Search

Background: Oncolytic viruses represent a promising therapy against cancers with acquired drug resistance. However, low efficacy limits its clinical application. The objective of this study is to investigate whether pharmacologically modulating autophagy could enhance oncolytic Newcastle disease virus (NDV) strain NDV/FMW virotherapy of drug-resistant lung cancer cells. Methods: The effect of NDV/FMW infection on autophagy machinery in A549 lung cancer cell lines resistant to cisplatin (A549/DDP) or paclitaxel (A549/PTX) was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, formation of double-membrane vesicles and conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). The effects of autophagy inhibitor chloroquine (CQ) and autophagy inducer rapamycin on NDV/FMW-mediated antitumor activity were evaluated both in culture cells and in mice bearing drug-resistant lung cancer cells. Results: We show that NDV/FMW triggers autophagy in A549/PTX cells via dampening the class I PI3K/Akt/mTOR/p70S6K pathway, which inhibits autophagy. On the contrary, NDV/FMW infection attenuates the autophagic process in A549/DDP cells through the activation of the negative regulatory pathway. Furthermore, combination with CQ or knockdown of ATG5 significantly enhances NDV/FMW-mediated antitumor effects on A549/DDP cells, while the oncolytic efficacy of NDV/FMW in A549/PTX cells is significantly improved by rapamycin. Interestingly, autophagy modulation does not increase virus progeny in these drug resistant cells. Importantly, CQ or rapamycin significantly potentiates NDV/FMW oncolytic activity in mice bearing A549/DDP or A549/PTX cells respectively. Conclusions: These results demonstrate that combination treatment with autophagy modulators is an effective strategy to augment the therapeutic activity of NDV/FMW against drug-resistant lung cancers. [ABSTRACT FROM AUTHOR]

Background A retrospective study was conducted to evaluate the advantages of anterolateral thigh (ALT) flap in tongue reconstruction. Method From September 2008 to February 2012, patients receiving ALT flap tongue reconstruction were included in the study. Patients undergoing ALT flap were compared with those undergoing similar surgery with radial forearm flap (RFF). The medical records of the included patients were reviewed, and a questionnaire was used to assess acceptability of the surgery. Results All flaps (both ALT and RFF) were successful In the ALT group, most patients were satisfied with the appearance of the reconstructed tongue and the intelligibility of their speech, and there were fewer complications with this technique compared with the RFF. Conclusion The ALT flap is an ideal method for tongue reconstruction. The thickness and volume of the ALT flap can be adjusted based on the individual extent of the defect, and it can not only provide bulk but also ensure mobility, and it has other advantages also, including a long pedicle and low donor site morbidity. [ABSTRACT FROM AUTHOR]

Under the conditions of potentiostatic electrolysis, the electropolymerization of o-toluidine (OT) and para-phenylenediamine (PPDA) and the electrocopolymerization between OT and PPDA on an indium tin oxide (ITO) conductive glass electrode at potentials of 0.7, 0.8, and 0.9 V were studied in detail by in situ ultraviolet-visible (UV-vis) spectrometry in 0.5 mol/L sulfuric acid media. It was shown that both OT and PPDA could be electropolymerized on the ITO electrode, which depended on the applied electrolysis potential and the concentration of the monomer. Furthermore, in situ UV-vis spectra indicated that the electrocopolymerization between OT and PPDA could happen. The presence of PPDA not only promoted polymerization but also accelerated polymerization, which was attributed to the formation of an intermediate result from the coupling of PPDA and the toluidine monomer cation radical. PPDA could be incorporated into the copolymer to make the copolymer have a phenazine or phenazine-like cyclic structure, which was proven by the reflectance Fourier transform infrared spectra of the polymer and copolymer. The scanning electron microscopy morphology images of the polymers obtained showed that, in addition to accelerating polymerization, PPDA also could change the method of nucleation for the polymer to make the copolymer possess a fibrous surface morphology. The diameter of the fibroid copolymer was about 100 nm, and the length of that reached about 1000 nm. In the article, a newer concerned mechanism of copolymerization was proposed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [ABSTRACT FROM AUTHOR]

Heavy metal contamination in surface sediments of the Jiaozhou Bay was investigated in this study. Sediment sample was collected from the Jiaozhou Bay and its rivers. Heavy metal concentration was determined by inductively coupled plasma atomic emission spectroscopy and graphite furnace atomic absorption spectrometry. The result shows that river sediment in the east coast of the Jiaozhou Bay was heavily polluted especially for the Cu, Pb, Cd, and Zn. A slightly increase of heavy metal concentration was observed at stations near the east coast in the Jiaozhou Bay; however, contaminated sediment from polluted river was constrained mostly near shore within 3–4 km. Downstream decrease of heavy metals in river mouth suggested dilution from strong tidal current. Rapid seaward decline in the east coast and alongshore band dispersal pattern of heavy metals in surface sediment indicated mixing and remobilizing enhanced by large tidal range that regulated dispersal of sediments and anthropogenic heavy metals in the Jiaozhou Bay area. [ABSTRACT FROM AUTHOR]

A new electrochemical procedure for electrosynthesis of organic carbonates from CO2 and alcohols has been established in CO2-saturated room temperature ionic liquid BMIMBF4 solution, followed by addition of an alkylating agent. The synthesis was carried out under mild (PCO2 =1.0 atm, T = 55 °C) and safe conditions. The use of volatile and toxic solvents and catalysts as well as of any additional supporting electrolytes has been avoided. The influence of temperature, cathode material, working potential, alcohol concentration and the charge passed on the reaction using methanol (1a) as the model compound was examined. The ionic liquid used for the reaction was recyclable. The obtained results showed that the primary and secondary alcohols were converted in good yields, whereas tertiary alcohol and phenol were unreactive. [ABSTRACT FROM AUTHOR]

The biosynthesis of seed oil and starch both depend on the supply of carbon from the maternal plant. The biochemical interactions between these two pathways are not fully understood. In the Arabidopsis mutant shrunken seed 1 ( sse1)/ pex16, a reduced rate of fatty acid synthesis leads to starch accumulation. To further understand the metabolic impact of the decrease in oil synthesis, we compared soluble metabolites in sse1 and wild type (WT) seeds. Sugars, sugar phosphates, alcohols, pyruvate, and many other organic acids accumulated in sse1 seeds as a likely consequence of the reduced carbon demand for lipid synthesis. The enlarged pool size of hexose-P, the metabolites at the crossroad of sugar metabolism, glycolysis, and starch synthesis, was likely a direct cause of the increased flow into starch. Downstream of glycolysis, more carbon entered the TCA cycle as an alternative to the fatty acid pathway, causing the total amount of TCA cycle intermediates to rise while moving the steady state of the cycle away from fumarate. To convert the excess carbon metabolites into starch, we introduced the Escherichia coli starch synthetic enzyme ADP-glucose pyrophosphorylase (AGPase) into sse1 seeds. Expression of AGPase enhanced net starch biosynthesis in the mutant, resulting in starch levels that reached 37% of seed weight. However, further increases above this level were not achieved and most of the carbon intermediates remained high in comparison with the WT, indicating that additional mechanisms limit starch deposition in Arabidopsis seeds. [ABSTRACT FROM AUTHOR]