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Find video protocols related to scientific articles indexed in Pubmed.
Designing a Cu(II)-ArCu(II)-ArCu(III)-Cu(I) Catalytic Cycle: Cu(II)-Catalyzed Oxidative Arene C-H Bond Azidation with Air as an Oxidant under Ambient Conditions.
J. Org. Chem.
PUBLISHED: 11-05-2014
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On the basis of our recent discovery of high valent organocopper compounds, we have designed and achieved efficient copper(II)-catalyzed oxidative arene C-H bond azidation under very mild aerobic conditions by using NaN3 as an azide source. In the presence of a Cu(II) catalyst, a number of azacalix[1]arene[3]pyridines underwent direct arene C-H bond cupration through an electrophilic aromatic metalation pathway to form an arylcopper(II) intermediate. Oxidized by a free copper(II) ion, the arylcopper(II) intermediate was transformed into an arylcopper(III) species that subsequently cross-coupled with azide to furnish the formation of aryl azide products with the release of a copper(I) ion. Under ambient catalytic reaction conditions, the copper(I) species generated was oxidized by air into copper(II), which entered into the next catalytic cycle. Application of the method was demonstrated by the synthesis of functional azacalix[1]arene[3]pyridines by means of simple and practical functional group transformations of azide. The showcase of the Cu(II)-ArCu(II)-ArCu(III)-Cu(I) catalytic cycle would provide a new strategy for the design of copper(II)-catalyzed aerobic oxidative arene C-H bond activation and transformations.
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Investigation of plasmonic whispering-gallery mode characteristics for graphene monolayer coated dielectric nanodisks.
Opt Lett
PUBLISHED: 11-01-2014
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In this Letter, we theoretically studied high-quality (Q) factor plasmonic whispering-gallery modes (WGMs) with ultrasmall mode volumes in graphene monolayer coated semiconductor nanodisks in the mid-infrared range. The influence of the chemical potential, the relaxation time of graphene, and the radius of the nanodisk on the cavity Q factor and the mode volume was numerically investigated. The numerical simulations showed that the plasmonic WGMs excited in this cavity had a deep subwavelength mode volume of 1.4×10-5(?0/2n)3, a cavity Q factor as high as 266 at a temperature lower than 250 K, and, consequently, a large Purcell factor of ?1.2×107 when the chemical potential and relaxation time were assumed to be 0.9 eV and 1.4 ps, respectively. The results provide a possible application of plasmonic WGMs in the integration of nano-optoelectronic devices based on graphene.
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Establishment and evaluation on the animal models with coronary microcirculation dysfunction.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 11-01-2014
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Animal models of coronary microcirculation dysfunction are useful in research on the pathology of coronary microcirculation dysfunction and its intervention mechanisms. Currently,such animal modes are prepared mainly by mechanical obstruction and chemical damage form coronary microembolization or microthrombosis. This paper summarizes the currently available preparation techniques and compared their advantages and disadvantages.
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Nanoscale-Driven Crystal Growth of Hexaferrite Heterostructures for Magnetoelectric Tuning of Microwave Semiconductor Integrated Devices.
ACS Nano
PUBLISHED: 10-31-2014
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A nanoscale-driven crystal growth of magnetic hexaferrites was successfully demonstrated at low growth temperatures (25-40% lower than the temperatures required often for crystal growth). This outcome exhibits thermodynamic processes of crystal growth, allowing ease in fabrication of advanced multifunctional materials. Most importantly, the crystal growth technique is considered theoretically and experimentally to be universal and suitable for the growth of a wide range of diverse crystals. In the present experiment, the conical spin structure of Co2Y ferrite crystals was found to give rise to an intrinsic magnetoelectric effect. Our experiment reveals a remarkable increase in the conical phase transition temperature by ?150 K for Co2Y ferrite, compared to 5-10 K of Zn2Y ferrites recently reported. The high quality Co2Y ferrite crystals, having low microwave loss and magnetoelectricity, were successfully grown on a wide bandgap semiconductor GaN. The demonstration of the nanostructure materials-based "system on a wafer" architecture is a critical milestone to next generation microwave integrated systems. It is also practical that future microwave integrated systems and their magnetic performances could be tuned by an electric field because of the magnetoelectricity of hexaferrites.
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Catalytic Asymmetric Difunctionalization of Stable Tertiary Enamides with Salicylaldehydes: Highly Efficient, Enantioselective, and Diastereoselective Synthesis of Diverse 4-Chromanol Derivatives.
Org. Lett.
PUBLISHED: 10-30-2014
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Catalyzed by a chiral BINOL-Ti(OiPr)4 complex, various stable tertiary enamides reacted with salicylaldehydes to afford diverse cis,trans-configured 4-chromanols that contain three continuous stereogenic centers in good yields with excellent diastereoselectivity and enantioselectivity. The reaction proceeded through the addition of enamide to aldehyde followed by the intramolecular interception of the resulting iminium by the hydroxy group. Oxidation of the resulting 4-chromanols yielded almost quantitatively chroman-4-one derivatives which underwent diastereospecific reduction with NaBH4 to produce cis,cis-configured 4-chromanols.
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Direct sewage filtration for concentration of organic matters by dynamic membrane.
Water Sci. Technol.
PUBLISHED: 10-30-2014
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Sewage treatment is experiencing a paradigm shift whereby sewage should be treated as a resource with maximum reuse of water, nutrients and energy. Concentration of sewage for organic matter enrichment is essential for improved energy recovery. In this study, the concentrating performance of direct sewage filtration by a dynamic membrane was investigated. A novel double-layer cloth-media membrane module was developed. A 50 ?m Daron cloth was selected as inner layer and a 1 ?m propene polymer cloth as outer layer. Quick formation of the dynamic membrane was observed and it agreed with the complete blocking model. The results of continuous-flow experiments showed that chemical oxygen demand (COD) was concentrated to about 4500 mg/L within nine operation cycles in 70 hours. Trans-membrane pressure increased quickly to 80 kPa at the end of each cycle. Theoretical concentrating efficiency (?) was 77% and the carbon balance calculation showed 70.7% COD was retained in the reactor during the concentrating process. Scanning electron microscopy analysis showed that the cake layer was almost completely removed after physical cleaning and the gel layer was not remarkable. A sequencing sewage concentrating process was proposed for long-term operation.
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Modeled behavioral evaluation of the neuropathic pain with social defect in rats: a preliminary methodology evaluation.
Med Sci Monit Basic Res
PUBLISHED: 10-29-2014
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Background Social defect and chronic pain are 2 major health problems and recent data has demonstrated that they generally exist concurrently. However, a powerful evaluation model on the behavioral change is lacking. This study was designed to evaluate the behavioral curves using a statistically modeled trajectory analysis in neuropathic animals with or without social defect exposure. Material and Methods After approval by the institutional animal care committee, Sprague-Dawley rats were randomized into different interventional groups with 15 animals each. Sprague-Dawley rats underwent spared nerve injury (SNI) to establish the neuropathic pain model, of which the mechanical withdrawal threshold was measured using von Frey filaments for a period of 105 days. Otherwise, a modified version of the resident (Long-Evans rats)-intruder paradigm was applied to produce a social defect animal model through the elevated plus maze (EPM). After raw data collection, we modeled them into a powerful statistical effects analysis to build up the behavioral change tendency in single SNI or in combined SNI and social defect animals. Results The random and fixed effects analyses of the pain behavior after SNI were successfully modeled and demonstrated a gradient recovery tendency during the 15-week post-injury observational period. Correspondingly, SNI rats exhibited increased social defected symptoms, as indicated by the increased anxiety-like behavior in the EPM test. In addition, continuous social defect stress for 5 days or 10 days, respectively, partially attenuated and exacerbated SNI-induced allodynia in both random and fixed effects models. Five days but not 10 days social defect ameliorated SNI-associated anxiety-like behavior. Conclusions These data suggest that statistically powerful analysis of nerve injury-induced neuropathic pain is a highly sensitive model to determine the behavioral change tendency and distinguish them among behavior curves with or without social defect, and the combination of SNI with resident-intruder paradigm may be a suitable model for behavior evaluation of neuropathic pain with social defect.
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Regular intermittent bolus provides similar incidence of maternal fever compared with continuous infusion during epidural labor analgesia.
Saudi Med J
PUBLISHED: 10-16-2014
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To compare the effects of regular intermittent bolus versus continuous infusion for epidural labor analgesia on maternal temperature and serum interleukin-6 (IL-6) level.
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Regulated assemblies and anion responsive vesicles based on 1,3-alternate oxacalix[2]arene[2]triazene amphiphiles.
Chem. Commun. (Camb.)
PUBLISHED: 09-16-2014
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Regulated assemblies from vesicles to micelles based on 1,3-alternate oxacalix[2]arene[2]triazine amphiphilic molecules were reported. The vesicular entities were responsive to anions and followed the selectivity in the order NO3(-) > Cl(-) > Br(-) > ClO4(-), driven by cooperative anion-? interactions and hydrogen bonding.
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[LncRNAs and cardiovascular diseases].
Sheng Li Ke Xue Jin Zhan
PUBLISHED: 09-16-2014
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Cardiovascular disease has been a huge threat to human health. Studies of cardiovascular disease is always an important field of basic medicine. Noncoding RNAs, once thought to be useless, are gaining attention from researchers along with the development of genetics and medical informatics. Most of noncoding RNAs are long noncoding RNA. Evidences suggest that long noncoding RNAs are connected to cardiovascular doisease, yet we still dont know much about their functions and how they work. Here we review the functions and characteristics of long noncoding RNAs and the relationship between long noncoding RNAs and cardiovascular disease. These studies may contribute to better comprehension of the etiology and pathophysiology of cardiovascular disease.
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[Endothelial cell damaging mechanism in aging organism].
Sheng Li Ke Xue Jin Zhan
PUBLISHED: 09-16-2014
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Aging includes various changes, from the dysfunction of different organs to cellular damages. Recent years, there is a growing attention on the relationship between aging and endothelial cell damage. Aging bodies' endothelial cells are damaged through many ways, all contribute to structural and functional changes. And these pathways are being researched more and more deeply. This paper reviews the change of aging organism and the effects on endothelial cells, focuses on the different pathways on endothelial damage, and also discusses the relevant regulatory factors, which can be treated as new direction for inhibiting endothelial damages and provide relevant strategies for delaying damages.
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Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line.
Mol Med Rep
PUBLISHED: 08-04-2014
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The development of tumor cell drug resistance is the primary reason for treatment failure in lung cancer chemotherapy. Therefore, overcoming multidrug resistance is currently an urgent issue to be addressed in lung cancer treatment. Sunitinib is a tyrosine kinase inhibitor with confirmed inhibitory effects on tumor growth and metastasis; however, the effects of sunitinib and mechanisms of action in lung cancer multidrug resistance are yet to be determined. The present study was designed to examine the effects of sunitinib and the mechanisms underlying lung cancer multidrug resistance. It was observed that sunitinib was able to improve the sensitivity of A549/DDP lung cancer cells to cisplatin, enhance tumor apoptosis, arrest the cell cycle in G0/G1 phase, upregulate intracellular Rh-123 content, downregulate the expression of P-glycoprotein, multidrug resistance protein 1, multidrug resistance-associated protein 1, lung resistance protein, glutathione-S-transferase, ERCC1, survivin and Bcl-2 in tumor cells, phosphorylation of AKT and extracellular signal-regulated kinase (ERK), glutathione activity, and transcriptional activity of nuclear factor-?B, Twist, Snail and AP-1. The results demonstrated that sunitinib was able to reverse the multidrug resistance of A549/DDP lung cancer cells, which was possibly associated with the downregulation of multidrug resistance-associated gene expression and the inhibition of AKT and ERK phosphorylation.
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Synthesis of Quaternary-Carbon-Containing and Functionalized Enantiopure Pentanecarboxylic Acids from Biocatalytic Desymmetrization of meso-Cyclopentane-1,3-Dicarboxamides.
Chem Asian J
PUBLISHED: 08-02-2014
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Catalyzed by Rhodococcus erythropolis AJ270, a nitrile hydratase-amidase containing microbial whole-cell catalyst under mild conditions, enantioselective desymmetrizations of meso-cyclopentane-1,3-dicarbonitriles and cyclopentane-1,3-dicarboxamides were studied. Although the nitrile hydratase was found to exhibit high enzymatic activity, but low 1R enantioselectivity toward dinitriles, a number of 2,2-unsymmetrically substituted meso-cyclopentane-1,3-dicarboxamide substrates were converted by the 1S enantioselective amidase into quaternary carbon-bearing enantiopure (1S,2R,3R)-3-carbamoylcyclopentanecarboxylic acids in yields up to 94?%. The application of the method was demonstrated by convenient and practical transformations of the resulting (1S,2R,3R)-2-allyl-3-carbamoylcyclopentanecarboxylic acid derivatives into functionalized cyclopentane-fused ?-lactam and ?-lactone compounds.
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Structural insights for the design of new borate-phosphates: synthesis, crystal structure and optical properties of Pb?O(BO?)(PO?) and Bi?O?(BO?)(PO?).
Dalton Trans
PUBLISHED: 07-15-2014
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Two new metal borate-phosphates, Pb4O(BO3)(PO4) (1) and Bi4O3(BO3)(PO4) (2), have been successfully designed and synthesized. The structures of the title compounds were determined by single-crystal X-ray diffraction. The title compounds have similar crystal structures consisting of oxygen-centered (OPb4) or (OBi4) tetrahedra as well as isolated BO3 and PO4 groups. Structural comparison and the Madelung energy calculation indicate that the title compounds also exhibit a strong correlation with the known metal borates and phosphates. In addition, a strategy of BO3-PO4 substitution is proposed for designing new borate-phosphates. Thermal analyses, IR spectroscopy and UV-vis-NIR diffuse reflectance spectroscopy have also been performed.
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New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling.
FEBS Lett.
PUBLISHED: 07-11-2014
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As a well-characterized master player in epigenetic regulatory network, EZH2 is widely implicated in the development of many malignancies. We previously found that EZH2 promoted Wnt/?-catenin activation through downregulation of CXXC4 expression. In this report, we demonstrated that CXXC4 inhibited MAPK signaling through binding to ERK-1/2 and abrogating the interaction of ERK 1/2 with MEK1/2. L183, the critical residue in CXXC4 ERK D domain, was found to be essential for CXXC4-ERK 1/2 interaction and the growth inhibitory effect of CXXC4 in human cancer cells. In summary, CXXC4 directly disrupted MEK1/2-ERK 1/2 interaction to inactivate MAPK signaling. L183 site is indispensable for the binding of CXXC4 to ERK1/2 and growth inhibitory effect of CXXC4. Therefore, EZH2 can activate MAPK signaling by inhibiting CXXC4 expression.
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Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of oestrogen receptor-positive breast cancers.
Nat Commun
PUBLISHED: 07-02-2014
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Characterizing the genetic alterations leading to the more aggressive forms of oestrogen receptor-positive (ER+) breast cancers is of critical significance in breast cancer management. Here we identify recurrent rearrangements between the oestrogen receptor gene ESR1 and its neighbour CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal B tumours, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170-positive tumours. These fusions encode amino-terminally truncated CCDC170 proteins (?CCDC170). When introduced into ER+ breast cancer cells, ?CCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity and enhanced xenograft tumour formation. Mechanistic studies suggest that ?CCDC170 engages Gab1 signalosome to potentiate growth factor signalling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer.
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Inhibitory effect of ?-elemene on human breast cancer cells.
Int J Clin Exp Pathol
PUBLISHED: 06-15-2014
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It has been approved for the clinical application of ?-elemene to treat various cancers mainly brain tumors in China. In the present study, we found that ?-elemene significantly inhibited the in vitro growth of human breast cancer cells by inducing apoptosis. In addition, ?-elemene also induced the conversion of LC3-I into LC3-II as well as the formation of autolysosomes, indicating the activation of autophagy. Interestingly, inhibition of autophagy significantly potentiated the growth-inhibitory effect of ?-elemene on breast cancer cells. In summary, ?-elemene induced cytoprotective autophagy in human breast cancer cells in addition to apoptosis. Inhibition of autophagy significantly enhanced the cytotoxicity of ?-elemene to human breast cancer cells. Therefore, combination of ?-elemene with autophagy inhibitors could be a promising strategy for the treatment of breast cancer.
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YY1-MIR372-SQSTM1 regulatory axis in autophagy.
Autophagy
PUBLISHED: 06-11-2014
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Autophagy is a self-proteolytic process that degrades intracellular material to enable cellular survival under unfavorable conditions. However, how autophagy is activated in human carcinogenesis remains largely unknown. Herein we report an epigenetic regulation of autophagy in human cancer cells. YY1 (YY1 transcription factor) is a well-known epigenetic regulator and is upregulated in many cancers. We found that YY1 knockdown inhibited cell viability and autophagy flux through downregulating SQSTM1 (sequestosome 1). YY1 regulated SQSTM1 expression through the epigenetic modulation of the transcription of MIR372 (microRNA 372) which was found to target SQSTM1 directly. During nutrient starvation, YY1 was stimulated to promote SQSTM1 expression and subsequent autophagy activation by suppressing MIR372 expression. Similar to YY1 depletion, MIR372 overexpression blocked autophagy activation and inhibited in vivo tumor growth. SQSTM1 upregulation and competent autophagy flux thus contributed to the oncogenic function of YY1. YY1-promoted SQSTM1 upregulation might be a useful histological marker for cancer detection and a potential target for drug development.
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[The mechanisms of high-phosphate-induced vascular calcification in patients with chronic kidney disease].
Sheng Li Ke Xue Jin Zhan
PUBLISHED: 05-31-2014
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Vascular calcification is the leading cause of cardiovascular diseases in chronic kidney disease (CKD) patients. Hyperphosphatemia is common in CKD patients, mainly because of dysfunction of kidney and dysregulation of hormones. Many studies indicate that elevated plasma phosphate level has direct effects on vascular smooth muscle cells (VSMCs) and drives calcification. Recent findings suggest that elevated phosphate can induce chondrogenic/osteogenic differentiation of VSMCs, promote VSMC apoptosis and activate oxidative stress and inflammation, all of which contribute to vascular calcification. In this review, we highlight the advances in the mechanisms of vascular calcification caused by elevated phosphate and the preventing effects of phosphate control therapy on vascular calcification.
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Nanomaterials and nanoclusters based on DNA modulation.
Curr. Opin. Biotechnol.
PUBLISHED: 05-17-2014
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Besides the inherent chirality, DNA is enriched by nitrogen and oxygen functional groups that are preferential to coordinate with transition metal ions, and its self-assembled structures, including the G-quadruplex, the i-motif, and the conventional Watson-Crick duplex, etc., can be adjusted via different base pairings. Recently biotemplating on the basis of DNA self-assembly has been considered as an attractive method to construct switchable nanomaterials, to direct crystal growth and to design enantioselective selectors/catalysts. This review briefly covers the recent progress relevant to DNA modulated nano/subnano materials. The long-term goal of this area of research is to explore novel promisingly environmental-benign approaches to construct switchable nanomachines, nano/subnano clusters and enantioselective recognition platforms respectively, through DNA-based modulation.
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Regulating the formation of self-supported LiCoO2 nanostructure by alkaline concentration and study on its electrochemical property.
J Nanosci Nanotechnol
PUBLISHED: 04-17-2014
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LiCoO2 nanosheets with high crystallinity and large area were synthesized via a facile hydrothermal route. The structure and morphology properties of the nanosheet are identified by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area analysis. The experimental results show that the morphology and the thickness of the nanosheet can be tuned by simply regulating the concentration of the NaOH solution. The higher the NaOH concentration, the thinner (less than 100 nm) and larger (up to several microm) the nanosheet becomes. Moreover, the electrical properties of the as-designed nanosheet also change with the thickness of the nanosheet. The charge-discharge capacity of the LiCoO2 nanosheet tends to increase in the thinner nanosheet with a larger surface area. We proposed that the reason may be attributed to the accelerated intercalation and de-intercalation process of the lithium ion in the nanosheet.
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Factors related to the use of reperfusion strategies in elderly patients with acute myocardial infarction.
J Cardiothorac Surg
PUBLISHED: 04-01-2014
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About eighty percent of acute myocardial infarction (AMI) cases occur in the elderly, we aim to examine the use of reperfusion strategies in elderly patients (?65 years) with AMI and to investigate the factors affecting the use of these strategies.
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Surface-plasmon-polariton whispering-gallery mode analysis of the graphene monolayer coated InGaAs nanowire cavity.
Opt Express
PUBLISHED: 03-26-2014
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In this article, we proposed and numerically studied the surface plasmon polariton whispering gallery mode properties of the graphene coated InGaAs nanowire cavity. The quality factor and the mode area were investigated as a function of the chemical potential, the cavity radius and the wavelength. A high cavity quality factor of 235 is predicted for a 5 nm radius cavity, accompanied by a mode area as small as3.75×10(-5)(?(0))(2), when the chemical potential is 1.2 eV. The proposed structure offers a potential solution to high density integration of the nanophotonic devices with an ultra-compact footprint.
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Anti-inflammatory effects of triptolide by inhibiting the NF-?B signalling pathway in LPS-induced acute lung injury in a murine model.
Mol Med Rep
PUBLISHED: 03-25-2014
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Triptolide is one of the main active components in the Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to possess anti?inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)?induced acute lung injury (ALI) in mice and to explore the possible mechanisms. Mice were administered LPS intranasally to induce lung injury, and triptolide was administered intraperitoneally 1 h prior to the LPS challenge. Triptolide?treated mice exhibited significantly reduced levels of leukocytes, myeloperoxidase activity and edema of the lung, as well as tumour necrosis factor??, interleukin (IL)?1? and IL?6 production in the bronchoalveolar lavage fluid compared with LPS?treated mice. Additionally, western blot analysis showed that triptolide inhibited the LPS?induced phosphorylation of nuclear factor of ? light polypeptide gene enhancer in B cells inhibitor?? and nuclear factor ??light?chain?enhancer of activated B cells?p65 (NF??B p65) and the expression of Toll?like receptor 4 (TLR4). In conclusion, the results from the present study suggest that the anti?inflammatory effect of triptolide against LPS?induced ALI may be due to its ability to inhibit the TLR4?mediated NF??B signalling pathway. Triptolide may therefore be a promising potential therapeutic agent for ALI treatment, which may ultimately aid the clinical therapy for patients with ALI.
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Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non-small-cell lung cancer.
Mol Clin Oncol
PUBLISHED: 03-21-2014
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Epidermal growth factor receptor (EGFR) somatic mutations are found in the majority of non-small-cell lung cancers (NSCLCs) and patients with NSCLC who harbor EGFR mutations have been shown to exhibit increased sensitivity to the small-molecule EGFR-tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. However, the majority of tumors develop acquired resistance to EGFR-TKIs after a median of 10-16 months, which limits the clinical efficacy of these drugs. Autophagy, an important homeostatic cellular recycling mechanism, has emerged as a potential target for the acquired resistance phenotype. Recently, several studies demonstrated that autophagy may be induced in a dose-dependent manner by treatment of multiple cancer cell lines with EGFR-TKIs in vitro. Furthermore, it was recently reported that autophagy, as a cytoprotective response, may be activated by EGFR-TKIs in lung cancer cells and that the inhibition of autophagy enhanced the cytotoxic effect of EGFR-TKIs. In this review, we aimed to focus on the association between resistance to EGFR-TKIs and autophagy, and assess whether autophagy inhibition represents a promising approach to improve the efficacy of EGFR-TKIs in the treatment of NSCLC patients.
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Cutaneous metastasis from pancreatic cancer: A case report and systematic review of the literature.
Oncol Lett
PUBLISHED: 03-12-2014
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Cutaneous metastasis from pancreatic cancer is uncommon, therefore, the outcome of this progression has rarely been investigated. The aim of the present report was to evaluate the clinical characteristics of patients exhibiting cutaneous metastasis from pancreatic cancer. Thus, the current report presents a rare case of cutaneous metastatic disease from pancreatic cancer and describes a systematic review of the literature. A total of 54 articles comprising 63 cases were included for analysis. The relevant clinical and pathological characteristics, as well as the treatment strategies and survival outcomes of this rare disease presentation were reviewed. The average patient was was aged 63.9 years and males constituted a marginally greater proportion of the cohort (61.9%). The predominant manifestation of the cutaneous metastasis was a nodule or mass (73%) and the most common site of the skin lesion was non-umbilicus rather than umbilicus. The majority (66.7%) of the skin lesions were singular, particularly in patients exhibiting Sister Mary Joseph's nodule (90%). A wide range of histological subtypes presented, with a predominance of adenocarcinoma (84.1%). Of the cases that specified the tumor differentiation grade, 78.2% were moderately or poorly differentiated. Immunohistochemistry revealed that cytokeratin (CK)20-negative, and CK7-, CK19- and carbohydrate antigen (CA)19-9-positive were specific diagnostic markers for pancreatic cancer. Distal metastases, excluding the skin, were observed in 68.3% of patients and the median survival period was 5 months. Treatment strategies including surgery, radiation, chemotherapy or a combination improved survival time from 3.0 to 8.3 months. Cutaneous metastasis from pancreatic cancer is a rare finding, often providing the only external indication of an internal malignancy and, therefore, should be considered in the differential diagnosis of skin lesions. Metastasis to the skin indicates a widespread, general dissemination and a poor prognosis. A combination of surgery, radiotherapy and chemotherapy appears to result in improved survival rates.
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mTOR in viral hepatitis and hepatocellular carcinoma: function and treatment.
Biomed Res Int
PUBLISHED: 03-07-2014
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As the fifth most common cancer in men and the eighth most common cancer in women, hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, with standard chemotherapy and radiation being minimally effective in prolonging survival. Virus hepatitis, particularly HBV and HCV infection is the most prominent risk factor for HCC development. Mammalian target of rapamycin (mTOR) pathway is activated in viral hepatitis and HCC. mTOR inhibitors have been tested successfully in clinical trials for their antineoplastic potency and well tolerability. Treatment with mTOR inhibitor alone or in combination with cytotoxic drugs or targeted therapy drug scan significantly reduces HCC growth and improves clinical outcome, indicating that mTOR inhibition is a promising strategy for the clinical management of HCC.
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Increased circulating microRNA-155 as a potential biomarker for breast cancer screening: a meta-analysis.
Molecules
PUBLISHED: 02-21-2014
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The objective of this meta-analysis was to determine the diagnostic accuracy of circulating microRNA-155 (miR-155) for breast cancer (BC). PubMed, Embase, EBSCO (ASP/BSP), Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched up to 30 January 2014 for eligible studies. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the quality of the included studies. Meta-analysis were performed in Meta-Disc 1.4 and Stata 12.0. Three studies with total 184 BC patients and 75 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS scores 12 or 13). The summary estimates revealed that the pooled sensitivity is 79% (95% confidence interval (CI): 72%-84%) and the specificity is 85% (95% CI: 75%-92%), for the diagnosis of breast cancer. In addition, the area under the summary ROC curve (AUC) is 0.9217. The current evidence suggests that circulating miR-155 has the potential diagnostic value with a high sensitivity and specificity for BC. More prospective studies on the diagnostic value of circulating miR-155 for BC are needed in the future.
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Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in cervical artery dissection: a meta-analysis.
Cerebrovasc. Dis.
PUBLISHED: 02-18-2014
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Cervical artery dissection (CAD) is a recognized cause of ischemic stroke. Hyperhomocysteinemia (HHcy), i.e. an elevated concentration of plasma homocysteine, is identified as an independent risk factor for stroke prevalence. However, an association between HHcy and CAD has so far remained unknown.
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p53 suppresses stress-induced cellular senescence via regulation of autophagy under the deprivation of serum.
Mol Med Rep
PUBLISHED: 02-07-2014
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The tumor suppressor p53 is widely known for its ability to induce cell cycle arrest or cell death, therefore preventing neoplastic progression. Previous studies have demonstrated novel roles for p53 in the regulation of autophagy and senescence. p53 can not only exert cell cycle?arresting and senescence?promoting or suppressing functions, but can also induce autophagic ?ux, particularly under conditions of nutrient deprivation. The present study demonstrated that p53 was capable of activating autophagy, which permits cell survival under conditions of serum starvation, and suppresses cellular senescence through inhibition of the mammalian target of rapamycin pathway. These results suggest that active autophagy may be a potential mechanism by which p53 suppresses cellular senescence, in response to serum starvation. The findings of the present study provide a potential mechanism for suppression of senescence by p53.
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A genome-wide association study of limb bone length using a Large White?×?Minzhu intercross population.
Genet. Sel. Evol.
PUBLISHED: 01-28-2014
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In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length.
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JNK confers 5-fluorouracil resistance in p53-deficient and mutant p53-expressing colon cancer cells by inducing survival autophagy.
Sci Rep
PUBLISHED: 01-24-2014
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Deficiency or mutation in the p53 tumor suppressor gene commonly occurs in human cancer and can contribute to disease progression and chemotherapy resistance. Currently, although the pro-survival or pro-death effect of autophagy remains a controversial issue, increasing data seem to support the idea that autophagy facilitates cancer cell resistance to chemotherapy treatment. Here we report that 5-FU treatment causes aberrant autophagosome accumulation in HCT116 p53(-/-) and HT-29 cancer cells. Specific inhibition of autophagy by 3-MA, CQ or small interfering RNA treatment targeting Atg5 or Beclin 1 can potentiate the re-sensitization of these resistant cancer cells to 5-FU. In further analysis, we show that JNK activation and phosphorylation of Bcl-2 are key determinants in 5-FU-induced autophagy. Inhibition of JNK by the compound SP600125 or JNK siRNA suppressed autophagy and phosphorylation of c-Jun and Bcl-2 but increased 5-FU-induced apoptosis in both HCT116 p53(-/-) and HT29 cells. Taken together, our results suggest that JNK activation confers 5-FU resistance in HCT116 p53(-/-) and HT29 cells by promoting autophagy as a pro-survival effect, likely via inducing Bcl-2 phosphorylation. These results provide a promising strategy to improve the efficacy of 5-FU-based chemotherapy for colorectal cancer patients harboring a p53 gene mutation.
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Dynamic observation of artery endothelial cell layers in response to bare metal stent and paclitaxel-eluting stent in vitro.
J Interv Cardiol
PUBLISHED: 01-16-2014
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We aimed to investigate the mechanism of paclitaxel-eluting stent (PES) induced thrombosis by real-time dynamic monitoring of live endothelial cells.
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Cell transfer therapy for cancer: past, present, and future.
J Immunol Res
PUBLISHED: 01-09-2014
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Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells.
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Size-regulable vesicles based on anion-? interactions.
Chemistry
PUBLISHED: 01-08-2014
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Taking tetraoxacalix[2]arene[2]triazine as a functionalization platform, a series of new amphiphilic molecules were synthesized in 18 to 53?% yields by using a fragment coupling protocol. These amphiphilic molecules self-assembled into stable vesicles in a mixture of THF and water, with the surface of the vesicles engineered by electron-deficient cavities. Various anions are able to selectively influence the size of self-assembled vesicles, following the order of F(-) < ClO4(-) < SCN(-) < BF4(-) < Br(-) < Cl(-) < NO3(-), as revealed by DLS measurements. Such a sequence was independent with the hydration cost and in agreement with the binding strength of anions with tetraoxacalix[2]arene[2]triazine host molecule, indicating that the anion-? interaction most probably competed over other possible weak interactions and accounted for this interesting selectivity. In addition, the chloride permeation process across the membrane of the vesicles was also preliminarily studied by means of fluorescent experiments. This study, in addition to providing the potentiality of heteracalixaromatics as new models to construct functional vesicles, opens a new avenue to study the anion-? interactions in aqueous and also potentially in living systems.
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High-mobility Bi2Se3 nanoplates manifesting quantum oscillations of surface states in the sidewalls.
Sci Rep
PUBLISHED: 01-03-2014
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Magnetotransport measurements of topological insulators are very important to reveal the exotic topological surface states for spintronic applications. However, the novel properties related to the surface Dirac fermions are usually accompanied by a large linear magnetoresistance under perpendicular magnetic field, which makes the identification of the surface states obscure. Here, we report prominent Shubnikov-de Haas (SdH) oscillations under an in-plane magnetic field, which are identified to originate from the surface states in the sidewalls of topological insulator Bi2Se3 nanoplates. Importantly, the SdH oscillations appear with a dramatically weakened magnetoresistance background, offering an easy path to probe the surface states directly when the coexistence of surface states and bulk conduction is inevitable. Moreover, under a perpendicular magnetic field, the oscillations in Hall conductivity have peak-to-valley amplitudes of 2?e(2)/h, giving confidence to achieve a quantum Hall effect in this system. A cross-section view of the nanoplate shows that the sidewall is (015) facet dominant and therefore forms a 58° angle with regard to the top/bottom surface instead of being perpendicular; this gives credit to the surface states' behavior as two-dimensional transport.
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Regulation of CRADD-caspase 2 cascade by histone deacetylase 1 in gastric cancer.
Am J Transl Res
PUBLISHED: 01-01-2014
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CRADD, also referred as RAIDD, is an adaptor protein that could interact with both caspase 2 and RIP that can promote apoptosis once activated. HDAC inhibitors are promising anti-cancer agents by inducing apoptosis of various cancer cells. In this study, we found that CRADD was induced by TSA (trichostatin A) to activate caspase 2-dependent apoptosis. CRADD was downregulated in gastric cancer and the restoration of its expression suppressed the viability of gastric cancer cells. HDAC1 was responsible for its downregulation in gastric cancer since HDAC1 siRNA upregulated CRADD expression and HDAC1 directly bound to the promoter of CRADD. Therefore, the high expression of HDAC1 can downregulate CRADD to confer gastric cancer cells the resistance to caspase 2-dependent apoptosis. HDAC inhibitors, potential anti-cancer drugs under investigation, can promote caspase 2-dependent apoptosis by inducing the expression of CRADD.
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EGFR-TKI resistance in NSCLC patients: mechanisms and strategies.
Am J Cancer Res
PUBLISHED: 01-01-2014
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The epidermal growth factor receptor (EGFR) is a kind of receptor tyrosine kinase (RTK) that plays a critical role in the initiation and development of malignant tumors via modulating downstream signaling pathways. In non-small cell lung cancer (NSCLC), the activating mutations located in the tyrosine kinase domains of EGFR have been demonstrated in multiple researches as the "Achilles' heel" of this deadly disease since they could be well-targeted by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, it's still too early to celebrate since the first-generation EGFR-TKIs such as gefitinib and erlotinib have only achieved limited clinical benefits and acquired resistance to this kind of drugs occurred inevitably in almost all the NSCLC patients. In order to make the most of EGFR-TKIs and develop more effective regimens for the NSCLC patients, researchers majoring in different aspects start a battle against EGFR-TKI resistance. Challenging as it is, we still progress stably and step firmly toward the final victory. This review will summarize the major mechanisms of acquired resistance to EGFR-TKIs, and then discuss the development of rationally designed molecular target drugs in accordance with each mechanism, in the hope of shedding light on the great achievements we have obtained and tough obstacles we have to overcome in the battle against this deadly disease.
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Mouse mammary tumor virus-like virus infection and the risk of human breast cancer: a meta-analysis.
Am J Transl Res
PUBLISHED: 01-01-2014
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Despite a large number of molecular epidemiological studies, the association of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) infection with the risk of human breast cancer remains inconclusive mainly due to the heterogeneity in populations involved. We performed a systematic search of multiple bibliographic databases, up to October 2013, to identify all studies on detection of MMTV-LV DNA in human breast cancer using polymerase chain reaction (PCR) and conducted the first comprehensive meta-analysis of published literature to explore the relevance of MMTV-LV to human breast cancer. As a result, meta-analysis of twelve case-control studies identified from the systematic search revealed a significantly increased risk for breast cancer development after MMTV-LV infection (OR=15.20; 95% CI: 9.98-23.13). However, there was no significant correlation between MMTV-LV infection and the transformation from ductal carcinoma in situ to invasive ductal carcinoma (OR=1.16; 95% CI: 0.27-4.97). In addition, MMTV-LV infection was not associated with the expression of estrogen receptor (ER) (OR=0.89; 95% CI: 0.48-1.65), progesterone receptor (PR) (OR=0.73; 95% CI: 0.22-2.42), HER-2 (OR=0.65; 95% CI: 0.30-1.43) or p53 (OR=1.47; 95% CI: 0.79-2.73). Finally, we found that the prevalence of MMTV-LV in breast carcinoma was significantly higher in patients from Western countries (prevalence=40.4%, 95% CI: 28.9%-51.9%) than in Asian patients (prevalence: 8.5%; 95% CI: -7.1%-24.1%) in a subgroup and meta-regression analysis (p=0.015). In summary, the meta-analysis of published studies revealed a significantly increased risk for breast cancer development after MMTV-LV infection. In addition, the prevalence of MMTV-LV is much higher in breast cancer patients from Western countries than Asian patients.
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Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.
PLoS ONE
PUBLISHED: 01-01-2014
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Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.
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Epigenetic biomarkers: potential applications in gastrointestinal cancers.
ISRN Gastroenterol
PUBLISHED: 01-01-2014
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Genetics and epigenetics coregulate the cancer initiation and progression. Epigenetic mechanisms include DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs. Aberrant epigenetic modifications play a fundamental role in the formation of gastrointestinal cancers. Advances in epigenetics offer a better understanding of the carcinogenesis and provide new insights into the discovery of biomarkers for diagnosis, and prognosis prediction of human cancers. This review aims to overview the epigenetic aberrance and the clinical applications as biomarkers in gastrointestinal cancers mainly gastric cancer and colorectal cancer.
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Outcome prediction values of soluble human epidermal growth factor receptor-2 extracellular domain in metastatic breast cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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HER-2 overexpression is an independent predictor for poor prognosis of breast cancer patients. Recently, extracellular domain of HER-2 (ECD) was found detectable in the serum of breast cancer patients. In this prospective study, we wonder whether ECD levels predict the clinical outcome of metastatic breast cancer patients.
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Clinical study of the hypothesis of endogenous collateral wind on acute coronary syndrome: a review.
Afr J Tradit Complement Altern Med
PUBLISHED: 01-01-2014
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Acute Coronary Syndrome (ACS), is a serious threat to people's health, and life, and in recent years, the incidence has increased yearly. This study was to propose the hypothesis of "endogenous collateral wind" based on the patho-mechanism of thrombogenesis complicated by ruptured plaque on ACS, and the theory of traditional Chinese medicine.
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[Carvacrol pretreatment attenuates myocardial oxidative stress and apoptosis following myocardial ischemia-reperfusion in mice].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 11-26-2013
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To investigate the effect of carvacrol pretreatment on myocardial ischemia-reperfusion (I/R) injury and its underlying mechanisms.
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Intermedin inhibits macrophage foam-cell formation via tristetraprolin-mediated decay of CD36 mRNA.
Cardiovasc. Res.
PUBLISHED: 11-18-2013
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CD36-mediated uptake of oxidized low-density lipoprotein (oxLDL) plays a pivotal role in macrophage foam-cell formation and atherogenesis. Previously we reported on intermedin (IMD), a novel member of the calcitonin gene-related peptide family, in atherosclerotic plaque reducing atherogenesis in apolipoprotein E-deficient (apoE(-/-)) mice. Here, we studied the role of IMD in CD36-mediated macrophage foam-cell formation.
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[Multiple-locus variable number tandem repeat analysis of Staphylococcus aureus in one food poisoning case].
Wei Sheng Yan Jiu
PUBLISHED: 11-14-2013
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To type Staphylococcus aureus strains from a food poisoning case by MLVA method, detect staphylococcal enterotoxin, and provide lab evidence for molecular epidemiological study and analysis of evolution.
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Lentivirus mediated GOLPH3 shRNA inhibits growth and metastasis of esophageal squamous cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-02-2013
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To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer.
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LC3B-II deacetylation by histone deacetylase 6 is involved in serum-starvation-induced autophagic degradation.
Biochem. Biophys. Res. Commun.
PUBLISHED: 10-30-2013
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Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum-starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation.
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Downregulation of histone deacetylase 1 by microRNA-520h contributes to the chemotherapeutic effect of doxorubicin.
FEBS Lett.
PUBLISHED: 09-26-2013
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Doxorubicin induces DNA damage to exert its anti-cancer function. Histone deacetylase 1 (HDAC1) can protect the genome from DNA damage. We found that doxorubicin specifically downregulates HDAC1 protein expression and identified HDAC1 as a target of miR-520h, which was upregulated by doxorubicin. Doxorubicin-induced cell death was impaired by exogenous HDAC1 or by miR-520h inhibitor. Moreover, HDAC1 reduced the level of ?H2AX by preventing the interaction of doxorubicin with DNA. In summary, doxorubicin downregulates HDAC1 protein expression, by inducing the expression of HDAC1-targeting miR-520h, to exacerbate DNA-doxorubicin interaction. The upregulation of HDAC1 protein may contribute to drug resistance of human cancer cells and targeting HDAC1 is a promising strategy to increase the clinical efficacy of DNA damage-inducing chemotherapeutic drugs.
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Regulation and function of mitophagy in development and cancer.
Autophagy
PUBLISHED: 09-26-2013
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Beyond its role in recycling intracellular components nonselectively to sustain survival in response to metabolic stresses, autophagy can also selectively degrade specific cargoes such as damaged or dysfunctional organelles to maintain cellular homeostasis. Mitochondria, known as the power plant of cells, are the critical and dynamic organelles playing a fundamental role in cellular metabolism. Mitophagy, the selective autophagic elimination of mitochondria, has been identified both in yeast and in mammalian cells. Moreover, defects in mitophagy may contribute to a variety of human disorders such as neurodegeneration and myopathies. However, the role of mitophagy in development and cancer remains largely unclear. In this review, we summarize our current knowledge of the regulation and function of mitophagy in development and cancer.
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Synthesis of electron-deficient oxacalix[2]arene[2]triazines and their isomeric analogs from a one-pot reaction of perfluorinated dihydroxybenzenes with dichlorotriazines.
Org. Lett.
PUBLISHED: 08-27-2013
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Efficient synthesis of tetraoxacalix[2]perfluoroarene[2]triazines and their isomeric analogs from a one-pot macrocyclic condensation reaction of methoxy- and amino-substituted dichlorotriazines with tetrafluorobenzene-1,3-, -1,4-, and -1,2-diols was developed. X-ray analysis demonstrates that they adopt drastically different 1,3-alternate conformations in the crystalline state while in solution they undergo very fast conformational changes relative to the NMR time scale.
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Highly Active Subnano Palladium Clusters Embedded in i-Motif DNA.
Langmuir
PUBLISHED: 08-16-2013
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Highly active subnano Pd clusters were synthesized using i-motif DNA as the template through characterization via ESI MS, DLS, XPS, UV-vis, and FTIR. It is indicated that Pd1-Pd5 clusters are generated at a [Pd]/[base] ratio of 0.2, Pd8 to Pd9 clusters are generated at a [Pd]/[base] ratio of 0.5, and large nanoparticles with the size about 2.6 nm are formed at a [Pd]/[base] ratio of 2.0. The i-motif-stabilized Pd8-Pd9 clusters show high catalytic activity toward the reduction of 4-nitrophenol with a relative rate constant value of 2034 min(-1) (mM Pd)(-1). DFT calculations disclose that the unique structure of the i-motif with consecutive hemiprotonated CH(+)·C pairs can efficiently ligate Pd ions at the N3 sites of cytosines and that the synthesized Pd clusters consist of metallic Pd atoms as well as positively charged Pd that is ligated by nucleobases, which is capable of facilitating the activation of the nitryl group of 4-nitrophenol. This work suggests a promising pathway to preparing subnano metal catalysts with enhanced catalytic activity using programmable DNA scaffolds.
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Synthesis of Multifunctionalized 1,2,3,4-Tetrahydropyridines, 2,3-Dihydropyridin-4(1H)-ones, and Pyridines from Tandem Reactions Initiated by [5+1] Cycloaddition of N-Formylmethyl-Substituted Enamides to Isocyanides: Mechanistic Insight and Synthetic Appl
Chemistry
PUBLISHED: 08-15-2013
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Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4-tetrahydropyridines, 2,3-dihydropyridin-4(1H)-ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)2 -mediated [5+1] cycloaddition of N-formylmethyl-substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me4 NBH(OAc)3 afforded 1,6-disubstituted trans-3-hydroxy-4-arylamino- or -alkylamino-1,2,3,4-tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6-disubstituted 3-acyloxy-2,3-dihydropyridin-4(1H)-ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl-group transfer from the pyridinium nitrogen to the 3-hydroxy moiety, thereby yielding substituted 3-acyloxy-4-aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis-4,5-dihydroxy-2-phenylpiperidine and trans,trans-4-amino-5-hydroxy-2-phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.
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Deficiency of cartilage oligomeric matrix protein causes dilated cardiomyopathy.
Basic Res. Cardiol.
PUBLISHED: 06-17-2013
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Alterations in cardiac extracellular matrix are involved in dilated cardiomyopathy (DCM) and its progression to heart failure. The matricellular protein cartilage oligomeric matrix protein (COMP) has been indicated localized in the heart. However, the role of COMP in cardiac homeostasis and disease remains elusive. COMP (-/-) mice, both male and female, developed DCM spontaneously at young age (3-5 months), with impaired cardiac function. Assessment of postnatal COMP (-/-) heart at 1 month, although functionally normal, revealed severe cardiac ultrastructure defect, in parallel with cardiomyocyte apoptosis, myofilament loss, connexin-43 deficiency and matrix metalloproteinase activation. Decreased COMP expression was observed in the heart sample of DCM patients compared with donor heart. Mechanistically, COMP (-/-) heart exhibited reduced integrin ?1 expression and signaling. Ectopic expression of COMP or integrin ?1 rescued COMP-deficiency-induced cardiomyocyte apoptosis, myofilament dissolution, and connexin-43 aberrance. Additionally, COMP directly bonded to the extracellular ?-tail domain of integrin ?1, prevented integrin ?1 ubiquitination/degradation, and maintained the cardiac homeostasis. COMP-integrin ?1 axis is a potential target of DCM.
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Epidermal stem cells and their epigenetic regulation.
Int J Mol Sci
PUBLISHED: 06-05-2013
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Stem cells play an essential role in embryonic development, cell differentiation and tissue regeneration. Tissue homeostasis in adults is maintained by adult stem cells resident in the niches of different tissues. As one kind of adult stem cell, epidermal stem cells have the potential to generate diversified types of progeny cells in the skin. Although its biology is still largely unclarified, epidermal stem cells are widely used in stem cell research and regenerative medicine given its easy accessibility and pluripotency. Despite the same genome, cells within an organism have different fates due to the epigenetic regulation of gene expression. In this review, we will briefly discuss the current understanding of epigenetic modulation in epidermal stem cells.
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Acupuncture therapy related cardiac injury.
Chin J Integr Med
PUBLISHED: 06-05-2013
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Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.
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Endocardial endothelium is a key determinant of force-frequency relationship in rat ventricular myocardium.
J. Appl. Physiol.
PUBLISHED: 05-23-2013
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We tested the hypothesis that removing endocardial endothelium (EE) negatively impacts the force-frequency relationship (FFR) of ventricular myocardium and dissected the signaling that underlies this phenomenon. EE of rat trabeculae was selectively damaged by brief (<1 s) exposure to 0.1% Triton X-100. Force, intracellular Ca(2+) transient (iCa(2+)), and activity of protein kinase A (PKA) and protein kinase C (PKC) were determined. In control muscles, force and iCa(2+) increased as the stimulation frequency increased in steps of 0.5 Hz up to 3.0 Hz. However, EE-denuded (EED) muscles exhibited a markedly blunted FFR. Neither isoproterenol (ISO; 0.1-5 nmol/l) nor endothelin-1 (ET-1; 10-100 nmol/l) alone restored the slope of FFR in EED muscles. Intriguingly, however, a positive FFR was restored in EED preparations by combining low concentrations of ISO (0.1 nmol/l) and ET-1 (20 nmol/l). In intact muscles, PKA and PKC activity increased proportionally with the increase in frequency. This effect was completely lost in EED muscles. Again, combining ISO and ET-1 fully restored the frequency-dependent rise in PKA and PKC activity in EED muscles. In conclusion, selective damage of EE leads to significantly blunted FFR. A combination of low concentrations of ISO and ET-1 successfully restores FFR in EED muscles. The interdependence of ISO and ET-1 in this process indicates cross-talk between the ?1-PKA and ET-1-PKC pathways for a normal (positive) FFR. The results also imply that dysfunction of EE and/or EE-myocyte coupling may contribute to flat (or even negative) FFR in heart failure.
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A structure-differential binding method for elucidating the interactions between flavonoids and cytochrome-c by ESI-MS and molecular docking.
Talanta
PUBLISHED: 04-16-2013
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The study of noncovalent interactions between pharmaceutical molecules and proteins is essential for understanding molecular mechanisms of protein function, and provides foundations for de novo therapeutic agent design. Electrospray ionization mass spectrometry (ESI-MS) has nowadays become a popular tool for analyzing the noncovalent protein complexes, however it usually has difficulty in determining the interaction sites and binding mechanisms. In this work, a new structure-differential binding (SDB) method, combined with ESI-MS and molecular docking (MD) techniques (SDB-ESIMS-MD), was developed and applied to a study of the binding interactions in noncovalent protein-small drug molecule complexes for the characterization of binding sites and binding modes. Using this developed method, protein complexes of flavonoid and flavonoid glycoside ligands and cytochrome-c (Cyt-c) were studied in detail. ESI-MS was used to determine the relative binding affinities and dissociation constants of flavonoid-Cyt-c complexes, and to measure the changes in the stability of the protein complexes with the structural modifications of the ligands for identifying effective binding functional groups. Molecular docking simulations complemented ESI-MS experiments by providing the protein-ligand interaction profile of each complex and displaying the binding mode for each interaction. This SDB-ESIMS-MD method can be applied to a broad range of protein-drug interactions and used to guide further research in the study of structure-binding relationship between drug molecules and targeted biomacromolecules.
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Analytical chemistry of the persistent organic pollutants identified in the Stockholm Convention: A review.
Anal. Chim. Acta
PUBLISHED: 04-08-2013
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Persistent organic pollutants (POPs) are major environmental concern due to their persistence, long-range transportability, bio-accumulation and potentially adverse effects on living organisms. Analytical chemistry plays an essential role in the measurement of POPs and provides important information on their distribution and environmental transformations. Much effort has been devoted during the last two decades to the development of faster, safer, more reliable and more sensitive analytical techniques for these pollutants. Since the Stockholm Convention (SC) on POPs was adopted 12 years ago, analytical methods have been extensively developed. This review article introduces recent analytical techniques and applications for the determination of POPs in environmental and biota samples, and summarizes the extraction, separation and instrumental analyses of the halogenated POPs. Also, this review covers important aspects for the analyses of SC POPs (e.g. lipid determination and quality assurance/quality control (QA/QC)), and finally discusses future trends for improving the POPs analyses and for potential new POPs.
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Pre-stem cell formation by non-platelet RNA-containing particle fusion.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 03-29-2013
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We found a group of non-platelet RNA-containing particles (NPRCP) in human umbilical cord blood. To understand the origin, characterization and differentiation of NPRCP, we examined cord blood-isolated NPRCP in vitro. The NPRCP range in size from < 1 to 5 ?m, have a thin bilayer membrane and various morphological features, contain short RNA and microRNA and express octamer-binding transcription factor 4 (OCT4), sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). On coculture with nucleated cells from umbilical cord blood, NPRCP fuse to small, active, non-nucleated cells called particle fusion-derived non-nucleated cells (PFDNC). The PFDNC are approximately 8 ?m in diameter and are characterized by their twisting movement in culture plates. They can easily move into and out of nucleated cells and finally differentiate into mesenchymal-like cells. In addition, the larger non-nucleated cellular structures that are derived from the aggregation and fusion of multiple NPRCP can further differentiate into large stem cells that also release OCT4- and SOX2-positive non-nucleated small cells. Our data provide strong evidence that NPRCP can fuse into PFDNC, which further differentiate into mesenchymal-like cells. Multiple NPRCP also fuse into other types of large stem cells. We believe that stem cells are derived from NPRCP fusion. There is considerable potential for the use of NPRCP in clinical therapy.
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Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study.
Evid Based Complement Alternat Med
PUBLISHED: 03-13-2013
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Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.
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Methylated DNA and microRNA in Body Fluids as Biomarkers for Cancer Detection.
Int J Mol Sci
PUBLISHED: 03-11-2013
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Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification of circulating cell-free nuclear acids, increasing evidence demonstrated great potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection.
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Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue.
J. Biol. Chem.
PUBLISHED: 02-17-2013
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Type 2 diabetes is a chronic inflammatory metabolic disease, the key point being insulin resistance. Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of type 2 diabetes. Previously, we found that hyperhomocysteinemia (HHcy) induced insulin resistance in adipose tissue. Here, we hypothesized that HHcy induces ER stress, which in turn promotes insulin resistance. In the present study, the direct effect of Hcy on adipose ER stress was investigated by the use of primary rat adipocytes in vitro and mice with HHcy in vivo. The mechanism and the effect of G protein-coupled receptor 120 (GPR120) were also investigated. We found that phosphorylation or expression of variant ER stress markers was elevated in adipose tissue of HHcy mice. HHcy activated c-Jun N-terminal kinase (JNK), the downstream signal of ER stress in adipose tissue, and activated JNK participated in insulin resistance by inhibiting Akt activation. Furthermore, JNK activated c-Jun and p65, which in turn triggered the transcription of proinflammatory cytokines. Both in vivo and in vitro assays revealed that Hcy-promoted macrophage infiltration aggravated ER stress in adipose tissue. Chemical chaperones PBA and TUDCA could reverse Hcy-induced inflammation and restore insulin-stimulated glucose uptake and Akt activation. Activation of GPR120 reversed Hcy-induced JNK activation and prevented inflammation but not ER stress. Therefore, HHcy inhibited insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote proinflammatory cytokine production and facilitating macrophage infiltration. These findings reveal a new mechanism of HHcy in the pathogenesis of insulin resistance.
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The neurobehavioral impact of manganese: results and challenges obtained by a meta-analysis of individual participant data.
Neurotoxicology
PUBLISHED: 02-06-2013
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Results from a meta-analysis of aggregated data provoked a new analysis using individual data on the neuropsychological performance of occupationally exposed workers. Data from eight studies examining 579 exposed and 433 reference participants were included, 28 performance variables analyzed. The performance scores were adjusted for well-known individual-level covariates; the influence of possible, but unknown study-level covariates was attenuated by means of a z-normalization. Associations between performance and exposure were estimated by ANOVAs and ANCOVAs, the latter representing multi-level models. Four cognitive and motor performance variables each indicated significantly lower performances of exposed individuals when confounding was considered; slowed motor performances and deficits in attention and short-term memory were found. Performance on a single test was significantly related to the biomarker manganese in blood. The outcomes on susceptibility were weak. The slowing of responses was the most distinct feature of performances of exposed workers. It remains unclear, whether this result is related to the employed tests or provides important information about early stages of the neurotoxic impairment. More specific cognitive tests need to be employed to answer this question. The lack of dose-response relationships was related to features of the biomarker: it does not reflect the Mn in brain responsible for changes in performances.
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Kidney regeneration by non-platelet RNA-containing particle-derived cells.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 02-01-2013
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We found a group of non-platelet RNA-containing particles (NPRCPs) in human umbilical cord blood. These particles can aggregate, fuse and become non-nucleated cells when cocultured with nucleated cells in vitro. The non-nucleated cells further differentiate into nucleated cells expressing octamer binding transcription factor 4 (OCT4). The NPRCPs are approximately 1-5 ?m in diameter, have a thin bilayer membrane, contain short RNAs and microRNAs and express OCT4, sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). To confirm the function of NPRCPs in vivo, we examined the effects of tail vein-injected green fluorescent protein (GFP)-labelled NPRCPs on mouse kidneys damaged by prior ischaemia and reperfusion from Day 1 to Week 6. Within 1 day of injection of NPRCPs, immunofluorescence and immunohistochemistry revealed a large number of extravasated NPRCPs in the renal calyces, damaged glomeruli and duct tubules. During the course of regeneration, NPRCPs fused into large, non-nucleated cellular structures that further became large nucleated cells to regenerate multicellular kidney tubules. In addition, many NPRCPs became tiny nucleated cellular structures that further differentiated into interstitial cells in connective tissue. The extravasated NPRCPs also arranged themselves into non-cell glomerular structures before further regenerating into nucleated cells of the glomerulus. In conclusion, the results demonstrate that, via different patterns of differentiation, NPRCP-derived cells can regenerate mouse kidney tissue damaged by ischaemia.
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Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release.
Kidney Int.
PUBLISHED: 01-30-2013
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Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro phosphate-induced calcification model of vascular smooth muscle cells (VSMCs) and in an in vivo model of chronic renal failure, autophagy was inhibited by the superoxide dismutase mimic MnTMPyP, superoxide dismutase-2 overexpression, and by knockdown of the sodium-dependent phosphate cotransporter Pit1. Although phosphate-induced VSMC apoptosis was reduced by an inhibitor of autophagy (3-methyladenine) and knockdown of autophagy protein 5, calcium deposition in VSMCs was increased during inhibition of autophagy, even with the apoptosis inhibitor Z-VAD-FMK. An inducer of autophagy, valproic acid, decreased calcification. Furthermore, 3-methyladenine significantly promoted phosphate-induced matrix vesicle release with increased alkaline phosphatase activity. Thus, autophagy may be an endogenous protective mechanism counteracting phosphate-induced vascular calcification by reducing matrix vesicle release. Therapeutic agents influencing the autophagic response may be of benefit to treat aging or disease-related vascular calcification and osteoporosis.
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Isolation and purification of a peptide from Bullacta exarata and its impaction of apoptosis on prostate cancer cell.
Mar Drugs
PUBLISHED: 01-25-2013
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Bullacta exarata was hydrolyzed with trypsin to prepare peptides; Hydrolysates were isolated by ultrafiltration and purified using G-25 gel filtration. The purity of the Bullacta exarata was demonstrated by HPLC and its peptide sequence analysis was detected. The effects of BEPT II and BEPT II-1 on the proliferation of PC-3 cells were examined using a MTT assay. BEPT II and BEPT II-1 significantly inhibited the proliferation of PC-3 cells in a time- and dose-dependent manner. Annexin V/PI double staining studies showed exposing PC-3 cells to 5, or 15 mg/mL BEPT II-1 for 24 h increased the percentage of the early stage of apoptotic cells from 11.22% to 22.09%. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. These data support that BEPT II-1 has anticancer properties and merits further investigation to understand the mechanisms of BEPT II-1-induced apoptosis in PC-3 cells.
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Leptin induces cell proliferation and reduces cell apoptosis by activating c-myc in cervical cancer.
Oncol. Rep.
PUBLISHED: 01-18-2013
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Leptin may be involved in the pathogenesis of numerous cancer types by activation of cellular signal-transduction pathways. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in cervical carcinoma cells. Firstly, we examined the expression of leptin in 80 cases of cervical carcinoma using immunohistochemical staining. The results showed that the levels of leptin correlated significantly with the grades of cervical carcinoma. At the same time, the expression of leptin correlated positively with c-myc and its downstream gene, bcl-2. The expression of c-myc and bcl-2 was evaluated in leptin-treated HeLa cells by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Recombinant leptin significantly activated the expression of bcl-2 and c-myc in HeLa cells. Finally, the apoptotic index, the proliferative activity and the expression levels of c-myc and bcl-2 were determined in the HeLa cells treated with silencing of leptin. We found that silencing of leptin inhibited the proliferation of HeLa cells and reduced the expression of bcl-2 and c-myc. Our data demonstrated that leptin interferes with the expression of oncogenic c-myc and anti-apoptotic bcl-2, and regulates cell turnover and facilitates the progression of cervical cancer.
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A retrospective analysis on the diagnostic value of ultrasound-guided percutaneous biopsy for peritoneal lesions.
World J Surg Oncol
PUBLISHED: 01-15-2013
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Routine examinations have a low specificity and a low positive rate for the diagnosis of peritoneal lesions. This study aimed to evaluate the diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion biopsies in patients with ascites and/or abdominal distension with unclear causes.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.