中性环境中铝盐絮凝剂对典型作物的生态毒性效应

采用种子发芽和根伸长抑制的陆生生态毒理方法,在中性条件(pH=7.0)下对铝盐絮凝剂(AlCl₃)的生态毒性效应进行了研究.结果表明,AlCl₃溶液在pH=7.0时,与其酸性条件(pH=4.0)相比对萝卜、白菜和小麦等受试作物种子发芽和根伸长均表现出抑制作用,且发芽抑制率和根伸长抑制率与铝浓度均呈极显著相关(P＜0.01).尽管在酸性条件下AlCl₃对白菜和小麦根伸长抑制效应比相同浓度中性条件更为强烈,但对萝卜根伸长的抑制程度在相同铝浓度条件下则是pH=7.0时明显大于pH=4.0时,在低浓度时萝卜发芽抑制率也是中性条件明显高于酸性条件.同时,铝盐在中性条件下对萝卜、白菜的发芽和根伸长产生明显抑制效应的起始浓度低于酸性条件(＜2.0 mg·L^-1).     

白茶对弹性蛋白酶活性的抑制研究

为了解白茶对弹性蛋白酶活性的作用,测定了6个白茶样品对猪胰弹性蛋白酶(PPE)活性的抑制作用。结果表明,6个白茶样品中CB4对PPE抑制活性最强,为69.73%;且随体积分数增加,酶抑制活性增强,呈剂量依赖性抑制。白茶水提液的4个萃取层中乙酸乙酯层(WEA)的抑制活性最强,达到82.58%。CB4的多酚总量(TPs)较高,且表没食子儿茶素没食子酸酯(EGCG)、表儿茶素没食子酸酯(ECG)和咖啡碱(CAF)含量最高。WEA萃取层中TPs、EGCG、ECG和ECG含量均最高,CAF含量极低。PPE活性抑制率与TPs、EGCG和CAF含量呈极显著正相关,相关系数均大于0.90。0.1～1.0 mg/mL EGCG和0.05～2.0 mg/mL CAF对PPE无抑制活性,0.05～2.0 mg/mL没食子酸(GA)对PPE活性具有促进作用,且GA的促进作用与其浓度呈正相关。可见,白茶具有潜在抗衰老活性,但对PPE起抑制作用的活性成分不是EGCG、GA和CAF。     

昆仑雪菊提取物对α-葡萄糖苷酶的抑制作用

目的：探讨昆仑雪菊提取物对α-葡萄糖苷酶的抑制活性。方法：将昆仑雪菊干燥花序粉碎,分别用水提法和乙醇法制备5种提取物。采用α-葡萄糖苷酶体外活性抑制模型,测定昆仑雪菊的5种提取物对α-葡萄糖苷酶的抑制活性。结果：这5种提取物对α-葡萄糖苷酶活性有较强的抑制作用,抑制活性均高于阿卡波糖。其中提取物Ⅰ的抑制活性最强,IC50=28.2 mg/L。结论：昆仑雪菊提取物具有较高的α-葡萄糖苷酶抑制活性,提示昆仑雪菊在抗糖尿病产品开发方面具有很好的应用前景。     

SL-01, an oral derivative of gemcitabine,inhibited human breast cancer growth through induction of apoptosis

SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.     

Extracellular Signal-regulated Kinase and Glycogen Synthase Kinase 3β Regulate Gephyrin Postsynaptic Aggregation and GABAergic Synaptic Function in a Calpain-dependent Mechanism

Molecular mechanisms of plasticity at GABAergic synapses are currently poorly understood. To identify signaling cascades that converge onto GABAergic postsynaptic density proteins, we performed MS analysis using gephyrin isolated from rat brain and identified multiple novel phosphorylation and acetylation residues on gephyrin. Here, we report the characterization of one of these phosphoresidues, Ser-268, which when dephosphorylated leads to the formation of larger postsynaptic scaffolds. Using a combination of mutagenesis, pharmacological treatment, and biochemical assays, we identify ERK as the kinase phosphorylating Ser-268 and describe a functional interaction between residues Ser-268 and Ser-270. We further demonstrate that alterations in gephyrin clustering via ERK modulation are reflected by amplitude and frequency changes in miniature GABAergic postsynaptic currents. We unravel novel mechanisms for activity- and ERK-dependent calpain action on gephyrin, which are likely relevant in the context of cellular signaling affecting GABAergic transmission and homeostatic synaptic plasticity in pathology.     

Effects of Sleep Loss and Circadian Rhythm on Executive Inhibitory Control in the Stroop and Simon Tasks

This study assessed the influence of sleep loss and circadian rhythm on executive inhibitory control (i.e., the ability to inhibit conflicting response tendencies due to irrelevant information). Twelve ordinarily diurnally active, healthy young male participants performed the Stroop and the Simon task every 3?h in a 40-h constant routine protocol that comprised constant wakefulness under controlled behavioral and environmental conditions. In both tasks, overall performance showed clear circadian rhythm and sleep-loss effects. However, both Stroop and Simon interference remained unchanged across the 40?h of wakefulness, suggesting that neither cumulative sleep loss nor the circadian clock affects executive inhibitory control. The present findings challenge the widely held view that executive functions are especially vulnerable to the influence of sleep loss and circadian rhythm. (Author correspondence: daniel.bratzke@uni-tuebingen.de)     

Inhibition of xanthine oxidase by theaflavin: Possible mechanism for anti-hyperuricaemia effect in mice

Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Excessive production of uric acid leads to hyperuricaemia. Due to the serious side effects of allopurinol, it is an urgent need to explore new XO inhibitors. Herein, the effects of theaflavin (TF1) on XO and anti-hyperuricaemia effect in hyperuricemic mice were investigated. Kinetic analysis indicate that TF1 is a reversible competitive inhibitor and has a significant inhibitory effect on XO with an IC₅₀ value of 63.17 ± 0.13 μmol/L. Analysis of fluorescence spectra suggests that TF1 causes the obvious fluorescence quenching of XO, which is mainly driven by hydrophobic interactions and hydrogen bonds. Docking studies demonstrate that TF1 interacts with dozens of amino acid residues surrounded in the active cavity of XO, including Glu-879, Pro-1012, Thr-1010, Val-1011, Lys-771, Glu-802, Pro-1076, Leu-873, Leu-1014, Asn-768, Leu-648 and Phe-649. The inhibitory mechanism may be the insertion of TF1 into the active site of XO, which hinders the substrate xanthine to enter into the site. Furthermore, the results from animal experiments demonstrate that TF1 is effective in reducing serum uric acid in mice. These findings suggest that TF1 may be a potential drug candidate for the treatment of hyperuricaemia.     

Effect of inhibitors formed during wheat straw pretreatment on ethanol fermentation by Pichia stipitis

The inhibitory effect of the main inhibitors (acetic acid, furfural and 5-hydroxymethylfurfural) formed during steam explosion of wheat straw was studied through ethanol fermentations of model substrates and hydrolysates from wheat straw by Pichia stipitis. Experimental results showed that an increase in acetic acid concentration led to a reduction in ethanol productivity and complete inhibition was observed at 3.5 g/L. Furfural produced a delay on sugar consumption rates with increasing concentration and HMF did not exert a significant effect. Fermentations of the whole slurry from steam exploded wheat straw were completely inhibited by a synergistic effect due to the presence of 1.5 g/L acetic acid, 0.15 g/L furfural and 0.05 g/L HMF together with solid fraction. When using only the solid fraction from steam explosion, hydrolysates presented 0.5 g/L of acetic acid, whose fermentations have submitted promising results, providing an ethanol yield of 0.45 g ethanol/g sugars and the final ethanol concentration reached was 12.2 g/L (10.9 g ethanol/100 g DM).     

Extensive mannose phosphorylation on leukemia inhibitory factor (LIF) controls its extracellular levels by multiple mechanisms

In addition to soluble acid hydrolases, many nonlysosomal proteins have been shown to bear mannose 6-phosphate (Man-6-P) residues. Quantification of the extent of mannose phosphorylation and the relevance to physiological function, however, remain poorly defined. In this study, we investigated the mannose phosphorylation status of leukemia inhibitory factor (LIF), a previously identified high affinity ligand for the cation-independent mannose 6-phosphate receptor (CI-MPR), and we analyzed the effects of this modification on its secretion and uptake in cultured cells. When media from LIF-overexpressing cells were fractionated using a CI-MPR affinity column, 35-45% of the total LIF molecules were bound and specifically eluted with free Man-6-P thus confirming LIF as a bona fide Man-6-P-modified protein. Surprisingly, mass spectrometric analysis of LIF glycopeptides enriched on the CI-MPR column revealed that all six N-glycan sites could be Man-6-P-modified. The relative utilization of these sites, however, was not uniform. Analysis of glycan-deleted LIF mutants demonstrated that loss of glycans bearing the majority of Man-6-P residues leads to higher steady-state levels of secreted LIF. Using mouse embryonic stem cells, we showed that the mannose phosphorylation of LIF mediates its internalization thereby reducing extracellular levels and stimulating embryonic stem cell differentiation. Finally, immunofluorescence experiments indicate that LIF is targeted directly to lysosomes following its biosynthesis, providing another mechanism whereby mannose phosphorylation serves to control extracellular levels of LIF. Failure to modify LIF in the context of mucolipidosis II and its subsequent accumulation in the extracellular space may have important implications for disease pathogenesis.