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Find video protocols related to scientific articles indexed in Pubmed.
FGFR1 mediates recombinant thrombomodulin domain-induced angiogenesis.
Cardiovasc. Res.
PUBLISHED: 11-10-2014
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The recombinant epidermal growth factor-like domain plus the serine/threonine-rich domain of thrombomodulin (rTMD23) promotes angiogenesis and accelerates the generation of activated protein C (APC), which facilitates angiogenesis. The aim of this study was to elucidate the molecular mechanisms underlying the angiogenic activity of rTMD23.
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Ophiopogonin D Attenuates Doxorubicin-Induced Autophagic Cell Death by Relieving Mitochondrial Damage in vitro and in vivo.
J. Pharmacol. Exp. Ther.
PUBLISHED: 11-08-2014
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It has been reported that Ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against DOX-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of ROS in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio and up-regulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine (3-MA). In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by anti-oxidative effects through down-regulating the expression of both phosphorylated JNK and ERK. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.
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[Treatment of stage 3b diabetic kidney disease patients with macroalbuminuria by qizhi jiangtang capsule: a multicenter randomized control clinical study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To observe the efficacy and safety of Qizhi Jiangtang Capsule (QJC) in treating stage 3b diabetic kidney disease (DKD) patients with macroalbuminuria.
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[Ophiopogonin D protects cardiomyocytes against doxorubicin-induced injury through suppressing endoplasmic reticulum stress].
Yao Xue Xue Bao
PUBLISHED: 10-18-2014
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This study aimed to examine whether ophiopogonin D (OP-D) is capable of protecting cardiomyocytes against DOX-induced injury and the mechanisms involved. H9c2 cells were cultured. MTT assay was used to evaluate cell viability and toxicity. Mito-tracker as fluorescence probe was used to measure ROS content raised from mitochondria. The mRNA and protein expression of ATF6alpha, GRP78 and CHOP were analyzed using real-time PCR and Western blotting, respectively. The results showed that a significant endoplasmic reticulum stress (ERS) was induced upon exposure of H9c2 cells to DOX as indicated by the increase in the expression of ERS related proteins, which was paralleled with the accumulation of reactive oxygen species (ROS) and decrease in the viability of H9c2 cells. Whereas, DOX-induced ROS accumulation and up-regulation of ERS related proteins were partially abolished by pretreatment with OP-D. Consequently, a DOX-induced ERS was mitigated by application of OP-D. Similarly, DOX-induced decrease in cell viability was partially attenuated by either inhibiting CHOP or pretreatment with N-acetylcysteine (NAC), an antioxidant. Moreover, cardiac ultrastructural abnormalities seen in mouse receiving DOX injections were obviously ameliorated by pretreatment of OP-D. Taken together, the present study proved that OP-D protects cardiomyocytes against DOX-induced injury, at least in part, through reducing ROS accumulation and alleviating ERS.
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[Expression of NKG2A and NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To investigatethe expressions of NKG2A, NKG2C receptors and their ligand HLA-E in decidua of preeclampsia patients.
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A Mechanistic study of Plasma Treatment Effects on Demineralized Dentin Surfaces for Improved Adhesive/Dentin Interface Bonding.
Clin Plasma Med
PUBLISHED: 10-01-2014
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Our previous work has shown that non-thermal plasma treatment of demineralized dentin significantly (p<0.05) improved adhesive/dentin bonding strength for dental composite restoration as compared with the untreated controls. This study is to achieve mechanistic understanding of the plasma treatment effects on dentin surface through investigating the plasma treated dentin surfaces and their interaction with adhesive monomer, 2-Hydroxyethyl methacrylate (HEMA). The plasma treated dentin surfaces from human third molars were evaluated by water contact angle measurements and scanning electron microscopy (SEM). It was found that plasma-treated dentin surface with subsequent HEMA immersion (Plasma/HEMA Treated) had much lower water contact angle compared with only plasma-treated (Plasma Treated) or only HEMA immersed (HEMA Treated) dentin surfaces. With prolong water droplet deposition time, water droplets spread out completely on the Plasma/HEMA Treated dentin surfaces. SEM images of Plasma/HEMA Treated dentin surfaces verified that dentin tubules were opened-up and filled with HEMA monomers. Extracted type I collagen fibrils, which was used as simulation of the exposed dentinal collagen fibrils after acid etching step, were plasma treated and analyzed with Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) spectra. FT-IR spectra of the Plasma/HEMA Treated collage fibrils showed broadened amide I peak at 1660 cm(-1) and amide II at 1550 cm(-1), which indicate secondary structure changes of the collagen fibrils. CD spectra indicated that 67.4% collagen helix structures were denatured after plasma treatment. These experimental results demonstrate that non-thermal argon plasma treatment was very effective in loosing collagen structure and enhancing adhesive monomer penetration, which are beneficial to thicker hybrid layer and longer resin tag formation, and consequently enhance adhesive/dentin interface bonding.
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Spinal cord injury enables aromatic L-amino acid decarboxylase cells to synthesize monoamines.
J. Neurosci.
PUBLISHED: 09-05-2014
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Serotonin (5-HT), an important modulator of both sensory and motor functions in the mammalian spinal cord, originates mainly in the raphe nuclei of the brainstem. However, following complete transection of the spinal cord, small amounts of 5-HT remain detectable below the lesion. It has been suggested, but not proven, that this residual 5-HT is produced by intraspinal 5-HT neurons. Here, we show by immunohistochemical techniques that cells containing the enzyme aromatic l-amino acid decarboxylase (AADC) occur not only near the central canal, as reported by others, but also in the intermediate zone and dorsal horn of the spinal gray matter. We show that, following complete transection of the rat spinal cord at S2 level, AADC cells distal to the lesion acquire the ability to produce 5-HT from its immediate precursor, 5-hydroxytryptophan. Our results indicate that this phenotypic change in spinal AADC cells is initiated by the loss of descending 5-HT projections due to spinal cord injury (SCI). By in vivo and in vitro electrophysiology, we show that 5-HT produced by AADC cells increases the excitability of spinal motoneurons. The phenotypic change in AADC cells appears to result from a loss of inhibition by descending 5-HT neurons and to be mediated by 5-HT1B receptors expressed by AADC cells. These findings indicate that AADC cells are a potential source of 5-HT at spinal levels below an SCI. The production of 5-HT by AADC cells, together with an upregulation of 5-HT2 receptors, offers a partial explanation of hyperreflexia below a chronic SCI.
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Temperature-dependent phase transition and desorption free energy of sodium dodecyl sulfate at the water/vapor interface: approaches from molecular dynamics simulations.
Langmuir
PUBLISHED: 08-22-2014
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Adsorption of surfactants at the water/vapor interface depends upon their chemical potential at the interface, which is generally temperature-dependent. Molecular dynamics simulations have been performed to reveal temperature influences on the microstructure of sodium dodecyl sulfate (SDS) molecule adsorption layer. At room temperature, SDS molecules aggregate at the interface, being in a liquid-expanded phase, whereas they tend to spread out and probably transit to a gaseous phase as the temperature increases to above 318 K. This phase transition has been confirmed by the temperature-dependent changes in two-dimensional array, tilt angles, and immersion depths to the aqueous phase of SDS molecules. The aggregation of SDS molecules accompanies with larger immersion depths, more coordination of Na(+) ions, and less coordination of water. Desorption free energy profiles show that higher desorption free energy appears for SDS molecules at the aggregate state at low temperatures, but no energy barrier is observed. The shapes of desorption free energy profiles depend upon the distribution of SDS at the interface, which, in turn, is related to the phase state of SDS. Our study sheds light on the development of adsorption thermodynamics and kinetics theories.
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Arsenic trioxide and resveratrol show synergistic anti-leukemia activity and neutralized cardiotoxicity.
PLoS ONE
PUBLISHED: 08-21-2014
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Cardiotoxicity is an aggravating side effect of many clinical antineoplastic agents such as arsenic trioxide (As2O3), which is the first-line treatment for acute promyelocytic leukemia (APL). Clinically, drug combination strategies are widely applied for complex disease management. Here, an optimized, cardiac-friendly therapeutic strategy for APL was investigated using a combination of As2O3 and genistein or resveratrol. Potential combinations were explored with respect to their effects on mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity, autophagy, and apoptosis in both NB4 cells and neonatal rat left ventricular myocytes. All experiments consistently suggested that 5 µM resveratrol remarkably alleviates As2O3-induced cardiotoxicity. To achieve an equivalent effect, a 10-fold dosage of genistein was required, thus highlighting the dose advantage of resveratrol, as poor bioavailability is a common concern for its clinical application. Co-administration of resveratrol substantially amplified the anticancer effect of As2O3 in NB4 cells. Furthermore, resveratrol exacerbated oxidative stress, mitochondrial damage, and apoptosis, thereby reflecting its full range of synergism with As2O3. Addition of 5 µM resveratrol to the single drug formula of As2O3 also further increased the expression of LC3, a marker of cellular autophagy activity, indicating an involvement of autophagy-mediated tumor cell death in the synergistic action. Our results suggest a possible application of an As2O3 and resveratrol combination to treat APL in order to achieve superior therapeutics effects and prevent cardiotoxicity.
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Effect of CYP2C9 genetic polymorphism on the metabolism of flurbiprofen in vitro.
Drug Dev Ind Pharm
PUBLISHED: 08-21-2014
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Abstract CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, and 57 cytochrome P450 2C9 alleles have been previously reported. To examine the enzymatic activity of the CYP2C9 alleles, kinetic parameters for 4'-hydroxyflurbiprofen were determined using recombinant human P450s CYP2C9 microsomes from insect cells Sf21 carrying wild-type CYP2C9*1 and other variants. The results showed that the enzyme activity of most of the variants decreased comparing with the wild type as the previous studies reported, while the enzyme activity of some of them increased, which were not in accordance with the previous researches. Of the 36 tested CYP2C9 allelic isoforms, two variants (CYP2C9*53 and CYP2C9*56) showed a higher intrinsic clearance value than the wild-type protein, especially for CYP2C9*56, exhibited much higher intrinsic clearance (197.3%) relative to wild-type CYP2C9*1, while the remaining 33 CYP2C9 allelic isoforms exhibited significantly decreased clearance values (from 0.6 to 83.8%) compared to CYP2C9*1. This study provided the most comprehensive data on the enzymatic activities of all reported CYP2C9 variants in the Chinese population with regard to the commonly used non-steroidal anti-inflammatory drug, flurbiprofen (FP). The results indicated that most of the tested rare alleles decreased the catalytic activity of CYP2C9 variants toward FP hydroxylation in vitro. This is the first report of all these rare alleles for FP metabolism providing fundamental data for further clinical studies on CYP2C9 alleles for FP metabolism in vivo.
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Comparison of root transcriptomes and expressions of genes involved in main medicinal secondary metabolites from Bupleurum chinense and Bupleurum scorzonerifolium, the two Chinese official Radix bupleuri source species.
Physiol Plant
PUBLISHED: 08-13-2014
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Radix bupleuri, roots of Bupleurum species, is a widely used traditional Chinese medicine. Here, we compared the root transcriptomes of both Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. A total of 313?483 and 342?263 high quality expressed sequence tags were obtained, respectively. In addition, 17?117 (59.2%) and 19?416 (62.8%) unigenes for B. chinense and B. scorzonerifolium had homologous genes in the opposite dataset. For B. chinense, Kyoto Encyclopedia of Genes and Genomes database (KEGG) annotation identified carbohydrate metabolism, energy metabolism and amino acid metabolism as the three highest groups in the metabolism category. For B. scorzonerifolium, the lipid metabolism group had the most unigenes. Genes that may participate in the biosynthesis of terpenoid, triterpenoid, sterol, lignan and flavonoids were identified according to their annotations. (Tri)terpenoid-related genes were predominantly found in B. chinense. The expressions of certain genes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in the roots of the two species. A total of 558 putative transcription factors (TFs) and 137 transcriptional regulators (TRs) among 1364 TFs and 327 TRs, and 610 TFs and 129 TRs among 1600 TFs and 323 TRs were specific for B. chinense and B. scorzonerifolium, respectively. Our transcriptome comparison reflects the different types and proportions of metabolites synthesized by the two species. The data, especially, those genes involved in the biosynthesis of particular types of metabolites, will provide the basis for further investigations of the secondary metabolite repertoire of the two Bupleurum species, as well as other species from the genus of Bupleurum.
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Plasma deactivation of oral bacteria seeded on hydroxyapatite disks as tooth enamel analogue.
Am J Dent
PUBLISHED: 07-09-2014
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To study the plasma treatment effects on deactivation of oral bacteria seeded on a tooth enamel analogue.
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Cotton-based Diagnostic Devices.
Sci Rep
PUBLISHED: 06-30-2014
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A good diagnostic procedure avoids wasting medical resources, is easy to use, resists contamination, and provides accurate information quickly to allow for rapid follow-up therapies. We developed a novel diagnostic procedure using a "cotton-based diagnostic device" capable of real-time detection, i.e., in vitro diagnostics (IVD), which avoids reagent contamination problems common to existing biomedical devices and achieves the abovementioned goals of economy, efficiency, ease of use, and speed. Our research reinforces the advantages of an easy-to-use, highly accurate diagnostic device created from an inexpensive and readily available U.S. FDA-approved material (i.e., cotton as flow channel and chromatography paper as reaction zone) that adopts a standard calibration curve method in a buffer system (i.e., nitrite, BSA, urobilinogen and uric acid assays) to accurately obtain semi-quantitative information and limit the cross-contamination common to multiple-use tools. Our system, which specifically targets urinalysis diagnostics and employs a multiple biomarker approach, requires no electricity, no professional training, and is exceptionally portable for use in remote or home settings. This could be particularly useful in less industrialized areas.
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Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.
Microb. Cell Fact.
PUBLISHED: 06-29-2014
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Background Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes.ResultsBy the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L).ConclusionsWe have identified and characterized a TetR family transcriptional regulator, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual regulatory mechanism of erythromycin biosynthesis, and provides a novel strategy towards Er-A overproduction by engineering transcriptional regulators of S. erythraea.
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Insights into targeting NEMO for pharmacological regulation.
Curr Drug Targets
PUBLISHED: 06-12-2014
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NF-?B essential modulator (NEMO), the non-catalytic regulatory subunit of the I?B kinase (IKK) complex, is essential for the canonical NF-?B activation pathway. It has been identified as a molecular platform for assembling the IKK complex and recruiting upstream IKK activators. However, the exact mechanism for regulating IKK activity has still remained elusive. This review describes structural and functional characteristics of NEMO protein, covers the feasible polyubiquitin-mediated NEMO-dependent IKK complex activation mechanism, and briefly summarizes some proteins that bind to NEMO for enhancing or suppressing IKK complex activity. Furthermore, it also discusses several bioactive compounds that disrupt the protein-protein interactions (PPI) involving NEMO, as these PPI may act as alternative routes to develop novel pharmacological agents for inflammation and cancer therapy.
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Investigation of the intermolecular recognition mechanism between the E3 ubiquitin ligase Keap1 and substrate based on multiple substrates analysis.
J. Comput. Aided Mol. Des.
PUBLISHED: 06-08-2014
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E3 ubiquitin ligases are attractive drug targets due to their specificity to the ubiquitin machinery. However, the development of E3 ligase inhibitors has proven challenging for the fact that they must disrupt protein-protein interactions (PPIs). The E3 ligase involved in interactome provide new hope for the discovery of the E3 ligase inhibitors. These currently known natural binding partners of the E3 ligase can benefit the discovery of other unknown substrates and also the E3 ligase inhibitors. Herein, we present a novel strategy that using multiple substrates to elucidate the molecular recognition mechanism of E3 ubiquitin ligase. Molecular dynamics simulation, molecular mechanics-generalized born surface area (MM-GBSA) binding energy calculation and energy decomposition scheme were incorporated to evaluate the quantitative contributions of sub-pocket and per-residue to binding. In this case, Kelch-like ECH-associated protein-1 (Keap1), a substrate adaptor component of the Cullin-RING ubiquitin ligases complex, is applied for the investigation of how it recognize its substrates, especially Nrf2, a master regulator of the antioxidant response. By analyzing multiple substrates binding determinants, we found that both the polar sub-pockets (P1 and P2) and the nonpolar sub-pockets (P4 and P5) of Keap1 can make remarkable contributions to intermolecular interactions. This finding stresses the requirement for substrates to interact with the polar and nonpolar sub-pockets simultaneously. The results discussed in this paper not only show the binding determinants of the Keap1 substrates but also provide valuable implications for both Keap1 substrate discovery and PPI inhibitor design.
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Classification of Subpopulations of Cells Within Human Primary Brain Tumors by Single Cell Gene Expression Profiling.
Neurochem. Res.
PUBLISHED: 05-27-2014
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Brain tumors are heterogeneous with respect to genetic and histological properties of cells within the tumor tissue. To study subpopulations of cells, we developed a protocol for obtaining viable single cells from freshly isolated human brain tissue for single cell gene expression profiling. We evaluated this technique for characterization of cell populations within brain tumor and tumor penumbra. Fresh tumor tissue was obtained from one astrocytoma grade IV and one oligodendroglioma grade III tumor as well as the tumor penumbra of the latter tumor. The tissue was dissociated into individual cells and the expression of 36 genes was assessed by reverse transcription quantitative PCR followed by data analysis. We show that tumor cells from both the astrocytoma grade IV and oligodendroglioma grade III tumor constituted cell subpopulations defined by their gene expression profiles. Some cells from the oligodendroglioma grade III tumor proper shared molecular characteristics with the cells from the penumbra of the same tumor suggesting that a subpopulation of cells within the oligodendroglioma grade III tumor consisted of normal brain cells. We conclude that subpopulations of tumor cells can be identified by using single cell gene expression profiling.
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Occurrence and fate of triclosan and triclocarban in a subtropical river and its estuary.
Mar. Pollut. Bull.
PUBLISHED: 05-25-2014
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The occurrence of triclosan (TCS) and triclocarban (TCC) in a subtropical river (Jiulong River) and its estuary was investigated for two years. TCS and TCC were ubiquitously detected in the Jiulong River and its estuary. The levels of TCS and TCC ranged from less than the method detection limit to 64ng/L and from 0.05 to 14.1ng/L in the river, respectively. The levels of TCS and TCC in the estuary ranged from 2.56 to 27.25ng/L and 0.38 to 5.76ng/L, respectively. Temporal and spatial variations of TCS and TCC in the Jiulong River and its estuary were observed during the investigation. The weather conditions did not show significant correlations with TCS and TCC, whereas several water quality parameters showed high correlations with TCS and TCC. The microcosm studies showed that both direct photolysis and biodegradation contributed to TCS removal, whereas indirect photolysis was important for TCC removal in the surface water.
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COQ2 p.V393A variant, rs148156462, is not associated with Parkinson's disease in a Taiwanese population.
Neurobiol. Aging
PUBLISHED: 05-23-2014
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A recent collaborative study that combined linkage analysis with whole-genome sequencing of family members of multiplex families with multiple system atrophy (MSA) has identified COQ2 gene as a causative gene for MSA. The common variant, c.T1178C (p.V393A, rs148156462), in the COQ2 gene was found to be associated with an increased risk of sporadic MSA. There is overlapping clinical characteristics between MSA and Parkinson's disease (PD), and the pathologic hallmark of both diseases is ?-synucleinopathy. We therefore aim to analyze the COQ2 p.V393A variant in a large Taiwanese cohort with PD patients. We genotyped COQ2 p.V393A variant in a total of 1005 participants, comprising 500 patients with PD and 505 age/gender-matched control subjects. The frequency of TC/CC genotype was comparable between PD patients and control subjects (odds ratio: 0.81, 95% confidence interval: 0.42-1.56, p = 0.53). COQ2 p.V393A variant is not a genetic risk factor for PD, suggesting its specificity in disease susceptibility to MSA.
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IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma.
J. Invest. Dermatol.
PUBLISHED: 05-19-2014
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Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) has been reported to be a novel marker of melanoma progression. However, the mechanisms by which it impacts melanoma are incompletely understood. In this study, we investigate the clinical significance of IMP-3 in melanoma progression and also its underlying mechanisms. We found that IMP-3 expression was much higher in advanced stage/metastatic melanomas and that it was associated with a poor prognosis (P=.001). Univariate analysis showed IMP-3 expression was associated with stage III/IV melanomas (odds ratio=5.40, P=.031) and the acral lentiginous subtype (odds ratio=3.93, P=.0034). MeWo cells with overexpression of IMP-3 showed enhanced proliferation and migration and significantly increased tumorigenesis and metastatic ability in nude mice. We further demonstrated that IMP-3 could bind and enhance the stability of the mRNA of HMGA2. It was also confirmed that IMP-3 played an important role in melanoma invasion and metastasis through regulating HMGA2 mRNA expression. IMP-3 expression was positively correlated with HMGA2 expression in melanoma cells and also in melanoma tissues. Our results show that IMP-3 expression is a strong prognostic factor for melanoma, especially the acral lentiginous melanoma.Journal of Investigative Dermatology accepted article preview online, 07 November 2014. doi:10.1038/jid.2014.480.
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[Odor emission rate of municipal solid waste from landfill working area].
Huan Jing Ke Xue
PUBLISHED: 05-13-2014
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Emission rates of volatile organic compounds (VOCs), H2S and odor unit from the surface of a municipal solid waste (MSW) landfill working area were measured with a wind tunnel sampler. The results show that the emission rate of odor from the non-point source of landfill is the function of environmental temperature and surface sweeping velocity. The emission rate measured in the high temperature season can be 6 times higher of that in the low temperature season. Within the experimental range of 0.6-4 m x s(-1) wind sweeping velocity, the emission rate shows a linear relationship with wind sweeping velocity. In summer, the emission rates of VOCs (measured by PID as isobutylene), H2S and odor unit are 385-680 microg x (m(2) x s)(-1), 4-7 microg x (m(2) x s)(-1), and 46.5-136 OU x (m(2) x s)(-1) respectively. The continuous sweeping experiment shows that the emission rate measured with clean air sweeping is the maximum possible emission rate, which needs to be adjusted when it is used to estimate the odor concentration of more than 10 min sample time or an area emission load.
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Relation of diabetes to coronary artery ectasia: A meta-analysis study.
Anadolu Kardiyol Derg
PUBLISHED: 05-02-2014
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Previous studies have shown a significant negative association between diabetes and abdominal aortic aneurysm. However, the relation of diabetes to coronary artery ectasia (CAE) has not well established. The aim of the current study was to conduct a systemic review for evaluating the relationship between diabetes and CAE.
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Photobody Localization of Phytochrome B Is Tightly Correlated with Prolonged and Light-Dependent Inhibition of Hypocotyl Elongation in the Dark.
Plant Physiol.
PUBLISHED: 04-25-2014
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Photobody localization of Arabidopsis (Arabidopsis thaliana) phytochrome B (phyB) fused to green fluorescent protein (PBG) correlates closely with the photoinhibition of hypocotyl elongation. However, the amino-terminal half of phyB fused to green fluorescent protein (NGB) is hypersensitive to light despite its inability to localize to photobodies. Therefore, the significance of photobodies in regulating hypocotyl growth remains debatable. Accumulating evidence indicates that under diurnal conditions, photoactivated phyB persists into darkness to inhibit hypocotyl elongation. Here, we examine whether photobodies are involved in inhibiting hypocotyl growth in darkness by comparing the PBG and NGB lines after the red light-to-dark transition. Surprisingly, after the transition from 10 ?mol m(-2) s(-1) red light to darkness, PBG inhibits hypocotyl elongation three times longer than NGB. The disassembly of photobodies in PBG hypocotyl nuclei correlates tightly with the accumulation of the growth-promoting transcription factor PHYTOCHROME-INTERACTING FACTOR3 (PIF3). Destabilizing photobodies by either decreasing the light intensity or adding monochromatic far-red light treatment before the light-to-dark transition leads to faster PIF3 accumulation and a dramatic reduction in the capacity for hypocotyl growth inhibition in PBG. In contrast, NGB is defective in PIF3 degradation, and its hypocotyl growth in the dark is nearly unresponsive to changes in light conditions. Together, our results support the model that photobodies are required for the prolonged, light-dependent inhibition of hypocotyl elongation in the dark by repressing PIF3 accumulation and by stabilizing the far-red light-absorbing form of phyB. Our study suggests that photobody localization patterns of phyB could serve as instructive cues that control light-dependent photomorphogenetic responses in the dark.
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Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages.
J. Neurosci.
PUBLISHED: 04-25-2014
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Cognitive decline is associated with gene expression changes in the brain, but the transcriptional mechanisms underlying memory impairments in cognitive disorders, such as Alzheimer's disease (AD), are largely unknown. Here, we aimed to elucidate relevant mechanisms responsible for transcriptional changes underlying early memory loss in AD by examining pathological, behavioral, and transcriptomic changes in control and mutant ?-amyloid precursor protein (APPSw,Ind) transgenic mice during aging. Genome-wide transcriptome analysis using mouse microarrays revealed deregulation of a gene network related with neurotransmission, synaptic plasticity, and learning/memory in the hippocampus of APPSw,Ind mice after spatial memory training. Specifically, APPSw,Ind mice show changes on a cAMP-responsive element binding protein (CREB)-regulated transcriptional program dependent on the CREB-regulated transcription coactivator-1 (Crtc1). Interestingly, synaptic activity and spatial memory induces Crtc1 dephosphorylation (Ser151), nuclear translocation, and Crtc1-dependent transcription in the hippocampus, and these events are impaired in APPSw,Ind mice at early pathological and cognitive decline stages. CRTC1-dependent genes and CRTC1 levels are reduced in human hippocampus at intermediate Braak III/IV pathological stages. Importantly, adeno-associated viral-mediated Crtc1 overexpression in the hippocampus efficiently reverses A?-induced spatial learning and memory deficits by restoring a specific subset of Crtc1 target genes. Our results reveal a critical role of Crtc1-dependent transcription on spatial memory formation and provide the first evidence that targeting brain transcriptome reverses memory loss in AD.
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Fabrication and characterization for the nanoconjugates of pyridyldithio-functionalized multiwalled carbon nanotubes and cytochrome c in Langmuir-Blodgett films.
J Nanosci Nanotechnol
PUBLISHED: 04-25-2014
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Monolayers and Langmuir-Blodgett (LB) films of pyridyldithio-functionalized multiwalled carbon nanotubes (pythio-MWNTs) conjugated with cytochrome c were investigated. Quartz crystal microbalance measurements revealed that monolayers of pythio-MWNTs could be deposited on the substrate surface with a surface density of about 270 ng/cm2. The as-prepared LB films of pythio-MWNTs could act as a support to immobilize cytochrome c with the surface density of about 5.2 microg/cm2. Composition, structure and morphology of the films were characterized by using absorption and X-ray photoelectron spectra as well as atomic force microscope. A reversible redox process for the immobilized cytochrome c was revealed with the cathodic and anionic potentials at about -0.55 and -0.3 V versus Ag/AgCl, respectively.
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Tunable optical and magneto-optical properties of ferrofluid in the terahertz regime.
Opt Express
PUBLISHED: 03-26-2014
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The dielectric property and magneto-optical effects of ferrofluids have been investigated in the terahertz (THz) regime by using THz time-domain spectroscopy. The experiment results show that the refractive index and absorption coefficient of ferrofluid for THz waves rise up with the increase of nanoparticle concentration in the ferrofluid. Moreover, two different THz magneto-optical effects have been found with different external magnetic fields, of which mechanisms have been theoretically explained well by microscopic structure induced refractive index change in the magnetization process and the transverse magneto-optical effect after the saturation magnetization, respectively. This work suggests that ferrofluid is a promising magneto-optical material in the THz regime which has widely potential applications in THz functional devices for THz sensing, modulation, phase retardation, and polarization control.
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Telomere length in peripheral blood leukocytes and lung cancer risk: a large case-control study in Caucasians.
Cancer Res.
PUBLISHED: 03-11-2014
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Telomere dysfunction is a crucial event in malignant transformation and tumorigenesis. Telomere length in peripheral blood leukocytes has been associated with lung cancer risk, but the relationship has remained controversial. In this study, we investigated whether the association might be confounded by study of different histological subtypes of lung cancer. We measured relative telomere lengths in patients in a large case-control study of lung cancer and performed stratified analyses according to the two major histologic subtypes [adenocarcinoma and squamous cell carcinoma (SCC)]. Notably, patients with adenocarcinoma had longer telomeres than controls, whereas patients with SCC had shorter telomeres compared with controls. Long telomeres were associated with increased risk of adenocarcinoma, with the highest risk associated with female sex, younger age (<60 years), and lighter smoking (<30 pack-years). In contrast, long telomeres were protective against SCC, particularly in male patients. Our results extend the concept that telomere length affects risk of lung cancer in a manner that differs with histologic subtype.
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Caregiver Burden, Health Status, and Learned Resourcefulness of Older Caregivers.
West J Nurs Res
PUBLISHED: 03-11-2014
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As caregivers undertake caregiving responsibilities over a long period of time, the burdens placed on them could lead to undue stress and affect their health. This correlation study examined the current situations and relationships among caregiver burden, health status, and learned resourcefulness (LR) of older caregivers who care for disabled older adults, and predicted the important factors that affect their caregiver burden. In all, 108 older caregivers were recruited from home care services of two hospitals. Structured questionnaire interviews were applied to collect data: the Caregiver Burden Scale, the SF-36 Health Survey (SF-36), and the Rosenbaum's Self-Control Schedule. Results indicated that the caregiver burden was negatively correlated with physical health, mental health, and LR. Physical and mental health were positively correlated with LR. The predictors of caregiver burden included LR, health status, economic status, and activities of daily living, which accounted for 58.60% of the total caregiver burden variance.
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Structural characteristics of the nonallosteric human cytosolic malic enzyme.
Biochim. Biophys. Acta
PUBLISHED: 03-07-2014
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Human cytosolic NADP(+)-dependent malic enzyme (c-NADP-ME) is neither a cooperative nor an allosteric enzyme, whereas mitochondrial NAD(P)(+)-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by fumarate. This study examines the molecular basis for the different allosteric properties and quaternary structural stability of m-NAD(P)-ME and c-NADP-ME. Multiple residues corresponding to the fumarate-binding site were mutated in human c-NADP-ME to correspond to those found in human m-NAD(P)-ME. Additionally, the crystal structure of the apo (ligand-free) human c-NADP-ME conformation was determined. Kinetic studies indicated no significant difference between the wild-type and mutant enzymes in Km,NADP, Km,malate, and kcat. A chimeric enzyme, [51-105]_c-NADP-ME, was designed to include the putative fumarate-binding site of m-NAD(P)-ME at the dimer interface of c-NADP-ME; however, this chimera remained nonallosteric. In addition to fumarate activation, the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME is quite different; c-NADP-ME is a stable tetramer, whereas m-NAD(P)-ME exists in equilibrium between a dimer and a tetramer. The quaternary structures for the S57K/N59E/E73K/S102D and S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G mutants of c-NADP-ME are tetrameric, whereas the K57S/E59N/K73E/D102S m-NAD(P)-ME quadruple mutant is primarily monomeric with some dimer formation. These results strongly suggest that the structural features near the fumarate-binding site and the dimer interface are highly related to the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME. In this study, we attempt to delineate the structural features governing the fumarate-induced allosteric activation of malic enzyme.
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Kinetically-controlled template-free synthesis of hollow silica micro-/nanostructures with unusual morphologies.
Nanotechnology
PUBLISHED: 03-05-2014
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We report a kinetically-controlled template-free room-temperature production of hollow silica materials with various novel morphologies, including tubes, crutches, ribbons, bundles and bells. The obtained products, which grew in a well-controlled manner, were monodispersed in shape and size. The role of ammonia, sodium citrate, polyvinylpyrrolidone, chloroauric acid and NaCl in shape control is discussed in detail. The oriented growth of these micro-/nanostructures directed by reverse micelles followed a solution-solution-solid (SSS) mechanism, similar to the classic vapor-liquid-solid mechanism. The evolution processes of silica rods, tubes, crutches, bundles and bells were recorded using transmission electron microscopy to prove the SSS mechanism.
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TDDFT study of UV-vis spectra of permethrin, cypermethrin and their beta-cyclodextrin inclusion complexes: a comparison of dispersion correction DFT (DFT-D3) and DFT.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 02-26-2014
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A comparative study of DFT and DFT-D3 has been carried out on the UV-vis absorption of permethrin, cypermethrin and their ?-cyclodextrin inclusion complexes. The TDDFT method with PCM (or COSMO) model was adopted and B3LYP, BLYP and BLYP-D3 functionals were selected. Comparing the simulated spectra with experimental one, we can notice that pure BLYP functional can better reproduce the UV-vis spectra than hybrid B3LYP, but empirical dispersion corrections BLYP-D3 has better performance than BLYP. BLYP-D3 calculations reveal that the main absorption bands of permethrin and cypermethrin arise from the ???(*) transition, after encapsulated by ?-CD to form inclusion complexes, the host-guest intermolecular charge transfer (ICT) makes the main absorption bands to be changed significantly in wavelength and intensity.
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Clinical effects of soluble interleukin-6 receptor detection on autoimmune rheumatic disease patients.
Pak J Med Sci
PUBLISHED: 02-24-2014
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Objective : This study aims to explore the effects of soluble interleukin-6 receptor (IL-6R) on the clinical diagnosis and treatment of autoimmune rheumatic disease (ARD) patients.
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Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis.
J. Med. Chem.
PUBLISHED: 02-21-2014
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Keap1 is known to mediate the ubiquitination of Nrf2, a master regulator of the antioxidant response. Directly interrupting the Keap1-Nrf2 interaction has been emerged as a promising strategy to develop novel class of antioxidant, antiinflammatory, and anticancer agents. On the basis of the molecular binding determinants analysis of Keap1, we successfully designed and characterized the most potent protein-protein interaction (PPI) inhibitor of Keap1-Nrf2, compound 2, with K(D) value of 3.59 nM binding to Keap1 for the first time to single-digit nanomolar. Compound 2 can effectively disrupt the Nrf2-Keap1 interaction with an EC50 of 28.6 nM in the fluorescence polarization assay. It can also activate the Nrf2 transcription activity in the cell-based ARE-luciferase reporter assay in a dose-dependent manner. The qRT-PCR results of Nrf2 transcription targets gave the consistent results. These results confirm direct and highly efficient interruption of the Keap1-Nrf2 PPI can be fully achieved by small molecules.
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Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin-induced murine model of asthma.
Allergy Asthma Immunol Res
PUBLISHED: 02-20-2014
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Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.
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Prostaglandin E2 accelerates invasion by upregulating Snail in hepatocellular carcinoma cells.
Tumour Biol.
PUBLISHED: 02-14-2014
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Our previous studies showed that prostaglandin E2 (PGE2) promotes hepatoma cell growth and migration, as well as invasion; however, the precise mechanism remains elusive. Snail and p65 protein levels were detected in human samples with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC) staining. HCC cell lines (Huh-7 and Hep3B) were used for in vitro experiments. PGE2/Akt/NF-?B pathway was investigated in Huh-7 and Hep3B cells after treatment with PGE2, EP4 receptor (EP4R) agonist, Akt inhibitor, and NF-?B inhibitor, respectively, by real-time reverse transcription (RT)-PCR, Western blotting, and immunofluorescence (IF) staining. In vitro cell invasion assay was performed to evaluate the effect of PGE2 on tumor invasiveness. Knockdown of EP4R was carried out in Huh-7 cells through plasmid-based small interfering RNA (siRNA) approach to confirm the regulation of PGE2 on Snail by EP4R. Dual luciferase reporter assay was performed to assess Snail promoter activity in Huh-7 cell after treatment with EP4R agonist. We found that the protein levels of Snail were higher in HCC tissues than those in control and that PGE2 and EP4R agonist treatment significantly increased Snail expression in Huh-7 and Hep3B cells. EP4R agonist also profoundly promoted invasiveness of Huh-7 cells. Knockdown of the EP4R by siRNA completely blocked the PGE2-induced upregulation of Snail expression and reduced invasiveness of Huh-7 cells. We failed to find that EP4R-induced upregulation of Snail was reversed by inhibition of cAMP response element-binding protein (CREB), a canonical downstream target of EP4R. Alternatively, EP4R agonist treatment significantly increased the levels of phosphorylated EGFR and Akt both in Huh-7 and Hep3B cells. AG1478, an EGFR inhibitor, blocked the phosphorylation of Akt. The levels of phosphorylated I?B increased in Huh-7 cells after treatment with EP4R agonist for 30 min. The levels of phosphorylated p65 started to increase in Huh-7 cells treated with EP4R agonist for 4 h, and p65 translocated into the nucleus. In EP4R-agonist-treated Hep3B, the levels of phosphorylated p65 were also increased compared to the control group. The phosphorylation levels of p65 were significantly decreased in Huh-7 and Hep3B cells after treatment with the Akt signaling inhibitor LY294002 and EP4R agonist for 24 h. Treatment with the NF-?B inhibitor pyrrolidine dithiocarbamate (PDTC) at 10 ?M for 24 h blocked EP4R-agonist-induced Snail upregulation in Huh-7 and Hep3B cells. Furthermore, we obtained human Snail promoter sequence from TRED-Promoter Database and identified a putative binding site of NF-?B in the sequence through TFSEARCH analysis. Subsequently, we treated Huh-7 cells with EP4R agonist or EP4R agonist and PDTC (NF-?B antagonist) and found significantly increased Snail promoter activity after EP4R agonist treatment for 12 h. The increased Snail promoter activity could be partially abolished by additional PDTC treatment. In addition, p65 protein levels were found increased together with Snail in HCC tissues compared to normal liver tissues. In conclusion, PGE2 activates Akt/NF-?B signaling and then upregulates Snail via the EP4R/EGFR to promote migration and invasion in hepatoma cells. These findings may help future evaluation of novel chemo-preventive strategies for HCC.
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Prostaglandin E? receptor EP2 mediates Snail expression in hepatocellular carcinoma cells.
Oncol. Rep.
PUBLISHED: 02-12-2014
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Prostaglandin E2 (PGE2) has been shown to influence cell invasion and metastasis in several types of cancer, including hepatocellular carcinoma (HCC). however, the molecular mechanisms underlying it remain to be further elucidated. Snail, as one of key inducers of epithelial-mesenchymal transition (EMT), plays pivotal roles in HCC invasion and metastasis. The present study was designed to evaluate the possible signaling pathways through which PGE2 regulates Snail protein expression in HCC cell lines. PGE2 markedly enhanced Huh-7 cell invasion and migration ability by upregulating the expression level of Snail protein, and EP2 receptor played an important role in this process. Src, EGFR, Akt and mTOR were all activated and involved in the regulation of snail protein expression. Our findings suggest that PGE2 could upregulate the expression level of Snail protein through the EP2/Src/EGFR/Akt/mTOR pathway in Huh-7 cells, which promotes HCC cell invasion and migration.
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Clinical features of coronary artery ectasia in the elderly.
J Geriatr Cardiol
PUBLISHED: 02-08-2014
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To investigate the incidence, imaging and clinical characteristics in elderly patients with coronary artery ectasia (CAE).
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Radiosensitization effect of nedaplatin on nasopharyngeal carcinoma cells in different status of Epstein-Barr virus infection.
Biomed Res Int
PUBLISHED: 02-04-2014
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This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 ?g/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 ?g/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.
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Isolation, purification, and cultivation of primary retinal microvascular pericytes: a novel model using rats.
Microcirculation
PUBLISHED: 01-30-2014
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To isolate, purify, and cultivate primary retinal microvascular pericytes (RMPs) from rats to facilitate the study of their properties in vitro.
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Heme oxygenase-1 is involved in sodium hydrosulfide-induced lateral root formation in tomato seedlings.
Plant Cell Rep.
PUBLISHED: 01-28-2014
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By using pharmacological and molecular approaches, we discovered the involvement of HO-1 in NaHS-induced lateral root formation in tomato seedlings. Heme oxygenase-1 (HO-1) and hydrogen sulfide (H2S) regulate various responses to abiotic stress and root development, but their involvement in the simultaneous regulation of plant lateral root (LR) formation is poorly understood. In this report, we observed that the exogenously applied H2S donor sodium hydrosulfide (NaHS) and the HO-1 inducer hemin induce LR formation in tomato seedlings by triggering intracellular signaling events involving the induction of tomato HO-1 (SlHO-1), and the modulation of cell cycle regulatory genes, including the up-regulation of SlCDKA;1 and SlCYCA2;1, and simultaneous down-regulation of SlKRP2. The response of NaHS in the induction of LR formation was impaired by the potent inhibition of HO-1, which was further blocked when 50 % saturation of carbon monoxide (CO) aqueous solution, one of the catalytic by-products of HO-1, was added. Further molecular evidence revealed that the NaHS-modulated gene expression of cell cycle regulatory genes was sensitive to the inhibition of HO-1 and reversed by cotreatment with CO. The impairment of LR density and length as well as lateral root primordia number, the decreased tomato HO-1 gene expression and HO activity caused by an H2S scavenger hypotaurine were partially rescued by the addition of NaHS, hemin and CO (in particular). Together, these results revealed that at least in our experimental conditions, HO-1 might be involved in NaHS-induced tomato LR formation. Additionally, the use of NaHS and hemin compounds in crop root organogenesis should be explored.
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A multivariate approach to the integration of multi-omics datasets.
BMC Bioinformatics
PUBLISHED: 01-22-2014
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To leverage the potential of multi-omics studies, exploratory data analysis methods that provide systematic integration and comparison of multiple layers of omics information are required. We describe multiple co-inertia analysis (MCIA), an exploratory data analysis method that identifies co-relationships between multiple high dimensional datasets. Based on a covariance optimization criterion, MCIA simultaneously projects several datasets into the same dimensional space, transforming diverse sets of features onto the same scale, to extract the most variant from each dataset and facilitate biological interpretation and pathway analysis.
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A wheat SIMILAR TO RCD-ONE gene enhances seedling growth and abiotic stress resistance by modulating redox homeostasis and maintaining genomic integrity.
Plant Cell
PUBLISHED: 01-17-2014
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Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability.
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Corrosion resistance improvement for 316L stainless steel coronary artery stents by trimethylsilane plasma nanocoatings.
J. Biomed. Mater. Res. Part B Appl. Biomater.
PUBLISHED: 01-15-2014
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To improve their corrosion resistance and thus long-term biocompatibility, 316L stainless steel coronary artery stents were coated with trimethylsilane (TMS) plasma coatings of 20-25 nm in thickness. Both direct current (DC) and radio-frequency (RF) glow discharges were utilized for TMS plasma coatings and additional NH?/O? plasma treatment to tailor the surface properties. X-ray photoelectron spectroscopy (XPS) was used to characterize the coating surface chemistry. It was found that both DC and RF TMS plasma coatings had Si- and C-rich composition, and the O- and N-contents on the surfaces were substantially increased after NH?/O? plasma treatment. Surface contact angle measurements showed that DC TMS plasma nanocoating with NH?/O? plasma treatment generated very hydrophilic surface. The corrosion resistance of TMS plasma coated stents was evaluated through potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The potentiodynamic polarization demonstrated that the TMS plasma coated stents imparted higher corrosion potential and pitting potential, as well as lower corrosion current densities as compared with uncoated controls. The surface morphology of stents before and after potentiodynamic polarization testing was analyzed with scanning electron microscopy, which indicated less corrosion on coated stents than uncoated controls. It was also noted that, from EIS data, the hydrophobic TMS plasma nanocoatings showed stable impedance modulus at 0.1 Hz after 21 day immersion in an electrolyte solution. These results suggest improved corrosion resistance of the 316L stainless steel stents by TMS plasma nanocoatings and great promise in reducing and blocking metallic ions releasing into the bloodstream.
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Hydrogen-rich water alleviates aluminum-induced inhibition of root elongation in alfalfa via decreasing nitric oxide production.
J. Hazard. Mater.
PUBLISHED: 01-14-2014
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One of the earliest and distinct symptoms of aluminum (Al) toxicity is the inhibition of root elongation. Although hydrogen gas (H2) is recently described as an important bio-regulator in plants, whether and how H2 regulates Al-induced inhibition of root elongation is largely unknown. To address these gaps, hydrogen-rich water (HRW) was used to investigate a physiological role of H2 and its possible molecular mechanism. Individual or simultaneous (in particular) exposure of alfalfa seedlings to Al, or a fresh but not old nitric oxide (NO)-releasing compound sodium nitroprusside (SNP), not only increased NO production, but also led to a significant inhibition of root elongation. Above responses were differentially alleviated by pretreatment with 50% saturation of HRW. The addition of HRW also alleviated the appearance of Al toxicity symptoms, including the improvement of seedling growth and less accumulation of Al. Subsequent results revealed that the removal of NO by the NO scavenger, similar to HRW, could decrease NO production and alleviate Al- or SNP-induced inhibition of root growth. Thus, we proposed that HRW alleviated Al-induced inhibition of alfalfa root elongation by decreasing NO production. Such findings may be applicable to enhance crop yield and improve stress tolerance.
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Light-regulated gene repositioning in Arabidopsis.
Nat Commun
PUBLISHED: 01-07-2014
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Plant genomes are extremely sensitive to, and can be developmentally reprogrammed by environmental light cues. Here using rolling-circle amplification of gene-specific circularizable oligonucleotides coupled with fluorescence in situ hybridization, we demonstrate that light triggers a rapid repositioning of the Arabidopsis light-inducible chlorophyll a/b-binding proteins (CAB) locus from the nuclear interior to the nuclear periphery during its transcriptional activation. CAB repositioning is mediated by the red/far-red photoreceptors phytochromes (PHYs) and is inhibited by repressors of PHY signalling, including COP1, DET1 and PIFs. CAB repositioning appears to be a separate regulatory step occurring before its full transcriptional activation. Moreover, the light-inducible loci RBCS, PC and GUN5 undergo similar repositioning behaviour during their transcriptional activation. Our study supports a light-dependent gene regulatory mechanism in which PHYs activate light-inducible loci by relocating them to the nuclear periphery; it also provides evidence for the biological importance of gene positioning in the plant kingdom.
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Mutational analysis of angiogenin gene in Parkinson's disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Mutations in the angiogenic factor, angiogenin (ANG), have been identified in patients with both familial and sporadic amyotrophic lateral sclerosis (ALS) and are thought to have a neuroprotective function. Parkinsonism has been noted in kindreds with ANG mutations and variants in the ANG gene have been found to associate with PD in two Caucasian populations. We therefore hypothesized that mutations in ANG may also contribute to idiopathic Parkinson's disease (PD). We sequenced ANG gene in a total of 1498 participants comprising 750 PD patients and 748 age/gender matched controls from Taiwan. We identified one novel synonymous substitution, c.C100T (p.L10L), in a single heterozygous state in one PD patient, which was not observed in controls. The clinical phenotypes and [99mTc]-TORDAT-SPECT images of the p.L10L carrier were similar to that seen in idiopathic PD. In addition, we also identified one common variant, c.T330G (p.G110G, rs11701), which was previously reported to associate with PD risk in Caucasians. However, the frequency of TG/GG genotype was comparable between PD cases and controls (odds ratio: 0.85, 95% confidence interval: 0.29-2.55, P?=?0.78). Our results did not support that ANG rs11701 variant is a genetic risk factor for PD in our population. We conclude that mutations in ANG are not a common cause for idiopathic PD.
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Silver(I)-directed growth of metal-organic complex nanocrystals with bidentate ligands of hydroquinine anthraquinone-1,4-diyl diethers as linkers at the water-chloroform interface.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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Immiscible liquid-liquid interfaces provide unique double phase regions for the design and construction of nanoscale materials. Here, we reported Ag(I)-directed growth of metal-organic complex nanocrystals by using AgNO3 as a connector in the aqueous solution and bidentate ligand of 1,4-bis(9-O-dihydroquininyl)anthraquinone [(DHQ)2AQN] and its enantiomer of (DHQD)2AQN in the chloroform solutions as linkers. The Ag-(DHQ)2AQN and Ag-(DHQD)2AQN complex nanocrystals were formed at the liquid-liquid interfaces and characterized by using UV-vis absorption and fluorescence spectroscopy and X-ray photoelectron spectroscopy, as well as by using scanning electron microscopy. Screw-like nanocrystals were formed at the initial 30 min after the interfacial coordination reaction started, then they grew into nanorods after several days, and finally became cubic microcrystals after 2 weeks. The pure ligand showed two emission bands centered at about 363 and 522 nm in the methanol solution, the second one of which was quenched and shifted to about 470 nm in the Ag-complex nanocrystals. Two couples of reversible redox waves were recorded for the Ag-complex nanocrystals; one centered at about -0.25 V (vs. Ag/AgCl) was designated to one electron transfer process of Ag?-?(DHQ)2AQN and Ag?-?(DHQ)2AQN(+), and the other one centered at about 0.2 V was designated to one electron transfer process of Ag?-?(DHQ)2AQN and Ag(+)?-?(DHQ)2AQN.
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The associations between the family education and mortality of patients on peritoneal dialysis.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate whether education level of family members predicts all-cause and cardiovascular death and initial-episode peritonitis in patients on peritoneal dialysis (PD).
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[Analysis of measles immunity level in persistent populations in Beijing, 2012].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 12-30-2013
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To analyze the measles immunity level of persistent population in Beijing.
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Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial.
Chin. Med. J.
PUBLISHED: 11-19-2013
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A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.
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Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element.
J. Biol. Chem.
PUBLISHED: 10-22-2013
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The mylk1 gene encodes a 220-kDa nonmuscle myosin light chain kinase (MLCK), a 130-kDa smooth muscle MLCK (smMLCK), as well as the non-catalytic product telokin. Together, these proteins play critical roles in regulating smooth muscle contractility. Changes in their expression are associated with many pathological conditions; thus, it is important to understand the mechanisms regulating expression of mylk1 gene transcripts. Previously, we reported a highly conserved CArG box, which binds serum response factor, in intron 15 of mylk1. Because this CArG element is near the promoter that drives transcription of the 130-kDa smMLCK, we examined its role in regulating expression of this transcript. Results show that deletion of the intronic CArG region from a ?-galactosidase reporter gene abolished transgene expression in mice in vivo. Deletion of the CArG region from the endogenous mylk1 gene, specifically in smooth muscle cells, decreased expression of the 130-kDa smMLCK by 40% without affecting expression of the 220-kDa MLCK or telokin. This reduction in 130-kDa smMLCK expression resulted in decreased phosphorylation of myosin light chains, attenuated smooth muscle contractility, and a 24% decrease in small intestine length that was associated with a significant reduction of Ki67-positive smooth muscle cells. Overall, these data show that the CArG element in intron 15 of the mylk1 gene is necessary for maximal expression of the 130-kDa smMLCK and that the 130-kDa smMLCK isoform is specifically required to regulate smooth muscle contractility and small intestine smooth muscle cell proliferation.
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Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors.
J Chem Inf Model
PUBLISHED: 10-07-2013
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Protein-protein interactions (PPIs) play a crucial role in cellular function and form the backbone of almost all biochemical processes. In recent years, protein-protein interaction inhibitors (PPIIs) have represented a treasure trove of potential new drug targets. Unfortunately, there are few successful drugs of PPIIs on the market. Structure-based pharmacophore (SBP) combined with docking has been demonstrated as a useful Virtual Screening (VS) strategy in drug development projects. However, the combination of target complexity and poor binding affinity prediction has thwarted the application of this strategy in the discovery of PPIIs. Here we report an effective VS strategy on p53-MDM2 PPI. First, we built a SBP model based on p53-MDM2 complex cocrystal structures. The model was then simplified by using a Receptor-Ligand complex-based pharmacophore model considering the critical binding features between MDM2 and its small molecular inhibitors. Cascade docking was subsequently applied to improve the hit rate. Based on this strategy, we performed VS on NCI and SPECS databases and successfully discovered 6 novel compounds from 15 hits with the best, compound 1 (NSC 5359), K(i) = 180 ± 50 nM. These compounds can serve as lead compounds for further optimization.
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Matrine attenuates allergic airway inflammation and eosinophil infiltration by suppressing eotaxin and Th2 cytokine production in asthmatic mice.
J Ethnopharmacol
PUBLISHED: 09-07-2013
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Matrine has been isolated from Sophora flavescens, and found to show anti-inflammatory effects in macrophages and anti-cachectic effects in hepatomas. The present study investigated whether matrine suppressed eosinophil infiltration and airway hyperresponsiveness (AHR) in mice, and decreased the inflammatory response of tracheal epithelial cells.
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Uterine massage to reduce blood loss after vaginal delivery: a randomized controlled trial.
Obstet Gynecol
PUBLISHED: 08-24-2013
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To evaluate whether sustained transabdominal uterine massage can reduce blood loss after vaginal delivery.
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Improved Early Postresuscitation EEG Activity for Animals Treated with Hypothermia Predicted 96?hr Neurological Outcome and Survival in a Rat Model of Cardiac Arrest.
Biomed Res Int
PUBLISHED: 08-13-2013
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Purpose. To investigate the effect of hypothermia on 96?hr neurological outcome and survival by quantitatively characterizing early postresuscitation EEG in a rat model of cardiac arrest. Materials and Methods. In twenty male Sprague-Dawley rats, cardiac arrest was induced through high frequency transesophageal cardiac pacing. Cardiopulmonary resuscitation was initiated after 5?mins untreated arrest. Immediately after resuscitation, animals were randomized to either 2?hrs of hypothermia (N = 10) or normothermia (N = 10). EEG, ECG, aortic pressure, and core temperature were continuously recorded for 6?hrs. Neurological outcome was evaluated daily during the 96?hrs postresuscitation period. Results. No differences in the baseline measurements and resuscitation outcome were observed between groups. However, 96?hr neurological deficit score (204 ± 255 versus 500 ± 0, P = 0.005) and survival (6/10 versus 0/10, P = 0.011) were significantly better in the hypothermic group. Quantitative analysis of early postresuscitation EEG revealed that burst frequency and spectrum entropy were greatly improved in the hypothermic group and correlated with 96?hr neurological outcome and survival. Conclusion. The improved burst frequency during burst suppression period and preserved spectrum entropy after restoration of continuous background EEG activity for animals treated with hypothermia predicted favorable neurological outcome and survival in this rat model of cardiac arrest.
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Novel strategies for the prevention and treatment of biofilm related infections.
Int J Mol Sci
PUBLISHED: 08-08-2013
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Biofilm formation by human bacterial pathogens on implanted medical devices causes major morbidity and mortality among patients, and leads to billions of dollars in healthcare cost. Biofilm is a complex bacterial community that is highly resistant to antibiotics and human immunity. As a result, novel therapeutic solutions other than the conventional antibiotic therapies are in urgent need. In this review, we will discuss the recent research in discovery of alternative approaches to prevent or treat biofilms. Current anti-biofilm technologies could be divided into two groups. The first group focuses on targeting the biofilm forming process of bacteria based on our understanding of the molecular mechanism of biofilm formation. Small molecules and enzymes have been developed to inhibit or disrupt biofilm formation. Another group of anti-biofilm technologies focuses on modifying the biomaterials used in medical devices to make them resistant to biofilm formation. While these novel anti-biofilm approaches are still in nascent phases of development, efforts devoted to these technologies could eventually lead to anti-biofilm therapies that are superior to the current antibiotic treatment.
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Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.
Infect. Genet. Evol.
PUBLISHED: 07-26-2013
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The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China.
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Effects of low-level hexabromocyclododecane (HBCD) exposure on cardiac development in zebrafish embryos.
Ecotoxicology
PUBLISHED: 07-18-2013
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Hexabromocyclododecane (HBCD) is one of the most widely used brominated flame retardants. In the present study, zebrafish embryos were exposed to HBCD at the low concentrations of 0, 2, 20 and 200 nM. The results showed HBCD exposure resulted in an increase in heart rate and cardiac arrhythmia after exposure for 72 h, though the survival rate and the whole malformation rate were not significantly affected. These results demonstrated that the heart might be a target of HBCD. Low-level HBCD exposure may not share the same mechanisms as exposure to high concentrations, since no obvious increase of apoptotic cells around the heart was observed in the HBCD-treated groups. It was observed that the expression of Tbx5 and Nkx2.5 was significantly elevated by HBCD treatment in a dose-dependent manner using real-time quantitative PCR, which may be mainly responsible for the alteration of heart rate, given that Tbx5 and Nkx2.5 are two factors regulating ventricle conduction. The mRNA expression of RyR2 and Atp2a2b (SERCA2a) was up-regulated in the exposure group, which may be one of reasons to affect the normal heart rate, since SERCA2a and RyR2 play an important role in calcium ion transport of cadiomyocytes. However, HBCD exposure did not significantly change the expression of Actc1l, Tnnt2, and Myh6, which are mainly muscle contractile genes that play key roles in the formation of cardiac structure. These results were consistent with the lack of effect seen on the other measurements of cardiac function, end diastolic volume, end-systolic volume, stroke volume, and cardiac output.
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Epidemiology of human respiratory viruses in children with acute respiratory tract infections in Jinan, China.
Clin. Dev. Immunol.
PUBLISHED: 07-13-2013
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The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.
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BST1 rs11724635 interacts with environmental factors to increase the risk of Parkinsons disease in a Taiwanese population.
Parkinsonism Relat. Disord.
PUBLISHED: 07-09-2013
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A recently published genome-wide association study in Caucasian and Asian populations showed a significant association between the bone marrow stromal cell antigen 1 (BST1) SNP rs11724635 and increased risk for Parkinsons disease (PD). To investigate whether BST1 rs11724635 increases the risk of PD, either by itself or in combination with environmental factors, we performed an association analysis of BST1 rs11724635 in a large cohort of Taiwanese patients with PD and age matched controls. The study used TaqMan genotyping, logistic regression, and haplotype methods. The genotype distribution of rs11724635 in PD patients (N = 468; p = 0.50) and control subjects (N = 487; p = 0.44) was consistent with Hardy-Weinberg equilibrium. Compared with the AA genotype, the frequency of both CA and CC genotypes was not significantly different between the patient and control groups. The adjusted odd ratios (ORs) for CA and CC were not statistically significant (CA: OR = 0.962, 95% CI = 0.643-1.439, p = 0.850; CC: OR = 0.992, 95% CI = 0.654-1.503, p = 0.969). Of note, ever use of well water before the onset of PD symptoms had an impact on the occurrence of PD through interactions with BST1 rs11724635 AC (OR = 1.453, p = 0.024) and CC (OR = 1.623, p = 0.008). Our results show that the BST1 rs11724635 polymorphism alone is not associated with the development of PD, but it can interact with well water drinking to increase the risk of PD in this Taiwanese population.
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Vitamin D receptor genetic variants and Parkinsons disease in a Taiwanese population.
Neurobiol. Aging
PUBLISHED: 07-06-2013
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Patients with Parkinsons disease (PD) have hypovitaminosis D status and genetic variants of vitamin D receptor (VDR) gene are recently shown to be associated with PD in a large-scale genome-wide association study in a Caucasian population. Few studies examined VDR genetic variants in large-scale Asian patients with PD. We therefore genotyped 6 VDR genetic variants in a total of 1492 Taiwanese subjects, including 700 patients with PD and 792 age and/or gender matched control subjects. We did not observe any significant associations between the studied genetic variants of VDR and the risk of PD. Our data suggest that genetic variations of the VDR gene did not play a major role in a Taiwanese PD population. Further studies of VDR and its interaction with serum vitamin D levels are warranted to clarify the potential role of vitamin D in PD pathogenesis.
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The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats.
Biomed Res Int
PUBLISHED: 06-26-2013
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The purpose of this study was to determine the effect of apigenin on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Healthy male SD rats were randomly divided into four groups: A group (the control group), B group (the long-term administration of 165?mg/kg apigenin for 15 days), C group (a single dose of 165?mg/kg apigenin), and D group (a single dose of 252?mg/kg apigenin). The serum concentrations of imatinib and N-desmethyl imatinib were measured by HPLC, and pharmacokinetic parameters were calculated using DAS 3.0 software. The parameters of AUC(0-t), AUC(0-?), T max, V z /F, and CL z /F for imatinib in group B were different from those in group A (P < 0.05). Besides, MRT(0-t) and MRT(0-?) in groups C and D differed distinctly from those in group A as well. The parameters of AUC(0-t) and C max for N-desmethyl imatinib in group C were significantly lower than those in group A (P < 0.05); however, compared with groups B and D, the magnitude of effect was modest. Those results indicated that apigenin in the short-term study inhibited the metabolism of imatinib and its metabolite N-desmethyl imatinib, while in the long-term study the metabolism could be accelerated.
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Noise Attenuation in the ON and OFF States of Biological Switches.
ACS Synth Biol
PUBLISHED: 06-25-2013
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Biological switches must sense changes in signal concentration and at the same time buffer against signal noise. While many studies have focused on the response of switching systems to noise in the ON state, how systems buffer noise at both ON and OFF states is poorly understood. Through analytical and computational approaches, we find that switching systems require different dynamics at the OFF state than at the ON state in order to have good noise buffering capability. Specifically, we introduce a quantity called the input-associated Signed Activation Time (iSAT) that concisely captures an intrinsic temporal property at either the ON or OFF state. We discover a trade-off between achieving good noise buffering in the ON versus the OFF states: a large iSAT corresponds to noise amplification in the OFF state in contrast to noise buffering in the ON state. To search for biological circuits that can buffer noise in both ON and OFF states, we systematically analyze all three-node circuits and identify mutual activation as a central motif. We also study connections among signal sensitivity, iSAT, and noise amplification. We find that a large iSAT at the ON state maintains signaling sensitivity while minimizing noise propagation. Taken together, the analysis of iSATs helps reveal the noise properties of biological networks and should aid in the design of robust switches that can both repress noise at the OFF state and maintain a reliable ON state.
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Inclusion complexes of cypermethrin and permethrin with monochlorotriazinyl-beta-cyclodextrin: a combined spectroscopy, TG/DSC and DFT study.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 06-02-2013
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The suitable size hydrophobic cavity and monochlorotriazinyl group as a reactive anchor make MCT-?-CD to be widely used in fabric finishing. In this paper, the inclusion complexes of monochlorotriazinyl-beta-cyclodextrin (MCT-?-CD) with cypermethrin (CYPERM) and permethrin (PERM) are synthesized and analyzed by TG/DSC, FT-IR and Raman spectroscopy. TG/DSC reveals that the decomposed temperatures of inclusion complexes are lower by 25-30 °C than that of physical mixtures. DFT calculations in conjunction with FT-IR and Raman spectral analyses are used to study the structures of MCT-?-CD and their inclusion complexes. Four isomers of trisubstituted MCT-?-CD are designed and DFT calculations reveal that 1,3,5-trisubstituted MCT-?-CD has the lowest energy and can be considered as main component of MCT-?-CD. The ground-state geometries, vibrational wavenumbers, IR and Raman intensities of MCT-?-CD and their inclusion complexes were calculated at B3LYP/6-31G (d) level of theory. Upon examining the optimized geometry of inclusion complex, we find that the CYPERM and PERM are inserted into the toroid of MCT-?-CD from the larger opening. The band at 1646 cm(-1) in IR and at 1668 cm(-1) in Raman spectrum reveals that monochloroazinyl group of MCT-?-CD exists in ketone form but not in anion form. The noticeable IR and Raman shift of phenyl reveals that these two benzene rings of CYPERM and PERM stays inside the cavity of MCT-?-CD and has weak interaction with MCT-?-CD. This spectroscopy conclusion is consistent with theoretical predicted structure.
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Decomposition of NO in automobile exhaust by plasma-photocatalysis synergy.
Environ Sci Pollut Res Int
PUBLISHED: 05-30-2013
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The combination of plasma discharge and TiO2 photocatalysis exhibits high performances in the removal of nitrogen monoxide (NO). This article is aimed at elucidating the relationships between NO decomposition efficiency and various experimental parameters, including voltages, humidity and temperature. The experimental results indicate that the efficiency of NO removal by synergic plasma-catalyst coupling is significantly higher than plasma only or photocatalyst only systems. Moreover, the NO removal efficiency improves with the increase of applied voltage. Meanwhile, a higher humidity results in a reduced number of electron-hole pairs at the surface of TiO2 photocatalyst, leading to lower synergic purification efficiencies. Finally, the efficiency of NO removal is raised with the increase of temperature due to the fact that the adsorption of NO and water by nano-TiO2 is affected by environmental temperature.
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Interfacial self-assembly and characterization of chiral coordination polymer multilayers with bidentate ligands of hydroquinine anthraquinone-1,4-diyl diether as linkers.
Langmuir
PUBLISHED: 05-14-2013
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Chiral coordination polymers (CPs) have been prepared at the air-water interface by using the ligand of 1,4-bis(9-O-dihydroquininyl)anthraquinone [(DHQ)2AQN] and its enantiomer of 1,4-bis(9-O-dihydroquinidinyl)anthraquinone [(DHQD)2AQN] as linkers and AgNO3 as the connector. Surface pressure-area isotherms indicated that both ligands could form insoluble monomolecular layers on the pure water and AgNO3 subphase surfaces. Compared with the average molecular area on the pure water surface, that of the ligand increased about 10% when its monolayer was formed on the AgNO3 subphase surface due to the formation of Ag-(DHQ)2AQN and Ag-(DHQD)2AQN chiral CPs. These monolayers were deposited on the quartz, Si, and indium tin oxide (ITO) substrate surfaces via the Langmuir-Blodgett (LB) method. The as-prepared LB films were characterized by using UV-vis absorption and fluorescence spectroscopy, circular dichroism and X-ray photoelectron spectroscopy, as well as by using a scanning electron microscope and atomic force microscope. Broad fluorescence emissions were measured at about 365 and 525 nm for the ligands in the methanol solutions. The second emission red shifted to about 555 nm in the LB films of both pure ligands and their Ag-directed CPs. A couple of well-reversible redox waves were recorded and centered at about -0.2 ~ -0.3 V (vs Ag/AgCl) for the ITO electrode covered by the LB films of (DHQ)2AQN, (DHQD)2AQN, or of the Ag(+)-directed CPs, which were designated to one electron transfer process of the ligands. Small aggregates were observed for the LB films prepared at the lower surface pressures, which were compressed to form more uniform two-dimensional layers at the higher surface pressures.
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Characterization of in vivo and in vitro metabolites of furanodiene in rats by high performance liquid chromatography-electrospray ionization mass spectrometry and nuclear magnetic resonance spectra.
J Pharm Biomed Anal
PUBLISHED: 05-09-2013
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Furanodiene is an active ingredient of Rhizoma Curcumae, a very famous Traditional Chinese Medicine (TCM) widely used for the treatment of cancer. Although the anti-tumor effect of furanodiene has well been established, its metabolic profile in vivo and in vitro is still unclear. In the present study, the metabolites of furanodiene in rats were studied. After oral administration of furanodiene, the rats urine, feces and bile were collected and produced seven metabolites by the use of macroporous adsorption resin chromatography, and semi-preparative high performance liquid chromatography. Their structures were identified by mass spectrometry and NMR data including (1)H, (13)C, and two-dimensional NMR data. All of these metabolites were phase I metabolites, with three new compounds including 2?-hydroxyl-aeruginolactone (2), 14-hydroxyl-aeruginolactone (3), 1?,8?-dihydroxyeudesm-4,7(11)-dien-8?,12-olide (4a), and four known compounds, 1?,10?,4?,5?-diepoxy-8?-hydroxy-glechoman-8?,12-olide (1), 1?,8?-dihydroxyeudesm-4(14),7(11)-dien-8?,12-olide (4b), 1?,8?-dihydroxyeudesm-3,7(11)-dien-8?,12-olide (5) and aeruginolactone (6). Interestingly, the metabolite 6 was found to be a primary metabolite in urine, bile and feces. All metabolites were found to be both in urine and bile but only few metabolites except the metabolite 6 presented in feces after oral dose of furanodiene to rats. Furthermore, the metabolic pathways of furanodiene were proposed using an in vitro assay by incubation of furanodiene and its metabolites in vivo with rat liver S9 or liver microsomes. Clearly, aeruginolactone (6) seemed to be a major precursor for other metabolites.
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Target expression of Staphylococcus enterotoxin A from an oncolytic adenovirus suppresses mouse bladder tumor growth and recruits CD3+ T cell.
Tumour Biol.
PUBLISHED: 05-07-2013
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We recently engineered an oncolytic adenovirus (PPE3-SEA) that expresses the superantigen, Staphylococcus enterotoxin A (SEA), and that has enhanced tumor specificity because the telomerase reverse transcriptase and hypoxia-inducible factor promoters regulate expression of E1A and E1B genes, respectively. Here, we evaluated the PPE3-SEA adenovirus anti-tumor activity against MB49 mouse bladder cancer cell proliferation in vitro and in vivo. PPE3-SEA infection of murine MB49 cells in vitro induced cytopathic effects, and significant expression of SEA mRNA and protein, as measured by RT-PCR and western blot, respectively. Subcutaneous MB29 bladder tumors were established in syngeneic C57BL/6 mice. After 10 days, tumors were injected with either oncolytic virus or PBS. Tumor dimensions were measured on days 1, 3, 5, 7, 9, and 11 post-treatment and tumor volumes were calculated. One of eight PPE3-SEA-treated mice had no tumor by day 9. PPE3-SEA treated group had significantly lower mean tumor volume beginning on day 5 post-treatment (p < 0.01), more fibrous tissue in the tumor, and increased presence of infiltrating CD3+ T cells than those of the control group. Gross appearance and histologic sections from the livers and kidneys of the PPE3-SEA-treated group were similar to those of the control group. In conclusion, oncolytic adenoviruses can provide a novel delivery vehicle for SEA to tumor sites, and PPE3-SEA warrants further study as a potential anti-tumor agent for bladder cancer.
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