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Find video protocols related to scientific articles indexed in Pubmed.
Ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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A novel ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones is described. The process proceeded smoothly under metal-free conditions with high stereoselectivity and good functional group tolerance. The reaction mechanism was revealed to proceed through a domino reaction of oxidation and elimination after the radical addition to alkenes.
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Composition-structure-property relationships for non-classical ionomer cements formulated with zinc-boron germanium-based glasses.
J Biomater Appl
PUBLISHED: 11-14-2014
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Non-classical ionomer glasses like those based on zinc-boron-germanium glasses are of special interest in a variety of medical applications owning to their unique combination of properties and potential therapeutic efficacy. These features may be of particular benefit with respect to the utilization of glass ionomer cements for minimally invasive dental applications such as the atruamatic restorative treatment, but also for expanded clinical applications in orthopedics and oral-maxillofacial surgery. A unique system of zinc-boron-germanium-based glasses (10 compositions in total) has been designed using a Design of Mixtures methodology. In the first instance, ionomer glasses were examined via differential thermal analysis, X-ray diffraction, and (11)B MAS NMR spectroscopy to establish fundamental composition - structure-property relationships for the unique system. Secondly, cements were synthesized based on each glass and handling characteristics (working time, Wt, and setting time, St) and compression strength were quantified to facilitate the development of both experimental and mathematical composition-structure-property relationships for the new ionomer cements. The novel glass ionomer cements were found to provide Wt, St, and compression strength in the range of 48-132?s, 206-602?s, and 16-36?MPa, respectively, depending on the ZnO/GeO2 mol fraction of the glass phase. A lower ZnO mol fraction in the glass phase provides higher glass transition temperature, higher N4 rate, and in combination with careful modulation of GeO2 mol fraction in the glass phase provides a unique approach to extending the Wt and St of glass ionomer cement without compromising (in fact enhancing) compression strength. The data presented in this work provide valuable information for the formulation of alternative glass ionomer cements for applications within and beyond the dental clinic, especially where conventional approaches to modulating working time and strength exhibit co-dependencies (i.e. the enhancement of one property comes at the expense of the other) and therefore limit development strategies.
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Overexpressing the NH2-terminal fragment of dentin sialophosphoprotein (DSPP) aggravates the periodontal defects in Dspp knockout mice.
J Oral Biosci
PUBLISHED: 11-12-2014
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Previous studies have shown that dentin sialophosphoprotein (DSPP) is not only essential to the formation and mineralization of dentin but also plays an important role in forming and maintaining a healthy periodontium. Under physiological conditions, DSPP is proteolytically processed into the NH2-terminal and COOH-terminal fragments, and these fragments are believed to perform different functions in the mineralized tissues. Previous studies in our group have demonstrated that the NH2-terminal fragment of DSPP inhibits the formation and mineralization of dentin, while the role of this fragment in periodontium is unclear.
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[Recognizing the vaccination strategy of pertussis according to the family aggregation feature of transmission].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 11-08-2014
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To understand the age distribution of pertussis patients admitted in the children hospital and to analyze the source of infection as well as its transmission patterns.
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Lipocalin-2 Promotes M1 Macrophages Polarization in a Mouse Cardiac Ischemia-Reperfusion Injury Model.
Scand. J. Immunol.
PUBLISHED: 11-01-2014
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Ischemia-reperfusion (IR) injury is a major issue in cardiac transplantation. Inflammatory processes play a major role in myocardial IR injury. Lipocalin-2 (Lcn2), which is also known as neutrophil gelatinase-associated lipocalin, has multiple functions that include the regulation of cell death/survival, cell migration/invasion, cell differentiation, and iron delivery. In our study, the hearts of C57BL/6 mice were flushed with and stored in cold Bretschneider solution for 8 hours and then transplanted into a syngeneic recipient. We found that Lcn2 neutralization decreased the recruitment of neutrophils and macrophages. Troponin T (TnT) production, 24 hours after myocardial IR injury, was reduced through anti-Lcn2 antibody administration. The cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts administrated with anti-Lcn2 antibody administration (anti-Lcn-2: 58.9 ± 5.62 ml/min; control: 25.8 ± 4.1 ml/min; P<0.05). Anti-Lcn2 antibody treatment suppressed M1 marker (IL-12, IL-23, and iNOS) expression but increased M2 marker (IL-10, Arg1, and Mrc1) expression. Furthermore, in our vitro and vivo experiments, we found that anti-Lcn2 antibody treatment failed to induce M1-related gene expression in response to LPS and that Lcn2 neutralization enhanced the expression of M2-related genes following IL-4 treatment. In conclusion, Lcn2 promotes M1 polarization, and Lcn2 neutralization attenuates cardiac IR injury. This article is protected by copyright. All rights reserved.
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Solvents Induced ZnO Nanoparticles Aggregation Associated with Their Interfacial Effect on Organic Solar Cells.
ACS Appl Mater Interfaces
PUBLISHED: 10-13-2014
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ZnO nanofilm as a cathode buffer layer has surface defects due to the aggregations of ZnO nanoparticles, leading to poor device performance of organic solar cells. In this paper, we report the ZnO nanoparticles aggregations in solution can be controlled by adjusting the solvents ratios (chloroform vs methanol). These aggregations could influence the morphology of ZnO film. Therefore, compact and homogeneous ZnO film can be obtained to help achieve a preferable power conversion efficiency of 8.54% in inverted organic solar cells. This improvement is attributed to the decreased leakage current and the increased electron-collecting efficiency as well as the improved interface contact with the active layer. In addition, we find the enhanced maximum exciton generation rate and exciton dissociation probability lead to the improvement of device performance due to the preferable ZnO dispersion. Compared to other methods of ZnO nanofilm fabrication, it is the more convenient, moderate, and effective to get a preferable ZnO buffer layer for high-efficiency organic solar cells.
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Synthesis and Photophysical Properties of a Sc3 N@C80 -Corrole Electron Donor-Acceptor Conjugate.
Chemistry
PUBLISHED: 10-09-2014
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Embedding endohdedral metallofullerenes (EMFs) into electron donor-acceptor systems is still a challenging task owing to their limited quantities and their still largely unexplored chemical properties. In this study, we have performed a 1,3-dipolar cycloaddition reaction of a corrole-based precursor with Sc3 N@C80 to regioselectively form a [5,6]-adduct (1). The successful attachment of the corrole moiety was confirmed by mass spectrometry. In the electronic ground state, absorption spectra suggest sizeable electronic communications between the electron acceptor and the electron donor. Moreover, the addition pattern occurring at a [5,6]-bond junction is firmly proven by NMR spectroscopy and electrochemical investigations performed with 1. In the electronically excited state, which is probed in photophysical assays with 1, a fast electron-transfer yields the radical ion pair state consisting of the one-electron-reduced Sc3 N@C80 and of the one-electron-oxidized corrole upon its exclusive photoexcitation. As such, our results shed new light on the practical work utilizing EMFs as building blocks in photovoltaics.
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Free fatty acid receptor 2, a candidate target for type 1 diabetes, induces cell apoptosis through ERK signaling.
J. Mol. Endocrinol.
PUBLISHED: 10-08-2014
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Recent reports have highlighted the roles of free fatty acid receptor 2 (FFAR2) in the regulation of metabolic and inflammatory processes. However, the potential function of FFAR2 in type 1 diabetes (T1D) remains unexplored. Our results indicated that the mRNA level of FFAR2 was upregulated in peripheral blood mononuclear cells of T1D patients. The human FFAR2 promoter regions were cloned, and luciferase reporter assays revealed that NF?B activation induced FFAR2 expression. Furthermore, we showed that FFAR2 activation by overexpression induced cell apoptosis through ERK signaling. Finally, treatment with the FFAR2 agonists acetate or phenylacetamide 1 attenuated the inflammatory response in multiple-low-dose streptozocin-induced diabetic mice, and improved the impaired glucose tolerance. These results indicate that FFAR2 may play a protective role by inducing apoptosis of infiltrated macrophage in the pancreas through its feedback upregulation and activation, thus, in turn, improving glucose homeostasis in diabetic mice. These findings highlight FFAR2 as a potential therapeutic target of T1D, representing a link between immune response and glucose homeostasis.
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Research on effect of minor bupleurum decoction of proliferation and apoptosis of esophageal cancer cell strain eca-109 cell.
Pak J Pharm Sci
PUBLISHED: 09-29-2014
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The research protocol is MTT (Methyl ThiazolylTetrazolium) method, Hoechst33342 staining method and flow cytometry detection to observe the effect of minor bupleurum decoction on proliferation inhibition and apoptosis-inducing of esophageal cancer cell strain Eca-109 cell and its purpose is to discuss the effect. The result of MTT method shows that minor buplerum decoction can obviously inhibit proliferation of esophageal cancer cell strain Eca-109 cell. Apoptosis number ofesophageal cancer cell increased with the increase of concentration of tetrandrine by the Hoechst 35528 staining experiment of cancer cell in three different concentrations. Flow cytometry detection result showed that cells in cell cycle G0/G1 of esophageal cancer cell strain Eca-109 cell increased obviously and cell in s period decreased significantly. This research proved that minor bupleurum decoction had anti-tumor effect and can influent proliferation and apoptosis of esophageal cancer cell strain Eca-109 cell.
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Photoelectric cooperative patterning of liquid permeation on the micro/nano hierarchically structured mesh film with low adhesion.
Nanoscale
PUBLISHED: 09-17-2014
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Stimuli-responsive surface wettability has been intensively studied, especially wettability controlled by photoelectric cooperation, which appears to be a trend for more effective surface wetting. In this field, the patterning of controllable surface wettability is still a challenge in the application of liquid-printing techniques because of the high adhesion and high responsive voltage, as well as low mechanical strength, of the substrate. Herein, we have demonstrated the patterning of liquid permeation controlled by photoelectric cooperative wetting on the micro/nano hierarchically structured ZnO mesh film. The special micro/nano hierarchically structured ZnO mesh is beneficial for lowering adhesion force on the mesh surface than those of the TiO2/AAO nanopore array films previously reported for the discontinuous tri-phase contact line, in addition to precisely controlled microscale liquid movement with considerably lower threshold voltage for the hierarchical structure. Moreover, the stainless-steel mesh with different pore sizes as a substrate behaves with higher mechanical strength and lower cost, compared with the anodized Ti mesh. Thus, this work is promising for accelerating the development of patterned liquid permeation and extending the application of micro/nanofluidic system and micronanoelectronic technology.
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miR-103/107 modulates multidrug resistance in human gastric carcinoma by downregulating Cav-1.
Tumour Biol.
PUBLISHED: 09-11-2014
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MicroRNAs (miRNAs) are a class of non-protein-coding small RNAs with the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In the present study, we analyzed miRNA expression levels between multidrug-resistant gastric carcinoma cell line SGC7901/ADR and its parent cell line SGC7901 using a miRNA microarray. MiR-103/107 was downregulated compared with parental SGC7901 cells. Overexpression of miR-103/107 sensitized SGC7901/ADR cells to doxorubicin (DOX), as demonstrated by in vitro and in vivo drug sensitivity assay. We further confirmed that miR-103/107 inhibited P-gp function in gastric cancer SGC7901/ADR cells. Finally, we verified that caveolin-1 (Cav-1), a critical component of lipid rafts, was a target of miR-103/107.
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Highly regioselective 1,3-dipolar cycloaddition of diphenylnitrilimine to Sc3N@I(h)-C80 affording a very stable, unprecedented pyrazole-ring fused derivative of endohedral metallofullerenes.
Chem. Commun. (Camb.)
PUBLISHED: 09-09-2014
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Formation of a very stable, unprecedented pyrazole-ring fused derivative of endohedral metallofullerenes was achieved by the first 1,3-dipolar cycloaddition reaction of Sc3N@C80 with diphenylnitrilimine in a highly regioselective manner.
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Overexpression of glucosylceramide synthase and its significance in the clinical outcome of non-small cell lung cancer.
Chin. Med. J.
PUBLISHED: 09-06-2014
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Glucosylceramide synthase (GCS), an enzyme responsible for ceramide glycosylation, plays an important role in multidrug resistance (MDR) in some tumors in vitro; however, its expression and clinicopathological significance in non-small cell lung cancer (NSCLC) remains unclear.
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Acute and subchronic toxicities of QX100626, a 5-HT4 receptor agonist, in rodents and Beagle dogs.
Regul. Toxicol. Pharmacol.
PUBLISHED: 08-07-2014
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Serotonin 5-hydroxytryptamine 4(5-HT4) receptor agonists have been widely prescribed as a prokinetics drug for patients with gastro-esophageal reflux disease and functional dyspepsia. QX100626, one of the 5-HT4 receptor agonists, has been studied as a promising agent for this clinical use. The objective of the present study was to identify possible target organs of toxicity and propose a non-toxic dose of QX100626 for clinical usage. After single lethal dose oral and intravenous testing in rodents, some signs indicative of adverse CNS effects were observed. The minimum toxic dose of QX100626 for a single oral administration for dogs was 90.0mg/kgb.w., and the severe toxic dose was more than 300mg/kgb.w. The No Observed Adverse Effect Level (NOAEL) of QX100626 by daily oral administration for rats and dogs was 20mg/kg and 10mg/kg, respectively, whereas the minimum toxic dosages were 67 and 30mg/kg, respectively. All of the adverse effects suggested that kidney, digestive tract, as well as nervous, hematological, and respiratory systems might be the target organs of toxicity for humans induced by QX100626. The compound could be a safe alternative to other existing prokinetic agents for the treatment of functional bowel disorders.
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TiO2 nanotube array-graphene-CdS quantum dots composite film in Z-scheme with enhanced photoactivity and photostability.
ACS Appl Mater Interfaces
PUBLISHED: 07-31-2014
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The most efficient solar energy utilization is achieved in natural photosynthesis through elaborate cell membrane with many types of molecules ingeniously transferring photogenerated electrons to reactants in a manner similar to the so-called Z-scheme mechanism. However, artificial photosynthetic systems based on semiconductor nanoparticles are inevitably accompanied by undesired non-Z-scheme electron transfer and back reactions, which adversely affect the photoactivity and photostability of the systems. Herein, we report on a novel Z-scheme system with an electrochemically converted graphene (GR) film as the electron mediator interlayer contacted with both TiO2 nanotube (TNT) array and CdS quantum dots (CdS QDs) on two sides. The obtained TiO2 nanotube array-graphene-CdS quantum dots (TNT-GR-CdS) composite film shows higher photoelectric response and photocatalytic activities than other bare TNT, TNT-CdS, TNT-GR, and TNT-CdS-GR. Moreover, compared to TNT-CdS, the activity stability is significantly improved, and the residual amount of Cd element in reaction solution is reduced ?8 times over TNT-GR-CdS. Various measurements of photoelectrochemistry and radicals reveal that the enhanced photoactivity and photostabilities of TNT-GR-CdS are due to the efficient spatial separation of the photogenerated electron-hole pairs and the restricted photocorrosion of CdS via an efficient Z-scheme mechanism under simulated sunlight.
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[Effect of intermediate-dose cytarabine on mobilization of peripheral blood hematopoietic stem cell in acute myeloid leukemia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 07-24-2014
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To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT).
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Multifunctional non-viral gene vectors with enhanced stability, improved cellular and nuclear uptake capability, and increased transfection efficiency.
Nanoscale
PUBLISHED: 07-22-2014
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We have developed a new multifunctional, non-viral gene delivery platform consisting of cationic poly(amine-co-ester) (PPMS) for DNA condensation, PEG shell for nanoparticle stabilization, poly(?-glutamic acid) (?-PGA) and mTAT (a cell-penetrating peptide) for accelerated cellular uptake, and a nuclear localization signal peptide (NLS) for enhanced intracellular transport of DNA to the nucleus. In vitro study showed that coating of the binary PPMS/DNA polyplex with ?-PGA promotes cellular uptake of the polyplex particles, particularly by ?-glutamyl transpeptidase (GGT)-positive cells through the GGT-mediated endocytosis pathway. Conjugating PEG to the ?-PGA led to the formation of a ternary PPMS/DNA/PGA-g-PEG polyplex with decreased positive charges on the surface of the polyplex particles and substantially higher stability in serum-containing aqueous medium. The cellular uptake rate was further improved by incorporating mTAT into the ternary polyplex system. Addition of the NLS peptide was designed to facilitate intracellular delivery of the plasmid to the nucleus--a rate-limiting step in the gene transfection process. As a result, compared with the binary PPMS/LucDNA polyplex, the new mTAT-quaternary PPMS/LucDNA/NLS/PGA-g-PEG-mTAT system exhibited reduced cytotoxicity, remarkably faster cellular uptake rate, and enhanced transport of DNA to the nucleus. All these advantageous functionalities contribute to the remarkable gene transfection efficiency of the mTAT-quaternary polyplex both in vitro and in vivo, which exceeds that of the binary polyplex and commercial Lipofectamine™ 2000/DNA lipoplex. The multifunctional mTAT-quaternary polyplex system with improved efficiency and reduced cytotoxicity represents a new type of promising non-viral vectors for the delivery of therapeutic genes to treat tumors.
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Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis.
Stem Cell Reports
PUBLISHED: 07-08-2014
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Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.
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Tolvaptan plus Pasireotide Shows Enhanced Efficacy in a PKD1 Model.
J. Am. Soc. Nephrol.
PUBLISHED: 07-05-2014
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Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of ESRD. A central defect associated with ADPKD pathology is elevated levels of 3', 5'-cyclic AMP (cAMP). Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression. Here, we tested the efficacy of these compounds individually and in combination in a hypomorphic PKD1 model, Pkd1(R3277C/R3277C) (Pkd1(RC/RC)), in a 5-month preclinical trial. Initially, the Pkd1(RC/RC) model was inbred into the C57BL/6 background, minimizing disease variability, and the pathogenic effect of elevating cAMP was confirmed by treatment with the AC6 stimulant desmopressin. Treatment with tolvaptan or pasireotide alone markedly reduced cyst progression and in combination showed a clear additive effect. Furthermore, combination treatment significantly reduced cystic and fibrotic volume and decreased cAMP to wild-type levels. We also showed that Pkd1(RC/RC) mice experience hepatic hypertrophy that can be corrected by pasireotide. The observed additive effect reinforces the central role of AC6 and cAMP in ADPKD pathogenesis and highlights the likely benefit of combination therapy for patients with ADPKD.
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Hyaluronan Tetrasaccharide Exerts Neuroprotective Effect and Promotes Functional Recovery After Acute Spinal Cord Injury in Rats.
Neurochem. Res.
PUBLISHED: 06-25-2014
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The objective of this study was to explore the therapeutic efficiency of hyaluronan tetrasaccharide (HA4) treatment after spinal cord injury (SCI) in rats and to investigate the underlying mechanism. Locomotor functional and electrophysiological evaluations revealed that the behavioral function of rats in the HA4-treated group was significantly improved compared with the vehicle-treated group. The expression of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), cluster determinant (CD44) and Toll-like receptor-4 (TLR-4) was obviously upregulated in the HA4-treated group than that in the sham and vehicle-treated group. Furthermore, HA4 could induce BDNF and VEGF expression in the astrocytes in vitro. In addition, the high expression of BDNF and VEGF could be inhibited by blocking CD44 and TLR-4. These findings indicate that HA4 could be useful as a promising therapeutic agent for SCI and might exert the effect by interaction with the CD44 and TLR-4.
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Synthesis and characterization of phosphorylated galactomannan: the effect of DS on solution conformation and antioxidant activities.
Carbohydr Polym
PUBLISHED: 06-19-2014
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Phosphorylated derivatives of galactomannan from guar gum (GG) with the degree of substitution (DS) of 0.35-0.52 were synthesized using POCl3/pyridine. FT-IR, (13)C NMR and XPS results revealed that phosphorylation had occurred and C-6 substitution was predominant in phosphorylated guar gum (PGG). PGG showed an increase in Mw and more broad molar mass distribution in size exclusion chromatography (SEC) analysis. Higher reaction temperature (above 60 °C) resulted in a higher MW value in PGG. It might be due to the cross-linking of polysaccharide chains by POCl3 via di-ester which was also supported by monosaccharide composition result. Results of M(W) - (S(2))(z)(1/2) showed a decrease in fractal dimension (df) values. DS had greater influence on its conformation in aqueous solution. The introduction of -PO3H2 groups improved significantly the stiffness of the chains due to the electrostatic effect. Furthermore, antioxidant experiments revealed that high DS could enhance the scavenging activities of radicals of PGG in vitro.
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Photoelectrocatalytic degradation of rhodamine B on TiO? photonic crystals.
Phys Chem Chem Phys
PUBLISHED: 06-19-2014
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As the inverse-opal structure facilitates the separation of electron-hole pairs and electron transfer, it may generate many radical species with strong oxidation capability. When a low bias voltage was applied on the TiO2 electrodes with inverse-opal structure, they exhibited more excellent photoelectrochemical properties and photoelectrocatalytic activity than TiO2 film under simulated solar light irradiation. When different types of active species scavengers were added, the different performances of TiO2 photonic crystals in rhodamine B degradation showed that besides ?OH and holes, which were the main active species in the photocatalysis, O2?(-) played a vital role in the photoelectrocatalytic degradation process. Furthermore, the stronger signal of ?OH-trapping photoluminescence and the variation in the concentration of nitroblue tetrazolium reflected that more ?OH and O2?(-) could be generated in the photoelectrocatalysis than that in the photocatalysis, and O2?(-) was partially obtained from the cathode surface. At last, the roles active species played in the photoelectrocatalytic and photocatalytic processes were compared, and the possible degradation mechanisms of TiO2 photonic crystals in photoelectrocatalytic and photocatalytic systems were put forward, which could provide a good insight into the mechanism of photoelectrocatalytic degradation on TiO2 photonic crystals.
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Effective dispersion and crosslinking in PVA/cellulose fiber biocomposites via solid-state mechanochemistry.
Int. J. Biol. Macromol.
PUBLISHED: 06-17-2014
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A mechanochemical approach to improve the dispersion and the degree of crosslinking between cellulose fiber and polymer matrix is presented herein to create high performance poly(vinyl alcohol) (PVA)/cellulose biocomposites in a solvent-free and catalyst-free system. During a pan-milling process, the hydrogen bonds in both cellulose and PVA were effectively broken up, and the released hydroxyl groups could react with succinic anhydride (SA) to form covalent bonds between the two components. This stress-induced chemical reaction was verified by fourier transform infrared spectroscopy. The reaction kinetics was discussed according to the conversion rate of SA during the pan-milling process. Soxhlet extraction with hot water showed that the crosslinked PVA/cellulose retained more PVA in the composites due to the homogeneous and heterogeneous crosslinking. Scanning electron microscope images indicated the dispersion and interfacial interactions between PVA and cellulose were largely improved. The resulting composites exhibited remarkably enhanced mechanical properties. The tensile strength increased from 8.8MPa (without mechanochemical treatment) to 18.2MPa, and elongation at break increased from 76.8 to 361.7% after the treatment. Their thermal stability was also significantly improved.
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Spectroscopic analyses on interaction of bovine serum albumin with novel spiro[cyclopropane-pyrrolizin].
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 06-16-2014
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The interaction between novel spiro[cyclopropane-pyrrolizin] (NSCP) and bovine serum albumin (BSA) was analyzed by fluorescence and ultraviolet-visible (UV-Vis) spectroscopy at 298K, 304K and 310K under simulative physiological conditions. The results showed that NSCP can effectively quench the intrinsic fluorescence of BSA via static quenching. The binding constants, binding sites of NSCP with BSA were calculated. Hydrogen binds and van der Waals force played a major role in stabilizing the complex and the binding reaction were spontaneous. According to the Förster non-radiation energy transfer theory, the average binding distances between NSCP and BSA were obtained. What is more, the synchronous fluorescence spectra indicated that the conformation of BSA has been changed.
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Overexpression of Dmp1 fails to rescue the bone and dentin defects in Fam20C knockout mice.
Connect. Tissue Res.
PUBLISHED: 06-13-2014
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FAM20C is a kinase phosphorylating the small-integrin-binding ligand, N-linked glycoproteins (SIBLINGs), a group of extracellular matrix proteins that are essential for bone and dentin formation. Previously, we showed that Sox2-Cre;Fam20Cfl/fl mice had bone and dentin defects, along with hypophosphatemia and significant downregulation of dentin matrix protein 1 (DMP1). While the assumed phosphorylation failure of the SIBLINGs is likely associated with the defects in the Fam20C-deficient mice, it remains unclear if the downregulation of Dmp1 contributes to these phenotypes. In this study, we crossed 3.6?kb Col1-Dmp1 transgenic mice with 3.6?kb Col1-Cre;Fam20Cfl/fl mice to overexpress Dmp1 in the mineralized tissues of Fam20C conditional knockout (cKO) mice. X-ray, micro-computed tomography, serum biochemistry and histology analyses showed that expressing the Dmp1 transgene failed to rescue the bone and dentin defects, as well as the serum levels of FGF23 and phosphate in the Fam20C-cKO mice. These results indicated that the downregulation of Dmp1 may not directly associate with, or significantly contribute to the bone and dentin defects in the Fam20C-cKO mice.
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Physical lysis only (PLO) methods suitable as rapid sample pretreatment for qPCR assay.
Appl. Microbiol. Biotechnol.
PUBLISHED: 06-12-2014
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Quantitative PCR (qPCR) enables rapid and sensitive gene quantification and is widely used in genomics, such as biological, medical, environmental, and food sciences. However, sample pretreatment requires the use of conventional DNA extraction kits which are time-consuming and labor intensive. In this study, we investigated four physical lysis only (PLO) methods which are rapid and could serve as alternatives to conventional DNA extraction kits. These PLO methods are bead mill, heating, sonication, and freeze-thaw. Using ethidium bromide-based assay, their performance was evaluated and compared. The effects of cell debris and its removal were also investigated. Bead mill method without cell debris removal appeared to yield the best qPCR results among the four PLO methods. In addition, bead mill method also performed better than conventional DNA extraction kits. It is probably due to the substantial loss of DNA material during the extensive purification of the conventional DNA extraction kits. The bead mill method has been demonstrated to successfully quantify 10(2) to 10(7) copies of the PAH-RHD? gene of Pseudomonas putida.
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Huangqi-Honghua combination and its main components ameliorate cerebral infarction with Qi deficiency and blood stasis syndrome by antioxidant action in rats.
J Ethnopharmacol
PUBLISHED: 05-22-2014
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Combination of Radix Astragali (Huangqi) and Carthamus tinctorius L. (Honghua) has been extensively used as traditional herb medicine in China for the treatment of stroke and myocardial ischemia diseases with Qi deficiency and blood stasis (QDBS) syndrome.
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Genetic and Environmental Variances of Bone Microarchitecture and Bone Remodeling Markers: A Twin Study.
J. Bone Miner. Res.
PUBLISHED: 05-14-2014
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All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size - void volumes (porosity) which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) Caucasian female twin pairs aged 40 to 61 years. Images obtained using high-resolution peripheral quantitative computed tomography were analysed using StrAx1.0, a non-threshold based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72-1% (standard errors ? 18%) for the distal tibial total, cortical and medullary cross-sectional area (CSA), 67% and 61% for total cortical porosity, before and after adjusting for total CSA respectively, 51% for trabecular vBMD (all p?
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Targeting the neddylation pathway to suppress the growth of prostate cancer cells: therapeutic implication for the men's cancer.
Biomed Res Int
PUBLISHED: 05-10-2014
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The neddylation pathway has been recognized as an attractive anticancer target in several malignancies, and its selective inhibitor, MLN4924, has recently advanced to clinical development. However, the anticancer effect of this compound against prostate cancer has not been well investigated. In this study, we demonstrated that the neddylation pathway was functional and targetable in prostate cancer cells. Specific inhibition of this pathway with MLN4924 suppressed the proliferation and clonogenic survival of prostate cancer cells. Mechanistically, MLN4924 treatment inhibited cullin neddylation, inactivated Cullin-RING E3 ligases (CRLs), and led to accumulation of tumor-suppressive CRLs substrates, including cell cycle inhibitors (p21, p27, and WEE1), NF-?B signaling inhibitor I?B?, and DNA replication licensing proteins (CDT1 and ORC1). As a result, MLN4924 triggered DNA damage, G2 phase cell cycle arrest, and apoptosis. Taken together, our results demonstrate the effectiveness of targeting the neddylation pathway with MLN4924 in suppressing the growth of prostate cancer cells, implicating a potentially new therapeutic approach for the men's cancer.
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Bufalin enhances TRAIL-induced apoptosis by redistributing death receptors in lipid rafts in breast cancer cells.
Anticancer Drugs
PUBLISHED: 04-09-2014
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Studies have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells. However, breast cancer cells are generally resistant to TRAIL. In the present study, we explored the effect of bufalin on TRAIL-induced breast cancer cell apoptosis. The results showed that bufalin enhanced TRAIL-induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by activating the extrinsic apoptotic pathway. Bufalin also promoted the clustering of death receptor 4 (DR4) and DR5 in aggregated lipid rafts. The cholesterol-sequestering agent methyl-?-cyclodextrin reversed the DR4 and DR5 clustering and reduced bufalin+TRAIL-induced apoptosis. Overall, these results indicate that bufalin enhanced TRAIL-induced apoptosis in breast cancer cells by the partial redistribution of DRs in lipid rafts.
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Alteration in Chondroitin Sulfate Proteoglycan Expression at the Epicenter of Spinal Cord is Associated with the Loss of Behavioral Function in Tiptoe Walking Yoshimura Mice.
Neurochem. Res.
PUBLISHED: 04-08-2014
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The objective of this study was to explore the correlation between the alteration in chondroitin sulfate proteoglycan (CSPG) expression at the epicenter of spinal cord and the loss of behavioral function in tiptoe walking Yoshimura mice. The tiptoe walking Yoshimura mice (twy) and Institute of Cancer Research (ICR) mice, aged 20 and 26 weeks, were used in the present study. The behavior assessment, micro-computed tomography and immunofluorescent staining were performed. The compressed spinal cord was histologically analyzed. The results showed that the expression of CSPG was statistically higher at the compressed spinal cord for twy mice compared with that at the normal spinal cord for ICR mice. At the 26th week, a large ossification block at the posterior longitudinal ligament of C1-3 was obviously observed at the micro-CT image We observed the BMS Score was significantly correlated with the expression of glial fibrillary acidic protein, CSPG and hyaluronan (P < 0.05). These findings suggest that compression injury induces the higher CSPG expression at the compressed spinal cord in the twy mice. Furthermore, the alteration in CSPG expression at the epicenter of spinal cord is associated with the loss of behavioral function in twy mice.
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Antischistosomal versus antiandrogenic properties of aryl hydantoin Ro 13-3978.
Am. J. Trop. Med. Hyg.
PUBLISHED: 03-31-2014
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In the early 1980s, the antischistosomal aryl hydantoin Ro 13-3978 (AH01), a close structural analogue of the androgen receptor antagonist nilutamide, was discovered. Administration of 100 mg/kg oral doses of AH01 to mice infected with adult and juvenile Schistosoma mansoni produced 95% and 64% total worm burden reductions, confirming its high activity against adult worms, and showing that AH01 is also effective against juvenile infections. AH01 had no measureable interaction with the androgen receptor in a ligand competition assay, but it did block dihydrotestosterone-induced cell proliferation in an androgen-dependent human prostate cancer cell line. For AH01, nilutamide, and three closely related aryl hydantoin derivatives, there was no correlation between antischistosomal activity and androgen receptor interaction.
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HIV and syphilis prevalence trends among men who have sex with men in Guangxi, China: yearly cross-sectional surveys, 2008-2012.
BMC Infect. Dis.
PUBLISHED: 03-28-2014
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Men who have sex with men (MSM) represent the fastest growing key population for incident HIV cases in China. We examined five consecutive years of HIV and syphilis prevalence and risk factors data among MSM in Guangxi Province with the second highest estimated number of people living with HIV/AIDS (PLWHAs) in China in 2011.
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Cellulose hydrogels prepared from micron-sized bamboo cellulose fibers.
Carbohydr Polym
PUBLISHED: 03-26-2014
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We demonstrated for the first time that dimensionally stable hydrogels could be obtained from bamboo pulp fibers through dialysis against distilled water followed by a short time of ultrasonic treatment. Micron-sized short fibers rather than cellulose nanofibrils constituted the majority of fibers in the hydrogels. During the pulping process with HNO3 and KClO3, carboxylic groups could be introduced to cellulose due to the mild oxidation of hydroxyl groups. When presented in aqueous NaOH, the carboxylic groups could be converted into their sodium salt form. The subsequent dialysis treatment against water made the negatively charged COO(-) groups extensively exposed. The negatively charged cellulose fibers could induce considerable electrostatic repulsion between them, which was discovered to govern the formation of hydrogels. In addition, it was revealed that homogeneous hydrogels could be formed when the pH was at 7, 9 and 11. However, when salt was added, no dimensionally stable hydrogel was obtained.
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Study on the interaction between carbonyl-fused N-confused porphyrin and bovine serum albumin by spectroscopic techniques.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 03-22-2014
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The interaction between carbonyl-fused N-confused porphyrin (CF-NCP) and bovine serum albumin (BSA) was investigated by fluorescence and ultraviolet-visible (UV-Vis) spectroscopy. The results indicated that CF-NCP has strong ability to quench the intrinsic fluorescence of BSA by forming complexes. The binding constants (Ka), binding sites (n) were obtained. The corresponding thermodynamic parameters (?H, ?S and ?G) of the interaction system were calculated at three different temperatures. The results revealed that the binding process is spontaneous, and the acting force between CF-NCP and BSA were mainly electrostatic forces. According to Förster non-radiation energy transfer theory, the binding distance between CF-NCP and BSA was calculated to be 4.37nm. What is more, the conformation of BSA was observed from synchronous fluorescence spectroscopy.
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Distribution, origin, and transformation of metal and metalloid pollution in vegetable fields, irrigation water, and aerosols near a Pb-Zn mine.
Environ Sci Pollut Res Int
PUBLISHED: 03-05-2014
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Pollution of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), and zinc (Zn) in vegetable fields was investigated near a Pb-Zn mine that has been exploited for over 50 years without a tailing reservoir. A total of 205 water, soil, and aerosol samples were taken and quantified by combined chemical, spectrometric, and mineral analytical methods. The pollution origins were identified by Pb isotopes and the pathways of transformation and transport of the elements and minerals was studied. The data showed that the vegetable fields were seriously polluted by As, Cd, and Pb. Some concentrations in the samples were beyond the regulatory levels and not suitable for agricultural activities. This study revealed that: (1) particulate matter is a major pollution source and an important carrier of mineral particles and pollutants; (2) the elements from the polluted water and soils were strongly correlated with each other; (3) Pb isotope ratios from the samples show that Pb minerals were the major pollution sources in the nearby vegetable fields, and the aerosols were the main carrier of mining pollution; (4) the alkaline, rich-carbonate, and wet conditions in this area promoted the weathering and transformation of galena into the secondary minerals, anglesite and cerussite, which are significant evidence of such processes; (5) the soil and the aerosols are a recycled secondary pollution source for each other when being re-suspended with wind.Highlights• Mining activities generated heavy metal pollution in fields around a Pb-Zn mine• The elements from water and soils are strongly correlated• Anglesite and cerussite are evidence of galena transformation into secondary minerals• Particulate matter is an important transport carrier of pollution.
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Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice.
Parasitol. Res.
PUBLISHED: 03-04-2014
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The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100?S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10% calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 ?g/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 ?g/mL, whereas the corresponding LC95 values were 30.7 and 22.7 ?g/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9%, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4%. On the other hand, similar and higher total worm burden reductions (64.2-76.0%) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P?
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A phase I study of AST1306, a novel irreversible EGFR and HER2 kinase inhibitor, in patients with advanced solid tumors.
J Hematol Oncol
PUBLISHED: 03-04-2014
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AST1306 is an orally active irreversible small molecule inhibitor of EGFR (erbB1), HER2 (erbB2) and HER4 (erbB4) signaling. This is a phase I, open-label, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor effects of oral AST1306. In addition the effects of food on PK was tested.
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A prospective, randomized trial of intravenous glucocorticoids therapy with different protocols for patients with graves' ophthalmopathy.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-28-2014
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For patients with active moderate-to-severe Graves' ophthalmopathy (GO), a course of 4.5 g iv glucocorticoids (GCs) is the recommended therapy. The weekly protocol is preferred because of the potential safety concerns with the daily protocol. However, evidence for the superiority of different administration protocols is lacking.
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The cleaved cytoplasmic tail of polycystin-1 regulates Src-dependent STAT3 activation.
J. Am. Soc. Nephrol.
PUBLISHED: 02-27-2014
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Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and progression to renal failure in autosomal dominant polycystic kidney disease (ADPKD). The transcription factor STAT3 (signal transducer and activator of transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but the mechanisms leading to persistent STAT3 activation are unknown. A proteolytic fragment of PC1 corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD. Here, we show that PC1-p30 interacts with the nonreceptor tyrosine kinase Src, resulting in Src-dependent activation of STAT3 by tyrosine phosphorylation. The PC1-p30-mediated activation of Src/STAT3 was independent of JAK family kinases and insensitive to the STAT3 inhibitor suppressor of cytokine signaling 3. Signaling by the EGF receptor (EGFR) or cAMP amplified the activation of Src/STAT3 by PC1-p30. Expression of PC1-p30 changed the cellular response to cAMP signaling. In the absence of PC1-p30, cAMP dampened EGFR- or IL-6-dependent activation of STAT3; in the presence of PC1-p30, cAMP amplified Src-dependent activation of STAT3. In the polycystic kidney (PCK) rat model, activation of STAT3 in renal cystic cells depended on vasopressin receptor 2 (V2R) signaling, which increased cAMP levels. Genetic inhibition of vasopressin expression or treatment with a pharmacologic V2R inhibitor strongly suppressed STAT3 activation and reduced renal cyst growth. These results suggest that PC1, via its cleaved cytoplasmic tail, integrates signaling inputs from EGFR and cAMP, resulting in Src-dependent activation of STAT3 and a proliferative response.
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Uniaxially aligned electrospun all-cellulose nanocomposite nanofibers reinforced with cellulose nanocrystals: scaffold for tissue engineering.
Biomacromolecules
PUBLISHED: 01-24-2014
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Uniaxially aligned cellulose nanofibers with well oriented cellulose nanocrystals (CNCs) embedded were fabricated via electrospinning using a rotating drum as the collector. Scanning electron microscope (SEM) images indicated that most cellulose nanofibers were uniaxially aligned. The incorporation of CNCs into the spinning dope resulted in more uniform morphology of the electrospun cellulose/CNCs nanocomposite nanofibers (ECCNN). Polarized light microscope (PLM) and transmission electron microscope (TEM) showed that CNCs dispersed well in ECCNN nonwovens and achieved considerable orientation along the long axis direction. This unique hierarchical microstructure of ECCNN nonwovens gave rise to remarkable enhancement of their physical properties. By incorporating 20% loading (in weight) of CNCs, the tensile strength and elastic modulus of ECCNN along the fiber alignment direction were increased by 101.7 and 171.6%, respectively. Their thermal stability was significantly improved as well. In addition, the ECCNN nonwovens were assessed as potential scaffold materials for tissue engineering. It was elucidated from MTT tests that the ECCNN were essentially nontoxic to human cells. Cell culture experiments demonstrated that cells could proliferate rapidly not only on the surface but also deep inside the ECCNN. More importantly, the aligned nanofibers of ECCNN exhibited a strong effect on directing cellular organization. This feature made the scaffold particularly useful for various artificial tissues or organs, such as blood vessel, tendon, nerve, and so on, in which cell orientation was crucial for their performance.
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Activity of diimidazoline amides against African trypanosomiasis.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-09-2014
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We identified several diimidazoline mono- and diamides that were as potent as pentamidine against Trypanosoma brucei rhodesiense in vitro. All of these were also less cytotoxic than pentamidine, but none was as effective as the latter in a T. brucei rhodesiense-infected mouse model. A single imidazoline may be sufficient for high antitrypanosomal activity provided that a second weak base functional group is present.
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Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.
Colloids Surf B Biointerfaces
PUBLISHED: 01-09-2014
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A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ?-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition.
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In situ synthesis of MnO2 coated cellulose nanofibers hybrid for effective removal of methylene blue.
Carbohydr Polym
PUBLISHED: 01-07-2014
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A one-step and energy-efficient synthetic method was developed to fabricate manganese dioxide (MnO2)/cellulose nanofibers (CNFs) hybrid. In this process, bamboo CNFs acted as both a reducing reagent for the Mn (VII) and an ultralight support for the generated MnO2 nanosheets. Neither additional reducing reagents nor heating were adopted during the synthesis process. The phase constitutions, crystal structure and morphology of the hybrid were systematically investigated. Both oxidative and adsorptive decolorization of methylene blue (MB) were investigated to evaluate its efficiency on dye wastewater treatment. The results showed that the few-layer MnO2 nanosheets deposited on CNFs exhibited high decolorization efficiency for the oxidation and adsorption of MB. When slurry containing 25 mg MnO2/CNFs hybrid was dispersed in 25 mL 80 mg L(-1) MB solution, the removal of MB was more than 99.8% within 2 min.
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Trps1 is associated with the multidrug resistance of osteosarcoma by regulating MDR1 gene expression.
FEBS Lett.
PUBLISHED: 01-07-2014
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Multidrug resistance (MDR) is a significant clinical problem in the chemotherapy of osteosarcoma and has been linked to the cellular expression of several multidrug-efflux transporters such as MDR1/P-gp. Our inhibition of the transcription factor Trps1 led to repression of MDR1/P-gp while its overexpression resulted in upregulation of MDR1/P-gp. Flow cytometric analysis suggested Trps1 increased the release of several anti-cancer drugs, thus decreasing their accumulation. Immunohistochemical analysis of clinical samples indicated that the expression of Trps1 directly correlated with MDR1/P-gp. Trps1 inhibited TGFbeta-1 and directly bound to the MDR1 promoter. Our data demonstrate a role for Trps1 in the regulation of MDR1 expression in osteosarcoma.
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Characterization of denaturation and renaturation of DNA for DNA hybridization.
Environ Health Toxicol
PUBLISHED: 01-01-2014
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The present study was designed to systematically characterize the denaturation and the renaturation of double stranded DNA (dsDNA), which is suitable for DNA hybridization.
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Clinical characteristics of 26 patients with primary extranodal Hodgkin lymphoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Most Hodgkin lymphoma (HL) patients present with disease in nodal regions. However, in a small subset, disease develops extranodal sites primarily, such as lung and liver. This study aims to identify the characteristics and outcomes of patients with primary extranodal HL.
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IMP3 expression is associated with epithelial-mesenchymal transition in breast cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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IMP3 plays an important role in tumor invasion and metastasis, to which epithelial to mesenchymal transition (EMT) also contributes. The purpose of this study was to investigate whether IMP3 can regulate invasion and metastasis through EMT in breast cancers. The protein expression levels of IMP3 and EMT markers were analyzed by immunohistochemistry in 180 paraffin-embedded human breast tissue samples. There was an inverse correlation of IMP3 with E-cadherin protein expression (P = 0.042). IMP3 expression directly correlated with both Slug (P = 0.004) and vimentin (P < 0.001). Changes in E-cadherin, vimentin, and Slug mRNA and protein levels were examined by quantitative real-time reverse polymerase chain reaction (qRT-PCR) and western blotting. Overexpression of IMP3 reduced the expression of E-cadherin and upregulated Slug and vimentin in transfected cells. In contrast, knocking down IMP3 had the opposite expression of the three proteins. Ribo-immunoprecipitation qPCR revealed that IMP3 binds Slug mRNA directly. In a transwell assay, overexpression of Slug rescued the cell migration and invasion caused by silencing IMP3 in MDA-MB-231 cells. On the other hand, knockdown of Slug in T47D-IMP3 cells could also have the opposite change. Our results strengthen the association of IMP3 with the regulation of EMT. Slug is a functional target of IMP3. IMP3 could therefore promote invasion and migration through the EMT in breast cancer cells.
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MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 12-11-2013
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Growing evidence has demonstrated that the aberrant expression of miRNA is a hallmark of malignancies, indicating the important roles of miRNA in the development and progression of cancer. MiR-7 is considered as a tumor suppressor miRNA in multiple types of cancer. However, the role of miR-7 in human hepatocellular carcinoma (HCC) and its underlying mechanism remain elusive. In this study, we found that overexpression of miR-7 arrested cell cycle at G1 to S transition in HCC. By combinational use of bioinformatic prediction, reporter assay, quantitative real-time PCR (qRT-PCR) and Western blot, we confirmed that CCNE1, an important mediator in G1/S transition is one of new direct target genes of miR-7. Further studies revealed that silencing of CCNE1 recapitulated the effects of miR-7 overexpression, whereas enforced expression of CCNE1 reversed the suppressive effects of miR-7 in cell cycle regulation. Finally, analysis of qRT-PCR showed a reciprocal relationship between miR-7 and CCNE1 in clinical cancer tissues and multiple types of tumor cell lines. These findings indicate that miR-7 exerts tumor-suppressive effects in hepatocarcinogenesis through the suppression of oncogene CCNE1 expression and suggest a therapeutic application of miR-7 in HCC.
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Epigenetic Regulation of miR-302 by JMJD1C Inhibits Neural Differentiation of Human Embryonic Stem Cells.
J. Biol. Chem.
PUBLISHED: 12-06-2013
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It has been recently reported that the regulatory circuitry formed by OCT4, miR-302, and NR2F2 controls both pluripotency and neural differentiation of human embryonic stem cells (hESCs). We show here that JMJD1C, a H3K9 demethylase expressed in hESCs, directly interacts with this circuitry. hESCs with stable knockdown of JMJD1C remain pluripotent, while having reduced miR-302 expression, decreased BMP signaling, and enhanced TGF? signaling. JMJD1C binds to miR-302 promoter and reduces H3K9 methylation. Withdrawal of bFGF from the culture induces neural differentiation of the knockdown, but not the control, cells within 3 days, accompanied by elevated NR2F2 expression. This can be attenuated with miR-302 mimics or a H3K9 methytransferase inhibitor. Together, our findings suggest that JMJD1C represses neural differentiation of hESCs at least partially by epigenetically sustaining miR-302 expression, and that JMJD1C knockdown is sufficient to trigger neural differentiation upon withdrawal of exogenous bFGF.
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Effects of pretreatment on the denaturation and fragmentation of genomic DNA for DNA hybridization.
Environ Sci Process Impacts
PUBLISHED: 10-28-2013
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DNA hybridization is an important step for a number of bioassays such as fluorescence in situ hybridization, microarrays, as well as the NanoGene assay. Denaturation and fragmentation of genomic DNA are two critical pretreatments for DNA hybridization. However, no thorough and systematic characterization on denaturation and fragmentation has been carried out for the NanoGene assay so far. In this study, we investigated the denaturation and fragmentation of the bacterial gDNA with physical treatments (i.e., heating and sonication) and chemical treatments (i.e., dimethyl sulfoxide). First of all, a simple approach for indicating the denaturation fraction was developed based on the absorbance difference (i.e., hyperchromic effect) between the double-stranded DNA and single-stranded DNA fragments. Then the denaturation capabilities of the treatments to the gDNA were elucidated, followed by the examination of the possible renaturation over time. The fragmentation of the gDNA by each treatment was also investigated. Based on denaturation efficiency, minimum renaturation tendency, and fragmentation, the sonication method was found to be the best among the six methods. We further demonstrated that the sonication method produced the best result among the treatments examined for the DNA hybridization in the NanoGene assay.
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Bingel-Hirsch monoadducts of TiSc2N@Ih-C80versus Sc3N@Ih-C80: reactivity improvement via internal metal atom substitution.
Chem. Commun. (Camb.)
PUBLISHED: 10-15-2013
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The first Bingel-Hirsch reaction of TiSc2N@Ih-C80 afforded two unconventional singly bonded monoadducts, revealing the dramatically improved reactivity compared to Sc3N@Ih-C80 and obvious change in the addition pattern.
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Arabidopsis co-chaperonin CPN20 antagonizes Mg-chelatase H subunit to derepress ABA-responsive WRKY40 transcription repressor.
Sci China Life Sci
PUBLISHED: 10-14-2013
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Our previous study demonstrated that a chloroplast co-chaperonin 20 (CPN20), one of the interaction partners of the magnesium-protoporphyrin IX chelatase H subunit (CHLH/ABAR), negatively regulates ABA signaling at the same node with ABAR but upstream of WRKY40 transcription repressor in Arabidopsis thaliana. In the present experiment, we showed that ABA directly inhibits the ABAR-CPN20 interaction, and also represses expression of CPN20, which depends on ABAR. CPN20 inhibits ABAR-WRKY40 interaction by competitively binding to ABAR. ABAR downregulates, but CPN20 upregulates, WRKY40 expression. The cpn20-1 mutation induces downregulation of WRKY40, and suppresses the upregulated level of WRKY40 due to the cch mutation in the ABAR gene. ABA-induced repressive effect of the WRKY40 gene is strengthened by downregulation of CPN20 but reduced by upregulation of CPN20. Together with our previously reported genetic data, we provide evidence that CPN20 functions through antagonizing the ABAR-WRKY40 coupled pathway, and ABA relieves this pathway of repression by inhibiting the ABAR-CPN20 interaction to activate ABAR-WRKY40 interaction.
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Single-focus x-ray zone plate by stagger arrangement of zones.
Opt Express
PUBLISHED: 10-10-2013
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In this paper a novel single-focus x-ray zone plate is proposed by stagger arrangement of zones, which would be technically easier to manufacture. Theoretical design shows that the transmission function of the plate is a cosine function of radius, like that of a Gabor zone plate. Numerical simulation at the wavelength of 0.275 nm shows that the plate is of single-order focusing, with spatial resolution limit the same as that of the corresponding conventional zone plate, and the first-order diffraction efficiency of 11.5%. The plate can also work for single-order focusing at other x-ray wavelengths.
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Dissolution enhancement of cefdinir with hydroxypropyl-?-cyclodextrin.
Drug Dev Ind Pharm
PUBLISHED: 10-04-2013
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The solid state properties and dissolution behavior of binary systems of cefdinir (CEF) with hydroxypropyl-?-cyclodextrin (HP-?-CD) were investigated. CEF-HP-?-CD interaction in the solution state was studied by phase-solubility analysis and demonstrates the ability of HP-?-CD to complex with CEF giving A(L) type profile with 65.28 ± 1.3 M(-1) stability constant. The freeze drying technique was adopted to prepare binary systems of CEF with HP-?-CD in 1:1 molar ratio. The solid inclusion was characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD), and scanning electron microscopy (SEM). Aqueous solubility of CEF-HP-?-CD inclusion complex was 2.36-fold of pure CEF. The dissolution profiles of inclusion complexes were determined and compared with those of CEF alone and their physical mixtures. The dissolution rate of inclusion complex was superior than the CEF alone. These approaches indicated that CEF was able to form an inclusion complex with HP-?-CD, and the inclusion compounds exhibited different spectroscopic features and properties.
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Fabrication and catalytic performance of highly stable multifunctional core-shell zeolite composites.
Inorg Chem
PUBLISHED: 09-16-2013
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Multifunctional Fe3O4@SiO2-Au@silicalite-1 core-shell magnetic zeolite composites were fabricated by combining a series of sol-gel process and vapor-phase transfer of silicalite-1 zeolite nanocrystal-seeded silica shells. The obtained composite has high magnetization (32.00 emu/g), stably confined and active gold nanoparticles (ca. 15 nm), and a hierarchical silicalite-1 outer shell. The core-shell composite exhibits a high efficiency of magnetic separability, excellent catalytic performance, and reusability for the reduction of 4-nitrophenol with conversion of 98% in 12 min. Moreover, it preserves a good stability after a high-temperature hydrothermal treatment.
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Amino ozonides exhibit in vitro activity against Echinococcus multilocularis metacestodes.
Int. J. Antimicrob. Agents
PUBLISHED: 08-16-2013
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Artemisinin is an antimalarial sesquiterpene lactone that contains a 1,2,4-trioxane heterocycle. Dihydroartemisinin and artesunate demonstrated activity against Echinococcus multilocularis metacestodes in vitro but were not effective in a mouse model. In this study, the in vitro effects of a small library of synthetic ozonides (1,2,4-trioxolanes) were investigated. Initial compound screening against E. multilocularis metacestodes was performed at 20?M, and selected ozonides were further assessed in dose-response studies in metacestode cultures and mammalian cells. Transmission electron microscopy (TEM) was employed to characterise compound-induced structural alterations. At 20?M, the most potent ozonides (OZ401, OZ455, OZ491 and OZ494) led to death of ca. 60-100% of the parasites. Subsequent dose-response experiments demonstrated that OZ401, OZ455 and OZ491, which contain an aminopropylether substructure, were the most potent, with 50% inhibitory concentrations ranging from 11?M to 14?M. Cytotoxicity for these three ozonides, assessed in human foreskin fibroblasts, rat hepatoma cells and green monkey epithelial kidney (Vero) cells, was evident only at high concentrations. TEM demonstrated that OZ401 and OZ491 treatment induced considerable metabolic impairment in metacestodes at 1 day post exposure. At Day 3 post exposure, the germinal layer was severely distorted, although some intact cells were still visible, demonstrating that not all cell types in the parasite tissue were equally affected. Complete destruction of the germinal layer was noted at 5 days post exposure. Synthetic ozonides could represent interesting leads that will be further investigated in a suitable in vivo model of E. multilocularis infection.
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Regioselective synthesis of sulfated guar gum: Comparative studies of structure and antioxidant activities.
Int. J. Biol. Macromol.
PUBLISHED: 08-12-2013
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We reported here a new synthesis of C-2 and C-3 sulfated guar gum (SRSGG) with low degree of substitution (DSS) of 0.58, employing triphenylchloromethane (TrCl) as a protected precursor. The yield and DSTr (calculated from the weight of triphenylmethanol) of triphenylmethylated GG (GGTr) was 165.6% and 0.71, respectively. In addition, low ratio (1:4) of chlorosulfuric acid to pyridine (1:4) was chosen in sulfation reaction since the protecting group was slightly sensitive to acid. Results of FT-IR and (13)C NMR spectroscopy indicated that C-2 and C-3 substitution was predominant but not fully sulfated in SRSGG. Size-exclusion chromatograph combined with multi-angle laser photometer (SEC-LLS) showed a decrease in molecular weight in the reaction. This might be due to the degradation in sulfation and deprotection process. Finally, we investigated the effect of structure features on the antioxidant activities in vitro. Vitro antioxidant experiments revealed that the regioselective sulfation at C-2 and C-3 and low molecular weight afforded strong antioxidant activities showing a much higher scavenging abilities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical than that by the known C-6-sulfated derivative. The antioxidant activities of sulfated polysaccharides were not a function of a single factor but a combination of molecular weight, DSS and substitution positions.
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Failure to process dentin sialophosphoprotein into fragments leads to periodontal defects in mice.
Eur. J. Oral Sci.
PUBLISHED: 08-12-2013
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Dentin sialophosphoprotein (DSPP) plays a vital role in dentinogenesis. Previously, we showed that, in addition to dentin, DSPP is also highly expressed in alveolar bone and cellular cementum, and plays a crucial role in maintaining periodontal integrity; Dspp-deficient mice demonstrate severe periodontal defects, including alveolar bone loss, decreased cementum deposition, abnormal osteocyte morphology in the alveolar bone, and apical migration of periodontal ligament. Dentin sialophosphoprotein in dentin and bone is cleaved into NH? -terminal and COOH-terminal fragments. Whilst our previous study showed that the proteolytic processing of DSPP is critical for dentinogenesis, it is unclear whether the post-translational cleavage of DSPP also plays an essential role in maintaining a healthy periodontium. In this study, we analyzed the periodontal tissues from transgenic mice expressing the uncleavable full-length DSPP in the Dspp knockout (Dspp-KO) background (named Dspp-KO/D452A-Tg mice), in comparison with those from wild-type mice, Dspp-KO mice, and mice expressing the normal Dspp transgene in the Dspp-KO background (designated Dspp-KO/normal-Tg mice). We found that transgenic expression of the normal DSPP fully rescued the periodontal defects of the Dspp-KO mice, whereas this was not the case in Dspp-KO/D452A-Tg mice. These results indicate that proteolytic processing of DSPP is essential to periodontal integrity.
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Interactome analysis reveals that C1QBP (complement component 1, q subcomponent binding protein) is associated with cancer cell chemotaxis and metastasis.
Mol. Cell Proteomics
PUBLISHED: 08-07-2013
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The complement component 1, q subcomponent binding protein (C1QBP/p32/HABP1) is a ubiquitously expressed and multicompartmental cellular protein involved in various biological processes. In order to further understand its biological functions, we conducted proteomics analysis of its interactome in this study. An improved sample preparation and mass spectrometric identification strategy was developed combining high-speed centrifugation, formaldehyde labeling, and two-dimensional reverse-phase liquid chromatography. Using this approach, we identified 187 interacting proteins and constructed a highly connected interacting network for C1QBP. Moreover, we explored the interaction between C1QBP and protein kinase C ?, a key regulator of cell polarity and migration. The results indicated that C1QBP regulated the activity of protein kinase C ? and modulated EGF-induced cancer cell chemotaxis. In addition, C1QBP was required for breast cancer metastasis in a severe combined immunodeficiency mouse model. Furthermore, C1QBP was observed to be overexpressed in breast cancer tissues, and its expression level was closely linked with distant metastasis and TNM stages. In summary, C1QBP was identified as a novel regulator of cancer metastasis that may serve as a therapeutic target for breast cancer treatment.
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Evaluation of subchronic toxicity of GRD081, a dual PI3K/mTOR inhibitor, after 28-day repeated oral administration in Sprague-Dawley rats and beagle dogs.
Food Chem. Toxicol.
PUBLISHED: 07-16-2013
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GRD081, a newly developed dual PI3K/mTOR inhibitor, is now being considered for evaluation in phase I clinical trial. In this work, the subchronic toxicity of GRD081 in Sprague-Dawley (SD) rats and beagle dogs has been characterized. Rats and dogs received GRD081 orally (2, 5, 10 and 1, 2, 4mg/kg/day, respectively) on a consecutive daily dosing schedule for 28days following a 14days of recovery period. The treatment resulted in unscheduled mortality in rats receiving 5mg/kg/day and 10mg/kg/day. The adverse effects of GRD081 on rats and dogs mainly included myelosuppression, immunosuppression, hematological toxicity, and moderate liver, pancreas and kidney toxicity. These observations are consistent with pharmacologic perturbations of physiologic processes associated with the intended molecular targets for this class of PI3K/mTOR signaling inhibitors. Most of the treatment-induced effects were reversible upon discontinuation of treatment. The no-observed-adverse-effect level (NOAEL) of GRD081 was 1mg/kg/day for beagle dogs and less than 2mg/kg/day for SD rats.
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Progesterone negatively regulates BCRP in progesterone receptor-positive human breast cancer cells.
Cell. Physiol. Biochem.
PUBLISHED: 07-03-2013
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Breast cancer resistance protein (BCRP) plays a crucial role in multidrug resistance (MDR). Previous studies have shown that steroid hormones, like progesterone (PROG), regulate BCRP expression. The presence of a progesterone response element (PRE) in the BCRP promoter, suggests that PROG may regulate transcription of BCRP.
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Harmful effect of ER? on BCRP-mediated drug resistance and cell proliferation in ER?/PR-negative breast cancer.
FEBS J.
PUBLISHED: 06-28-2013
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The role of estrogen receptor ? (ER?) in breast cancer is still under investigation. Various studies have provided evidence that ER? behaves as a tumor suppressor in breast cancer, whereas some studies of estrogen receptor ? (ER?) negative breast cancer reported a positive correlation between high ER? expression and poor prognostic phenotypes, such as induced proliferation, invasion and metastasis. In the present immunohistochemistry study of 99 ER?/progesterone receptor (PR)-negative breast cancer samples, nuclear expression of ER? was positively associated with membranous expression of breast cancer resistance protein (BCRP), Ki67 (proliferation marker) and tumor size. Moreover, both endogenous and exogenous ER? upregulated BCRP expression which induced BCRP-mediated drug resistance and enhanced proliferation of ER?-/PR- breast cancer cells in the presence of 17?-estradiol, whereas these effects were reversed by additional use of tamoxifen (TAM). In addition, the regulation of BCRP via specific binding between ER? and estrogen response element (ERE) was demonstrated in an electrophoretic mobility shift assay. Overall, our findings manifest that ER? might act as a tumor promoter of cell proliferation and BCRP-mediated drug resistance in ER?-/PR- breast cancer. TAM routinely used for patients with ER?+/PR+, ER?+/PR- and ER?-/PR+ breast cancer might also be effective in ER?-/PR- but ER?+ breast cancer. Therefore, the detection of ER? in clinic is valuable and should not be neglected in breast cancer, especially for the ER?-/PR- phenotype.
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Overexpression of CARM1 in breast cancer is correlated with poorly characterized clinicopathologic parameters and molecular subtypes.
Diagn Pathol
PUBLISHED: 06-21-2013
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Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. CARM1 has been reported to be associated with high grade tumors in breast cancer. It still remains unknown the expression pattern of CARM1 in breast cancer and its relationships with clinicopathological characteristics and molecular subtypes.
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The investigation of the interaction between Tropicamide and bovine serum albumin by spectroscopic methods.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 06-12-2013
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The fluorescence and ultraviolet-visible (UV-Vis) spectroscopy were explored to study the interaction between Tropicamide (TA) and bovine serum albumin (BSA) at three different temperatures (292, 301 and 310K) under imitated physiological conditions. The experimental results showed that the fluorescence quenching mechanism between TA and BSA was static quenching procedure. The binding constant (Ka), binding sites (n) were obtained. The corresponding thermodynamic parameters (?H, ?S and ?G) of the interaction system were calculated at different temperatures. The results revealed that the binding process is spontaneous, hydrogen binds and vander Waals were the main force to stabilize the complex. According to Förster non-radiation energy transfer theory, the binding distance between TA and BSA was calculated to be 4.90 nm. Synchronous fluorescence spectroscopy indicated the conformation of BSA changed in the presence of TA. Furthermore, the effect of some common metal ions (Mg(2+), Ca(2+), Cu(2+), and Ni(2+)) on the binding constants between TA and BSA were examined.
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One-step synthesis of Cl(-)-doped Pt(IV)/Bi2WO6 with advanced visible-light photocatalytic activity for toluene degradation in air.
J Colloid Interface Sci
PUBLISHED: 05-17-2013
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In this study, Cl(-) doped Pt(IV)/Bi2WO6 photocatalyst was successfully synthesized via a one-step hydrothermal route by adding H2PtCl6 immediately in the reaction system. X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption-desorption isotherms and photoluminescence spectra (PL) were utilized to analyze the morphology, chemical states, surface area and optical properties of as-prepared catalysts. The addition of H2PtCl6 to the reaction system inhibited the growth of Bi2WO6 square nanoplates but facilitated the generation of irregular Bi2WO6 nanosheets with enlarged surface area and extended visible light absorption. In the resulted sample, it was observed that Pt(IV) was uniformly dispersed on the surface of Bi2WO6 irregular nanosheets and Cl(-) other than that from PtCl4 was doped into the sample by forming ionic bond with [Bi2O2](2+). Compared with pure Bi2WO6 nanosheets, Cl(-) doped Pt(IV)/Bi2WO6 showed enhanced activity in photocatalytic decomposition of toluene under visible light irradiation (420 nm
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Novel mutations of SLC26A4 in Chinese patients with nonsyndromic hearing loss.
Acta Otolaryngol.
PUBLISHED: 05-03-2013
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This study demonstrated high prevalence of GJB2, SLC26A4, and mtDNA A1555G mutations in Chinese patients with nonsyndromic hearing loss and discovered eight novel mutations in SLC26A4. Most of these novel mutations were predicted pathogenic variants.
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Identification of ?1-antitrypsin as a potential prognostic biomarker for advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors by proteomic analysis.
J. Int. Med. Res.
PUBLISHED: 04-23-2013
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This retrospective study attempted to identify serum biomarkers that could help to indicate treatment response in advanced nonsmall-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.
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Changes in age distribution of hemorrhagic fever with renal syndrome: an implication of Chinas expanded program of immunization.
BMC Public Health
PUBLISHED: 04-19-2013
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Vaccination against hemorrhagic fever with renal syndrome (HFRS) has been applied successfully for more than 20 years in China, and since 2008, the government has implemented the Expanded Program of Immunization (EPI) in regions with high incidence. In this study, we analyzed the EPI-related changes in age distribution in reported cases of HFRS and proposed new recommendations for prevention and control of the disease.
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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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