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AIM: To investigate the effect of naringin (NRG) on cisplatin (DDP) resistance in human lung cancer A549/DDP cells and its possible mechanism. METHODS: A549/DDP cells were cultured in vitro and treated with NRG and/or DDP at different concentrations for 24 h, and then the cell viability were measured by CCK-8 assay. The combination index (CI) of NRG and DDP were analyzed by Chou-Talalay method. The apoptosis rate was analyzed by flow cytometry. Western blot was performed to detect the protein levels of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), p-Akt, CXC chemokine receptor 4 (CXCR4), cleaved caspase-3, Bcl-2 and Bax.RESULTS: The protein levels of P-gp, MRP1, p-Akt and CXCR4 in the A549/DDP cells were higher than those in the A549 cells (P<0.05). The cell viability was remarkably reduced in a dose-dependent manner when A549/DDP cells were exposed to NRG and/or DDP (P<0.05), and the IC50 values of NRG and DDP were 36.92 μmol/L and 129.77 μmol/L, respectively. When the inhibition rate exceeded 15%, NRG in combination with DDP produced a synergistic effect (CI<1). Combination treatment with NRG and DDP significantly induced apoptosis (P<0.05), up-regulated the protein levels of cleaved caspase-3 and Bax, and down-regulated the protein level of Bcl-2 (P<0.05). Meanwhile, NRG remarkably down-regulated the protein levels of P-gp, MRP1, p-Akt and CXCR4 in a dose-dependent manner (P<0.05). CONCLUSION: NRG may enhance the sensibility of A549/DDP cells to DDP most likely via up-regulating the protein level of Bax and down-regulating the protein levels of Bcl-2, P-gp, MRP1, p-Akt and CXCR4. 相似文献
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[目的]明确敌百虫在水产养殖中的安全性。[方法]全池泼洒0.5 mg/L敌百虫,采用气相色谱法测定敌百虫在乌鳢体内的代谢动力学和残留消除规律。[结果]乌鳢组织和水样中敌百虫的最低检测限为0.02μg/m L。随着时间的延长,敌百虫在乌鳢血液中的浓度逐渐升高,120 h达最高,为0.072 mg/kg,至360 h时未检出。肌肉中12 h内未检出,24 h浓度为0.023 mg/kg,120 h检出最大浓度0.051 mg/kg,至288 h未检出。肝脏8 h未检出,12 h检出浓度为0.026 mg/kg。使用敌百虫后,乌鳢体内的药物残留量均低于我国的兽药最高残留限量要求,但在养殖水体中的残留时间较长,降解半衰期为35.19 h。[结论]为确保敌百虫使用后对水生态环境及食品安全,建议敌百虫使用后的休药期为150℃·d。 相似文献
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Rabies is a neglected disease with an estimated annual mortality of 55,000 human deaths, affecting mainly low-income countries. Over 95% of these cases result from virus transmission through the bite of infected dogs and for this reason there is a real need for a cheap and effective rabies veterinary vaccine to be used in mass vaccination campaigns. In this work, we describe the establishment of a simple platform for the production of a virus-like particles based rabies vaccine using mammalian cells and roller bottles as culture system. Adherent cells were cultured during more than 15 days and VLPs were continuously produced and secreted to the culture supernatant. Immunogenicity and protective efficacy of VLPs were tested through rabies virus neutralizing antibody test and NIH potency test. These viral particles induced high titer of long lasting neutralizing antibodies and protected mice against active virus challenge. Therefore, this development represents a promising platform for the production of a new generation and virus-free rabies vaccine candidate for veterinary applications. 相似文献
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Cutaneous leishmaniasis (CL) is an infectious disease that commonly caused by Leishmania (L.) major and L.tropica. Recently there has been a growing interest in proteomics analysis on Leishmania for drug target discovery. Therefore, we aimed to distinguish proteins which might be characteristic for each of the species from those shared by both to the detection of drug targets, which may become helpful for designing new drugs for CL. To identify differences in protein profiles of L. major and L. tropica, we conducted a Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) analysis. Totally 67 differentially expressed proteins (DEPs) (fold change> 2 and p < 0.05) were identified between species. Of these, 42 and 25 proteins were up-regulated in L. major and L. tropica, respectively. Several enriched GO terms were identified via biological process of up-regulated proteins. Furthermore, the small molecule metabolic process and translation were detected as significant biological processes for up-regulated proteins in L. major, while translation was identified for L. tropica. Also, KEGG analysis has revealed glycolysis/gluconeogenesis and translation as the top pathways in the proteins up-regulated in L. major and L. tropica, respectively. Finally glycosomal malate dehydrogenase was identified as putative drug target using network and homology analyses. The DEPs between the species are essential in host-pathogen interactions and parasite survival in the macrophage. Furthermore, L. major and L. tropica possibly uses different pathogenicity mechanisms that leads to anthroponotic or zoonotic CL. Our results may help in the drug discovery and chemotherapeutic interventions. 相似文献