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101.
Youguang Zheng Ming Zheng Xin Ling Yi Liu Yunsheng Xue Lin An Ning Gu Min Jin 《Bioorganic & medicinal chemistry letters》2013,23(12):3523-3530
Novel pyrazole–benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence. 相似文献
102.
103.
Rong-Guo Fu Tao Zhang Li Wang Yan Du Li-Ning Jia Jing-Jing Hou Gang-Lian Yao Xiao-Dan Liu Lei Zhang Ling Chen Bao-Song Gui Rong-Liang Xue 《PloS one》2014,9(1)
Objective
KCa3.1 channel participates in many important cellular functions. This study planned to investigate the potential involvement of KCa3.1 channel in premature senescence, myofibroblast phenotype transition and proliferation of mesangial cells.Methods & Materials
Rat mesangial cells were cultured together with TGF-β1 (2 ng/ml) and TGF-β1 (2 ng/ml) + TRAM-34 (16 nM) separately for specified times from 0 min to 60 min. The cells without treatment served as controls. The location of KCa3.1 channels in mesangial cells was determined with Confocal laser microscope, the cell cycle of mesangial cells was assessed with flow cytometry, the protein and mRNA expression of KCa3.1, α-smooth muscle actin (α-SMA) and fibroblast-specific protein-1 (FSP-1) were detected with Western blot and RT-PCR. One-way analysis of variance (ANOVA) and Student-Newman-Keuls-q test (SNK-q) were used to do statistical analysis. Statistical significance was considered at P<0.05.Results
Kca3.1 channels were located in the cell membranes and/or in the cytoplasm of mesangial cells. The percentage of cells in G0-G1 phase and the expression of Kca3.1, α-SMA and FSP-1 were elevated under the induction of TGF-β1 when compared to the control and decreased under the induction of TGF-β1+TRAM-34 when compared to the TGF-β1 induced (P<0.05 or P<0.01).Conclusion
Targeted disruption of KCa3.1 inhibits TGF-β1-induced premature aging, myofibroblast-like phenotype transdifferentiation and proliferation of mesangial cells. 相似文献104.
Background
As the murine model of laser-induced choroidal neovascularization (CNV) is becoming the most established and commonly utilized model worldwide for studying the pathogenesis of CNV and its response to treatment, specific operating standards are yet to be clarified. The purpose of this study is to compare the lesion size of CNV in mice with different ages, sex, durations of CNV process, and treated positions of laser spots, to make recommendations that may improve and optimize the quality of the model.Methods and Results
C57/BL6 mice of different ages were treated with diode laser photocoagulation per eye and perfused with PBS containing fluorescein-labeled dextran at different time of observation. Choroid flat mounts, were then examined by fluorescence microscopy for the measurement of CNV area. Messenger-RNA expression levels of several angiogenic cytokines in eye cups of male and female C57BL/6 mice at 5–8 and 16–20 week-old were analyzed by real-time RT-PCR assay. The results showed significantly more CNV area in eyes of female mice compared to male mice with the expression level of several angiogenic cytokines elevated. 16–20-week-old female mice developed the biggest area of CNV. The mean area of CNV increased significantly at the 14th day after photocoagulation. Laser spots delivered 1PD away from the optic disc induced the biggest area of CNV compared to those 2PD or 3PD away. Interaction of NV was observed in laser spots delivered less than 1PD away from each other.Conclusion
The current results suggest that 16–20-week-old female C57BL/6 mice developed the most distinct CNV lesion size with laser spots delivered 1PD away from the optic disc. The best time to observe and analyze is the 14th day after photocoagulation. 相似文献105.
Background
Aflibercept is a human recombinant fusion protein with antiangiogenic effects that functions as a decoy receptor to bind vascular endothelial growth factor A. Proteinuria is one of its major adverse effects with a substantial variation in the incidence rate, and the overall risk of proteinuria has not been systematically studied. We performed a meta-analysis of published clinical trials to quantify the incidence and relative risk of proteinuria in cancer patients treated with aflibercept.Methods
The electronic databases were searched, including PubMed, Embase, Cochrane databases, and ASCO (American Society of Clinical Oncology) abstracts. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity data on proteinuria. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies.Results
A total of 4,596 patients with a variety of solid tumors from 16 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade proteinuria in cancer patients were 33.9% (95% CI: 27.3–42.1%) and 7.9% (95% CI: 6.1–10.2%). The relative risks of proteinuria of aflibercept compared to control were increased for all-grade (RR = 1.41, 95% CI: 1.13–1.77) and high-grade (RR = 6.18, 95% CI: 3.78–10.12) proteinuria. The risk of developing all-grade and high-grade proteinuria with aflibercept was substantially higher than that of bevacizumab (all-grade: RR 1.85, 95% CI: 1.63–2.11; high-grade: RR 2.37, 95% CI: 1.84–3.05).Conclusions
Aflibercept is associated with an increased risk of developing proteinuria. Appropriate monitoring and treatment is strongly recommended to prevent potential renal damage. Future studies are still needed to investigate the risk reduction and possible use of aflibercept in cancer patients. 相似文献106.
上海郊区人群的体质特征和遗传关系 总被引:2,自引:0,他引:2
本项研究收集了上海郊区的 13个具有明显方言差异的人群的各类人类遗传学数据 5 3项进行聚类分析 ,发现黄浦江以东的人群相对较纯 ,而黄浦江以西的则较混杂 ,两组群体都分别可以聚成较远的 3类。由此认为上海郊区的人群大致有 3种起源 ,上海奉贤区金汇镇和闵行区马桥镇为代表的居民与南方土著民族较近 ,崇明县、嘉定区、浦东新区和南汇区的居民与北方民族较近 ,而奉贤区的头桥镇、金山区、青浦区的朱家角和商榻、松江区天马山等地的居民又是另一类。这与历史记载他们的不同来源有关。 相似文献
107.
108.
Juan Huang Jialin Wang Lijie Gu Jinfang Bao Jun Yin Zhihuan Tang Ling Wang Weijie Yuan 《PloS one》2013,8(11)
A low-protein diet supplemented with ketoacids maintains nutritional status in patients with diabetic nephropathy. The activation of autophagy has been shown in the skeletal muscle of diabetic and uremic rats. This study aimed to determine whether a low-protein diet supplemented with ketoacids improves muscle atrophy and decreases the increased autophagy observed in rats with type 2 diabetic nephropathy. In this study, 24-week-old Goto-Kakizaki male rats were randomly divided into groups that received either a normal protein diet (NPD group), a low-protein diet (LPD group) or a low-protein diet supplemented with ketoacids (LPD+KA group) for 24 weeks. Age- and weight-matched Wistar rats served as control animals and received a normal protein diet (control group). We found that protein restriction attenuated proteinuria and decreased blood urea nitrogen and serum creatinine levels. Compared with the NPD and LPD groups, the LPD+KA group showed a delay in body weight loss, an attenuation in soleus muscle mass loss and a decrease of the mean cross-sectional area of soleus muscle fibers. The mRNA and protein expression of autophagy-related genes, such as Beclin-1, LC3B, Bnip3, p62 and Cathepsin L, were increased in the soleus muscle of GK rats fed with NPD compared to Wistar rats. Importantly, LPD resulted in a slight reduction in the expression of autophagy-related genes; however, these differences were not statistically significant. In addition, LPD+KA abolished the upregulation of autophagy-related gene expression. Furthermore, the activation of autophagy in the NPD and LPD groups was confirmed by the appearance of autophagosomes or autolysosomes using electron microscopy, when compared with the Control and LPD+KA groups. Our results showed that LPD+KA abolished the activation of autophagy in skeletal muscle and decreased muscle loss in rats with type 2 diabetic nephropathy. 相似文献
109.
110.
对1例新型冠状病毒肺炎疫情流行早期的无症状感染者临床标本进行SARS-CoV-2实验室鉴定和全基因组测定,在分子水平了解新型病毒的基因特点和变异情况,追溯病毒潜在来源.实时荧光定量PCR扩增丽水市庆元县首例确诊患者密切接触者的痰液标本SARS-CoV-2核酸,阳性RNA逆转录为cDNA构建文库后进行基于NGS的宏基因组深度测序,生物学软件分析处理数据.该密接无任何症状及体征,痰液标本SARS-CoV-2核酸阳性.测序数据包含有足够的病毒序列,组装成功后hCoV-19/Lishui/LS556/2020长29 887bp,G+C含量37.99%,在ORF1ab和N区域发现4个SNP,对应1个错义突变和3个同义突变.LS556与SARS-CoV-2参考序列核苷酸/氨基酸同源性在99.2%/97.4%以上,不同序列之间存在4~17个核苷酸差异,与蝙蝠病毒RaTG13核苷酸差异仅3.7%,存在1141个SNP,与穿山甲病毒Guangdong/1相似性90.9%.LS556属于β冠状病毒Lineage B谱系,与LS003和ZJU-06共享完全相同的病毒,与蝙蝠/穿山甲冠状病毒进化上最相关.结合流行病学、核酸诊断、病毒溯源判定其为无症状感染者.LS556组成和结构符合SARS-CoV-2典型的基因特征,为高覆盖率序列,在流行早期与其他SARS-CoV-2基因组具有高度的同一性,突变率保持在较低水平,多数导致氨基酸位点保守置换. 相似文献