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Find video protocols related to scientific articles indexed in Pubmed.
Hepatoprotective and Anti-oxidant Activities of Glossogyne tenuifolia Against Acetaminophen-Induced Hepatotoxicity in Mice.
Am. J. Chin. Med.
PUBLISHED: 11-12-2014
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The present study investigated the anti-oxidative and hepatoprotective effects of Glossogyne tenuifolia (GT) Cassini, against acetaminophen-induced acute liver injury in BALB/c mice. The extracts of GT by various solvents (hot water, 50% ethanol and 95% ethanol) were compared for their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, total phenolic content, and total anti-oxidant capacity. The results showed that hot water (HW) extracts of GT contained high levels of phenolics and exerted an excellent anti-oxidative capacity; thus, these were used in the animal experiment. The male BALB/c mice were randomly divided into control group, acetaminophen (APAP) group, positive control group and two GT groups at low (GT-L) and high (GT-H) dosages. The results showed that mice treated with GT had significantly decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). GT-H increased glutathione levels and the ratios of reduced glutathione and oxidized glutathione (GSH/GSSG) in the liver, and inhibited serum and lipid peroxidation. This experiment was the first to determine phenolic compounds, chlorogenic acid and luteolin-7-glucoside in HW extract of GT. In conclusion, HW extract of GT may have potential anti-oxidant capacity and show hepatoprotective capacities in APAP-induced liver damaged mice.
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A new design of facial artery perforator flaps for the reconstruction of small- to medium-sized intraoral defects.
J Craniofac Surg
PUBLISHED: 11-08-2014
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The aim of this study was to investigate the reliability and outcomes of a new design of facial artery perforator flaps, extending from the angle of the mouth to the border of the mandible, for the reconstruction of small- to medium-sized intraoral defects.
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Approaches and challenges to optimising primary care teams' electronic health record usage.
Inform Prim Care
PUBLISHED: 09-11-2014
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Although the presence of an electronic health record (EHR) alone does not ensure high quality, efficient care, few studies have focused on the work of those charged with optimising use of existing EHR functionality.
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[Effect of pretreatment with qishen yiqi dropping pills on right cardiac function of patients undergoing valve replacement].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-11-2014
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In this study, 120 patients with rheumatic heart disease undergoing valve replacement were randomly divided into the control group and the Qishen group, with 60 cases in each group. Before the operation, the control group was given routine heart and diuretic treatments and placebo of Qishen Yiqi dropping pills for seven days (0.5 g each time, three times a day); While the Qishen group was given Qishen Yiqi dropping pills for seven days (0.5 g each time after meal, three times a day) on the basis of the routine treatments. The right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (SV) and right ventricular ejection fraction (RVEF) were detected after the operation. The results showed that patients in the two groups showed significantly lower right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV) and stroke volume (SV) decreased than that before the operation, but with significantly higher Ejection fraction (RVEF) significantly than that before the operation. However, the Qishen group showed a significantly lower right heart function reduction than the control group, with the statistical significance in the differences (P < 0.05). This indicated that the pretreatment with Qishenyiqi Drop Pills showed a remarkable efficacy in the improvement of right ventricular function after valve replacement.
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Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts.
Age (Dordr)
PUBLISHED: 08-27-2014
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Exercise training is considered a benefit to heart function, but the benefit in aging hearts remains unknown. Activation of the PI3K-Akt survival pathway and suppression of Fas/FADD/caspase-8 apoptotic signaling by exercise training in hearts from young subjects have been described in our previous studies. However, the mechanisms are still unclear and need to be explored in aging hearts. Thus, 18-month-old rats were used as a model and underwent swimming exercise training, resveratrol treatment (15 mg/kg/day), or exercise training with resveratrol treatment for 1 month. The results showed that heart function in each group improved. However, the 18-month-old rats in the exercise-only group experienced the slightly inevitable impact of increased TNF-?, cell apoptosis, and fibrosis. In the protein analysis, the PI3K-Akt pathway was slightly increased with exercise training and resveratrol treatment, but Sirtuin 1 (SIRT1) was only highly activated with resveratrol treatment in the aged rat hearts. Moreover, the exercise training plus resveratrol group benefited from SIRT1 and PI3K-Akt dual pathways and blocked FOXO3 accumulation. Our experimental results strongly suggest that resveratrol treatment improves the beneficial effects of exercise training in aging rat hearts.
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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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Beclin-1-independent autophagy positively regulates internal ribosomal entry site-dependent translation of hypoxia-inducible factor 1? under nutrient deprivation.
Oncotarget
PUBLISHED: 08-14-2014
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Hypoxia has been shown to induce hypoxia-inducible factor-1alpha (HIF-1?) expression to support many cellular changes required for tumor growth and metastasis. In addition to hypoxia, nutrient deprivation is another stress condition widely existing in solid tumors due to the poor blood supply. Our data showed that nutrient deprivation induces a significant HIF-1? protein expression and potentiates the HIF-1? responses of hypoxia and CoCl2. This effect is not because of enhancement of HIF-1? stability or transcription. Rather we found it is through the cap-independent but internal ribosome entry site (IRES)-dependent translation. Notably inhibition of autophagy by si-ATG5, 3-methyladenine and chloroquine, but not si-Beclin-1, significantly reverses nutrient deprivation-induced HIF-1? responses. Furthermore, it is interesting to note the contribution of IRES activation for hypoxia-induced HIF-1? expression, however, different from nutrient starvation, si-Beclin 1 but not si-ATG5 can inhibit hypoxia-induced HIF-1? IRES activation and protein expression. Taken together, we for the first time highlight a link from alternative autophagy to cap-independent protein translation of HIF-1? under two unique stress conditions. We demonstrate Beclin 1-independent autophagy is involved to positively regulate nutrient deprivation induced-HIF-1? IRES activity and protein expression, while ATG5-independent autophagy is involved in the HIF-1 IRES activation caused by hypoxia.
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Molecular kinetics. Ras activation by SOS: allosteric regulation by altered fluctuation dynamics.
Science
PUBLISHED: 07-05-2014
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Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.
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Establishment of epithelial polarity--GEF who's minding the GAP?
J. Cell. Sci.
PUBLISHED: 07-02-2014
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Cell polarization is a fundamental process that underlies epithelial morphogenesis, cell motility, cell division and organogenesis. Loss of polarity predisposes tissues to developmental disorders and contributes to cancer progression. The formation and establishment of epithelial cell polarity is mediated by the cooperation of polarity protein complexes, namely the Crumbs, partitioning defective (Par) and Scribble complexes, with Rho family GTPases, including RhoA, Rac1 and Cdc42. The activation of different GTPases triggers distinct downstream signaling pathways to modulate protein-protein interactions and cytoskeletal remodeling. The spatio-temporal activation and inactivation of these small GTPases is tightly controlled by a complex interconnected network of different regulatory proteins, including guanine-nucleotide-exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine-nucleotide-dissociation inhibitors (GDIs). In this Commentary, we focus on current understanding on how polarity complexes interact with GEFs and GAPs to control the precise location and activation of Rho GTPases (Crumbs for RhoA, Par for Rac1, and Scribble for Cdc42) to promote apical-basal polarization in mammalian epithelial cells. The mutual exclusion of GTPase activities, especially that of RhoA and Rac1, which is well established, provides a mechanism through which polarity complexes that act through distinct Rho GTPases function as cellular rheostats to fine-tune specific downstream pathways to differentiate and preserve the apical and basolateral domains. This article is part of a Minifocus on Establishing polarity.
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Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.
J. Infect. Dis.
PUBLISHED: 06-18-2014
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High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM).
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Engineering a light-regulated GABAA receptor for optical control of neural inhibition.
ACS Chem. Biol.
PUBLISHED: 05-22-2014
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Optogenetics has become an emerging technique for neuroscience investigations owing to the great spatiotemporal precision and the target selectivity it provides. Here we extend the optogenetic strategy to GABAA receptors (GABAARs), the major mediators of inhibitory neurotransmission in the brain. We generated a light-regulated GABAA receptor (LiGABAR) by conjugating a photoswitchable tethered ligand (PTL) onto a mutant receptor containing the cysteine-substituted ?1-subunit. The installed PTL can be advanced to or retracted from the GABA-binding pocket with 500 and 380 nm light, respectively, resulting in photoswitchable receptor antagonism. In hippocampal neurons, this LiGABAR enabled a robust photoregulation of inhibitory postsynaptic currents. Moreover, it allowed reversible photocontrol over neuron excitation in response to presynaptic stimulation. LiGABAR thus provides a powerful means for functional and mechanistic investigations of GABAAR-mediated neural inhibition.
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Kernel-machine testing coupled with a rank-truncation method for genetic pathway analysis.
Genet. Epidemiol.
PUBLISHED: 04-09-2014
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Traditional genome-wide association studies (GWASs) usually focus on single-marker analysis, which only accesses marginal effects. Pathway analysis, on the other hand, considers biological pathway gene marker hierarchical structure and therefore provides additional insights into the genetic architecture underlining complex diseases. Recently, a number of methods for pathway analysis have been proposed to assess the significance of a biological pathway from a collection of single-nucleotide polymorphisms. In this study, we propose a novel approach for pathway analysis that assesses the effects of genes using the sequence kernel association test and the effects of pathways using an extended adaptive rank truncated product statistic. It has been increasingly recognized that complex diseases are caused by both common and rare variants. We propose a new weighting scheme for genetic variants across the whole allelic frequency spectrum to be analyzed together without any form of frequency cutoff for defining rare variants. The proposed approach is flexible. It is applicable to both binary and continuous traits, and incorporating covariates is easy. Furthermore, it can be readily applied to GWAS data, exome-sequencing data, and deep resequencing data. We evaluate the new approach on data simulated under comprehensive scenarios and show that it has the highest power in most of the scenarios while maintaining the correct type I error rate. We also apply our proposed methodology to data from a study of the association between bipolar disorder and candidate pathways from Wellcome Trust Case Control Consortium (WTCCC) to show its utility.
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Correction: Determining the degradation efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS.
Chem Cent J
PUBLISHED: 04-07-2014
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This is a correction to the following paper: Determining the degradation efficiency and mechanisms of ethyl violet using HPLC-PDA-ESI-MS and GC-MS, Wen-Hsin Chung, Chung-Shin Lu, Wan-Yu Lin, Jian-Xun Wang, Chia-Wei Wu, Chiing-Chang Chen, Chemistry Central Journal 2012, 6:63 (30 June 2012).
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18F-FDG PET or PET/CT for detecting extensive disease in small-cell lung cancer: a systematic review and meta-analysis.
Nucl Med Commun
PUBLISHED: 04-04-2014
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The purpose of this study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of fluorine-18 2-fluoro-2-deoxy-D-glucose (F-FDG) PET or PET/computed tomography (CT) in the pretherapeutic staging of patients with small-cell lung cancer (SCLC). The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and summary receiver operating characteristic curves in the detection of extensive disease (ED) in patients with SCLC. Twelve studies with a total of 369 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, LR+, and LR- of F-FDG PET or PET/CT for the detection of ED in SCLC were 97.5% [95% confidence interval (CI), 94.2-99.2%], 98.2% (95% CI, 94.9-99.6%), 19.86 (95% CI, 9.79-40.30), and 0.06 (95% CI, 0.03-0.10), respectively. Whole-body F-FDG PET or PET/CT is a valuable imaging tool for the pretherapeutic assessment of ED in patients with SCLC.
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Endocannabinoid system activation contributes to glucose metabolism disorders of hepatocytes and promotes hepatitis C virus replication.
Int. J. Infect. Dis.
PUBLISHED: 04-02-2014
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Insulin resistance is highly prevalent in patients with chronic hepatitis C (CHC) and to some extent accounts for fibrosis and reducing viral eradication. Activated cannabinoid 1 receptor (CB1R) signaling has been implicated in the development of phenotypes associated with insulin resistance and steatosis. We investigated the role of the endocannabinoid system in glucose metabolism disorders induced by hepatitis C virus (HCV) replication.
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Over-expression of hypoxia-inducible factor-1 alpha in vitro protects the cardiac fibroblasts from hypoxia-induced apoptosis.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 03-04-2014
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A great number of studies indicate that cardiac fibroblasts are essential for maintaining the structure and function of heart. Hypoxia-inducible factor-1 alpha (HIF-1?) is a central transcriptional regulator of hypoxic response. The present study examined whether over-expression of HIF-1? could prevent hypoxia-induced injury in neonatal rat cardiac fibroblasts and, if so, its possible molecular targets.
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The impact of petrochemical industrialisation on life expectancy and per capita income in Taiwan: an 11-year longitudinal study.
BMC Public Health
PUBLISHED: 02-27-2014
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Petrochemical industries have been identified as important sources of emissions of chemical substances, and adverse health outcomes have been reported for residents who live nearby. The purpose of the current study was to examine the adverse effects of petrochemical industrialization in Taiwan on the life expectancy and personal income of people living in nearby communities.
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Establishment of Multiple Locus Variable-number Tandem Repeat Analysis Assay for Genotyping of Borrelia burgdorferi sensu lato Detected in China.
Biomed. Environ. Sci.
PUBLISHED: 02-19-2014
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Human Lyme Borreliosis (LB), which is caused by Borrelia burgdorferi sensu lato (B. burgdorferi), has been identified as a major arthropod-borne infectious disease in China. We aimed to develop a multiple locus variable-number tandem repeat (VNTR) analysis (MLVA) assay for the genotyping of Borrelia burgdorferi strains detected in China.
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H-Ras forms dimers on membrane surfaces via a protein-protein interface.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-10-2014
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The lipid-anchored small GTPase Ras is an important signaling node in mammalian cells. A number of observations suggest that Ras is laterally organized within the cell membrane, and this may play a regulatory role in its activation. Lipid anchors composed of palmitoyl and farnesyl moieties in H-, N-, and K-Ras are widely suspected to be responsible for guiding protein organization in membranes. Here, we report that H-Ras forms a dimer on membrane surfaces through a protein-protein binding interface. A Y64A point mutation in the switch II region, known to prevent Son of sevenless and PI3K effector interactions, abolishes dimer formation. This suggests that the switch II region, near the nucleotide binding cleft, is either part of, or allosterically coupled to, the dimer interface. By tethering H-Ras to bilayers via a membrane-miscible lipid tail, we show that dimer formation is mediated by protein interactions and does not require lipid anchor clustering. We quantitatively characterize H-Ras dimerization in supported membranes using a combination of fluorescence correlation spectroscopy, photon counting histogram analysis, time-resolved fluorescence anisotropy, single-molecule tracking, and step photobleaching analysis. The 2D dimerization Kd is measured to be ?1 × 10(3) molecules/µm(2), and no higher-order oligomers were observed. Dimerization only occurs on the membrane surface; H-Ras is strictly monomeric at comparable densities in solution. Analysis of a number of H-Ras constructs, including key changes to the lipidation pattern of the hypervariable region, suggest that dimerization is a general property of native H-Ras on membrane surfaces.
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In vitro and in vivo direct monitoring of miRNA-22 expression in isoproterenol-induced cardiac hypertrophy by bioluminescence imaging.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 02-07-2014
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Growing evidence suggests that microRNAs (miRNAs) play key roles in cardiac hypertrophy. To measure the expression of endogenous miRNAs is very conducive to understanding the importance of miRNAs in cardiac hypertrophy. However, current methods to monitor endogenous miRNA levels, such as Northern blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and microarrays cannot provide real-time information on miRNA biogenesis in vivo.
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Bioactive cembranoids, sarcocrassocolides P-R, from the Dongsha Atoll soft coral Sarcophyton crassocaule.
Mar Drugs
PUBLISHED: 01-17-2014
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New cembranoids, sarcocrassocolides P-R (1-3) and four known compounds (4-7) were isolated from the soft coral Sarcophyton crassocaule. The structures of the metabolites were determined by extensive spectroscopic analysis. Compounds 3-5 and 7 were shown to exhibit cytotoxicity toward a limited panel of cancer cell lines and all compounds 1-7 displayed potent in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by inhibiting the expression of inducible nitric oxide synthase (iNOS) protein. Compound 7 also showed significant activity in reducing the accumulation of cyclooxygenase-2 (COX-2) protein in the same macrophage cells.
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Syk Mediates IL-17-Induced CCL20 Expression by Targeting Act1-Dependent K63-Linked Ubiquitination of TRAF6.
J. Invest. Dermatol.
PUBLISHED: 01-07-2014
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IL-17 has an important role in the immunopathogenesis of autoimmune diseases, and spleen tyrosine kinase (Syk) has been implicated as a critical molecule in the signaling pathways of various immunoreceptors. Chemokine (C-C motif) ligand 20 (CCL20) interacts with chemokine (C-C motif) receptor 6 to recruit IL-17-producing cells into the skin to promote progression of psoriasis. Herein we investigate how Syk regulates IL-17 signaling to affect CCL20 expression in primary human epidermal keratinocytes. We found that IL-17 can induce CCL20 expression and activate TAK, IKK, NF-?B, c-Jun N-terminal kinase, and Syk. Data of TAK inhibitor and Syk small interfering RNA (siRNA) indicate Syk being an upstream molecule of TAK in IL-17-elicited signaling. The promoter activity assay combined with site-directed mutagenesis showed that IL-17-elicited CCL20 upregulation is depending on the Syk-mediated NF-?B pathway. Immunoprecipitation also indicated the interaction of Syk with signal molecules of IL-17R, such as TRAF6 and Act1, under IL-17A stimulation. However, the essential signaling events including TRAF6 interaction with Act1 and TRAF6 polyubiquitination under IL-17A stimulation were diminished by Syk siRNA and pharmacologically inhibiting Syk. Taken together, we identify Syk as an upstream signaling molecule in IL-17A-induced Act1-TRAF6 interaction in keratinocytes, and inhibition of Syk can attenuate CCL20 production, which highlights Syk as a potential therapeutic target for inflammatory skin diseases such as psoriasis.Journal of Investigative Dermatology advance online publication, 23 October 2014; doi:10.1038/jid.2014.383.
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Biological evaluation of 131I- and CF750-labeled Dmab(scFv)-Fc antibodies for xenograft imaging of CD25-positive tumors.
Biomed Res Int
PUBLISHED: 01-07-2014
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A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was produced via recombinant expression in Pichia pastoris. The Dmab(scFv)-Fc antibody forms a dimer in solution, and it specifically binds CD25-positive tumor cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was labeled with the 131I isotope and CF750 fluorescent dye, respectively. After intravenous injection of mice bearing CD25-positive tumor xenografts, tumor uptake of the (131)I-Dmab(scFv)-Fc antibody was visible at 1 h, and clear images were obtained at 5 h using SPECT/CT. After systemic administration of the CF750-Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1 h, and tumor xenografts could be kinetically imaged within 9?h after injection. These results indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25-positive tumor cells, suggesting the potential of this antibody as an imaging agent for the diagnosis of lymphomatous-type ATLL.
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Impact of right-ventricular apical pacing on the optimal left-ventricular lead positions measured by phase analysis of SPECT myocardial perfusion imaging.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 01-02-2014
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The use of SPECT phase analysis to optimize left-ventricular (LV) lead positions for cardiac resynchronization therapy (CRT) was performed at baseline, but CRT works as simultaneous right ventricular (RV) and LV pacing. The aim of this study was to assess the impact of RV apical (RVA) pacing on optimal LV lead positions measured by SPECT phase analysis.
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Poly(Ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor.
PLoS ONE
PUBLISHED: 01-01-2014
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High-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR) can be prepared from a structurally simple material, poly(ethylene glycol) (PEG). The PEG-based blockers (PQ1-5), comprised of a flexible octa(ethylene glycol) scaffold and two terminal quaternary ammonium groups, exert low- to sub-micromolar affinities for the open AChR pore (measured via single-channel analysis of AChRs expressed in human embryonic kidney cells). PQ1-5 are comparable in pore-binding affinity to the strongest AChR open-channel blockers previously reported, which have complex molecular structures. These results suggest a general approach for designing potent open-channel blockers from a structurally flexible polymer. This design strategy involves simple synthetic procedures and does not require detailed information about the structure of an ion-channel pore.
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IFITM3 Polymorphism rs12252-C Restricts Influenza A Viruses.
PLoS ONE
PUBLISHED: 01-01-2014
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The IFITM3 polymorphism rs12252-C, which encodes an IFITM3 isoform (?21 IFITM3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with H1N1 influenza A virus (IAV) infections. In vitro studies have shown that ?21 IFITM3 loses its ability to restrict H1N1 IAV. Subsequent research has also revealed that tyrosine 20 is the key determinant for IFITM3 endocytic trafficking, which is essential for the efficient anti-viral activity of IFITM3. In contrast to previous studies, we demonstrated that both ?21 IFITM3 and an IFITM3 variant (Y20A IFITM3), in which tyrosine 20 is substituted with alanine, strongly restricted entry mediated by IAV H1, H3, H5, and H7 proteins. ?21 IFITM3 also efficiently suppressed replication of H1N1 and, to a lesser extent, H3N2 IAV. ?21 IFITM3 and Y20A IFITM3 had broader subcellular distributions than full-length IFITM3 but an abundant amount of both IFITM3 variants still localized to late endosomes and lysosomes. Our data indicate that tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated IAV restriction. They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.
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Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.
PLoS ONE
PUBLISHED: 01-01-2014
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The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points). A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s). In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR) based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.
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Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized.
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Conductivity enhancement of multiwalled carbon nanotube thin film via thermal compression method.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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For the first time, the thermal compression method is applied to effectively enhance the electrical conductivity of carbon nanotube thin films (CNTFs). With the assistance of heat and pressure on the CNTFs, the neighbor multiwalled carbon nanotubes (CNTs) start to link with each other, and then these separated CNTs are twined into a continuous film while the compression force, duration, and temperature are quite enough for the reaction. Under the compression temperature of 400°C and the compression force of 100 N for 50 min, the sheet resistance can be reduced from 17 to 0.9 k ?/sq for the CNTFs with a thickness of 230 nm. Moreover, the effects of compression temperature and the duration of thermal compression on the conductivity of CNTF are also discussed in this work.
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EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.
PLoS ONE
PUBLISHED: 01-01-2014
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Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-? (HIF-?) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration.
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Association testing of clustered rare causal variants in case-control studies.
PLoS ONE
PUBLISHED: 01-01-2014
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Biological evidence suggests that multiple causal variants in a gene may cluster physically. Variants within the same protein functional domain or gene regulatory element would locate in close proximity on the DNA sequence. However, spatial information of variants is usually not used in current rare variant association analyses. We here propose a clustering method (abbreviated as "CLUSTER"), which is extended from the adaptive combination of P-values. Our method combines the association signals of variants that are more likely to be causal. Furthermore, the statistic incorporates the spatial information of variants. With extensive simulations, we show that our method outperforms several commonly-used methods in many scenarios. To demonstrate its use in real data analyses, we also apply this CLUSTER test to the Dallas Heart Study data. CLUSTER is among the best methods when the effects of causal variants are all in the same direction. As variants located in close proximity are more likely to have similar impact on disease risk, CLUSTER is recommended for association testing of clustered rare causal variants in case-control studies.
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Rare variant association testing by adaptive combination of P-values.
PLoS ONE
PUBLISHED: 01-01-2014
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With the development of next-generation sequencing technology, there is a great demand for powerful statistical methods to detect rare variants (minor allele frequencies (MAFs)<1%) associated with diseases. Testing for each variant site individually is known to be underpowered, and therefore many methods have been proposed to test for the association of a group of variants with phenotypes, by pooling signals of the variants in a chromosomal region. However, this pooling strategy inevitably leads to the inclusion of a large proportion of neutral variants, which may compromise the power of association tests. To address this issue, we extend the [Formula: see text]-MidP method (Cheung et al., 2012, Genet Epidemiol 36: 675-685) and propose an approach (named 'adaptive combination of P-values for rare variant association testing', abbreviated as 'ADA') that adaptively combines per-site P-values with the weights based on MAFs. Before combining P-values, we first imposed a truncation threshold upon the per-site P-values, to guard against the noise caused by the inclusion of neutral variants. This ADA method is shown to outperform popular burden tests and non-burden tests under many scenarios. ADA is recommended for next-generation sequencing data analysis where many neutral variants may be included in a functional region.
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Transmembrane TNF-? Promotes Suppressive Activities of Myeloid-Derived Suppressor Cells via TNFR2.
J. Immunol.
PUBLISHED: 12-30-2013
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It has been reported that TNFR2 is involved in regulatory T cell induction and myeloid-derived suppressor cell (MDSC) accumulation, two kinds of immunosuppressive cells contributing to tumor immune evasion. Because transmembrane TNF-? (tmTNF-?) is the primary ligand for TNFR2, we hypothesized that tmTNF-? is mainly responsible for the activation of MDSCs. Indeed, we found that tmTNF-?, rather than secretory TNF-? (sTNF-?), activated MDSCs with enhanced suppressive activities, including upregulating arginase-1 and inducible NO synthase transcription, promoting secretion of NO, reactive oxygen species, IL-10, and TGF-?, and enhancing inhibition of lymphocyte proliferation. This effect of tmTNF-? was mediated by TNFR2, as TNFR2 deficiency significantly impaired tmTNF-?-induced release of IL-10 and NO and inhibition of T cell proliferation by MDSC supernatant. Furthermore, tmTNF-? caused p38 phosphorylation and NF-?B activation, whereas inhibition of NF-?B or p38 with an inhibitor pyrrolidine dithiocarbamate or SB203580 abrogated tmTNF-?-mediated increased suppression of lymphocyte proliferation by MDSCs. Consistently, our in vivo study showed that ectopic expression of uncleavable tmTNF-? mutant by 4T1 cells significantly promoted tumor progression and angiogenesis, accompanied with more accumulation of MDSCs and regulatory T cells in the tumor site, increased production of NO, IL-10, and TGF-?, as well as poor lymphocyte infiltration. In contrast, enforced expression of sTNF-? mutant by 4T1 cells that only released sTNF-? without expression of surface tmTNF-? markedly reduced MDSC accumulation and induced more lymphocyte infiltration instead, showing obvious tumor regression. Our data suggest that tmTNF-? acts as a potent activator of MDSCs via TNFR2 and reveals another novel immunosuppressive effect of this membrane molecule that promotes tumor immune escape.
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Nitrite Activation to Nitric Oxide via One-fold Protonation of Iron(II)-O,O-nitrito Complex: Relevance to the Nitrite Reductase Activity of Deoxyhemoglobin and Deoxyhemerythrin.
J. Am. Chem. Soc.
PUBLISHED: 12-05-2013
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The reversible transformations [(Bim)3Fe(?(2)-O2N)][BF4] (3) ? [(Bim)3Fe(NO)(?(1)-ONO)][BF4]2 (4) were demonstrated and characterized. Transformation of O,O-nitrito-containing complex 3 into [(Bim)3Fe(?-O)(?-OAc)Fe(Bim)3](3+) (5) along with the release of NO and H2O triggered by 1 equiv of AcOH implicates that nitrite-to-nitric oxide conversion occurs, in contrast to two protons needed to trigger nitrite reduction producing NO observed in the protonation of [Fe(II)-nitro] complexes.
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Cytoprotective effect of american ginseng in a rat ethanol gastric ulcer model.
Molecules
PUBLISHED: 11-04-2013
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Panax quinquefolium L. (American Ginseng, AG) is one of the most popular herbal medicines in the World. We aimed to investigate whether chronic (28-day) supplementation with AG could protect against ethanol-induced ulcer in gastric tissue. Furthermore, we investigated the possible molecular mechanisms leading to AG-mediated gastric mucosal protection. We randomized 32 male Wistar rats into four groups for treatment (n = 8 per group): supplementation with water (vehicle) and low-dose (AG-1X), medium-dose (AG-2X) and high-dose (AG-5X) AG at 0, 250, 500, and 1250 mg/kg, respectively. In the first experiment, animals were fed vehicle or AG treatments for 4 weeks. At day 29, 75% ethanol was given orally to each animal at 10 mL/kg to induce gastric ulceration for 2 h. In a second experiment, animals were pretreated orally with each treatment for 1 hr before a single oral administration of ethanol (70%, 10 mL/kg). Trend analysis revealed that AG treatments inhibited ethanol-induced gastric mucosal damage. AG supplementation dose-dependently decreased the pro-inflammatory levels of interleukin 1? and cyclooxygenase 2 and the expression of pro-apoptotic proteins tBid, cytochrome C, and caspases-9 and -3 and increased the levels of anti-apoptotic proteins Bcl-2, Bcl-xL and p-Bad. AG could have pharmacological potential for treating gastric ulcer.
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Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study.
Clin. Infect. Dis.
PUBLISHED: 10-21-2013
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Background.?Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. Methods.?ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. Results.?One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. Conclusions.?Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.
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The tyrosine kinase Syk differentially regulates Toll-like receptor signaling downstream of the adaptor molecules TRAF6 and TRAF3.
Sci Signal
PUBLISHED: 08-22-2013
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Toll-like receptors (TLRs) are a major family of pattern recognition receptors, and they play a crucial role in innate immune responses. Activation of TLR4 signaling at the plasma membrane by its ligand lipopolysaccharide (LPS) stimulates a proinflammatory pathway dependent on the E3 ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6) and the kinase TAK1 (transforming growth factor ?-activated kinase 1), whereas TLR4 signaling at endosomes stimulates the production of type I interferons (IFNs) through a pathway that depends on TRAF3 and the kinase TBK1 (TANK-binding kinase-1). We found that the nonreceptor tyrosine kinase Syk partially mediated the endocytosis of TLR4, but it also played a dual role in TLR4-mediated signaling. LPS-dependent stimulation of TLR4 in Syk-deficient macrophages led to enhanced activation of TAK1 and increased production of proinflammatory cytokines compared to that in wild-type macrophages. In contrast, Syk-deficient macrophages exhibited decreased TLR4-dependent activation of TBK1 signaling and production of type I IFNs. We found that Syk was present in both TRAF6- and TRAF3-containing signaling complexes; however, the LPS-dependent, lysine 63-linked ubiquitination of TRAF6 and TRAF3 was oppositely regulated by Syk. We identified the domains of Syk that interacted with TRAF3, TRAF6, TAK1, and TBK1, factors activated by multiple TLRs, which suggests that Syk may act as a common regulator of various TLR responses. Together, our results demonstrate the opposing regulatory roles of Syk in TLR-mediated TRAF6 and TRAF3 signaling pathways, which suggests that Syk may fine-tune the innate immune response to lessen inflammation.
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Virus-induced gene silencing unravels multiple transcription factors involved in floral growth and development in Phalaenopsis orchids.
J. Exp. Bot.
PUBLISHED: 08-20-2013
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Orchidaceae, one of the largest angiosperm families, has significant commercial value. Isolation of genes involved in orchid floral development and morphogenesis, scent production, and colouration will advance knowledge of orchid flower formation and facilitate breeding new varieties to increase the commercial value. With high-throughput virus-induced gene silencing (VIGS), this study identified five transcription factors involved in various aspects of flower morphogenesis in the orchid Phalaenopsis equestris. These genes are PeMADS1, PeMADS7, PeHB, PebHLH, and PeZIP. Silencing PeMADS1 and PebHLH resulted in reduced flower size together with a pelaloid column containing petal-like epidermal cells and alterations of epidermal cell arrangement in lip lateral lobes, respectively. Silencing PeMADS7, PeHB, and PeZIP alone resulted in abortion of the first three fully developed flower buds of an inflorescence, which indicates the roles of the genes in late flower development. Furthermore, double silencing PeMADS1 and PeMADS6, C- and B-class MADS-box genes, respectively, produced a combinatorial phenotype with two genes cloned in separate vectors. Both PeMADS1 and PeMADS6 are required to ensure the normal development of the lip and column as well as the cuticle formation on the floral epidermal cell surface. Thus, VIGS allows for unravelling the interaction between two classes of MADS transcription factors for dictating orchid floral morphogenesis.
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Hepatoprotective effects of Ixora parviflora extract against exhaustive exercise-induced oxidative stress in mice.
Molecules
PUBLISHED: 08-13-2013
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Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE) has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, reducing power, and ferrous ion-chelating ability. However, whether IPE is efficacious against oxidative damage in vivo is not known. The purpose of this study was to determine the protective effects of IPE treatment on hepatic oxidative stress and antioxidant defenses after exhaustive exercise in mice. Fifty male C57BL/6 mice (6 week old) were randomly divided into five groups and designated a sedentary control with vehicle (C), and exhaustive exercise with vehicle (IPE0), low dosage (IPE10), medium dosage (IPE50) and high dosage (IPE100) of IPE at 0, 10, 50, and 100 mg/kg, respectively. After a single bout of exhaustive swimming exercise challenge, levels of blood ammonia and creatine kinase (CK), and hepatic superoxide dismutase (SOD) protein expression, thiobarbituric acid-reactive substance (TBARS), and gp91(phox), p22(phox), and p47(phox) subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressions in the IPE0 group were significantly affected compared to those of the C group, but they were all significantly inhibited by the IPE treatments. Results of the present in vivo study in mice indicate that I. parviflora extract possesses antioxidative and hepatoprotective potential following exhaustive exercise.
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Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein.
J. Cell. Sci.
PUBLISHED: 08-13-2013
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Myosin X (Myo10) is an unconventional myosin with two known isoforms: full-length (FL)-Myo10 that has motor activity, and a recently identified brain-expressed isoform, headless (Hdl)-Myo10, which lacks most of the motor domain. FL-Myo10 is involved in the regulation of filopodia formation in non-neuronal cells; however, the biological function of Hdl-Myo10 remains largely unknown. Here, we show that FL- and Hdl-Myo10 have important, but distinct, roles in the development of dendritic spines and synapses in hippocampal neurons. FL-Myo10 induces formation of dendritic filopodia and modulates filopodia dynamics by trafficking the actin-binding protein vasodilator-stimulated phosphoprotein (VASP) to the tips of filopodia. By contrast, Hdl-Myo10 acts on dendritic spines to enhance spine and synaptic density as well as spine head expansion by increasing the retention of VASP in spines. Thus, this study demonstrates a novel biological function for Hdl-Myo10 and an important new role for both Myo10 isoforms in the development of dendritic spines and synapses.
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Survey on nitrogen removal and membrane filtration characteristics of Chlorella vulgaris Beij. on treating domestic type wastewaters.
Water Sci. Technol.
PUBLISHED: 08-09-2013
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The main objective of this study is to evaluate the nitrogen assimilation and filtration characteristics of Chlorella vulgaris Beij. when treating domestic wastewaters. Chlorella could assimilate organic nitrogen, ammonia and nitrate in wastewater, and the mean cell residence time (MCRT) to achieve the maximum biomass content in a bioreactor was different for each individual nitrogen source used. The experimental results showed that using nitrate as the only nitrogen source was the most favorable for biomass growth. With ammonia and nitrate coexisting in the aquatic phase, Chlorella possibly utilized ammonia first, and this was unfavorable to subsequent biomass growth. Nitrifying bacteria in wastewaters significantly affected Chlorella growth as they possibly competed with Chlorella in assimilating ammonia and nitrate in domestic wastewater. In a submerged ultrafiltration (UF) membrane module, with an initial concentration of 850 mg/L of Chlorella, the optimized flux was 0.02 m(3)/(m(2)·h), and the filtration cycle was 30 min. A dual membrane bioreactor (MBR) configuration using UF membranes for Chlorella incubation was proposed. MBR1 provides an environment with long MCRT for efficient nitrification. The converted nitrate is assimilated by Chlorella in MBR2 to sustain its growth. UF permeate from MBR1 is bacteria-free and does not affect the growth of Chlorella in MBR2. MCRT of Chlorella growth is controlled by the UF membrane of MBR2, providing the flexibility to adjust variations of nitrogen composition in the wastewater.
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Optimization of pulse-field gel electrophoresis for Borrelia burgdorferi subtyping.
Biomed. Environ. Sci.
PUBLISHED: 07-31-2013
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To optimize the performance of Pulsed-Field Gel Electrophoresis (PFGE) for the comparison of inter-laboratory results and information exchange of Borrelia burgdorferi subtyping.
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Three-dimensional mapping of evolving internal waves during the Shallow Water 2006 experiment.
J. Acoust. Soc. Am.
PUBLISHED: 07-19-2013
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Detailed knowledge of sound speed profiles and the sound speed profiles spatial and temporal variability resulting from internal waves (IWs) are indispensable to investigating significant acoustic field fluctuations in shallow water. A strategy to obtain a time-varying, three-dimensional (3D) IW temperature field is presented. It uses two types of simultaneous measurements: dense observations from a farm of thermistor strings and IW surface expressions from a ship-based radar. Using data from the Shallow Water 2006 experiment, the temperature field, over multiple kilometers in range, was reconstructed and, fed to a 3D acoustic model to demonstrate IW impacts on acoustic propagation.
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[Effect of zinc ion on polymerization and cytotoxicity of sTRAIL in tumor cells].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-18-2013
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Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is potentially a novel anti-cancer drug due to its superior selective cytotoxicity in a wide variety of tumor cells. Zinc ion (Zn2+) insufficiency might be an important cause for weak cytotoxicity of sTRAIL prepared by gene engineering. In this paper, the sTRAIL protein is highly-expressed with insertion of the synthesized gene encoding sTRAIL into pQE30 plasmid. The polymerization and cytotoxicity in tumor cells of sTRAIL prepared in presence of different concentrations of Zinc ions were compared. It was found that the sTRAIL protein prepared in absence of Zinc ions mainly existed as monomer with weak cytotoxicity. However, in the presence of Zinc ions, sTRAIL formed homotrimer and showed strong cytotoxicity in tumor cells. These results demonstrate that Zinc ion is very important for cytotoxicity of sTRAIL. It is necessary for keeping stable activity of sTRAIL by addition of proper concentration of Zinc ion in the media.
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MicroRNA-22 downregulation by atorvastatin in a mouse model of cardiac hypertrophy: a new mechanism for antihypertrophic intervention.
Cell. Physiol. Biochem.
PUBLISHED: 06-10-2013
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Growing evidence shows that microRNAs (miRNAs) are involved in various cardiac processes including cardiac hypertrophy. However, the modulation of miRNA by pharmacological intervention in cardiomyocyte hypertrophy has not been disclosed yet. methods: We constructed neonatal rat cardiomyocyte hypertrophy induced by angiotensin II stimulation and subjected to cardiomyocyte immunochemistry, qRT-PCR and immunoblotting analysis. In addition, we constructed the mouse cardiac hypertrophy using angomir-22 stimulation and demonstrated the potential antihypertrophic mechnism of atorvastatin.
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Identification and cloning of the second type transglutaminase from Litopenaeus vannamei, and its transcription following pathogen infection and in relation to the haemolymph coagulation.
Fish Shellfish Immunol.
PUBLISHED: 06-06-2013
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Complementary (c)DNA encoding transglutaminaseII (TGII) messenger (m)RNA of white shrimp, Litopenaeus vannamei, was cloned from haemocytes by a reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) using oligonucleotide primers based on the TG sequence of the horseshoe crab, Tachypleus tridentatus (accession no.: BAA02134), tiger shrimp, Penaeus monodon (AAV49005; AAO33455), kuruma shrimp, Marsupenaeus japonicus (BAD36808) and Pacifastacus leniusculus (AAK69205) TG. The 2405-bp cDNA contained an open reading frame (ORF) of 2292 bp, a 31-bp 5-untranslated region (UTR), and an 82-bp 3-UTR containing a poly A tail. The molecular mass of the deduced amino acid (aa) sequence (764 aa) was 85.9 kDa with an estimated pI of 5.32. The L. vannamei TGII (abbreviated LvTGII) contains a typical TG-like homologue, two putative integrin binding motif (RGD and KGD), and five calcium-binding sites; three catalytic triad is present as in arthropod TG. Sequence comparison and phylogenetic analysis revealed that shrimp TG can be separated into two groups, STGI and STGII, and LvTGII is more closely related to STGII than to STGI. LvTGII mRNA was detected in all tested tissues of L. vannamei, and was highly expressed in haemocytes. The haemocytes of L. vannamei injected with Vibrio alginolyticus showed a significant increase of LvTGI and LvTGII mRNA expression at 6 h followed by a notable decrease at 24 h in LvTGI and a continually increase in LvTGII indicating a complementary effect, which implied that both LvTGs involved in the immune response of shrimp, and LvTGII was more important in the later defense response. The gene silencing of LvTGII in shrimp significantly decreased LvTGII expression and TG activity of haemocytes, and significantly increased clotting time of haemolymph, suggests that the cloned LvTGII is a clotting enzyme involved in haemolymph coagulation of L. vannamei. In conclusion, the cloned LvTGII is a clotting enzyme involved in coagulation of haemolymp and immune response of white shrimp, L. vannamei.
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Knockdown of mTOR by lentivirus?mediated RNA interference suppresses atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy in apolipoprotein E?deficient mice.
Int. J. Mol. Med.
PUBLISHED: 06-04-2013
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Atherosclerotic plaque destabilization and rupture leads to acute coronary syndromes which cause serious damage to human health worldwide. However, there is currently a lack of efficient therapeutic methods. Mammalian target of rapamycin (mTOR) has been suggested to be involved in the development of atherosclerotic plaques and serves as a therapeutic target. The present study was performed to determine whether RNA interference (RNAi) of mTOR in vivo by LV?mediated small hairpin RNA (shRNA) was capable of inhibiting the progression of atherosclerotic plaques. LV?mediated shRNA against mTOR (LV?shmTOR) was designed and obtained. Male apolipoprotein E?deficient mice were fed a high?fat diet and a constrictive collar was placed around the right carotid arteries of these mice to induce plaque formation. Eight weeks after surgery, mice were randomly divided into the mTOR RNA interference (LV?shmTOR) group, receiving treatment with LV?mTOR?shRNA; the LV?shCON group, receiving treatment with LV?non?specific?shRNA; and the control group, receiving treatment with phosphate?buffered saline. Following transfection, the mice were sacrificed to evaluate the effects of mTOR expression silencing on atherosclerosis. Transfection of LV?mTOR?shRNA markedly inhibited the mRNA and protein expression levels. Knockdown of mTOR ameliorated dysregulated blood lipid metabolism and stabilized aortic atherosclerotic plaques by decreasing the plaque area and increasing the fibrous cap and cap?to?core ratio. Furthermore, macrophages were decreased by silencing mTOR in atherosclerotic plaques. In addition, western blot analysis revealed that the knockdown of mTOR increased autophagy?related protein 13 (Atg13) dephosphorylation and light chain 3?I/light chain 3?II (LC3?I/LC3?II) ratios, both of which were associated with a high activity of autophagy, suggesting an increase of autophagy in atherosclerotic plaques. Moreover, genes including matrix metalloproteinase 2, monocyte chemoattractant protein 1 and tissue factor, which promote plaque instability, were downregulated by silencing mTOR. These results demonstrate that LV?mediated mTOR silencing by RNAi treatment induces macrophage autophagy and is a potential strategy for the treatment of atherosclerotic plaques.
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Multicenter research on the BACTEC MGIT 960 system for the second-line drugs susceptibility testing of Mycobacterium tuberculosis in China.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 05-20-2013
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The reliability of the BACTEC MGIT 960 system for the second-line drugs (capreomycin [CPM], kanamycin [KAN], ofloxacin [OFX] and ethionamide [ETH]) susceptibility testing (DST) of Mycobacterium tuberculosis (M. tuberculosis) was compared to that of traditional Lowenstein-Jensen (L-J) proportion method (PM) among four different sites in China. After resolution of discrepant results by retesting the strains using both methods in the National Reference Laboratory of tuberculosis, the overall concordance values between the 2 systems were 99.7% (kappa value: 0.97) for CPM, 99.7% (kappa value: 0.97) for KAN, 100.0% (kappa value: 1.00) for OFX, and 98.6% (kappa value: 0.95) for ETH. The average turnaround time with BACTEC MGIT 960 system among four sites was 8.9 ± 1.7 days, significantly shorter than 28 days with the traditional L-J PM. Therefore, the BACTEC MGIT 960 system is a reliable and rapid method for the second-line drug susceptibility testing of tuberculosis in China. Notably, a stricter quality control program should be routinely carried out when clinical laboratories perform the second-line DST with BACTEC MGIT 960 system.
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[Expressions of SIgA and alpha 1-AR in benign prostatic hyperplasia combined with chronic prostatitis and their implications].
Zhonghua Nan Ke Xue
PUBLISHED: 05-18-2013
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To explore the expressions of SIgA and alpha l-AR in benign prostatic hyperplasia (BPH) complicated by chronic prostatitis (CP) and their implications.
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[Effects of qishenyiqi gutta pills on calcium/calmodulin dependent protein kinase II in rats with renal hypertension].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-11-2013
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To explore the effects of qishenyiqi gutta pills on myocardial hypertrophy of left ventricle and calcium/calmodulin dependent protein kinase II (CAMK II) in rats with renal hypertension and elucidate its intervention mechanism for myocardial hypertrophy.
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Haplotype kernel association test as a powerful method to identify chromosomal regions harboring uncommon causal variants.
Genet. Epidemiol.
PUBLISHED: 05-01-2013
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For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called "rare variants" (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the "missing heritability" because very few people may carry these rare variants. The genetic variants that are likely to fill in the "missing heritability" include uncommon causal variants (MAF < 5%), which are generally untyped in association studies using tagging single-nucleotide polymorphisms (SNPs) or commercial SNP arrays. Developing powerful statistical methods can help to identify chromosomal regions harboring uncommon causal variants, while bypassing the genome-wide or exome-wide next-generation sequencing. In this work, we propose a haplotype kernel association test (HKAT) that is equivalent to testing the variance component of random effects for distinct haplotypes. With an appropriate weighting scheme given to haplotypes, we can further enhance the ability of HKAT to detect uncommon causal variants. With scenarios simulated according to the population genetics theory, HKAT is shown to be a powerful method for detecting chromosomal regions harboring uncommon causal variants.
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EGFR-driven up-regulation of decoy receptor 3 in keratinocytes contributes to the pathogenesis of psoriasis.
Biochim. Biophys. Acta
PUBLISHED: 03-20-2013
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Decoy receptor 3 (DcR3) is a soluble receptor of Fas ligand (FasL), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A) and plays pleiotropic roles in many inflammatory and autoimmune disorders and malignant diseases. In cutaneous biology, DcR3 is expressed in primary human epidermal keratinocytes and is upregulated in skin lesions in psoriasis, which is characterized by chronic inflammation and angiogenesis. However, the regulatory mechanisms of DcR3 over-expression in skin lesions of psoriasis are unknown. Here, we demonstrate that DcR3 can be detected in both dermal blood vessels and epidermal layers of psoriatic skin lesions. Analysis of serum samples showed that DcR3 was elevated, but FasL was downregulated in psoriatic patients compared with normal individuals. Additional cell studies revealed a central role of epidermal growth factor receptor (EGFR) in controlling the basal expression of DcR3 in keratinocytes. Activation of EGFR by epidermal growth factor (EGF) and transforming growth factor (TGF)-? strikingly upregulated DcR3 production. TNF-??enhanced DcR3 expression in both keratinocytes and endothelial cells compared with various inflammatory cytokines involved in psoriasis. Additionally, TNF-?-enhanced DcR3 expression in keratinocytes was inhibited when EGFR was knocked down or EGFR inhibitor was used. The NF-?B pathway was critically involved in the molecular mechanisms underlying the action of EGFR and inflammatory cytokines. Collectively, the novel regulatory mechanisms of DcR3 expression in psoriasis, particularly in keratinocytes and endothelial cells, provides new insight into the pathogenesis of psoriasis and may also contribute to the understanding of other diseases that involve DcR3 overexpression.
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The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish.
Water Res.
PUBLISHED: 03-19-2013
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Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly being used for enhanced treatment of water or wastewater processes; however, the fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear. We investigated bioaccumulation and lethal-to-sublethal toxic effects on early life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25-200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)-stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and developmental toxic effects in embryos, with lesser and the least effects with Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity in the oxygenic solution, which led to a combination of hypoxia and production of reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI. The antioxidant balance was differentially altered by induced intracellular ROS in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI and its oxidized products in early life stages of medaka fish using different organizational levels of biomarker assays. The toxicity results implicate a potential eco-toxicological impact of nZVI on the aquatic environment.
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Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma.
Int. J. Radiat. Biol.
PUBLISHED: 02-27-2013
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Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of radioimmunotherapy against Her2 in prostate cancer were investigated.
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A study of the technique of western blot for diagnosis of lyme disease caused by Borrelia afzelii in China.
Biomed. Environ. Sci.
PUBLISHED: 02-22-2013
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To study the technique of Western blot for the diagnosis of Lyme disease caused by Borrelia afzelii in China and to establish the standard criteria by operational procedure.
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Seroepidemiological investigation of lyme disease and human granulocytic anaplasmosis among people living in forest areas of eight provinces in China.
Biomed. Environ. Sci.
PUBLISHED: 02-22-2013
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Lyme disease and Human granulocytic anaplasmosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum respectively. We have investigated infection and co-infection of the two diseases in the population of forest areas of eight provinces in China by measuring seroprevalence of antibodies against B. burgdorferi and A. phagocytophilum.
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Hepatoprotective Effects of Swimming Exercise against D-Galactose-Induced Senescence Rat Model.
Evid Based Complement Alternat Med
PUBLISHED: 02-18-2013
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This study investigates whether a 12-week swimming exercise training can prevent liver damage or senescence associated biomarkers in an experimental aging model in rats. Twenty-three male Sprague-Dawley rats were divided into four groups: vehicle treatment with sedentary control (C, n = 6), aging induction with sedentary (A, n = 6), vehicle treatment with swimming exercise (SW, n = 5), and aging induction with swimming exercise (A + SW, n = 6). Rats in groups A and AS received intraperitoneal d-galactose injections (150?mg/kg/day) for 12 weeks to induce aging. Rats in groups SW and A + SW were subjected to swimming exercise training for 12 weeks. Body weight, liver weight, epididymal fat mass, blood biochemistry, and liver pathology were performed at the end of the experiment. Hepatic senescence protein markers such as ?-galactosidase, p53, and p21, as well as the inflammatory mediator, IL-6, were examined. The d-galactose-treated rats exhibited increases in AST and ? -GT plasma levels and ?-galactosidase protein expression compared to the control group. Swimming exercise significantly reduced BW, epididymal fat mass, ? -GT activity, and p53, p21, and IL-6 protein levels compared to the aging group. These results suggest that a 12-week swimming exercise program suppresses senescence markers and downregulates inflammatory mediator in the liver tissues of d-galactose-induced aging rats.
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A mass resulting from cerebral spinal fluid collection of ventriculopleural shunt: radiographic and radionuclide findings.
Clin Nucl Med
PUBLISHED: 02-16-2013
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A 49-year-old man was brought to our hospital because of lethargy. His medical history was hydrocephalus with ventriculoperitoneal shunt initially. The ventriculoperitoneal shunt was replaced several times owing to malfunction, and it was later replaced with a right-sided ventriculopleural shunt. The chest radiograph revealed a mass at the right lung. The mass was a capsular collection of cerebral spinal fluid (CSF) in the right pleural cavity diagnosed based on radionuclide shuntogram findings.
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Use of FDG-PET or PET/CT to detect recurrent colorectal cancer in patients with elevated CEA: a systematic review and meta-analysis.
Int J Colorectal Dis
PUBLISHED: 02-02-2013
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The purpose of the present study was to conduct a systematic review and meta-analysis of the published literature to assess the diagnostic performance of FDG-PET or PET/CT in the detection of recurrent colorectal cancer (CRC) rising in patients with elevated CEA.
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Ganoderma tsugae hepatoprotection against exhaustive exercise-induced liver injury in rats.
Molecules
PUBLISHED: 01-24-2013
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Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E), exhaustive exercise with low dosage (EL), medium dosage (EM) and high dosage (EH) GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.
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Association between the endothelial nitric oxide synthase gene Glu298Asp polymorphism and coronary heart disease: a meta?analysis of 39 case?control studies.
Mol Med Rep
PUBLISHED: 01-23-2013
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Numerous studies have indicated that the human endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism is associated with coronary heart disease (CHD) susceptibility, however, their conclusions are inconsistent. The present meta?analysis aimed to evaluate the precise result by searching the PubMed database and using 39 case?control studies comprising 7489 cases and 7051 controls.Each study tested the association between the eNOS Glu298Asp polymorphism and CHD. A meta?analysis was then conducted using the Comprehensive Meta Analysis 2.2 software to calculate the pooled odds ratios (ORs) of five genetic models with 95% confidence intervals (CIs). Publication bias was also explored. The meta?analysis showed a significant association between the eNOS Glu298Asp polymorphism and CHD susceptibility for all the genetic models [Asp vs. Glu, OR 1.26, 95% CI 1.14?1.40, P<0.001; Asp/Asp vs. Glu/Glu, OR 1.58, 95% CI 1.23?2.02, P<0.001; Glu/Asp vs. Glu/Glu, OR 1.12, 95% CI 1.03?1.22, P=0.001; (Glu/Asp+Asp/Asp) vs. Glu/Glu, OR 1.17, 95% CI 1.07?1.27, P<0.001; Asp/Asp vs. (Glu/Glu+Glu/Asp), OR 1.59, 95% CI 1.25?2.03, P<0.001]. Subgroup and sensitivity analyses indicated that the result was robust. A weak publication bias was detected. The results indicated that the eNOS Glu298Asp polymorphism is a risk factor for developing CHD, particularly in the Asian population.
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A comparison of Re-188-MN-16ET-lipiodol and transcatheter arterial chemoembolization in the treatment of hepatoma: an animal study.
Nucl. Med. Biol.
PUBLISHED: 01-23-2013
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In patients with unresectable HCC, transcatheter arterial chemoembolization (TACE) is a widely used treatment. Recently, as an alternative treatment modality for HCC, transcatheter arterial embolization with radioisotopes has been investigated. In this study, we compared the therapeutic efficacy of an intra-hepatic arterial injection of Re-188-MN-16ET-lipiodol and the TACE method in rats with liver tumors.
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Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting peptide in tumor cells.
PLoS ONE
PUBLISHED: 01-21-2013
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Tumor-homing peptides that recognize specific markers on tumor cells have shown potential as drug carriers for targeted cancer therapy. Bombesin receptors are frequently overexpressed or ectopically expressed in a wide range of human tumors. Bombesin and its analogues have been widely used as drug carriers for tumor imaging and tumor therapy. However, the cargos used in previous studies, including radioactive and chemotherapeutic agents, are usually small molecules. Mitochondrial-disrupting peptides depolarize the mitochondria and trigger apoptosis after entering tumor cells. We are interested in whether the bombesin analogue, Bn(6-14), which contains a bombesin receptor-binding motif, can specifically deliver the mitochondria-disrupting peptide, B28, to tumor cells. To this end, we created a chimeric peptide, B28Bn(6-14), by conjugating B28 to Bn(6-14) at its N-terminus. The cytotoxicity of B28Bn(6-14) in tumor cells was much stronger than unconjugated B28. The IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) were approximately 10 times lower than B28. However, conjugation of B28 to Bn(2-7), which lacks the bombesin receptor-binding motif, did not increase its cytotoxicity. In addition, the IC50 values of B28Bn(6-14) in tumor cells (1.7-3.5 µM) was 3-10 times lower than in normal cells (10.8-16.8 µM). We found that selective binding of B28Bn(6-14) to tumor cells is Bn(6-14)-dependent. Upon entering the tumor cell, B28Bn(6-14) accumulated in the mitochondria and triggered caspase-dependent apoptosis. Intratumoral and intraperitoneal administration of B28Bn(6-14) substantially suppressed the growth of DU145 tumor xenografts in mice. These results demonstrate that Bn(6-14) is able to deliver the mitochondria-disrupting peptide to tumor cells, and B28Bn(6-14) should be further developed as novel anti-cancer agent.
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Production and characterization of human soluble CD83 fused with the fragment crystallizable region of human IgG1 in Pichia pastoris.
Appl. Microbiol. Biotechnol.
PUBLISHED: 01-19-2013
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The cell surface protein CD83 belongs to the immunoglobulin superfamily and is highly expressed on mature dendritic cells. The soluble form of CD83, sCD83, is a potential immune suppressor. In a previous study, recombinant soluble CD83 was expressed in Escherichia coli, resulting in a lack of functional glycosylation. Although eukaryotic cell systems for producing sCD83 offer the advantages of protein processing, folding, and posttranslational modification, these systems are complicated, expensive, and produce low levels of protein. To obtain more efficient expression of sCD83, we expressed human sCD83 fused with fragment crystallizable region of human IgG1 (hIgG1 Fc) in Pichia pastoris. Under the optimal conditions (time of induction, 48 h; inoculum density (OD600), 80; concentration of methanol, 3.0 %; pH 7.0-8.0; concentration of casamino acid, 5.0 %), the purified human sCD83-hIgG1 Fc (hsCD83-Ig) fusion protein existed as dimers at 25-30 mg/L culture. Treatment with PNGase F showed that purified hsCD83-Ig was modified by N-linked glycosylation. Moreover, the hsCD83-Ig expressed in the P. pastoris system could suppress lymphocyte proliferation in ConA-stimulated and one-way mixed lymphocyte reaction systems. Thus, hsCD83-Ig expressed in P. pastoris is functional and may be used in experimental therapies for graft rejection, graft-versus-host disease, and autoimmune diseases.
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Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase.
Biochim. Biophys. Acta
PUBLISHED: 01-18-2013
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The Warburg effect is known to be crucial for cancer cells to acquire energy. Nutrient deficiencies are an important phenomenon in solid tumors, but the effect on cancer cell metabolism is not yet clear. In this study, we demonstrate that starvation of HeLa cells by incubation with Hanks buffered salt solution (HBSS) induced cell apoptosis, which was accompanied by the induction of reactive oxygen species (ROS) production and AMP-activated protein kinase (AMPK) phosphorylation. Notably, HBSS starvation increased lactate production, cytoplasmic pyruvate content and decreased oxygen consumption, but failed to change the lactate dehydrogenase (LDH) activity or the glucose uptake. We found that HBSS starvation rapidly induced pyruvate dehydrogenase kinase (PDK) activation and pyruvate dehydrogenase (PDH) phosphorylation, both of which were inhibited by compound C (an AMPK inhibitor), NAC (a ROS scavenger), and the dominant negative mutant of AMPK. Our data further revealed the involvement of ROS production in AMPK activation. Moreover, DCA (a PDK inhibitor), NAC, and compound C all significantly decreased HBSS starvation-induced lactate production accompanied by enhancement of HBSS starvation-induced cell apoptosis. Not only in HeLa cells, HBSS-induced lactate production and PDH phosphorylation were also observed in CL1.5, A431 and human umbilical vein endothelial cells. Taken together, we for the first time demonstrated that a low-nutrient condition drives cancer cells to utilize glycolysis to produce ATP, and this increases the Warburg effect through a novel mechanism involving ROS/AMPK-dependent activation of PDK. Such an event contributes to protecting cells from apoptosis upon nutrient deprivation.
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18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma.
Clin Imaging
PUBLISHED: 01-16-2013
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We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC).
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Novel Species Including Mycobacterium fukienense sp. Is Found from Tuberculosis Patients in Fujian Province, China, Using Phylogenetic Analysis of Mycobacterium chelonae/abscessus Complex.
Biomed. Environ. Sci.
PUBLISHED: 01-14-2013
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To identify the novel species Mycobacterium fukienense sp. nov of Mycobacterium chelonae/abscessus complex from tuberculosis patients in Fujian Province, China.
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Propyl gallate inhibits TPA-induced inflammation via the nuclear factor-?B pathway in human THP-1 monocytes.
Exp Ther Med
PUBLISHED: 01-10-2013
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Propyl gallate (PG) is an antioxidant that has been used as an additive in several foods to protect against oxidation. The present study examined the anti-inflammatory effect of PG on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in human THP-1 monocytes. Pretreatment with PG markedly inhibited the TPA-induced expression levels of cyclooxygenase-2 and prostaglandin E2. The application of PG significantly inhibited the nuclear translocation of p65, a subunit of nuclear factor-?B (NF-?B) and phosphorylation of p65 (Ser536) in TPA-treated THP-1 cells. PG also inhibited the phosphorylation of I?B and I?B kinase. These results indicate that PG inhibits the inflammatory response by blocking the NF-?B signaling pathway in TPA-induced THP-1 monocytes. Therefore, PG may be useful as a therapeutic agent in inflammatory diseases.
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Therapeutic efficacy of 188Re-MN-16ET lipiodol in an animal model of hepatocellular carcinoma.
Ann Nucl Med
PUBLISHED: 01-09-2013
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In our recent study, we developed a new radiopharmaceutical (Re-188 MN-16ET lipiodol) with encouraging results for the treatment of liver malignancy. In this study, we further evaluated the therapeutic efficacy of this radiopharmaceutical by measuring tumor response and survival times in rats with liver tumors after intra-hepatic arterial injection of Re-188 MN-16ET lipiodol.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.