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91.
Jing Fang Heng Yin Zhixiang Zheng Panpan Zhu Xi Peng Zhicai Zuo Hengmin Cui Yi Zhou Ping Ouyang Yi Geng Junliang Deng 《Biological trace element research》2018,181(1):142-153
Aflatoxin B1 (AFB1) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G2/M cell cycle arrest of broiler’s jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB1 (AFB1 group), 0.4 mg/kg Se (+Se group), and 0.6 mg/kg AFB1 + 0.4 mg/kg Se (AFB1 + Se group) for 21 days, respectively. The histological observation and morphological analysis revealed that 0.4 mg/kg Se prevented the AFB1-associated lesions of jejunum including the shedding of the apical region of villi, the decreased villus height, and villus height/crypt ratio. The cell cycle analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB1-induced G2/M phase arrest in jejunal cells. Moreover, the expressions of ATM, Chk2, p53, Mdm2, p21, PCNA, Cdc25, cyclin B, and Cdc2 analyzed by immunohistochemistry and qRT-PCR demonstrated that 0.4 mg/kg Se restored these parameters to be close to those in the control group. In conclusion, Se promoted cell cycle recovery from the AFB1-induced G2/M phase arrest by the molecular regulation of ATM pathway in the jejunum of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium’s essentiality and its protective roles against AFB1. 相似文献
92.
Xia Wang Yan Li Winnie Deuther-Conrad Fang Xie Xin Chen Meng-Chao Cui Xiao-Jun Zhang Jin-Ming Zhang Jörg Steinbach Peter Brust Bo-Li Liu Hong-Mei Jia 《Bioorganic & medicinal chemistry》2013,21(1):215-222
We report the synthesis and evaluation of a series of fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives as potential σ1 receptor ligands. In vitro competition binding assays showed that 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-(2-fluoroethoxy)benzyl)piperazine (6) exhibits low nanomolar affinity for σ1 receptors (Ki = 1.85 ± 1.59 nM) and high subtype selectivity (σ2 receptor: Ki = 291 ± 111 nM; Kiσ2/Kiσ1 = 157). [18F]6 was prepared in 30–50% isolated radiochemical yield, with radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic 18F? substitution of the corresponding tosylate precursor. The log DpH 7.4 value of [18F]6 was found to be 2.57 ± 0.10, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiotracers in organs known to contain σ1 receptors, including the brain, lungs, kidneys, heart, and spleen. Administration of haloperidol 5 min prior to injection of [18F]6 significantly reduced the concentration of radiotracers in the above-mentioned organs. The accumulation of radiotracers in the bone was quite low suggesting that [18F]6 is relatively stable to in vivo defluorination. The ex vivo autoradiography in rat brain showed high accumulation of radiotracers in the brain areas known to possess high expression of σ1 receptors. These findings suggest that [18F]6 is a suitable radiotracer for imaging σ1 receptors with PET in vivo. 相似文献
93.
建立了利用显微操作技术分离植物单个染色体的方法。以黑麦(Secale cereale L.)为材料,以其标准染色体组型图为依据,识别出黑麦含抗病基因的1R染色体。经显微操作,将单条1R染色体放入Ep-pendorf管中。研究表明,用α-溴奈饱和液对细胞进行预处理,可快速鉴别出黑麦1R染色体。采用去壁低渗制片技术,可明显地改善显微分离单染色体的条件。 相似文献
94.
Evans RC Morera-Herreras T Cui Y Du K Sheehan T Kotaleski JH Venance L Blackwell KT 《PLoS computational biology》2012,8(4):e1002493
Calcium through NMDA receptors (NMDARs) is necessary for the long-term potentiation (LTP) of synaptic strength; however, NMDARs differ in several properties that can influence the amount of calcium influx into the spine. These properties, such as sensitivity to magnesium block and conductance decay kinetics, change the receptor's response to spike timing dependent plasticity (STDP) protocols, and thereby shape synaptic integration and information processing. This study investigates the role of GluN2 subunit differences on spine calcium concentration during several STDP protocols in a model of a striatal medium spiny projection neuron (MSPN). The multi-compartment, multi-channel model exhibits firing frequency, spike width, and latency to first spike similar to current clamp data from mouse dorsal striatum MSPN. We find that NMDAR-mediated calcium is dependent on GluN2 subunit type, action potential timing, duration of somatic depolarization, and number of action potentials. Furthermore, the model demonstrates that in MSPNs, GluN2A and GluN2B control which STDP intervals allow for substantial calcium elevation in spines. The model predicts that blocking GluN2B subunits would modulate the range of intervals that cause long term potentiation. We confirmed this prediction experimentally, demonstrating that blocking GluN2B in the striatum, narrows the range of STDP intervals that cause long term potentiation. This ability of the GluN2 subunit to modulate the shape of the STDP curve could underlie the role that GluN2 subunits play in learning and development. 相似文献
95.
Zou T Rao JN Liu L Xiao L Cui YH Jiang Z Ouyang M Donahue JM Wang JY 《American journal of physiology. Cell physiology》2012,303(1):C102-C111
Polyamines regulate multiple signaling pathways and are implicated in many aspects of cellular functions, but the exact molecular processes governed by polyamines remain largely unknown. In response to environmental stress, repression of translation is associated with the assembly of stress granules (SGs) that contain a fraction of arrested mRNAs and are thought to function as mRNA storage. Here we show that polyamines modulate the assembly of SGs in normal intestinal epithelial cells (IECs) and that induced SGs following polyamine depletion are implicated in the protection of IECs against apoptosis. Increasing the levels of cellular polyamines by ectopic overexpression of the ornithine decarboxylase gene decreased cytoplasmic levels of SG-signature constituent proteins eukaryotic initiation factor 3b and T-cell intracellular antigen-1 (TIA-1)-related protein and repressed the assembly of SGs induced by exposure to arsenite-induced oxidative stress. In contrast, depletion of cellular polyamines by inhibiting ornithine decarboxylase with α-difluoromethylornithine increased cytoplasmic eukaryotic initiation factor 3b and TIA-1 related protein abundance and enhanced arsenite-induced SG assembly. Polyamine-deficient cells also exhibited an increase in resistance to tumor necrosis factor-α/cycloheximide-induced apoptosis, which was prevented by inhibiting SG formation with silencing SG resident proteins Sort1 and TIA-1. These results indicate that the elevation of cellular polyamines represses the assembly of SGs in normal IECs and that increased SGs in polyamine-deficient cells are crucial for increased resistance to apoptosis. 相似文献
96.
YM Cui XW Dong W Chen WJ Wang YG Li HL Zhu 《Journal of enzyme inhibition and medicinal chemistry》2012,27(4):528-532
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. 相似文献
97.
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. 相似文献
98.
Theone C. Kon Adrian Onu Laurentiu Berbecila Emilia Lupulescu Alina Ghiorgisor Gideon F. Kersten Yi-Qing Cui Jean-Pierre Amorij Leo Van der Pol 《PloS one》2016,11(3)
The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween®, either Triton™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months. 相似文献
99.
100.
Proteome analysis of human lung squamous carcinoma 总被引:11,自引:0,他引:11
Few lung cancer-specific molecular markers have been established in regard of "early-stage" diagnosis and prognosis. In this study the proteome analysis of human lung squamous carcinoma (hLSC) was carried out using two strategies to explore the carcinogenic mechanisms and identify its molecular markers more directly and comprehensively. Comparative proteome analysis on 20 hLSC tissues and paired normal bronchial epithelial tissues revealed 76 differential proteins, among which 68 proteins were identified by PMF. The identified proteins fell into three categories: oncoproteins, cell cycle regulators and signaling molecules. To validate the identified differential proteins, the expressions levels of three differential proteins mdm2, c-jun and EGFR were determined by immunohistochemical staining and immunoblots. The results verified proteome analysis results. Serological proteome analysis (SERPA) of ten hLSC tissues was performed to identify the tumor-associated antigens. The results revealed 36 +/- 8 differential proteins reactive with patients' autologous sera, of which 14 proteins were identified. Six of the 14 proteins, alpha enolase, pre-B cell-enhancing factor precursor, triosephosphate isomerase, phosphoglycerate mutase 1, fructose-bisphosphate aldolase A, and guanine nucleotide-binding protein beta subunit-like protein, were also up-regulated in hLSCs in the comparative proteomic study, which suggests potential application of these 6 hLSC-associated antigens in diagnosis and therapy of hLSC. 相似文献