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171.
Lan T Liu W Xie X Xu S Huang K Peng J Shen X Liu P Wang L Xia P Huang H 《Molecular endocrinology (Baltimore, Md.)》2011,25(12):2094-2105
Diabetic nephropathy is characterized by accumulation of glomerular extracellular matrix proteins, such as fibronectin (FN). Here, we investigated whether sphingosine kinase (SphK)1 pathway is responsible for the elevated FN expression in diabetic nephropathy. The SphK1 pathway and FN expression were examined in streptozotocin-induced diabetic rat kidney and glomerular mesangial cells (GMC) exposed to high glucose (HG). FN up-regulation was concomitant with activation of the SphK1 pathway as reflected in an increase in the expression and activity of SphK1 and sphingosine 1-phosphate (S1P) production in both diabetic kidney and HG-treated GMC. Overexpression of wild-type SphK1 (SphK(WT)) significantly induced FN expression, whereas treatment with a SphK inhibitor, N,N-dimethylsphingosine, or transfection of SphK1 small interference RNA or dominant-negative SphK1 (SphK(G82D)) abolished HG-induced FN expression. Furthermore, addition of exogenous S1P significantly induced FN expression in GMC with an induction of activator protein 1 (AP-1) activity. Inhibition of AP-1 activity by curcumin attenuated the S1P-induced FN expression. Finally, by inhibiting SphK1 activity, both N,N-dimethylsphingosine and SphK(G82D) markedly attenuated the HG-induced AP-1 activity. Taken together, these results demonstrated that the SphK1 pathway plays a critical role in matrix accumulation in GMC under diabetic condition, suggesting that the SphK1 pathway could be a potential therapeutic target for diabetic nephropathy. 相似文献
172.
主要探讨了T细胞免疫原TI对口蹄疫疫苗的免疫增强作用。设计并原核表达产生了一种包含口蹄疫病毒VP1,VP4,3A和3D蛋白上多个T细胞表位与两个通用T细胞表位的T细胞免疫原,命名为TI;同时表达了O和Asia 1两个型口蹄疫病毒 VP1 蛋白的串联编码基因,表达产物命名为OA-VP1。将上述T细胞免疫原分别与OA-VP1和口蹄疫灭活疫苗按不同剂量组合免疫小鼠,于免疫后不同时间测定各组小鼠的体液与细胞免疫应答情况。采用微量中和试验检测小鼠O型和Asia1型中和抗体,采用流式细胞检测技术和测定γ-干扰素的水平来分析不同免疫组小鼠细胞免疫的水平。结果显示,与灭活疫苗或OA-VP1单独免疫组相比,添加TI抗原后灭活疫苗 (P<0.01) 和OA-VP1免疫组(P<0.05)小鼠均能产生高水平的特异性中和抗体;且CD4+ T细胞数量显著增多,IFN-γ产生水平显著升高 (P<0.01)。说明TI抗原具有很好的诱导特异性体液与细胞免疫应答的作用,是一种很好的免疫增效剂,可作为口蹄疫蛋白亚单位疫苗和灭活疫苗中的一种有效成分,以提高疫苗的免疫效果。 相似文献
173.
Lin KW Huang AM Hour TC Yang SC Pu YS Lin CN 《Bioorganic & medicinal chemistry》2011,19(14):4274-4285
Twenty six 18β-glycyrrhetinic acid (GA) (1) derivatives 2-27 including twelve new GA derivatives 10, 11, 13-17, 21-25 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell lines). seco-Compounds 9, 25, and 27 are the most potent compounds of this series, inhibiting cell growth of human NTUB1 cells with an IC(50) values of 2.34 ± 0.28, 4.76 ± 1.15, and 3.31 ± 0.61 μM, respectively. Exposure of NTUB1 to 25 for 24h significantly increased the production of reactive oxygen species (ROS). Flow cytometric analysis exhibited that treatment of NTUB1 with 25 did not induce cell cycle arrest but accompanied by an increase of apoptotic cell death in a dose-dependant manner after 24h. Mitochondrial membrane potential (MMP) decreased significantly in a dose-dependant manner when the NTUB1 cells were exposed to 25 for 24h. Marked collapse of the MMP suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by 25. Western blot analysis shows that NTUB1 cells treated with 25 increased the level of p-p53 in a dose-dependant manner. Further, NAC treatment prevented p53 phosphorylation stimulated by 25. These results suggested that 25 induced a mitochondrial-mediated apoptosis in NTUB1 cells through activation of p53, which are mainly mediated ROS generated by 25. 相似文献
174.
巢湖叶绿素a浓度的时空分布及其与氮、磷浓度关系 总被引:6,自引:1,他引:5
基于巢湖水体2002~2007年水质监测资料,对叶绿素a浓度的分布、动态及与TN、TP的关系进行了统计分析。巢湖叶绿素a浓度与TN、TP的浓度分布存在明显的空间差异,西半湖叶绿素a浓度全年高于20μg/L,TN为1.94~3.84mg/L,TP为0.20~0.42mg/L;东半湖叶绿素a浓度全年小于5.5μg/L,TN为0.95~1.83mg/L,TP为0.08~0.14mg/L。在东半湖,叶绿素a含量与TN呈不明显的正线性关系,当TP浓度较低时,叶绿素a随TP的增加小幅上升,但是当TP>0.15mg/L时,叶绿素a随TP的增加而明显上升;在西半湖,当水体TN<5.8mg/L或者TP<2.0mg/L时,叶绿素a含量与TN、TP关系为正线性关系,当TN在5.8~9.4mg/L或者TP介于0.2~0.3mg/L间时,叶绿素a含量与TN、TP关系为不显著的负线性关系,当TP浓度>0.3mg/L时,叶绿素a含量与TP关系又为正线性关系。西半湖叶绿素a浓度的变化可能是藻类生物活动与沉积物及水体中营养盐的相互作用结果。在治理巢湖富营养化时,应优先控制西半湖的磷元素。 相似文献
175.
升振山姜的选育和生物学特性研究 总被引:2,自引:1,他引:1
采用杂交育种技术,以姜科(Zingiberaceae)植物草豆蔻(Alpinia hainanensis K.Schumann)为亲本,母本于1975年从广东引种,具乳白色小苞片;父本于1983年从广西引种,具淡粉红色小苞片.经多年多代分离、筛选和鉴定,从其杂交后代中选育出花卉新品种升振山姜(A.hainanensis... 相似文献
176.
检测旋毛虫感染大鼠血清中的总IgE、特异性IgE和观察IgE介导的肥大细胞脱颗粒,并进一步探讨抗体依赖的(肥大)细胞介导的细胞毒性(Antibody dependent cell mediated cytotoxicity,ADCC)在旋毛虫病免疫机理中的作用。采用雄性Wistar大鼠为旋毛虫感染的动物模型,将90只大鼠随机分为10组。试验时,以ELISA双抗体夹心法和间接法分别动态检测总IgE和特异性IgE;肥大细胞脱颗粒试验采用直接法;然后采用细胞培养法观察免疫血清对肥大细胞杀伤旋毛虫肌幼虫作用的影响。在免疫血清存在时,无论感染鼠还是正常鼠的肥大细胞对旋毛虫幼虫均有杀伤作用,但以感染鼠的作用更强。肥大细胞在ADCC效应机制中对杀伤旋毛虫肌幼虫发挥了重要的作用。 相似文献
177.
178.
179.
Chen J Li Q Zhang Y Yang P Zong Y Qu S Liu Z 《Journal of physiology and biochemistry》2011,67(2):153-163
The reported data indicate that oleic acid (OA) decreases cholesterol absorption. To explore the underlying mechanisms, the
effects of OA on the expression of cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the unfolded protein
response (UPR) pathway were studied in CaCo-2 enterocytes by incubating CaCo-2 cells with taurocholate micelles or taurocholate
micelles containing different concentrations of OA (0.25–1.0 mM). We show that OA effectively induces XBP1 mRNA splicing,
a key component of the UPR signaling, and the expression of BiP and mature ATF6 proteins in a concentration-dependent manner,
leading to the induction of endoplasmic reticulum (ER) stress and activation of the UPR. Interestingly, OA decreases NPC1L1
expression in a dose-dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2, ABCG8, and ACAT2 protein
level. In CaCo-2 cells treated with 1.0 mM OA, both the NPC1L1 mRNA level and the NPC1L1 protein expression in brush-border
membrane fractions were decreased by 39% and 37%, respectively (P < 0.01). A dose of 1 mM dithiothreitol (DTT), a positive control for ER stress induction, also decreases NPC1L1 mRNA and
protein expression by 27% and 23%, respectively (P < 0.05). Furthermore, 4-phenyl-butyric acid, an UPR inhibitor, blocks OA- and DTT-induced reduction on NPC1L1 mRNA and protein
levels. The results suggest that OA down-regulates NPC1L1 mRNA and protein expression via the induction of the UPR, which
may play an important role in reducing intestinal cholesterol absorption. 相似文献
180.
Cui S Zhang D Jiang S Pu H Hu Y Guo H Chen M Su T Zhu C 《Fish & shellfish immunology》2011,31(2):173-181
Macrophage migration inhibitory factor (MIF) is an important cytokine and plays a crucial role as a pivotal regulator of innate immunity. In this study, a MIF cDNA was identified and characterized from the pearl oyster Pinctada fucata (designated as PoMIF). The full-length of PoMIF was 1544 bp and consisted of a 5'-untranslated region (UTR) of 45 bp, a 3'-UTR of 1139 bp with a polyadenylation signal (AATAAA) at 12 nucleotides upstream of the poly (A) tail. The open reading frame (ORF) of PoMIF was 360 bp which encoded a polypeptide of 120 amino acids with an estimated molecular mass of 13.3 kDa and a predicted pI of 6.1. SMART analysis showed that PoMIF contained the catalytic-sites P2 and K33 for tautomerase activity, a motif C??GSV?? for oxidoreductase activity and a MIF family signature D??PCGSVEVYSIGALG??. Homology analysis revealed that the PoMIF shared 40.3-65.5% similarity and 26.9-45.0% identity to other known MIF sequences. PoMIF mRNA was constitutively expressed in seven selected tissues of healthy pearl oysters, with the highest expression level in digestive gland. Eight hours after P. fucata was injected with Vibrio alginolyticus, the expression of PoMIF mRNA was significantly up-regulated in digestive gland, gills, hemocytes and intestine. The cDNA fragment encoding mature protein of PoMIF was subcloned to expression vector pRSET and transformed into Escherichia coli BL21 (DE3). The recombinant PoMIF (rPoMIF) was expressed and purified under optimized conditions. Function analysis showed that rPoMIF had oxidoreductase activity and could utilize dithiothreitol (DTT) as reductant to reduce insulin. 相似文献