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Find video protocols related to scientific articles indexed in Pubmed.
[A standard protocol for detection of EGFR mutations in cytologic specimens].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 10-21-2014
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The aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens.
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A novel miniaturized passively Q-switched pulse-burst laser for engine ignition.
Opt Express
PUBLISHED: 10-17-2014
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A novel miniaturized Cr4+:YAG passively Q-switched Nd:YAG pulse-burst laser under 808 nm diode-laser pulse-pumping was demonstrated for the purpose of laser-induced plasma ignition, in which pulse-burst mode can realize both high repetition rate and high pulse energy simultaneously in a short period. Side-pumping configuration and two different types of laser cavities were employed. The pumping pulse width was constant at 250 ?s. For the plane-plane cavity, the output beam profile was flat-top Gaussian and the measured M2 value was 4.1 at the maximum incident pump energy of 600 mJ. The pulse-burst laser contained a maximum of 8 pulses, 7 pulses and 6 pulses for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The energy obtained was 15.5 mJ, 14.9 mJ and 13.9 mJ per pulse for pulse-burst repetition rate of 10 Hz, 50 Hz and 100 Hz, respectively. The maximum repetition rate of laser pulses in pulse-burst was 34.6 kHz for 8 pulses at the incident pump energy of 600 mJ and the single pulse width was 13.3 ns. The thermal lensing effect of Nd:YAG rod was investigated, and an plane-convex cavity was adopted to compensate the thermal lensing effect of Nd:YAG rod and improve the mode matching. For the plane-convex cavity, the output beam profile was quasi-Gaussian and the measured M2 value was 2.2 at the incident pump energy of 600 mJ. The output energy was 10.6 mJ per pulse for pulse-burst repetition rate of 100 Hz. The maximum repetition rate of laser pulses in pulse-burst was 27.4 kHz for 6 pulses at the incident pump energy of 600 mJ and the single pulse width was 14.2 ns. The experimental results showed that this pulse-burst laser can produce high repetition rate (>20 kHz) and high pulse energy (>10 mJ) simultaneously in a short period for both two different cavities.
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Development of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (Higher Basidiomycetes) polysaccharides injection formulation.
Int J Med Mushrooms
PUBLISHED: 10-02-2014
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Biochemical and pharmacological research has demonstrated that Lingzhi or Reishi medicinal mushroom Ganoderma lucidum polysaccharides (GLPS) have significant anticancer, antitumor, and antioxidant activities. To investigate the effect of injecting GLPS into hosts for clinical studies, aqueous polysaccharide extracts from G. lucidum fruit bodies were purified by deproteinization using the Sevage method, anion-exchange chromatography elution (cellulose DEAE-52 chromatography), dialysis, ethanol precipitation, and active carbon and millipore membrane filtration techniques. The purified GLPS were used for injection in mice. Polysaccharide indexes, protein, tannin, heavy metal, arsenic salt, oxalate, potassium ion, resin, pH, ignition residue measurements, evaluation criterion for allergic reactions, and total solids content of the GLPS injection were all performed using the reference methods in the Chinese Pharmacopoeia. Our results showed that polysaccharide was the key component of injection mixtures. The ignition residue and total solids content in the injection mixture were 1.4% and 2.4%, respectively. The other indices were all within the expected safety ranges. Furthermore, studies from mice functional assays showed that the injection mixture improved the antifatigue capacity of mice without any effect on weight loss/gain. In addition, the injection mixture was safe, which was confirmed by allergy testing in guinea pigs. The development of a GLPS injection offers a novel approach for future medicinal mushroom utilization and holds great commercial promise.
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Realizing semiconductor-half-metal transition in zigzag graphene nanoribbons supported on hybrid fluorographene-graphane nanoribbons.
Phys Chem Chem Phys
PUBLISHED: 09-26-2014
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Hydrogenation and fluorination provide promising applications for tuning the properties of graphene-based nanomaterials. Using first-principles calculations, we investigate the electronic and magnetic properties of zigzag graphene nanoribbons (ZGNRs) supported on hydrogenated and fluorinated ZGNRs. Our results indicate that the support of zigzag graphane nanoribbon with its full width has less impact on the electronic and magnetic properties of ZGNRs, whereas the ZGNRs supported on fluorographene nanoribbons can be tuned to metal with almost degenerated ferro- and anti-ferromagnetic states due to the intrinsic polarization of substrate. The ZGNRs supported on zigzag hybrid fluorographene-graphane nanoribbons are spin-polarized half-semiconductors with distinct band gaps for spin-up and spin-down channels. Interestingly, in the absence of an external electric field, the spin-polarized band gaps of supported ZGNRs can be well modulated in the opposite direction by changing the ratio of fluorination to hydrogenation concentration in hybrid substrates. Furthermore, the ZGNRs supported on hybrid nanoribbons exhibit the half-semiconducting to half-metallic behavior transition as the interlayer spacing is gradually reduced, which is realized more easily for the hybrid support with a relatively wide fluorographene moiety compared to its narrow counterpart. Present results provide a novel way for designing substrate-supported graphene spintronic devices.
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Preparation of self-assembled nanoparticles of chitosan oligosaccharide-graft-polycaprolactone as a carrier of bovine serum albumin drug.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Chitosan oligosaccharides graft polycaprolactone copolymer (PHCSO-g-PCL) has been synthesized via initiating the polymerization of e-caprolactone (CL) monomer through an amino group protection route using phthaloyl chitosan oligosaccharide (PHCSO) as intermediate. The grafting reaction was carried out in Pyridine at 120 °C with the hydroxyl group of the chitosan oligosaccharide (CSO) as initiator and the tin 2-ethylhexanoate (Sn (Oct)2) as catalyst. The PHCSO-g-PCL nanoparticles with and without bovine serum albumin (BSA) drug were prepared through the self-assembled approach in Dimethylformamide (DMF) organic solvents. PHCSO-PCL copolymer was investigated by Fourier transform infrared spectroscopy (FTIR), 1H NMR spectrum and scanning electron microscopy (SEM). The physicochemical properties of the hydrophobized PHCSO-g-PCL nanoparticles were characterized by fluorescence spectroscopy and dynamic light scattering (DLS). The results of DLS showed that the hydrodynamic diameters and particle size distribution with various concentrations of PHCSO-g-PCL nanoparticles were from 69.82 nm to 195.9 nm with a narrow polydispersity factor of 0.212 to 0.172. The results of DLS also showed that the hydrodynamic diameters and particle size distribution of PHCSO-g-PCL (5 mg/ml) nanoparticles without and with BSA drug (0.4 mg/ml) were from 168.44 nm to 200.7 nm. The polydispersity factor was from 0.119 to 0.159.
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Human FcR polymorphism and disease.
Curr. Top. Microbiol. Immunol.
PUBLISHED: 08-14-2014
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Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical Fc?Rs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture.
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Novel celastrol derivatives inhibit the growth of hepatocellular carcinoma patient-derived xenografts.
Oncotarget
PUBLISHED: 07-23-2014
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The molecular co-chaperone CDC37 is over-expressed in hepatocellular carcinoma (HCC) cells, where it functions with HSP90 to regulate the activity of protein kinases in multiple oncogenic signaling pathways that contribute towards hepatocarcinogenesis. Disruption of these signaling pathways via inhibition of HSP90/CDC37 interaction is therefore a rational therapeutic approach. We evaluated the anti-tumor effects of celastrol, pristimerin, and two novel derivatives (cel-D2, and cel-D7) on HCC cell lines in vitro and on orthotopic HCC patient-derived xenografts in vivo. All four compounds preferentially inhibited viability of HCC cells in vitro,and significantly inhibited the growth of three orthotopic HCC patient-derived xenografts in vivo; with the novel derivatives cel-D2 and cel-D7 exhibiting lower toxicity. All four compounds also induced cell apoptosis; and promoted degradation and inhibited phosphorylation of protein kinases in the Raf/MEK/ERK and PI3K/AKT/mTOR signaling pathways. We demonstrated that HSP90/CDC37 antagonists are potentially broad spectrum agents that might be beneficial for treating the heterogeneous subtypes of HCC, either as monotherapy, or in combination with other chemotherapeutic agents.
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IDMA-based MAC protocol for satellite networks with consideration on channel quality.
ScientificWorldJournal
PUBLISHED: 07-13-2014
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In order to overcome the shortcomings of existing medium access control (MAC) protocols based on TDMA or CDMA in satellite networks, interleave division multiple access (IDMA) technique is introduced into satellite communication networks. Therefore, a novel wide-band IDMA MAC protocol based on channel quality is proposed in this paper, consisting of a dynamic power allocation algorithm, a rate adaptation algorithm, and a call admission control (CAC) scheme. Firstly, the power allocation algorithm combining the technique of IDMA SINR-evolution and channel quality prediction is developed to guarantee high power efficiency even in terrible channel conditions. Secondly, the effective rate adaptation algorithm, based on accurate channel information per timeslot and by the means of rate degradation, can be realized. What is more, based on channel quality prediction, the CAC scheme, combining the new power allocation algorithm, rate scheduling, and buffering strategies together, is proposed for the emerging IDMA systems, which can support a variety of traffic types, and offering quality of service (QoS) requirements corresponding to different priority levels. Simulation results show that the new wide-band IDMA MAC protocol can make accurate estimation of available resource considering the effect of multiuser detection (MUD) and QoS requirements of multimedia traffic, leading to low outage probability as well as high overall system throughput.
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Longitudinal changes in tear fluid lipidome brought about by eyelid-warming treatment in a cohort of meibomian gland dysfunction.
J. Lipid Res.
PUBLISHED: 07-03-2014
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Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and ocular discomfort characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface. Herein, we elucidated longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks. Remarkably, eyelid-warming resulted in stark reductions in lysophospholipids (P < 0.001 for lyso-plasmalogen phosphatidylethanolamine, lysophosphatidylcholine, and lysophosphatidylinositol), as well as numerous PUFA-containing diacylglyceride species in tears, accompanied by significant increases in several PUFA-containing phospholipids. These changes in tear lipidomes suggest that eyelid-warming leads to diminished activity of tear phospholipases that preferentially target PUFA-containing phospholipids. In addition, treatment led to appreciable increases (P < 0.001) in O-acyl-?-hydroxy-FAs (OAHFAs), which are lipid amphiphiles critical to the maintenance of tear film stability. Longitudinal changes in the tear lipids aforementioned also significantly (P < 0.05) correlated with reduced rate of ocular evaporation and improvement in ocular symptoms. The foregoing data thus indicate that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.
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Concentration dependent halogen-bond density in the 2D self-assembly of a thienophenanthrene derivative at the aliphatic acid/graphite interface.
Chem. Commun. (Camb.)
PUBLISHED: 07-02-2014
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The supramolecular patterns of a thienophenanthrene derivative could be switched among dissimilar polymorphs with different halogen-bond densities by solution concentration, which is demonstrated through a combination of STM and density functional theory (DFT) calculations.
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High-repetition-rate and short-pulse-width electro-optical cavity-dumped YVO?/Nd:GdVO? laser.
Appl Opt
PUBLISHED: 06-13-2014
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In this paper, an electro-optical cavity-dumped 1.06 ?m laser using YVO4/Nd:GdVO4 composite crystal under 808 nm diode-laser pumping was reported. Theoretical calculations showed that the temperature distribution in YVO4/Nd:GdVO4 crystal was lower than that in GdVO4/Nd:GdVO4 and Nd:GdVO4 crystals under the same conditions. A constant 3.8±0.3??ns pulse width was obtained and the repetition rate could reach up to 50 kHz with a maximum average output power of 5.6 W and slope efficiency of 40.7%, corresponding to a peak power of 31.1 kW.
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Two new spirooxindole alkaloids from rhizosphere strain Streptomyces sp. xzqh-9.
Bioorg. Med. Chem. Lett.
PUBLISHED: 06-02-2014
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Two new spirooxindole alkaloids spindomycins A (1) and B (2) were isolated from rhizosphere strain Streptomyces sp. xzqh-9. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and MS data. The absolute configurations of 1 and 2 were determined by experimental and theoretical calculation of electronic circular dichroism (ECD). Antitumor, lactate dehydrogenase, and tyrosine kinase inhibitory activities of two compounds were evaluated, while only spindomycin B (2) exhibited weak inhibitory activity against tyrosine kinase Bcr-Abl.
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[Systematic review of primary stenting for arteriosclerotic occlusion in below-the-knee arteries].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-24-2014
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To evaluate the clinical value of primary stenting for treating peripheral arterial diseases in below-the-knee arteries by comparing to percutaneous transluminal angioplasty (PTA).
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Steric matching and the concentration induced self-assembled structural variety of 2,7-bis(n-alkoxy)-9-fluorenone at the aliphatic solvent/graphite interface.
Phys Chem Chem Phys
PUBLISHED: 05-17-2014
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Controlling and unraveling structural polymorphism has received special attention in 2D self-assembled monolayers. In this work, we investigated the steric matching and solution concentration controlled structural variety in the self-assembly of 2,7-bis(n-alkoxy)-9-fluorenone (F-OCn) at the n-tetradecane and n-tridecane/graphite interface under different concentrations, respectively. Scanning tunneling microscopy (STM) revealed that the coadsorbed adlayers of F-OCn and solvents (n = 12 to 16) were formed and exhibited concentration dependent 2D phases due to the steric matching. The self-assembled monolayer of F-OCn (n = 12 to 16) evolved from a low-density coadsorbed linear lamellar packing, which was formed at low concentrations, to higher-density patterns at relatively high concentrations. F-OC14 exhibited a complex structural variety, in which a systematic trend of decrease in the molecular density per unit cell with decreasing concentration was obtained. Except for F-OCn (n = 13, 15, 17), the zigzag structure showing the linear lamella with dimers was observed. Systematic experiments revealed that the self-assembly of F-OCn was chain-length dependent. The results provide insight into the structural variety exhibited by a series of organic molecules and furnish important guidelines to control the morphology by changing the solution concentration.
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[Therapeutic effects of Bacille Calmette-Guerin vaccine on asthma airway remodeling in rats and its mechanism].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-26-2014
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To explore the therapeutic effects and mechanism of Bacillus Calmette-Guerin (BCG) vaccine on airway remodeling in rats.
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MPINet: metabolite pathway identification via coupling of global metabolite network structure and metabolomic profile.
Biomed Res Int
PUBLISHED: 04-01-2014
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High-throughput metabolomics technology, such as gas chromatography mass spectrometry, allows the analysis of hundreds of metabolites. Understanding that these metabolites dominate the study condition from biological pathway perspective is still a significant challenge. Pathway identification is an invaluable aid to address this issue and, thus, is urgently needed. In this study, we developed a network-based metabolite pathway identification method, MPINet, which considers the global importance of metabolites and the unique character of metabolomic profile. Through integrating the global metabolite functional network structure and the character of metabolomic profile, MPINet provides a more accurate metabolomic pathway analysis. This integrative strategy simultaneously captures the global nonequivalence of metabolites in a pathway and the bias from metabolomic experimental technology. We then applied MPINet to four different types of metabolite datasets. In the analysis of metastatic prostate cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of the two type 2 diabetes datasets, we show that MPINet has the potentiality for identifying novel pathways related with disease and is reliable for analyzing metabolomic data. Finally, we extensively applied MPINet to identify drug sensitivity related pathways. These results suggest MPINet's effectiveness and reliability for analyzing metabolomic data across multiple different application fields.
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Identification of antihyperlipidemic constituents from the roots of Rubia yunnanensis Diels.
J Ethnopharmacol
PUBLISHED: 03-30-2014
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The roots of Rubia yunnanensis Diels (Rubiaceae) have been used as an alternative for Rubia cordifolia for the treatment of various diseases including cardiovascular disease and metabolic disease for a long history in traditional Chinese medicine. To evaluate antihyperlipidemic activity of the roots of Rubia. yunnanensis Diels and to identify active compounds from the active fraction.
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Lophomonas blattarum infection presented as acute exacerbation of chronic obstructive pulmonary disease.
J Thorac Dis
PUBLISHED: 03-28-2014
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The present case described a 70-year-old male who was initially diagnosed and treated as acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Ultimately Lophomonas blattarum (L. blattarum), a rare protozoan causing opportunistic infection, was found in suction sputum smear. Bronchoscopy showed a lot of purulent sputum in airways, diffusely swelling and friable mucus on bronchus. After single tinidazole treatment, symptoms and image showed marked improvement. It indicates though in the untraditional immunocompromised case, the suspect of opportunistic diseases is necessary, especially in the cases failed to improvement under empirical treatment. It also supports the tinidazole treatment is efficacy in L. blattarum infection.
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Coenzyme Q10 promotes macrophage cholesterol efflux by regulation of the activator protein-1/miR-378/ATP-binding cassette transporter G1-signaling pathway.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 03-27-2014
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Recent studies have shown the role of miRNAs in macrophage reverse cholesterol transport and atherogenesis. We hypothesized that coenzyme Q10 (CoQ10) may increase macrophage reverse cholesterol transport by regulating miRNA expression that contributes to the prevention of atherosclerosis.
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Catalytic activity of Pd-doped Cu nanoparticles for hydrogenation as a single-atom-alloy catalyst.
Phys Chem Chem Phys
PUBLISHED: 03-25-2014
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The single atom alloy of extended surfaces is known to provide remarkably enhanced catalytic performance toward heterogeneous hydrogenation. Here we demonstrate from first principles calculations that this approach can be extended to nanostructures, such as bimetallic nanoparticles. The catalytic properties of the single-Pd-doped Cu55 nanoparticles have been systemically examined for H2 dissociation as well as H atom adsorption and diffusion, following the concept of single atom alloy. It is found that doping a single Pd atom at the edge site of the Cu55 shell can considerably reduce the activation energy of H2 dissociation, while the single Pd atom doped at the top site or in the inner layers is much less effective. The H atom adsorption on Cu55 is slightly stronger than that on the Cu(111) surface; however, a larger nanoparticle that contains 147 atoms could effectively recover the weak binding of the H atoms. We have also investigated the H atom diffusion on the 55-atom nanoparticle and found that spillover of the produced H atoms could be a feasible process due to the low diffusion barriers. Our results have demonstrated that facile H2 dissociation and weak H atom adsorption could be combined at the nanoscale. Moreover, the effects of doping one more Pd atom on the H2 dissociation and H atom adsorption have also been investigated. We have found that both the doping Pd atoms in the most stable configuration could independently exhibit their catalytic activity, behaving as two single-atom-alloy catalysts.
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Downregulation of PPP2R5E expression by miR-23a suppresses apoptosis to facilitate the growth of gastric cancer cells.
FEBS Lett.
PUBLISHED: 03-24-2014
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PPP2R5E belongs to the phosphatase 2A regulatory subunit B family and acts as a tumor suppressor in human cancer. However, the role of PPP2R5E in the tumorigenesis of gastric cancer is unclear. Here, we declare that PPP2R5E is downregulated by miR-23a and induces cell growth inhibition and apoptosis in gastric cancer cells. Furthermore, ASO-miR-23a suppresses tumor growth derived from MGC803 cells in vivo. PPP2R5E is identified as a new target of miR-23a. Moreover, overexpression of PPP2R5E reversed the negative effects of miR-23a. We highlight the significance of miR-23a and PPP2R5E in the proliferation and apoptosis of gastric cancer cells.
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Technical details and clinical outcomes of transpopliteal venous stent placement for postthrombotic chronic total occlusion of the iliofemoral vein.
J Vasc Interv Radiol
PUBLISHED: 02-26-2014
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To evaluate the technical aspects and early clinical results of stent placement for managing postthrombotic chronic total occlusion (CTO) of the iliofemoral vein through ipsilateral popliteal access.
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The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia.
Neurobiol. Aging
PUBLISHED: 02-26-2014
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Despite its importance as the leading cause of vascular dementia, the primary pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have remained elusive. Because of the lack of approved therapeutic agents for SIVD, there is a pressing need to identify novel therapeutic targets. Comparative lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's disease, MixD) may also confer new insights pertaining to the possible interaction between neurodegenerative and vascular mechanisms in the pathogenesis of dementia. Liquid chromatography coupled to mass spectrometry was used to comprehensively analyze the lipidomes of white and gray matter from the temporal cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular profiles highlighted the pathologic relevance of gray matter sphingolipid fatty acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and lysobisphosphatidic acids were progressively increased in the temporal cortex gray matter from control to SIVD to MixD. White matter phospholipid profiles indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic ischemia in SIVD and elevated membrane degradation in MixD.
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Serum lipids, apolipoproteins, and mortality among coronary artery disease patients.
Biomed Res Int
PUBLISHED: 02-24-2014
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The proatherogenic effect of low-density lipoprotein cholesterol (LDL-C) and antiatherogenic effect of high-density lipoprotein cholesterol (HDL-C) have been confirmed in general population. But controversy arises among coronary artery disease (CAD) patients. The goal of this study was to identify the association of different lipid measurements with CAD prognosis. The study cohort included 1916 CAD patients who were 40-85 years of age. Cox proportional hazards regression models were used to estimate the association of baseline 6 lipid factors and 3 ratios with all-cause and cardiovascular (CVD) mortality. During a median follow-up of 3.1 years, 147 deaths were recorded, 113 of which were due to CVD. When lipid factors were categorized, HDL-C showed a U-shape association with all-cause and CVD mortality after adjustment for major CVD risk factors. Serum LDL-C, apoB, LDL/HDL ratio, and apoB/apoA-I ratio were positively, and apoA-I level was inversely associated with the risk of CVD mortality. After further pairwise comparison of lipid-related risk, LDL/HDL ratio and LDL-C had stronger association with all-cause and CVD mortality than other proatherogenic measurements among Chinese CAD patients.
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Endovascular treatment for symptomatic stent failures in long-segment chronic total occlusion of femoropopliteal arteries.
J. Vasc. Surg.
PUBLISHED: 02-20-2014
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The objective of this study was to evaluate the outcomes of the secondary endovascular treatment (SEVT) for symptomatic recurrences in long-segment chronic total occlusion (CTO) of femoropopliteal arteries (FPAs) and to investigate the factors affecting the outcomes.
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Targeting the Fc receptor in autoimmune disease.
Expert Opin. Ther. Targets
PUBLISHED: 02-14-2014
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The Fc receptors (FcRs) and their interactions with immunoglobulin and innate immune opsonins, such as C-reactive protein, are key players in humoral and cellular immune responses. As the effector mechanism for some therapeutic monoclonal antibodies, and often a contributor to the pathogenesis and progression of autoimmunity, FcRs are promising targets for treating autoimmune diseases.
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APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease.
Neural Regen Res
PUBLISHED: 02-13-2014
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Current evidence shows that apolipoprotein E (APOE), apolipoprotein CI (APOC1) and low density lipoprotein receptor-related protein (LRP) variations are related to late-onset Alzheimer's disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer's disease patients. We performed a 30-month longitudinal cohort study to investigate the relationship between Alzheimer's disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer's disease were recruited form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess patients' cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE ?4 carriers compared with non-carriers. In addition, the APOE ?4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive impairment progression group. In conclusion, APOE ?4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ?4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer's disease.
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Nano composite emulsion for sustained drug release and improved bioavailability.
Pharm. Res.
PUBLISHED: 01-25-2014
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To propose a novel composite nanoemulsion formulation that contains no surfactant, but offers great stability and improved oral absorption capabilities.
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Comparative proteomic analysis of Saccharomyces cerevisiae under different nitrogen sources.
J Proteomics
PUBLISHED: 01-24-2014
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In cultures containing multiple sources of nitrogen, Saccharomyces cerevisiae exhibits a sequential use of nitrogen sources through a mechanism known as nitrogen catabolite repression (NCR). To identify proteins differentially expressed due to NCR, proteomic analysis of S. cerevisiae S288C under different nitrogen source conditions was performed using two-dimensional gel electrophoresis (2-DE), revealing 169 candidate protein spots. Among these 169 protein spots, 121 were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF). The identified proteins were closely associated with four main biological processes through Gene Ontology (GO) categorical analysis. The identification of the potential proteins and cellular processes related to NCR offer a global overview of changes elicited by different nitrogen sources, providing clues into how yeast adapt to different nutritional conditions. Moreover, by comparing our proteomic data with corresponding mRNA data, proteins regulated at the transcriptional and post-transcriptional level could be distinguished. Biological significance In S. cerevisiae, different nitrogen sources provide different growth characteristics and generate different metabolites. The nitrogen catabolite repression (NCR) process plays an important role for S. cerevisiae in the ordinal utilization of different nitrogen sources. NCR process can result in significant shift of global metabolic networks. Previous works on NCR primarily focused on transcriptomic level. The results obtained in this study provided a global atlas of the proteome changes triggered by different nitrogen sources and would facilitate the understanding of mechanisms for how yeast could adapt to different nutritional conditions.
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Polyethylene glycol-modified dendrimer-entrapped gold nanoparticles enhance CT imaging of blood pool in atherosclerotic mice.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH2) modified by PEG monomethyl ether (G5.NH2-mPEG20) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 ?M. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.
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Atomistic deformation mechanisms in twinned copper nanospheres.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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In the present study, we perform molecular dynamic simulations to investigate the compression response and atomistic deformation mechanisms of twinned nanospheres. The relationship between load and compression depth is calculated for various twin spacing and loading directions. Then, the overall elastic properties and the underlying plastic deformation mechanisms are illuminated. Twin boundaries (TBs) act as obstacles to dislocation motion and lead to strengthening. As the loading direction varies, the plastic deformation transfers from dislocations intersecting with TBs, slipping parallel to TBs, and then to being restrained by TBs. The strengthening of TBs depends strongly on the twin spacing.
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Allelic-dependent expression of an activating fc receptor on B cells enhances humoral immune responses.
Sci Transl Med
PUBLISHED: 12-20-2013
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B cells are pivotal regulators of acquired immune responses, and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of B cell function can substantially alter immunological responses. The balance of negative and positive signals in maintaining an appropriate B cell activation threshold is critical in B lymphocyte immune tolerance and autoreactivity. Fc?RIIb (CD32B), the only recognized Fc? receptor on B cells, provides immunoglobulin G (IgG)-mediated negative modulation through a tyrosine-based inhibition motif, which down-regulates B cell receptor-initiated signaling. These properties make Fc?RIIb a promising target for antibody-based therapy. We report the discovery of allele-dependent expression of the activating Fc?RIIc on B cells. Identical to Fc?RIIb in the extracellular domain, Fc?RIIc has a tyrosine-based activation motif in its cytoplasmic domain. In both human B cells and B cells from mice transgenic for human Fc?RIIc, Fc?RIIc expression counterbalances the negative feedback of Fc?RIIb and enhances humoral responses to immunization in mice and to BioThrax vaccination in a human anthrax vaccine trial. Moreover, the FCGR2C-ORF allele is associated with the risk of development of autoimmunity in humans. Fc?RIIc expression on B cells challenges the prevailing paradigm of unidirectional negative feedback by IgG immune complexes via the inhibitory Fc?RIIb, is a previously unrecognized determinant in human antibody/autoantibody responses, and opens the opportunity for more precise personalized use of B cell-targeted antibody-based therapy.
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Lipidomic analysis of human tear fluid reveals structure-specific lipid alterations in dry eyesyndrome.
J. Lipid Res.
PUBLISHED: 11-28-2013
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As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. In this study, a comprehensive lipidomic platform designated for analysis of human tear lipidome was employed to characterize changes in tear lipid compositions from a cohort of 93 subjects of different clinical subgroups classified based on the presence of dry eye symptoms and signs. Positive correlations were observed between the tear levels of cholesteryl sulfates and glycosphingolipids with physiological secretion of tears, which indicated the possible lacrimal (instead of meibomian) origin of these lipids. Notably, we found wax esters of low molecular masses and those containing saturated fatty acyl moieties were specifically reduced with disease and significantly correlated with various DES clinical parameters such as ocular surface disease index, tear breakup time and Schirmers I test (i.e. both symptoms and signs). These structure-specific changes in tear components with DES could potentially serve as unifying indicators of disease symptoms and signs. In addition, the structurally-specific aberrations in tear lipids reported above were found in patients with or without aqueous-deficiency, suggesting a common pathology for both DES subtypes. ?
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Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles.
J. Lipid Res.
PUBLISHED: 11-28-2013
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The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention due to the limiting concentrations of these lipid amphiphiles in tears that render their detection and accurate quantitation tedious. Using systematic and sensitive lipidomic approaches, we validated different tear collection techniques and report the most comprehensive human tear lipidome to date; comprising more than 600 lipid species from 17 major lipid classes. Our study confers novel insights to the compositional details of existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-omega-hydroxy fatty acids, and various sphingolipids and phospholipids in tears. The discovery and quantitation of the relative abundances of various tear lipid amphiphiles reported herein are expected to have profound impact on the current understanding of the existent human tear film model.
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Systematic review and meta-analysis of balloon angioplasty versus primary stenting in the infrapopliteal disease.
Vasc Endovascular Surg
PUBLISHED: 11-07-2013
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Objectives: We performed a systematic review and meta-analysis of comparing balloon angioplasty and primary stenting for symptomatic infrapopliteal disease to evaluate the clinical value of primary stenting in treating infrapopliteal diseases. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. PubMed (1984-present), ScienceDirect (1980-present), Embase (1990-present), and CBM (1988-present) databases were searched for relevant articles. Finally, 16 studies (published between 2001 and 2013) satisfying the inclusion criteria were identified. The outcome parameters were immediate technical success, 1-year primary patency rate, 1-year limb salvage rate, and 1-year target vessel revascularization (TVR)-free rate. Comparisons were made with balloon angioplasty and primary stenting, and based on the different types of stents, we divided the primary stent group into the bare metal stent (BMS) group and drug-eluting stent (DES) group. Results: A total of 3789 patients and 4339 limbs constituted our final study population. The technical success rate of balloon angioplasty was 92.29% (95% confidence interval [CI] 88.75%-94.78%). Only 2 study reported the technical failure rates as 4% and 5.2% in the primary stent group. The pooled estimates of 1-year primary patency and TVR-free rate were similarly low in the balloon angioplasty group and BMS group (primary patency: 57.65%, 95% CI 53.54%-61.67% vs 60.95%, 95% CI 48.31%-72.28%, P = .38; TVR-free rate: 73.41%, 95% CI 66.51%-80.08% vs 73.66%, 95% CI 63.58%-81.75%, P = .91). The pooled estimates of 1-year primary patency and TVR-free rate in DES group were 81.10% (95% CI 75.48%-85.67%) and 90.30% (95% CI 85.30%-93.73%), respectively, which were better than those of the BMS and balloon angioplasty groups (P < .001 for both). The pooled estimate of 1-year limb salvage in the balloon angioplasty, BMS, and DES groups was 88.61% (95% CI 85.01%-91.43%), 94.41% (95% CI 89.52%-97.1%), and 95.20% (95% CI 86.97%-98.33%), respectively (P < .001). The BMS and DES groups had higher limb salvage rates than the balloon angioplasty group (P < .001 for both comparisons). The rates of severe complications were low both in the balloon angioplasty and in the primary stent groups. Conclusion: Primary BMS implantation had no advantage over balloon angioplasty in reducing restenosis or revascularization for infrapopliteal disease. Primary DES implantation seems to be a promising treatment for focal infrapopliteal lesions. Publication bias could not be ruled out, and the results should be treated with caution.
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Metabolic engineering of the regulators in nitrogen catabolite repression to reduce the production of ethyl carbamate in a model rice wine system.
Appl. Environ. Microbiol.
PUBLISHED: 11-01-2013
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Rice wine has been one of the most popular traditional alcoholic drinks in China. However, the presence of potentially carcinogenic ethyl carbamate (EC) in rice wine has raised a series of food safety issues. During rice wine production, the key reason for EC formation is urea accumulation, which occurs because of nitrogen catabolite repression (NCR) in Saccharomyces cerevisiae. NCR represses urea utilization by retaining Gln3p in the cytoplasm when preferred nitrogen sources are present. In order to increase the nuclear localization of Gln3p, some possible phosphorylation sites on the nuclear localization signal were mutated and the nuclear localization regulation signal was truncated, and the disruption of URE2 provided an additional method of reducing urea accumulation. By combining these strategies, the genes involved in urea utilization (DUR1,2 and DUR3) could be significantly activated in the presence of glutamine. During shake flask fermentations of the genetically modified strains, very little urea accumulated in the medium. Furthermore, the concentrations of urea and EC were reduced by 63% and 72%, respectively, in a model rice wine system. Examination of the normal nutrients in rice wine indicated that there were few differences in fermentation characteristics between the wild-type strain and the genetically modified strain. These results show that metabolic engineering of the NCR regulators has great potential as a method for eliminating EC during rice wine production.
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Hyperglycemia and mortality among patients with coronary artery disease.
Diabetes Care
PUBLISHED: 10-02-2013
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Objective:Known diabetes is an independent predictor for mortality in coronary artery disease (CAD) patients, however, whether other glucose abnormalities are associated with death risk in CAD patients is unclear. The goal of this study was to examine the association between different glucose states and the risks of all-cause and cardiovascular disease (CVD) mortality among CAD patients.Research Design and Methods:The study cohort included 1726 CAD patients who were 40-85 years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional hazards regression models were used to estimate the association of baseline glucose status with risk of mortality.Results:During a median follow-up of 3.1 years, 129 deaths were recorded, 109 of which were due to CVD. The multivariable-adjusted (age, sex, education, marriage, leisure-time physical activity, smoking, alcohol drinking, body mass index, systolic blood pressure, total and high-density lipoprotein cholesterol, glomerular filtration rate, type, severity, duration, and treatment of CAD, history of heart failure, and use of antihypertensive, cholesterol-lowering, and anti-platelet drugs) hazard ratios in normoglycemia, impaired glucose regulation (IGR), newly diagnosed diabetes, and known diabetes were 1.00, 1.58 (95% CI 0.90-2.77), 2.41 (1.42-4.11), and 2.29 (1.36-3.84) for all-cause mortality, and 1.00, 1.89 (95% CI 1.01-3.54), 2.74 (1.50-5.01), and 2.73 (1.52-4.91) for CVD mortality. Assessing fasting plasma glucose only, impaired fasting glucose, newly diagnosed and known diabetes were also associated with increased risks of all-cause and CVD mortality compared with normoglycemia.Conclusions:CAD patients with IGR, newly diagnosed diabetes, and known diabetes have increased risk of CVD mortality.
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Erythrocyte membrane fatty acid composition is related to overloaded plasma ferritin in Chinese males with angiographic coronary artery disease.
Food Funct
PUBLISHED: 09-24-2013
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Not only is iron deficiency an abnormal iron status, but iron overload is also harmful for human health. It has been reported that overloaded iron stores are positively associated with increased coronary artery disease (CAD) risk, which is called the "iron-heart hypothesis". Previous studies evaluating the relationships between fatty acids (FAs) and body iron status only focused on participants with iron deficiency. However, whether FA composition is related to overloaded iron remains unclear. Therefore, this study was designed to investigate the relationships between erythrocyte membrane FA (Ery-FA) composition and overloaded body iron status as measured by plasma ferritin levels in Chinese CAD patients. A total of 446 subjects with angiographically identified CAD (mean age 63.1 years, 76.9% males) were recruited in a hospital between 2009 and 2010. Ery-FAs were measured by gas chromatography and the activities of FA desaturases, which are involved in the de novo synthesis of unsaturated FAs, were evaluated by using FA product-to-precursor ratios. Results showed that the average iron status was a bit overloaded in the population (median ferritin levels of 234.1 ng mL(-1) and 40.4% males of overload). Moreover, in males, saturated FAs (SFAs) were positively correlated (22 : 0, r = 0.182, p = 0.001; 24 : 0, r = 0.214, p < 0.001), whereas monounsaturated FAs (MUFAs) and n-6 polyunsaturated FAs (PUFAs) were negatively correlated (18 : 1n-9, r = -0.120, p = 0.028; 18 : 2n-6, r = -0.216, p < 0.001) with plasma ferritin levels. A negative correlation (r < 0, p < 0.05) between stearoyl-CoA desaturase (SCD) activity and ferritin levels was also found in males. However, all the significant associations above were not observed in females. In conclusion, the Ery-FA composition was related to overloaded plasma ferritin levels only in Chinese males with angiographic CAD, which might be linked to the change of SCD activity. The results may contribute to the understanding of the mechanism of the iron-heart hypothesis.
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Concordance between self-reported substance use and toxicology among HIV-infected and uninfected at risk youth.
Drug Alcohol Depend
PUBLISHED: 09-10-2013
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Substance use by youth living with HIV (YLWH) is a concern, given potential interactions with virus-associated immune suppression and adverse effects on risk behaviors, neurocognition, and adherence. Self-report substance use measures provide efficient cost-effective assessments. Analyses describe self-reported substance use among YLWH and examine agreement with toxicology assays.
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Plasma S-adenosylhomocysteine is associated with the risk of cardiovascular events in patients undergoing coronary angiography: a cohort study.
Am. J. Clin. Nutr.
PUBLISHED: 09-04-2013
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Although cross-sectional studies have shown that plasma S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine, is associated with cardiovascular disease, the prospective relation between plasma SAH and cardiovascular disease risk is unknown.
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Functional combination strategy for prioritization of human miRNA target.
Gene
PUBLISHED: 08-12-2013
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MicroRNAs (miRNAs) are a class of non-coding RNAs known to play important regulatory roles through targets, which can affect human cell proliferation, differentiation, and metabolism. Overlaps between different miRNA target prediction algorithms (MTPAs) are small, which limit the understanding of miRNAs biological functions. However, the overlaps increase on functional levels, such as Gene Ontology (GO), Protein-Protein Interaction Network (PPIN) and pathways. Here, we performed prioritization on existing predicted target sets for each miRNA by considering all the possible combinations of 7 functional levels. After analyzing the results of both single and multiple functional levels, we found that functional combination strategies including pathways and GO performed better in the prioritization of human miRNA target. The combination which performed best was "Pathway+GO BP+GO MF+GO CC+Target+PPIN". For the prioritized result of this combination, the valid target had top ranking, and our method performed better than the MTPAs after comparison adopting the validated ranking levels. Top genes in ranking lists generated by this strategy were either validated by experiments or share same functions with the corresponding miRNA/its validated genes in disease related biological processes.
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Pressure-induced stromal keratopathy as a result of ocular trauma after laser in situ keratomileusis.
JAMA Ophthalmol
PUBLISHED: 08-10-2013
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Pressure-induced stromal keratopathy is a rare kind of complication of laser in situ keratomileusis (LASIK) that may cause vision loss in affected eyes. Herein, we described the clinical features and treatment of 2 cases of pressure-induced stromal keratopathy due to traumatic hyphema in post-LASIK eyes.
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Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations.
PLoS Genet.
PUBLISHED: 08-01-2013
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Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic, epigenetic, and environmental risk factors. To assess the role of DNA methylation in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE patients and 58 controls, and performed genome-wide DNA methylation analysis with Illumina Methylation 450 microarrays. We identified 166 CpGs in B-cells, 97 CpGs in monocytes, and 1,033 CpGs in T-cells with highly significant changes in DNA methylation levels (p < 1 × 10(-8)) among SLE patients. Common to all three cell-types were widespread and severe hypomethylation events near genes involved in interferon signaling (type I). These interferon-related changes were apparent in patients collected during active and quiescent stages of the disease, suggesting that epigenetically-mediated hypersensitivity to interferon persists beyond acute stages of the disease and is independent of circulating interferon levels. This interferon hypersensitivity was apparent in memory, naïve and regulatory T-cells, suggesting that this epigenetic state in lupus patients is established in progenitor cell populations. We also identified a widespread, but lower amplitude shift in methylation in CD4+ T-cells (> 16,000 CpGs at FDR < 1%) near genes involved in cell division and MAPK signaling. These cell type-specific effects are consistent with disease-specific changes in the composition of the CD4+ population and suggest that shifts in the proportion of CD4+ subtypes can be monitored at CpGs with subtype-specific DNA methylation patterns.
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SFRP5 correlates with obesity and metabolic syndrome and increases after weight loss in children.
Clin. Endocrinol. (Oxf)
PUBLISHED: 07-18-2013
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Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine, which has been shown as a mediator between obesity and its comorbidities. The aim of this study was to evaluate the associations of SFRP5 with metabolic syndrome (MetS) and the effects of lifestyle interventions on circulating SFRP5 levels in children.
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Synthesis of hierarchical TiO? nanoflower with anatase-rutile heterojunction as Ag support for efficient visible-light photocatalytic activity.
Dalton Trans
PUBLISHED: 07-02-2013
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Hierarchical flower-like TiO? with an anatase-rutile heterojunction was prepared by a hydrothermal process in the presence of titanium trichloride and poly(sodium-p-styrenesulfonate) (PSS). The morphology evolution process and formation mechanism of the as-obtained products were investigated in detail. It was found that morphology and crystalline phase can be easily adjusted by changing the reaction time or solution system. On the basis of this hierarchical nanoflower structure, a visible light sensitive Ag/hierarchical flower-like TiO? plasmonic photocatalyst was fabricated. The obtained composite exhibited significantly visible-light photocatalytic activity, which could be attributed to the existence of a large number of uniformly distributed Ag-TiO? effective nanojunctions, enhanced visible light-harvesting and improved charge separation due to the migration across the anatase-rutile interface.
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Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases.
World J Nephrol
PUBLISHED: 06-29-2013
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Matrix metalloproteinases (MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial-mesenchymal transition (EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition (EndoMT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, has been shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-? (TGF-?). However, MMP-9 was found by us and others to be up-regulated by TGF-?1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.
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Porous graphene oxide/carboxymethyl cellulose monoliths, with high metal ion adsorption.
Carbohydr Polym
PUBLISHED: 06-14-2013
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Orderly porous graphene oxide/carboxymethyl cellulose (GO/CMC) monoliths were prepared by a unidirectional freeze-drying method. The porous monoliths were characterized by Fourier transform infrared spectra, X-ray diffraction and scanning electron microscopy. Their properties including compressive strength and moisture adsorption were measured. The incorporation of GO changed the porous structure of the GO/CMC monoliths and significantly increased their compressive strength. The porous GO/CMC monoliths exhibited a strong ability to adsorb metal ions, and the Ni(2+) ions adsorbed on GO/CMC monolith were reduced by NaBH4 to obtain Ni GO/CMC monolith which could be used as catalyst in the reduction of 4-nitrophenol to 4-aminophenol. Since CMC is biodegradable and non-toxic, the porous GO/CMC monoliths are potential environmental adsorbents.
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Nitrogen regulation involved in the accumulation of urea in Saccharomyces cerevisiae.
Yeast
PUBLISHED: 06-13-2013
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Rice wine is a popular traditional alcoholic drink with a long history in China. However, the presence of the potential carcinogen ethyl carbamate (EC) raises a series of food safety concerns. Although the metabolic pathway of urea (the major precusor of EC) has been characterized in Saccharomyces cerevisiae, the regulation of urea accumulation remains unclear, making the efficient elimination of urea difficult. To demonstrate the regulatory mechanisms governing urea accumulation, three key nitrogen sources that can inhibit urea utilization for a commercial S. cerevisiae strain were identified. In addition, regulators of nitrogen catabolite repression (NCR) and target of rapamycin (TOR) pathways were identified as being involved in urea accumulation by real-time quantitative PCR. Based on these results, preferred nitrogen sources were found to repress urea utilization by converting them to glutamine or glutamate. Moreover, the results indicated that the manner of urea metabolism regulation was different for two positive regulators involved in NCR; Gln3p can be retained in the cytoplasm by glutamine, while Gat1p can be retained by glutamine and glutamate. Furthermore, this was confirmed by fluorescence location detection. These new findings provide new targets for eliminating EC and other harmful nitrogen-containing compounds in fermented foods.
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Catalytic formation of ketones from unactivated esters through rhodium chelation-assisted C-O bond activation.
J. Org. Chem.
PUBLISHED: 06-10-2013
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A new method for building aryl aryl ketones containing heterocyclic rings through chelation-assisted C-O bond activation catalyzed by a rhodium complex has been developed. In this reaction, methyl quinoline-8-carboxylate, methyl quinoxaline-5-carboxylate, and their derivatives were reacted with an excess amount of a substituted phenyl boronic acid in the presence of a rhodium(I) complex to give substituted phenyl(quinolin-8-yl)methanone, phenylquinoxalin-5-ylmethanone, and their derivatives in medium to high yields. The current method offers a highly favorable synthetic pathway to efficiently build related drugs with an 8-benzoylquinoline core structure. This method may prove especially valuable for medicinal chemists for the late-stage introduction of versatile ketone moieties into complex scaffolds for diversity-oriented synthetic strategies.
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Dietary protein and plasma total homocysteine, cysteine concentrations in coronary angiographic subjects.
Nutr J
PUBLISHED: 06-07-2013
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Dietary patterns are associated with plasma total homocysteine (tHcy) concentrations in healthy populations, but the associations between dietary protein and tHcy, total cysteine (tCys) in high risk populations are unclear. We therefore examined the association between dietary protein and tHcy and tCys concentrations in coronary angiographic subjects.
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Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents at the liquid/solid interface.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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Two-dimensional self-assembly of dendritic amphiphilic molecule with ferroncenyl subsitutuents (2,3,4-tri-(11-ferroncenyl)undecyloxybenzoic acid, Fc3COOH) on highly oriented pyrolytic graphite surface was investigated by scanning tunneling microscopy at the liquid/solid interface. Fc3COOH molecule formed an ordered molecular nanostructure--an alternating big/small bright dots pattern on the graphite surface extended to several hundred nanometers. On the basis of the simulation and combined with our STM results, it is concluded that the molecular adsorption conformation has an appreciable effect on the interactions of molecule-molecule and molecule-substrate. The pi-pi interactions between ferrocene groups together with the van der Waals interactions between alkyl chains direct the stacking behavior of Fc3COOH molecules. Due to the steric constraints, no hydrogen bonding between the carboxyl groups was formed during the self-assembly.
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Designing robust alumina nanowires-on-nanopores structures: superhydrophobic surfaces with slippery or sticky water adhesion.
J Colloid Interface Sci
PUBLISHED: 04-25-2013
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Hierarchical alumina surfaces with different morphologies were fabricated by a simple one-step anodization method. These alumina films were fabricated by a new raw material: silica gel plate (aluminum foil with a low purity of 97.17%). The modulation of anodizing time enabled the formation of nanowires-on-nanopores hybrid nanostructures having controllable nanowires topographies through a self-assembly process. The resultant structures were demonstrated to be able to achieve superhydrophobicity without any hydrophobic coating layer. More interestingly, it is found that the as-prepared superhydrophobic alumina surfaces exhibited high contrast water adhesion. Hierarchical alumina film with nanowire bunches-on-nanopores (WBOP) morphology presents extremely slippery property which can obtain a sliding angle (SA) as low as 1°, nanowire pyramids-on-nanopores (WPOP) structure shows strongly sticky water adhesion with the adhesive ability to support 15 ?L inverted water droplet at most. The obtained superhydrophobic alumina surfaces show remarkable mechanical durability even treated by crimping or pressing without impact on the water-repellent performance. Moreover, the created surfaces also show excellent resistivity to ice water, boiling water, high temperature, organic solvent and oil contamination, which could expand their usefulness and efficacy in harsh conditions.
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Zhizhu decoction promotes gastric emptying and protects the gastric mucosa.
J Med Food
PUBLISHED: 04-10-2013
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The aim of this study was to evaluate the effects of the Zhizhu decoction on gastric emptying and gastric mucosal protection. The Zhizhu decoction is composed of Aurantii fructus and Atractylodes macrocephala Rhizoma. Results showed that oral administration of the Zhizhu decoction accelerated gastric emptying in mouse and protected gastric mucosa from ethanol-induced ulcers in rat. Our investigations demonstrated that the Zhizhu decoction accelerated gastric emptying, at least in part, by activating the muscarinic and 5-HT3 receptors. The gastroprotective effect is involved in its antioxidant effects and increased vascular endothelial growth factor expression.
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Genome-wide analysis of the Sus gene family in cotton.
J Integr Plant Biol
PUBLISHED: 04-01-2013
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Sucrose synthase (Sus) is a key enzyme in plant sucrose metabolism. In cotton, Sus (EC 2.4.1.13) is the main enzyme that degrades sucrose imported into cotton fibers from the phloem of the seed coat. This study demonstrated that the genomes of Gossypium arboreum L., G. raimondii Ulbr., and G. hirsutum L., contained 8, 8, and 15 Sus genes, respectively. Their structural organizations, phylogenetic relationships, and expression profiles were characterized. Comparisons of genomic and coding sequences identified multiple introns, the number and positions of which were highly conserved between diploid and allotetraploid cotton species. Most of the phylogenetic clades contained sequences from all three species, suggesting that the Sus genes of tetraploid G. hirsutum derived from those of its diploid ancestors. One Sus group (Sus I) underwent expansion during cotton evolution. Expression analyses indicated that most Sus genes were differentially expressed in various tissues and had development-dependent expression profiles in cotton fiber cells. Members of the same orthologous group had very similar expression patterns in all three species. These results provide new insights into the evolution of the cotton Sus gene family, and insight into its members physiological functions during fiber growth and development.
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Expansion of breast cancer stem cells with fibrous scaffolds.
Integr Biol (Camb)
PUBLISHED: 03-27-2013
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Cancer stem cells (CSCs) are hypothesized as tumor-initiating cells within tumors and main contributors of tumor growth, metastasis and recurrence. Mammary cancer cells, MCF-7 cells, were cultured on 3D polycaprolactone (PCL) fibrous scaffolds, showing an increased proportion of CSCs. The expression of stem cell markers, including OCT3/4 and SOX2, and breast CSC-specific markers, SOX4 and CD49f, was significantly upregulated, and the mammosphere-forming capability in cells cultured on PCL fibrous scaffolds increased. The fibrous scaffolds also induced the elongation of MCF-7 cells and extended cell proliferation. The increase of CSC properties after being cultured on fibrous scaffolds was further confirmed with two luminal-type mammary cell lines, T47D and SK-BR-3, and a basal-type cell line, MDA-MB-231, by ALDEFLUOR assay and mammosphere formation assay. Moreover, we observed the upregulation of epithelial to mesenchymal transition and increased invasive capability in cells cultured on PCL fibrous scaffolds. These data suggest that the increase of CSC proportion in a 3D culture system may account for the enhanced malignancy. Therefore, our PCL fibrous scaffolds can potentially be used for CSCs enrichment and anti-cancer drug screening.
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Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease.
Mediators Inflamm.
PUBLISHED: 03-16-2013
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To evaluate whether serum interleukin-6 (IL-6) is associated with increased risk of mortality in coronary artery disease (CAD) patients.
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Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ?3 and ?4 knock-in mice.
Neurobiol. Aging
PUBLISHED: 02-27-2013
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Apolipoprotein E (ApoE) is important in facilitating the transport of lipids (cholesterol, phospholipids, and sulfatides) and plays a fundamental role in normal lipid metabolism. High cholesterol levels increases the risk of developing Alzheimers disease. In this study, we investigated the effects of a high-fat high cholesterol (HFHC) diet on brain lipid profiles in 95 young and aged APOE ?3 and ?4 knock-in mice to determine whether diet leads to altered brain levels of a number of glycerophospholipids, sphingolipids, cholesterol precursors, cholesterol, cholesterol oxidation products, and cholesterol esters. The results in this study revealed significant changes in lipid levels. The HFHC-enriched diet influenced the levels of cholesterol esters. A sharp increase in cholesterol ester levels, particularly in the aged APOE ?4 diet-enriched group, might be suggestive of abnormal acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT) activity and/or levels. Age exerts appreciable effects on the brain lipidome, especially with regard to polar lipid species.
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Hydrogen-bonding-induced polymorphous phase transitions in 2D organic nanostructures.
Chem Asian J
PUBLISHED: 02-27-2013
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The 2D self-assembly of various 2-hydroxy-7-alkoxy-9-fluorenone (HAF) molecules has been investigated by scanning tunneling microscopy (STM) at the liquid/solid interface. A systematic study revealed that HAF molecules with different numbers of carbon atoms in their alkoxy chains could form two or three different kinds of nanostructures, that is, less-ordered, flower-like, and zig-zag patterns, owing to the formation of different types of intermolecular hydrogen bonds. The observed structural transition was found to be driven by molecular thermodynamics, surface diffusion, and the voltage pulse that was applied to the STM tip. The zig-zag pattern was the most stable of these configurations. An odd-even effect on the flower-like structure, as induced by the odd and even number of carbon atoms in the side chain, was observed by STM. The influence of the odd-even effect on the melting point has a close relationship with the molecular self-assembled pattern. Our results are significant for understanding the influence of hydrogen-bonding interactions on the dominant adsorption behavior on the surface and provide a new visual approach for observing the influence of the odd-even effect on the phase transition.
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Memantine hydrochloride in the treatment of dementia subtypes.
J Clin Neurosci
PUBLISHED: 02-24-2013
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Memantine hydrochloride is a first-line therapeutic drug approved by the US Food and Drug Administration for the management of moderate to severe Alzheimers disease (AD). We conducted a review of the literature to determine the changes to the central glutamatergic neurotransmitter system in dementia subtypes and the available clinical evidence regarding the use of memantine in the treatment of different dementia subtypes. We conclude from our review that memantine may be an effective therapeutic option in managing AD, frontotemporal dementia, dementia with Lewy bodies, Parkinsons disease dementia and vascular dementia. When a diagnosis of the dementia subtype cannot be clearly identified or when there is no clear therapeutic option, memantine may be simple and safe.
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A simple procedure for protein ubiquitination detection in Saccharomyces cerevisiae: Gap1p as an example.
J. Microbiol. Methods
PUBLISHED: 02-11-2013
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We established a simple procedure for protein ubiquitination detection in Saccharomyces cerevisiae. Enhanced green fluorescent protein (EGFP) was split into two parts, an N-terminal (GN) and a C-terminal (GC) region. The fusion fragments GN-UBI3 and multi-cloning site (MCS)-GC were inserted into the vector pY26-TEF/GPD, resulting in pUbDetec16. pUbDetec16 was designed for use in detecting protein ubiquitination. Any gene of interest can be inserted into the MCS and the recombinant plasmid can be transferred into a ?ura3 auxotrophic S. cerevisiae strain. Protein ubiquitination can then be detected using a fluorescence microscope. The ubiquitination of a protein can be determined based on a fluorescence signal. To validate the reliability of this procedure, Gap1p, a protein known to be ubiquitinated, was used as a positive control. A triple mutant of Gap1p, Gap1p(K9R,K16R,K76R), which did not contain any ubiquitination site, was used as a negative control. pUbDetec16-GAP1 and pUbDetec16-GAP1(K9R,K16R,K76R) were constructed and transferred into the ?ura3 auxotrophic S. cerevisiae strain CEN.PK2-1D. Transformants of pUbDetec16-GAP1 emitted fluorescence, while the pUbDetec16-GAP1(K9R,K16R,K76R) transformants did not. The ubiquitination of Gap1p and Gap1p(K9R, K16R, K76R) was further verified using classical SDS-PAGE analysis. This procedure significantly simplifies manipulation involving ubiquitination detection using the BiFC approach, particularly on a large scale.
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In situ controlled growth of ZnIn2S4 nanosheets on reduced graphene oxide for enhanced photocatalytic hydrogen production performance.
Chem. Commun. (Camb.)
PUBLISHED: 02-11-2013
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A reduced graphene oxide (RGO)-ZnIn(2)S(4) nanosheet composite was successfully synthesized via an in situ controlled growth process. The as-obtained RGO-ZnIn(2)S(4) composite showed excellent visible light H(2) production activity in the absence of noble metal cocatalysts.
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Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans.
Gene
PUBLISHED: 02-07-2013
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Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited. In this study, we explored the effects of rs10118757 in MTAP gene on CAD and MI by performing association analysis in a Chinese Han population. rs10118757 was genotyped in 1007 CAD patients (including 338 MI patients) and 885 healthy controls. Allelic analysis showed that allele A of rs10118757 was associated with increased risk of CAD, with OR (95%CI)=1.193 (1.035-1.376), and P=0.015. After adjusted for age, BMI, gender, hypertension and smoking, rs10118757 was still significantly associated with CAD under additive and dominant models, with OR (95%CI)=1.252 (1.070-1.465), P=0.005, and OR (95%CI)=1.698 (1.168-2.467), P=0.006, respectively. Compared to additive model, dominant model may be the best-fitting model (P=6.63E-10 vs P=6.70E-10). As reported previously, rs10118757 was not associated with MI in the current study. Our study firstly reported that SNP rs10118757 was associated with CAD risk in a Chinese Han population, indicating that MTAP gene may play a potential role in the pathophysiological process of CAD.
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The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes.
J. Radiat. Res.
PUBLISHED: 02-07-2013
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Background The purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1-3, 4-9 and ?10 positive axillary nodes). Methods: A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as Radio + /ECE + , Radio-/ECE + , Radio + /ECE- or Radio-/ECE- according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. Results: ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1-3 (P = 0.5720), ?10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4-9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). Conclusion: In our study, regardless of the ECE status, PMRT didnt significantly improve the LRFFS for patients with 1-3 or ?10 positive axillary nodes. However, for patients with 4-9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.
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An acid catalyzed reversible ring-opening/ring-closure reaction involving a cyano-rhodamine spirolactam.
Org. Biomol. Chem.
PUBLISHED: 02-05-2013
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Cyanamide was introduced into the rhodamine spirolactam framework to produce a colorless and non-fluorescent compound RBCN. It shows a reversible ring-opening/ring-closure process in response to the solution pH, which exhibits an "ON/OFF" switching in its fluorescence. Different from other rhodamine-type dyes, the ring-open form of RBCN is stable in protic solvents under neutral, near neutral and basic conditions, showing a pink color and very strong fluorescence. We also demonstrated the potential of RBCN in live cell imaging.
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Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage.
Lab. Invest.
PUBLISHED: 01-28-2013
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A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.
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Molecular photoacoustic imaging of follicular thyroid carcinoma.
Clin. Cancer Res.
PUBLISHED: 01-24-2013
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To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma.
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MRI of iron oxide nanoparticle-labeled ADSCs in a model of hindlimb ischemia.
Biomaterials
PUBLISHED: 01-19-2013
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Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.
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Recombinant purine nucleoside phosphorylases from thermophiles: preparation, properties and activity towards purine and pyrimidine nucleosides.
FEBS J.
PUBLISHED: 01-13-2013
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Thermostable nucleoside phosphorylases are attractive biocatalysts for the synthesis of modified nucleosides. Hence we report on the recombinant expression of three high molecular mass purine nucleoside phosphorylases (PNPs) derived from the thermophilic bacteria Deinococcus geothermalis, Geobacillus thermoglucosidasius and from the hyperthermophilic archaeon Aeropyrum pernix (5-methythioadenosine phosphorylase; ApMTAP). Thermostability studies, kinetic analysis and substrate specificities are reported. The PNPs were stable at their optimal temperatures (DgPNP, 55 °C; GtPNP, 70 °C; ApMTAP, activity rising to 99 °C). Substrate properties were investigated for natural purine nucleosides [adenosine, inosine and their C2-deoxy counterparts (activity within 50-500 U·mg(-1))], analogues with 2-amino modified 2-deoxy-adenosine and -inosine (within 0.1-3 U·mg(-1)) as well as 2-deoxy-2-fluoroadenosine (9) and its C2-arabino diastereomer (10, within 0.01-0.03 U·mg(-1)). Our results reveal that the structure of the heterocyclic base (e.g. adenine or hypoxanthine) can play a critical role in the phosphorolysis reaction. The implications of this finding may be helpful for reaction mechanism studies or optimization of reaction conditions. Unexpectedly, the diastereomeric 2-deoxyfluoro adenine ribo- and arabino-nucleosides displayed similar substrate properties. Moreover, cytidine and 2-deoxycytidine were found to be moderate substrates of the prepared PNPs, with substrate activities in a range similar to those determined for 2-deoxyfluoro adenine nucleosides 9 and 10. C2-modified nucleosides are accepted as substrates by all recombinant enzymes studied, making these enzymes promising biocatalysts for the synthesis of modified nucleosides. Indeed, the prepared PNPs performed well in preliminary transglycosylation reactions resulting in the synthesis of 2-deoxyfluoro adenine ribo- and arabino- nucleosides in moderate yield (24%).
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The prognosis of synchronous and metachronous bilateral breast cancer in Chinese patients.
Tumour Biol.
PUBLISHED: 01-09-2013
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This study was undertaken to determine the differences in the clinicopathology and survival between synchronous bilateral breast cancer (sBBC) and metachronous bilateral breast cancer (mBBC). Additionally, we analyzed the risk factors for single tumors to develop as sBBC or mBBC. Of the 190 bilateral breast cancer (BBC) cases, 84 cases were sBBC and 106 were mBBC. We defined sBBC as two tumors that developed within 12 months, while mBBC was defined as two tumors that developed over more than 12 months. The peak age of onset of the first mBBC tumors was significantly younger than that of sBBC tumors (p = 0.001). There was a higher concordance rate of ER/ER positivity and PR/PR positivity in the first and second tumors of sBBC than mBBC. The two sBBC breast cancers had relatively similar hormone conditions because of the low rate of ER and PR transformation from positive to negative or vice versa. We determined that patients who presented with extracapsular extension (p = 0.008) and ER positivity (p = 0.001) tend to have synchronous cancers, while patients with 3+ HER2 were more likely to develop metachronous tumors. The prognosis for mBBC was better than that for sBBC when the survival time of mBBC was measured from the initial observation of the first tumors.
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