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991.
Chunlin Zhuang Chunquan Sheng Woo Shik Shin Yuelin Wu Jin Li Jianzhong Yao Guoqiang Dong Wen Zhang Yuk Yin Sham Zhenyuan Miao Wannian Zhang 《Oncotarget》2014,5(21):10830-10839
The p53 and nuclear factor κB (NF-κB) pathways play crucial roles in human cancer development. Simultaneous targeting of both pathways is an attractive therapeutic strategy against cancer. In this study, we report an antitumor molecule that bears a pyrrolo[3,4-c]pyrazole scaffold and functions as an enantiomeric inhibitor against both the p53-MDM2 interaction and the NF-κB activation. It is a first-in-class enantiomeric inhibitor with dual efficacy for cancer therapy. Synergistic effect was observed in vitro and in vivo. Docking and molecular dynamics simulation studies further provided insights into the nature of stereoselectivity. 相似文献
992.
Oxygen dynamics at paraspinal muscles during exertion using near-infrared spectroscopy in patients with degenerative lumbar scoliosis 总被引:1,自引:0,他引:1
Motoo Miyake Yoshiaki Harada Masuo Senda Kou Oda Hajime Inoue 《Journal of orthopaedic science》2003,8(2):187-191
Oxygen dynamics were measured in both sides of the paraspinal muscles of patients with degenerative lumbar scoliosis. The
objective was to investigate the extent of stress by measuring the changes in oxygenation and blood flow volume using near-infrared
spectroscopy. There were 44 patients with degenerative lumbar scoliosis (7 men, 37 women) and 11 controls with no scoliosis
(2 men, 9 women). The measured recovery time for deoxyhemoglobin indicated the recovery from energy deficit after exercise.
The average recovery time of the 11 control subjects was 2.4 ± 0.7 s on the right and 2.4 ± 0.8 s on the left. Among the 44
patients the average recovery time was 3.8 ± 1.8 s on the convex side and 2.1 ± 1.1 s on the concave side. There was a significant
difference between the two groups. The recovery time on the concave side in patients was faster than that on the convex side.
The results of the current study support the theory that stretching the muscles at the convex side results in chronic increases
in the intramuscular compartment and reduced muscular blood flow.
Received: May 23, 2002 / Accepted: October 29, 2002
Offprint requests to: M. Miyake, Department of Orthopaedic Surgery, Eiko Hospital, 1381 Takuma, Takuma-cho, Mitoyo-gun, Kagawa 769-1101, Japan 相似文献
993.
目的: 建立HPLC-FD测定大鼠尿液中儿茶酚胺类化合物(CAs)的含量,为虚热证的药理学研究提供参考. 方法: 采用酸性氧化铝吸附法制备大鼠尿样;使用HiQSil C18V色谱柱,流动相0.02 mol·L-1 KH2PO4水溶液,流速0.5 mL·min-1,激发波长(EX)280 nm,发射波长(EM)316 nm,柱温40℃. 结果: 大鼠尿样供试液中的儿茶酚胺类化合物可以与各干扰组分达到基线分离;CAs各组分线性、精密度和重复性良好;该法制备的样品溶液在16 h内测定,RSD<2%;CAs的回收率在65%~71%,试验中测得适应期后大鼠尿液中CAs含量稳定. 结论: 该文采用的供试品溶液制备方法简便,建立的色谱分析方法稳定、可靠,适合于大鼠尿液中CAs的含量测定. 相似文献
994.
目的:观察针刺期门穴对慢性胆囊炎患者低张力胆囊运动影响的时效规律。方法:B超测定针刺前即时及进针后第5 min、10 min、20 min、30 min、40 min、50 min、60 min的量胆囊体积、收缩率,描记针刺期门对胆囊运动影响的时效规律曲线。结果:针刺的最初40 min内胆囊发生2次收缩,并在进针40 min后达到收缩峰值( P<0.05)。结论:针刺期门修复低张力胆囊动力学的最佳留针时间以40 min左右为佳,以每天治疗2次为宜。 相似文献
995.
Background
Studies have highlighted asymmetries in knee joint moments in individuals with osteoarthritis and joint replacements. However, there is a need to investigate the forces at the knee joints to establish the extent of loading asymmetries.Methods
Twenty healthy (mean age, 62; range, 55–79 years) and 34 pre- to post-knee arthroplasty (mean age, 64; range, 39–79 years) participants performed gait and sit–stand activities in a motion capture laboratory. Knee joint forces and moments were predicted using inverse dynamics and used to calculate peak loading and impulse data which were normalized to body weight. Comparisons were made between affected and contralateral limbs, and changes from pre- to post-knee arthroplasty.Findings
Pre-knee arthroplasty peak vertical knee forces were greater in the contralateral limb compared to the affected limb during both gait 3.5 vs. 3.2 ∗ body weight and sit–stand 1.8 vs. 1.5 ∗ body weight. During gait, peak knee adduction moment asymmetries significantly changed from pre- to post-knee arthroplasty (− 0.3 to 0.8 ∗ % body weight ∗ m ∗ height), although differences in vertical knee forces remained. There were no significant changes in loading during sit-stand from pre- to post-knee arthroplasty. The healthy participants showed no noteworthy asymmetries.Interpretation
This study showed loading asymmetries in knee forces between affected and contralateral limbs both pre- and post-knee arthroplasty. Continued over reliance of the contralateral limb could lead to pathology. 相似文献996.
The use of lipoplexes for the intracellular delivery of nucleic acids typically involves the optimization of several parameters that are known to affect delivery. Researchers commonly vary charge ratio, and often incorporate different amounts of helper lipids (e.g., cholesterol) to optimize formulations for transfection in cell culture and in vivo. The results of such experiments are often interpreted in the context of nuclease resistance and cell association, but effects on the protein corona are usually not considered. While many studies have demonstrated that lipoplex structure and function can be dramatically compromised in the presence of serum, little attention has been paid to the adsorption of specific proteins and how this might be affected by formulation parameters. In this study, we characterize changes in the protein corona that occur as DOTAP-based lipoplexes are formulated with different amounts of cholesterol and prepared at different charge ratios. Our results demonstrate a significant effect of lipid composition on both total protein adsorption as well as the individual proteins from fetal calf serum that are associated with lipoplexes. In addition, we show that PEGylation increases protein adsorption with our formulations; effects that depend on the type of PEG conjugate employed in the lipoplex. Attempts to identify a specific protein responsible for enhancing transfection were unsuccessful. 相似文献
997.
998.
Experimental and theoretical study of selective protein deposition using focused micro laminar flows
The present work describes an experimental method and design tools which enable the precise localization of an analyte, a
few microns in width, both temporally and spatially using laminar flows and thus improves previous methods in hydrodynamic
focusing. The technique is used to adsorb proteins to selected regions within a microfluidic device without any contamination
of the surroundings and may serve in applications requiring selective conveying of other reagents. The regions not coated
by proteins are modified with poly(ethylene glycol; PEG), known to efficiently resist protein and cell adhesion. Human endothelial
and fibroblast cells are later introduced into the device selectively attaching to the protein coated regions and cultured
for a few days. A simulation of the convection–diffusion characteristics of the system is presented and compared to the known
T-sensor. The results reveal that, by proper design, reagents concentration may be kept nearly constant along the flow direction.
This phenomenon is demonstrated here by achieving particularly precise patterning of cells but may be utilized for numerous
other applications as well.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
999.
The appropriate level of microtubule stability is fundamental in neurons to assure correct polarity, migration, vesicles transport and to prevent axonal degeneration. In the present study, we have identified Notch pathway as an endogenous microtubule stabilizer. Stimulation of Notch receptors by exposure of mouse cortical neurons to the Notch ligand Jagged1 resulted in increased microtubule stability, as measured by using antibodies against post-translationally modified alpha tubulin, and changes in axonal morphology and branching, with varicosity loss, thicker neurites and enlarged growth cones. Similar effects were found after exposure of the cells to different doses of Taxol. However, contrary to Taxol, Jagged1 induced downregulation of the microtubule severing protein Spastin. We suggest that a fine-tuned manipulation of Notch signaling may represent a novel approach to modulate neuronal cytoskeleton plasticity. 相似文献
1000.
Andreote FD Rossetto PB Souza LC Marcon J Maccheroni W Azevedo JL Araújo WL 《Journal of basic microbiology》2008,48(5):338-346
Harmless bacteria inhabiting inner plant tissues are termed endophytes. Population fluctuations in the endophytic bacterium Pantoea agglomerans associated with two species of field cultured citrus plants were monitored over a two-year period. The results demonstrated that populations of P. agglomerans fluctuated in Citrus reticulata but not C. sinensis. A cryptic plasmid pPA3.0 (2.9 kb) was identified in 35 out of 44 endophytic isolates of P. agglomerans and was subsequently sequenced. The origins of replication were identified and nine out of 18 open reading frames (ORFs) revealed homology with described proteins. Notably, two ORFs were related to cellular transport systems and plasmid maintenance. Plasmid pPA3.0 was cloned and the gfp gene inserted to generate the pPAGFP vector. The vector was introduced into P. agglomerans isolates and revealed stability was dependent on the isolate genotype, ninety-percent stability values were reached after 60 hours of bacterial cultivation in most evaluated isolates. In order to definitively establish P. agglomerans as an endophyte, the non-transformed bacterium was reintroduced into in vitro cultivated seedlings and the density of inner tissue colonization in inoculated plants was estimated by bacterium re-isolation, while the tissue niches preferred by the bacterium were investigated by scanning electronic microscopy (SEM). Cells from P. agglomerans (strain ARB18) at similar densities were re-isolated from roots, stems and leaves and colonization of parenchyma and xylem tissues were observed. Data suggested that P. agglomerans is a ubiquitous citrus endophyte harboring cryptic plasmids. These characteristics suggest the potential to use the bacterium as a vehicle to introduce new genes in host plants via endophytic bacterial transformation. 相似文献