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Find video protocols related to scientific articles indexed in Pubmed.
Factors that influence the turnover intention of Chinese village doctors based on the investigation results of Xiangyang City in Hubei Province.
Int J Equity Health
PUBLISHED: 11-04-2014
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IntroductionThis study analyzes the factors that influence the turnover intention of village doctors by investigating village clinic workers in rural areas, particularly in Xiangyang City, Hubei Province.MethodsA total of 1184 village clinics were sampled randomly in Xiangyang City. The research assistants distributed 1930 questionnaires to village doctors. This study had a response rate of 97.88%. A total of 1889 village doctors completed the questionnaires.ResultsThe results of the investigation conducted in Xiangyang City indicated that 63.2% of the village doctors did not plan to leave the organization where they were currently employed. However, more than one-third (36.8%) of the village doctors considered leaving their posts voluntarily. Some job satisfaction indexes affect their intention to resign. The results showed that income satisfaction and the way organization policies are put into practice, in addition, my pay and the amount of work I do, the chances for advancement on this job and the work conditions are significant factors that contribute to the turnover intention of village doctors.ConclusionsThis study may interest heath care management administrator and highlight the influence of job satisfaction on turnover intention of village doctors. Our findings outline some issues that contribute to these problems and suggest an approach for health care policy maker to implement a broader national process and organizational strategies to improve the job satisfaction and stability of the village doctors.
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Dr.VIS v2.0: an updated database of human disease-related viral integration sites in the era of high-throughput deep sequencing.
Nucleic Acids Res.
PUBLISHED: 10-31-2014
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Dr.VIS is a database of human disease-related viral integration sites (VIS). The number of VIS has grown rapidly since Dr.VIS was first released in 2011, and there is growing recognition of the important role that viral integration plays in the development of malignancies. The updated database version, Dr.VIS v2.0 (http://www.bioinfo.org/drvis or bminfor.tongji.edu.cn/drvis_v2), represents 25 diseases, covers 3340 integration sites of eight oncogenic viruses in human chromosomes and provides more accurate information about VIS from high-throughput deep sequencing results obtained mainly after 2012. Data of VISes for three newly identified oncogenic viruses for 14 related diseases have been added to this 2015 update, which has a 5-fold increase of VISes compared to Dr.VIS v1.0. Dr.VIS v2.0 has 2244 precise integration sites, 867 integration regions and 551 junction sequences. A total of 2295 integration sites are located near 1730 involved genes. Of the VISes, 1153 are detected in the exons or introns of genes, with 294 located up to 5 kb and a further 112 located up to 10 kb away. As viral integration may alter chromosome stability and gene expression levels, characterizing VISes will contribute toward the discovery of novel oncogenes, tumor suppressor genes and tumor-associated pathways.
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Synergistic effects of inorganic salt and surfactant on phenanthrene removal from aqueous solution by sediment.
Water Sci. Technol.
PUBLISHED: 10-30-2014
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The economic and effective application of surfactant enhanced remediation (SER) technology in a sediment-freshwater/saline water system was investigated by batch method using the combined effects of inorganic salt (sodium chloride, NaCl) and anionic surfactant (sodium dodecylbenzene sulfonate (SDBS)) on phenanthrene (PHE) removal via sorption by sediment. In all cases, PHE sorption followed a linear equation and partition as the main mechanism for PHE removal from aqueous solution. Separate addition of SDBS (2 mmol L(-1)) and NaCl (2-100 mmol L(-1)) moderately enhanced PHE removal, while with their combined addition the enhancement was substantial, and the removal efficiency achieved a peak of 92.8%. The combined effect expressed a synergy, and the sorption enhancement increased by factors of 2.7, 3.2 and 3.4 when compared with the sum of the separate entities at elevated salinity. This was because the sorbed SDBS, with increasing amount and a high packing conformation at elevated salinity, outcompeted aqueous SDBS for PHE partition. Moreover, a combination of 2 mmol L(-1) SDBS and 2 mmol L(-1) NaCl was optimal for PHE removal. Therefore, SER technology appears more effective for PHE removal in saline water than in freshwater, and preliminary water quality monitoring is essential for economic and efficient SER application.
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[Recent advances in Sphingobium sp. SYK-6 for lignin aromatic compounds degradation--a review].
Wei Sheng Wu Xue Bao
PUBLISHED: 10-28-2014
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Lignin is complex heteropolymer produced from hydroxycinnamyl alcohols through radical coupling. In nature, white-rot fungi are assumed initially to attack native lignin and release lignin-derived-low-molecular-weight compounds, and soil bacteria play an importent role for completely degradation of these compounds. Study on the soil bacteria degrading lignin-derived-low-molecular-weight compounds will give way to understand how aromatic compounds recycle in nature, and to utilize lignin compounds as the renewable materials for valuable materials production. Sphingobium sp. SYK-6 that grows on lignin biphenyl (5,5'-dehydrodivanillate) had been isolated from pulp effluent in 1987. We have researched this bacterium more than 25 years, a serious aromatic metabolic pathway has been determined, and related genes have been isolated. As the complete genome sequence of SYK-6 has been opened to the public in 2012, the entire aromatic compounds degradation mechanisms become more clear. Main contents in our review cover: (1) genome information; (2) aryl metabolism; (3) biphenyl metabolism; (4) ferulate metabolism; (5) tetrahydrofolate-dependent O-demethylation system for lignin compound degrdation; (6) protocatechuate 4,5-cleavage pathway; (7) multiple pathways for 3-O-methylgallate metabolism.
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[Application of noninvasive fetal trisomy testing based on massively parallel sequencing for the detection of chromosomal deletions and duplications].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 10-10-2014
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To assess the value of noninvasive fetal trisomy testing based on massively parallel sequencing for the detection of chromosomal deletions and duplications.
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[Determination of streptomycin and dihydrostreptomycin in pollens by high performance liquid chromatography-tandem mass spectrometry].
Se Pu
PUBLISHED: 10-02-2014
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A method was established for the determination of streptomycin (STR) and dihydrostreptomycin (DHS) in pollens based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The sample was extracted and cleaned-up by a C18 solid phase extraction cartridge. The separation was carried out on a Protemix WCX-NP5 column (100 mm x 2.1 mm, 5 microm) with a gradient elution using 5% (v/v) formic acid, 20 mmol/L ammonium acetate and methanol as mobile phases. The analysis of streptomycin and dihydrostreptomycin was performed under electrospray positive ionization mode. The limits of detection (LOD, S/N = 3) and limits of quantification (LOQ, S/N = 10) for the both were 5 microg/kg and 10 microg/kg, respectively. Good linearities (r > 0.99) were achieved for the target compounds over the range of 10-200 microg/L. The recoveries at three spiked levels (10, 20, 50 microg/kg) in the blank matrices, such as pollen pini, corn pollen, camellia pollen, sunflower pollen, rape pollen and bee pollen, were from 76.8% to 100.3% with the relative standard deviations varied from 3.70% to 12.6%. The method is accurate, practical, and can be applied to most of the contaminated matrices. With this method, heptafluorobutyric acid is not required as mobile phase which is harmful to MS spectrometer.
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IFN-stimulated gene LY6E in monocytes regulates the CD14/TLR4 pathway but inadequately restrains the hyperactivation of monocytes during chronic HIV-1 infection.
J. Immunol.
PUBLISHED: 09-15-2014
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Owing to ongoing recognition of pathogen-associated molecular patterns, immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication, some might exert compensatory immune suppression to limit pathological dysfunctions, although the mechanisms are not fully understood. In this study, we report that the ISG lymphocyte Ag 6 complex, locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection, the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however, the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together, the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation, which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.
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Preparation, physical characterization and pharmacokinetic study of paclitaxel nanocrystals.
Drug Dev Ind Pharm
PUBLISHED: 08-26-2014
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Abstract Paclitaxel (PTX) is a natural broad-spectrum anticancer drug with poor aqueous solubility. PTX nanocrystals were formulated to improve the water solubility, and PTX nanosuspensions were prepared using anti-solvent precipitation, and then organic solvent and surfactants were removed by filtering through a vacuum system. The physical characterization of PTX nanocrystals were measured by transmission electron microscope, X-ray diffraction and differential scanning calorimetry. In addition, saturation solubility, in vitro release, stability and pharmacokinetic characteristics were examined. The average particle size of PTX nanocrystals was ?200?nm, and they had a stable potential and a uniform distribution. Paclitaxel nanocrystals can effectively improve drug solubility and in vitro release. PTX pharmacokinetic and tissue distribution studies were compared after intravenous administration of nanocrystals versus a commercial injection formulation. PTX nanocrystals were rapidly distributed with a longer elimination phase. Moreover, tissue distribution indicated that PTX nanocrystals are mainly absorbed by the liver and spleen and may offer reduced renal and cardiovascular toxicity which may reduce side effects.
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Microvascular protective role of pericytes in melatonin-treated spinal cord injury in the C57BL/6 mice.
Chin. Med. J.
PUBLISHED: 08-23-2014
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Pericytes, located on microvessels, help to maintain vascular stability and blood-brain barrier integrity. The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear. Therefore, the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.
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Supramolecular [60]Fullerene Liquid Crystals Formed By Self-Organized Two-Dimensional Crystals.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-21-2014
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Fullerene-based liquid crystalline materials have both the excellent optical and electrical properties of fullerene and the self-organization and external-field-responsive properties of liquid crystals (LCs). Herein, we demonstrate a new family of thermotropic [60]fullerene supramolecular LCs with hierarchical structures. The [60]fullerene dyads undergo self-organization driven by ?-? interactions to form triple-layer two-dimensional (2D) fullerene crystals sandwiched between layers of alkyl chains. The lamellar packing of 2D crystals gives rise to the formation of supramolecular LCs. This design strategy should be applicable to other molecules and lead to an enlarged family of 2D crystals and supramolecular liquid crystals.
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Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.
Science
PUBLISHED: 08-09-2014
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Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to ?7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA.
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Berberine attenuates autophagy in adipocytes by targeting BECN1.
Autophagy
PUBLISHED: 07-23-2014
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The lysosomal degradation pathway, autophagy, is essential for the maintenance of cellular homeostasis. Recently, autophagy has been demonstrated to be required in the process of adipocyte conversion. However, its role in mature adipocytes under physiological and pathological conditions remains unclear. Here, we report a major function of BECN1 in the regulation of basal autophagy in mature adipocytes. We also show that berberine, a natural plant alkaloid, inhibits basal autophagy in adipocytes and adipose tissue of mice fed a high-fat diet via downregulation of BECN1 expression. We further demonstrate that berberine has a pronounced effect on the stability of Becn 1 mRNA through the Mir30 family. These findings explore the potential of BECN1 as a key molecule and a drug target for regulating autophagy in mature adipocytes.
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Transactivation of epidermal growth factor receptor through platelet-activating factor/receptor in ovarian cancer cells.
J. Exp. Clin. Cancer Res.
PUBLISHED: 07-22-2014
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BackgroundWe previously identified platelet-activating factor receptor (PAFR) as being overexpressed in ovarian cancer and found that its ligand PAF evoked EGFR phosphorylation using the phospho-antibody microarray. Epidermal growth factor receptor (EGFR) are also overexpressed in ovarian cancer and contribute to the growth of ovarian cancer cells. Here, we investigated the mechanisms of crosstalk between PAFR and EGFR signaling in ovarian cancer cells to further determine whether the interaction between PAFR and EGFR synergistic contribute to the progression of ovarian cancer.MethodsExpression and localization of PAFR in several ovarian cancer cell lines were assessed by Western blot, realtime-PCR and immunofluorescence. The ovarian cancer cells were stimulated with PAF or PAF and in some experiments also pharmacological inhibitors. Phosphorylation of proteins in signaling pathways were measured by Western blot. HB-EGF concentrations of the supernatant from stimulated ovarian cancer cells were measured by enzyme-linked immunosorbent assay.ResultsOur data show that PAF increases EGFR phosphorylation through PAFR in a time- and dose- dependent manner in SKOV-3 ovarian cancer cells. This transactivation is dependent on phospholipase C-ß and intracellular calcium signaling. This pathway is also Src tyrosine kinase- and metalloproteinase- dependent. PAF triggers EGFR activation through the increased heparin-binding EGF-like growth factor (HB-EGF) release in metalloprotease-dependent manner. Several studies involving EGFR transactivation through G-protein coupled receptor (GPCR) have demonstrated EGFR-dependent increase in ERK1/2 phosphorylation. Yet in SKOV-3 cells, PAF treatment also increases ERK1/2 phosphorylation in a EGFR-independent manner.ConclusionsThe results suggest that in SKOV-3 ovarian cancer cells, PAF transactivates EGFR and downstream ERK pathways, thus diversifying the GPCR-mediated signal. The crosstalk between PAFR and EGFR suggests a potentially important signaling linkage between inflammatory and growth factor signaling in ovarian cancer cells.
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Comparative proteomic study reveals 17?-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-15-2014
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Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17?-hydroxysteroid dehydrogenase-13 (17?-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17?-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17?-HSD family plays an important role in lipid metabolism, 17?-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17?-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirus-mediated hepatic overexpression of human 17?-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17?-HSD13 as a pathogenic protein in the development of NAFLD.
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A tryptophan responsive fluorescent and wettable dual-signal switch.
Org. Biomol. Chem.
PUBLISHED: 07-04-2014
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A new fluorescent dianthracene calix[4]arene (C4DA) was designed and synthesized via coupling the fluorescent anthracene units and calix[4]arene units. Then it was used to form self-assembled monolayers (C4DA-SAMs) by the simple click reaction to give the first fluorescent and wettable dual-signal switch for tryptophan (Trp) on a micro- and nano-structured silicon surface. The switch for Trp on the C4DA functional surface was confirmed by contact angle (CA) measurements and fluorescent spectroscopy (FL). Furthermore, the wettability-responsive C4DA functional interface can be re-used for six cycles. The responsive switch can potentially be applied in many fields including nanodevices and intelligent microfluidic switching.
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PAX6 downregulates miR-124 expression to promote cell migration during embryonic stem cell differentiation.
Stem Cells Dev.
PUBLISHED: 06-26-2014
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PAX6-null mice exhibit defects in multiple organs leading to neonatal lethality, but the mechanism by which this occurs has not yet fully elucidated. In this study, we generated induced pluripotent stem cells (iPSCs) from Pax6-mutant mice and investigated the effect of PAX6 on cell fate during embryoid body (EB) formation. We found that PAX6 promotes cell migration by directly downregulating miR-124, which is important for the fate transition of migratory cells during gastrulation of embryonic stem (ES) cells. Although several downstream targets of miR-124 have been reported, little is known regarding the upstream regulation of miR-124. When we observed EB formation of iPSCs from Pax6-mutant mice, we found that higher levels of miR-124 in Pax6 homozygous EBs (Homo-EBs) inhibited cell migration, whereas inhibition of miR-124 in Homo-EBs rescued the migratory phenotypes associated with PAX6 deficiency. Further, we found that PAX6 binds to the promoter regions of the miR-124-3 gene and directly represses its expression. Therefore, we propose a novel PAX6-miR-124 pathway that controls ES cell migration. Our findings may provide important information for studies on ES cell differentiation and embryonic development.
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Numerical Evaluation of Myofiber Orientation and Transmural Contractile Strength on Left Ventricular Function.
J Biomech Eng
PUBLISHED: 06-24-2014
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The left ventricle (LV) of the heart is composed of a complex organization of cardiac muscle fibers, which contract to generate force and pump blood into the body. It has been shown that both the orientation and contractile strength of these myofibers vary across the ventricular wall. The hypothesis of the current study is that the transmural distributions of myofiber orientation and contractile strength interdependently impact LV pump function. In order to quantify these interactions a finite element model of the LV was generated, which incorporated transmural variations. The influence of myofiber orientation and contractile strength on the Starling relationship and the end-systolic apex twist of the LV was assessed. The results suggest that reductions in contractile strength within a specific transmural layer amplified the effects of altered myofiber orientation in the same layer, causing greater changes in stroke volume. Furthermore, when the epicardial myofibers contracted the strongest, the twist of the LV apex was greatest, regardless of myofiber orientation. These results demonstrate the important role of transmural distribution of myocardial contractile strength and its interplay with myofiber orientation. The coupling between these two physiologic parameters could play a critical role in the progression of heart failure.
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Intrathymic Tfh/B Cells Interaction Leads to Ectopic GCs Formation and Anti-AChR Antibody Production: Central Role in Triggering MG Occurrence.
Mol. Neurobiol.
PUBLISHED: 06-23-2014
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Myasthenia gravis is a typical acetylcholine receptor (AChR) antibody-mediated autoimmune disease in which thymus frequently presents follicular hyperplasia or thymoma. It is now widely accepted that the thymus is probably the site of AChR autosensitization and autoantibody production. However, the exact mechanism that triggers intrathymic AChR antibody production is still unknown. T follicular helper cells, recently identified responsible for B cell maturation and antibody production in the secondary lymphoid organs, were involved in many autoimmune diseases. Newly studies found T follicular helper (Tfh) cells increased in the peripheral blood of myasthenia gravis (MG). Whether it appears in the thymus of MG and its role in the intrathymic B cells help and autoantibody production is unclear. Therefore, this study aims to determine in more detail whether Tfh/B cell interaction exist in MG thymus and to address its role in the ectopic germinal centers (GCs) formation and AChR antibody production. We observed the frequency of Tfh cells and its associated transcription factor Bcl-6, key cytokine IL-21 enhanced both in the thymocytes and peripheral blood mononuclear cells (PBMCs) of MG patients. In parallel, we also showed increased B cells and autoantibody titers in MG peripheral blood and thymus. Confocal microscope results demonstrated Tfh and B cells co-localized within the ectopic GCs in MG thymus, suggesting putative existence of Tfh/B cells interaction. In vitro studies further showed dynamic behavior of Tfh/B cells interaction and Tfh cells induced autoantibody secretion might through its effector cytokine IL-21. Altogether, our data demonstrated that intrathymic Tfh/B cells interaction played a key role in thymic ectopic GCs formation and anti-AChR antibody production, which might trigger MG occurrence.
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In vitro differentiation of bone marrow mesenchymal stem cells into endometrial epithelial cells in mouse: a proteomic analysis.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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Mouse bone marrow mesenchymal stem cells (BMSCs) have been demonstrated to differentiate into female endometrial epithelial cells (EECs) in vivo. Our previous studies demonstrated that BMSCs can differentiate in the direction of EECs when co-cultured with endometrial stromal cells in vitro. Here, we obtain and analyse differential proteins and their relevant pathways in the process of BMSCs differentiating into EECs by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis.
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Clinical value of serum Epstein-Barr virus DNA assay in the diagnosis of nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 05-19-2014
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Serum Epstein-Barr virus DNA has been approved for diagnosing nasopharyngeal carcinoma (NPC). The goal of this meta-analysis was to evaluate the clinical value of the serum Epstein-Barr virus DNA in the diagnosis of NPC. The PubMed, Embase, Web of Knowledge, Chinese Wanfang Med Online, and National Knowledge Infrastructure (CNKI) databases were searched to identify suitable studies. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) of the serum Epstein-Barr virus DNA for the diagnosis of NPC were calculated. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 and Stata 12.0 softwares were used to analyze the data. A total of 2,520 patients from ten trials were subjected to meta-analysis. The summary estimates of the serum Epstein-Barr virus DNA for NPC diagnosis were as follows: sensitivity 0.69 (95 % confidence interval (CI) 0.65-0.72), specificity 0.84 (95 % CI?=?0.82-0.86), LR?+?4.81 (95 % CI?=?2.94-7.88), LR?-?0.25 (95 % CI?=?0.13-0.48), DOR 24.65 (95 % CI?=?12.64-48.07), and area under the summary receiver operator characteristic (SROC) curve (AUC) was 0.8979. Our study demonstrates that the serum Epstein-Barr virus DNA could be a useful tumor marker for NPC diagnosis.
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Further study of multigranulation T-fuzzy rough sets.
ScientificWorldJournal
PUBLISHED: 05-15-2014
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The optimistic multigranulation T-fuzzy rough set model was established based on multiple granulations under T-fuzzy approximation space by Xu et al., 2012. From the reference, a natural idea is to consider pessimistic multigranulation model in T-fuzzy approximation space. So, in this paper, the main objective is to make further studies according to Xu et al., 2012. The optimistic multigranulation T-fuzzy rough set model is improved deeply by investigating some further properties. And a complete multigranulation T-fuzzy rough set model is constituted by addressing the pessimistic multigranulation T-fuzzy rough set. The full important properties of multigranulation T-fuzzy lower and upper approximation operators are also presented. Moreover, relationships between multigranulation and classical T-fuzzy rough sets have been studied carefully. From the relationships, we can find that the T-fuzzy rough set model is a special instance of the two new types of models. In order to interpret and illustrate optimistic and pessimistic multigranulation T-fuzzy rough set models, a case is considered, which is helpful for applying these theories to practical issues.
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C/EBP? promotes angiogenesis through secretion of IL-6, which is inhibited by genistein, in EGFRvIII-positive glioblastoma.
Int. J. Cancer
PUBLISHED: 05-13-2014
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To study the mechanisms underlying the IL-6-promoted angiogenic microenvironment in EGFRvIII-positive glioblastoma, VEGF expression in EGFRvIII positive/negative tumors was determined by optical molecular imaging. Next, the HUVEC tube formation assay, Western blot, qPCR, RNA silencing, chromatin immuno-precipitation, luciferase reporter, and ELISA assays were performed to examine the role of IL-6 and C/EBP? in the formation of the angiogenic microenvironment in EGFRvIII-positive tumors. Finally, in vitro and in vivo genistein treatment experiments were conducted to challenge the interaction between the IL-6 promoter and C/EBP?. Optical imaging revealed greater VEGF expression in EGFRvIII-positive tumor-bearing mice, suggesting an angiogenic microenvironment. In vitro experiments demonstrated that C/EBP?-mediated regulation of IL-6 was indispensable for maintenance of this angiogenic microenvironment. In contrast, genistein-mediated up-regulation of CHOP impeded C/EBP? interaction with the IL-6 promoter, thus disturbing the angiogenic microenvironment. This more malignant microenvironment in EGFRvIII glioblastoma is generated, at least in part, by greater VEGF, IL-6, and C/EBP? expression. Interaction of C/EBP? with the IL-6 promoter maintains this angiogenic microenvironment, while disturbance of this dynamically balanced interaction inhibits EGFRvIII tumor proliferation by reducing both VEGF and IL-6 expression. © 2014 Wiley Periodicals, Inc.
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Efficient thermolysis route to monodisperse Cu?ZnSnS? nanocrystals with controlled shape and structure.
Sci Rep
PUBLISHED: 05-09-2014
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Monodisperse Cu2ZnSnS4 (CZTS) nanocrystals with tunable shape, crystalline phase, and composition are synthesized by efficient thermolysis of a single source precursor of mixed metal-oleate complexes in hot organic solvents with dissolved sulfur sources. Suitable tuning of the synthetic conditions and the Cu/(Zn + Sn) ratio of the precursor has enabled precise control of the crystalline phase in the form of kesterite, or a newly observed wurtzite structure. Nanocrystals with morphology in the form of spherical, rice-like, or rod-like shapes are obtained over a wide range of compositions (0.5 ? Cu/(Zn + Sn) ? 1.2). Both the final products and intermediates for each shape exhibit consistent composition and structure, indicating homogenous nucleation and growth of single-phase nanocrystals. Thin films prepared from colloidal nanocrystal suspensions display interesting shape-dependent photoresponse behavior under white light illumination from a solar simulator.
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[Clinical analysis of 81 cases of malignant lymphoma treated with autologous hematopoietic stem cell transplantation].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 04-25-2014
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To investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma.
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Estrogen promotes Leydig cell engulfment by macrophages in male infertility.
J. Clin. Invest.
PUBLISHED: 04-24-2014
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Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor ? (ER?KO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ER? signaling. E2 stimulated LCs to produce growth arrest-specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ER?-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility.
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Prostaglandin E2 EP1 receptor enhances TGF??1-induced mesangial cell injury.
Int. J. Mol. Med.
PUBLISHED: 04-20-2014
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Increasing evidence indicates that transforming growth factor-?1 (TGF-?1) is a pivotal mediator in the pathogenesis of renal fibrosis. Mesangial cells (MCs) are important for glomerular function under both physiological and pathological conditions. Studies have found that the expression level of prostaglandin E2 (PGE2) in MCs increases under high glucose conditions, that PGE2 affects the proliferation and hypertrophy of MCs mainly through the EP1 pathway, and that the proliferation of MCs and the accumulation of extracellular matrix are the main events leading to glomerular fibrosis. In this study, we investigated the effects and mechanisms of action of the EP1 receptor, which is induced by transforming growth factor (TGF)-?1, on the proliferation of mouse MCs, the accumulation of extracellular matrix and the expression of PGE2 synthase. Primary mouse glomerular MCs were isolated from EP1 receptor-deficient mice (EP1-/- mice, in which the EP1 receptor was knocked down) and wild-type (WT) mice (WT MCs). In our preliminary experiments, we found that cell proliferation, as well as the mRNA and protein expression of cyclin D1, proliferating cell nuclear antigen (PCNA), fibronectin (FN), collagen ? (Col?), membrane-associated PGE2 synthase-1 (mPGES-1) and cyclooxygenase-2 (COX-2) in the WT MCs were significantly increased following treatment with 10 ng/ml TGF-?1 for 24 h. Compared with the WT MCs, following the knockdown of the EP1 gene, the TGF-?1-induced MC injury was markedly suppressed. The aforementioned changes were notably enhanced following treatment with the EP1 agonist, 17-phenyl trinor PGE2 ethyl amide. Additionally, TGF-?1 induced extracellular signal-regulated kinase (ERK) phosphorylation. We found that the TGF-?1-induced ERK phosphorylation was alleviated by EP1 knockdown and promoted by EP1 expresion. These results suggest that the EP1 receptor plays a role in the proliferation of mouse MCs, in the accumulation of extracellular matrix and in the expression of mPGES-1 induced by TGF-?1. Its mechanisms of action are possibly related to the reinforcement of ERK phosphorylation.
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The uptake mechanism and biocompatibility of graphene quantum dots with human neural stem cells.
Nanoscale
PUBLISHED: 04-17-2014
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Cellular imaging after transplantation may provide important information to determine the efficacy of stem cell therapy. We have reported that graphene quantum dots (GQDs) are a type of robust biological labeling agent for stem cells that demonstrate little cytotoxicity. In this study, we examined the interactions of GQDs on human neural stem cells (hNSCs) with the aim to investigate the uptake and biocompatibility of GQDs. We examined the mechanism of GQD uptake by hNSCs and investigated the effects of GQDs on the proliferation, metabolic activity, and differentiation potential of hNSCs. This information is critical to assess the suitability of GQDs for stem cell tracking. Our results indicated that GQDs were taken up into hNSCs in a concentration- and time-dependent manner via the endocytosis mechanism. Furthermore, no significant change was found in the viability, proliferation, metabolic activity, and differentiation potential of hNSCs after treatment with GQDs. Thus, these data open a promising avenue for labeling stem cells with GQDs and also offer a potential opportunity to develop GQDs for biomedical applications.
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Cyclosporine A protects podocytes via stabilization of cofilin-1 expression in the unphosphorylated state.
Exp. Biol. Med. (Maywood)
PUBLISHED: 04-15-2014
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Podocyte foot process (FP) is dysregulated in nephrotic syndrome. The effacement of podocyte FPs typically arises following perturbations in the actin cytoskeleton. Recent data suggest that the effects of calcineurin (CaN) inhibitor cyclosporine A (CsA) are independent of its effects on T-cells, and CsA has been identified as stabilizing the actin cytoskeleton through stabilizing synaptopodin in podocytes, and thereby directly reducing proteinuria. Other studies showed that CsA could regulate cofilin-1 directly within tubular epithelial cells. However, whether synaptopodin is the only target of CsA or whether the antiproteinuric role of CsA is played by regulating cofilin-1 in podocytes has not been studied. In the present study, changes in the expression and distribution of nephrin, synaptopodin, cofilin-1 and phosphorylated cofilin-1 (pho-cofilin-1) were detected in both puromycin aminonucleoside (PAN) induced nephrotic rats treated with CsA and cultured podocytes exposed to PAN with/without CsA. Cofilin-1, synaptopodin mRNA was knocked down or combined by siRNA to investigate whether cofilin-1 was critical for the protective effect of CsA and whether the effect of CsA on cofilin-1 was independent of its effect on synaptopodin. We found that CsA reduced proteinuria and repaired FP effacement of PAN-induced nephropathy, restored expression of nephrin, synaptopodin, cofilin-1, pho-cofilin-1 both in vivo and in vitro. CsA also repaired actin cytoskeleton impaired by PAN in vitro. The protective effect of CsA was diminished when cofilin-1 was knocked down compared to negative control. Synaptopodin knocked down had no effect on cofilin-1. The protective effect of CsA decreased significantly when cofilin-1 and synaptopodin were simultaneously knocked down compared to only cofilin-1 knock down. In conclusion, the antiproteinuric effect of CsA is derived from the stabilization of the podocyte actin cytoskeleton by upregulating expression of cofilin-1, which was independent of its effect on synaptopodin.
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Reduced levels of interleukin?1 receptor antagonist act as a marker for pneumonia in the elderly.
Mol Med Rep
PUBLISHED: 04-14-2014
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Pneumonia is a disease causing serious inflammation and infection of the lungs and accounts for >50,000 mortalities annually. The elderly are at an increased risk of developing pneumonia. Pneumonia is more serious in the elderly than in any other age group due to the increased inflammation and risk of community?acquired pneumonia associated with aging. Interleukin?1 receptor antagonist (IL?1RA) is an anti?inflammatory protein that counteracts the destructive effects of inflammatory proteins. Therefore, the possible association between pneumonia in elderly individuals and reduced levels of IL?1RA was investigated in the present study. The number of lymphocytes was counted in all subjects and the relative protein expression levels of IL?1RA were determined using western blot analysis. In addition, the immunological activities of IL?1RA were measured using ELISA. The results demonstrated that the numbers of lymphocytes in the serum and bronchoalveolar lavage fluid (BALF) were significantly higher in elderly patients than those in young patients. Furthermore, the serum and BALF levels of IL?1RA in elderly patients were significantly lower than those in young patients (P<0.05 and P<0.01, respectively). Therefore, reduced levels of IL?1RA in BALF may act as a marker for pneumonia in the elderly and may be a potential adjuvant for the diagnosis of pneumonia in elderly individuals. The results also showed that smoking was associated with significant reductions in the levels of IL?1RA in the BALF of elderly patients. The association between smokers and non?smokers found in this study provides support for the hypothesis that smoking may contribute to the pathogenesis of pneumonia by further reducing IL?IRA levels in certain elderly patients.
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Melatonin Treatment Protects Against Acute Spinal Cord Injury-Induced Disruption of Blood Spinal Cord Barrier in Mice.
J. Mol. Neurosci.
PUBLISHED: 04-08-2014
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The spinal cord microcirculation plays a critically important role in maintaining the normal function of spinal cord neurons, glial cells, and axons. Previous researches were largely focused on improved neurological manifestations of spinal cord injury (SCI) while ignoring to improve spinal cord microcirculation disorder after melatonin treatment. Therefore, the mechanism of melatonin that affects blood spinal cord barrier (BSCB) integrity and microcirculation in SCI remains unclear. The present study was performed to investigate the effect of melatonin on the BSCB in a SCI mice model. Melatonin (5, 10, 25, 50, 100 mg/kg i.p.) was administered to mice immediately following SCI. Compared to the 48 h post-SCI group, mice treated with melatonin (50 mg/kg) exhibited significantly reduced BSCB permeability. Additionally, melatonin treatment restrained microvessel loss; attenuated edema; protected the tight junction proteins, endothelial cells, and pericytes; decreased the number of cell apoptosis; and reduced MMP3/AQP4/HIF-1?/VEGF/VEGFR2 expression after SCI. Above all, our results clearly demonstrated that melatonin could stabilize microvascular barrier function and microcirculation of SCI, whose mechanism was to promote the repair of the damaged BSCB.
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Comparison of glucocorticoids alone and combined with cyclosporine a in patients with IgA nephropathy: a prospective randomized controlled trial.
Intern. Med.
PUBLISHED: 04-04-2014
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The aim of this study was to investigate the effects of two different treatment regimes in patients with IgA nephropathy (IgAN): steroids alone and in combination with a medium dose of cyclosporine A (CsA).
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Complement-related proteins control the flavivirus infection of Aedes aegypti by inducing antimicrobial peptides.
PLoS Pathog.
PUBLISHED: 04-01-2014
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The complement system functions during the early phase of infection and directly mediates pathogen elimination. The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism. Thioester (TE)-containing proteins (TEPs), which show high similarity to mammalian complement C3, are thought to play a key role in innate immunity in arthropods. Herein, we report that a viral recognition cascade composed of two complement-related proteins limits the flaviviral infection of Aedes aegypti. An A. aegypti macroglobulin complement-related factor (AaMCR), belonging to the insect TEP family, is a crucial effector in opposing the flaviviral infection of A. aegypti. However, AaMCR does not directly interact with DENV, and its antiviral effect requires an A. aegypti homologue of scavenger receptor-C (AaSR-C), which interacts with DENV and AaMCR simultaneously in vitro and in vivo. Furthermore, recognition of DENV by the AaSR-C/AaMCR axis regulates the expression of antimicrobial peptides (AMPs), which exerts potent anti-DENV activity. Our results both demonstrate the existence of a viral recognition pathway that controls the flaviviral infection by inducing AMPs and offer insights into a previously unappreciated antiviral function of the complement-like system in arthropods.
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FAM3A activates PI3K p110?/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis.
Hepatology
PUBLISHED: 03-27-2014
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FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found a marked reduction of FAM3A expression in the livers of db/db and high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression of FAM3A markedly attenuated hyperglycemia, insulin resistance, and fatty liver with increased Akt (pAkt) signaling and repressed gluconeogenesis and lipogenesis in the livers of those mice. In contrast, small interfering RNA (siRNA)-mediated knockdown of hepatic FAM3A resulted in hyperglycemia with reduced pAkt levels and increased gluconeogenesis and lipogenesis in the livers of C57BL/6 mice. In vitro study revealed that FAM3A was mainly localized in the mitochondria, where it increases adenosine triphosphate (ATP) production and secretion in cultured hepatocytes. FAM3A activated Akt through the p110? catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca(2+) levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM).
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Streptococcus suis type 2 SSU0587 protein is a beta-galactosidase that contributes to bacterial adhesion but not to virulence in mice.
J. Vet. Med. Sci.
PUBLISHED: 03-27-2014
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Bacterial surface proteins play key roles in virulence and often contribute to bacterial adhesion and invasion. We discovered that the Streptococcus suis type 2 (SS2) gene SSU0587 encodes a protein of 1,491 amino acids that possesses ?-galactosidase activity. The surface association of the protein was dependent upon sortase activity. Deleting SSU0587 from clinical SS2 isolate JX081101 caused a loss of both ?-galactosidase activity and adherence to microvascular endothelial cells. Deleting SSU0587 had no measurable impact on either invasion of microvascular endothelial cells or on virulence in a murine infection model, although the concentration of JX081101?SSU0587 was reduced in the brains of infected mice, as compared with the pathogen loads of the wild-type strain.
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Synergistic effects of combined platelet-activating factor receptor and epidermal growth factor receptor targeting in ovarian cancer cells.
J Hematol Oncol
PUBLISHED: 03-14-2014
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Genetic alterations, including the overexpression of epidermal growth factor receptor (EGFR), play a crucial role in ovarian carcinogenesis. To date, EGFR targeting has shown limited antitumor effects in ovarian cancer when administered as monotherapy. We previously identified platelet-activating factor receptor (PAFR) as being overexpressed in ovarian cancer and found that its ligand PAF evoked EGFR phosphorylation. To determine whether PAFR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a PAFR antagonist (WEB2086) in conjunction with an EGFR inhibitor (AG1478).
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Emodin up-regulates glucose metabolism, decreases lipolysis, and attenuates inflammation in vitro.
J Diabetes
PUBLISHED: 03-13-2014
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Emodin, the major bioactive component of Rheum palmatum, has many different activities, including antitumor, anti-inflammatory, and antidiabetes effects. Recently, emodin was reported to regulate energy metabolism. In the present study, we further explored the effects of emodin on glucose and lipid metabolism.
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Efficacy of kidney-tonifying traditional Chinese medicine prescriptions in hypoplastic uterus treatment: a systematic review and meta-analysis.
J. Obstet. Gynaecol. Res.
PUBLISHED: 03-12-2014
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To review and evaluate the efficacy of kidney-tonifying traditional Chinese medicine prescriptions (KT-TCMP) in hypoplastic uterus (HU) treatment.
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Fracture property of Y-shaped cracks of brittle materials under compression.
ScientificWorldJournal
PUBLISHED: 03-11-2014
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In order to investigate the properties of Y-shaped cracks of brittle materials under compression, compression tests by using square cement mortar specimens with Y-shaped crack were conducted. A true triaxial loading device was applied in the tests, and the major principle stresses or the critical stresses were measured. The results show that as the branch angle ? between the branch crack and the stem crack is 75°, the cracked specimen has the lowest strength. In order to explain the test results, numerical models of Y-shaped cracks by using ABAQUS code were established, and the J-integral method was applied in calculating crack tip stress intensity factor (SIF). The results show that when the branch angle ? increases, the SIF K I of the branch crack increases from negative to positive and the absolute value K II of the branch crack first increases, and as ? is 50°, it is the maximum, and then it decreases. Finally, in order to further investigate the stress distribution around Y-shaped cracks, photoelastic tests were conducted, and the test results generally agree with the compressive test results.
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Fusion-expressed CTB improves both systemic and mucosal T-cell responses elicited by an intranasal DNA priming/intramuscular recombinant vaccinia boosting regimen.
J Immunol Res
PUBLISHED: 03-07-2014
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Previous study showed that CTB (Cholera toxin subunit B) can be used as a genetic adjuvant to enhance the systemic immune responses. To further investigate whether it can also be used as a genetic adjuvant to improve mucosal immune responses, we constructed DNA and recombinant Tiantan vaccinia (rTTV) vaccines expressing OVA-CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were measured by IFN-? ELISPOT and specific antibody responses were determined by ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA intramuscular boosting), pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB intramuscular boosting group significantly improved the magnitudes of T-cell responses at spleen (1562 ± 567 SFCs/10(6) splenocytes versus 330 ± 182 SFCs/10(6) splenocytes, P < 0.01), mesenteric LN (96 ± 83 SFCs/10(6) lymphocytes versus 1 ± 2 SFCs/10(6) lymphocytes, P < 0.05), draining LNs of respiratory tract (109 ± 60 SFCs/10(6) lymphocytes versus 2 ± 2 SFCs/10(6) lymphocytes, P < 0.01) and female genital tract (89 ± 48 SFCs/10(6) lymphocytes versus 23 ± 21 SFCs/10(6) lymphocytes, P < 0.01). These results collectively demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve both systemic and mucosal T-cell responses.
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A photoresponsive wettability switch based on a dimethylamino calix[4]arene.
Chemistry
PUBLISHED: 03-05-2014
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A photoreversible switch based on a photoresponsive host-guest system consisting of dimethylamino calix[4]arene L and 4-(phenylazo)benzoic acid (O) is reported. The host L exhibited selective binding and release of O on UV and visible irradiation at 450 and 365?nm, respectively. Moreover, the photoresponsive host-guest complex was applied as a photocontrolled wettability switch on a functional micro/nanostructured silicon surface, and is thus promising for applications in sensors and microfluidic devices.
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Facile synthesis and optical properties of polymer-laced ZnO-Au hybrid nanoparticles.
Nanoscale Res Lett
PUBLISHED: 02-27-2014
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Bi-phase dispersible ZnO-Au hybrid nanoparticles were synthesized via one-pot non-aqueous nanoemulsion using the triblock copolymer poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) as the surfactant. The characterization shows that the polymer-laced ZnO-Au nanoparticles are monosized and of high crystallinity and demonstrate excellent dispersibility and optical performance in both organic and aqueous medium, revealing the effects of quantum confinement and medium. The findings show two well-behaved absorption bands locating at approximately 360 nm from ZnO and between 520 and 550 nm from the surface plasmon resonance of the nanosized Au and multiple visible fingerprint photoluminescent emissions. Consequently, the wide optical absorbance and fluorescent activity in different solvents could be promising for biosensing, photocatalysis, photodegradation, and optoelectronic devices.
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Decreased PPAR-? expression in the conjunctiva and increased expression of TNF-? and IL-1? in the conjunctiva and tear fluid of dry eye mice.
Mol Med Rep
PUBLISHED: 02-25-2014
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The aim of this study was to investigate the expression of peroxisome proliferator-activated receptor ? (PPAR-?), tumor necrosis factor (TNF)-? and interleukin (IL)-1? in the conjunctiva and the association between inflammatory cytokines and PPAR-? in dry eye mice. Dry eye was induced in 6-week-old female C57 mice. mRNA expression of PPAR-?, TNF-? and IL-1? were measured. PPAR-? protein expression in the conjunctiva, and the contents of TNF-? and IL-1? in the conjunctiva and tear-wash fluid were determined. A PPAR-? agonist, pioglitazone (PIO), was used to treat dry eye mice. Dry eye mice presented with similar manifestations as in humans. The PPAR-? expression in the conjunctiva of dry eye mice was downregulated, accompanied by increased contents of TNF-? and IL-1?. PIO treatment markedly reduced the contents of TNF-? and IL-1? in tear fluid of dry eye mice. Following PIO treatment, the PPAR-? expression increased markedly. PIO may activate PPAR-? to inhibit the expression of the inflammatory cytokines TNF-? and IL-1? in dry eye mice. This suppresses the inflammatory progression, increases the tear fluid production, elevates the tear film stability and reduces the damage to the ocular surface, exerting a therapeutic effect on dry eye.
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Serum Zta antibody of Epstein-Barr virus exerts potential function in the diagnosis of nasopharyngeal cancer.
Tumour Biol.
PUBLISHED: 02-21-2014
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The diagnosis of nasopharyngeal cancer (NPC) remains a clinical challenge. Many studies have assessed the diagnostic potential of Zta antibody of the Epstein-Barr virus (EBV) in NPC patients but with controversial results. This study aims to summarize the overall diagnostic performance of EBV Zta antibody in NPC. Based on a comprehensive search of the Pubmed and Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Databases and China Citation Databases, we identified outcome data from all articles estimating diagnostic accuracy of EBV Zta antibody for NPC. A summary estimation for sensitivity, specificity, and other diagnostic indexes were pooled using a bivariate model. The overall measure of accuracy was calculated using summary receiver operating characteristic curve and the area under curve (AUC) was calculated. According to our inclusion criteria, 17 studies with 11,822 subjects (1,645 NPC cases, 10,177 controls) were included. The summary estimates were: sensitivity 0.87 (95 % confidence interval [CI]?= 0.86-0.89), specificity 0.94 (95 % CI = 0.93-0.94), positive likelihood ratio 8.05 (95 % CI = 5.59-11.59), negative likelihood ratio 0.16 (95 % CI = 0.12-0.21), diagnostic odds ratio 52.93 (95 % CI = 29.95-93.56), the AUC and Q* index were 0.9352 and 0.8714, respectively. In conclusion, serum EBV Zta had a better diagnostic performance for NPC. Further studies should be performed to confirm our findings.
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Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy.
Gynecol. Oncol.
PUBLISHED: 02-20-2014
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Traditional chemotherapy drugs have an obvious drawback of nonspecific biodistribution in treating ovarian cancer. Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor which is mainly expressed in reproductive system, is an important drug target in developing novel therapeutics.
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The role of survivin in podocyte injury induced by puromycin aminonucleoside.
Int J Mol Sci
PUBLISHED: 01-24-2014
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Survivin is a member of the inhibitor of apoptosis protein family, which uniquely promotes mitosis and regulates apoptosis in cancer cells. Recent studies have demonstrated that survivin also expresses in several normal adult cells. In the present study, we aimed to investigate the function of survivin in the terminally differentiated epithelial cells, podocytes.
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Association between diabetes mellitus with metabolic syndrome and diabetic microangiopathy.
Exp Ther Med
PUBLISHED: 01-12-2014
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The aim of this study was to investigate the association between diabetes mellitus (DM), mainly type II, with metabolic syndrome (MS) and diabetic nephropathy (DN)/diabetic retinopathy (DR). Based on the analysis of the prevalence of MS, patients with DM were divided into MS and non-MS groups according to the presence or absence of MS. The correlation between DN, DR and certain factors, including gender, age, disease duration and the presence or absence of a family history of MS, were analyzed. The prevalence of MS among the patients with DM was 62.50%. The prevalence of DN was 55.33% in the MS group and that of DR was 26.00%. DN was positively correlated with age, gender, blood pressure, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and blood uric acid. DR was positively correlated with traceable disease duration and LDL-C. In conclusion, DM occurred more frequently in concurrence with MS than without MS, and the prevalence of DN/DR in the MS group was higher than that in the non-MS group. Age, gender, blood pressure, TG, LDL-C and blood uric acid were risk factors for DN and the traceable disease duration and LDL-C were risk factors for DR.
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Arabidopsis HSP90 protein modulates RPP4-mediated temperature-dependent cell death and defense responses.
New Phytol.
PUBLISHED: 01-12-2014
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Plant defense responses are regulated by temperature. In Arabidopsis, the chilling-sensitive mutant chs2-1 (rpp4-1d) contains a gain-of-function mutation in the TIR-NB-LRR (Toll and interleukin 1 receptor-nucleotide binding-leucine-rich repeat) gene, RPP4 (RECOGNITION OF PERONOSPORA PARASITICA 4), which leads to constitutive activation of the defense response at low temperatures. Here, we identified and characterized two suppressors of rpp4-1d from a genetic screen, hsp90.2 and hsp90.3, which carry point mutations in the cytosolic heat shock proteins HSP90.2 and HSP90.3, respectively. The hsp90 mutants suppressed the chilling sensitivity of rpp4-1d, including seedling lethality, activation of the defense responses and cell death under chilling stress. The hsp90 mutants exhibited compromised RPM1 (RESISTANCE TO PSEUDOMONAS MACULICOLA 1)-, RPS4 (RESISTANCE TO P. SYRINGAE 4)- and RPP4-mediated pathogen resistance. The wild-type RPP4 and the mutated form rpp4 could interact with HSP90 to form a protein complex. Furthermore, RPP4 and rpp4 proteins accumulated in the cytoplasm and nucleus at normal temperatures, whereas the nuclear accumulation of the mutated rpp4 was decreased at low temperatures. Genetic analysis of the intragenic suppressors of rpp4-1d revealed the important functions of the NB-ARC and LRR domains of RPP4 in temperature-dependent defense signaling. In addition, the rpp4-1d-induced chilling sensitivity was largely independent of the WRKY70 or MOS (modifier of snc1) genes. [Correction added after online publication 11 March 2013: the expansions of TIR-NB-LRR and RPS4 were amended] This study reveals that Arabidopsis HSP90 regulates RPP4-mediated temperature-dependent cell death and defense responses.
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Responses of kinetics and capacity of phenanthrene sorption on sediments to soil organic matter releasing.
Environ Sci Pollut Res Int
PUBLISHED: 01-09-2014
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Soil organic matter (SOM) releasing with dissolved organic matter (DOM) formed in solution was confirmed in a sediment/water system, and the effects of SOM releasing on the sorption of phenanthrene on sediments were investigated. Inorganic salt (0-0.1 mol L(-1) NaCl) was used to adjust SOM releasing, and two sediments were prepared, the raw sediment (S1) from Weihe River, Shann'xi, China, and the eluted sediments with and without DOM supernatant remained, termed as S2a and S2b, respectively. The FTIR and (1)H NMR analysis indicate that the low molecular weight hydrophilic SOM fraction released prior to the high molecular weight hydrophobic fraction. As a response, phenanthrene sorption kinetics on S1 showed atypical and expressed as three stages: rapid sorption, pseudo sorption with partial desorption, and slow sorption, thus a defined "sorption valley" occurred in kinetic curve. In all cases, partition dominates the sorption, and sorption capacity (Kd) ranked as S2b > S1 > S2a. Compared with the alterations of sediment characters, DOM solubilization produced by SOM releasing exhibited a greater inhibitory effect on sorption with a relative contribution of 0.67. Distribution coefficients (K(doc)) of PHE into DOM clusters were 2.10 × 10(4)-4.18 × 10(4) L kg(-1), however a threshold concentration of 6.83 mg L(-1) existed in DOM solubilization. The study results will help to clarify PAHs transport and their biological fate in a sediment/water system.
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Epidemiologic report and serologic findings for household contacts of three cases of influenza A (H7N9) virus infection.
J. Clin. Virol.
PUBLISHED: 01-07-2014
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We conducted epidemiologic investigations and serologic assays on household contacts that were extensively exposed to three influenza A (H7N9) virus infected case-patients before infection-control practices were implemented.
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Mammalian target of rapamycin complex 2 signaling pathway regulates transient receptor potential cation channel 6 in podocytes.
PLoS ONE
PUBLISHED: 01-01-2014
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Transient receptor potential cation channel 6 (TRPC6) is a nonselective cation channel, and abnormal expression and gain of function of TRPC6 are involved in the pathogenesis of hereditary and nonhereditary forms of renal disease. Although the molecular mechanisms underlying these diseases remain poorly understood, recent investigations revealed that many signaling pathways are involved in regulating TRPC6. We aimed to examine the effect of the mammalian target of rapamycin (mTOR) complex (mTOR complex 1 [mTORC1] or mTOR complex 2 [mTORC2]) signaling pathways on TRPC6 in podocytes, which are highly terminally differentiated renal epithelial cells that are critically required for the maintenance of the glomerular filtration barrier. We applied both pharmacological inhibitors of mTOR and specific siRNAs against mTOR components to explore which mTOR signaling pathway is involved in the regulation of TRPC6 in podocytes. The podocytes were exposed to rapamycin, an inhibitor of mTORC1, and ku0063794, a dual inhibitor of mTORC1 and mTORC2. In addition, specific siRNA-mediated knockdown of the mTORC1 component raptor and the mTORC2 component rictor was employed. The TRPC6 mRNA and protein expression levels were examined via real-time quantitative PCR and Western blot, respectively. Additionally, fluorescence calcium imaging was performed to evaluate the function of TRPC6 in podocytes. Rapamycin displayed no effect on the TRPC6 mRNA or protein expression levels or TRPC6-dependent calcium influx in podocytes. However, ku0063794 down-regulated the TRPC6 mRNA and protein levels and suppressed TRPC6-dependent calcium influx in podocytes. Furthermore, knockdown of raptor did not affect TRPC6 expression or function, whereas rictor knockdown suppressed TRPC6 protein expression and TRPC6-dependent calcium influx in podocytes. These findings indicate that the mTORC2 signaling pathway regulates TRPC6 in podocytes but that the mTORC1 signaling pathway does not appear to exert an effect on TRPC6.
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Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China.
PLoS ONE
PUBLISHED: 01-01-2014
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More and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals.
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Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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We determined the efficacy and safety of chitosan (CS)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV). The newly constructed vaccine contained DNA (the F gene) of NDV. The Newcastle disease virus (NDV) F gene deoxyribonucleic acid (DNA) plasmid (pFDNA)-CS/PLGA-NPs were spherical (diameter =699.1 ± 5.21 nm [mean ± standard deviation]) and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs) was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine.
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Activation of the Wnt pathway through Wnt2 promotes metastasis in pancreatic cancer.
Am J Cancer Res
PUBLISHED: 01-01-2014
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Wnt signaling pathway plays an important role in physiological and pathological process, including in the occurrence and development of tumor. The purpose of this study is to determine whether Wnt2 and sFRP4, key molecules of signaling pathway, are of prognostic value for survival in patients with pancreatic cancer. We performed immunohistochemistry on tissue microarrays containing 90 pancreatic cancer specimens to evaluate the protein expression of Wnt2 and sFRP4. Our results showed that the cytoplasmic expression level of Wnt2 in pancreatic cancer tissues was significantly associated with LNM (P=0.029) and AJCC stage (P=0.008). Additionally, Kaplan-Meier analysis indicated that high Wnt2 expression was significantly correlated with poor clinical outcomes of patients with pancreatic cancer. In conclusion, Wnt2 may play an important role in the development of pancreatic cancer through activation of the Wnt pathways and serve as a potential candidate for treatment target of pancreatic cancer.
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Expression of Indian hedgehog is negatively correlated with APC gene mutation in colorectal tumors.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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The regulatory mechanism of Indian hedgehog (IHH) in colorectal carcinogenesis has not been elucidated. In the current study, the expression of IHH were investigated in 7 digestive tract cancer cell lines, and in 10 normal colorectal mucosas (NCs), 30 hyperplastic polyps (HPs), 35 colorectal adenomas (ADs), and 40 colorectal adenocarcinomas (CAs) by semi-quantitative RT-PCR and immunohistochemical staining. Moreover, the mutational status of adenomatous polyposis coli (APC) and ?-catenin in these tumors were analyzed by direct sequencing. IHH mRNA was lost in the 4 colon cancer cell lines harboring APC mutation. IHH mRNA was significantly decreased in CAs (0.17 ± 0.22), compared with that in ADs (0.38 ± 0.35) and HPs (0.56 ± 0.38, P < 0.05). IHH protein was expressed at a very low level or absent in both ADs (7.51 ± 11.92) and CAs (5.15 ± 9.21) in comparison to that in HPs (19.47 ± 17.91) and NCs (42.40 ± 13.67, P < 0.05). Moreover, APC mutations were negatively correlated with IHH mRNA expression (Spearman's R = -0.636, P < 0.01) and IHH protein expression (Spearman's R = -0.426, P < 0.01). In conclusion, down-regulation of IHH expression might be an early event during the carcinogenesis of colorectal cancer. The activation of Wnt signaling by APC mutation might contribute to the down-regulation or loss of IHH expression in colorectal tumors.
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Identification and validation of reference genes for quantitative real-time PCR in Drosophila suzukii (Diptera: Drosophilidae).
PLoS ONE
PUBLISHED: 01-01-2014
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To accurately evaluate gene expression levels and obtain more accurate quantitative real-time RT-PCR (qRT-PCR) data, normalization relative to reliable reference gene(s) is required. Drosophila suzukii, is an invasive fruit pest native to East Asia, and recently invaded Europe and North America, the stability of its reference genes have not been previously investigated. In this study, ten candidate reference genes (RPL18, RPS3, AK, EF-1?, TBP, NADH, HSP22, GAPDH, Actin, ?-Tubulin), were evaluated for their suitability as normalization genes under different biotic (developmental stage, tissue and population), and abiotic (photoperiod, temperature) conditions. The three statistical approaches (geNorm, NormFinder and BestKeeper) and one web-based comprehensive tool (RefFinder) were used to normalize analysis of the ten candidate reference genes identified ?-Tubulin, TBP and AK as the most stable candidates, while HSP22 and Actin showed the lowest expression stability. We used three most stable genes (?-Tubulin, TBP and AK) and one unstably expressed gene to analyze the expression of P-glycoprotein in abamectin-resistant and sensitive strains, and the results were similar to reference genes ?-Tubulin, TBP and AK, which show good stability, while the result of HSP22 has a certain bias. The three validated reference genes can be widely used for quantification of target gene expression with qRT-PCR technology in D.suzukii.
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Epidermal growth factor induces platelet-activating factor production through receptors transactivation and cytosolic phospholipase A2 in ovarian cancer cells.
J Ovarian Res
PUBLISHED: 01-01-2014
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Among the pro-inflammatory lipid mediators, platelet-activating factor (PAF) is a major primary and secondary messenger that binds to the PAF-receptor (PAFR). Epidermal growth factor (EGF) is a polypeptide growth factor that binds to the EGF-receptor (EGFR). Evidence suggests that both PAF and EGF play a significant role in oncogenic transformation, tumor growth, neoangiogenesis and metastasis, including ovarian cancer. PAF has the potential to transactivate EGFR in ovarian cancer cells. This study explores the mechanisms involved in EGF-induced PAF production.
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Development of a convenient in vivo hepatotoxin assay using a transgenic zebrafish line with liver-specific DsRed expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Previously we have developed a transgenic zebrafish line (LiPan) with liver-specific red fluorescent protein (DsRed) expression under the fabp10a promoter. Since red fluorescence in the liver greatly facilitates the observation of liver in live LiPan fry, we envision that the LiPan zebrafish may provide a useful tool in analyses of hepatotoxicity based on changes of liver red fluorescence intensity and size. In this study, we first tested four well-established hepatotoxins (acetaminophen, aspirin, isoniazid and phenylbutazone) in LiPan fry and demonstrated that these hepatotoxins could significantly reduce both liver red fluorescence and liver size in a dosage-dependent manner, thus the two measurable parameters could be used as indicators of hepatotoxicity. We then tested the LiPan fry with nine other chemicals including environmental toxicants and human drugs. Three (mefenamic acid, lindane, and arsenate) behave like hepatotoxins in reduction of liver red fluorescence, while three others (17?-estradiol, TCDD [2,3,7,8-tetrachlorodibenzo-p-dioxin] and NDMA [N-nitrosodimethylamine]) caused increase of liver red fluorescence and the liver size. Ethanol and two other chemicals, amoxicillin (antibiotics) and chlorphenamine (pain killer) did not resulted in significant changes of liver red fluorescence and liver size. By quantitative RT-PCR analysis, we found that the changes of red fluorescence intensity caused by different chemicals correlated to the changes of endogenous fabp10a RNA expression, indicating that the measured hepatotoxicity was related to fatty acid transportation and metabolism. Finally we tested a mixture of four hepatotoxins and observed a significant reduction of red fluorescence in the liver at concentrations below the lowest effective concentrations of individual hepatotoxins, suggesting that the transgenic zebrafish assay is capable of reporting compound hepatotoxicity effect from chemical mixtures. Thus, the LiPan transgenic fry provide a rapid and convenient in vivo hepatotoxicity assay that should be applicable to high-throughput hepatotoxicity test in drug screening as well as in biomonitoring environmental toxicants.
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Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-23-2013
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A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1? were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.
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Double-Sided Brush-Shaped TiO2 Nanostructure Assemblies with Highly Ordered Nanowires for Dye-Sensitized Solar Cells.
ACS Appl Mater Interfaces
PUBLISHED: 12-19-2013
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We describe a seeded hydrothermal process for the growth of unique double-sided brush-shaped (DSBS) TiO2 nanostructure assemblies consisting of highly ordered rutile nanowires vertically aligned around an annealed TiO2 nanoparticle layer. The annealed TiO2 nanoparticle layer seeds the nanowire growth and also supports the DSBS structure. The morphology of the DSBS TiO2 nanostructure depends on the hydrothermal reaction time. The diameter of the nanowires is about 6.6 nm, and with increasing reaction time from 1 to 8 h the nanowire length increases from 0.6 to 6.2 ?m, whereas the thickness of the nanoparticle layer decreases from 4.3 to 2.8 ?m. These free-standing nanowire arrays provide large internal surface area, which is essential for minimizing carrier recombination in high performance photovoltaic devices. Furthermore, the nanowire architecture can help increase the rate of charge transport as compared to particulate films because of lower concentration of grain boundaries. The power conversion efficiency of backside (DSBS TiO2/FTO photoanode) illuminated dye-sensitized solar cells fabricated using the DSBS TiO2 nanostructure assembly is found to be depended on the nanowire length. A cell fabricated using 15.2 ?m thick nanostructures sensitized by N719 has a short-circuit current density of 12.18 mA cm(-2), 0.78 V open circuit potential, and a 0.59 filling factor, yielding a maximum power conversion efficiency of 5.61% under AM 1.5 illumination.
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Structure-Activity Relationship (SAR) Optimization of 6-(Indol-2-yl)pyridine-3-sulfonamides: Identification of Potent, Selective, and Orally Bioavailable Small Molecules Targeting Hepatitis C (HCV) NS4B.
J. Med. Chem.
PUBLISHED: 12-04-2013
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A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the optimal combination of substituents at the indole N-1, C-5, and C-6 positions and the sulfonamide group to limit the potential for in vivo oxidative metabolism and to achieve an acceptable pharmacokinetic profile. Compound 4t has excellent potency against the HCV 1b replicon, with an EC50 = 2 nM and a selectivity index of >5000 with respect to cellular GAPDH. Compound 4t has an overall favorable pharmacokinetic profile with oral bioavailability values of 62%, 78%, and 18% in rats, dogs, and monkeys, respectively, as well as favorable tissue distribution properties with a liver to plasma exposure ratio of 25 in rats.
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In-vitro and in-vivo evaluation of ciprofloxacin liposome for pulmonary administration.
Drug Dev Ind Pharm
PUBLISHED: 11-21-2013
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Abstract Objective: The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats. Methods: Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry. Ciprofloxacin liposome released in vitro was performed using simulated lung fluid. In-vivo studies, pharmacokinetics and pulmonary distribution, HPLC method was established to determine the concentration of ciprofloxacin in rat plasma and lung tissue. The pulmonary pathological section was used to observe the change of pulmonary pathology. Results: The optimized ciprofloxacin liposome, which had a high encapsulation efficiency of 93.96%, and an average particle size of 349.6?nm with a span of 0.42, showed sustained in-vitro release. The optimized ciprofloxacin liposome was further examined in the in-vivo study in rats. The concentration of ciprofloxacin in lung and blood was simultaneously determined in each rat. The ratio of the AUClung value between ciprofloxacin liposome and ciprofloxacin solution was 288.33, whereas the relative bioavailability was 72.42%, and the drug targeting efficiency of ciprofloxacin liposome and ciprofloxacin solution by intratracheal administration were 799.71 and 2.01, respectively. Conclusion: Ciprofloxacin liposome for pulmonary administration offered an attractive alternative that was able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the local irritation.
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Noninvasive quantification of postocclusive reactive hyperemia in mouse thigh muscle by near-infrared diffuse correlation spectroscopy.
Appl Opt
PUBLISHED: 11-13-2013
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Many vasculature-related diseases affecting skeletal muscle function have been studied in mouse models. Noninvasive quantification of muscle blood flow responses during postocclusive reactive hyperemia (PORH) is often used to evaluate vascular function in human skeletal muscles. However, blood flow measurements during PORH in small skeletal muscles of mice are rare due to the lack of appropriate technologies coupled with the challenge of measurement setup resulting from the lack of large enough test sites. In this study, we explored adapting diffuse correlation spectroscopy (DCS) for noninvasive measurement of the relative changes of blood flow (rBF) in mouse thigh muscles during PORH. A small fiber-optic probe was designed and glued on the mouse thigh to reduce the motion artifact induced by the occlusion procedure. Arterial occlusion was created by tying a polyvinyl chloride (PVC) tube around the mouse thigh while the muscle rBF was continuously monitored by DCS to ensure the success of the occlusion. After 5 min, the occlusion was rapidly released by severing the PVC tube using a cautery pen. Typical rBF responses during PORH were observed in all mice (n=7), which are consistent with those observed by arterial-spin-labeled magnetic resonance imaging (ASL-MRI) as reported in the literature. On average, rBF values from DCS during occlusion were lower than 10% (3.1±2.2%) of the baseline values (assigning 100%), indicating the success of arterial occlusion in all mice. Peak values of rBF during PORH measured by the DCS (357.6±36.3%) and ASL-MRI (387.5±150.0%) were also similar whereas the values of time-to-peak (the time duration from the end of occlusion to the peak rBF) were quite different (112.6±35.0??s versus 48.0±27.0??s). Simultaneous measurements by these two techniques are needed to identify the factors that may cause such discrepancy. This study highlights the utility of DCS technology to quantitatively evaluate tissue blood flow responses during PORH in mouse skeletal muscles. DCS holds promise as valuable tool to assess blood flow regulation in mouse models with a variety of vascular diseases (e.g., hypercholesterolemia, diabetes, peripheral artery disease).
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Hg2+ wettability and fluorescence dual-signal responsive switch based on a cysteine complex of piperidine-calix[4]arene.
Org. Biomol. Chem.
PUBLISHED: 10-29-2013
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The recognition of the mercury(II) ion (Hg(2+)) is essential because of its extreme toxicity in the environment and food. Hence we reported a novel cysteine (Cys) complex of piperidine-calix[4]arene (L) as a convenient and effective dual-signal responsive switch for Hg(2+). This switch system exhibited excellent selectivity toward Hg(2+) by fluorescence (FL), (1)H NMR spectroscopy and the atomic force microscopy (AFM). More importantly, the Hg(2+)-responsive switch had an important and potential application by water contact angle (CA) on a functional micro-nano silicon surface, including intelligent microfluidic and laboratory-on-chip devices, controllable drug delivery, and self-cleaning surfaces.
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Downregulation of PTEN expression in psoriatic lesions.
Int. J. Dermatol.
PUBLISHED: 10-29-2013
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Considerable studies showed that tumor suppressor phosphatase and tensin homolog (PTEN) deleted on chromosome 10 is a major tumor suppressor, which inhibits cell proliferation through inactivation of the PI3 kinase (PI3K)/Akt signal pathway. In many human tumors, there is loss of function or mutations in PTEN. In our previous study, it was found that Akt activity in psoriatic lesions increased compared with that in normal controls. However, the expression of PTEN and the correlation between PTEN and PI3K/Akt have not been investigated in patients with psoriasis.
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Phosphorylation regulates VCIP135 function in Golgi membrane fusion during the cell cycle.
J. Cell. Sci.
PUBLISHED: 10-25-2013
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The Golgi apparatus in mammalian cells consists of stacks that are often laterally linked into a ribbon-like structure. During cell division, the Golgi disassembles into tubulovesicular structures in the early stages of mitosis and reforms in the two daughter cells by the end of mitosis. Valosin-containing protein p97-p47 complex-interacting protein, p135 (VCIP135), an essential factor involved in p97-mediated membrane fusion pathways, is required for postmitotic Golgi cisternae regrowth and Golgi structure maintenance in interphase. However, how VCIP135 function is regulated in the cell cycle remains unclear. Here, we report that VCIP135 depletion by RNA interference results in Golgi fragmentation. VCIP135 function requires membrane association and p97 interaction, both of which are inhibited in mitosis by VCIP135 phosphorylation. We found that wild-type VCIP135, but not its phosphomimetic mutants, rescues Golgi structure in VCIP135-depleted cells. Our results demonstrate that VCIP135 phosphorylation regulates its Golgi membrane association and p97 interaction, and thus contributes to the tight control of the Golgi disassembly and reassembly process during the cell cycle.
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Ultrafast saturable absorption of two-dimensional MoS2 nanosheets.
ACS Nano
PUBLISHED: 10-07-2013
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Employing high-yield production of layered materials by liquid-phase exfoliation, molybdenum disulfide (MoS2) dispersions with large populations of single and few layers were prepared. Electron microscopy verified the high quality of the two-dimensional MoS2 nanostructures. Atomic force microscopy analysis revealed that ~39% of the MoS2 flakes had thicknesses of less than 5 nm. Linewidth and frequency difference of the E(1)2g and A1g Raman modes confirmed the effective reduction of flake thicknesses from the bulk MoS2 to the dispersions. Ultrafast nonlinear optical (NLO) properties were investigated using an open-aperture Z-scan technique. All experiments were performed using 100 fs pulses at 800 nm from a mode-locked Ti:sapphire laser. The MoS2 nanosheets exhibited significant saturable absorption (SA) for the femtosecond pulses, resulting in the third-order NLO susceptibility Im?((3)) ~ 10(-15) esu, figure of merit ~10(-15) esu cm, and free-carrier absorption cross section ~10(-17) cm(2). Induced free carrier density and the relaxation time were estimated to be ~10(16) cm(-3) and ~30 fs, respectively. At the same excitation condition, the MoS2 dispersions show better SA response than the graphene dispersions.
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Safe pseudovirus-based assay for neutralization antibodies against influenza A(H7N9) virus.
Emerging Infect. Dis.
PUBLISHED: 09-20-2013
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Serologic studies are urgently needed to assist in understanding an outbreak of influenza A(H7N9) virus. However, a biosafety level 3 laboratory is required for conventional serologic assays with live lethal virus. We describe a safe pseudovirus-based neutralization assay with preliminary assessment using subtype H7N9-infected samples and controls.
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Relationship between platelet volume indices with macrovasular and peripheral neuropathy complications in type 2 diabetic patients.
J Diabetes
PUBLISHED: 09-17-2013
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The relationship of platelet volume indices including mean platelet volume (MPV) and platelet distribution width (PDW) with carotid intima-media thickness (IMT) as well as vibration perception threshold (VPT) was investigated in type 2 diabetic patients.
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Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro.
J Ovarian Res
PUBLISHED: 09-12-2013
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RNA interference technology has shown high therapeutic potential for cancer treatment. However, serum instability, poor tissue permeability and non-specific uptake of short interfering RNA (siRNA) limit its administration in vivo. To overcome these limitations and improve the specificity for ovarian cancer, we developed a targeted nanoparticle delivery system for siRNA. This system included follicle-stimulating hormone (FSH) beta 33--53 peptide as a targeting moiety that specifically recognized FSH receptor (FSHR) expressed on ovarian cancer cells. Growth regulated oncogene alpha (gro-alpha) has been reported to be involved in ovarian cancer development and progression. Thus, siRNA targeted to gro-alpha was used as an antitumor drug in this delivery system.
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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.