]<sub>3</sub>PW<sub>12</sub>O<sub>40</sub> and [BSmim]<sub>3</sub>PW<sub>12</sub>O<sub>40</sub> could be easily recovered and reused six times without any obvious decrease in catalytic activity

    EVO sensitize the effect of DOX without inhibiting P-glycoprotein.

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    <p>MCF-7 (<b>A</b>) and MCF-7/ADR (<b>B</b>) cells were pretreated with EVO and Verapamil for 12 h, and then incubated Dox (2 µM) for another 4 h, then the intracellular level of Dox was determined using flow cytometry. (<b>C</b>) Effects of EVO on the expression levels of P-gp protein in MCF-7/ADR cells. After 24 h treatment of EVO and verapamil, protein levels in cell lysates were analyzed by Western blot. GAPDH was used as an internal control. Similar results were obtained in two or three separate experiments. (<b>D</b>) After 12 h treatment, the MDR pump activities were determined using a fluorimetric MDR assay kit (Abcam). Results are expressed as mean ± SE.</p
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