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71.
Koichiro Saka Masahiro Kawahara Jinying Teng Makoto Otsu Hiromitsu Nakauchi Teruyuki Nagamune 《Journal of biotechnology》2013
The technique to expand hematopoietic stem cells (HSCs) ex vivo is eagerly anticipated to secure an enough amount of HSCs for clinical applications. Previously we developed a scFv-thrombopoietin receptor (c-Mpl) chimera, named S-Mpl, which can transduce a proliferation signal in HSCs in response to a cognate antigen. However, a remaining concern of the S-Mpl chimera may be the magnitude of the cellular expansion level driven by this molecule, which was significantly less than that mediated by endogenous wild-type c-Mpl. In this study, we engineered a tyrosine motif located in the intracellular domain of S-Mpl based on a top-down approach in order to change the signaling properties of the chimera. The truncated mutant (trunc.) and an amino-acid substitution mutant (Q to L) of S-Mpl were constructed to investigate the ability of these mutants to expand HSCs. The result showed that the truncated and Q to L mutants gave higher and considerably lower number of the cells than unmodified S-Mpl, respectively. The proliferation level through the truncated mutant was even higher than that of non-transduced HSCs with the stimulation of a native cytokine, thrombopoietin. Moreover, we analyzed the signaling properties of the S-Mpl mutants in detail using a pro-B cell line Ba/F3. The data indicated that the STAT3 and STAT5 activation levels through the truncated mutant increased, whereas activation of the Q to L mutant was inhibited by a negative regulator of intracellular signaling, SHP-1. This is the first demonstration that a non-natural artificial mutant of a cytokine receptor is effective for ex vivo expansion of hematopoietic cells compared with a native cytokine receptor. 相似文献
72.
73.
Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen species (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells. 相似文献
74.
The evolutionarily conserved JAK/STAT pathway plays important roles in development and disease processes in humans. Although the signaling process has been well established, we know relatively little about what the relevant target genes are that mediate JAK/STAT activation during development. Here, we have used genome-wide microarrays to identify JAK/STAT targets in the optic lobes of the Drosophila brain and identified 47 genes that are positively regulated by JAK/STAT. About two-thirds of the genes encode proteins that have orthologs in humans. The STAT targets in the optic lobe appear to be different from the targets identified in other tissues, suggesting that JAK/STAT signaling may regulate different target genes in a tissue-specific manner. Functional analysis of Nop56, a cell-autonomous STAT target, revealed an essential role for this gene in the growth and proliferation of neuroepithelial stem cells in the optic lobe and an inhibitory role in lamina neurogenesis. 相似文献
75.
Feng Teng Lihong Zhai Ruixiang Liu Wei Bai Liqiu Wang Dongao Huo Yongsheng Tao Yonglian Zheng Zuxin Zhang 《The Plant journal : for cell and molecular biology》2013,73(3):405-416
Maize plant height is closely associated with biomass, lodging resistance and grain yield. Determining the genetic basis of plant height by characterizing and cloning plant height genes will guide the genetic improvement of crops. In this study, a quantitative trait locus (QTL) for plant height, qPH3.1, was identified on chromosome 3 using populations derived from a cross between Zong3 and its chromosome segment substitution line, SL15. The plant height of the two lines was obviously different, and application of exogenous gibberellin A3 removed this difference. QTL mapping placed qPH3.1 within a 4.0 cM interval, explaining 32.3% of the phenotypic variance. Furthermore, eight homozygous segmental isolines (SILs) developed from two larger F2 populations further narrowed down qPH3.1 to within a 12.6 kb interval. ZmGA3ox2, an ortholog of OsGA3ox2, which encodes a GA3 β‐hydroxylase, was positionally cloned. Association mapping identified two polymorphisms in ZmGA3ox2 that were significantly associated with plant height across two experiments. Quantitative RT‐PCR showed that SL15 had higher ZmGA3ox2 expression relative to Zong3. The resultant higher GA1 accumulation led to longer internodes in SL15 because of increased cell lengths. Moreover, a large deletion in the coding region of ZmGA3ox2 is responsible for the dwarf mutant d1‐6016. The successfully isolated qPH3.1 enriches our knowledge on the genetic basis of plant height in maize, and provides an opportunity for improvement of plant architecture in maize breeding. 相似文献
76.
研究氧化海藻酸——低分子量聚乙烯亚胺两性刷型共聚物 (Algin-a-te-graft-PEI, Alg-g-PEI) 与血管内皮生长因子质粒 (pVEGF) 复合后对体内血管生成的影响。采用细胞和斑马鱼实验检测了Alg-g-PEI/pVEGF复合物的毒性;通过凝胶电泳实验评价了Alg-g-PEI对DNA的保护作用;利用鸡胚绒毛尿囊膜 (CAM) 和斑马鱼模型,选用PEI 25K/pVEGF作为阳性对照、生理盐水为空白对照,观察复合物对血管新生的促进作用。结果发现:Alg-g-PEI对质粒有较好的保护作用;Alg-g-PEI/pVEGF复合物具有较低的细胞、斑马鱼毒性,能显著促进CAM和斑马鱼的血管生成,且具有剂量依赖性,当pVEGF用量等于2.4 μg/CAM时,复合物对CAM血管生成的促进作用最明显,血管面积和CAM面积比 (VA/CAM) 为44.04%,高于阳性对照组 (35.90%) 和空白对照组 (24.03%) (**P<0.01)。复合物对斑马鱼血管新生的促进作用随氮磷比 (N/P) 的增加而增强,其中N/P=110时,血管新生最明显:肠下血管总长度和面积分别为1.11 mm和1.70×103像素,高于空白对照组 (0.69 mm和0.95×103像素) (**P<0.01) 和阳性对照组 (0.82 mm和1.11×103像素) (**P<0.01) 。综上所述,Alg-g-PEI/pVEGF能于体内促进血管生成,该载体有望用于临床缺血性疾病的治疗。 相似文献
77.
目的 探讨表没食子儿茶素没食子酸酯(EGCG)对高脂饮食大鼠脂肪组织中肿瘤坏死因子-α(TNF-α)表达的影响及其与胰岛素敏感性的相关性.方法 将30只SPF级雄性SD大鼠随机分为正常饮食组(ND组,n=10)和高脂饮食组(HFD组,n=20).喂养16w,当两组大鼠体质量出现显著差异后(P〈0.05),将HFD组按随机区组原则分为单纯高脂组(HFD组,n=10)和EGCG干预组(HFD+0.32%EGCG,EGCG组,n=10).干预16w.留取血清及附睾周脂肪组织.检测每组大鼠空腹血糖(FBG)、胰岛素水平(FINS)及游离脂肪酸(FFAs),并计算胰岛素抵抗指数(HOMA-IR);应用Real-time PCR及Western blot方法检测附睾周脂肪组织中TNF-α表达水平.结果 (1)与HFD组相比,EGCG组FINS水平显著下降[分别为(13.83±0.79)mIU/l vs.(31.71±3.61)mIU/l,P〈0.05];HOMA-IR值下降[分别为(3.36±0.31) vs.(7.59±0.99),P〈0.05];FFAs值亦明显下降[分别为(0.38±0.08)mmol/l vs.(0.81±0.11)mmol/l,P〈0.05];三组大鼠FBG水平无明显统计学差异(P〉0.05).(2)与ND组相比,HFD组脂肪组织中TNF-αmRNA水平显著升高[分别为(0.0033±0.00070)vs.(0.0010±0.00008),P〈0.01];而EGCG组较HFD组则明显下降[分别为(0.0018±0.00037)vs.(0.0033±0.00070),P〈0.05];同时,EGCG组TNF-α蛋白表达量低于HFD组[分别为(0.42±0.09)vs.(0.67±0.09),P〈0.05];(3)EGCG组与ND组无明显差异(P〉0.05).结论 EGCG改善高脂饮食大鼠胰岛素敏感性可能与减轻脂肪组织TNF-α介导的炎症状态相关. 相似文献
78.
Jing Hui Xiao-jie Yu Xiao-jin Cui Teng Mu Jia-shuai Lin Pei Ni 《Bioscience, biotechnology, and biochemistry》2013,77(9):1514-1521
It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44?kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2–ΔSak and ΔSak–ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29?kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic. 相似文献
79.
80.
Androgen Inhibits Abdominal Fat Accumulation and Negatively Regulates the PCK1 Gene in Male Chickens
Jinlin Duan Fan Shao Yonggang Shao Junying Li Yao Ling Kedao Teng Hongwei Li Changxin Wu 《PloS one》2013,8(3)
Capons are male chickens whose testes have been surgically incised. Capons show a significant increase in fat accumulation compared to intact male chickens. However, while caponization leads to a significant reduction in androgen levels in roosters, little is known about the molecular mechanisms through which androgen status affects lipogenesis in avian species. Therefore, investigation of the influence of androgens on fat accumulation in the chicken will provide insights into this process. In this study, Affymetrix microarray technology was used to analyze the gene expression profiles of livers from capons and intact male chickens because the liver is the major site of lipogenesis in avian species. Through gene ontology, we found that genes involved in hepatic lipogenic biosynthesis were the most highly enriched. Interestingly, among the upregulated genes, the cytosolic form of the phosphoenolpyruvate carboxykinase (PCK1) gene showed the greatest fold change. Additionally, in conjunction with quantitative real-time PCR data, our results suggested that androgen status negatively regulated the PCK1 gene in male chickens. 相似文献