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Find video protocols related to scientific articles indexed in Pubmed.
Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells.
Oncotarget
PUBLISHED: 11-06-2014
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Resistin is a recently discovered adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. Chondrosarcoma is a highly malignant tumor known to frequently metastasize; however, the role of resistin in the metastasis of human chondrosarcoma is largely unknown. Here, we found that the expression of resistin was higher in chondrosarcoma biopsy tissues than in normal cartilage. Moreover, treatment with resistin increased matrix metalloproteinase (MMP)-2 expression and promoted cell migration in human chondrosarcoma cells. Co-transfection with microRNA (miR)-519d mimic resulted in reversed resistin-mediated cell migration and MMP-2 expression. Additionally, AMP-activated protein kinase (AMPK) and p38 inhibitors or siRNAs reduced the resistin-increased cell migration and miR-519d suppression, and inhibition of resistin expression resulted in suppression of MMP-2 expression and lung metastasis in vivo. Taken together, our results indicate that resistin promotes chondrosarcoma metastasis and MMP-2 expression through activation of the AMPK/p38 signaling pathway and down-regulation of miR-519d expression. Therefore, resistin may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.
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Genetic Analysis of a Novel Tubulin Mutation That Redirects Synaptic Vesicle Targeting and Causes Neurite Degeneration in C. elegans.
PLoS Genet.
PUBLISHED: 11-01-2014
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Neuronal cargos are differentially targeted to either axons or dendrites, and this polarized cargo targeting critically depends on the interaction between microtubules and molecular motors. From a forward mutagenesis screen, we identified a gain-of-function mutation in the C. elegans ?-tubulin gene mec-12 that triggered synaptic vesicle mistargeting, neurite swelling and neurodegeneration in the touch receptor neurons. This missense mutation replaced an absolutely conserved glycine in the H12 helix with glutamic acid, resulting in increased negative charges at the C-terminus of ?-tubulin. Synaptic vesicle mistargeting in the mutant neurons was suppressed by reducing dynein function, suggesting that aberrantly high dynein activity mistargeted synaptic vesicles. We demonstrated that dynein showed preference towards binding mutant microtubules over wild-type in microtubule sedimentation assay. By contrast, neurite swelling and neurodegeneration were independent of dynein and could be ameliorated by genetic paralysis of the animal. This suggests that mutant microtubules render the neurons susceptible to recurrent mechanical stress induced by muscle activity, which is consistent with the observation that microtubule network was disorganized under electron microscopy. Our work provides insights into how microtubule-dynein interaction instructs synaptic vesicle targeting and the importance of microtubule in the maintenance of neuronal structures against constant mechanical stress.
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RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-30-2014
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Neurons remodel their connectivity in response to various insults, including microtubule disruption. How neurons sense microtubule disassembly and mount remodeling responses by altering genetic programs in the soma are not well defined. Here we show that in response to microtubule disassembly, the Caenorhabditis elegans PLM neuron remodels by retracting its synaptic branch and overextending the primary neurite. This remodeling required RHGF-1, a PDZ-Rho guanine nucleotide exchange factor (PDZ-RhoGEF) that was associated with and inhibited by microtubules. Independent of the myosin light chain activation, RHGF-1 acted through Rho-dependent kinase LET-502/ROCK and activated a conserved, retrograde DLK-1 MAPK (DLK-1/dual leucine zipper kinase) pathway, which triggered synaptic branch retraction and overgrowth of the PLM neurite in a dose-dependent manner. Our data represent a neuronal remodeling paradigm during development that reshapes the neural circuit by the coordinated removal of the dysfunctional synaptic branch compartment and compensatory extension of the primary neurite.
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Gold-catalyzed carboalkoxylations of 2-ethynylbenzyl ethers to form 1- and 3-substituted 2-methoxy-1-H-indenes: Brønsted acids versus gold catalysis.
Org. Biomol. Chem.
PUBLISHED: 10-30-2014
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Selective synthesis of 1- and 3-substituted 2-methoxyindenes from the carboalkoxylations of 2-ethynylbenzyl ethers is described; the former is obtained efficiently with P(t-Bu)2(o-biphenyl)AuCl/NaBARF in DCM/MS 4 Å whereas the latter is produced preferably with P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 in pre-dried DCM. Both 1- and 3-substituted 2-indenyl ethers are subjected to ozone oxidations to afford two distinct carbonyl products. Our new data indicate that 1-substituted 2-indenyl ethers are generated from gold catalysts whereas their 3-substituted analogues arise from Brønsted acids.
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The chemokine (CCL2-CCR2) signaling axis mediates perineural invasion.
Mol. Cancer Res.
PUBLISHED: 10-15-2014
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Perineural invasion (PNI) is a form of cancer progression where cancer cells invade along nerves. This behavior is associated with poor clinical outcomes; therefore, it is critical to identify novel ligand-receptor interactions between nerves and cancer cells that support the process of PNI. A proteomic profiler chemokine array was used to screen for nerve-derived factors secreted from tissue explants of dorsal root ganglion (DRG), and CCL2 was identified as a lead candidate. Prostate cancer cell line expression of CCR2, the receptor to CCL2, correlated closely with MAPK and Akt pathway activity and cell migration towards CCL2 and DRG. In vitro nerve and cancer co-culture invasion assays of PNI demonstrated that cancer cell CCR2 expression facilitates PNI. PNI is significantly diminished in co-culture assays when using DRG harvested from CCL2-/- knockout mice as compared with control CCL2+/+ mice, indicating that CCR2 is required for PNI in this murine model of PNI. Furthermore, 20/21 (95%) of patient specimens of prostate adenocarcinoma with PNI exhibited CCR2 expression by immunohistochemistry, while just 3/13 (23%) lacking PNI expressed CCR2. In summary, nerve-released CCL2 supports prostate cancer migration and PNI though CCR2-mediated signaling. Implications: These results reveal CCL2-CCR2 signaling as a key ligand-receptor mechanism that mediates cancer cell communication with nerves during PNI and highlight a potential future therapeutic target.
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CCN1 induces oncostatin M production in osteoblasts via integrin-dependent signal pathways.
PLoS ONE
PUBLISHED: 09-04-2014
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Inflammatory response and articular destruction are common symptoms of osteoarthritis. Cysteine-rich 61 (CCN1 or Cyr61), a secreted protein from the CCN family, is associated with the extracellular matrix involved in many cellular activities like growth and differentiation. Yet the mechanism of CCN1 interacting with arthritic inflammatory response is unclear. This study finds CCN1 increasing expression of oncostatin m (OSM) in human osteoblastic cells. Pretreatment of ?v?3 monoclonal antibody and inhibitors of focal adhesion kinase (FAK), c-Src, phosphatidylinositol 3-kinase (PI3K), and NF-?B inhibited CCN1-induced OSM expression in osteoblastic cells. Stimulation of cells with CCN1 increased phosphorylation of FAK, c-Src, PI3K, and NF-?B via ?v?3 receptor; CCN1 treatment of osteoblasts increased NF-?B-luciferase activity and p65 binding to NF-?B element on OSM promoter. Results indicate CCN1 heightening OSM expression via ?v?3 receptor, FAK, c-Src, PI3K, and NF-?B signal pathway in osteoblastic cells, suggesting CCN1 as a novel target in arthritis treatment.
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[Microbial diversity and ammonia-oxidizing microorganism of a soil sample near an acid mine drainage lake].
Huan Jing Ke Xue
PUBLISHED: 08-28-2014
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The main physicochemical parameters of the soil sample which was collected near an acid mine drainage reservoir in Anhui province was analyzed. The microbial diversity and community structure was studied through the construction of bacteria and archaea 16S rRNA gene clone libraries and ammonia monooxygenase gene clone library of archaea. The functional groups which were responsible for the process of ammonia oxidation were also discussed. The results indicated that the soil sample had extreme low pH value (pH < 3) and high ions concentration, which was influenced by the acid mine drainage (AMD). All the 16S rRNA gene sequences of bacteria clone library fell into 11 phyla, and Acidobacteria played the most significant role in the ecosystem followed by Verrucomicrobia. A great number of acidophilic bacteria existed in the soil sample, such as Candidatus Koribacter versatilis and Holophaga sp.. The archaea clone library consisted of 2 phyla (Thaumarchaeota and Euryarchaeota). The abundance of Thaumarchaeota was remarkably higher than Euryarchaeota. The ammonia oxidation in the soil environment was probably driven by ammonia-oxidizing archaea, and new species of ammonia-oxidizing archaea existed in the soil sample.
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Impact of RNA-Guided Technologies for Target Identification and Deconvolution.
J Biomol Screen
PUBLISHED: 08-27-2014
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For well over a decade, RNA interference (RNAi) has provided a powerful tool for investigators to query specific gene targets in an easily modulated loss-of-function setting, both in vitro and in vivo. Hundreds of publications have demonstrated the utility of RNAi in arrayed and pooled-based formats, in a wide variety of cell-based systems, including clonal, stem, transformed, and primary cells. Over the years, there have been significant improvements in the design of target-specific small-interfering RNA (siRNA) and short-hairpin RNA (shRNA), expression vectors, methods for mitigating off-target effects, and accurately interpreting screening results. Recent developments in RNAi technology include the Sensor assay, high-efficiency miR-E shRNAs, improved shRNA virus production with Pasha (DRGC8) knockdown, and assessment of RNAi off-target effects by using the C9-11 method. An exciting addition to the arsenal of RNA-mediated gene modulation is the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas) system for genomic editing, allowing for gene functional knockout rather than knockdown.
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Global disulfide bond profiling for crude snake venom using dimethyl labeling coupled with mass spectrometry and RADAR algorithm.
Anal. Chem.
PUBLISHED: 08-20-2014
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Snake venom consists of toxin proteins with multiple disulfide linkages to generate unique structures and biological functions. Determination of these cysteine connections usually requires the purification of each protein followed by structural analysis. In this study, dimethyl labeling coupled with LC-MS/MS and RADAR algorithm was developed to identify the disulfide bonds in crude snake venom. Without any protein separation, the disulfide linkages of several cytotoxins and PLA2 could be solved, including more than 20 disulfide bonds. The results show that this method is capable of analyzing protein mixture. In addition, the approach was also used to compare native cytotoxin 3 (CTX III) and its scrambled isomer, another category of protein mixture, for unknown disulfide bonds. Two disulfide-linked peptides were observed in the native CTX III, and 10 in its scrambled form, X-CTX III. This is the first study that reports a platform for the global cysteine connection analysis on a protein mixture. The proposed method is simple and automatic, offering an efficient tool for structural and functional studies of venom proteins.
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CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma.
Genes Dev.
PUBLISHED: 08-17-2014
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One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC.
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Leptin induces oncostatin M production in osteoblasts by downregulating miR-93 through the Akt signaling pathway.
Int J Mol Sci
PUBLISHED: 08-04-2014
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Inflammatory response and articular destruction are common symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA). Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Yet, the mechanism of leptin interacting with the arthritic inflammatory response is unclear. This study finds that leptin increased expression of oncostatin M (OSM) in human osteoblasts in a concentration- and time-dependent manner. In addition, OBRl, but not OBRs receptor antisense oligonucleotide, abolished the leptin-mediated increase of OSM expression. On the other hand, leptin inhibited miR-93 expression; an miR-93 mimic reversed leptin-increased OSM expression. Stimulation of osteoblasts with leptin promoted Akt phosphorylation, while pretreatment of cells with Akt inhibitor or siRNA reversed leptin-inhibited miR-93 expression. Our results showed that leptin heightened OSM expression by downregulating miR-93 through the Akt signaling pathway in osteoblasts, suggesting leptin as a novel target in arthritis treatment.
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Actor and partner effects of perceived HIV stigma on social network components among people living with HIV/AIDS and their caregivers.
Glob Health Promot
PUBLISHED: 08-03-2014
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Few studies have investigated the relationship between HIV stigma and social network components at the dyadic level. The objective of this study was to examine the actor and partner effects of perceived HIV stigma by people living with HIV/AIDS (PLWHAs) and their caregivers on social network variables at the dyadic level.
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Executive function and endocrinological responses to acute resistance exercise.
Front Behav Neurosci
PUBLISHED: 08-01-2014
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First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to changes in arousal, possibly modulated by the serum cortisol levels.
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Predictive factors of silent reflux in subjects with erosive esophagitis.
Dig Liver Dis
PUBLISHED: 07-21-2014
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Asymptomatic erosive esophagitis by definition is a condition lacking any reflux symptom.
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Event-specific risk factors predicting episodes of unprotected anal intercourse with male nonregular partners among men who have sex with men using case-crossover study design.
Biomed Res Int
PUBLISHED: 07-20-2014
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This study investigated event-specific factors that determine episodes of unprotected and protected anal intercourse (UAI and PAI) among 215 men who have sex with men (MSM), who used condoms inconsistently with nonregular partners (NRP) in the last six months, in Hong Kong. A case-crossover study design was used. Lower likelihood of episodes involving UAI with NRP was associated with (1) five partner attributes (NRP were <35 years old, at least three previous anal sex experiences with the NRP, perception that participant and the NRP had asymmetrical sexual experience, perception that the NRP was feminine, and liking toward the NRP; OR?=?0.16-0.52), (2) six situational variables (the participant having had UAI with another man in the last week, having discussed condom use, perception that the NRP liked to use condom, partner's suggestion to have PAI, participant's suggestion to have PAI, and participant's plan to use condoms; OR?=?0.11-0.39), and (3) four environmental/setting variables (condoms already placed at the venue, display of condom use promotion materials, participant's possession of a condom, and the NRP possessed a condom; OR?=?0.27-0.45). HIV prevention targeting MSM should focus on event-specific protective factors, which may be different from those obtained from studies distinguishing condom users versus nonusers.
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Optimization of long-range order in solvent vapor annealed poly(styrene)-block-poly(lactide) thin films for nanolithography.
ACS Appl Mater Interfaces
PUBLISHED: 07-16-2014
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Detailed experiments designed to optimize and understand the solvent vapor annealing of cylinder-forming poly(styrene)-block-poly(lactide) thin films for nanolithographic applications are reported. By combining climate-controlled solvent vapor annealing (including in situ probes of solvent concentration) with comparative small-angle X-ray scattering studies of solvent-swollen bulk polymers of identical composition, it is concluded that a narrow window of optimal solvent concentration occurs just on the ordered side of the order-disorder transition. In this window, the lateral correlation length of the hexagonally close-packed ordering, the defect density, and the cylinder orientation are simultaneously optimized, resulting in single-crystal-like ordering over 10 ?m scales. The influences of polymer synthesis method, composition, molar mass, solvent vapor pressure, evaporation rate, and film thickness have all been assessed, confirming the generality of this behavior. Analogies to thermal annealing of elemental solids, in combination with an understanding of the effects of process parameters on annealing conditions, enable qualitative understanding of many of the key results and underscore the likely generality of the main conclusions. Pattern transfer via a Damascene-type approach verified the applicability for high-fidelity nanolithography, yielding large-area metal nanodot arrays with center-to-center spacing of 38 nm (diameter 19 nm). Finally, the predictive power of our findings was demonstrated by using small-angle X-ray scattering to predict optimal solvent annealing conditions for poly(styrene)-block-poly(lactide) films of low molar mass (18 kg mol(-1)). High-quality templates with cylinder center-to-center spacing of only 18 nm (diameter of 10 nm) were obtained. These comprehensive results have clear and important implications for optimization of pattern transfer templates and significantly advance the understanding of self-assembly in block copolymer thin films.
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Review of treatment assessment using DCE-MRI in breast cancer radiation therapy.
World J Methodol
PUBLISHED: 06-26-2014
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As a noninvasive functional imaging technique, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is being used in oncology to measure properties of tumor microvascular structure and permeability. Studies have shown that parameters derived from certain pharmacokinetic models can be used as imaging biomarkers for tumor treatment response. The use of DCE-MRI for quantitative and objective assessment of radiation therapy has been explored in a variety of methods and tumor types. However, due to the complexity in imaging technology and divergent outcomes from different pharmacokinetic approaches, the method of using DCE-MRI in treatment assessment has yet to be standardized, especially for breast cancer. This article reviews the basic principles of breast DCE-MRI and recent studies using DCE-MRI in treatment assessment. Technical and clinical considerations are emphasized with specific attention to assessment of radiation treatment response.
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Synthesis of short graphene oxide nanoribbons for improved biomarker detection of Parkinson's disease.
Biosens Bioelectron
PUBLISHED: 06-06-2014
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We demonstrate the microwave-assisted synthesis of short graphene oxide nanoribbons (GONRs) through unzipping cut multiwalled carbon nanotubes (MWCNTs). Transmission electron microscopy and dynamic light scattering spectroscopy were used to examine the length, size, and morphology, i. e. unzipping level, of our various products. The nanotube core and nanoribbon shell can be observed from short GONRs via a modified unzipping recipe. Then the short GONRs were adopted to modify the glassy carbon electrode for the electrochemical detection of ascorbic acid (AA), uric acid (UA), and dopamine (DA). Compared to other nanomaterials, cyclic voltammograms of short GONRs show higher anodic oxidation currents for AA, UA, and DA. The detection limits of three analytes are 26, 98, and 24nM, respectively, in amperometric current-time measurements. Especially, the sensitivity for DA is improved to be 40.86?A?M(-1)cm(-2). The improved detection signals are due to the increased active sites of the open ends of short GONRs. Moreover, the width side of short GONRs could be more active than their length side. All above-mentioned results reveal that the short GONRs can provide a novel platform for electrochemically biomarker detection of Parkinson's disease.
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A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 05-30-2014
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Vascular endothelial growth factor (VEGF) expression is higher in triple-negative breast cancers (TNBC) compared to other subtypes and is reported to predict incidence of distant metastases and shorter overall survival. We investigated the therapeutic impact of a vaccinia virus (VACV) GLV-1h164 (derived from its parent virus GLV-1h100), encoding a single-chain antibody (scAb) against VEGF (GLAF-2) in an orthotopic TNBC murine model. GLV-1h164 was tested against multiple TNBC cell lines. Viral infectivity, cytotoxicity, and replication were determined. Mammary fat pad tumors were generated in athymic nude mice using MDA-MB-231 cells. Xenografts were treated with GLV-1h164, GLV-1h100, or PBS and followed for tumor growth. Viral infectivity was time- and concentration-dependent. GLV-1h164 killed TNBC cell lines in a dose-dependent fashion with greater than 90 % cytotoxicity within 4 days at a multiplicity of infection of 5.0. In vitro, cytotoxicity of GLV-1h164 was identical to GLV-1h100. GLV-1h164 replicated efficiently in all cell lines with an over 400-fold increase in copy numbers from the initial viral dose within 4 days. In vivo, mean tumor volumes after 2 weeks of treatment were 73, 191, and 422 mm(3) (GLV-1h164, GLV-1h100, and PBS, respectively) (p < 0.05). Both in vivo Doppler ultrasonography and immuno-staining showed decreased neo-angiogenesis in GLV-1h164-treated tumors compared to both GLV-1h100 and PBS controls (p < 0.05). This is the first study to demonstrate efficient combination of oncolytic and anti-angiogenic activity of a novel VACV on TNBC xenografts. Our results suggest that GLV-1h164 is a promising therapeutic agent that warrants testing for patients with TNBC.
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The study of anthropometric estimates in the visceral fat of healthy individuals.
Nutr J
PUBLISHED: 05-14-2014
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Abdominal visceral fat affects the metabolic processes, and is an important risk factor for morbidity and mortality. The purpose of the study was to develop a quick and accurate estimate in the visceral fat area (VFA) of the L4-L5 vertebrae using anthropometric predictor variables that can be measured conveniently.
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Study on screening and antagonistic mechanisms of Bacillus amyloliquefaciens 54 against bacterial fruit blotch (BFB) caused by Acidovorax avenae subsp. citrulli.
Microbiol. Res.
PUBLISHED: 05-13-2014
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Bacterial fruit blotch (BFB) was a serious threat to cucurbitaceae crops. It was caused by the gram-negative bacterium Acidovorax avenae subsp. citrulli. Two hundred strains, which have the potential in controlling plant diseases in our laboratory's biocontrol strain library, were employed to this research to screen some antagonistic bacteria, which can efficiently control bacterial fruit blotch disease. Based on the results of antagonistic activity experiments, greenhouse tests and field trials, 5 of the test strains have high abilities to control BFB. One of the 5 bacteria strains has the highest potential to control BFB named 54. The biocontrol efficacy of 54 was up to 60%. To characterize the strain, we used series of methods to evaluate the bacterium, including morphology analysis, physiological biochemical test and biomolecular assay. We found that the bacterium 54 belongs to the species Bacillus amyloliquefaciens. The colonization test results showed that 54 had the highest colonization levels, and the density of the strain on leaves was up 10(5)colony forming units (CFU) per gram of leaf tissue. Our recent results show that B. amyloliquefaciens 54 can promote the plant growth due to raised the contents of available N, P, K and the leaf chlorophyll. The antagonistic bacterium 54 can significantly control the BF B by increasing the expression level of defense-related gene PR1 and the accumulation the hydrogen peroxide in the plant. The results of trail experiment was also verified this efficient results of bacterium. This is also the first report of B. amyloliquefaciens strain that is able to control BFB.
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GFR?1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-28-2014
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The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)?1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFR?1 released by nerves enhances PNI, even in the absence of cancer cell GFR?1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFR?1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFR?1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFR?1(+/-) mice compared with GFR?1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFR?1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFR?1 expression, suggesting an alternate source of GFR?1 in PNI. These findings collectively demonstrate that GFR?1 released by nerves enhances PNI through GDNF-RET signaling and that GFR?1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.
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Situation-specific factors predicting nonadherence to methadone maintenance treatment: a cross-sectional study using the case-crossover design in Guangzhou, China.
AIDS Care
PUBLISHED: 04-15-2014
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Methadone maintenance treatment (MMT) is a key risk reduction measure for controlling HIV transmission among drug users. Studies using traditional methods exist to distinguish between drop outs and nondrop outs. However, many nondrop outs use MMT discontinuously and no study has identified situation-specific factors predicting their showing or not showing up. This study used a case-crossover design comparing situation-specific factors appearing on the last episode of attendance versus those of the last episode of nonattendance. A total of 133 participants were recruited from two MMT clinics in Guangzhou, China. Participants were asked separately whether various situation-specific factors existed in the last episodes of nonattendance and attendance of MMT. Matched odds ratios (ORs) based on conditional logistic regression analysis were presented. The results showed that the participants attended the MMT clinics on average for 25 days in the last month. Situation-specific factors significantly predicting nonattendance included: (1) physical and mental health status: in illness (OR = 33.0, P < 0.001), in a bad mood (OR = 7.5, P < 0.001), and occurrence of an unhappy event (OR = 18.0, P < 0.001); (2) other engagement: work engagement (OR = 40.0, P < 0.001), trip to other places (OR = 83.0, P < 0.001), and social activities (OR = 10.0, P = 0.012); (3) interpersonal relationship: conflicts with family (OR = 19.0, P = 0.004); and (4) structural situational factors: financial difficulty (OR = 19.0, P = 0.004) and worrying about police arrest (OR = 12.0, P = 0.003). Other factors such as interaction with drug users and heroin use were marginally significant, while reduced methadone dosage was nonsignificant. Interventions to improve MMT adherence need to consider situation-specific factors. Ancillary psychosocial services should be integrated with current MMT; MMT should also provide more flexible services to the clients. Furthermore, efforts should be taken to build up interdisciplinary teams and to connect with MMT in order to provide holistic harm reduction, rehabilitation, and health care.
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Socio-ecological factors associated with depression, suicidal ideation and suicidal attempt among female injection drug users who are sex workers in China.
Drug Alcohol Depend
PUBLISHED: 04-14-2014
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Female injection drug users who are also sex workers (FSW-IDUs) occupy a pivotal population in HIV transmission, whereas their mental health problems are largely overlooked. We aimed to investigate prevalence and associated socio-ecological factors of depression, suicidal ideation and suicidal attempts among FSW-IDUs in China.
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Heterogeneous domain adaptation and classification by exploiting the correlation subspace.
IEEE Trans Image Process
PUBLISHED: 04-09-2014
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We present a novel domain adaptation approach for solving cross-domain pattern recognition problems, i.e., the data or features to be processed and recognized are collected from different domains of interest. Inspired by canonical correlation analysis (CCA), we utilize the derived correlation subspace as a joint representation for associating data across different domains, and we advance reduced kernel techniques for kernel CCA (KCCA) if nonlinear correlation subspace are desirable. Such techniques not only makes KCCA computationally more efficient, potential over-fitting problems can be alleviated as well. Instead of directly performing recognition in the derived CCA subspace (as prior CCA-based domain adaptation methods did), we advocate the exploitation of domain transfer ability in this subspace, in which each dimension has a unique capability in associating cross-domain data. In particular, we propose a novel support vector machine (SVM) with a correlation regularizer, named correlation-transfer SVM, which incorporates the domain adaptation ability into classifier design for cross-domain recognition. We show that our proposed domain adaptation and classification approach can be successfully applied to a variety of cross-domain recognition tasks such as cross-view action recognition, handwritten digit recognition with different features, and image-to-text or text-to-image classification. From our empirical results, we verify that our proposed method outperforms state-of-the-art domain adaptation approaches in terms of recognition performance.
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Epithelial-mesenchymal transition enhances response to oncolytic herpesviral therapy through nectin-1.
Hum. Gene Ther.
PUBLISHED: 04-02-2014
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Cancers exhibiting epithelial-mesenchymal transition (EMT) are associated with aggressive behavior and increased metastatic potential. Therapies that are able to target EMT would have significant clinical value. Nectin-1 is a cell surface herpes simplex virus type 1 (HSV-1) receptor that also forms a component of intercellular adherens junctions, which are typically disrupted in EMT. To explore relationships between HSV-1 sensitivity and EMT, we generated cell lines with a stable EMT phenotype from human follicular thyroid cancer (WRO82-1) through E-cadherin silencing with short hairpin RNA (shEcadWRO). HSV-1 viral attachment and gene expression were both enhanced in shEcadWRO as compared with shControl. Immunoblotting and immunostaining revealed enhanced nectin-1 expression by shEcadWRO. Receptor-blocking assays demonstrated that increased herpesviral entry into shEcadWRO as compared with shControl was mediated predominantly through nectin-1. Colocalization of green fluorescent protein-tagged HSV-1 and tdTomato-tagged nectin-1 confirmed an increase in viral attachment to nectin-1 in shEcadWRO. Cell viability assays demonstrated increased susceptibility of shEcadWRO to HSV-1 oncolysis, and a murine flank tumor model showed significantly enhanced regression of shEcadWRO tumors in response to oncolytic HSV-1 as compared with control tumors. A separate model of EMT induction through transforming growth factor-? stimulation confirmed enhanced HSV-1 susceptibility in Panc1 cells. These results demonstrate that the process of EMT leads to increased herpesviral susceptibility through enhanced cell surface nectin-1 expression, suggesting that cancers exhibiting EMT may be naturally sensitive targets for herpesviral therapy.
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Antioxidant effects of Genkwa flos flavonoids on Freund?s adjuvant-induced rheumatoid arthritis in rats.
J Ethnopharmacol
PUBLISHED: 03-17-2014
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Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV).
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Suppression of prolactin signaling by pyrrolidine dithiocarbamate is alleviated by N-acetylcysteine in mammary epithelial cells.
Eur. J. Pharmacol.
PUBLISHED: 02-28-2014
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Prolactin is the key hormone to stimulate milk synthesis in mammary epithelial cells. It signals through the Jak2-Stat5 pathway to induce the expression of ?-casein, a milk protein which is often used as a marker for mammary differentiation. Here we examined the effect of pyrrolidine dithiocarbamate (PDTC) on prolactin signaling. Our results show that PDTC downregulates prolactin receptor levels, and inhibits prolactin-induced Stat5 tyrosine phosphorylation and ?-casein expression. This is not due to its inhibitory action on NF-?B since application of another NF-?B inhibitor, BAY 11-7082, and overexpression of I-?B? super-repressor do not lead to the same results. Instead, the pro-oxidant activity of PDTC is involved as inclusion of the antioxidant N-acetylcysteine restores prolactin signaling. PDTC triggers great extents of activation of ERK and JNK in mammary epithelial cells. These do not cause suppression of prolactin signaling but confer serine phosphorylation of insulin receptor substrate-1, thereby perturbing insulin signal propagation. As insulin facilitates optimal ?-casein expression, blocking insulin signaling by PDTC might pose additional impediment to ?-casein expression. Our results thus imply that lactation will be compromised when the cellular redox balance is dysregulated, such as during mastitis.
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A silk-elastinlike protein polymer matrix for intraoperative delivery of an oncolytic vaccinia virus.
Head Neck
PUBLISHED: 02-19-2014
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Background: Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately following surgical resection. Methods: Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastinlike protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results: GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in PBS, and at one week retains a thousand fold greater infectious plaque forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and show increased viral ?-galactosidase expression as compared to PBS. Conclusions: The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. Head Neck, 2014.
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The role of quality of care and attitude towards disability in the relationship between severity of disability and quality of life: findings from a cross-sectional survey among people with physical disability in China.
Health Qual Life Outcomes
PUBLISHED: 02-19-2014
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People with physical disability (PWPD) is the largest subgroup of people with disability (PWD) in China, but few studies have been conducted among this vulnerable population. The objective of this study was to investigate the level of quality of life (QoL), self-perceived quality of care and support (QOCS), severity of disability and personal attitude towards disability among people with physical disability in China, as well as to identify how QoL can be affected by severity of disability through QOCS and personal attitude towards disability among PWPD.
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Role of Nogo?A in the regulation of hepatocellular carcinoma SMMC?7721 cell apoptosis.
Mol Med Rep
PUBLISHED: 02-18-2014
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Nogo-A has been identified as an inhibitor of neurite outgrowth specific to the central nervous system. However, little is known about the role of Nogo-A in hepatocellular carcinoma (HCC), the most common primary malignant tumor with a high mortality rate. This study aimed to investigate the role of endogenous Nogo-A in human liver cancer cells. Reverse transcription polymerase chain reaction was used to detect the expression of Nogo-A in four liver cancer cell lines. A lentivirus vector was then constructed to mediate RNA interference (RNAi) targeting of Nogo?A (LV?Nogo-A?siRNA) and was confirmed to successfully suppress the expression of the Nogo-A gene in SMMC-7721 cells. Furthermore, Nogo-A was observed to be highly expressed in liver cancer cell lines. RNAi of Nogo-A using the LV?Nogo-A?siRNA construct significantly decreased Nogo-A protein expression and specifically inhibited the growth of SMMC-7721 cells. This growth inhibitory effect may be attributed to an increase in G2/M phase arrest and apoptosis in SMMC-7721 cells containing Nogo-A?siRNA. The results of this study demonstrate that Nogo-A may represent a novel therapeutic target for the treatment of liver cancer, in addition to its potent roles in neural systems.
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Curative use of forequarter amputation for recurrent breast cancer over an axillary area: a case report and literature review.
World J Surg Oncol
PUBLISHED: 02-13-2014
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Axillary recurrence of breast cancer that involves the brachial neurovascular bundle is uncommon. However, for many patients with such recurrence, forequarter amputation can play a palliative role in relieving excruciating pain and paralysis of the upper limb. Further, for those patients who do not have distant metastasis or other local-regional recurrence, forequarter amputation provides a chance for a cure. Only a few case reports of curative amputations for recurrent breast cancer are present in the literature. Here, we report a case of forequarter amputation for curative treatment of axillary recurrent breast cancer, together with a literature review. To date, we have followed the patient for three years after amputation, during which there has been no evidence of recurrence or metastasis. Although radical resection is feasible, it can be accompanied by surgical wound complications and psychosocial stress. Therefore, an organized multidisciplinary approach is needed to ensure the success of radical resection.
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Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson's disease is associated with loss of Mg2+ efflux function.
Parkinsonism Relat. Disord.
PUBLISHED: 02-11-2014
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Sequence variants in SLC41A1 have been reported to be associated with Parkinson's disease (PD). This study investigates whether the genetic variants in SLC41A1 contribute to Taiwanese PD.
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Impact of acute aerobic exercise and cardiorespiratory fitness on visuospatial attention performance and serum BDNF levels.
Psychoneuroendocrinology
PUBLISHED: 02-06-2014
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The purpose of the current study was to explore various behavioral and neuroelectric indices after acute aerobic exercise in young adults with different cardiorespiratory fitness levels when performing a cognitive task, and also to gain a mechanistic understanding of the effects of such exercise using the brain-derived neurotrophic factor (BDNF) biochemical index. Sixty young adults were separated into one non-exercise-intervention and two exercise intervention (EI) (i.e., EIH: higher-fit and EIL: lower-fit) groups according to their maximal oxygen consumption. The participants' cognitive performances (i.e., behavioral and neuroelectric indices via an endogenous visuospatial attention task test) and serum BDNF levels were measured at baseline and after either an acute bout of 30min of moderate intensity aerobic exercise or a control period. Analyses of the results revealed that although acute aerobic exercise decreased reaction times (RTs) and increased the central Contingent Negative Variation (CNV) area in both EI groups, only the EIH group showed larger P3 amplitude and increased frontal CNV area after acute exercise. Elevated BDNF levels were shown after acute exercise for both EI groups, but this was not significantly correlated with changes in behavioral and neuroelectric performances for either group. These results suggest that both EI groups could gain response-related (i.e., RT and central CNV) benefits following a bout of moderate acute aerobic exercise. However, only higher-fit individuals could obtain particular cognition-process-related efficiency with regard to attentional resource allocation (i.e., P3 amplitude) and cognitive preparation processes (i.e., frontal CNV) after acute exercise, implying that the mechanisms underlying the effects of such exercise on neural functioning may be fitness dependent. However, the facilitating effects found in this work could not be attributed to the transient change in BDNF levels after acute exercise.
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Smilax riparia reduces hyperuricemia in mice as a potential treatment of gout.
Am. J. Chin. Med.
PUBLISHED: 01-29-2014
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The roots and rhizomes of Smilax riparia, called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we examined the efficacy of S. riparia in reducing serum uric acid levels in a potassium oxonate-induced hyperuricemia mouse model. We observed that the total saponins of S. riparia could down-regulate renal mURAT1, resulting in the enhancement of urate excretion in the kidney of hyperuricemic mice. These results suggest that S. riparia could be an active anti-gout herbal medicine, which would contribute to the enhancement of uric acid excretion in the kidney.
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Adaptation of the Chinese edition of the CSBS-DP: a cross-cultural comparison of prelinguistic development between Taiwanese and American toddlers.
Res Dev Disabil
PUBLISHED: 01-28-2014
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This study was conducted with 171 toddlers aged 1-2 in Taiwan using the Chinese version of the Communication and Symbolic Behavior Scale-Developmental Profile (CSBS-DP). A significant difference in the scores for the symbolic subscale was observed between the test subjects in Taiwan and the norm established in the original CSBS-DP in the United States. Furthermore, this difference varied across the three assessment tools of the CSBS-DP: the Infant-Toddler Checklist, the Caregiver Questionnaire, and the Behavior Sample. In the checklist and caregiver questionnaires, the scores in the language comprehension cluster and the object use cluster were significantly lower for Taiwanese toddlers than for their counterparts in the United States. In the behavior samples, however, the toddlers in Taiwan scored significantly higher than their peers in the United States in the object use cluster and lower than their American counterparts in the language comprehension cluster. This discrepancy suggests that cultural factors have a potential impact on performance, and thus such factors need to be considered in future endeavors to improve upon the Chinese version of the CSBS-DP.
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Natural product-based design, synthesis and biological evaluation of anthra[2,1-d]thiazole-6,11-dione derivatives from rhein as novel antitumour agents.
Eur J Med Chem
PUBLISHED: 01-23-2014
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Two series of novel 2-substituted 5,7-dihydroxyanthra[2,1-d]thiazole-6,11-dione derivatives from natural rhein were designed, synthesized and evaluated for their antitumour activities against human cancer cell lines A549 and HeLa in vitro.
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Effects of circuit exercise and Tai Chi on body composition in middle-aged and older women.
Geriatr Gerontol Int
PUBLISHED: 01-21-2014
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To investigate the impact of circuit exercise and Tai Chi exercise on body composition in middle-aged and older women.
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Effect of side chain length on intrahelical interactions between carboxylate- and guanidinium-containing amino acids.
Amino Acids
PUBLISHED: 01-15-2014
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The charge-containing hydrophilic functionalities of encoded charged amino acids are linked to the backbone via different numbers of hydrophobic methylenes, despite the apparent electrostatic nature of protein ion pairing interactions. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on ion pairing interactions, ?-helical peptides containing Zbb-Xaa (i, i + 3), (i, i + 4) and (i, i + 5) (Zbb = carboxylate-containing residues Aad, Glu, Asp in decreasing length; Xaa = guanidinium residues Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by circular dichroism spectroscopy (CD). The helicity of Aad- and Glu-containing peptides was similar and mostly pH independent, whereas the helicity of Asp-containing peptides was mostly pH dependent. Furthermore, the Arg-containing peptides consistently exhibited higher helicity compared to the corresponding Agp-, Agb-, and Agh-containing peptides. Side chain conformational analysis by molecular mechanics calculations showed that the Zbb-Xaa (i, i + 3) and (i, i + 4) interactions mainly involved the ? 1 dihedral combinations (g+, g+) and (g-, g+), respectively. These low energy conformations were also observed in intrahelical Asp-Arg and Glu-Arg salt bridges of natural proteins. Accordingly, Asp and Glu provides variation in helix characteristics associated with Arg, but Aad does not provide features beyond those already delivered by Glu. Importantly, nature may have chosen the side chain length of Arg to support helical conformations through inherent high helix propensity coupled with stabilizing intrahelical ion pairing interactions with the carboxylate-containing residues.
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Benzochalcogenodiazole-based donor-acceptor-acceptor molecular donors for organic solar cells.
ChemSusChem
PUBLISHED: 01-13-2014
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Four new molecules with a donor-acceptor-acceptor (D-A-A) configuration, in which 2,1,3-benzoxadiazole or 2,1,3-benzoselenodiazole were adopted as the central bridging acceptor, were synthesized as electron donors for small-molecule organic solar cells. In conjunction with two previously reported 2,1,3-benzothiadiazole-based compounds, the influences of the benzochalcogenodiazole acceptor unit and the ditolylarylamine donor moiety on the molecular structure, electrochemical behavior, and optical properties of the materials were investigated systematically to obtain a clear structure-property relationship. Vacuum-deposited hybrid planar mixed-heterojunction devices fabricated with the new donors and C70 as the acceptor showed power conversion efficiencies in the range of 2.9-4.3 % under 1 sun (100 mW cm(-2) ) AM 1.5 G simulated solar illumination. The current density-voltage characteristics of solar cells at various light intensities were measured, which revealed a high bimolecular recombination.
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Cyclosporine A induces connective tissue growth factor expression in human gingival fibroblasts: Suppression by epigallocatechin-3-gallate.
J. Formos. Med. Assoc.
PUBLISHED: 01-09-2014
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Transforming growth factor-? (TGF-?) plays an important role in the pathogenesis of cyclosporine A (CsA)-induced gingival overgrowth (GO). Connective tissue growth factor (CTGF/CCN2) acts as a cofactor with TGF-? to induce the maximal profibrotic effects of TGF-?. We investigated the effects of CsA on CCN2 expression in human gingival fibroblasts (HGFs) and the potential chemopreventive agent for CsA-induced GO.
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Clinical proteomics identifies potential biomarkers in Helicobacter pylori for gastrointestinal diseases.
World J. Gastroenterol.
PUBLISHED: 01-06-2014
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The development of gastrointestinal diseases has been found to be associated with Helicobacter pylori (H. pylori) infection and various biochemical stresses in stomach and intestine. These stresses, such as oxidative, osmotic and acid stresses, may bring about bi-directional effects on both hosts and H. pylori, leading to changes of protein expression in their proteomes. Therefore, proteins differentially expressed in H. pylori under various stresses not only reflect gastrointestinal environment but also provide useful biomarkers for disease diagnosis and prognosis. In this regard, proteomic technology is an ideal tool to identify potential biomarkers as it can systematically monitor proteins and protein variation on a large scale of cell's translational landscape, permitting in-depth analyses of host and pathogen interactions. By performing two-dimensional polyacrylamide gel electrophoresis (2-DE) followed by liquid chromatography-nanoESI-mass spectrometry (nanoLC-MS/MS), we have successfully pinpointed alkylhydroperoxide reductase (AhpC), neutrophil-activating protein and non-heme iron-binding ferritin as three prospective biomarkers showing up-regulation in H. pylori under oxidative, osmotic and acid stresses, respectively. Further biochemical characterization reveals that various environmental stresses can induce protein structure change and functional conversion in the identified biomarkers. Especially salient is the antioxidant enzyme AhpC, an abundant antioxidant protein present in H. pylori. It switches from a peroxide reductase of low-molecular-weight (LMW) oligomers to a molecular chaperone of high-molecular-weight (HMW) complexes under oxidative stress. Different seropositivy responses against LMW or HMW AhpC in H. pylori-infected patients faithfully match the disease progression from disease-free healthy persons to patients with gastric ulcer and cancer. These results has established AhpC of H. pylori as a promising diagnostic marker for gastrointestinal maladies, and highlight the utility of clinical proteomics for identifying disease biomarkers that can be uniquely applied to disease-oriented translational medicine.
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A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter.
J. Exp. Clin. Cancer Res.
PUBLISHED: 01-02-2014
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Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with (99m)Tc pertechnetate scintigraphy and ¹²?I positron emission tomography (PET).
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BMP-7 Enhances Cell Migration and ?v?3 Integrin Expression via a c-Src-Dependent Pathway in Human Chondrosarcoma Cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Bone morphogenic protein (BMP)-7 is a member of the transforming growth factor (TGF)-beta superfamily, which is originally identified based on its ability to induce cartilage and bone formation. In recent years, BMP-7 is also defined as a potent promoter of cell motility, invasion, and metastasis. However, there is little knowledge of the role of BMP-7 and its cellular function in chondrosarcoma cells. In the present study, we investigated the biological impact of BMP-7 on cell motility using transwell assay. In addition, the intracellular signaling pathways were also investigated by pharmacological and genetic approaches. Our results demonstrated that treatment with exogenous BMP-7 markedly increased cell migration by activating c-Src/PI3K/Akt/IKK/NF-?B signaling pathway, resulting in the transactivation of ?v?3 integrin expression. Indeed, abrogation of signaling activation, by chemical inhibition or expression of a kinase dead form of the protein attenuated BMP-7-induced expression of integrin ?v?3 and cell migration. These findings may provide a useful tool for diagnostic/prognostic purposes and even therapeutically in late-stage chondrosarcoma as an anti-metastatic agent.
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The relationship between health-related fitness and quality of life in postmenopausal women from Southern Taiwan.
Clin Interv Aging
PUBLISHED: 01-01-2014
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Health-related fitness has been reported to be associated with improved quality of life (QoL) in the elderly. Health-related fitness is comprised of several dimensions that could be enhanced by specific training regimens. It has remained unclear how various dimensions of health-related fitness interact with QoL in postmenopausal women.
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The influence of pathological mutations and proline substitutions in TDP-43 glycine-rich peptides on its amyloid properties and cellular toxicity.
PLoS ONE
PUBLISHED: 01-01-2014
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TAR DNA-binding protein (TDP-43) was identified as the major ubiquitinated component deposited in the inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in 2006. Later on, numerous ALS-related mutations were found in either the glycine or glutamine/asparagine-rich region on the TDP-43 C-terminus, which hinted on the importance of mutations on the disease pathogenesis. However, how the structural conversion was influenced by the mutations and the biological significance of these peptides remains unclear. In this work, various peptides bearing pathogenic or de novo designed mutations were synthesized and displayed their ability to form twisted amyloid fibers, cause liposome leakage, and mediate cellular toxicity as confirmed by transmission electron microscopy (TEM), circular dichroism (CD), Thioflavin T (ThT) assay, Raman spectroscopy, calcein leakage assay, and cell viability assay. We have also shown that replacing glycines with prolines, known to obstruct ?-sheet formation, at the different positions in these peptides may influence the amyloidogenesis process and neurotoxicity. In these cases, GGG308PPP mutant was not able to form beta-amyloid, cause liposome leakage, nor jeopardized cell survival, which hinted on the importance of the glycines (308-310) during amyloidogenesis.
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p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer.
Cell
PUBLISHED: 01-01-2014
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The p53 tumor suppressor coordinates a series of antiproliferative responses that restrict the expansion of malignant cells, and as a consequence, p53 is lost or mutated in the majority of human cancers. Here, we show that p53 restricts expression of the stem and progenitor-cell-associated protein nestin in an Sp1/3 transcription-factor-dependent manner and that Nestin is required for tumor initiation in vivo. Moreover, loss of p53 facilitates dedifferentiation of mature hepatocytes into nestin-positive progenitor-like cells, which are poised to differentiate into hepatocellular carcinomas (HCCs) or cholangiocarcinomas (CCs) in response to lineage-specific mutations that target Wnt and Notch signaling, respectively. Many human HCCs and CCs show elevated nestin expression, which correlates with p53 loss of function and is associated with decreased patient survival. Therefore, transcriptional repression of Nestin by p53 restricts cellular plasticity and tumorigenesis in liver cancer.
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[Microeukaryotic biodiversity in the waste ore samples surrounding an acid mine drainage lake].
Huan Jing Ke Xue
PUBLISHED: 12-25-2013
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The abandoned mineral samples were collected in an acid mine drainage area in Anhui Province. Molecular ecological methods were used to construct 18S rDNA clone libraries after analyzing the main physicochemical parameters, and then the microeukaryotic diversity and community structure in the acid mine drainage area were studied. The results showed that the region was strongly acidic (pH <3), and the concentrations of Fe, SO2-(4), P, NO-(3) -N showed the same trend, all higher in the bare waste ore samples PD and 1 M than in the vegetation covered samples LW and XC. Four eukaryotic phyla were detected in the abandoned mineral samples: Ascomycota, Basidiomycota, Glomeromycota and Arthropoda. Glomeromycota can form an absolute symbiotic relationship with the plant, and it was a key factor for early plant to adapt the terrestrial environment. The biodiversity of the vegetation covered samples LW and XC, which contained Glomeromycota, was much higher than that of the bare abandoned rock samples PD and 1 M. Moreover, many sequences in the libraries were closely related to some isolated strains, which are tolerant to low pH and heavy metals, such as Penicillium purpurogenum, Chaetothyriales sp. and Staninwardia suttonii.
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Vaccinia virus GLV-1h153 in combination with 131I shows increased efficiency in treating triple-negative breast cancer.
FASEB J.
PUBLISHED: 11-01-2013
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We investigated the therapeutic efficacy of a replication-competent oncolytic vaccinia virus, GLV-1h153, carrying human sodium iodide symporter (hNIS), in combination with radioiodine in an orthotopic triple-negative breast cancer (TNBC) murine model. In vitro viral infection was confirmed by immunoblotting and radioiodine uptake assays. Orthotopic xenografts (MDA-MB-231 cells) received intratumoral injection of GLV-1h153 or PBS. One week after viral injection, xenografts were randomized into 4 treatment groups: GLV-1h153 alone, GLV-1h153 and (131)I (?5 mCi), (131)I alone, or PBS, and followed for tumor growth. Kruskal-Wallis and Wilcoxon tests were performed for statistical analysis. Radiouptake assay showed a 178-fold increase of radioiodine uptake in hNIS-expressing infected cells compared with PBS control. Systemic (131)I-iodide in combination with GLV-1h153 resulted in a 6-fold increase in tumor regression (24 compared to 146 mm(3) for the virus-only treatment group; P<0.05; d 40). We demonstrated that a novel vaccinia virus, GLV-1h153, expresses hNIS, increases the expression of the symporter in TNBC cells, and serves both as a gene marker for noninvasive imaging of virus and as a vehicle for targeted radionuclide therapy with (131)I.-Gholami, S., Chen, C-H., Lou, E., Belin, L. J., Fujisawa, S., Longo, V. A. Chen, N. G., Gönen, M., Zanzonico, P. B., Szalay, A. A., Fong, Y. Vaccinia virus GLV-1h153 in combination with (131)I shows increased efficiency in treating triple-negative breast cancer.
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Effects of Cardiorespiratory Fitness Enhancement on Deficits in Visuospatial Working Memory in Children with Developmental Coordination Disorder: A Cognitive Electrophysiological Study.
Arch Clin Neuropsychol
PUBLISHED: 10-29-2013
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The present study aimed to explore the effectiveness of chronic aerobic exercise intervention on the behavioral and neuroelectric performances of children with developmental coordination disorder (DCD) when carrying out a visuospatial working memory (VSWM) task. Twenty typically developing children and 40 children with DCD, equally divided into DCD-training and DCD nontraining groups, performed the cognitive task with concomitant event-related potential recording before and after 16 weeks of endurance training. Results indicated that the children with DCD displayed VSWM deficits with regard to behavioral performance (i.e., slower reaction time and low accuracy rate) and the neuroelectric indices (i.e., smaller P3 and pSW amplitudes) during the retrieval-process phase as reported in previous studies. However, after the exercise intervention, DCD-training group showed significantly higher accuracy rates and enhanced P3 amplitudes during the encoding and retrieval-process phases, compared with their pre-training performances. These findings suggest that increased cardiorespiratory fitness could effectively improve the performance of the VSWM task in children with DCD, by enabling the allocation of greater working memory resources related to encoding and retrieval.
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Delineating the membrane-disrupting and seeding properties of the TDP-43 amyloidogenic core.
Chem. Commun. (Camb.)
PUBLISHED: 10-24-2013
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The amyloidogenic core in the TAR DNA-binding protein (TDP-43) C-terminal fragment has been characterized with its chemical, biochemical, and structural properties delineated. Various properties of the core sequence, including membrane impairment ability and the seeding effect, have also been studied.
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Neuronal aging: learning from C. elegans.
J Mol Signal
PUBLISHED: 10-23-2013
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The heterogeneity and multigenetic nature of nervous system aging make modeling of it a formidable task in mammalian species. The powerful genetics, simple anatomy and short life span of the nematode Caenorhabditis elegans offer unique advantages in unraveling the molecular genetic network that regulates the integrity of neuronal structures and functions during aging. In this review, we first summarize recent breakthroughs in the morphological and functional characterization of C. elegans neuronal aging. Age-associated morphological changes include age-dependent neurite branching, axon beading or swelling, axon defasciculation, progressive distortion of the neuronal soma, and early decline in presynaptic release function. We then discuss genetic pathways that modulate the speed of neuronal aging concordant with alteration in life span, such as insulin signaling, as well as cell-autonomous factors that promote neuronal integrity during senescence, including membrane activity and JNK/MAPK signaling. As a robust genetic model for aging, insights from C. elegans neuronal aging studies will contribute to our mechanistic understanding of human brain aging.
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[Progress in anti-cancer research of American ginseng: with an example of colorectal cancer].
Yao Xue Xue Bao
PUBLISHED: 10-19-2013
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Cancer is a group of various diseases, all of which involve unregulated cell growth. Many currently used chemotherapeutic drugs are derived from botanicals. Thus, searching botanical sources for novel oncology medications, including identifying the lead compounds and their derivatives for chemoprevention, is an essential step in advancing cancer therapeutics. This article mainly focuses on the data from our previous American ginseng anti-colon cancer studies. In addition to the potential role of American ginseng on cancer, the herb as an adjuvant for cancer treatment is presented, including describing the attenuation of adverse events induced by chemotherapeutic agents and increasing of quality of cancer patient life. Since heat-treated American ginseng and ginsenoside gut microbiome metabolites showed significant increases in cancer chemopreventive effects, active constituents of the steamed herb and their gut metabolites should be clearly identified, and the structure-activity relationship should be further explored. Data obtained from herbal medicine studies and clinical trials will help develop useful anticancer agents.
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Combination of ATRA and ATRC for the Synthesis of Periodic Vinyl Copolymers.
Macromol Rapid Commun
PUBLISHED: 09-16-2013
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A new approach to periodic vinyl copolymers via combination of atom transfer radical addition (ATRA) and atom transfer radical coupling (ATRC) is reported. The two examples are methyl methacrylate (MMA) and styrene (St) periodic copolymer (P(SMMS)) and acrylonitrile (AN) and St periodic copolymer (P(SAAS)). First, two monomer sequence units (MSU) with built-in sequence, SMMS and SAAS, are synthesized through the controlled ATRA of two ATRP initiators with St. Then, the ATRC of SMMS and SAAS are conducted at high radical conditions to generate two types of high-molecular-weight copolymers, P(SMMS) and P(SAAS). Though side reactions can not be totally avoided, characterizations of the polymer structure with a variety of means confirm that the main chain structures of P(SMMS) and (PSAAS) are predominantly with the periodic sequences from the MSUs. Attempts to suppress the side reactions are successful via the MNP-mediated ATRC of SMMS and SAAS.
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Typology of older female sex workers and sexual risk for HIV infection in China: a qualitative study.
Cult Health Sex
PUBLISHED: 09-02-2013
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The HIV epidemic continues to develop among older adults in China, including older female sex workers. Yet, few studies have been conducted among this relatively hidden population. The objectives of this study were to investigate the reasons for womens entry into sex work during their 30s and to develop typology of older women sex workers. Semi-structured in-depth interviews were conducted with 63 older women sex workers and six focus-group interviews with stakeholders in three cities in China in 2012. Data were analysed inductively using constant comparative method. The mean age of participants was 43 years and the mean age of entry into sex work was 39 years. The primary reasons for entry into sex work included heavy economic burdens, limited employment opportunities and the appealing nature of sex work. Street-based and venue-based older sex workers were identified based on where they solicited clients. Street-based older sex workers were more likely to engage in unsafe commercial sex due to financial incentives, whereas those in entertainment venues were unlikely to use condoms with regular clients. The development of effective HIV interventions needs to consider older women sex workers unique characteristics and target factors that impede safer-sex practices.
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HLA correlates in a cohort of slow progressors from China: effects on HIV-1 disease progression.
AIDS
PUBLISHED: 08-15-2013
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We looked at our HIV?+?slow progressors cohort to determine if there were any human leukocyte antigen (HLA) correlates for protection. No statistically significant allelic differences were found between the HIV?+?and control cohorts using regression analysis, though trends were noted. Data for Elite Controllers showed an increased frequency of B*57. Likewise, no correlation was inferred with the clinical data of the HIV?+?cohort. We hypothesize that the protective effect of HLA alleles may have been lost over time.
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Application of quantitative estimates of fecal hemoglobin concentration for risk prediction of colorectal neoplasia.
World J. Gastroenterol.
PUBLISHED: 06-30-2013
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To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors.
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En bloc pancreaticoduodenectomy and right colectomy in the treatment of locally advanced colon cancer.
Dis. Colon Rectum
PUBLISHED: 06-07-2013
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Carcinoma of the right colon invading the pancreas or duodenum is rare. Evidence of the indication, operative morbidity, and survival of en bloc pancreaticoduodenectomy and right colectomy for right colon cancer invading adjacent organs is limited.
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AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma.
Cell Commun. Signal
PUBLISHED: 04-17-2013
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Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1?, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor ?B (NF-?B) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-?B signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-?B pathways.
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Meta-analysis of the short-term effects of lamivudine treatment for severe chronic hepatitis B.
Virol. J.
PUBLISHED: 04-11-2013
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To evaluate the short-term effect of lamivudine (LMV) treatment for severe chronic hepatitis B.
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High Prevalence of HIV and Syphilis Among Men Who Have Sex With Men Recruited by Respondent-Driven Sampling in a City in Eastern China.
Asia Pac J Public Health
PUBLISHED: 03-29-2013
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Increasing prevalence of sexually transmitted diseases (STD) was reported among men who have sex with men (MSM) in China. A total of 407 MSMs were recruited by respondent-driven sampling (RDS) from May to July 2008 in Nanjing, China. Face-to-face interviews were conducted to collect information on demographic and risk behaviors; blood samples were collected for HIV and syphilis antibodies testing. The adjusted HIV and syphilis prevalence were, respectively, 7.3% (confidence interval [CI] = 2.6%-10.2%) and 14.4% (95% CI = 9.3%-21.1%). Recruiting male sex partners mostly from saunas and receptive anal intercourse with men in the last 6 months were independently associated with positive HIV status. Risk factors for positive syphilis status included being older than 28 years, low level of HIV-related knowledge, having been a male sex worker, and having unprotected anal sex with casual male sex partners in the past 6 months. High HIV/STD prevalence was detected. HIV/STD prevention strategies are urgently warranted.
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Effect of basal metabolic rate on the bone mineral density in middle to old age women in Taiwan.
Maturitas
PUBLISHED: 03-20-2013
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Basal metabolic rate (BMR) reflects a combination of cardiopulmonary function and lean body mass resulting from regular physical activity. Though many studies have examined the relationships between bone mineral density (BMD) and body composition, little is known regarding the relationship between BMD and BMR.
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Comparative proteomics analysis of degenerative eye lenses of nocturnal rice eel and catfish as compared to diurnal zebrafish.
Mol. Vis.
PUBLISHED: 03-18-2013
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The aim of this study was to determine the lens crystallin diversity of degenerative eyes from the rice eel (Monopterus albus) and walking catfish (Clarias batrachus) as compared to that of zebrafish (Danio rerio) by using comparative proteomics methodologies. We endeavored to investigate the evolution of vertebrate lenses particularly concerning the functional loss of lenses in degenerative eyes of rice eels and catfishes living under an environment of perpetual darkness.
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Gay saunas and the risks of HIV and syphilis transmissions in China--results of a meta-analysis.
J Sex Med
PUBLISHED: 03-06-2013
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Previous studies suggest the risk of human immunodeficiency virus (HIV) transmission among men who have sex with men (MSM) is associated with characteristics of venues. However, very few studies have systematically compared HIV/sexually transmitted disease (STD) prevalence among MSM according to key venue type for sourcing sex partners.
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Design and synthesis of pyrido[3,2-?]carbazole derivatives and their analogues as potent antitumour agents.
Eur J Med Chem
PUBLISHED: 03-05-2013
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A series of pyrido[3,2-?]carbazole derivatives and their analogues have been prepared and evaluated for their antitumour activity against human lung cancer A549 cells and colon cancer HT29 cells. The intermediates 4a-4k are successfully synthesized from 1a-1k and ethyl 2-(3-bromopyridin-2-yl)acetate by Knoevenagel condensation and intramolecular Heck-type reaction, and this is a novel and efficient synthetic approach to the core scaffold of the target compounds. These target compounds have shown an interesting antitumour profile towards the tested cell lines with IC50 values ranging from 0.07 ?M to 4.45 ?M. Among all the compounds synthesized, 8 compounds show higher potency than R16, 12 compounds are as potent as R16, and 6 compounds are less potent than R16. The best compound 24 is 7 times and approximately 10 times as potent as R16 against A549 and HT29 cells, respectively.
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p42.3: a promising biomarker for the progression and prognosis of human colorectal cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-04-2013
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As a novel cell cycle-related gene, p42.3 has been shown to play a key role in the cell proliferation and tumorigenicity of gastric cancer. To date, the association between p42.3 and colorectal cancer (CRC) has not been reported. This study investigated the expression of p42.3 and its potential role in human colorectal cancers.
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Oncolytic vaccinia virus therapy of salivary gland carcinoma.
JAMA Otolaryngol Head Neck Surg
PUBLISHED: 02-23-2013
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To examine the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) against a panel of 5 human salivary gland carcinoma cell lines.
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Gold-catalyzed cyclization/oxidative [3+2]?cycloadditions of 1,5-enynes with nitrosobenzenes without additional oxidants.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-20-2013
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Golden control: The title reaction (see scheme) proceeds with high stereocontrol to generate the heterocyclic products in good yield. Experiments to probe the mechanism were performed.
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Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer.
Breast Cancer Res.
PUBLISHED: 02-13-2013
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INTRODUCTION: Surgery is currently the definitive treatment for early-stage breast cancer. However, the rate of positive surgical margins remains unacceptably high. The human sodium iodide symporter (hNIS) is a naturally occurring protein in human thyroid tissue, which enables cells to concentrate radionuclides. The hNIS has been exploited to image and treat thyroid cancer. We therefore investigated the potential of a novel oncolytic vaccinia virus GLV1h-153 engineered to express the hNIS gene for identifying positive surgical margins after tumor resection via positron emission tomography (PET). Furthermore, we studied its role as an adjuvant therapeutic agent in achieving local control of remaining tumors in an orthotopic breast cancer model. METHODS: GLV-1h153, a replication-competent vaccinia virus, was tested against breast cancer cell lines at various multiplicities of infection (MOIs). Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice. To determine the utility of GLV-1h153 in identifying positive surgical margins, 90% of the mammary fat pad tumors were surgically resected and subsequently injected with GLV-1h153 or phosphate buffered saline (PBS) in the surgical wound. Serial Focus 120 microPET images were obtained six hours post-tail vein injection of approximately 600 ?Ci of 124I-iodide. RESULTS: Viral infectivity, measured by green fluorescent protein (GFP) expression, was time- and concentration-dependent. All cell lines showed less than 10% of cell survival five days after treatment at an MOI of 5. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 27 million viral plaque forming units (PFU) ( <10,000-fold increase from the initial viral dose ) by Day 4. Administration of GLV-1h153 into the surgical wound allowed positive surgical margins to be identified via PET scanning. In vivo, mean volume of infected surgically resected residual tumors four weeks after treatment was 14 mm3 versus 168 mm3 in untreated controls (P < 0.05). CONCLUSIONS: This is the first study to our knowledge to demonstrate a novel vaccinia virus carrying hNIS as an imaging tool in identifying positive surgical margins of breast cancers in an orthotopic murine model. Moreover, our results suggest that GLV-1h153 is a promising therapeutic agent in achieving local control for positive surgical margins in resected breast tumors.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.