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Find video protocols related to scientific articles indexed in Pubmed.
Photocatalytic H2 evolution on MoS2-TiO2 catalysts synthesized via mechanochemistry.
Phys Chem Chem Phys
PUBLISHED: 11-20-2014
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At present, composite photocatalysts containing MoS2 as a co-catalyst and a subjective semiconductor material are usually obtained via various complex reduction methods using NH4MoS4 or Na2MoO4 as a precursor. In this work, a simple method was proposed to synthesize MoS2-TiO2 composite photocatalysts via mechanochemistry using MoS2 as a direct precursor. 4.0% MoS2-TiO2 after ball-milling at 300 rpm for 2 h possessed the maximum photocatalytic activity for H2 evolution. The rate of H2 evolution was up to 150.7 ?mol h(-1), which was 48.6 times higher than that of pure TiO2. The MoS2-TiO2 composite possesses stable photocatalytic performance for H2 evolution. Photoelectrochemical measurements confirmed the electronic interaction between TiO2 and MoS2. The photo-generated electrons on the conduction band of TiO2 could easily transfer to the MoS2 co-catalyst, which promoted efficient charge separation and improved the photocatalytic performance.
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Osteogenic Commitment of Mesenchymal Stem Cells in Apatite Nanorods-Aligned Ceramics.
ACS Appl Mater Interfaces
PUBLISHED: 11-19-2014
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It is significant to process the clinically-used biomaterials into a scaffold with specific nanotopographies which can act as physical cues to regulate the osteogenic commitment of mesenchymal stem cells. In this study, hydroxyapatite (HAP) was considered as the processed objective and a facile, hydrothermal method was developed to grow the vertically-oriented HAP nanorods in porous HAP ceramics. Experiments demonstrated that the formation of the HAP nanorods in porous ceramics was decided by a novel epitaxial growth mechanism and length of nanorods could be well controlled by the growth time. Cell experiments demonstrated that such novel stereo-topographical cues could regulate bone marrow mesenchymal stem cells to differentiate into the osteogenic lineage, thereby displaying that the porous ceramics with the HAP nanorods-aligned stereo-topographies have a good prospect for applications in regen-erative medicine of hard tissues.
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[Update on isolation and functional research of hepatic stellate cells].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 10-28-2014
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Hepatic stellate cells (HSCs), also called Ito cells or lipocytes, are one of inherent liver nonparenchymal cell types located in the Dissé space between hepatocytes and sinusoidal endothelial cells, and account for up to 50%-80% of vitamin A in the form of lipid drops. The methods of primary HSCs isolation mainly focus on density gradient centrifugation combined with centrifugal elutriation, side scatter-activated cell sorting, UV-excited autofluorescence or antibody-based flow cytometry, etc., and will provide solid foundation for the research on physiological and pathological HSCs function. The research of this vitamin A-storing cells has developed and expanded vigorously. In physiological conditions, HSCs are quiescent and play pivotal roles in the synthesis of extracellular matrix (ECM) to maintain its stability with broad uptake and storage of vitamin A, and also regulate liver regeneration. But in pathological conditions, HSCs are activated by constant stimulations or liver injury, then with activated proliferation, reduced lipid drops, and increased ECM synthesis. Morphology of these cells also changes from the star-shaped stellate cells to that of fibroblasts or myofibroblasts with obvious contractibility and secretion of cytokines and chemokines including a variety of proinflammatory factors and adhesion molecules, suggesting that the activation of HSCs is one of the key events in the development of liver fibrosis. Study on the isolation and function of HSCs is always one of the hot topics for liver biology. In this review, we systematically summarize and discuss the recent advances in our understanding of the isolation methods and improvements of HSCs, and functional research of HSCs biology in health and disease, as well as potential directions.
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Doping Hydroxylated Cationic Lipid into PEGylated Cerasome Boosts in Vivo siRNA Transfection Efficacy.
Bioconjug. Chem.
PUBLISHED: 10-10-2014
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The therapeutic application of small interfering RNA (siRNA) requires safe nanocarriers for specific and efficient delivery in vivo. Herein, PEGylated cationic cerasomes (PCCs) were fabricated by doping a cationic lipid with a hydroxyl group into nanohybrid cerasomes. Multiple properties of PCCs provide a solution to many of the limitations associated with current platforms for the delivery of siRNA. The polyorganosiloxane surface imparts PCCs with higher morphological stability than conventional liposomes. The PEGylation of the cationic cerasome could protect the cerasome nanoparticles from agglomeration and macrophage capture, reduce protein absorption, and consequently prolong the blood circulating time and enhance the siRNA delivery efficiency. In addition, incorporation of the lipid containing a hydroxyl group further facilitates endosome release. Moreover, PCCs were further used to transport siRNA into the cytosol primarily via endocytosis. When applied to systemic administration, PCCs have demonstrated effective delivery into the liver and preferential uptake by hepatocytes in mice, thereby leading to high siRNA gene-silencing activity. All these results show potential therapeutic applications of PCCs-mediated delivery of siRNA for liver diseases.
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Independent impact of gout on the risk of diabetes mellitus among women and men: a population-based, BMI-matched cohort study.
Ann. Rheum. Dis.
PUBLISHED: 10-04-2014
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Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women.
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In vitro activity of novel oxazolidinone analogs and 13 conventional antimicrobial agents against clinical isolates of Staphylococcus aureus in Beijing, China.
Jpn. J. Infect. Dis.
PUBLISHED: 09-23-2014
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Methicillin-resistant Staphylococcus aureus (MRSA) has been a public health concern since it was first identified in the United Kingdom in 1961. In this study, we investigated the prevalence of MRSA in the PLA 309 Hospital located in Beijing, China, and we determined the susceptibility of S. aureus to novel oxazolidinone analogs and 13 conventional antimicrobial agents. It was shown that drug resistant patterns were severe among the clinical isolates, and the average rate of MRSA among the S. aureus strains was 56.3%. All the S. aureus strains tested were completely susceptible to linezolid, but the minimum inhibitory concentration distribution drifted upwards. Among the novel oxazolidinone analogs, sy142 exhibited more potent antimicrobial activity than linezolid against both the standard and clinical S. aureus strains. This observation provides an impetus for the development of potential novel agents based on sy142 in the near future to combat MRSA and linezolid-resistant S. aureus.
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Transportation of perishable and refrigerated foods in mylar foil bags and insulated containers: a time-temperature study.
J. Food Prot.
PUBLISHED: 09-09-2014
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Data are lacking on the temperature changes of food during transport without the use of refrigerated trucks. The purpose of this study was to evaluate the ability of several insulated and noninsulated containers with or without frozen gel packs to keep perishable and refrigerated foods within the temperature safe zone in relationship to duration of transport. The study was designed to duplicate the practices exhibited by customers purchasing perishable food products from a cash-and-carry business. Approximately 40 perishable food items were evaluated. Four types of containers were tested: a mylar foil bag, a commercial insulated bag, a generic insulated bag, and a commercial insulated blanket. Mixed foods were placed into these containers with or without frozen gel packs, transported in unrefrigerated vehicles, and monitored for 4 h for temperature changes. Two environmental temperatures, room temperature of 21.1°C and a stress temperature of 37.8°C, were evaluated. The internal temperature and surface temperature of the food products in these containers increased slowly but remained well below the U.S. Food and Drug Administration Food Code requirements. The various containers were similar in their ability to retain coolness. The presence of frozen gel packs dramatically enhanced the cold-holding capacity of the containers. The temperature of foods increased more rapidly when stressed in a heated environment. The containers tested used with the frozen gel packs can keep the surface and internal temperatures of various perishable foods (starting at 4.4°C or less) within the Food Code recommendation of under 21.1°C for 4 h. Cash-and-carry businesses should strongly encourage their retail customers to utilize these containers with frozen gel packs to safely transport perishable foods.
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Assessment of Platycodon grandiflorum germplasm resources from northern Anhui province based on ISSR analysis.
Mol. Biol. Rep.
PUBLISHED: 08-28-2014
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Based on genetic diversity analysis with ISSR-PCR, this study was to access the germplasm resources of Platycodon grandiflorum in northern Anhui province. Ten primers that could produce more distinct and repeatable bands were used for ISSR-PCR. Statistic analysis was conducted by POPGENE v. 1.32, Arlequin3.l, NTSYS-pc version 2.1. (1) Seventy-four polymorphic bands (76.29 %) out of a total of 97 were generated from 105 individuals in five populations. (2) Shannon index of diversity ranged from 0.307 to 0.260, diversity at species level was 0.3581, which means superior genetic diversity. (3) Genetic diversity across all the populations revealed by AMOVA indicated that 86.02 % occurred within populations. (4) The Fst value was 0.1398, indicating a intermediate genetic differentiation among populations. (5) Dendrogram relationship illustrated genetic distance was correlated with geographic distance. ISSR markers can be used for studying genetic diversity of P. grandiflorum. Degradation of populations doesn't happen in northern Anhui province, bank of germplasm preservation should be established for cultivation of excellent variety of P. grandiflorum.
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Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.
Neurosci. Lett.
PUBLISHED: 08-22-2014
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Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels. Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain. Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence. Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders.
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Serum HER2 extracellular domain as a potential alternative for tissue HER2 status in metastatic gastric cancer patients.
Biomark Med
PUBLISHED: 08-16-2014
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We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to test tissue HER2 status in metastatic gastric cancer.
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A DFT study on the reaction mechanism of dimerization of methyl methacrylate catalyzed by N-heterocyclic carbene.
Phys Chem Chem Phys
PUBLISHED: 08-15-2014
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Reaction mechanisms of the N-heterocyclic carbene (NHC)-catalyzed dimerization of methyl methacrylate were studied using density functional theory (DFT) at the M05-2X/6-31G(d,p) level of theory. Four possible reaction channels (A, B, C, and D) have been investigated in this work. Particularly, we proposed a novel reaction pathway, where the proton transfers are assisted by a different molecule. The calculated results indicate that the channels B and D are more energetically favourable channels. The obtained results suggest that the E-isomer product is the main product, which is in agreement with the experimental results. Further calculations and analyses of global and local reactivity indices reveal the role of the NHC catalysts in the title reaction. The mechanistic insights gained are valuable for not only rational design of more efficient NHC catalysts but also for understanding the similar reaction mechanism.
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Magnetic Prussian blue nanoparticles for targeted photothermal therapy under magnetic resonance imaging guidance.
Bioconjug. Chem.
PUBLISHED: 08-15-2014
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This paper reported a core-shell nanotheranostic agent by growing Prussian blue (PB) nanoshells of 3-6 nm around superparamagnetic Fe3O4 nanocores for targeted photothermal therapy of cancer under magnetic resonance imaging (MRI) guidance. Both in vitro and in vivo experiments proved that the Fe3O4@PB core-shell nanoparticles showed significant contrast enhancement for T2-weighted MRI with the relaxivity value of 58.9 mM(-1)·s(-1). Simultaneously, the composite nanoparticles exhibited a high photothermal effect under irradiation of a near-infrared laser due to the strong absorption of PB nanoshells, which led to more than 80% death of HeLa cells with only 0.016 mg·mL(-1) of the nanoparticles with the aid of the magnetic targeting effect. Using tumor-bearing nude mice as the model, the near-infrared laser light ablated the tumor effectively in the presence of the Fe3O4@PB nanoparticles and the tumor growth inhibition was evaluated to be 87.2%. Capabilities of MRI, magnetic targeting, and photothermal therapy were thus integrated into a single agent to allow efficient MRI-guided targeted photothermal therapy. Most importantly, both PB and Fe3O4 nanoparticles were already clinically approved drugs, so the Fe3O4@PB nanoparticles as a theranostic nanomedicine would be particularly promising for clinical applications in the human body due to the reliable biosafety.
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Association between transforming growth factor-?1gene-509C/T polymorphism and susceptibility of IgA nephropathy: a meta-analysis.
Ren Fail
PUBLISHED: 08-12-2014
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Abstract A role for transforming growth factor-?1gene has been suggested in the etiology of IgA nephropathy. However, results have been inconsistent. In this study, a meta-analysis was performed to further clarify the association between transforming growth factor-?1-509C/T gene polymorphism and the susceptibility of IgA nephropathy. PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals were calculated using a fixed-effects model or random-effects model. A total of eight publications involving 1355 IgA nephropathy patients and 1464 controls met the inclusion and were analyzed. The pooled ORs for the association between TGF-?1gene-509C/T polymorphism and IgA nephropathy risk were not statistically significant under all genetic models (for CT+TT vs. CC: OR?=?1.09; 95% CI?=?0.92-1.29, p?=?0.490; for TT vs. CT+CC: OR?=?1.14; 95% CI?=?0.94-1.38, p?=?0.081; for CC vs. TT: OR?=?0.87; 95% CI?=?0.69-1.08, p?=?0.195; for C allele vs. T allele: OR?=?0.92; 95% CI?=?0.83-1.03, p?=?0.149). In the stratified analysis by ethnicity, results also showed no significant association between TGF-?1 gene-509C/T polymorphism and IgA nephropathy risk in both European and Asian populations. This meta-analysis does not support the hypothesis that TGF-?1 gene-509C/T polymorphism is a risk factor for the development of IgA nephropathy.
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Construction of a novel expression system for use in Corynebacterium glutamicum.
Plasmid
PUBLISHED: 08-07-2014
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Corynebacterium glutamicum is an important microorganism for production of amino acids in industrial fermentation. Suitable vectors are needed for metabolic engineering in C. glutamicum. Most available vectors used in C. glutamicum carry antibiotic resistant genes as a genetic labeling for rapid identification of recombinant strains, and antibiotics have to be added to maintain the vector when growing the cells. These vectors, though excellent for laboratory use, are not preferable choices for industry-scale fermentation. In this work, we developed a novel expression system for use in C. glutamicum, which do not require antibiotics when used for industrial fermentation. This system includes two vectors: the shuttle vector pJYW-4 for expression of genes and the vector pJYW-6 for deletion of the essential gene alr in C. glutamicum. The vector pJYW-4 contains a large multiple cloning site for cloning multiple genes and two selective markers: one is the kanamycin-resistant gene kan and the other is an essential gene alr. The selective marker kan facilitates molecular manipulation or fermentations in the laboratory, and the selection marker alr is good for use in industry-scale fermentation, allowing in vivo maintenance of the expression vector through auxotrophic complementation; therefore, the two selection markers in pJYW-4 make it useful for both laboratory research and industrial fermentation, and convenient to transfer valuable laboratory-developed strains into industrial production. This newly-constructed expression system was successfully used to increase L-valine production in C. glutamicum ATCC 14067, indicating its potential on developing amino acid-producing C. glutamicum strains.
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Graphene frameworks promoted electron transport in quantum dot-sensitized solar cells.
ACS Appl Mater Interfaces
PUBLISHED: 08-07-2014
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Graphene frameworks (GFs) were incorporated into TiO2 photoanode as electron transport medium to improve the photovoltaic performance of quantum dot-sensitized solar cells (QDSSCs) for their excellent conductivity and isotropic framework structure that could permit rapid charge transport. Intensity modulated photocurrent/photovoltage spectroscopy and electrochemical impedance spectroscopy results show that the electron transport time (?(d)) of 1.5 wt % GFs/TiO2 electrode is one-fifth of that of the TiO2 electrode, and electron lifetime (?(n)) and diffusion path length (Ln) are thrice those of the TiO2 electrode. Results also revealed that the GFs/TiO2 electrode has a shorter electron transport time (?(d)), as well as longer electron lifetime (?(n)) and diffusion path length (Ln), than conventional 2D graphene sheets/TiO2 electrode, thus indicating that GFs could promote rapid electron transfer in TiO2 photoanodes. Photocurrent-voltage curves demonstrated that when incorporating 1.5 wt % GFs into TiO2 photoanode, a maximum power conversion efficiency of 4.2% for QDSSCs could be achieved. This value was higher than that of TiO2 photoanode and 2D graphene sheets/TiO2 electrode. In addition, the reasons behind the sensitivity of photoelectric conversion efficiency to the graphene concentration in the TiO2 were also systematically investigated. Our results provide a basic understanding of how GFs can efficiently promote electron transport in TiO2-based solar cells.
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Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance.
J. Med. Genet.
PUBLISHED: 07-23-2014
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Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-telopeptide of type II collagen (uCTX-II).
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Two Enzyme Cooperatively Catalyzed Tandem Polymerization for the Synthesis of Polyester Containing Chiral (R)- or (S)-Ibuprofen Pendants.
Macromol Rapid Commun
PUBLISHED: 07-16-2014
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An interesting cooperation between Candida antarctica Lipase B (CAL-B) and alkaline protease from Bacillus subtilis (BSP) in the copolymerization of bulky ibuprofen-containing hydroxyacid methyl ester (HAEP) and ?-caprolactone (?-CL) is observed. This cooperation improved the M¯n of the polymers from 3130 (CAL-B) to 9200 g mol(-1) (CAL-B/BSP). Experimental results clearly indicate that CAL-B mainly catalyzes the ring-opening polymerization (ROP) of ?-CL under the initiation of HAEP to form the homopolymer of ?-CL, while BSP catalyzes the subsequent polycondensation of the ROP product to yield the copolymer with increased molecular weight. Furthermore, using suitable chemo-enzymatic methods, valuable polyesters with chiral (R)- or (S)-ibuprofen pendants can be tailor-made.
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Prognostic significance of survivin in breast cancer: meta-analysis.
Breast J
PUBLISHED: 07-08-2014
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Survivin, an inhibitor of apoptosis protein, is a potentially prognostic factor and therapeutic target in breast carcinoma, but no consensus exists based on heterogeneous data. The aim of this present study is to clarify the prognostic relevance of survivin in breast cancer patients. Relevant articles were screened in PubMed and EMBASE databases. Patients' clinical characteristics, overall survival (OS), disease/recurrence-free survival (DFS/RFS) and positive expressed survivin rates were extracted for further analysis. Statistics extracted from Kaplan-Meier survival curves were calculated indirectly with methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis data were used directly in Stata 11.0. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of survivin in breast cancer. Online literature search identified 23 articles containing 3,259 breast cancer patients. Our meta-analysis of all included studies about survival outcomes showed positive correlation between poor prognosis and survivin expression. Pooled HRs (95% CIs) for OS and DFS/RFS were 1.37 (1.12-1.68) and 1.34 (1.02-1.76), respectively. Subgroup analyses considering methods used to detect survivin (immunohistochemistry or not) and localization of survivin (whole, nuclear or cytoplasm of the cell) were also conducted, and all the above analyses supported the stability of the prognostic role of survivin. In addition, our study revealed a significant association between survivin expression and lymph node metastasis (OR: 2.74; 95% CI: 1.27-5.93) or stage of breast cancer (OR: 2.01; 95% CI: 1.29-3.13). Positive expression of survivin demonstrated a significantly higher risk of recurrence and decreased OS rates in breast cancer.
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A theoretical study on the mechanisms of the reactions between 1,3-dialkynes and ammonia derivatives for the formation of five-membered N-heterocycles.
Org. Biomol. Chem.
PUBLISHED: 07-08-2014
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The reactions between 1,3-dialkynes and ammonia derivatives (such as hydrazine and hydroxylamine) for the formation of five-membered N-heterocycles (i.e. 3,5-disubstituted pyrazole and 3,5-disubstituted isoxazole) have been investigated using the density functional theory (DFT) method. The calculated results indicate that the favorable mechanism of this kind of reaction generally contains four processes: (1) the Cope-type hydroamination reaction between the reactants coupled with the hydrazine/hydroxylamine-assisted proton transfer process or the trimolecular hydroamination reaction via a six-membered transition state, (2) the bimolecular proton transfer process for the formation of an allenyl oxime intermediate, (3) the cyclization process, and (4) another bimolecular or hydrazine/hydroxylamine-assisted proton transfer process to afford the final products (3,5-disubstituted pyrazole and 3,5-disubstituted isoxazole). The computational results demonstrate that the novel bimolecular proton transfer process occurs in a stepwise manner and the first step of the novel bimolecular proton transfer process is calculated to be the rate-determining step in both the reactions, and their energy barriers are 28.45 kcal mol(-1) associated with the formation of 3,5-disubstituted pyrazole and 31.07 kcal mol(-1) associated with the formation of 3,5-disubstituted isoxazole. In particular, the novel bimolecular proton transfer process has reasonably explained in detail on how and why this kind of reaction occurs, and this would provide valuable clues for the rational design of Brønsted acid/base catalysts to promote the synthesis of the five-membered N-heterocyclic compounds.
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Axl as a downstream effector of TGF-?1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma.
Tumour Biol.
PUBLISHED: 06-29-2014
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The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-?1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-?1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-?1 level, tumor differentiation, lymph node metastasis, and clinical stage (p?
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A single-component white-emitting CaSr2Al2O6:Ce3+, Li+, Mn2+ phosphor via energy transfer.
Inorg Chem
PUBLISHED: 06-26-2014
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A series of single-component Ce(3+), Li(+), Mn(2+) ions codoped color-tunable CaSr2Al2O6 phosphors were synthesized by a high-temperature solid-state reaction, and the photoluminescence properties as well as the energy transfer mechanism from Ce(3+) to Mn(2+) ions have been investigated in detail. The Ce(3+) activated phosphors have strong absorption in the range of 250-420 nm and can give a blue emission centered at about 460 nm. When Mn(2+) ions are codoped, the emission of CaSr2Al2O6:Ce(3+), Li(+), Mn(2+) phosphors can be tuned from blue to red through adjusting the doping concentration of the Mn(2+) ions, under the irradiation of 358 nm. When the concentration of Mn(2+) is increased to 0.02, a warm-white light can be obtained with good CIE coordinates of (0.388, 0.323) and a low CCT of 3284 K. The energy transfer mechanism from the Ce(3+) to Mn(2+) ions is demonstrated to be a quadrupole-quadrupole interaction based on the analysis of the decay curves of the phosphors. The thermal quenching stability was also investigated. The results indicate that CaSr2Al2O6:Ce(3+), Li(+), Mn(2+) samples might have potential applications in w-LEDs.
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DFT study on the reaction mechanisms and stereoselectivities of NHC-catalyzed [2 + 2] cycloaddition between arylalkylketenes and electron-deficient benzaldehydes.
Org. Biomol. Chem.
PUBLISHED: 06-19-2014
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In this paper, two possible mechanisms (mechanisms A and B) on the stereoselective [2 + 2] cycloaddition of aryl(alkyl)ketenes and electron-deficient benzaldehydes catalyzed by N-heterocyclic carbenes (NHCs) have been investigated using density functional theory (DFT). Our calculated results indicate that the favorable mechanism (mechanism A) includes three processes: the first step is the nucleophilic attack on the arylalkylketene by the NHC catalyst to form an intermediate, the second step is the [2 + 2] cycloaddition of the intermediate and benzaldehyde for the formation of a ?-lactone, and the last step is the dissociation of the NHC catalyst and the ?-lactone. Notably, the [2 + 2] cycloaddition, in which two chiral centers associated with four configurations (SS, RR, SR and RS) are formed, is demonstrated to be both the rate- and stereoselectivity-determining step. Moreover, the reaction pathway associated with the SR configuration is the most favorable pathway and leads to the main product, which is in good agreement with the experimental results. Furthermore, the analysis of global and local reactivity indexes has been performed to explain the role of the NHC catalyst in the [2 + 2] cycloaddition reaction. Therefore, this study will be of great use for the rational design of more efficient catalysts for this kind of cycloaddition.
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Structure of an antibacterial peptide ATP-binding cassette transporter in a novel outward occluded state.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-11-2014
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Enterobacteriaceae produce antimicrobial peptides for survival under nutrient starvation. Microcin J25 (MccJ25) is an antimicrobial peptide with a unique lasso topology. It is secreted by the ATP-binding cassette (ABC) exporter McjD, which ensures self-immunity of the producing strain through efficient export of the toxic mature peptide from the cell. Here we have determined the crystal structure of McjD from Escherichia coli at 2.7-Å resolution, which is to the authors' knowledge the first structure of an antibacterial peptide ABC transporter. Our functional and biochemical analyses demonstrate McjD-dependent immunity to MccJ25 through efflux of the peptide. McjD can directly bind MccJ25 and displays a basal ATPase activity that is stimulated by MccJ25 in both detergent solution and proteoliposomes. McjD adopts a new conformation, termed nucleotide-bound outward occluded. The new conformation defines a clear cavity; mutagenesis and ligand binding studies of the cavity have identified Phe86, Asn134, and Asn302 as important for recognition of MccJ25. Comparisons with the inward-open MsbA and outward-open Sav1866 structures show that McjD has structural similarities with both states without the intertwining of transmembrane (TM) helices. The occluded state is formed by rotation of TMs 1 and 2 toward the equivalent TMs of the opposite monomer, unlike Sav1866 where they intertwine with TMs 3-6 of the opposite monomer. Cysteine cross-linking studies on the McjD dimer in inside-out membrane vesicles of E. coli confirmed the presence of the occluded state. We therefore propose that the outward-occluded state represents a transition intermediate between the outward-open and inward-open conformation of ABC exporters.
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Comparative analysis of pathology and boronophenylalanine uptake in experimental orthotopic and heterotopic amelanotic melanoma.
Melanoma Res.
PUBLISHED: 06-11-2014
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Pathobiologic characteristics of cerebral and cutaneous melanoma may cause an increase in mortality resulting from brain metastases in advanced melanoma patients, in addition to anatomic lesions and biological effects caused by the tumor location. We established intracranial and subcutaneous melanoma models using cultured malignant cells derived from amelanotic melanoma. The median survival times in a mouse model with intracranial tumors was 20 days, but a mouse model with subcutaneous tumors did not show cachexia until they were killed 28 days after inoculation with tumor cells. Histopathological analysis showed that a high karyokinesis phase and nuclear pleomorphism appeared in the intracranial model compared with the subcutaneous tumor model mice. The tumor boron concentration at 2.5?h after boronophenylalanine administration was 15.21±3.88??g/g in an intracranial melanoma xenograft and 19.85±3.63??g/g in a subcutaneous melanoma xenograft. Intracranial melanoma showed more malignancy and shorter survival time than did subcutaneous melanoma when the same number of tumor cells were injected, and subcutaneous and intracranial amelanotic malignant melanoma tumors are both fitted for boron neutron capture therapy.
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DFT study on the mechanisms and diastereoselectivities of Lewis acid-promoted ketene-alkene [2 + 2] cycloadditions: what is the role of Lewis acid in the ketene and C = X (X = O, CH?, and NH) [2 + 2] cycloaddition reactions?
J Phys Chem A
PUBLISHED: 06-06-2014
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The detailed mechanisms and diastereoselectivities of Lewis acid-promoted ketene-alkene [2 + 2] cycloaddition reactions have been studied by density functional theory (DFT). Four possible reaction channels, including two noncatalyzed diastereomeric reaction channels (channels A and B) and two Lewis acid (LA) ethylaluminum dichloride (EtAlCl2) catalyzed diastereomeric reaction channels (channels C and D), have been investigated in this work. The calculated results indicate that channel A (associated with product R-configurational cycloputanone) is more energy favorable than channel B (associated with the other product S-configurational cyclobutanone) under noncatalyzed condition, but channel D leading to S-configurational cyclobutanone is more energy-favorable than channel C, leading to R-configurational cycloputanone under a LA-promoted condition, which is consistent with the experimental results. And Lewis acid can make the energy barrier of ketene-alkene [2 + 2] cycloaddition much lower. In order to explore the role of LA in ketene and C = X (X = O, CH2, and NH) [2 + 2] cycloadditions, we have tracked and compared the interaction modes of frontier molecular orbitals (FMOs) along the intrinsic reaction coordinate (IRC) under the two different conditions. Besides by reducing the energy gap between the FMOs of the reactants, our computational results demonstrate that Lewis acid lowers the energy barrier of the ketene and C = X [2 + 2] cycloadditions by changing the overlap modes of the FMOs, which is remarkably different from the traditional FMO theory. Furthermore, analysis of global reactivity indexes has also been performed to explain the role of LA catalyst in the ketene-alkene [2 + 2] cycloaddition reaction.
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Histone H4 Lys 20 methyltransferase SET8 promotes androgen receptor-mediated transcription activation in prostate cancer.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-30-2014
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Histone methylation status in different lysine residues has an important role in transcription regulation. The effect of H4K20 monomethylation (H4K20me1) on androgen receptor (AR)-mediated gene transcription remains unclear. Here we show that AR agonist stimulates the enrichment of H4K20me1 and SET8 at the promoter of AR target gene PSA in an AR dependent manner. Furthermore, SET8 is crucial for the transcription activation of PSA. Co-immunoprecipitation analyses demonstrate that SET8 interacts with AR. Therefore, we conclude that SET8 is involved in AR-mediated transcription activation, possibly through its interaction with AR and H4K20me1 modification.
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Understanding the effects on constitutive activation and drug binding of a D130N mutation in the ?2 adrenergic receptor via molecular dynamics simulation.
J Mol Model
PUBLISHED: 05-16-2014
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G-protein-coupled receptors (GPCRs) are currently one of the largest families of drug targets. The constitutive activation induced by mutation of key GPCR residues is associated closely with various diseases. However, the structural basis underlying such activation and its role in drug binding has remained unclear. Herein, we used all-atom molecular dynamics simulations and free energy calculations to study the effects of a D130N mutation on the structure of ?2 adrenergic receptor (?2AR) and its binding of the agonist salbutamol. The results indicate that the mutation caused significant changes in some key helices. In particular, the mutation leads to the departure of transmembrane 3 (TM3) from transmembrane 6 (TM6) and marked changes in the NPxxY region as well as the complete disruption of a key ionic lock, all of which contribute to the observed constitutive activation. In addition, the D130N mutation weakens some important H-bonds, leading to structural changes in these regions. Binding free energy calculations indicate that van der Waals and electrostatic interactions are the main driving forces in binding salbutamol; however, binding strength in the mutant ?2AR is significantly enhanced mainly through modifying electrostatic interactions. Further analysis revealed that the increase in binding energy upon mutation stems mainly from the H-bonds formed between the hydroxyl group of salbutamol and the serine residues of TM5. This observation suggests that modifications of the H-bond groups of this drug could significantly influence drug efficacy in the treatment of diseases associated with this mutation.
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[Effects of carbon and nitrogen sources on 5-keto-gluconic acid production].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 05-14-2014
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Gluconobacter oxydans is known to oxidize glucose to gluconic acid (GA), and subsequently, to 2-keto-gluconic acid (2KGA) and 5-keto-gluconic acid (5KGA), while 5KGA can be converted to L-(+)-tartaric acid. In order to increase the production of 5KGA, Gluconobacter oxydans HGI-1 that converts GA to 5KGA exclusively was chosen in this study, and effects of carbon sources (lactose, maltose, sucrose, amylum and glucose) and nitrogen sources (yeast extract, fish meal, corn steep liquor, soybean meal and cotton-seed meal) on 5KGA production were investigated. Results of experiment in 500 mL shake-flask show that the highest yield of 5KGA (98.20 g/L) was obtained using 100 g/L glucose as carbon source. 5KGA reached 100.20 g/L, 109.10 g/L, 99.83 g/L with yeast extract, fish meal and corn steep liquor as nitrogen source respectively, among which the optimal nitrogen source was fish meal. The yield of 5KGA by corn steep liquor is slightly lower than that by yeast extract. For the economic reason, corn steep liquor was selected as nitrogen source and scaled up to 5 L stirred-tank fermentor, and the final concentration of 5KGA reached 93.80 g/L, with its maximum volumetric productivity of 3.48 g/(L x h) and average volumetric productivity of 1.56 g/(L x h). The result obtained in this study showed that carbon and nitrogen sourses for large-scale production of 5KGA by Gluconobacter oxydans HGI-1 were glucose and corn steep liquor, respectively, and the available glucose almost completely (85.93%) into 5KGA.
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Prognostic value of microvessel density in hepatocellular carcinoma patients: a meta-analysis.
Int. J. Biol. Markers
PUBLISHED: 05-01-2014
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The identification of microvessel density (MVD) in patients suffering from different types of cancer has become a hot point as an emerging and promising biomarker. The aim of the present study is to clarify the prognostic relevance of MVD in hepatocellular carcinoma (HCC).
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Axl mediates tumor invasion and chemosensitivity through PI3K/Akt signaling pathway and is transcriptionally regulated by slug in breast carcinoma.
IUBMB Life
PUBLISHED: 04-17-2014
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The invasion and chemoresistance are crucial causes of morbidity and relapse for cancer patients. Axl is implicated in the modulation of cell invasion, cancer metastasis, and chemosensitivity in human breast carcinoma cell lines. Both breast cancer cell lines and tissues displayed increased expression of Axl, and it over expressed in highly metastatic breast cancer. The altered expression level of Axl was corresponding to the changed invasive phenotype and chemosensitivity of MDA-MB-231 cells both in vitro and in vivo. Further data indicated that experimental inhibition of Axl by RNAi assay inhibited phosphatidylinositol 3-kinase (PI3K)/Akt/GSK3? signaling pathway, resulted in the decrease of Slug expression, and further suppressed cell invasion properties and chemosensitivity. What is more, after the detection and statistics in human breast cancer specimens, we found the Axl expression was closely correlated with histological grade, lymph node metastasis, and clinical stage (P?
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[IL-17A promotes pulmonary inflammation in rats with pulmonary fibrosis induced by bleomycin].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 04-12-2014
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To investigate the role of IL-17A in the development of pulmonary fibrosis in rats.
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A platinum(II) complex bearing deprotonated 2-(diphenylphosphino)benzoic acid for superior phosphorescence of monomers.
Dalton Trans
PUBLISHED: 04-10-2014
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The (ppy)-based Pt(II) complex (Pt-1) with deprotonated 2-(diphenylphosphino)benzoic acid as an anionic ligand displays phosphorescence of monomers with a remarkably higher quantum yield than that of the corresponding iridium complex (Ir-1). A prototype OLED using Pt-1 exhibits high performance with an external quantum efficiency of 4.93%.
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Heavy metal pollution in vegetables grown in the vicinity of a multi-metal mining area in Gejiu, China: total concentrations, speciation analysis, and health risk.
Environ Sci Pollut Res Int
PUBLISHED: 04-01-2014
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A field survey was conducted to investigate the present situation and health risk of arsenic (As), lead (Pb), cadmium (Cd), copper (Cu), and zinc (Zn) in soils and vegetables in a multi-metal mining area, Gejiu, China. Furthermore, three vegetables (water spinach, potato, and summer squash) containing high metal concentrations were selected to further analyze metal speciation. The results showed that the average concentrations of five metals in soil exceeded the limiting values, and their bioavailable concentrations were significantly positively correlated to the total ones. Heavy metals in the edible parts of vegetables also exceeded the corresponding standards. The leaves of pakchoi, peppermint, and coriander had a strong metal-accumulative ability and they were not suitable for planting. Except the residue forms, the main forms of metals in the edible parts of three selected vegetables were ethanol-, NaCl-, and HAc-extractable fractions for As, Pb, and Cd, respectively; however, Cu was mainly presented as NaCl-extractable and Zn as HAc-extractable fractions. A high proportion of ethanol-extractable As showed that As bioactivity and toxic effects were the highest. Although the total and bioavailable Cd were high in soil, its speciation in vegetables was mainly presented as HAc-extractable fraction, which has a relatively low bioactivity. Lead and arsenic were imposing a serious threat on the local residents via vegetable consumption.
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p16 Methylation is associated with chemosensitivity to fluorouracil in patients with advanced gastric cancer.
Med. Oncol.
PUBLISHED: 03-30-2014
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No effective biomarkers have been confirmed to predict chemosensitivity for patients with gastric cancer. The purpose of this study was to investigate whether DNA methylation is associated with chemosensitivity in patients with gastric cancer. Tumors and matched non-tumor biopsy tissues collected from 134 advanced gastric cancer (AGC) patients prior to fluorouracil-based chemotherapy were retrospectively analyzed. The methylation status of p16, E-cadherin (CDH1), MGMT (O-6-methylguanine-DNA methyltransferase), and human mutL homolog 1 (hMLH1) was evaluated using a Methylight assay, and the association between p16 methylation and the sensitivity of 5-fluorouracil in cell lines was determined by in vitro assay. The methylation of p16 (17.9 vs. 0 %, P = 0.002), CDH1 (20.9 vs. 2.2 %, P < 0.001), MGMT (17.9 vs. 0 %, P = 0.052), and hMLH1 (14.9 vs. 2.2 %, P = 0.024) was more common in gastric cancer tissues (n = 134) than in non-tumor tissues (n = 46). For all patients, a reverse correlation was only found between p16 methylation and clinical response (P = 0.017), which suggested that p16 methylation might be associated with chemosensitivity of fluorouracil in gastric cancer patients. Results from in vitro experiments demonstrated that p16 methylation was closely correlated with the sensitivity of 5-fluorouracil in gastric cancer cells. The present results indicated that the methylation of p16, CDH1, MGMT, and hMLH1 was both frequent and specific in gastric cancer tissues. p16 Methylation might be used to predict chemosensitivity of fluorouracil for patients with AGC when validated in large samples in the future.
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[The value of transbronchial needle aspiration combined with rapid on-site evaluation of cytology in the diagnosis of lung cancer].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 03-27-2014
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There have been several studys about transbronchial needle aspiration (TBNA) combined with rapid on-site evaluation (ROSE) so far at home and abroad, yet few studys were especially for patients with lung cancer. The aim of our study is to investigate the effect of TBNA combined with ROSE in the diagnosis of lung cancer.
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Allopurinol initiation and all-cause mortality in the general population.
Ann. Rheum. Dis.
PUBLISHED: 03-26-2014
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Allopurinol is the most commonly used urate-lowering therapy, with rare but potentially fatal adverse effects. However, its impact on overall mortality remains largely unknown. In this study, we evaluated the impact of allopurinol initiation on the risk of mortality among individuals with hyperuricaemia and among those with gout in the general population.
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DFT study on the mechanisms and stereoselectivities of the [4 + 2] cycloadditions of enals and chalcones catalyzed by N-heterocyclic carbene.
J. Org. Chem.
PUBLISHED: 03-24-2014
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The possible reaction mechanisms of stereoselective [4 + 2] cycloaddition of enals and chalcones catalyzed by N-heterocyclic carbene (NHC) have been investigated using density functional theory (DFT). The calculated results indicate that the most favorable reaction channel occurs through five steps. The first step is the nucleophilic attack on the enal by NHC. Then, there are two consecutive acid (AcOH)-assisted proton-transfer steps. Subsequently, the fourth step is the [4 + 2] cycloaddition process associated with the formation of two chiral centers, followed by dissociation of NHC and product. Our computational results demonstrate that the [4 + 2] cycloaddition is the rate-determining and stereoselectivity-determining step. The energy barrier for the SS configurational channel (17.62 kcal/mol) is the lowest one, indicating the SS configurational product should be the main product, which is in agreement with experiment. Moreover, the role of NHC catalyst in the [4 + 2] cycloaddition of enal and chalcone was explored by the analysis of global reactivity indexes. This work should be helpful for realizing the significant roles of catalyst NHC and the additive AcOH and thus provide valuable insights on the rational design of potential catalyst for this kind of reactions.
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Vitamin D Therapy in Experimental Allergic Encephalomyelitis Could be Limited by Opposing Effects of Sphingosine 1-Phosphate and Gelsolin Dysregulation.
Mol. Neurobiol.
PUBLISHED: 03-23-2014
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Several studies support a protective effect of vitamin D on multiple sclerosis and experimental allergic encephalomyelitis (EAE), but the mechanisms of these favorable effects are unclear. Our study demonstrates that sphingosine 1-phosphate (S1P) is upregulated in the serum and spinal cords of EAE rats, but that vitamin D reverses the upregulation to alleviate inflammation. Vitamin D, however, cannot prevent the disease process, suggesting that other factors may be involved. To identify additional factors that might limit vitamin D efficacy, we assessed the effects of vitamin D on plasma gelsolin (pGSN), a regulator of S1P that is downregulated in the CSF of MS patients. Our results show that pGSN is downregulated in the serum of EAE rats, whereas its cellular form, cytoplasmic gelsolin (cGSN), is upregulated in the spinal cord of EAE rats. Importantly, vitamin D causes a downregulation of both pGSN and cGSN, which may counteract the positive effects of S1P decrease. Furthermore, 48 and 42?kDa caspase-3 cleavage products of cGSN are detected in EAE spinal cords, suggesting enhanced apoptotic activity, but these cleaved products undergo a similar decrease upon vitamin D treatment. To directly test the role of cGSN in the apoptotic process, we performed RNA interference in PC-12, a rat sympathetic nerve cell line. Results verify that cGSN suppresses apoptosis induced by TNF-?. Collectively, these results support a therapeutic effect of vitamin D that is derived from its ability to reduce S1P, but is limited by its simultaneous effect in reducing pGSN and cGSN. Based on these observations, we postulate that combined therapy with recombinant human pGSN and vitamin D may produce more beneficial effect in treating multiple sclerosis.
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Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides.
Nat. Chem. Biol.
PUBLISHED: 03-13-2014
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The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our work provides an explanation on the narrow activity spectrum of lasso peptides and opens the path to the development of new antibacterials.
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Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.
Tumour Biol.
PUBLISHED: 03-08-2014
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Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.
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Treatment of asymptomatic hyperuricemia and prevention of vascular disease: a decision analytic approach.
J. Rheumatol.
PUBLISHED: 03-01-2014
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Elevated serum urate may be associated with an increase in cardiovascular (CV) disease. Treating asymptomatic hyperuricemia with urate-lowering drugs such as allopurinol may reduce CV events. We designed a model to simulate the effect of allopurinol treatment on reducing frequency of CV events in individuals with elevated serum urate.
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ST6GalNAcII mediates the invasive properties of breast carcinoma through PI3K/Akt/NF-?B signaling pathway.
IUBMB Life
PUBLISHED: 02-26-2014
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Metastasis of tumor cells is the most deadly attribute of breast cancer patients. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. The objective of this study is to clarify the possible role and mechanism of ST6GalNAcII in the metastasis process of breast carcinoma. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAc II in breast carcinoma cell lines and tissue specimens. PI3K/AKt signaling pathway was also analyzed. The high expression level of ST6GalNAcII was corresponding to invasive phenotype of breast cancer cells both in vitro and in vivo. Further data indicated that manipulation of ST6GalNAcII gene expression led to alter the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway. Blocking the PI3K/Akt pathway resulted in reduced capacity in invasion of MDA-MB-231 cells. ST6GalNAcII elucidated the unusual properties of invasion in breast cancer cell via modulating the PI3K/AKt signaling pathway.
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Combination of microtubule associated protein-tau and ?-tubulin III predicts chemosensitivity of paclitaxel in patients with advanced gastric cancer.
Eur. J. Cancer
PUBLISHED: 02-25-2014
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To investigate the role of microtubule associated protein-tau (MAP-tau) and ?-tubulin III (TUBB3) in predicting the chemosensitivity of paclitaxel in patients with advanced gastric cancer (GC).
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Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype.
Pathog Dis
PUBLISHED: 02-25-2014
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Sepsis is a systemic inflammatory response to infection, and early responses of macrophages are vital in controlling the infected microorganisms. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of cisplatin (0.1, 0.5 and 1 mg kg(-1) ) with respect to peritoneal macrophages, controlling peritoneal/blood bacterial infection, and systemic inflammation. We found that mice which received low-dose (0.1 and 0.5 mg kg(-1) ) i.p. cisplatin had lower mortality rate and improved clinical scores compared with mice in normal saline-treated group, and the level of IL-6 and TNF-? was significantly reduced after cisplatin administration in peritoneal fluid of mice underwent CLP. Although cisplatin had no directly bactericidal ability, the numbers of bacteria in peritoneal and blood were significantly reduced at 24 and 72 h after the onset of CLP. Besides, in vivo phagocytosis and killing assay showed that the ability of macrophage derived from peritoneum was significantly increased with cisplatin treatment (5, 10, and 15 ?M) for both gram-positive (Enterococcus faecalis) and gram-negative (Escherichia coli) bacteria. This was associated with the macrophage phenotype polarization from CD11b(+) F4/80(high) CD206(-) to CD11b(+) F4/80(low) CD206(-) M1 group. These findings underscore the importance of low-dose cisplatin in the treatment of sepsis.
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Molecular dynamics simulation on the conformational transition of the mad2 protein from the open to the closed state.
Int J Mol Sci
PUBLISHED: 02-21-2014
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The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the ?6 strand and an increase of space around the binding sites of ?6 strand due to the unfolding of the ?7/8 sheet and movement of the ?6/4/5 sheet close to the ?C helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the ?1 strand and ?7/8 sheet via communication of the ?5-?C loop and the ?6/4/5 sheet in this transition process.
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Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.
Mediators Inflamm.
PUBLISHED: 02-20-2014
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Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-?, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-? and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-? and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats.
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Real-time elastography in the diagnosis of patients suspected of having prostate cancer: a meta-analysis.
Ultrasound Med Biol
PUBLISHED: 02-14-2014
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The goal of the study described here was to assess the performance of real-time elastography (RTE) in the detection of prostate cancers using a meta-analysis. A literature search of PubMed, Medline, Embase and the Cochrane Library was conducted. Published studies that evaluated the diagnostic performance of RTE in the diagnosis of prostate cancer and using the histopathology of the radical prostatectomy specimen as a reference standard were included. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve were calculated to examine the accuracy of RTE. A total of seven studies that included 508 patients were analyzed. The pooled sensitivity and specificity for the diagnosis of prostate cancer by RTE were 0.72 (95% confidence interval: 0.70-0.74) and 0.76 (0.74-0.78), respectively. The summary diagnostic odds ratio was 12.59 (7.26-21.84), and the area under the curve was 0.841 (Q* = 0.773). In conclusion, RTE imaging has high accuracy in the detection of prostate cancers using the histopathology of the radical prostatectomy specimen as the reference standard and may reduce the number of core biopsies in the future.
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Encapsulating tantalum oxide into polypyrrole nanoparticles for X-ray CT/photoacoustic bimodal imaging-guided photothermal ablation of cancer.
Biomaterials
PUBLISHED: 02-10-2014
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A nanotheranostic agent has been readily fabricated by encapsulating tantalum oxide (TaOx) nanoparticles (NPs) into polypyrrole (PPy) NPs via a facile one-step chemical oxidation polymerization for bimodal imaging guided photothermal ablation of tumor. It was proved that the obtained composite nanoparticles (TaOx@PPy NPs) with an average diameter around 45 nm could operate as an efficient bimodal contrast agent to simultaneously enhance X-ray CT and photoacoustic (PA) imaging greatly in vivo. Systemically administered TaOx@PPy NPs could passively accumulate at the tumor site during the blood circulation, which was proved by both CT and PA imaging. In addition, the in vivo therapeutic examinations showed that TaOx@PPy NPs exhibited significant photothermal cytotoxicity under near infrared laser irradiation. The tumor growth inhibition was evaluated to be 66.5% for intravenously injection and 100% for intratumoral injection, respectively. This versatile agent can be developed as a smart and promising nanoplatform that integrates multiple capabilities for both accurate diagnosing and precise locating of cancerous tissue, as well as effective photoablation of tumor.
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Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway.
J. Nutr. Biochem.
PUBLISHED: 02-09-2014
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Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 ?M) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway.
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Quercetin attenuates chronic ethanol hepatotoxicity: implication of "free" iron uptake and release.
Food Chem. Toxicol.
PUBLISHED: 02-09-2014
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Emerging evidence has displayed that oxygen free radicals especially ones promoted by "free" iron play an important role in the development of alcoholic liver disease (ALD). Naturally-occurring quercetin has been reported to prevent ALD and iron overload-induced damage aside from the "free" iron. The purpose was to explore the potential mechanisms by which quercetin arrests alcohol-induced "free" iron disorder. Chronic alcohol (30% of total calories) or iron (0.2%)-fed adult male C57BL/J mice for 15 weeks resulted in significantly elevated levels of hepatic iron, labile iron pool-Fe and serum non-transferrin bound iron, accompanied with sustained oxidative damage. The hepatotoxicity was further exacerbated by ethanol and iron. Quercetin (100 mg/kg. body weight) alleviated the detrimental effects induced by ethanol and/or iron. The expressions of divalent metal transporter 1, zinc transporter member 14, mucolipin 1, transferrin receptor 1 (TfR1) and ferritin were up-regulated by ethanol and/or iron, which were partially normalized by quercetin. Quercetin prevented ethanol-induced hepatotoxicity, which may be partially attributed to the alleviated disorder of bound iron and "free" iron. The significant suppression of ethanol-stimulated molecules for "free" iron uptake and release may contribute to the hepatoprotective effect of quercetin, although TfR1-mediated physiological pathway of iron uptake also played a role.
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New mechanistic insight into stepwise metal-center exchange in a metal-organic framework based on asymmetric Zn(4) clusters.
Chemistry
PUBLISHED: 02-07-2014
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Herein, a mechanism of stepwise metal-center exchange for a specific metal-organic framework, namely, [Zn4 (dcpp)2 (DMF)3 (H2 O)2 ]n (H4 dcpp=4,5-bis(4'-carboxylphenyl)phthalic acid), is disclosed for the first time. The coordination stabilities between the central metal atoms and the ligands as well as the coordination geometry are considered to be dominant factors in this stepwise exchange mechanism. A new magnetic analytical method and a theoretical model confirmed that the exchange mechanism is reasonable. When the metathesis reaction occurs between Cu(II) ions and framework Zn(II) ions, the magnetic exchange interaction of each pair of Cu(II) centers gradually strengthens with increasing amount of framework Cu(II) ions. By analyzing the changes of coupling constants in the Cu-exchanged products, it was deduced that Zn4 and Zn3 are initially replaced, and then Zn1 and Zn2 are replaced later. The theoretical calculation further verified that Zn4 is replaced first, Zn3 next, then Zn1 and Zn2 last, and the coordination stability dominates the Cu/Zn exchange process. For the Ni/Zn and Co/Zn exchange processes, besides the coordination stability, the preferred coordination geometry was also considered in the stepwise-exchange behavior. As Ni(II) and Co(II) ions especially favor octahedral coordination geometry in oxygen-ligand fields, Ni(II) ions and Co(II) ions could only selectively exchange with the octahedral Zn(II) ions, as was also confirmed by the experimental results. The stepwise metal-exchange process occurs in a single crystal-to-single crystal fashion.
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IL-23 selectively promotes the metastasis of colorectal carcinoma cells with impaired Socs3 expression via the STAT5 pathway.
Carcinogenesis
PUBLISHED: 01-24-2014
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Interleukin-23 (IL-23) is a conventional proinflammatory IL related to colorectal carcinoma (CRC). The signal transducer and activator of transcription (STAT) and suppressors of cytokine signaling (Socs) molecules, respectively, serve as agonists and antagonists of IL-23-associated inflammation. However, it remains unknown whether IL-23 directly affects CRC metastasis. In this study, we measured the metastasis of several human CRC cell lines stimulated by IL-23 in vitro and in vivo. Interestingly, the prometastasis effect of IL-23 was observed only in SW-620 cells. IL-23-associated migration and invasion was mediated by the phosphorylation of STAT5. The expression of Socs3 in SW-620 was impaired by IL-23 via DNA methylation and DNA methyltransferase-1 (DNMT-1)-dependent way. The DNMT-1-associated regulation was not observed in the other three cells. Socs3 was further confirmed to inhibit the prometastatic function of IL-23 both in vitro and in vivo. We analyzed the clinical correlation between the level of IL-23 in tumors and the metastasis of CRC and found that higher IL-23 levels along with lower Socs3 in CRC tissues accounted for more metastatic cases. In conclusion, it was demonstrated that IL-23, assisted by STAT5, might only promote the metastasis of CRC with deficient Socs3 expression in which IL-23-induced DNMT-1 was involved. It was elucidated that Socs3 seemed to be one of the important factors that mediate the selectivity of IL-23. Taken together, these discoveries give rise to new insights into the role of IL-23 in cancer biology and provide additional preclinical data regarding IL-23-associated therapy for CRC.
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The joint effects of room temperature ionic liquids and ordered media on fluorescence characteristics of estrogens in water and methanol.
Spectrochim Acta A Mol Biomol Spectrosc
PUBLISHED: 01-23-2014
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This study investigated the steady-state and time-resolved fluorescence properties of 17?-ethinylestradiol (EE2) and 17?-estradiol (E2) in the presence of ordered media (?-cyclodextrins (?-CD) and cetyltrimethylammonium bromide (CTAB)). In addition, we analyzed the effects of four room temperature ionic liquids (RTILs) on the fluorescence intensities (FIs) of EE2/?-CD and E2/?-CD inclusion complexes in methanol. Both ?-CD and CTAB enhanced the fluorescence of EE2 and E2. The FIs of EE2 and E2 with ?-CD or CTAB in methanol were greater than those in water, possibly resulting from decreased oxygen-quenching in H2O molecules. ?-CD and CTAB may form inclusion complexes with estrogen in both water and methanol. The inclusion ratio of the complex was 1:1 and the inclusion constant (K) values in water were greater than those in methanol. The fluorescence lifetimes were 2.50 and 4.13 ns for EE2 and 2.58 and 4.03 ns for E2 in aqueous solution and methanol, respectively. The changing trend of fluorescence lifetimes for EE2 and E2 in ?-CD or CTAB was similar to the steady-state FIs. The four RTILs had a significant quenching effect on the FIs of EE2/?-CD and E2/?-CD, and the quenching process for EE2/?-CD and E2/?-CD by RTILs was demonstrated to be a dynamic quenching mechanism. Fluorescent data obtained from these complex systems provide a theoretical foundation for understanding the interaction mechanisms between ordered media and RTILs in the analysis of estrogens.
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Axitinib alone or in combination with chemotherapeutic drugs exerts potent antitumor activity against human gastric cancer cells in vitro and in vivo.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-21-2014
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As the new oral selective VEGFR tyrosine kinase inhibitor, axitinib (AG-013736) exerts powerful antitumor activity in multiple solid tumors, while its' effect was unclear in gastric cancer. We aimed to investigate the antitumor activity of axitinib alone or combined with chemotherapeutic drugs against human gastric cancer cells in vitro and in vivo.
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Rapid and simple detection of methicillin-resistance Staphylococcus aureus by orfX loop-mediated isothermal amplification assay.
BMC Biotechnol.
PUBLISHED: 01-21-2014
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Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most prevalent pathogens responsible for nosocomial infections throughout the world. As clinical MRSA diagnosis is concerned, current diagnostic methodologies are restricted by significant drawbacks and novel methods are required for MRSA detection. This study aimed at developing a simple loop-mediated isothermal amplification (LAMP) assay targeting on orfX for the rapid detection of methicillin-resistance Staphylococcus aureus (MRSA).
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Synovitis in knee osteoarthritis assessed by contrast-enhanced magnetic resonance imaging (MRI) is associated with radiographic tibiofemoral osteoarthritis and MRI-detected widespread cartilage damage: the MOST study.
J. Rheumatol.
PUBLISHED: 01-15-2014
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To examine the cross-sectional association of whole-knee synovitis assessed by contrast-enhanced magnetic resonance imaging (CEMRI) with radiographic tibiofemoral osteoarthritis (OA), non-CEMRI-assessed cartilage damage, and meniscal status.
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Targeting cancer stem cells by curcumin and clinical applications.
Cancer Lett.
PUBLISHED: 01-14-2014
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Curcumin is a well-known dietary polyphenol derived from the rhizomes of turmeric, an Indian spice. The anticancer effect of curcumin has been demonstrated in many cell and animal studies, and recent research has shown that curcumin can target cancer stem cells (CSCs). CSCs are proposed to be responsible for initiating and maintaining cancer, and contribute to recurrence and drug resistance. A number of studies have suggested that curcumin has the potential to target CSCs through regulation of CSC self-renewal pathways (Wnt/?-catenin, Notch, sonic hedgehog) and specific microRNAs involved in acquisition of epithelial-mesenchymal transition (EMT). The potential impact of curcumin, alone or in combination with other anticancer agents, on CSCs was evaluated as well. Furthermore, the safety and tolerability of curcumin have been well-established by numerous clinical studies. Importantly, the low bioavailability of curcumin has been dramatically improved through the use of structural analogues or special formulations. More clinical trials are underway to investigate the efficacy of this promising agent in cancer chemoprevention and therapy. In this article, we review the effects of curcumin on CSC self-renewal pathways and specific microRNAs, as well as its safety and efficacy in recent human studies. In conclusion, curcumin could be a very promising adjunct to traditional cancer treatments.
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Daily intake of polybrominated diphenyl ethers via dust and diet from an e-waste recycling area in China.
J. Hazard. Mater.
PUBLISHED: 01-13-2014
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This study was designed to estimate the human risk to polybrominated diphenyl ethers (PBDEs) exposure via two main exposure routes (dust and diet) in an e-waste recycling area in southern China. A total of 134 dust samples and 129 food samples were analyzed by gas chromatography/mass spectrometry (GC/MS). The mean concentration of ?PBDE in in-house dust (38,685ng/g dw) was higher than that in out-house dust (24,595ng/g). For food samples, the highest concentration of ?PBDE was found in fish and shellfish (2755ng/kg ww), followed in descending order by eggs (2423ng/kg), cereals (2239ng/kg) and meat (1799ng/kg). The estimated total daily dietary intake of PBDEs was 1671ng/day for adults and 952ng/day for children. The present study indicated that dust intake was the dominant PBDE exposure route for children, and the dietary intake was the dominant PBDE exposure route for adults. Our findings revealed high PBDE concentrations in dust and food samples collected at the center of e-waste recycling area, raising significant health concerns for residents in this particular region, especially for children.
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Oxymatrine prevents hypoxia- and monocrotaline-induced pulmonary hypertension in rats.
Free Radic. Biol. Med.
PUBLISHED: 01-07-2014
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Pulmonary hypertension is a progressive disease characterized by marked pulmonary arterial remodeling and increased vascular resistance. Inflammation and oxidative stress promote the development of pulmonary hypertension. Oxymatrine, one of the main active components of the Chinese herb Sophora flavescens Ait. (Kushen), plays anti-inflammatory and antioxidant protective roles, which effects on pulmonary arteries remain unclear. This study aimed to investigate the effects of oxymatrine on pulmonary hypertension development. Sprague-Dawley rats were exposed to hypoxia for 28 days or injected with monocrotaline, to develop pulmonary hypertension, along with administration of oxymatrine (50mg/kg/day). Hemodynamics and pulmonary arterial remodeling data from the rats were then obtained. The antiproliferative effect of oxymatrine was verified by in vitro assays. The inflammatory cytokine mRNA levels and leukocyte and T cell accumulation in lung tissue were detected. The antioxidative effects of oxymatrine were explored in vitro. Our study shows that oxymatrine treatment attenuated right-ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia or monocrotaline and inhibited proliferation of pulmonary arterial smooth muscle cells (PASMCs). Increased expression of inflammatory cytokine mRNA and accumulation of leukocytes and T cells around the pulmonary arteries were suppressed with oxymatrine administration. Under hypoxic conditions, oxymatrine significantly upregulated Nrf2 and antioxidant protein SOD1 and HO-1 expression, but downregulated hydroperoxide levels in PASMCs. In summary, this study indicates that oxymatrine may prevent pulmonary hypertension through its antiproliferative, anti-inflammatory, and antioxidant effects, thus providing a promising pharmacological avenue for treating pulmonary hypertension.
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Age-group-specific associations between the severity of obstructive sleep apnea and relevant risk factors in male and female patients.
PLoS ONE
PUBLISHED: 01-01-2014
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To seek accurate and credible correlation manner between gender, age, and obesity; and the severity of obstructive sleep apnea (OSA) in large-scale population.
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Brain activation during phonological and semantic processing of Chinese characters in deaf signers.
Front Hum Neurosci
PUBLISHED: 01-01-2014
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Previous studies found altered brain function in deaf individuals reading alphabetic orthographies. However, it is not known whether similar alterations of brain function are characteristic of non-alphabetic writing systems and whether alterations are specific to certain kinds of lexical tasks. Here we examined differences in brain activation between Chinese congenitally deaf individuals (CD) and hearing controls (HC) during character reading tasks requiring phonological and semantic judgments. For both tasks, we found that CD showed less activation than HC in left inferior frontal gyrus, but greater activation in several right hemisphere regions including inferior frontal gyrus, angular gyrus, and inferior temporal gyrus. Although many group differences were similar across tasks, greater activation in right middle frontal gyrus was more pronounced for the rhyming compared to the meaning task. Finally, within the deaf individuals better performance on the rhyming task was associated with less activation in right inferior parietal lobule and angular gyrus. Our results in Chinese CD are broadly consistent with previous studies in alphabetic languages suggesting greater engagement of inferior frontal gyrus and inferior parietal cortex for reading that is largely independent of task, with the exception of right middle frontal gyrus for phonological processing. The brain behavior correlations potentially indicate that CD that more efficiently use the right hemisphere are better readers.
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The role of ACT-like subdomain in bacterial threonine dehydratases.
PLoS ONE
PUBLISHED: 01-01-2014
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In bacteria, threonine dehydratases could convert L-threonine to 2-ketobutyrate. Some threonine dehydratases contain only a catalytic domain, while others contain an N-terminal catalytic domain and a C-terminal regulatory domain composed of one or two ACT-like subdomains. However, the role of the ACT-like subdomain in threonine dehydratases is not clear. Here, nine different bacterial threonine dehydratases were studied. Three of the nine contain no ACT-like subdomain, four of them contain a single ACT-like subdomain, and two of them contain two ACT-like subdomains. The nine genes encoding these threonine dehydratases were individually overexpressed in E. coli BL21(DE3), and the enzymes were purified to homogeneity. Activities of the purified enzymes were analyzed after incubation at different temperatures and different pHs. The results showed that threonine dehydratases with a single ACT-like subdomain are more stable at higher temperatures and a broad range of pH than those without ACT-like subdomain or with two ACT-like subdomains. Furthermore, the specific activity of threonine dehydratases increases with the increase of the number of ACT-like subdomains they contain. The results suggest that the ACT-like subdomain plays an important role in bacterial threonine dehydratases.
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Prognostic significance of MET amplification and expression in gastric cancer: a systematic review with meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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MET, the hepatocyte growth factor receptor, is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer. Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. We performed a systematic review and meta-analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer.
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Systematic study of the luminescent europium-based nonanuclear clusters with modified 2-hydroxybenzophenone ligands.
Inorg Chem
PUBLISHED: 11-13-2013
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The reaction of 2-hydroxybenzophenone derivatives with europium ions has afforded a new family of luminescent nonanuclear Eu(III) clusters. Crystal structure analysis of the clusters reveals that the metal core comprises two vertex-sharing square pyramidal units. Most of these complexes show emissions typical of Eu(3+) ion under visible light excitation (400-420 nm) at room temperature. Photophysical characterization and DFT study reveal a correlation between luminescent efficiencies of Eu(III) complexes and the electronic features of the ligands, which can be tuned by the nature of substituents in the 4-position of the ligands. The ligands with a fluorine substituent possess more suitable triplet energy levels, resulting in more intensive luminescence.
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Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study.
Rheumatology (Oxford)
PUBLISHED: 10-31-2013
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Objective. The objective of this study was to evaluate the incidence of diabetes among patients with PsA and RA in the general population.Methods. We conducted a cohort study using an electronic medical records database representative of the UK general population (1986-2010). We estimated hazard ratios (HRs) for incident diabetes in PsA, psoriasis and RA cohorts compared with age- and sex-matched comparison cohorts without the corresponding conditions, adjusting for BMI, smoking, alcohol use, co-morbidities and glucocorticoids at baseline.Results. Cohorts included 4196 persons with PsA, 59 281 with psoriasis and 11 158 with RA, with mean follow-up times of 5.9, 5.8 and 5.5 years, respectively. Incidence rates for diabetes were 7.3, 6.4 and 6.3 cases per 1000 person-years among individuals with PsA, psoriasis and RA, respectively. Age- and sex-matched HRs for diabetes were 1.72 (95% CI 1.46, 2.02) in PsA, 1.39 (95% CI 1.32, 1.45) in psoriasis and 1.12 (95% CI 1.01, 1.25) in RA. After adjustment for BMI, smoking and alcohol, the HRs were attenuated substantially (1.43, 1.24 and 1.00, respectively). With further adjustment for baseline glucocorticoid use and co-morbidities, the HRs were 1.33 (1.09, 1.61) in PsA, 1.21 (1.15, 1.27) in psoriasis and 0.94 (0.84, 1.06) in RA.Conclusion. This general population study suggests an increased incidence of diabetes in PsA and RA, which is substantially explained by obesity and lifestyle factors. These findings support the importance of managing such factors in PsA and RA patients.
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Transcription dynamics of inducible genes modulated by negative regulations.
Math Med Biol
PUBLISHED: 09-24-2013
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Gene transcription is a stochastic process in single cells, in which genes transit randomly between active and inactive states. Transcription of many inducible genes is also tightly regulated: It is often stimulated by extracellular signals, activated through signal transduction pathways and later repressed by negative regulations. In this work, we study the nonlinear dynamics of the mean transcription level of inducible genes modulated by the interplay of the intrinsic transcriptional randomness and the repression by negative regulations. In our model, we integrate negative regulations into gene activation process, and make the conventional assumption on the production and degradation of transcripts. We show that, whether or not the basal transcription is temporarily terminated when cells are stimulated, the mean transcription level grows in the typical up and down pattern commonly observed in immune response genes. With the help of numerical simulations, we clarify the delicate impact of the system parameters on the transcription dynamics, and demonstrate how our model generates the distinct temporal gene-induction patterns in mouse fibroblasts discerned in recent experiments.
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Syntheses, crystal structures and thermal properties of six coordination polymers based on 2-(p-methylphenyl)-imidazole dicarboxylate.
Dalton Trans
PUBLISHED: 08-29-2013
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Through solvothermal reactions of 2-(p-methylphenyl)-1H-imidazole-4,5-dicarboxylic acid (p-MePhH3IDC) with transition-metal ions, six coordination polymers [Pb2(p-MePhHIDC)(p-MePhH2IDC)2(phen)2]n (phen = 1,10-phenanthroline) (), [Pb(p-MePhH2IDC)2]n (), [Cd3(p-MePhHIDC)2(p-MePhH2IDC)2(H2O)2]n (), {[Cd(p-MePhHIDC)(H2O)]4·H2O}n (), {[Cd2(p-MePhHIDC)2(4,4-bipy)]·4H2O}n (4,4-bipy = 4,4-bipyridine) () and [Mn3(p-MePhHIDC)2(p-MePhH2IDC)2(4,4-bipy)]n () have been synthesized successfully. X-ray single-crystal analyses show that polymers have rich structural chemistry ranging from one-dimensional (), two-dimensional () to three-dimensional polymers (, , and ). In these polymers, the p-MePhH3IDC ligand shows flexible coordination modes tuned by different synthetical conditions, including the addition of coligands, temperature, pH value and so on. Furthermore, the polymers have been investigated by solid-state ultraviolet spectra and thermogravimetric analyses.
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Prognostic role of D-dimer in patients with lung cancer: a meta-analysis.
Tumour Biol.
PUBLISHED: 08-21-2013
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D-dimer detection in patients suffering from a variety of different types of cancer has become a hot point as an emerging and promising biomarker. In this study, therefore, we evaluated the prognostic role of D-dimer in lung cancer. Initial literature was identified using the PubMed, EMBASE, and CNKI. The primary data was hazard ratio (HR) with 95 % confidence interval (CI) of survival outcomes in candidate articles, including overall survival (OS) and disease-free survival (DFS). Finally, 11 eligible studies were included in this meta-analysis, which were published between 1996 and 2013. The estimated pooled HR and 95 % CI for OS of all studies was 2.06 (95 % CI 1.64-2.58, p?
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.