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目的探讨基于参考图压缩传感方法(RICS)的前列腺肿瘤定量DCE-MRI(qDCE-MRI)技术中图像重建的精确性和定量化药物代谢动力学参数估计的可靠性。方法比较RICS方法和全采样方法的qDCE-MR图像重建结果,以及由此估计的定量化药物代谢动力学参数。通过设置定量化指标,评估基于RICS的前列腺肿瘤qDCE-MRI的精确性和可靠性。结果 RICS法和传统全采样法的qDCE-MR图像重建结果之间的平均平方误差(MSE)在10-5量级,两种重建结果非常接近,但随加速倍数增加,两者差距增大。加速倍数为6时,通过RICS法和全采样法估计出的药物代谢动力学参数仍有较高相关性(两者之间的Ktrans和ve的Pearson相关系数分别为r=0.9260,P<0.01和r=0.9948,P<0.01)。结论基于RICS的前列腺肿瘤qDCE-MRI能够给出精确的图像重建结果,重建精确性随加速倍数增大而减小;加速倍数为6时,仍能估计出可靠的定量化药物代谢动力学参数。  相似文献   
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《Antiviral research》2009,81(3):360-369
Dengue virus (DENV) NS5 possesses methyltransferase (MTase) activity at its N-terminal amino acid sequence and is responsible for formation of a type 1 cap structure, m7GpppAm2′-O in the viral genomic RNA. Optimal in vitro conditions for DENV2 2′-O-MTase activity were characterized using purified recombinant protein and a short biotinylated GTP-capped RNA template. Steady-state kinetics parameters derived from initial velocities were used to establish a robust scintillation proximity assay for compound testing. Pre-incubation studies showed that MTase–AdoMet and MTase–RNA complexes were equally catalytically competent and the enzyme supports a random bi bi kinetic mechanism. The assay was validated with competitive inhibitory agents, S-adenosyl-homocysteine and two homologues, sinefungin and dehydrosinefungin. A GTP-binding pocket present at the N-terminal of DENV2 MTase was previously postulated to be the cap-binding site. Interestingly, inhibition of the enzyme by GTP was two-fold lower than with RNA cap analogues, G[5′]ppp[5′]A and m7G[5′]ppp[5′]A and about three-fold poorer than a two-way methylated analogue, m7G[5′]ppp[5′]m7G. This assay allows rapid and highly sensitive detection of 2′-O-MTase activity and can be readily adapted for high-throughput screening for inhibitory compounds. It is suitable for determination of enzymatic activities of a wide variety of RNA capping MTases.  相似文献   
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The H5N1 avian influenza virus (AIV) causes widespread infections in bird and human respiratory tracts, and vaccines and drug therapy are limited in their effectiveness. Recent studies of AIV structures have been published and provide new targets for designing antiviral drugs such as antisense oligonucleotides (AS ODNs), which effectively inhibit gene replication. In this study, we designed and synthesized three AS ODNs (NP267, NP628, NP749) that were specific for the RNA binding region of nucleoprotein (NP) based on AIV structure. Results showed that all three AS ODNs could inhibit viral replication in MDCK cells. The NP628 showed the best antiviral effect of all through viral titers, quantitative RT-PCR and indirect immunofluorescence (IFA) assays. In addition, the liposome mediated NP628 could partially protect the mice from a lethal H5N1 influenza virus challenge. Moreover, the NP628 group had a lower viral titer and lung index in the infected mice when compared with the viral control. Our results showed that AS ODN targeting of the AIV NP gene could potently inhibit AIV H5N1 reproduction, thus, formulating a candidate for an emergent therapeutic drug for the pathogenic H5N1 influenza virus infection.  相似文献   
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《Molecular immunology》2010,47(16):3462-3465
To evaluate the potential use of recombinant murine cytomegalovirus (MCMV) as an antigen delivery vector, we examined the cytokine and CD80 and CD86 expression profiles of MCMV encoding either enhanced green fluorescent protein gene (MCMV-EGFP) or human immunodeficiency virus-1 glycoprotein gp120 gene (MCMV-gp120) infected monocyte-derived dendritic cells (Mo-DC) and investigated the role of nuclear factor kappa B (NF-κB) in Mo-DC activation. Results showed that MCMV triggered the induction of inflammatory cytokines and/or CD80 and CD86 up-regulation in Mo-DC. UV-inactivated MCMV exhibited a reduced production of inflammatory cytokines and a lowered expression of CD80 and CD86 compared with live MCMV infection. Treatment of cells with a NF-κB peptide inhibitor prior to MCMV infection reduced the induction of cytokines and CD80 and CD86 up-regulation. Overall, the results suggest that recombinant MCMV vectors activate human Mo-DC in a NF-κB dependent pathway. The abortive infection or de novo gene expression greatly enhances the activation of Mo-DC by MCMV vectors.  相似文献   
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