Synthesis, inhibitory activity and molecular docking studies of two Cu(II) complexes against Helicobacter pylori urease

Two mononuclear copper(II) complexes, [Cu(C(15)H(16)NO(2))(2)] (1) and [Cu(C(6)H(9)N(2)O(4))(2)·3H(2)O] (2·3H(2)O), were synthesised and structurally characterised by single-crystal X-ray analysis. The copper(II) atom adopts a square-planar environment in complex 1, while the geometry in 2·3H(2)O could be described as the distorted square pyramidal. Complexes 1 and 2·3H(2)O were evaluated for their inhibitory activities against Helicobacter pylori (H. pylori) urease in vitro. They both were found to have strong inhibitory activities against H. pylori urease comparable to that of acetohydroxamic acid (AHA). A docking simulation was performed to position 2 into the H. pylori urease active site to determine the probable binding conformation.     

大鼠肾髓质活体微循环及观察方法

采用肾乳头暴露方法活体观察Sprague-Dawley大鼠肾髓质微循环。结果发现:正常成年大鼠肾乳头可暴露1.1±0.5mm; 乳头表面直血管数29.8±6.3;升、降支比例3.4:1。升支平均直径13.68±6.13μm,降支10.8±2.57μm。肾乳头连续暴露观察10h,其微循环未发生明显病理性改变。说明这一方法可以用于肾髓质微循环活体研究。     

ROCK1 induces ERK nuclear translocation in PDGF-BB-stimulated migration of rat vascular smooth muscle cells

It has been known that Rho-associated protein kinase (ROCK) signaling regulates the migration of vascular smooth muscle cells (VSMCs). However, the isoform-specific roles of ROCK and its underlying mechanism in VSMC migration are not well understood. The current study thus aimed to investigate the roles of ROCK1/2 and their relationship to the MAPK signaling pathway in platelet-derived growth factor (PDGF)-induced rat aorta VSMC migration by manipulating ROCK gene expression. The results revealed that ROCK1 small interfering ribonucleic acid (siRNA) rather than ROCK2 siRNA decreased PDGF-BB-generated VSMC migration, and upregulation of ROCK1 expression via transfection of constructed pEGFP-C1/ROCK1 plasmid further increased the migration of PDGF-BB-treated VSMCs. In PDGF-treated VSMCs, ROCK1 siRNA did not affect the phosphorylation levels of ERK and p38 in the cytoplasm, but decreased the level of ERK phosphorylation in the nucleus. These findings demonstrate that activated ROCK1 can promote VSMC migration through facilitating phosphorylation and nuclear translocation of ERK protein.     

Impaired long-term potentiation and long-term memory deficits in xCT-deficient sut mice

xCT is the functional subunit of the cystine/glutamate antiporter system xc-, which exchanges intracellular glutamate with extracellular cystine. xCT has been reported to play roles in the maintenance of intracellular redox and ambient extracellular glutamate, which may affect neuronal function. To assess a potential role of xCT in the mouse hippocampus, we performed fear conditioning and passive avoidance for long-term memories and examined hippocampal synaptic plasticity in wild-type mice and xCT-null mutants, sut mice. Long-term memory was impaired in sut mice. Normal basal synaptic transmission and short-term presynaptic plasticity at hippocampal Schaffer collateral-CA1 synapses were observed in sut mice. However, LTP (long-term potentiation) was significantly reduced in sut mice compared with their wild-type counterparts. Supplementation of extracellular glutamate did not reverse the reduction in LTP. Taken together, our results suggest that xCT plays a role in the modulation of hippocampal long-term plasticity.     

脐血干细胞移植治疗肝硬化的临床研究

目的:观察脐血干细胞移植治疗失代偿期肝硬化的临床疗效。方法:对60例失代偿期肝硬化患者进行自身对照的临床研究。在无菌条件下取健康产妇足月生产的脐带血,分离纯化脐血干细胞,通过肝动脉途径,将纯化的脐血干细胞移植入患者肝脏内,于移植后2周、4周、8周进行肝功能、凝血指标检测,并于4周及8周行腹部B超及胃镜检查,观察患者移植后不同时间症状改善情况及术后不良反应的发生情况。结果:60例接受脐血干细胞移植的肝硬化患者术中术后无明显不良反应发生。移植后,患者临床症状改善明显,食欲不振、乏力、腹水等减轻甚至消失;血清学检测:白蛋白水平较术前明显升高,凝血酶原时间、总胆红素较术前明显下降;术后8周复查胃镜,食道静脉曲张没有明显变化。结论:脐血干细胞移植治疗失代偿期肝硬化是一种安全、有效的方法,尤其是在提高白蛋白水平及改善凝血功能方面有很好的疗效,可作为肝移植治疗的过渡或补充治疗。     

Cell expansion and microtubule behavior in ray floret petals of Gerbera hybrida: responses to light and gibberellic acid

It is still unclear how light and gibberellins are integrated to regulate petal size. Here, we report that light improves both the length and the width of the ray floret petals in G. hybrid, but GA(3) promotes only the petal length. It is also revealed that the control of the petal size by light and GA(3) depends on modulating the cell size, which is governed by the behavior of cortical microtubule.Light and gibberellins are important regulators of plant organ growth. However, little is known about their roles in petal size determination. Here, we report how light and gibberellic acid (GA(3)) signals are integrated to regulate the ray floret (Rf) size in Gerbera hybrida. The inflorescences of G. hybrida at stages 1.5 were cultivated in vitro for 9 d followed by the determination of the Rf petal size. Results demonstrated that the light signal significantly enhanced both the length and the width of Rf petals, but GA(3) promoted only the petal length. Moreover, GA(3) displayed a synergistic positive effect on the length but an antagonistic effect on the width with the light signal. Measurements of the petal cells revealed that the cell size, not the cell number, exhibited a dominant contribution to the petal size in response to light and GA(3) signals. Furthermore, light and GA(3) signals not only induced an obvious reorientation of cortical microtubules (MTs) into transverse arrays but also promoted the recovery of the MT lengths in petal cells following oryzalin (an MT depolymerizing agent) treatment. Importantly, disruption of the MT lengths and arrays by oryzalin could inhibit the cell expansion and the petal enlargement induced by light or/and GA(3) signals. Taken together, it is concluded that the control of the petal size by light and GA(3) signals mainly depends on modulating the cell size and, moreover, the organization of the cortical MTs plays a crucial role in the control of the cell size and hence the Rf petal growth.     

The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.     

转基因农作物的研究进展

本文从转基因农作物的分类、优点、安全性问题和管理方面进行了阐述,同时展望了其发展前景。     

Autophagy promotes T-cell survival through degradation of proteins of the cell death machinery

Autophagy is implicated in regulating cell death in activated T cells, but the underlying mechanism is unclear. Here, we show that inhibition of autophagy via Beclin 1 gene deletion in T cells leads to rampant apoptosis in these cells upon TCR stimulation. Beclin 1-deficient mice fail to mount autoreactive T-cell responses and are resistant to experimental autoimmune encephalomyelitis. Compared with Th17 cells, Th1 cells are much more susceptible to cell death upon Beclin 1 deletion. Cell death proteins are highly increased in Beclin 1-deficient T cells and inhibition of caspases and genetic deletion of Bim reverse apoptosis. In addition, p62/sequestosome 1 binds to caspase-8 but does not control levels of procaspase-8 or other cell death-related proteins. These results establish a direct role of autophagy in inhibiting the programmed cell death through degradation of apoptosis proteins in activated T cells.