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Find video protocols related to scientific articles indexed in Pubmed.
Refractive index dependent real-time plasmonic nanoprobes on a single silver nanocube for ultrasensitive detection of the lung cancer-associated miRNAs.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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We developed a novel method for the real-time monitoring of the delicate change in refractive index (RI) when DNA or RNA hybridize near a DNA-capped silver nanocube (AgNC) surface. This method offers an alternative platform in the quantitative analysis of the trace lung cancer-associated miRNAs in label-free detection.
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Activity-dependent PI(3,5)P2 synthesis controls AMPA receptor trafficking during synaptic depression.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-29-2014
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Dynamic regulation of phosphoinositide lipids (PIPs) is crucial for diverse cellular functions, and, in neurons, PIPs regulate membrane trafficking events that control synapse function. Neurons are particularly sensitive to the levels of the low abundant PIP, phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], because mutations in PI(3,5)P2-related genes are implicated in multiple neurological disorders, including epilepsy, severe neuropathy, and neurodegeneration. Despite the importance of PI(3,5)P2 for neural function, surprisingly little is known about this signaling lipid in neurons, or any cell type. Notably, the mammalian homolog of yeast vacuole segregation mutant (Vac14), a scaffold for the PI(3,5)P2 synthesis complex, is concentrated at excitatory synapses, suggesting a potential role for PI(3,5)P2 in controlling synapse function and/or plasticity. PI(3,5)P2 is generated from phosphatidylinositol 3-phosphate (PI3P) by the lipid kinase PI3P 5-kinase (PIKfyve). Here, we present methods to measure and control PI(3,5)P2 synthesis in hippocampal neurons and show that changes in neural activity dynamically regulate the levels of multiple PIPs, with PI(3,5)P2 being among the most dynamic. The levels of PI(3,5)P2 in neurons increased during two distinct forms of synaptic depression, and inhibition of PIKfyve activity prevented or reversed induction of synaptic weakening. Moreover, altering neuronal PI(3,5)P2 levels was sufficient to regulate synaptic strength bidirectionally, with enhanced synaptic function accompanying loss of PI(3,5)P2 and reduced synaptic strength following increased PI(3,5)P2 levels. Finally, inhibiting PI(3,5)P2 synthesis alters endocytosis and recycling of AMPA-type glutamate receptors (AMPARs), implicating PI(3,5)P2 dynamics in AMPAR trafficking. Together, these data identify PI(3,5)P2-dependent signaling as a regulatory pathway that is critical for activity-dependent changes in synapse strength.
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[Evaluation of Orbscan II plus non-history double-K method in intraocular lens power calculation for patients after refractive surgery].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-15-2014
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To explore the accuracy of intraocular lens (IOL) power calculation with non-history method using the keratometric value derived from one zone of Orbscan II topography after laser in situ keratomileusis (LASIK).
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Mechanism of Cr(VI) reduction by Aspergillus niger: enzymatic characteristic, oxidative stress response, and reduction product.
Environ Sci Pollut Res Int
PUBLISHED: 10-13-2014
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Bioremediation of hexavalent chromium by Aspergillus niger was attributed to the reduction product (trivalent chromium) that could be removed in precipitation and immobilized inside the fungal cells and on the surface of mycelium. The site location of reduction was conducted with assays of the permeabilized cells, cell-free extracts, and cell debris, which confirmed that the chromate reductase was mainly located in the soluble fraction of cells. The oxidation-reduction process was accompanied by the increase of reactive oxygen species and antioxidant levels after hexavalent chromium treatment. Michaelis-Menten constant (K m) and maximum reaction rate (V max), obtained from the Lineweaver-Burk plot were 14.68 ?M and 434 ?M min(-1) mg(-1) of protein, respectively. Scanning electron microscopy and Raman spectra analyses manifested that both Cr(VI) and Cr(III) species were present on the mycelium. Fourier transform-infrared spectroscopy analysis suggested that carboxyl, hydroxide, amine, amide, cyano-group, and phosphate groups from the fungal cell wall were involved in chromium binding by the complexation with the Cr(III) and Cr(VI) species. A Cr(VI) removal mechanism of Cr(VI) reduction followed by the surface immobilization and intracellular accumulation of Cr(III) in living A. niger was present.
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Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist.
Molecules
PUBLISHED: 10-09-2014
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The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.
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Anti-inflammatory mechanism research of tanshinone II A by module-based network analysis.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA.
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[Agrobacterium-mediated transformation of LJAMP2 gene into 'Red Sun' kiwifruit and its molecular identification].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-13-2014
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Bacterial canker caused by Pseudomonas syringae pv. Actinidiae is one of the most important diseases of kiwifruit (Actinidia chinensis) and leads to considerable yield losses. In order to obtain transgenic plants with resistance for 'Red Sun' kiwifruit to canker disease, a non-specific lipid transfer protein-like antimicrobial protein gene (LJAMP2) from motherwort (Leonurus japonicus) was introduced into 'Red Sun' kiwifruit through Agrobacterium-mediated transformation. After two days of co-cultivation with A. tumefaciens strain LBA4404 harboring 35S:LJAMP2, the transformed explants were transferred to the selection medium containing 25 mg/L kanamycin+3.0 mg/L BA+1.0 mg/L NAA. The regeneration efficiency of kanamycin-resistant shoots reached to 85%. All (100%) of kanamycin-resistant shoots rooted on half-strength MS medium supplemented with 0.8 mg/L IBA and a total of 40 regenerated plantlets were obtained. PCR and histochemical GUS activity analysis show that 23 of 40 lines (57.50%) were positive, suggesting that the LJAMP2 gene was integrated into the genome of 'Red Sun' kiwifruit. Taken together, we established an efficient genetic transformation method for 'Red Sun' kiwifruit using A. tumefaciens and the transformation frequency reached 5.11%. This protocol will be useful for the genetic breeding of 'Red Sun' kiwifruit for improvement of disease resistance.
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Neurogenin 2 Mediates Amyloid-? Precursor Protein-stimulated Neurogenesis.
J. Biol. Chem.
PUBLISHED: 09-12-2014
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Amyloid-? precursor protein (APP) is well studied for its role in Alzheimer disease, although its normal function remains uncertain. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem/progenitor cells (NSPCs). In this study we examined the role of APP in NSPC differentiation. To identify proteins that may mediate the effect of APP on NSPC differentiation, we used a gene array approach to find genes whose expression correlated with APP-induced neurogenesis. We found that the expression of neurogenin 2 (Ngn2), a basic helix-loop-helix transcription factor, was significantly down-regulated in NSPCs from APP knock-out mice (APPKO) and increased in APP transgenic (Tg2576) mice. Ngn2 overexpression in APPKO NSPCs promoted neuronal differentiation, whereas siRNA knockdown of Ngn2 expression in wild-type NSPCs decreased neuronal differentiation. The results demonstrate that APP-stimulated neuronal differentiation of NSPCs is mediated by Ngn2.
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Curcumin Protects against CCl4-Induced Liver Fibrosis in Rats by Inhibiting HIF-1? Through an ERK-Dependent Pathway.
Molecules
PUBLISHED: 09-04-2014
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The ERK/HIF-1? signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1? and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1?/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and ?-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1? and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1? partly through the ERK pathway.
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Transcription-mediated chimeric RNAs in prostate cancer: time to revisit old hypothesis?
OMICS
PUBLISHED: 09-04-2014
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Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.
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[Relationship between fetal growth restriction and ovarian reserve in adulthood].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-02-2014
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To investigate the relationship between fetal growth restriction and decreased ovarian reserve (DOR) in adulthood to screen high-risk population for early interventions.
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Structural insight into the central element assembly of the synaptonemal complex.
Sci Rep
PUBLISHED: 08-22-2014
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The key step in meiosis is synaptonemal complex formation, which mediates homologous chromosome alignment and synapsis. False pairing between homologous chromosomes produces infertility. Here, we present a crystal structure of the mouse meiosis-specific protein SYCE3, which is a component of the synaptonemal complex central element. Our studies show that functional SYCE3 most likely forms a dimer or higher order oligomer in cells. Furthermore, we demonstrate that the SYCE3 N-helix interacts with the SYCE1 C-helix, which is another central element component. Our results suggest that helical packing may mediate intra- or inter-association of each central element protein component, thereby playing an essential role in forming the synaptonemal complex central elements.
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Reference interval for osteocalcin in Chinese Han ethnic males from the Fangchenggang Area Male Health and Examination Survey.
Clin. Lab.
PUBLISHED: 08-20-2014
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The aim of this study was to set a reference interval (RI) for osteocalcin (OC) in a healthy Han male population from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project and study the effects of age, BMI, smoking, and alcohol consumption.
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[Analysis of TEOAE and AABR hearing screening and follow-up in NICU].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To study the results of TEOAE and AABR hearing screening and follow-up in NICU.
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The tetraspanin CD9 is involved in pancreatic damage during caerulein-induced acute pancreatitis in mice.
J Dig Dis
PUBLISHED: 08-07-2014
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Pancreatic acinar cell necrosis and subsequent inflammatory response aggravate acute pancreatitis (AP), its underlying mechanism has not been fully elucidated. The tetraspanin CD9 was reported to mediate inflammatory signaling through regulating molecular organization at cell surface. This study aimed to investigate the role of CD9 during caerulein-induced experimental AP in mice.
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C-reactive protein: rethinking its role in evaluating the severity of hyperlipidemic acute pancreatitis.
Pancreas
PUBLISHED: 08-02-2014
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The goal of this study is to evaluate the role of C-reactive protein (CRP) in predicting the severity of hyperlipidemic acute pancreatitis (HLAP) compared with non-HLAP (NHLAP).
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Digital gene expression analysis of the pathogenesis and therapeutic mechanisms of ligustrazine and puerarin in rat atherosclerosis.
Gene
PUBLISHED: 07-02-2014
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Atherosclerosis (AS) is the leading cause of death in modern societies. Active substance from Traditional Chinese Medicine has been used for the treatment of AS, such as ligustrazine and puerarin. However, the pathogenesis of AS and the curative mechanisms of ligustrazine and puerarin stay unclear. In this work, we attempted to figure out these questions using a rat AS model and digital gene expression (DGE) system. Our results showed that DGE sequencing outcomes were high quality and reproductively. Differentially expressed genes were obtained from different comparisons. The Gene Ontology (GO) analysis revealed that mainly enriched GO terms due to the drug treatment were the same as those obtained from the control group vs. the AS model group. Pathway analysis indicated that metabolic pathways, oxidative phosphorylation, and PPAR single pathways were enriched in all comparisons. Our work provided a comprehensive basis for a better understanding of the pathogenesis of AS and the curative mechanisms of ligustrazine and puerarin.
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Effect of exogenous nitric oxide on antioxidative system and S-nitrosylation in leaves of Boehmeria nivea (L.) Gaud under cadmium stress.
Environ Sci Pollut Res Int
PUBLISHED: 06-28-2014
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Cadmium (Cd)-induced growth inhibition is one of the primary factors limiting phytoremediation effect of Boehmeria nivea (L.) Gaud in contaminated soil. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been evidenced to alleviate Cd toxicity in many plants. However, as an important mechanism of NO in orchestrating cellular functions, S-nitrosylation is still poorly understood in its relation with Cd tolerance of plants. In this study, higher exogenous NO levels were found to coincide with higher S-nitrosylation level expressed as content of S-nitrosothiols (SNO). The addition of low concentration (100 ?M) SNP increased the SNO content, and it simultaneously induced an alleviating effect against Cd toxicity by enhancing the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) and reduced the accumulation of H2O2 as compared with Cd alone. Application of S-nitrosoglutathione reductase (GSNOR) inhibitors dodecanoic acid (DA) in 100 ?M SNP group brought in an extra elevation in S-nitrosylation level and further reinforced the effect of SNP. While the additions of 400 ?M SNP and 400 ?M SNP?+?50 ?M DA further elevated the S-nitrosylation level, it markedly weakened the alleviating effect against Cd toxicity as compared with the addition of 100 ?M SNP. This phenomenon could be owing to excess consumption of glutathione (GSH) to form SNO under high S-nitrosylation level. Therefore, the present study indicates that S-nitrosylation is involved in the ameliorating effect of SNP against Cd toxicity. This involvement exhibited a concentration-dependent property.
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Cerebral Microemboli Increase ?-Amyloid Protein Deposition, MMP-9, and GFAP Expression in the Alzheimer's Model of APP/PS1 Double Transgenic Mice.
Curr Neurovasc Res
PUBLISHED: 05-26-2014
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We investigated the effects of cerebral arterial microemboli on amyloid ? protein (A?) deposition in the hippocampal region of amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice and evaluated the role of cerebral arterial microemboli in Alzheimer's disease (AD) pathogenesis. The mice were divided into a wild-type sham surgery group (n = 15), a wild-type coupled with microemboli group (n =15), an APP/PS1 double transgenic sham surgery group (n =15) and an APP/PS1 double transgenic coupled with microemboli group (n =15). The microemboli mice were injected via the left internal carotid artery with 300 ?L of a normal saline suspension containing 100 whole blood clot-derived microemboli (25-50 ?m). The sham surgery mice were injected with equal volumes of saline. After the mouse model was established for 1, 2 or 4 weeks, the A?1-42 24 deposition in the left hippocampal region and the matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) expression levels were determined through immunohistochemical staining. The A?1-42 deposition level in the left hippocampi of transgenic microemboli group was significantly greater than in the transgenic sham group at week 1 and 2 (P?0.001) but not at week 4. No A?1-42 deposition was detected in the wild-type groups. Only sporadic MMP-9- and GFAP-positive cells were observed in the wild-type sham group. Significantly more MMP-9- and GFAP-positive cells were detected in the transgenic groups (P?0.001), particularly in the transgenic microemboli group. An intragroup analysis of the time factor for the microemboli groups showed significantly more MMP-9- and GFAP-positive cells at week 1 than at week 2 or 4 (P?0.001). No difference was detected between time points in the sham groups. Cerebral microemboli increased A? deposition in the hippocampal region of APP/PS1 double transgenic mice. MMP-9 and GFAP expression may play an important role in excess A? deposition, which is caused by an imbalance between the protein's synthesis and removal.
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Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-20-2014
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Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 ?M. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 ?M. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 ?M. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.
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Arrhenius time-scaled least squares: a simple, robust approach to accelerated stability data analysis for bioproducts.
J Pharm Sci
PUBLISHED: 05-15-2014
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Defining a suitable product presentation with an acceptable stability profile over its intended shelf-life is one of the principal challenges in bioproduct development. Accelerated stability studies are routinely used as a tool to better understand long-term stability. Data analysis often employs an overall mass action kinetics description for the degradation and the Arrhenius relationship to capture the temperature dependence of the observed rate constant. To improve predictive accuracy and precision, the current work proposes a least-squares estimation approach with a single nonlinear covariate and uses a polynomial to describe the change in a product attribute with respect to time. The approach, which will be referred to as Arrhenius time-scaled (ATS) least squares, enables accurate, precise predictions to be achieved for degradation profiles commonly encountered during bioproduct development. A Monte Carlo study is conducted to compare the proposed approach with the common method of least-squares estimation on the logarithmic form of the Arrhenius equation and nonlinear estimation of a first-order model. The ATS least squares method accommodates a range of degradation profiles, provides a simple and intuitive approach for data presentation, and can be implemented with ease.
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Relationships Between Children's Exposure to Ethnic Produce and Their Dietary Behaviors.
J Immigr Minor Health
PUBLISHED: 05-13-2014
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The current study examined relationships between children's ethnic produce exposure and healthy dietary practices among Latino, Hmong and non-Hispanic white children. One hundred Latino, 100 Hmong, and 92 non-Hispanic white parents of children ages 5-8 years old in northern California completed a cross-sectional survey. Children's exposure to ethnic produce from Hmong and Latino cultures, overall fruit and vegetable consumption, and fast food and ethnic restaurant use were measured. The Kruskal-Wallis and Mann-Whitney tests were used to compare variables across different ethnic groups. Spearman's correlation was used to assess the relationship between variables. Children's overall ethnic produce exposure, as well as exposure to produce from other cultures, was significantly correlated with overall fruit and vegetable consumption. There was a marginal (p = 0.053) negative association between ethnic produce exposure and fast food restaurant use among Latino children. These findings suggest that promoting ethnic produce is an effective strategy for enhancing healthy dietary practices among children.
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Multi-modality imaging to determine the cellular heterogeneity of nasopharyngeal carcinoma components.
Oncotarget
PUBLISHED: 05-10-2014
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Nasopharyngeal carcinoma (NPC) is an endemic public health problem in South and Southeast Asian countries. The disease components at the molecular level are unclear and need exploration for the development of future individualized molecular medicine. The purpose of this study was to test the feasibility of target-specific agents to detect different components of NPC. The binding capability of human NPC cell lines was determined by incubation with either agents that specifically target the metabolic status, host cytokines, and stroma. Mice bearing human NPC xenografts were injected with the same test agents plus a clinical molecular imaging agent (18F-fluorodeoxyglucose) and computer tomography (CT) contrast agent. In vitro cell studies have demonstrated that target-specific agents bind to NPC cells with significantly higher signal intensities. Those agents not only bound to the cell membrane but also penetrated into the cytosol and cell nuclei. In vivo imaging demonstrated that the human NPC xenografts revealed high glucose uptake and a profound vasculature in the tumor. All agents were bound to the tumor regions with a high tumor-to-muscle ratio. Finally, all imaging data were validated by histopathological results. Multiple, target-specific agents determine the dynamic and heterogeneous components of NPC at the molecular level.
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Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-02-2014
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eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development.
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Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression.
J Control Release
PUBLISHED: 04-15-2014
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A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.
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Large dosage of chishao in formulae for cholestatic hepatitis: a systematic review and meta-analysis.
Evid Based Complement Alternat Med
PUBLISHED: 04-03-2014
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Objective. To evaluate the efficacy and safety of large dosage of Chishao in formulae for treatment of cholestatic hepatitis. Methods. The major databases (PubMed, Embase, Cochrane Library, Chinese Biomedical Database Wanfang, VIP medicine information system, and China National Knowledge Infrastructure) were searched until January 2014. Randomized controlled trials (RCTs) of large dosage of Chishao in formulae that reported on publications in treatment of cholestatic hepatitis with total efficacy rate, together with the biochemical indices including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), were extracted by two reviewers. The Cochrane tool was used for the assessment of risk of bias included trials. Data were analyzed with RevMan 5.2.7 software. Results. 11 RCTs involving 1275 subjects with cholestatic hepatitis were included. Compared with essential therapy, large dosage of Chishao in formulae demonstrated more efficiently with down regulation of serum ALT, AST, TBIL, DBIL. Meanwhile, there were no obvious adverse events. Conclusion. As a promising novel treatment approach, widely using large dosage of Chishao in formulae may enhance the curative efficacy for cholestatic hepatitis. Considering being accepted by more and more practitioners, further rigorously designed clinical studies are required.
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[Ultrasonic radio frequency analysis technique for noninvasive evaluation of carotid arteryintima-media thickness and elasticity in patients with dyslipidemia].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 03-28-2014
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To assess the value of ultrasonic radio frequency analysis technique for noninvasively evaluation of carotid artery intima-media thickness (IMT) and elasticity in patients with dyslipidemia.
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Diabetes induces lysine acetylation of intermediary metabolism enzymes in the kidney.
Diabetes
PUBLISHED: 03-27-2014
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Cells in which insulin is not required for glucose uptake are susceptible to the long-term complications of diabetes. Even in these tissues, however, the major perturbations that would otherwise be engendered by the greatly increased intracellular glucose concentration are mollified by adaptive changes in the enzymes of intermediary metabolism. These include allosteric regulation, product inhibition, and covalent modification as well as alterations in gene transcription. More recently, advances in proteomic technology have shown that reversible acetylation of the ?-amino group of lysine provides an additional means of modulating protein function and, in particular, enzyme activity. Here, we explored the extent of protein acetylation in an organ susceptible to the long-term complications of diabetes, examining the kidneys of rats with streptozotocin-induced diabetes and kidney cells exposed to high glucose. Using high-resolution mass spectrometry coupled with immunoaffinity enrichment, we identified 47 lysine-acetylated proteins in the kidneys of diabetic rats compared with 11 in control kidneys. Bioinformatic interrogation of the acetylome from diabetic animals showed a predominance of metabolic pathway involvement including the citrate acid cycle, glycolysis/gluconeogenesis, and metabolism of branched chain amino acids. Increased lysine acetylation was also noted in mesangial and tubular cells exposed to 25 mmol/L compared with 5.6 mmol/L glucose. These findings highlight acetylation as a posttranslational modification affecting numerous proteins. Current drug discovery efforts to develop small molecule inhibitors and activators of various lysine acetylases and deacetylases offer a new potential strategy to reduce the likelihood of diabetes complications.
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The inhibitory effects of extracellular ATP on the growth of nasopharyngeal carcinoma cells via P2Y2 receptor and osteopontin.
J. Exp. Clin. Cancer Res.
PUBLISHED: 03-17-2014
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Nasopharyngeal carcinoma (NPC) is a common malignant tumor observed in the populations of southern China and Southeast Asia. However, little is known about the effects of purinergic signal on the behavior of NPC cells. This study analyzed the effects of ATP on the growth and migration of NPC cells, and further investigated the potential mechanisms during the effects.
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Spectrum-effect relationships between UPLC fingerprints and bioactivities of crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi) and its three processed products on mitochondrial growth coupled with canonical correlation analysis.
J Ethnopharmacol
PUBLISHED: 03-03-2014
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Ethnopharmacological relevance: The crude secondary roots of Aconitum carmichaelii Debeaux (Fuzi), together with its processed products, including Yanfuzi, Heishunpian and Paofupian, are commonly applied in clinic using for thousands of years, such as collapse, syncope, rheumatic fever, painful joints and various tumors. Aim of the study: To explore the different effects of Fuzi and its processed products on energy metabolism, with mitochondria as the model with the aim of guiding the clinical use of Fuzi and its products. fingerprints of Fuzi, Yanfuzi, Heishunpian and Paofupian were established by Ultra-high Performance Liquid Chromatography (UPLC) and effects of Fuzi and its processed products on rat's liver?s mitochondrial metabolism were studied by microcalorimetry. Spectrum-effect relationships between UPLC fingerprints and energy metabolism of mitochondria were investigated using canonical correlation analysis (CCA). Results: Because of their inherent differences in chemical compositions, the main activities of energy metabolism of mitochondria were different among Fuzi and its processed products. The potential bioactivity sequence of the tested products was Fuzi>Heishunpian>Paofupian>Yanfuzi. Results of CCA showed that compounds mesaconitine, benzoylaconitine, and benzoylhypacoitine might be the principal active components. Conclusion: Altogether, this work provides a general model of combination of UPLC and microcalorimetry to study the spectrum-effect relationships of Fuzi and its processed products which can offer some references for detecting principal components of traditional Chinese medicine on bioactivity to mitochondrial growth.
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Expression, purification, and characterization of rhTyrRS.
BMC Biotechnol.
PUBLISHED: 03-02-2014
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Aminoacyl-tRNA synthetases (AARSs) catalyze the first step of protein synthesis. Emerging evidence indicates that AARSs may have additional functions, playing a role in signal transduction pathways regulating thrombopoiesis and inflammation. Recombinant human tyrosyl-tRNA synthetase (rhTyrRS) is engineered with a single amino acid substitution that unmasks its cytokine activity. An industrial production method that provides high yield as well as high purity, quality, and potency of this protein is required for preclinical research.
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Cell-based assay system to estimate the effect of 125I seeds on cancer cells: effect of osteopontin.
Recent Pat Anticancer Drug Discov
PUBLISHED: 02-18-2014
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A number of recent patents related to 125I seed and osteopontin have been awarded. In this study, we developed a new in vitro model to study the radiobiological effects of 125I seeds on cancer cells.
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The N-terminal fragment of the ?-amyloid precursor protein of Alzheimer's disease (N-APP) binds to phosphoinositide-rich domains on the surface of hippocampal neurons.
J. Neurosci. Res.
PUBLISHED: 02-10-2014
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The function of the ?-amyloid precursor protein (APP) of Alzheimer's disease is poorly understood. The secreted ectodomain fragment of APP (sAPP?) can be readily cleaved to produce a small N-terminal fragment (N-APP) that contains heparin-binding and metal-binding domains and that has been found to have biological activity. In the present study, we examined whether N-APP can bind to lipids. We found that N-APP binds selectively to phosphoinositides (PIPs) but poorly to most other lipids. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 )-rich microdomains were identified on the extracellular surface of neurons and glia in primary hippocampal cultures. N-APP bound to neurons and colocalized with PIPs on the cell surface. Furthermore, the binding of N-APP to neurons increased the level of cell-surface PI(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate. However, PIPs were not the principal cell-surface binding site for N-APP, because N-APP binding to neurons was not inhibited by a short-acyl-chain PIP analogue, and N-APP did not bind to glial cells which also possessed PI(4,5)P2 on the cell surface. The data are explained by a model in which N-APP binds to two distinct components on neurons, one of which is an unidentified receptor and the second of which is a PIP lipid, which binds more weakly to a distinct site within N-APP. Our data provide further support for the idea that N-APP may be an important mediator of APP's biological activity.
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Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation.
J Biomech
PUBLISHED: 02-10-2014
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It has been suggested that pituitary hormone might be associated with bone metabolism. To investigate the role of thyroid-stimulating hormone (TSH) in bone metabolism, we designed the present study as follows. After weaning, TSH receptor (TSHR) null mice (Tshr(-/-)) were randomly divided into a thyroxine treatment group (n=10) or non-treatment group (n=10); the treatment group received a dose of desiccated thyroid extract at 100 ppm daily for 5 weeks. Age-matched wild-type (Tshr(+/+), n=10) and heterozygote mice (Tshr(+/-), n=10) served as controls. After 5 weeks, the animals were sacrificed, and the femurs were collected for histomorphometrical and biomechanical analyses. In addition, the effect of TSH on osteoclastogenesis was examined in the RAW264.7 osteoclast cell line. We found that compared with Tshr(+/+) mice, Tshr(-/-) and Tshr(+/-) mice had lower bone strength. The histomorphometric results showed that trabecular bone volume, osteoid surface, osteoid thickness and osteoblast surface were significantly decreased, whereas the osteoclast surface was significantly increased in both Tshr(-/-) and Tshr(+/-) mice compared with Tshr(+/+) mice. Bone resorption and formation in Tshr(-/-) mice were further enhanced by thyroxine replacement. bTSH inhibited osteoclast differentiation in vitro, as demonstrated by reduced development of TRAP-positive cells and down-regulation of differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9 and cathepsin K in RAW264.7 cells. Our results confirm that TSH increased bone volume and improved bone microarchitecture and strength at least partly by inhibiting osteoclastogenesis.
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USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase.
J. Exp. Med.
PUBLISHED: 02-03-2014
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Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus-induced RIG-I polyubiquitination and RIG-I-mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-?/? production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow-derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I.
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The key role of nanoparticle seeds during site-selective growth of silver to fabricate core-shell or asymmetric dumbbell heterostructures.
Dalton Trans
PUBLISHED: 02-01-2014
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Herein, a novel method to induce site-specific deposition of plasmonic silver domain on controlled sites of seeded AgBr nanoparticles is designed. Novel core-shell heterostructures and dumbbell heterostructures are fabricated by heterogeneous silver growth. A curved silver shell with thickness up to 5 nm is generated covering the AgBr core in the core-shell metal-semiconductor hybrids. However, in the dumbbell hybrids, a large silver domain is exclusively grown on a single side of the AgBr seed with a solid contact like relationship between the head and the tail. Photogenerated electrons are facilitated to transfer from the semiconductor head to the metal tail enhancing charge separations. The significant role of seed size during seeded silver growth has been demonstrated.
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Downregulation of transketolase activity is related to inhibition of hippocampal progenitor cell proliferation induced by thiamine deficiency.
Biomed Res Int
PUBLISHED: 01-29-2014
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In animal experiments, hippocampal neurogenesis and the activity of thiamine-dependent transketolase decrease markedly under conditions of thiamine deficiency. To further investigate the effect of thiamine deficiency on the proliferation of hippocampal progenitor cells (HPCs) and the potential mechanisms involved in this effect, we cultured HPCs in vitro in the absence of thiamine and found that proliferation and transketolase activity were both significantly repressed. Furthermore, specific inhibition of transketolase activity by oxythiamine strongly inhibited HPC proliferation in a dose-dependent manner. However, thiamine deficiency itself inhibited the proliferation to a greater degree than did oxythiamine. Taken together, our results suggest that modulation of transketolase activity might be one of the mechanisms by which thiamine regulates the proliferation of hippocampal progenitor cells.
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Experimental research on a novel iodine-125 seed strand connected using magnesium alloy AZ31.
Recent Pat Anticancer Drug Discov
PUBLISHED: 01-24-2014
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Aim of this research is to study the in vivo degradation and biocompatibility in rabbits and the dose distribution of novel iodine-125 seed strands connected using magnesium alloy AZ31.
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Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-?B pathway in experimental pancreatitis.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-08-2014
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Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-?B p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-?B pathway.
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Detection of subclinical atherosclerosis in asymptomatic subjects using ultrasound radiofrequency-tracking technology.
PLoS ONE
PUBLISHED: 01-01-2014
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Atherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis.
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Immunization associated with erectile dysfunction based on cross-sectional and genetic analyses.
PLoS ONE
PUBLISHED: 01-01-2014
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Erectile dysfunction (ED) is a global disease affecting a large number of people. Some studies have found a relationship between low-grade inflammation and ED. We hypothesized that the immune system might play a key role in the outcome of ED. Five immune agents (C3, C4, IgA, IgM, and IgG) were collected based on the Fangchenggang Area Male Health and Examination Survey (FAMHES), using methods of a traditional cross-sectional analysis. Our results repeated the significant association between ED and metabolic syndrome, obesity, and so forth. However, there seemed to be no positive relation between the tested indexes and ED risk in the baseline analysis (C3: P?=?0.737; C4: P?=?0.274; IgA: P?=?0.943; IgG: P?=?0.069; IgM: P?=?0.985). Then, after adjusting for age and multivariate covariates, a potentially significant association between ED and IgG was discovered (P?=?0.025 and P?=?0.034, respectively). Meanwhile, in order to describe the development of ED on a gene level, SNP-set kernel-machine association test (SKAT) was applied with the known humoral immune genes involved. The outcomes suggested that PTAFR (binary P value: 0.0096; continuous P value: 0.00869), IL27 (0.0029; 0.1954), CD37 (0.0248; 0.5196), CD40 (0.7146; 0.0413), IL7R (0.1223; 0.0222), PSMB9 (0.1237; 0.0212), and CXCR3 (0.0849; 0.0478) might be key genes in ED, especially IL27, when we restricted the family-wise error rate (FWER) to 0.5. Our study shows that IgG and seven genes (PTAFR, CD37, CD40, IL7R, PSMB9, CXCR3, and especially IL27) might be key factors in the pathogenesis of ED, which could pave the way for future gene and immune therapies.
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Hepatoma SK Hep-1 Cells Exhibit Characteristics of Oncogenic Mesenchymal Stem Cells with Highly Metastatic Capacity.
PLoS ONE
PUBLISHED: 01-01-2014
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SK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity.
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Reduced topological efficiency in cortical-Basal Ganglia motor network of Parkinson's disease: a resting state FMRI study.
PLoS ONE
PUBLISHED: 01-01-2014
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Parkinson's disease (PD) is mainly characterized by dopamine depletion of the cortico-basal ganglia (CBG) motor circuit. Given that dopamine dysfunction could affect functional brain network efficiency, the present study utilized resting-state fMRI (rs-fMRI) and graph theoretical approach to investigate the topological efficiency changes of the CBG motor network in patients with PD during a relatively hypodopaminergic state (12 hours after a last dose of dopamimetic treatment). We found that PD compared with controls had remarkable decreased efficiency in the CBG motor network, with the most pronounced changes observed in rostral supplementary motor area (pre-SMA), caudal SMA (SMA-proper), primary motor cortex (M1), primary somatosensory cortex (S1), thalamus (THA), globus pallidus (GP), and putamen (PUT). Furthermore, reduced efficiency in pre-SMA, M1, THA and GP was significantly correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in PD patients. Together, our results demonstrate that individuals with PD appear to be less effective at information transfer within the CBG motor pathway, which provides a novel perspective on neurobiological explanation for the motor symptoms in patients. These findings are in line with the pathophysiology of PD, suggesting that network efficiency metrics may be used to identify and track the pathology of PD.
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Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-?B.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), the aglycone part of the flavonoid glycosides diosmin occurs naturally in citrus fruit, was considered to exhibit anti-inflammatory and antioxidant properties. Our study aimed to investigate the effect of diosmetin in a murine model of cerulein-induced acute pancreatitis (AP). Experimental AP was induced in mice by seven intraperitoneal injection of cerulein (50 ug/kg) at hourly intervals. Diosmetin (100 mg/kg) or vehicle was pretreated 2 h before the first cerulein injection. After 6 h, 9 h, 12 h of the first cerulein injection, the severity of acute pancreatitis was evaluated biochemically and morphologically. Pretreatment with diosmetin significantly reduced serum levels of amylase and lipase; the histological injury; the secretion of tumor necrosis factor (TNF)-?, interleukin (IL)-1?, and IL-6; myeloperoxidase (MPO) activity, trypsinogen activation peptide (TAP) level, the expression of inducible nitric oxide synthase (iNOS); and the nuclear factor (NF)-?B activation in cerulein-induced AP. This study showed that administration of diosmetin demonstrated a beneficial effect on the course of cerulein-induced AP in mice. Therefore, diosmetin may become a new therapeutic agent in future clinical trials for treatment of AP.
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Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China.
PLoS ONE
PUBLISHED: 01-01-2014
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Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications.
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HIF-1? inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein.
PLoS ONE
PUBLISHED: 01-01-2014
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Multidrug resistance (MDR) is one of the major reasons chemotherapy-based treatments fail. Hypoxia is generally associated with tumor chemoresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) gene/transporter P-glycoprotein (P-gp) remains unclear. This study aims to explore the molecular mechanisms of reversing colon cancer MDR by focusing on the target gene HIF-1?.
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Imbalance of Wnt/Dkk negative feedback promotes persistent activation of pancreatic stellate cells in chronic pancreatitis.
PLoS ONE
PUBLISHED: 01-01-2014
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The role of persistent activation of pancreatic stellate cells (PSCs) in the fibrosis associated with chronic pancreatitis (CP) is increasingly being recognized. Recent studies have shown that Wnt signaling is involved in the development of fibrosis in multiple organs, however, the role of specific Wnts in pancreatic fibrosis remains unknown. We investigated the role of Wnt signaling during PSC activation in CP and the effect of ?-catenin inhibition and Dickkopf-related protein 1 (Dkk1) restoration on the phenotype of PSCs. CP was induced in mice by repetitive caerulein injection and mouse PSCs were isolated and activated in vitro. The expression of Wnts, ?-catenin, secreted frizzled-related proteins (sFRPs) and Dkks was analyzed by quantitative RT-PCR and western blotting. The canonical Wnt signaling pathway was examined by immunofluorescence and western blot detection of nuclear ?-catenin expression. The effect of recombinant mouse Dkk-1 (rmDkk-1) on cell proliferation and apoptosis was assessed by flow cytometry, immunofluorescence, immunocytochemistry and Cell Counting Kit-8 (CCK-8) analysis. The expression of ?-catenin, collagen1?1, TGF?RII, PDGFR? and ?-SMA in PSCs treated with different concentrations of rmDkk-1 or siRNA against ?-catenin was determined by quantitative RT-PCR and western blotting. Wnt2 was the only Wnt whose expression was significantly upregulated in response to PSC activation, and Wnt2 and ?-catenin protein levels were significantly increased in the pancreas of CP mice, whereas Dkk-1 expression was evidently decreased. Nuclear ?-catenin levels were markedly increased in activated PSCs, and rmDkk-1 suppressed the nuclear translocation of ?-catenin and the proliferation and extracellular matrix production of PSCs through the downregulation of PDGFR? and TGF?RII. Upregulation of Dkk-1 expression increased apoptosis in cultured PSCs. These results indicate that Wnt signaling may mediate the profibrotic effect of PSC activation, and Wnt2/Dkk-1 could be potential therapeutic targets for CP.
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Gene expression profiling associated with angiotensin II type 2 receptor-induced apoptosis in human prostate cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Increased expression of angiotensin II type 2 receptor (AT2R) induces apoptosis in numerous tumor cell lines, with either Angiotensin II-dependent or Angiotensin II-independent regulation, but its molecular mechanism remains poorly understood. Here, we used PCR Array analysis to determine the gene and microRNA expression profiles in human prostate cancer cell lines transduced with AT2R recombinant adenovirus. Our results demonstrated that AT2R over expression leads to up-regulation of 6 apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2), 2 cytokine genes (IL6 and IL8) and 1 microRNA, and down-regulation of 1 apoptosis-related gene TNFSF10 and 2 cytokine genes (BMP6, BMP7) in transduced DU145 cells. HRK was identified as an up-regulated gene in AT2R-transduced PC-3 cells by real-time RT-PCR. Next, we utilized siRNAs to silence the up-regulated genes to further determine their roles on AT2R overexpression mediated apoptosis. The results showed downregulation of Gadd45a reduced the apoptotic effect by ?30% in DU145 cells, downregulation of HRK reduced AT2R-mediated apoptosis by more than 50% in PC-3 cells, while downregulation of TRAIL-R2 enhanced AT2R-mediated apoptosis more than 4 times in DU145 cells. We also found that the effects on AT2R-mediated apoptosis caused by downregulation of Gadd45a, TRAIL-R2 and HRK were independent in activation of p38 MAPK, p44/42 MAPK and p53. Taken together, our results demonstrated that TRAIL-R2, Gadd45a and HRK may be novel target genes for further study of the mechanism of AT2R-mediated apoptosis in prostate cancer cells.
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Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-09-2013
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Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phosphoinositide presumed to be localized to endosomes and lysosomes, where it recruits cytoplasmic peripheral proteins and regulates endolysosome-localized membrane channel activity. Cells lacking PI(3,5)P2 exhibit lysosomal trafficking defects, and human mutations in the PI(3,5)P2-metabolizing enzymes cause lysosome-related diseases. The spatial and temporal dynamics of PI(3,5)P2, however, remain unclear due to the lack of a reliable detection method. Of the seven known phosphoinositides, only PI(3,5)P2 binds, in the low nanomolar range, to a cytoplasmic phosphoinositide-interacting domain (ML1N) to activate late endosome and lysosome (LEL)-localized transient receptor potential Mucolipin 1 (TRPML1) channels. Here, we report the generation and characterization of a PI(3,5)P2-specific probe, generated by the fusion of fluorescence tags to the tandem repeats of ML1N. The probe was mainly localized to the membranes of Lamp1-positive compartments, and the localization pattern was dynamically altered by either mutations in the probe, or by genetically or pharmacologically manipulating the cellular levels of PI(3,5)P2. Through the use of time-lapse live-cell imaging, we found that the localization of the PI(3,5)P2 probe was regulated by serum withdrawal/addition, undergoing rapid changes immediately before membrane fusion of two LELs. Our development of a PI(3,5)P2-specific probe may facilitate studies of both intracellular signal transduction and membrane trafficking in the endosomes and lysosomes.
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Phosphatidylinositol 3,5-bisphosphate: Low abundance, high significance.
Bioessays
PUBLISHED: 10-28-2013
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Recent studies of the low abundant signaling lipid, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2 ), reveal an intriguingly diverse list of downstream pathways, the intertwined relationship between PI(3,5)P2 and PI5P, as well as links to neurodegenerative diseases. Derived from the structural lipid phosphatidylinositol, PI(3,5)P2 is dynamically generated on multiple cellular compartments where interactions with an increasing list of effectors regulate many cellular pathways. A complex of proteins that includes Fab1/PIKfyve, Vac14, and Fig4/Sac3 mediates the biosynthesis of PI(3,5)P2 , and mutations that disrupt complex function and/or formation cause profound consequences in cells. Surprisingly, mutations in this pathway are linked with neurological diseases, including Charcot-Marie-Tooth syndrome and amyotrophic lateral sclerosis. Future studies of PI(3,5)P2 and PI5P are likely to expand the roles of these lipids in regulation of cellular functions, as well as provide new approaches for treatment of some neurological diseases.
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Microcalorimetry coupled with chemometric techniques for toxicity evaluation of Radix Aconiti Lateralis Preparata (Fuzi) and its processed products on Escherichia coli.
Appl. Microbiol. Biotechnol.
PUBLISHED: 10-07-2013
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As a widely used traditional Chinese medicine (TCM), Radix Aconiti Lateralis Preparata (Fuzi) is not only efficacious but also poisonous. Its toxicity and processed products should be taken into account and effectively evaluated. In this study, a non-invasive and non-destructive microcalorimetric method was employed to evaluate and compare the toxicity of Fuzi and its three processed products including Yanfupian, Heifupian, and Danfupian on Escherichia coli (E. coli). Some important metabolic information, such as the power-time curves and some quantitative thermokinetic parameters including growth rate constant k, heat output power P, inhibitory ratio I, and half inhibitory concentration IC50, of E. coli growth affected by various concentrations of Fuzi and its processed products were obtained. Combined with chemometric techniques including multivariate analysis of variance and principal component analysis on this information, it could be seen that Fuzi and its processed products could be distinguished according to their toxic effects on E. coli. The IC50 values of 14.6 mg/mL for Fuzi, 59.2 mg/mL for Yanfupian, 118.3 mg/mL for Heifupian, and 182.7 mg/mL for Danfupian illustrated that the sequence of toxicity on E. coli was Fuzi > Yanfupian > Heifupian > Danfupian. This study provided a useful method and idea of the combination of microcalorimetry and chemometrics for studying the toxic effects of TCMs and other substances.
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Body Mass Index and Disability in Chinese Nonagenarians and Centenarians.
J Am Med Dir Assoc
PUBLISHED: 09-26-2013
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To examine the potential association between body mass index (BMI) and activities of daily living (ADLs) and instrumental activities of daily living (IADLs) disabilities in a population-based sample of Chinese nonagenarians and centenarians.
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Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.
J. Med. Genet.
PUBLISHED: 09-18-2013
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Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population.
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Intravenous immunoglobulin treatment for repeated IVF/ICSI failure and unexplained infertility: a systematic review and a meta-analysis.
Am. J. Reprod. Immunol.
PUBLISHED: 08-21-2013
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Intravenous immunoglobulin (IVIG) has been introduced empirically into IVF/ICSI programs with the hopes of improving in vitro fertilization (IVF) success. However, the effects of IVIG have been inconsistent. We investigated the effects of IVIG on hard outcomes, including implantation rate, clinical pregnancy rate, live birth rate, miscarriage rate, and live birth rate per embryo transferred. The PubMed, EMBASE, and CNKI databases were searched up to June of 2013 and 10 studies were included. Case-controlled studies comparing IVIG with placebo in IVF/ICSI women and/or unexplained infertility were included. Using fixed and random effects models, the pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated. The use of IVIG was significantly associated with a higher implantation rate and RR was 2.708 (95%CI: 1.302-5.629) compared with the placebo. The clinical pregnancy rate and the live birth rate were significantly increased in patients randomized to IVIG; RR was 1.475 (95%CI: 1.191-1.825) for the clinical pregnancy rate and RR was 1.616 (95%CI: 1.243-2.101) for the live birth rate. Moreover, the miscarriage rate was significantly less in patients randomized to IVIG (0.352, 95%CI: 0.168-0.738), but the live birthrate per embryo transferred was not (2.893; 95%CI: 0.810-10.331) less. Our results strongly support that IVIG is a useful treatment option for women undergoing repeated IVF failure.
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Barbituric acid-based magnetic N-halamine nanoparticles as recyclable antibacterial agents.
ACS Appl Mater Interfaces
PUBLISHED: 08-16-2013
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Novel recyclable bactericidal materials, barbituric acid-based magnetic N-halamine nanoparticles (BAMNH NPs), were fabricated by coating of magnetic silica nanoparticles (MS NPs) with barbituric acid-based N-halamine by the aid of the radical polymerization. The sterilizing effect on the bacterial strain is investigated by incubating Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis). The as-prepared BAMNH NPs exhibit higher biocidal activity than the bulk powder barbituric acid-based N-halamine due to the high activated surface area. The structural effect of N-halamine on antimicrobial performance was fully clarified through the comparison between BAMNH NPs and hydantoin-based magnetic N-halamine nanoparticles (HMNH NPs). BAMNH NPs exhibited promising stability toward repeated washing and long-term storage. BAMNH NPs with different chlorine content were comparatively chosen to investigate the influence of chlorine content on the antimicrobial activity. An antibacterial recycle experiment revealed that no significant change occurred in the structure and antibacterial efficiency of BAMNH NPs after five recycle experiments. The combination of barbituric acid-based N-halamine with magnetic component results in an obvious synergistic effect and facilitates the repeated antibacterial applications, providing potential and ideal candidates for sterilization or even for the control of disease.
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Tumor Necrosis Factor and Interleukin-6 Gene Polymorphisms and Endometriosis Risk in Asians: A Systematic Review and Meta-Analysis.
Ann. Hum. Genet.
PUBLISHED: 08-06-2013
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A relationship between endometriosis and tumor necrosis factor (TNF-?) and interleukin-6 (IL-6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta-analysis to explore whether TNF-?/IL-6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF-?/IL-6 gene polymorphisms and endometriosis risk. An association of TNF-? gene -1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29-0.83, I(2) = 10.6%, P = 0.327). In addition, TNF-?-238A/G and IL-6 -174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF-?-238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01-2.48). For the IL-6 -174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04-2.31). No associations were detected between the TNF-?-308A/G and IL-6 -634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF-? gene -1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF-?-238A/G and IL-6 -174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF-?-308A/G and IL-6 -634C/G gene polymorphisms.
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Further evidence for genetic association of CACNA1C and schizophrenia: New risk loci in a Han Chinese population and a meta-analysis.
Schizophr. Res.
PUBLISHED: 07-30-2013
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CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case-control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI: 1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (?(2)[1]=0.07, P=0.795), and the difference in pooled ORs between ancestries was not significant (Z=0.25, P=0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.
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Bactericidal evaluation of N-halamine-functionalized silica nanoparticles based on barbituric acid.
Colloids Surf B Biointerfaces
PUBLISHED: 07-18-2013
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Novel N-halamine-functionalized silica nanoparticles (NHFS NPs) were facilely fabricated from the 5-allylbarbituric acid (ABBA) by a seeded copolymerization using colloidal silica nanoparticles as support and ABBA-based N-halamine copolymers as shell. The NHFS NPs with spherical morphology and legible core-shell structure have the average diameter of 538.5nm and the average shell thickness of 19.8nm. The NHFS NPs possessed improved antimicrobial activity against both Gram-positive and Gram-negative bacteria compared with their bulk powder counterparts. The structural effect of N-halamine on bactericidal activity was clarified through the comparison between barbituric acid-based NHFS NPs and hydantoin-structural NHFS NPs. Effects of colloidal silica support and comonomer methyl methacrylate on particles morphology and the corresponding antimicrobial activity were comparatively investigated as well. Antibacterial tests revealed that N-halamine nanomaterials originated from barbituric acid derivative displayed powerful antibacterial performance and long-term stability.
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N-halamine-decorated polystyrene nanoparticles based on 5-allylbarbituric acid: from controllable fabrication to bactericidal evaluation.
J Colloid Interface Sci
PUBLISHED: 07-08-2013
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N-halamine-based antibacterial polystyrene nanoparticles with different particle size ranged from 91.5 nm to 562.5 nm were facilely fabricated by surfactant-free emulsion polymerization with 5-allylbarbituric acid served as N-halamine precursor. Effect of experimental parameters such as monomer concentration, initiator concentration, and ionic strength on particle size was investigated systematically. N-halamine-based antibacterial polystyrene nanoparticles showed enhanced antibacterial activity against both Gram-positive species Staphylococcus aureus and Gram-negative species Pseudomonas aeruginosa compared with bulk powder N-halamine. Biocidal activity of N-halamine-based antibacterial polystyrene nanoparticles can be tailored effectively by tuning particle size. Stability and bactericidal activity of N-halamine-based antibacterial polystyrene nanoparticles was detected as a function of extending period.
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Involvement of interleukin-17A in pancreatic damage in rat experimental acute necrotizing pancreatitis.
Inflammation
PUBLISHED: 07-05-2013
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Interleukin (IL)-17A is a proinflammatory cytokine, which has recently attracted much interest due to its pathogenic role in various inflammatory conditions such as ischemia/reperfusion injury, chronic inflammation, and autoimmune diseases, but the role of IL-17A in acute pancreatitis remains unclear. This study aimed to investigate the role of IL-17A in experimental acute necrotizing pancreatitis (ANP). We analyzed the expression of IL-17A during the pathogenesis of ANP in vivo induced by 3 % sodium taurocholate (NaTc), by microarray test, quantitative real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. The effects of IL-17A on pancreatic acinar cells and pancreatic stellate cells (PSCs) were further investigated in vitro using recombinant rat IL-17A (rIL-17A). Expression of IL-17A was significantly increased following experimental acute pancreatitis. In addition, rIL-17A induced rat pancreatic acinar cell necrosis and promoted expression of several target genes, including IL-6, IL-1?, CXCL1, CXCL2, and CXCL5, in acinar cells and PSCs. These findings suggest that IL-17A may be involved in pancreatic damage by regulating the expression of inflammatory cytokines and chemokines during experimental acute pancreatitis.
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Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis.
Stem Cells
PUBLISHED: 06-17-2013
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Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-?- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 10(6) EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy.
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A study exploring critical pathways in clear cell renal cell carcinoma.
Exp Ther Med
PUBLISHED: 06-10-2013
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Renal cell carcinoma (RCC) is the most lethal type of cancer in the urinary system and often presents as a metastatic disease. Furthermore, there are no effective treatments for the disease. Several studies based on gene expression profiling have been performed with the aim of gaining insights into the pathogenesis of RCC; however, few studies have investigated RCC at the pathway level to search for the possible pathways involved in clear cell RCC (CCRCC). In this study, gene set enrichment analysis (GSEA) was conducted on microarray datasets from CCRCC tissue. DAVID functional enrichment analysis was performed based on the dysregulated genes that were identified in a meta-analysis performed on the microarray datasets from CCRCC tissue. In GSEA, 17 down- and 12 upregulated pathways coexisted in six datasets. The majority of the upregulated pathways were associated with the immune system. In addition, 32 dysregulated pathways were obtained from DAVID functional enrichment analysis, based on the abnormal genes identified by meta-analysis. This study demonstrated that cross-GSEA is a useful method for exploring the critical pathways involved CCRCC; however, an individual dataset with a small sample may introduce bias. A cross-GSEA based on certain well-designed datasets may be required to further the progress made in this study, following the analysis of its results.
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Factors associated with the pressure pain threshold in healthy Chinese men.
Pain Med
PUBLISHED: 06-06-2013
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The goal of present study was to examine the influence of demographic characteristics, lifestyle, and metabolic factors on pressure-induced pain threshold.
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Consensus of Official Position of IOF/ISCD FRAX Initiatives in Asia-Pacific Region.
J Clin Densitom
PUBLISHED: 05-27-2013
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The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.
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Endogenous sex hormones and C-reactive protein in healthy Chinese men.
Clin. Endocrinol. (Oxf)
PUBLISHED: 05-25-2013
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To examine the association of endogenous sex hormones and sex hormone-binding globulin (SHBG) with C-reactive protein (CRP) in Chinese men.
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TAK1 inhibitor 5Z-7-oxozeaenol sensitizes neuroblastoma to chemotherapy.
Apoptosis
PUBLISHED: 05-24-2013
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Treatment failure in high risk neuroblastoma is largely due to development of chemoresistance. NF-?B activation is one of the resistance mechanisms for cancer cells to escape from chemotherapy-induced cell-death. TAK1 is an essential component in genotoxic stresses-induced NF-?B activation; however, the role of TAK1 in the development of chemoresistance in neuroblastoma remains unknown. Using a panel of neuroblastoma cell lines, we found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) on neuroblastoma cell lines. TAK1 inhibition also enhanced the inhibitory effect of Dox and VP-16 on anchorage-independent growth. Treatment of neuroblastoma cells with 5Z-7-oxozeaenol blocked Dox- and VP16-induced NF-?B activation and enhanced Dox- and VP16-induced apoptosis. Moreover, 5Z-7-oxozeaenol was able to overcome the established chemoresistance in LA-N-6 neuroblastoma cells. Using an orthotopic neuroblastoma mouse model, we found that 5Z-7-oxozeaenol significantly enhanced chemotherapeutic efficacy in vivo. Together, our results provide a proof-of-concept that TAK1 inhibition significantly increases the sensitivity of neuroblastoma cells to chemotherapy-induced cell-death and can serve as an effective adjunct to current chemotherapeutic regimens for high risk diseases.
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The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: A pooled analysis of 41 sets of data from case-control studies.
Gene
PUBLISHED: 05-23-2013
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Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR=0.92, 95%CI=0.852-0.994, P=0.034; I(2)=0%, P=0.042; allele analysis: pooled OR=0.915, 95%CI=0.874-0.958, P=0; I(2)=0%, P=0.424; codominant model: OR=0.835, 95%CI=0.762-0.916, P=0; I(2)=0%, P=0.684) and rs1570360/VEGF (recessive model: OR=0.596, 95%CI=0.421-0.843, P=0.003; I(2)=23.9%, P=0.269; codominant model: OR=0.576, 95%CI=0.404-0.820, P=0.002; I(2)=49.1%, P=0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR=0.834, 95%CI=0.769-0.904, P=0; allele analysis: OR=0.908, 95%CI=0.863-0.955, P=0; AA vs CC: OR=0.829, 95%CI=0.750-0.916, P=0; AC vs CC: OR=0.837, 95%CI=0.768-0.912, P=0). In addition, in Asians (allele analysis: OR=0.21, 95%CI=0.168-0.262, P=0) and Caucasians (recessive model: OR=0.453, 95%CI: 0.240-0.855, P=0.015; codominant model: OR=0.464, 95%CI=0.240-0.898, P=0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa.
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[Three-dimensional finite element study on the change of glossopharyngeum in patient with obstructive sleep apnea hypopnea syndrome during titrated mandible advancement].
Hua Xi Kou Qiang Yi Xue Za Zhi
PUBLISHED: 05-14-2013
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To construct a three-dimensional finite element model of the upper airway and adjacent structure of an obstructive sleep apnea hypopnea syndrome (OSAHS) patient for biomechanical analysis. And to study the influence of glossopharyngeum of an OSAHS patient with three-dimensional finite element model during titrated mandible advancement.
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Role of cystatin C in amyloid precursor protein-induced proliferation of neural stem/progenitor cells.
J. Biol. Chem.
PUBLISHED: 05-13-2013
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The amyloid precursor protein (APP) is well studied for its role in Alzheimer disease. However, little is known about its normal function. In this study, we examined the role of APP in neural stem/progenitor cell (NSPC) proliferation. NSPCs derived from APP-overexpressing Tg2576 transgenic mice proliferated more rapidly than NSPCs from the corresponding background strain (C57Bl/6xSJL) wild-type mice. In contrast, NSPCs from APP knock-out (APP-KO) mice had reduced proliferation rates when compared with NSPCs from the corresponding background strain (C57Bl/6). A secreted factor, identified as cystatin C, was found to be responsible for this effect. Levels of cystatin C were higher in the Tg2576 conditioned medium and lower in the APP-KO conditioned medium. Furthermore, immunodepletion of cystatin C from the conditioned medium completely removed the ability of the conditioned medium to increase NSPC proliferation. The results demonstrate that APP expression stimulates NSPC proliferation and that this effect is mediated via an increase in cystatin C secretion.
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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.