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Find video protocols related to scientific articles indexed in Pubmed.
Clinical significance of reduced SFRP1 expression in acute myeloid leukemia.
Leuk. Lymphoma
PUBLISHED: 10-28-2014
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Deregulation of secreted frizzled-related protein 1 (SFRP1) has been found in many types of cancer. However, the pattern of SFRP1 expression in acute myeloid leukemia (AML) is still unclear. This study determined SFRP1 expression in patients with AML. SFRP1 expression was decreased markedly in patients with AML compared to controls (p < 0.001). White blood cell (WBC) counts increased as SFRP1 expression decreased in AML (p = 0.016). Patients with low SFRP1 expression showed a different distribution of French-American-British (FAB) subtypes M1/M2/M3 from those with high SFRP1 expression (p = 0.031). NPM1 mutation was mainly observed in patients with low SFRP1 expression (p = 0.011). There was a weak trend that patients with AML with low SFRP1 expression had shorter overall survival (OS) than those with high SFRP1 expression (p = 0.103). Our results indicate that reduced SFRP1 expression is found more frequently in the less well-differentiated subgroups of AML and is associated with NPM1 mutation in AML.
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Tetrandrine induces apoptosis in gallbladder carcinoma in vitro.
Int J Clin Pharmacol Ther
PUBLISHED: 09-29-2014
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The aims of this study were to observe the apoptosis effects of tetrandrine on human gallbladder carcinoma cell line (SGC-996), and to explore its related mechanism.
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Spatially confined assembly of nanoparticles.
Acc. Chem. Res.
PUBLISHED: 09-22-2014
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Conspectus The ability to assemble NPs into ordered structures that are expected to yield collective physical or chemical properties has afforded new and exciting opportunities in the field of nanotechnology. Among the various configurations of nanoparticle assemblies, two-dimensional (2D) NP patterns and one-dimensional (1D) NP arrays on surfaces are regarded as the ideal assembly configurations for many technological devices, for example, solar cells, magnetic memory, switching devices, and sensing devices, due to their unique transport phenomena and the cooperative properties of NPs in assemblies. To realize the potential applications of NP assemblies, especially in nanodevice-related applications, certain key issues must still be resolved, for example, ordering and alignment, manipulating and positioning in nanodevices, and multicomponent or hierarchical structures of NP assemblies for device integration. Additionally, the assembly of NPs with high precision and high levels of integration and uniformity for devices with scaled-down dimensions has become a key and challenging issue. Two-dimensional NP patterns and 1D NP arrays are obtained using traditional lithography techniques (top-down strategies) or interfacial assembly techniques (bottom-up strategies). However, a formidable challenge that persists is the controllable assembly of NPs in desired locations over large areas with high precision and high levels of integration. The difficulty of this assembly is due to the low efficiency of small features over large areas in lithography techniques or the inevitable structural defects that occur during the assembly process. The combination of self-assembly strategies with existing nanofabrication techniques could potentially provide effective and distinctive solutions for fabricating NPs with precise position control and high resolution. Furthermore, the synergistic combination of spatially mediated interactions between nanoparticles and prestructures on surfaces may play an increasingly important role in the controllable assembly of NPs. In this Account, we summarize our approaches and progress in fabricating spatially confined assemblies of NPs that allow for the positioning of NPs with high resolution and considerable throughput. The spatially selective assembly of NPs at the desired location can be achieved by various mechanisms, such as, a controlled dewetting process, electrostatically mediated assembly of particles, and confined deposition and growth of NPs. Three nanofabrication techniques used to produce prepatterns on a substrate are summarized: the Langmuir-Blodgett (LB) patterning technique, e-beam lithography (EBL), and nanoimprint lithography (NPL). The particle density, particle size, or interparticle distance in NP assemblies strongly depends on the geometric parameters of the template structure due to spatial confinement. In addition, with smart design template structures, multiplexed NPs can be assembled into a defined structure, thus demonstrating the structural and functional complexity required for highly integrated and multifunction applications.
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MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression.
Tumour Biol.
PUBLISHED: 09-14-2014
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MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-492 plays an important role in cell tumorigenesis in multiple kinds of human cancer cells. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated miR-492's role in cell proliferation of breast cancer. MiR-492 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Overexpression of miR-492 promoted the proliferation and anchorage-independent growth of breast cancer cells. Bioinformatics analysis further revealed sex-determining region Y-box 7 (SOX7), a putative tumor suppressor, as a potential target of miR-492. Data from luciferase reporter assays showed that miR-492 directly binds to the 3'-untranslated region (3'-UTR) of SOX7 messenger RNA (mRNA) and repressed expression at both transcriptional and translational levels. Ectopic expression of miR-492 led to downregulation of SOX7 protein, which resulted in the upregulation of cyclin D1 and c-Myc. In functional assays, SOX7 silenced in miR-492-in-transfected ZR-75-30 cells has positive effect to promote cell proliferation, suggesting that direct SOX7 downregulation is required for miR-492-induced cell proliferation and cell cycle of breast cancer. In sum, these results suggest that miR-492 represents a potential onco-miR and participates in breast cancer carcinogenesis by suppressing SOX7 expression.
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Pentacene-fused diporphyrins.
Chemistry
PUBLISHED: 09-03-2014
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In this work, we report the synthesis, spectroscopic characterization, and theoretical analysis of a linearly conjugated pentacene-fused porphyrin dimer and cross-conjugated quinone-fused dinaphtho[2,3]porphyrins. These multichromophoric systems display non-typical UV-visible absorptions of either porphyrins or pentacenes/quinones. UV-visible, emission and magnetic circular dichroism (MCD) spectroscopy suggest strong electronic interactions among the multichromophores in the system. DFT calculations revealed the delocalization of the HOMOs and LUMOs spanning the entire dimer and linker assembly. The pentacene-fused porphyrin dimer is significantly more stable than both the corresponding pentacene and the heptacene derivatives. The availability of these huge ?-extended and electronically highly interactive multichromophoric systems promises unprecedented electronic and photophysical properties.
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Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells.
Molecules
PUBLISHED: 08-27-2014
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Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (??m) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-?B, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer.
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Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.
PLoS ONE
PUBLISHED: 08-15-2014
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Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.
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Antiparallel triple-strand architecture for prefibrillar A?42 oligomers.
J. Biol. Chem.
PUBLISHED: 08-12-2014
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A?42 oligomers play key roles in the pathogenesis of Alzheimer disease, but their structures remain elusive partly due to their transient nature. Here, we show that A?42 in a fusion construct can be trapped in a stable oligomer state, which recapitulates characteristics of prefibrillar A?42 oligomers and enables us to establish their detailed structures. Site-directed spin labeling and electron paramagnetic resonance studies provide structural restraints in terms of side chain mobility and intermolecular distances at all 42 residue positions. Using these restraints and other biophysical data, we present a novel atomic-level oligomer model. In our model, each A?42 protein forms a single ?-sheet with three ?-strands in an antiparallel arrangement. Each ?-sheet consists of four A?42 molecules in a head-to-tail arrangement. Four ?-sheets are packed together in a face-to-back fashion. The stacking of identical segments between different ?-sheets within an oligomer suggests that prefibrillar oligomers may interconvert with fibrils via strand rotation, wherein ?-strands undergo an ?90° rotation along the strand direction. This work provides insights into rational design of therapeutics targeting the process of interconversion between toxic oligomers and non-toxic fibrils.
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The effects of PTBP3 silencing on the proliferation and differentiation of MKN45 human gastric cancer cells.
Life Sci.
PUBLISHED: 08-10-2014
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PTBP3 overexpression inhibits the differentiation of leukemia cells; however, its effects on the differentiation and proliferation of solid cancer cells remain unclear. Thus, the impact of PTBP3 on the differentiation and proliferation of gastric cancer cells was investigated.
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Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and TLR4.
Infect. Immun.
PUBLISHED: 07-21-2014
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Toll-like receptors (TLRs) play a key role in the innate immune responses to periodontal pathogens in periodontal disease. The present study was performed to determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using a Porphyromonas gingivalis-associated ligature-induced periodontitis model in mice. Wild-type (WT), Tlr2(-/-), and Tlr4(-/-) mice (8 to 10 weeks old) in the C57/BL6 background were used. Silk ligatures were applied to the maxillary second molars in the presence or absence of live P. gingivalis infection. Ligatures were removed from the second molars on day 14, and mice were kept for another 2 weeks before sacrifice for final analysis (day 28). On day 14, there were no differences in alveolar bone resorption and gingival RANKL expression between mice treated with ligation plus P. gingivalis infection and mice treated with ligation alone. Gingival interleukin-1? (IL-1?) and tumor necrosis factor alpha (TNF-?) expression was increased, whereas IL-10 expression was decreased in WT and Tlr2(-/-) mice but not in Tlr4(-/-) mice. On day 28, WT and Tlr4(-/-) mice treated with ligation plus P. gingivalis infection showed significantly increased bone loss and gingival RANKL expression compared to those treated with ligation alone, whereas such an increase was diminished in Tlr2(-/-) mice. Gingival TNF-? upregulation and IL-10 downregulation were observed only in WT and Tlr4(-/-) mice, not in Tlr2(-/-) mice. In all mice, bone resorption induced by ligation plus P. gingivalis infection was antagonized by local anti-RANKL antibody administration. This study suggests that P. gingivalis exacerbates ligature-induced, RANKL-dependent periodontal bone resorption via differential regulation of TLR2 and TLR4 signaling.
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Kinetic analysis of the immunity in a pregnant patient infected with avian influenza H7N9.
Int J Clin Exp Med
PUBLISHED: 07-15-2014
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Human infection with avian influenza A H7N9 has emerged in China since February, 2013. The immunologic changes in pregnant women infected with H7N9 are not known.
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Wire-cylinder dielectric barrier discharge induced degradation of aqueous atrazine.
Chemosphere
PUBLISHED: 07-12-2014
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The wire-cylinder dielectric barrier discharge reactor was adopted for removal of aqueous atrazine. The effect of different parameters on the degradation efficiency of atrazine was investigated, and the degradation mechanism of atrazine was studied. The experimental results showed that when the discharge power was 50W and the air flow rate was 140Lh(-1), 93.7% of atrazine was degraded after 18min of discharge time. The concentrations of generated O3 and H2O2 increased with increasing discharge time. The pH decreased from 6.80 to 2.50, 12.7% of TOC was removed after 18min. The concentrations of generated Cl(-) and NO3(-) increased significantly during the degradation process of atrazine, and the decreasing toxicity trend was observed for the treated atrazine solution. The degradation byproducts of atrazine were identified using liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), which might be formed mainly in dechlorination hydroxylation, alkyl oxidation, dechlorination hydroxylation combined with alkyl oxidation and demethylation oxidation reactions.
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Synthesis, Crystal Structure, and Biological Activities of Two Chiral Mononuclear Mn((III)) Complexes.
Chirality
PUBLISHED: 06-23-2014
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Two new chiral mononuclear Mn((III)) complexes, [MnL((R)) Cl (C2 H5 OH)]•C2 H5 OH (1) and [MnL((S)) (CH3 OH)2 ]Cl•CH3 OH (2), {H2 L?=?(R,R)-or (S,S)-N,N'-bis-(2-hydroxy-1-naphthalidehydene)-cyclohexanediamine} were synthesized and characterized by various physicochemical techniques. Bond valence sum (BVS) calculations and the Jahn-Teller effect indicate that the Mn centers are in a +3 oxidation state. The statuses of the two complexes in the solution were confirmed as a pair of enantiomers by electrospray ionization, mass spectrometry (ESI-MS) spectrum. The binding ability of the complexes with calf thymus CT-DNA was investigated by spectroscopic and viscosity measurements. Both of the complexes could interact with CT-DNA via an intercalative mode with the order of 1 (R-enantiomer) >2 (S-enantiomer). Under the physiological conditions, the two compounds exhibit efficient DNA cleavage activities without any external agent, which also follows the order of R-enantiomer?>?S-enantiomer. Interestingly, the concentration-dependent DNA cleavage experiments indicate an optimal concentration of 17.5??M. In addition, the interaction of the compounds with bovine serum albumin (BSA) was also investigated, which indicated that the complexes could quench the intrinsic fluorescence of BSA by a static quenching mechanism. Chirality 00:000-000, 2014. © 2014 Wiley Periodicals, Inc.
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[Effect of the coexistence of chlorobenzene homologue on anaerobic degradation of hexachlorobenzene].
Huan Jing Ke Xue
PUBLISHED: 06-21-2014
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The anaerobic biodegradation of hexachlorobenzene is being an intensively studied technology for contaminated soil remediation. The effect of three coexisting chlorobenzene homologue (pentachlorobenzene, 1, 2, 4, 5-tetrachlorobenzene and 1, 2, 4-trichlorobenzene) on anaerobic degradation of hexachlorobenzene in dye processing industry contaminated soil was studied under different environmental conditions such as initial pH, reaction temperature and solid-liquid ratio. The result showed that the anaerobic degradation activity of hexachlorobenzene was reduced due to the feedback inhibition caused by accumulation of chlorobenzene homologue. The feedback inhibition and accumulation may vary based on different environmental conditions. Pentachlorobenzene exhibited the strongest inhibitive effect compared to the other two chlorobenzene homologue with low initial pH values, at room temperature and low solid-liquid ratio, respectively. Whereas 1, 2, 4-trichlorobenzene significantly inhibited the degradation with high initial pH values and at higher temperature. As a conclusion, optimization of environmental conditions and reduction of chlorobenzene homologue accumulation in the process can enhance the degradation of hexachorobenzene in contaminated soil.
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Cordycepin induces S phase arrest and apoptosis in human gallbladder cancer cells.
Molecules
PUBLISHED: 06-20-2014
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Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (??m) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.
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Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded tissues of breast cancer.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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MiR-24/378 is thought to be onco-miRNAs for their ability of enhancing tumor growth. The objective of this study was to evaluate the potential predictive value of miR-24/378 expression in formalin-fixed paraffin-embedded tissues of breast cancer patients.
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Activated protease receptor-2 induces GATA6 expression to promote survival in irradiated colon cancer cells.
Arch. Biochem. Biophys.
PUBLISHED: 05-09-2014
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The resistance to irradiation is common and a great drawback in the treatment of cancer with radiotherapy; the underlying mechanism is unclear. GATA binding protein 6 (GATA6) is associated with the pathogenesis of cancer. This study aims to investigate the role of GATA6 on compromising irradiation effect on HT55 and HT29 cells, 2 colorectal cancer cell lines.
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Combination use of protein-protein interaction network topological features improves the predictive scores of deleterious non-synonymous single-nucleotide polymorphisms.
Amino Acids
PUBLISHED: 05-03-2014
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Single-nucleotide polymorphisms (SNPs) are the most frequent form of genetic variations. Non-synonymous SNPs (nsSNPs) occurring in coding region result in single amino acid substitutions that associate with human hereditary diseases. Plenty of approaches were designed for distinguishing deleterious from neutral nsSNPs based on sequence level information. Novel in this work, combinations of protein-protein interaction (PPI) network topological features were introduced in predicting disease-related nsSNPs. Based on a dataset that was compiled from Swiss-Prot, a random forest model was constructed with an average accuracy value of 80.43% and an MCC value of 0.60 in a rigorous tenfold crossvalidation test. For an independent dataset, our model achieved an accuracy of 88.05% and an MCC of 0.67. Compared with previous studies, our approach presented superior prediction ability. Results showed that the incorporated PPI network topological features outperform conventional features. Our further analysis indicated that disease-related proteins are topologically different from other proteins. This study suggested that nsSNPs may share some topological information of proteins and the change of topological attributes could provide clues in illustrating functional shift due to nsSNPs.
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Bufalin induces cell cycle arrest and apoptosis in gallbladder carcinoma cells.
Tumour Biol.
PUBLISHED: 03-28-2014
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Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine Chan Su, has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro. However, no detailed studies have so far been reported on its action on human gallbladder carcinoma cells. In this study, bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (??m) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways. Intraperitoneal injection of bufalin for 3 weeks significantly inhibited the growth of gallbladder carcinoma (GBC-SD) xenografts in athymic nude mice. Taken together, the results indicate that bufalin may be a potential agent for the treatment of gallbladder cancer.
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Two water-soluble copper(II) complexes: synthesis, characterization, DNA cleavage, protein binding activities and in vitro anticancer activity studies.
J. Inorg. Biochem.
PUBLISHED: 03-25-2014
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Two water-soluble ternary copper(II) complexes of [Cu(L)Cl](ClO4) (1) and [Cu(L)Br2] (2) (L=(2-((quinolin-8-ylimino)methyl)pyridine)) were prepared and characterized by various physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square-pyramidal CuN3Cl2 (1) or CuN3Br2 (2) geometry in which Schiff-base L acts as a neutral tridentate ligand. Both complexes present intermolecular ?-? stacking interactions between quinoline and pyridine rings. The interaction of two complexes with CT-DNA (calf thymus-DNA) and BSA (bovine serum albumin) was studied by means of various spectroscopy methods, which revealed that 1 and 2 could interact with CT-DNA through intercalation mode, and could quench the intrinsic fluorescence of BSA in a static quenching process. Furthermore, the competition experiment using Hoechst 33258 indicated that two complexes may bind to CT-DNA by a minor groove. DNA cleavage experiments indicate that the complexes exhibit efficient DNA cleavage activities without any external agents, and hydroxyl radical (HO) and singlet oxygen ((1)O2) may serve as the major cleavage active species. Notably, the in vitro cytotoxicity of the complexes on three human tumor cells lines (HeLa, MCF-7, and A549) demonstrates that two compounds have broad-spectrum antitumor activity with quite low IC50 ranges of 0.43-1.85?M. Based on the cell cycle experiments, 1 and 2 could delay or inhibit cell cycle progression through the S phase.
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Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway.
Nat. Genet.
PUBLISHED: 03-23-2014
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Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR)<0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P=0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.
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MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway.
Cancer Biol. Ther.
PUBLISHED: 03-21-2014
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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway.
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SH2B1 in ?-cells promotes insulin expression and glucose metabolism in mice.
Mol. Endocrinol.
PUBLISHED: 03-19-2014
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Insulin deficiency drives the progression of both type 1 and type 2 diabetes. Pancreatic ?-cell insulin expression and secretion are tightly regulated by nutrients and hormones; however, intracellular signaling proteins that mediate nutrient and hormonal regulation of insulin synthesis and secretion are not fully understood. SH2B1 is an SH2 domain-containing adaptor protein. It enhances the activation of the Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription and the phosphatidylinositol 3-kinase pathways in response to a verity of hormones, growth factors, and cytokines. Here we identify SH2B1 as a new regulator of insulin expression. In rat INS-1 832/13 ?-cells, SH2B1 knockdown decreased, whereas SH2B1 overexpression increased, both insulin expression and glucose-stimulated insulin secretion. SH2B1-deficent islets also had reduced insulin expression, insulin content, and glucose-stimulated insulin secretion. Heterozygous deletion of SH2B1 decreased pancreatic insulin content and plasma insulin levels in leptin-deficient ob/ob mice, thus exacerbating hyperglycemia and glucose intolerance. In addition, overexpression of JAK2 increased insulin promoter activity, and SH2B1 enhanced the ability of JAK2 to activate the insulin promoter. Overexpression of SH2B1 also increased the expression of Pdx1 and the recruitment of Pdx1 to the insulin promoter in INS-1 832/13 cells, whereas silencing of SH2B1 had the opposite effects. Consistently, Pdx1 expression was lower in SH2B1-deficient islets. These data suggest that the SH2B1 in ?-cells promotes insulin synthesis and secretion at least in part by enhancing activation of JAK2 and/or Pdx1 pathways in response to hormonal and nutritional signals.
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Evaluation of particles released from single-wall carbon nanotube/polymer composites with or without thermal aging by an accelerated abrasion test.
J Occup Environ Hyg
PUBLISHED: 03-18-2014
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To provide data required for assessing the environmental health and safety risks of nanocomposites, abrasion-induced particle release from single-wall carbon nanotube (SWCNT)/polymer composites with or without thermal aging were evaluated by a shot blast system. First, overall composite weight loss (i.e., overall particle release) as a result of shot blasting was measured. Incorporating 5 wt% SWCNTs in polystyrene (PS) matrix was observed to reduce overall particle release by approximately 30% compared with pure PS. Heat treatment of the 5 wt% SWCNT/PS composites at 100°C for 10 days induced very slight change in overall particle release due to shot blasting. However, heat treatment at 350°C for 1 hr greatly deteriorated the abrasion resistance of the composites, enhancing overall particle release. Second, to verify the existence and form of SWCNTs released from the composites, released particles were observed by electron microscopy. Micron-sized particles with protruding SWCNTs and submicron-sized SWCNT clusters were observed in the particles released from the composites. Heat treatment of the composites at 350°C for 1 hr enhanced SWCNT release, which mainly formed clusters or rope-like bundles.
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Norditerpenoids from Flickingeria fimbriata and their inhibitory activities on nitric oxide and tumor necrosis factor-? production in mouse macrophages.
Molecules
PUBLISHED: 03-10-2014
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Bioassay-guided fractionation of the ethanolic extract of the leaves of Flickingeria flimbriata led to the isolation of two new degraded diterpenoids 1 and 2, a new ent-pimarane type diterpenoid 3, and four known steroids 4-7. The structures of 1-3 were elucidated by spectroscopic analysis, and their absolute configurations were determined by chemical methods, TDDFT quantum chemical calculations of ECD spectra, and CD exiton chirality method. Compounds 1 and 2, named flickinflimilins A and B, possess a rare 15,16-dinor-ent-pimarane skeleton. Compounds 1-7 were screened for the inhibitory activity against lipopolysaccharide (LPS)-induced NO and TNF-? production in RAW264.7 cells. Compounds 1-3 exhibited potent inhibitory activities, with IC50 values of less than 10 µM.
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Mouse hepatocyte overexpression of NF-?B-inducing kinase (NIK) triggers fatal macrophage-dependent liver injury and fibrosis.
Hepatology
PUBLISHED: 03-07-2014
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Damaged, necrotic, or apoptotic hepatocytes release damage-associated molecular patterns that initiate sterile inflammation, and liver inflammation drives liver injury and fibrosis. Here we identified hepatic nuclear factor kappa B (NF-?B)-inducing kinase (NIK), a Ser/Thr kinase, as a novel trigger of fatal liver inflammation. NIK is activated by a broad spectrum of stimuli. It was up-regulated in injured livers in both mice and humans. In primary mouse hepatocytes, NIK overexpression stimulated, independently of cell injury and death, release of numerous chemokines and cytokines that activated bone marrow-derived macrophages (BMDMs). BMDMs in turn secreted proapoptotic molecules that stimulated hepatocyte apoptosis. Hepatocyte-specific expression of the NIK transgene triggered massive liver inflammation, oxidative stress, hepatocyte apoptosis, and liver fibrosis, leading to weight loss, hypoglycemia, and death. Depletion of Kupffer cells/macrophages reversed NIK-induced liver destruction and death. Conclusion: the hepatocyte NIK-liver immune cell axis promotes liver inflammation, injury, and fibrosis, thus driving liver disease progression. (Hepatology 2014).
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Oridonin induces apoptosis and cell cycle arrest of gallbladder cancer cells via the mitochondrial pathway.
BMC Cancer
PUBLISHED: 03-06-2014
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Gallbladder cancer is the most frequent malignancy of the bile duct with high aggressive and extremely poor prognosis. The main objective of the paper was to investigate the inhibitory effects of oridonin, a diterpenoid isolated from Rabdosia rubescens, on gallbladder cancer both in vitro and in vivo and to explore the mechanisms underlying oridonin-induced apoptosis and cell cycle arrest.
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A proposed mechanism for the promotion of prion conversion involving a strictly conserved tyrosine residue in the ?2-?2 loop of PrPC.
J. Biol. Chem.
PUBLISHED: 03-04-2014
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The transmission of infectious prions into different host species requires compatible prion protein (PrP) primary structures, and even one heterologous residue at a pivotal position can block prion infection. Mapping the key amino acid positions that govern cross-species prion conversion has not yet been possible, although certain residue positions have been identified as restrictive, including residues in the ?2-?2 loop region of PrP. To further define how ?2-?2 residues impact conversion, we investigated residue substitutions in PrP(C) using an in vitro prion conversion assay. Within the ?2-?2 loop, a tyrosine residue at position 169 is strictly conserved among mammals, and transgenic mice expressing mouse PrP having the Y169G, S170N, and N174T substitutions resist prion infection. To better understand the structural requirements of specific residues for conversion initiated by mouse prions, we substituted a diverse array of amino acids at position 169 of PrP. We found that the substitution of glycine, leucine, or glutamine at position 169 reduced conversion by ? 75%. In contrast, replacing tyrosine 169 with either of the bulky, aromatic residues, phenylalanine or tryptophan, supported efficient prion conversion. We propose a model based on a requirement for tightly interdigitating complementary amino acid side chains within specific domains of adjacent PrP molecules, known as "steric zippers," to explain these results. Collectively, these studies suggest that an aromatic residue at position 169 supports efficient prion conversion.
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Triptolide induces s phase arrest and apoptosis in gallbladder cancer cells.
Molecules
PUBLISHED: 02-13-2014
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Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first time we investigated the effects of triptolide on gallbladder cancer cells and identified the mechanisms underlying its potential anticancer effects. The MTT assay showed that triptolide decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that triptolide strongly suppressed colony formation ability in GBC-SD and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S phase arrest in gallbladder cancer cells. In addition, triptolide induced apoptosis, as shown by the results of annexin V/propidium iodide double-staining and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial membrane potential (??m) in a dose-dependent manner. Finally, western blot analysis of triptolide-treated cells revealed the activation of caspase-3, caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that triptolide may be a promising drug to treat gallbladder carcinoma.
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Electrodeposited nitrogen-doped graphene/carbon nanotubes nanocomposite as enhancer for simultaneous and sensitive voltammetric determination of caffeine and vanillin.
Anal. Chim. Acta
PUBLISHED: 02-06-2014
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A nitrogen-doped graphene/carbon nanotubes (NGR-NCNTs) nanocomposite was employed into the study of the electrochemical sensor via electrodeposition for the first time. The morphology and structure of NGR-NCNTs nanocomposite were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. Meanwhile, the electrochemical performance of the glassy carbon electrode (GCE) modified with electrodeposited NGR-NCNTs (ENGR-NCNTs/GCE) towards caffeine (CAF) and vanillin (VAN) determination was demonstrated by cyclic voltammetry (CV) and square wave voltammetry (SWV). Under optimal condition, ENGR-NCNTs/GCE exhibited a wide linearity of 0.06-50 ?M for CAF and 0.01-10 ?M for VAN with detection limits of 0.02 ?M and 3.3×10(-3) ?M, respectively. Furthermore, the application of the proposed sensor in food products was proven to be practical and reliable. The desirable results show that the ENGR-NCNTs nanocomposite has promising potential in electrocatalytic biosensor application.
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Mild and novel electrochemical preparation of ?-cyclodextrin/graphene nanocomposite film for super-sensitive sensing of quercetin.
Biosens Bioelectron
PUBLISHED: 02-05-2014
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A mild and novel preparation tactics based on electrochemical techniques for the fabrication of electro-deposited graphene (E-GR) and polymerized ?-cyclodextrin (P-?CD) nanocomposite film were developed. The structure and morphology of GR-based nanocomposite were investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. Simultaneously, the electrochemical properties of this nanocomposite were characterized by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Based on the synergistic effect of E-GR and P-?CD, a super-sensitive electrochemical sensor for quercetin was successfully fabricated. Under optimum conditions, the determination range for quercetin was from 0.005 to 20 µM with a low detection limit of 0.001 µM (S/N=3). Moreover, this sensor also displays excellent sensitivity, fine reproducibility and stability. To further study the practical applicability of the proposed sensor, the determination of real samples was carried out with satisfactory results.
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Baicalin induces apoptosis of gallbladder carcinoma cells in vitro via a mitochondrial-mediated pathway and suppresses tumor growth in vivo.
Anticancer Agents Med Chem
PUBLISHED: 02-02-2014
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Baicalin, the main active ingredient in the Scutellaria baicalensis (SB), is prescribed for the treatment of various inflammatory diseases and tumors in clinics in China. In the present study, we evaluated the antitumor activity of baicalin for gallbladder carcinoma and the underlying mechanisms both in vitro and in vivo. Our results indicate that baicalin induced potent growth inhibition, cell cycle arrest, apoptosis and colony-formation inhibition in a dose-dependent manner in vitro. We observed inhibition of NF-?B nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, as well as increased caspase-3 and caspase-9 expression after baicalin treatment in vitro and in vivo, which indicates that the mitochondrial pathway was involved in baicalin-induced apoptosis. In addition, daily intraperitoneally injection of baicalin (15, 30 and 60 mg/kg) for 21 days significantly inhibited the growth of NOZ cells xenografts in nude mice, which improved the survival of baicalin-treated mice. In summary, baicalin exhibited a significant anti-tumor effect by suppressing cell proliferation, promoting apoptosis, and inducing cell cycle arrest in vitro, and by suppressing tumor growth and improving survival in vivo, which suggested that baicalin represents a novel therapeutic option for gallbladder carcinoma.
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The combined effect of hypertension and type 2 diabetes mellitus on aortic stiffness and endothelial dysfunction: an integrated study with high-resolution MRI.
Magn Reson Imaging
PUBLISHED: 01-28-2014
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The purpose of this study was to investigate the combined effect of hypertension and type 2 diabetes mellitus (DM2) on aortic stiffness and endothelial dysfunction by using an integrated MRI approach.
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Protease-activated receptor-2 modulates hepatic stellate cell collagen release and apoptotic status.
Arch. Biochem. Biophys.
PUBLISHED: 01-22-2014
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The pathogenesis of hepatic fibrosis is to be further investigated. Protease-activated receptor-2 (PAR2) plays a role in hepatic fibrosis. This study aims to elucidate the role of activation of PAR2 in the regulation of hepatic stellate cell activities. In this study, the expression of PAR2, Fas and caveolin-1 in human hepatic stellate cell line, HHStec cell (HHStecs) was assessed by real time RT-PCR and Western blot. The levels of collagen were determined by enzyme-linked immunosorbent assay. The PAR2 gene was silenced in HHStecs using RNA interference. Apoptosis of HHStecs was assessed by flow cytometry. The results showed that HHStecs expressed PAR2, which was up regulated by activation with phorbol myristate acetate (PMA). Activation of PAR2 increased the release of collagen from HHStecs. Exposure to PMA induced HHStec apoptosis, which was significantly inhibited by activation of PAR2. The PAR2 activation also suppressed the expression of caveolin-1 and Fas in HHStecs. Over expression of caveolin-1 in HHStecs blocked PAR2-reduced apoptosis. We conclude that HHStecs express PAR2. Activation of PAR2 increases HHStecs to release collagen and reduces the activation-induced HHStec apoptosis, which can be inhibited by the over expression of caveolin-1.
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Decreased circulating miR-375: a potential biomarker for patients with non-small-cell lung cancer.
Gene
PUBLISHED: 01-10-2014
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MicroRNAs (miRNAs) are directly involved in cancer initiation, progression and metastasis. Alterations of miRNAs expression in cancer tissue may be reflected in circulation.We attempted to investigate the expression and clinical significance of plasma miR-20a, miR-31 and miR-375 in patients with non-small cell lung cancer (NSCLC). The plasma levels of miR-20a, miR-31 and miR-375 in 164 NSCLC patients and 164 healthy controls (discovery cohort)were evaluated and compared among various clinicopathological characteristics. The relationship between miRNA expression and clinical outcome of NSCLC patients was examined in an independent cohort (53 cases and 53 controls). The expression level of miR-375 in tissue was also examined. Plasma miR-375 levels in NSCLC patients were significantly decreased in both patient cohorts (P b 0.05). In addition, patients with metastatic NSCLC had lower plasma miR-375 expression than those with non-metastatic NSCLC (P b 0.05). Survival analysis showed that patients with low miR-375 expression had worse overall survival rates than those with high miR-375 expression (hazard ratios (HR)=1.537 (1.046–2.258), P=0.029). This association was independently validated in a separate cohort of 53 NSCLC patients (HR=2.406, 95% CI 1.170–4.945, P=0.017). The expression level of miR-375 was also found to be significantly down-regulated in NSCLC tissues compared with paracancerous tissues (P b 0.001). These findings indicate that miR-375 has an important role in NSCLC initiation and progression, and may be an independent poor prognostic factor in NSCLC patients.
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Synthesis, characterization, and biological activities of two Cu(II) and Zn(II) complexes with one polyquinoline ligand.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 01-07-2014
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Two new complexes, [CuLCl]ClO4 (1) and [Zn2L2SO4(H2O)2](ClO4)2 (2) [L=N,N-bis(quinolin-2-ylmethyl)quinolin-8-amine], have been synthesized and structurally characterized. The interactions of two complexes with CT-DNA have been investigated by UV absorption, fluorescence spectroscopy, viscosity measurements and gel electrophoresis under physiological conditions. Results show that the complexes bind to CT-DNA with a moderate intercalative mode and exhibit efficient DNA cleavage activity on UV-A light of 365 nm. Furthermore, two complexes could quench the intrinsic fluorescence of BSA in a static quenching process based on BSA binding experiments. Notably, in vitro cytotoxicity study of two complexes on four human tumor cells lines (7404, HeLa, MCF-7, and HepG-2) indicate that both of them have the potential to act as effective anticancer drugs with low IC50 values.
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Epigenetic code and potential epigenetic-based therapies against chronic diseases in developmental origins.
Drug Discov. Today
PUBLISHED: 01-06-2014
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Accumulated findings have demonstrated that the epigenetic code provides a potential link between prenatal stress and changes in gene expression that could be involved in the developmental programming of various chronic diseases in later life. Meanwhile, based on the fact that epigenetic modifications are reversible and can be manipulated, this provides a unique chance to develop multiple novel epigenetic-based therapeutic strategies against many chronic diseases in early developmental periods. This article will give a short review of recent findings of prenatal insult-induced epigenetic changes in developmental origins of several chronic diseases, and will attempt to provide an overview of the current epigenetic-based strategies applied in the early prevention, diagnosis and possible therapies for human chronic diseases.
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Clinical Study of Effects of Jian Ji Ning, a Chinese Herbal Medicine Compound Preparation, in Treating Patients with Myasthenia Gravis via the Regulation of Differential MicroRNAs Expression in Serum.
Evid Based Complement Alternat Med
PUBLISHED: 01-05-2014
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Myasthenia gravis (MG) is an autoimmune disease, of which the pathogenesis has remained unclear. At present, MG does not have any effective treatment with minor side effects. Jian Ji Ning (JJN), a traditional Chinese medicine formula consisting of 11 medicinal plants, has been used in the treatment of MG for many years. The present study aims to determine if the Chinese herbal medicine JJN could lighten the clinical symptoms of patients with MG via the regulation of differential microRNAs (miRNAs) expression in serum. JJN should be orally administered twice a day for 6 months. In the efficacy evaluation adopting the Quantitative Myasthenia Gravis Score (QMG), we found that JJN could improve the clinical symptoms of patients with MG more effectively. Besides, we found that JJN could regulate differential miRNAs expression in serum of patients with MG. Accordingly, we speculate that the effects of JJN on improving clinical symptoms and blood test indicators of patients with MG may be due to its inhibition of apoptotic pathways of some immune cells and its connection with the regulation of serum miRNAs of some patients. In conclusion, we believe that JJN has a reliable curative effect on patients with MG-induced neuropathologic changes.
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Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB classification (P = 0.008), whereas smCEBPA occurred in almost all subtypes (P = 0.401). Patients with dmCEBPA had significantly younger age and higher WBC counts than those with wtCEBPA (P = 0.016 and 0.043, respectively). Both dmCEBPA and smCEBPA were mainly present in cytogenetically normal patients. Patients with dmCEBPA achieved higher rate of complete (CR) than wtCEBPA patients (88% vs. 51%, P = 0.037), whereas smCEBPA and wtCEBPA groups are similar (47% vs. 51%, P = 0.810). Patients with dmCEBPA had a superior overall survival (OS) compared with patients with wtCEBPA (P = 0.033), whereas patients with smCEBPA had a similar OS as patients with wtCEBPA (P = 0.976). dmCEBPA but not smCEBPA was also associated with favorable outcome in patients with wild-type NPM1 and FLT3-ITD (NPM1(wt)FLT3-ITD(wt) ). Our data confirm that dmCEBPA but not smCEBPA is prognostically favorable in NPM1(wt)FLT3-ITD(wt) AML, and suggest that the entity AML with mutated CEBPA should be definitely designated as AML with dmCEBPA in WHO classification and smCEBPA should be excluded from the favorable risk of molecular abnormalities.
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Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma cells.
Cancer Cell Int.
PUBLISHED: 01-01-2014
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Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro.
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The impact of pri-miR-218 rs11134527 on the risk and prognosis of patients with esophageal squamous cell carcinoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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MicroRNA-218 (miR-218) acts as a tumor suppressor in numerous types of cancer by regulation of the expression of target genes. The aim of this study was to investigate whether polymorphisms in miR-218 LAMB3 pathway were associated with the risk and prognosis of esophageal squamous cell carcinoma (ESCC). Pri-mir-218 rs11134527 and LAMB3 rs2566 were genotyped in ESCC patients and 745 controls to assess their associations with cancer risk and overall survival. Pri-mir-218 rs11134527 was significantly associated with a decreased risk of ESCC under codominant, recessive and additive models. Although there was a significant association between rs11134527 and better survival of ESCC patients under codominant, recessive and additive models, the association disappeared after adjustment for TNM and LNM. However, further stratified analysis revealed that the association remained significant in patients with TNM stages I and II or non-LNM. Our data suggest that pri-miR-218 rs11134527 may contribute to the genetic susceptibility and prognosis for ESCC in Chinese Han population.
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Decreased SFRP2 expression is associated with intermediate and poor karyotypes in de novo acute myeloid leukemia.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Dysregulation of secreted frizzled-related protein 2 (SFRP2) has been found in various cancers. However, it is little known about the pattern of SFRP2 expression in acute myeloid leukemia (AML). This study was aimed to analyze the expression status of SFRP2 gene in AML patients and explore its clinical significance using real-time quantitative PCR (RQ-PCR). The level of SFRP2 expression significantly decreased in AML compared to controls (P<0.001). Receiver operating characteristic curve (ROC) analysis revealed that an area under the ROC curve (AUC) of 0.871 (P<0.001) or 0.902 (P<0.001) in discriminating all patients or cytogenetically normal (CN) patients from controls, respectively. Low level of SFRP2 expression was found more frequently in cytogenetically intermediate and poor groups (72% and 62%, respectively) than in favorable group (42%) (P<0.05). However, there was no significant difference in the rate of complete remission (CR) and overall survival between the groups with low SFRP2 and high expression (P>0.05). SFRP2 expression significantly increased after CR compared to initial diagnosis (P<0.05). These findings suggest that decreased SFRP2 expression is associated with intermediate/poor karyotypes in AML patients and detection of SFRP2 expression may be helpful to the diagnosis and disease monitoring in CN-AML.
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Association of the expression of unc-51-Like kinase 1 with lymph node metastasis and survival in patients with esophageal squamous cell carcinoma.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Unc-51-Like Kinase 1 (ULK1) is regarded as a central role in autophagy. Although the details of how ULK1 triggers autophagy are obscure, the relationship between ULK1 expression and the diagnosis and prognosis of cancer patients may guide the clinical practice and scientific research. The aim of this study was to investigate and compare the expression level of ULK1 in 86 paired esophageal squamous cell carcinoma (ESCC) and paracancerous tissues, and to examine the effect of ULK1 expression on the prognosis of ESCC patients. ULK1 was primarily expressed in cytoplasm, but was rarely seen in nucleus. The levels of cytoplasmic ULK1 in ESCC tissues were higher than those in paracancerous tissue (P < 0.01) and significantly associated with lymph node metastasis (LNM) (P = 0.025). Survival analysis showed that patients with low expression of cytoplasmic ULK1 had worse survival time than those with high expression of cytoplasmic ULK1 (hazard ratio = 1.754, 95% confidence interval: 1.022-3.010, P = 0.041), which disappeared after adjustment for TNM stages and LNM (P = 0.319). In conclusion, ULK1 might play an important role in the occurrence and development of ESCC and represent a potential prognostic biomarker for ESCC patients. However, the precise impact of ULK1 on predicting the prognosis of patients with ESCC requires further investigation.
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ZBED6 modulates the transcription of myogenic genes in mouse myoblast cells.
PLoS ONE
PUBLISHED: 01-01-2014
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ZBED6 is a recently discovered transcription factor, unique to placental mammals, that has evolved from a domesticated DNA transposon. It acts as a repressor at the IGF2 locus. Here we show that ZBED6 acts as a transcriptional modulator in mouse myoblast cells, where more than 700 genes were differentially expressed after Zbed6-silencing. The most significantly enriched GO term was muscle protein and contractile fiber, which was consistent with increased myotube formation. Twenty small nucleolar RNAs all showed increased expression after Zbed6-silencing. The co-localization of histone marks and ZBED6 binding sites and the effect of Zbed6-silencing on distribution of histone marks was evaluated by ChIP-seq analysis. There was a strong association between ZBED6 binding sites and the H3K4me3, H3K4me2 and H3K27ac modifications, which are usually found at active promoters, but no association with the repressive mark H3K27me3. Zbed6-silencing led to increased enrichment of active marks at myogenic genes, in agreement with the RNA-seq findings. We propose that ZBED6 preferentially binds to active promoters and modulates transcriptional activity without recruiting repressive histone modifications.
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Synergism from the combination of ulinastatin and curcumin offers greater inhibition against colorectal cancer liver metastases via modulating matrix metalloproteinase-9 and E-cadherin expression.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Liver metastasis is a major cause of mortality in colorectal cancer (CRC). The current study was to investigate the ability of ulinastatin (UTI) and curcumin (CUR) to inhibit CRC liver metastases via modulating matrix metalloproteinase-9 (MMP-9) and E-cadherin expression. Human CRC HCT-116 cells were treated with compounds individually and in combination in order to understand the effect on cell migration and invasion. The HCT-116 cell line was established to stably express luciferase and green fluorescent protein (GFP) by lentiviral transduction (HCT-116-Luc-GFP). We identified an anti-metastasis effect of UTI and CUR on a CRC liver metastasis mouse model. Tumor development and therapeutic responses were dynamically tracked by bioluminescence imaging. Expression of MMP-9 and E-cadherin in metastatic tumors was detected by immunohistochemical assay. Results of wound healing and cell invasion assays suggest that treatment with UTI, CUR, and UTI plus CUR, respectively, significantly inhibit HCT-116 cell migration and invasion. Furthermore, results of CRC hepatic metastasis on a nude mouse model showed that treatment with UTI, CUR alone, and a combination notably inhibited hepatic metastases from CRC and prolonged survival of tumor-bearing mice, especially in the UTI plus CUR group. These results suggest that the combination of UTI and CUR together may offer greater inhibition against metastasis of CRC.
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Contribution of the resting-state functional connectivity of the contralesional primary sensorimotor cortex to motor recovery after subcortical stroke.
PLoS ONE
PUBLISHED: 01-01-2014
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It remains uncertain if the contralesional primary sensorimotor cortex (CL_PSMC) contributes to motor recovery after stroke. Here we investigated longitudinal changes in the resting-state functional connectivity (rsFC) of the CL_PSMC and their association with motor recovery. Thirteen patients who had experienced subcortical stroke underwent a series of resting-state fMRI and clinical assessments over a period of 1 year at 5 time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Thirteen age- and gender-matched healthy subjects were recruited as controls. The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rsFCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index (MI) scores. Compared with healthy controls, the rsFCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the inter-hemispheric rsFC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rsFC of the CL_PSMC was not correlated with the MI scores. This study shows dynamic changes in the rsFCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rsFC between the bilateral PSMC may facilitate motor recovery in stroke patients. However, generalization of our findings is limited by the small sample size of our study and needs to be confirmed.
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Separation of hydrophobic organic compound from surfactant solutions with activated carbon in a fixed bed.
Water Sci. Technol.
PUBLISHED: 12-03-2013
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The adsorption behavior of phenanthrene (PHE) in Triton X-100 (TX100) solutions with fixed activated carbon (AC) bed was studied to recover the surfactant. The effect of various parameters like bed depths, flow rates, influent TX100 concentration, and influent PHE concentration were investigated. The breakthrough time of both TX100 and PHE increased with the increase of bed height and decrease of flow rate and influent concentration. In the case of fixed length, a lower flow rate, higher concentration of TX100, and lower concentration of PHE will benefit the longer effective surfactant recovery time. The adsorption data were integrated into bed depth service time models. The height of exchange zone of TX100 should be much shorter than that of PHE, which provides conditions to separate the hydrophobic organic compound from surfactant solutions with AC in a fixed bed. It is likely that the adsorption process is controlled by hydrophobic interaction.
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[Application of multiple lines of evidence analysis technology in the assessment of sites contaminated by heavy metals].
Huan Jing Ke Xue
PUBLISHED: 12-03-2013
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A multiple lines of evidence analysis technology was applied to assess whether sites were contaminated by heavy metals (HMs). Firstly, the baseline upper limit concentration for As and Cr6+ were derived for the two investigated sites based on the analysis of the relative cumulative probability plots of the two metals and their spatial distribution in the soil. The results indicated that the baseline upper limit concentrations for As and Cr6+ at site 1 were 29. 8 mg x kg(-1) and 76. 1 mg x kg(-1), respectively, which were much higher than those reported for the local area by others. But at site 2, the baseline upper limit concentrations for As and Cr6+ were 10.6 mg x kg(-1) and 33 mg x kg(-1), respectively, which were only a little higher than the reported values. Taken the derived baseline concentrations as the assessment criteria, both sites were contaminated by the heavy metals to some degree, which is consistent with the site historical activities review results and element correlation analysis results. At site 1, the As concentration in 3.8% samples exceeded the derived baseline concentration, while the Cr6+ concentration in 6.0% samples exceeded the baseline concentration. At site 2, only the concentration of As in 5.2% samples exceeded the derived baseline value. All the above exceeding rates were much lower than those based on the reported baseline values, which were 77.7% and 96.7% for As and Cr6+ at site 1, respectively and 41.9% for As at site 2. The difference indicates that for a specific site, the baseline concentrations for heavy metals reported in literatures should not be directly applied as the criteria to assess whether the site is contaminated or not, which may cause the results to lose the objectivity and leading to the misallocation of lots of rare resource to remediate soil that maybe not contaminated.
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Serum miR-200c and clinical outcome of patients with advanced esophageal squamous cancer receiving platinum-based chemotherapy.
Am J Transl Res
PUBLISHED: 11-17-2013
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MicroRNA-200c (miR-200c) influences sensitivity to chemotherapy and radiotherapy in vitro. This study was designed to investigate the prognostic potential of serum miR-200c in patients with advanced esophageal squamous cancer (ESCC). The serum levels of miR-200c was assayed by quantitative RT-PCR in 157 healthy subjects and 157 patients with advanced ESCC who were treated with platinum-based chemotherapy. The serum levels of miR-200c in advanced ESCC patients was significantly increased compared with those in controls (P < 0.001). Serum miR-200c expression was significantly associated with TNM stage (P = 0.037) and treatment response (P = 0.021). Patients with high expression of serum miR-200c had a higher risk for death than those with low expression of serum miR-200c (adjusted hazard ratios = 1.665, 95% confidence intervals: 1.135-2.443, P = 0.009). In conclusion, serum miR-200c may serve as predictor of survival for advanced ESCC and provide information for personalized therapy in advanced ESCC.
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Plasma adrenomedullin levels are associated with long-term outcomes of acute ischemic stroke.
Peptides
PUBLISHED: 11-14-2013
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Plasma adrenomedullin concentration has been found to be enhanced in ischemic stroke. Up to now, little is known about the association of plasma adrenomedullin concentration with clinical outcomes of ischemic stroke. This study recruited 138 patients with ischemic stroke and 138 healthy volunteers. Unfavorable outcome was defined as modified Rankin Scale score >2 at 3 months. Plasma adrenomedullin concentrations were determined by enzyme-linked immunosorbent assay. Plasma adrenomedullin concentrations were statistically significantly higher in patients than in healthy individuals (79.9±27.3pg/mL vs. 36.8±10.4pg/mL; P<0.001). 3-Month mortality was 20.3% (28/138) and sixty-six patients (47.8%) had unfavorable outcome in 3 months. A logistic regression analysis identified plasma adrenomedullin concentration as an independent predictor of 3-month mortality (odds ratio, 1.211; 95% confidence interval, 1.101-1.582; P=0.004) and unfavorable outcome (odds ratio, 1.193; 95% confidence interval, 1.082-1.447; P=0.006). Receiver operating characteristic curve analysis showed that plasma adrenomedullin concentration predicted 3-month mortality (area under curve, 0.806; 95% confidence interval, 0.730-0.868) and unfavorable outcome (area under curve, 0.816; 95% confidence interval, 0.742-0.877) with the high predictive value. Its predictive performance was similar to that of National Institutes of Health Stroke Scale score (P=0.694 or 0.206). Its combined use with National Institutes of Health Stroke Scale score did not improve the predictive value (P=0.236 or 0.590). Thus, adrenomedullin may aid to predict long-term clinical outcomes of patients with ischemic stroke.
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Knowledge, attitudes and competence in nursing practice of typhoon disaster relief work among Chinese nurses: A questionnaire survey.
Int J Nurs Pract
PUBLISHED: 11-14-2013
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The aim of this paper is to examine the relationships among nurses knowledge of, attitudes towards and level of competence in nursing practice, as well as factors influencing nurses competence in nursing practice, in typhoon disaster relief work. A cross-sectional descriptive study was conducted using a self-developed questionnaire to obtain data from 607 nurses working in four tertiary hospitals and two secondary hospitals in Fujian, China, in November 2011. Our findings show that the nurses average percentage scores on their responses to questions in the domains of knowledge, attitudes and practice were 66.33%, 68.87% and 67.60%, respectively. The findings demonstrated a significant positive relationship between nurses attitudes and their practice. Nurses working unit, prior training in typhoon disaster relief, current position of employment and attitudes were significant predictors of nurses competence in practice. The results indicate that strategies need to be developed for nurses to improve their knowledge, attitudes and practice.
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Facile and novel electrochemical preparation of a graphene-transition metal oxide nanocomposite for ultrasensitive electrochemical sensing of acetaminophen and phenacetin.
Nanoscale
PUBLISHED: 11-08-2013
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A facile and novel preparation strategy based on electrochemical techniques for the fabrication of electrodeposited graphene (EGR) and zinc oxide (ZnO) nanocomposite was developed. The morphology and structure of the EGR-based nanocomposite were investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (XPS) and Raman spectroscopy. Meanwhile, the electrochemical performance of the nanocomposite was demonstrated with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Due to the synergistic effect of EGR and ZnO nanoparticles, an ultrasensitive electrochemical sensor for acetaminophen (AC) and phenacetin (PCT) was successfully fabricated. The linearity ranged from 0.02 to 10 ?M for AC and 0.06 to 10 ?M for PCT with high sensitivities of 54?295.82 ?A mM(-1) cm(2) for AC and 21?344.66 ?A mM(-1) cm(2) for PCT, respectively. Moreover, the practical applicability was validated to be reliable and desirable in pharmaceutical detections. The excellent results showed the promise of the proposed preparation strategy of EGR-transition metal oxide nanocomposite in the field of electroanalytical chemistry.
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[Reduced expression of gene correlates with good prognosis in acute myeloid leukemia].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-26-2013
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This study was aimed to investigate the expression pattern of gene PDLIM4 (PDZ and LIM domain 4) and analyze its clinical correlation with the patients suffered from acute myeloid leukemia (AML). The expression pattern of PDLIM4 in AML was detected by using EvaGreen real-time quantitative PCR (RQ-PCR). The results showed that the PDLIM4 transcript significantly decreased in 94 AML patients, compared with 21 controls (P < 0.01). The decrease of PDLIM4 transcript was found in 42 (45%) AML patients. PDLIM4 low-rexpression occurred among the subtypes of M1/M2/M3 more frequently than that in M4/M5/M6 (56% vs 20%, P < 0.01). AML patients with PDLIM4 low-expression had an overall survival (OS) higher than that in AML patients without PDLIM4 low-expression (P < 0.05). Analysis with receiver operating characteristic curve (ROC) displayed that PDLIM4 expression possesses the diagnostic value to differentiate AML from controls, with ROC curve area of 0.865 (95% CI: 0.801-0.930). It is concluded that reduced PDLIM4 expression is a common and favorable event for the good prognosis in AML, and can be used as a potential diagnostic biomarker of cancer.
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SH2B1 in ? cells regulates glucose metabolism by promoting ? cell survival and islet expansion.
Diabetes
PUBLISHED: 10-22-2013
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IGF-1 and insulin promote ? cell expansion by inhibiting ? cell death and stimulating ? cell proliferation, and the PI 3-kinase/Akt pathway mediates insulin and IGF-1 action. Impaired ? cell expansion is a risk factor for type 2 diabetes. Here we identified SH2B1, which is highly expressed in ? cells, as a novel regulator of ? cell expansion. Silencing of SH2B1 in INS-1 832/13 ? cells attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin (STZ)-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. Activation of the PI 3-kinase/Akt pathway in ? cells was impaired in pancreas-specific SH2B1 knockout (PKO) mice fed a high fat diet (HFD). HFD-fed PKO mice also had increased ? cell apoptosis, decreased ? cell proliferation, decreased ? cell mass, decreased pancreatic insulin content, impaired insulin secretion, and exacerbated glucose intolerance. Furthermore, PKO mice were more susceptible to STZ-induced ? cell destruction, insulin deficiency, and hyperglycemia. These data indicate that SH2B1 in ? cells is an important pro-survival and pro-proliferative protein and promotes compensatory ? cell expansion in the insulin resistant state and in response to ? cell stress.
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Linking ethylene to nitrogen-dependent leaf longevity of grass species in a temperate steppe.
Ann. Bot.
PUBLISHED: 10-17-2013
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Background and Aims Leaf longevity is an important plant functional trait that often varies with soil nitrogen supply. Ethylene is a classical plant hormone involved in the control of senescence and abscission, but its role in nitrogen-dependent leaf longevity is largely unknown. Methods Pot and field experiments were performed to examine the effects of nitrogen addition on leaf longevity and ethylene production in two dominant plant species, Agropyron cristatum and Stipa krylovii, in a temperate steppe in northern China. Key Results Nitrogen addition increased leaf ethylene production and nitrogen concentration but shortened leaf longevity; the addition of cobalt chloride, an ethylene biosynthesis inhibitor, reduced leaf nitrogen concentration and increased leaf longevity. Path analysis indicated that nitrogen addition reduced leaf longevity mainly through altering leaf ethylene production. Conclusions These findings provide the first experimental evidence in support of the involvement of ethylene in nitrogen-induced decrease in leaf longevity.
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Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-16-2013
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We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. ZBED6 was translated from a ZC3H11A transcript in which the ZBED6-containing intron was retained. ZBED6 was present in mouse ?TC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function-i.e., insulin production-because (i) the nuclear ZBED6 were the predominant forms in rapidly proliferating ?TC-6 cells, but not in human islet cells; (ii) down-regulation of ZBED6 in ?TC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis; (iii) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (iv) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.
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Hemodynamic analysis of renal artery stenosis using computational fluid dynamics technology based on unenhanced steady-state free precession magnetic resonance angiography: preliminary results.
Int J Cardiovasc Imaging
PUBLISHED: 08-22-2013
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This study aims to evaluate the feasibility of computational fluid dynamics (CFD) technology in analysis of renal artery stenosis (RAS) based on unenhanced MR angiography (MRA). Thirty hypertensive patients with unilateral RAS, and 10 normal volunteers, underwent unenhanced MRA on a 1.5 T MR scanner. 12 of 30 patients also underwent ultrasound (US) to detect peak systolic velocity. The patient-specific CFD based on MRA was carried out thereafter. Stenosis grades and hemodynamic variables at the stenosis of main renal artery, including pressure difference (PD), velocity and mass flow rate (MFR), were analysed. And the hemodynamic indices of stenoses were compared with the parameters of normal renal arteries and available US velocity profile. High intraclass correlation coefficient (value 0.995) and no significant difference (p > 0.05) was shown between maximum velocity of CFD and peak systolic velocity of US in 12 patients. For normal renal arteries, the average PD, velocity and MFR were all in the reported normal physiological range. However, for stenotic arteries, the translesional PD and velocity of main renal arteries increased with the severity of stenotic degrees, while the MFR decreased. 50 % diameter stenosis was the threshold at which all three hemodynamic parameters experienced significant changes (p < 0.01). This preliminary study shows that unenhanced-MRA-based CFD can be utilized to noninvasively analyse hemodynamic parameters of RAS. The acquired variables may provide meaningful information regarding stratification of the stenosis and further therapeutic treatment.
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Ring-opening polymerization of L-lactic acid O-carboxyanhydrides initiated by alkoxy rare earth compounds.
Molecules
PUBLISHED: 08-20-2013
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The ring-opening polymerization of L-lactic acid O-carboxyanhydrides was initiated by triisopropoxyneodymium in toluene-THF mixtures. Typically, high yields and relatively high molecular weight PLAs were obtained within 4 h at 25 °C. The reaction was highly controllable and easy to conduct, and the molecular weight distribution of the PLAs was rather narrow (Mw/Mn = 1.10-1.36). NMR analysis showed that one end of the PLA chain consisted of an isopropoxy group, while the other end of the chain contained a hydroxyl group. Due to their availability and high polymerizability, Lac-OCAs are promising monomers for the preparation of tailored architectures derived from well-defined PLAs.
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Synergistic Modulation of Surface Interaction to Assemble Metal Nanoparticles into Two-Dimensional Arrays with Tunable Plasmonic Properties.
Small
PUBLISHED: 07-11-2013
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A simple strategy based on the synergistic modulation of inter-particle and substrate-particle interaction is applied for the large-scale fabrication of two-dimensional (2D) Au and Ag nanoparticle arrays. The surface charge of the substrate is used to redistribute the double layer electric charges on the particles and to modulate the inter-particle distance within the 2D nanoparticle arrays on the substrate. The resultant arrays, with a wide range of inter-particle distances, display tunable plasmonic properties. It can be foreseen that such 2D nanoparticle arrays possess potential applications as multiplexed colorimetric sensors, integrated devices and antennas. Herein, it is demonstrated that these arrays can be employed as wavelength-selective substrates for multiplexed acquisition of surface-enhanced Raman scattering (SERS) spectra. This simple one step process provides an attractive and low cost strategy to produce high quality and large area 2D ordered arrays with tunable properties.
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Inclusion of the orientational entropic effect and low-resolution experimental information for protein-protein docking in Critical Assessment of PRedicted Interactions (CAPRI).
Proteins
PUBLISHED: 06-19-2013
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Inclusion of entropy is important and challenging for protein-protein binding prediction. Here, we present a statistical mechanics-based approach to empirically consider the effect of orientational entropy. Specifically, we globally sample the possible binding orientations based on a simple shape-complementarity scoring function using an FFT-type docking method. Then, for each generated orientation, we calculate the probability through the partition function of the ensemble of accessible states, which are assumed to be represented by the set of nearby binding modes. For each mode, the interaction energy is calculated using our ITScorePP scoring function that was developed in our laboratory based on principles of statistical mechanics. Using the above protocol, we present the results of our participation in Rounds 22-27 of the Critical Assessment of PRedicted Interactions (CAPRI) experiment for 10 targets (T46-T58). Additional experimental information, such as low-resolution small-angle X-ray scattering data, was used when available. In the prediction (or docking) experiments of the 10 target complexes, we achieved correct binding modes for six targets: one with high accuracy (T47), two with medium accuracy (T48 and T57), and three with acceptable accuracy (T49, T50, and T58). In the scoring experiments of seven target complexes, we obtained correct binding modes for six targets: one with high accuracy (T47), two with medium accuracy (T49 and T50), and three with acceptable accuracy (T46, T51, and T53). Proteins 2013; 81:2183-2191. © 2013 Wiley Periodicals, Inc.
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[Application and benefit evaluation of tiered health risk assessment approach on site contaminated by benzene].
Huan Jing Ke Xue
PUBLISHED: 06-11-2013
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The procedures of implementing tiered health risk assessment approach were introduced in detail, and took a large-scale site polluted by benzene in Beijing as an example, the difference on the remediation target of benzene in soil, as well as the corresponding soil remediation volume and costs, were compared. The results indicate that the benzene concentration in soil within 1.5 m in depth and the one below should be remediated to 0.26 mg x kg(-1) and 0.15 mg x kg(-1), respectively, in order to keep the cumulative carcinogenic health risk below 1 x 10(-6) based on tiered II assessment. However, according to tiered III assessment result, which is based on the benzene in soil gas within the contaminated areas in the investigated site, the soil in the corresponding depth should only be remediated to 2.6 mg x kg(-1) and 1.5 mg x kg(-1), respectively. That means the soil remediation volume delimited on tiered III assessment result is less than the one on tiered II by 139 537 m3 and the corresponding remediation costs will be reduced by 57 million Yuan, meaning the enormous economic benefits compared to the costs (around 100 thousands Yuan) spent to carry out tiered III assessment in the site.
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[Application of tiered approach to assess the impact of backfilling remediated soil on groundwater].
Huan Jing Ke Xue
PUBLISHED: 06-11-2013
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The tiered approach for assessing the impact of backfilling treated contaminated soil on groundwater was presented in details with a case study. The soil was contaminated by 1,2-dicholorenthane and 9 other organic pollutants and had been remediated before backfilling to meet the pre-set remediation goals based on health risk assessment. The results from tiered I assessment indicate that the concentrations of 8 contaminants in the leachate of the backfilling soil layer would exceed the assessment standards probably leading to groundwater contamination. However, the results from tiered II assessment, in which the adsorption and retardation of vadose zone soil was taken into account and the concentrations of pollutants reaching the groundwater table were predicated, reveal that only the concentrations of 6 contaminants would exceed the assessment standards. Further, taking the dilution and mixing of the groundwater into consideration, tiered III assessment was adopted and the results reveal that only 4 contaminants were beyond the standards. Finally, tiered IV assessment, aiming at predicting the concentration at the target well downstream, was carried out by considering the retardation of contaminants in saturated layer, and the results indicate only 1 pollutant was above the assessment standard. Therefore, it can be seen that the predicted concentrations of the target pollutants at advanced assessment levels will be closer to those at the target drinking water well and the amount of contaminants whose initially-set remediation goals need to be modified will decrease correspondingly, indicating the reduction in pollution prevention cost, although more efforts should be made and more field data should be collected to implement the advance assessment level.
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Temporal niche promotes biodiversity during adaptive radiation.
Nat Commun
PUBLISHED: 06-03-2013
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Understanding mechanisms underlying the origin and maintenance of biodiversity is a central goal of modern ecological and evolutionary research. Ecologists have recognized the potentially important role of temporal niche in promoting species coexistence and diversity, yet little is known about how temporal niche affects the evolution of biodiversity. Here we show that temporal niche strongly influences biodiversity dynamics in rapidly evolving bacteria. An ancestral bacterium quickly diversifies when provided with constant spatial niche opportunities or when experiencing temporal niche dynamics. However, only in communities with temporal niches, which promote frequency-dependent selection and the positive growth of new mutants, is the accumulated phenotypic diversity able to persist. Overall, the presence of temporal niche opportunities eliminates the overshooting dynamics of adaptive radiation typically seen in this and other systems. These results suggest that temporal niche may have an essential role in the maintenance of biodiversity over evolutionary time.
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[Preparation by spin-coating technology and characterization of UV-enhanced Lumogen film].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-24-2013
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As an effective way to increase the UV response for CCD/CMOS, the advantage of the Lumogen film is the simple process and low cost. In the present paper the Lumogen film was deposited onto fused silica slides by the spin-coating way, which has less damage than PVD physical vacuum deposition) way. The main test and analysis of the thin-film include transmission spectrum, absorption spectrum, and excitation and emission spectrum. It was showed that these coatings were transmitted well in visible region (lambda > 400 nm), and emitted a yellowish green glow centered at -525 nm together with a wide excitation spectrum range from 200 to 400 nm. The synthesis shows that Lumogen coatings match accurately with the detected spectrum of conventional silicon-based image sensors, which makes this kind of thin films an ultraviolet responsive coating for sensors.
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Automated large-scale file preparation, docking, and scoring: evaluation of ITScore and STScore using the 2012 Community Structure-Activity Resource benchmark.
J Chem Inf Model
PUBLISHED: 05-21-2013
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In this study, we use the recently released 2012 Community Structure-Activity Resource (CSAR) data set to evaluate two knowledge-based scoring functions, ITScore and STScore, and a simple force-field-based potential (VDWScore). The CSAR data set contains 757 compounds, most with known affinities, and 57 crystal structures. With the help of the script files for docking preparation, we use the full CSAR data set to evaluate the performances of the scoring functions on binding affinity prediction and active/inactive compound discrimination. The CSAR subset that includes crystal structures is used as well, to evaluate the performances of the scoring functions on binding mode and affinity predictions. Within this structure subset, we investigate the importance of accurate ligand and protein conformational sampling and find that the binding affinity predictions are less sensitive to non-native ligand and protein conformations than the binding mode predictions. We also find the full CSAR data set to be more challenging in making binding mode predictions than the subset with structures. The script files used for preparing the CSAR data set for docking, including scripts for canonicalization of the ligand atoms, are offered freely to the academic community.
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Maternal high-salt intake during pregnancy reprogrammed Renin-Angiotensin system-mediated cardiomyocyte apoptosis in the adult offspring heart.
Reprod Sci
PUBLISHED: 05-20-2013
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Aims: Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin-angiotensin system (RAS) that may mediate cardiac cell death. Methods and Results: Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells. Conclusion: Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway.
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[Case study on health risk assessment based on site-specific conceptual model].
Huan Jing Ke Xue
PUBLISHED: 05-15-2013
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Site investigation was carried out on an area to be redeveloped as a subway station, which is right downstream of the groundwater of a former chemical plant. The results indicate the subsurface soil and groundwater in the area are both polluted heavily by 1,2-dichloroethane, which was caused by the chemical plant upstream with the highest concentration was 104.08 mg.kg-1 for soil sample at 8.6 m below ground and the highest concentration was 18500 microg.L-1 for groundwater. Further, a site-specific contamination conceptual model, giving consideration to the specific structure configuration of the station, was developed, and the corresponding risk calculation equation was derived. The carcinogenic risks calculated with models developed on the generic site conceptual model and derived herein on the site-specific conceptual model were compared. Both models indicate that the carcinogenic risk is significantly higher than the acceptable level which is 1 x 10(-6). The comparison result reveals that the risk calculated with the former models for soil and groundwater are higher than the one calculated with the latter models by 2 times and 1.5 times, respectively. The finding in this paper indicates that the generic risk assessment model may underestimate the risk if specific site conditions and structure configuration are not considered.
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The Combined effects of hematoporphyrin monomethyl ether-SDT and doxorubicin on the proliferation of QBC939 cell lines.
Ultrasound Med Biol
PUBLISHED: 05-15-2013
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It is well established that both hematoporphyrin monomethyl ether-sonodynamic therapy (HMME-SDT) and doxorubicin (DOX) can induce cell apoptosis but each alone has its own limitations. To date, the combined effects of HMME-SDT and DOX on inducing cell apoptosis are little known and the mechanism for the combined effects remains poorly understood. In the present study, we reported the synergistic effects of HMME-SDT and DOX on inhibiting the proliferation of human cholangiocarcinoma QBC939 cells and investigated the mechanism of this synergy. The data from MTT assay, flow cytometer, Hoechst staining and cell arrest analysis showed that the combination of HMME-SDT and DOX exhibited higher inhibiting effects on proliferation of QBC939 cells than the sole application of HMME-SDT or DOX. In addition, the synergistic effects were shown to result from the DNA damage as demonstrated by single cell gel electrophoresis and DNA fragmentation. Furthermore, the expression of p53, Fas, Bax and activated caspase-3 protein was significantly upregulated in cells treated with HMME-SDT and DOX, whereas Bcl-2 protein was downregulated. Taken together, our data suggested that the application of HMME-SDT combined with DOX had better inhibiting effects on QBC939 cells and the effects were caused mainly by DNA damage.
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Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia.
Leuk. Res.
PUBLISHED: 05-13-2013
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Dysregulation of microRNA let-7a-3 has been identified in several solid tumors and is associated with prognosis of patients. However, the pattern of let-7a-3 expression and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of let-7a-3 and its clinical significance in AML patients using real-time quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de novo AML. There was no significant difference in age, blood parameters, FAB/WHO subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3 overexpression (P>0.05). The patients with let-7a-3 overexpression had similar rates of complete remission (CR) as those without let-7a-3 overexpression (50% vs. 56%, P=0.693). Although the overall survival (OS) of AML patients with let-7a-3 overexpression (median 12 months,) was shorter than those without overexpression (median 25 months), the difference was not statistically significant (P=0.228). However, among those 51 obtained CR, patients with let-7a-3 overexpression had significantly shorter OS than those without let-7a-3 overexpression (P=0.029). The difference in relapse-free survival (RFS) was also significant between two groups (P=0.005). These findings suggest that let-7a-3 overexpression is a common event and is associated with poor clinical outcome in AML.
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