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131.
Lifang Guo Xingchao Geng Li Liu Yufa Miao Zhi Lin Min Yu Yan Fu Lihong Liu Bo Li Yongzhang Luo 《Journal of biochemical and molecular toxicology》2019,33(3)
Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M2ES was evaluated by silver stain and reversed‐phase high‐performance liquid chromatography. Ultraviolet spectrum was used to examine the structural of M2ES and endostar. The bioactivity and antitumor efficacy of M2ES were evaluated using an in vitro endothelial cell migration model and athymic nude mouse xenograft model of a heterogeneous lung adenocarcinoma, respectively. A preclinical study was performed to evaluate the acute toxicity and safety pharmacology in rhesus monkeys. The purity of M2ES was more than 98%; PEG modification has no effect on endostatin structure. Compared with the control group, M2ES dramatically retards endothelial cell migration and tumor growth. After intravenous (IV) infusions of M2ES at a dose level of three and 75 mg/kg in rhesus monkeys, there was no observable serious adverse event in both acute toxicity and safety pharmacology study. On the basis of the quality and bioactivity study data of M2ES and the absence of serious side effect in rhesus monkeys, M2ES was authorized to initiate a phase I clinical trial. 相似文献
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133.
【目的】考察固态和液态两种培养方式对丝状真菌华根霉(Rhizopus chinensis)CCTCC M201021产胞外蛋白的影响,以加深对微生物固、液态培养特异性产酶的认识。【方法】利用成分相同的培养基对华根霉分别进行平板固态培养和液态培养,提取华根霉所产胞外蛋白,采用二维凝胶电泳(2-DE)结合质谱分析,分离鉴定差异蛋白。【结果】固态培养下华根霉所产胞外蛋白的蛋白酶活性是液态培养的9.2倍。胞外蛋白质组数据分析表明,华根霉固态和液态培养所产胞外蛋白存在显著差异,其中约70%是固态和液态培养下各自产生的特有蛋白。质谱鉴定进一步表明,固、液态培养对华根霉产胞外蛋白的种类和表达量都有显著影响,其中水解酶类所占比例较大,主要是与蛋白质降解相关的蛋白。【结论】固态和液态不同培养方式影响了华根霉产胞外蛋白的组成,有些基因只在特定培养方式下表达。固态培养下华根霉产胞外蛋白酶种类相对更多以及大部分蛋白酶的上调表达,可能是固态培养下胞外蛋白酶活性很高的原因。研究结果提示需要注意固液态不同培养方式下丝状真菌胞外酶的筛选和生产可能存在的不一致性。 相似文献
134.
海藻多糖抑制白细胞呼吸爆发作用研究 总被引:15,自引:0,他引:15
采用ESR、自旋捕集及自旋氧探针技术,研究了海藻硫酸多糖(SPS)对豆蔻酰佛波醇乙酯(PMA)刺激的多形核白细胞(PMN)呼吸爆发的影响.结果表明,SPS能显著抑制PMN呼吸爆发,10 g/L和5 g/L SPS几乎完全清除PMN呼吸爆发产生的自由基,1 g/L SPS可清除53.2%;10 g/L SPS对PMN的耗氧量也有较明显的抑制作用. 相似文献
135.
Zhang W Yue B Wang X Zhang X Xie Z Liu N Fu W Yuan Y Chen D Fu D Zhao B Yin Y Yan X Wang X Zhang R Liu J Li M Tang Y Hou R Zhang Z 《Molecular biology reports》2011,38(7):4257-4264
In order to investigate the mitochondrial genome of Panthera tigris amoyensis, two South China tigers (P25 and P27) were analyzed following 15 cymt-specific primer sets. The entire mtDNA sequence was found to be 16,957 bp and 17,001 bp long for P25 and P27 respectively, and this difference in length between P25 and P27 occurred in the number of tandem repeats in the RS-3 segment of the control region. The structural characteristics of complete P. t. amoyensis mitochondrial genomes were also highly similar to those of P. uncia. Additionally, the rate of point mutation was only 0.3% and a total of 59 variable sites between P25 and P27 were found. Out of the 59 variable sites, 6 were located in 6 different tRNA genes, 6 in the 2 rRNA genes, 7 in non-coding regions (one located between tRNA-Asn and tRNA-Tyr and six in the D-loop), and 40 in 10 protein-coding genes. COI held the largest amount of variable sites (9 sites) and Cytb contained the highest variable rate (0.7%) in the complete sequences. Moreover, out of the 40 variable sites located in 10 protein-coding genes, 12 sites were nonsynonymous. 相似文献
136.
An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C) 总被引:2,自引:0,他引:2
Yan D Li F Hall ML Sage C Hu WH Giallourakis C Upadhyay G Ouyang XM Du LL Bethea JR Chen ZY Yajnik V Liu XZ 《Journal of molecular biology》2006,357(3):755-764
The driving forces for the regulation of cell morphology are the Rho family GTPases that coordinate the assembly of the actin cytoskeleton. This dynamic feature is a result of tight coupling between the cytoskeleton and signal transduction and is facilitated by actin-binding proteins (ABPs). Mutations in the actin bundling and PDZ domain-containing protein harmonin are the causes of Usher syndrome type 1C (USH1C), a syndrome of congenital deafness and progressive blindness, as well as certain forms of non-syndromic deafness. Here, we have used the yeast two-hybrid assay to isolate molecular partners of harmonin and identified DOCK4, an unconventional guanine exchange factor for the Rho family of guanosine triphosphatases (Rho GEF GTPases), as a protein interacting with harmonin. Detailed molecular analysis revealed that a novel DOCK4 isoform (DOCK4-Ex49) is expressed in the brain, eye and inner ear tissues. We have further provided evidence that the DOCK4-Ex49 binds to nucleotide free Rac as effectively as DOCK2 and DOCK4 and it is a potent Rac activator. By immunostaining using a peptide antibody specific to DOCK4-Ex49, we showed its localization in the inner ear within the hair bundles along the stereocilia (SC). Together, our data indicate a possible Rac-DOCK4-ABP harmonin-activated signaling pathway in regulating actin cytoskeleton organization in stereocilia. 相似文献
137.
138.
Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex 总被引:9,自引:0,他引:9
Newby LJ Streets AJ Zhao Y Harris PC Ward CJ Ong AC 《The Journal of biological chemistry》2002,277(23):20763-20773
The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a "polycystin complex" involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavily N-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and co-immunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease. 相似文献
139.
140.
采用水培方式研究了LaCl3对140 mmol·L-1 NO3-硝酸盐胁迫下黄瓜幼苗光合特性的影响.结果表明: 硝酸盐胁迫显著降低了黄瓜幼苗叶绿素及类胡萝卜素含量,叶片Mg2+ ATPase、Ca2+ ATPase活性也随之降低;硝酸盐胁迫7 d,黄瓜幼苗叶片光合速率的降低以气孔限制为主,叶片AQY与CE下降,胁迫12 d则以非气孔限制为主.硝酸盐胁迫下,外加LaCl3可以使黄瓜叶片保持较高的Mg2+ ATPase、Ca2+ ATPase活性及叶绿素和类胡萝卜素含量,尤其是外加低浓度(20 μmol·L-1)LaCl3显著增加了叶片类胡萝卜素含量;LaCl3还具有降低气孔关闭、改善叶片气体交换功能,减缓叶片Fv/Fm、ФPSII、AQY、CE及qP的降低幅度等作用,使叶片在盐胁迫下保持较高的光能利用率及CO2同化能力.20 μmol·L-1 LaCl3可以有效缓解硝酸盐对黄瓜幼苗光合作用的影响,而200 μmol·L-1LaCl3在胁迫初期对黄瓜幼苗有缓解效果,后期则效果不明显.该结果可为设施土壤的改良提供新的途径. 相似文献