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Find video protocols related to scientific articles indexed in Pubmed.
The Noninvasive Detection of RAR?2 Promoter Methylation for the Diagnosis of Prostate Cancer.
Cell Biochem. Biophys.
PUBLISHED: 10-14-2014
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Prostate cancer is a kind of commonly diagnosed male malignancy. With the aging population in China, both incidence and mortality of prostate cancer are expected to keep increasing in the future. The methylation of RAR?2 gene promoter is a common molecular event in prostate cancer. Thus, we aimed at establishing a high-performance noninvasive DNA methylation assay based on pyrosequencing for screening of prostate cancer in this article. The assay is designed to detect aberrant promoter methylation of RAR?2 gene in ejaculate samples. The negative and positive control plasmids were constructed with different treatments by direct bisulfite conversion or conversion after Sss I Methylase methylation to establish quality control standard. The ejaculate and tissue samples were collected from patients with histologically confirmed adenocarcinoma of prostate (n = 43) and benign prostatic hyperplasia (n = 40). Significant correlation was observed between prostate cancer and methylation level of RAR?2 gene promoter. In addition, the results of pyrosequencing in ejaculate samples were compared with that of DNA sequencing in tissue samples from the same patients. There is no significant difference in the detection of RAR?2 promotor methylation between these two methods (p < 0.05). In conclusion, we have developed a high-performance noninvasive DNA methylation assay based on pyrosequencing which is more suitable for high-throughput detection of aberrant promoter methylation in ejaculate samples. Moreover, the acceptive degree of this noninvasive method makes it potentially promising for future screening of prostate cancer.
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Comparative Effectiveness of Di'ao Xin Xue Kang Capsule and Compound Danshen Tablet in Patients With Symptomatic Chronic Stable Angina.
Sci Rep
PUBLISHED: 08-18-2014
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A high proportion of patients with stable angina remains symptomatic despite multiple treatment options. Di'ao Xinxuekang (XXK) capsule and Compound Danshen (CDS) tablet have been approved for treating angina pectoris for more than 20 years in China. We compare the anti-anginal effectiveness of XXK capsule and CDS tablet in patients with symptomatic chronic stable angina. A randomized, multicenter, double-blind, parallel-group, superiority trial was conducted in 4 study sites. 733 patients with symptomatic chronic stable angina were included in the full analysis set. The primary outcomes were the proportion of patients who were angina-free and the proportion of patients with normal electrocardiogram (ECG) recordings during 20 weeks treatment. Compared with CDS, XXK significantly increased the proportion of angina-free patients, but no significant difference was noted in the proportion of patients with normal ECG recordings. Weekly angina frequency and nitroglycerin use were significantly reduced with XXK versus CDS at week 20. Moreover, XXK also improved the quality of life of angina patients as measured by the SAQ score and Xueyu Zheng (a type of TCM syndrome) score. We demonstrate that XXK capsule is more effective for attenuating anginal symptoms and improving quality of life in patients with symptomatic chronic stable angina, compared with CDS tablet.
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Gene expression profiling analysis of locus coeruleus in idiopathic Parkinson's disease by bioinformatics.
Neurol. Sci.
PUBLISHED: 08-13-2014
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This study aimed to explore the underlying molecular mechanisms of idiopathic Parkinson's disease (IPD) by bioinformatics analysis. Gene expression profile GSE34516 was downloaded from the Gene Expression Omnibus. Eight locus coeruleus post-mortem tissue samples derived from four IPD patients and four neurological healthy controls were used to identify the differentially expressed genes (DEGs) by paired t test. Based on the DEGs, principal components were analyzed. The Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the genome microarray data were then performed. Finally, protein-protein interaction (PPI) network of the DEGs was constructed. Total 261 DEGs including 195 up-regulated and 66 down-regulated DEGs were identified. Intracellular protein transport and RNA splicing via transesterification reactions were selected as the most two significantly enriched functions. Mismatch repair, N-glycan biosynthesis, spliceosome and nucleotide excision repair were the significantly enriched pathways. In the PPI network, CTSS, CD53, IGSF6, PTPRC and LAPTM5 were the hub nodes. Intracellular protein transport and RNA splicing via transesterification reactions were closely associated with IPD. The DEGs, such as CX3CR1, SLC5A7, CD53 and PTPRC may be the potential targets for IPD diagnosis and treatment.
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Distinguishing Characteristics of Idiopathic Calcium Oxalate Kidney Stone Formers with Low Amounts of Randall's Plaque.
Clin J Am Soc Nephrol
PUBLISHED: 08-04-2014
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Overgrowth of calcium oxalate on Randall's plaque is a mechanism of stone formation among idiopathic calcium oxalate stone-formers (ICSFs). It is less clear how stones form when there is little or no plaque.
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Validation of a serum screen for Alzheimer's disease across assay platforms, species, and tissues.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
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There is a significant need for rapid and cost-effective biomarkers of Alzheimer's disease (AD) for advancement of clinical practice and therapeutic trials.
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Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch?Schönlein purpura in children.
Mol Med Rep
PUBLISHED: 07-01-2014
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The present study aimed to investigate the distribution of paired box 2 (PAX2) gene polymorphisms in healthy populations and in patients with Henoch?Schönlein purpura (HSP), focusing on the association between PAX2 gene polymorphisms and the susceptibility and clinical characteristics of HSP. Genomic DNA was extracted from the peripheral venous blood of 100 healthy children (mean age: 5±1.9 years) and 118 children with HSP (mean age: 10.2±2.3 years). Polymerase chain reaction (PCR) was used to amplify exons 1?12 of the PAX2 gene. Denaturing high performance liquid chromatography and DNA sequencing analysis were conducted for screening of mutations in the PAX2 gene in the PCR products. No genetic polymorphism of the PAX2 gene was identified in exons 1?7, 9, 10 or 12. Two single nucleotide polymorphisms (SNPs), which presented as complete linkage haplotype 798C>T/909A>C, were identified in exon 8. An SNP (1164T>A) was also identified in exon 11. No significant difference in the allele and genotype frequency distribution of exon 8 (798C>T) or 11 (1164T>A) of the PAX2 gene was identified between the HSP and control groups (P>0.05). However, the frequency of the PAX2 heterozygous genotype 798C>T in the HSP with nephritis (HSPN) group was significantly higher than those in the controls and in the HSP without nephritis group (P<0.05). Furthermore, no significant correlation was identified between the PAX2 gene exon 8 polymorphism (798 C>T) and the renal pathology of children with HSPN. An SNP (1164T>A) was identified in exon 11. The PAX2 heterozygous genotype 798C>T did not increase susceptibility to HSP, however, it may be used clinically as a screening indicator for HSP in children with a high risk of renal involvement.
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Nucleic acid aptamers for living cell analysis.
Annu Rev Anal Chem (Palo Alto Calif)
PUBLISHED: 06-02-2014
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Cells as the building blocks of life determine the basic functions and properties of a living organism. Understanding the structure and components of a cell aids in the elucidation of its biological functions. Moreover, knowledge of the similarities and differences between diseased and healthy cells is essential to understanding pathological mechanisms, identifying diagnostic markers, and designing therapeutic molecules. However, monitoring the structures and activities of a living cell remains a challenging task in bioanalytical and life science research. To meet the requirements of this task, aptamers, as "chemical antibodies," have become increasingly powerful tools for cellular analysis. This article reviews recent advances in the development of nucleic acid aptamers in the areas of cell membrane analysis, cell detection and isolation, real-time monitoring of cell secretion, and intracellular delivery and analysis with living cell models. Limitations of aptamers and possible solutions are also discussed.
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[Analysis of reoperation for infertility women with tubal pregnancy after conservative surgery].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-24-2014
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To evaluate the cause of infertility and tubal abnormality in women of tubal pregnancy after conservative treatment with laparotomy or laparoscopy through a combination of laparoscopy, hysteroscopic tubal catheterization and hydrotubation.
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Tumor sites and microscopic indicators are independent prognosis predictors of gastrointestinal stromal tumors.
Tohoku J. Exp. Med.
PUBLISHED: 05-16-2014
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Gastrointestinal stromal tumors (GISTs) are the most common among gastrointestinal mesenchymal tumors, but its prognosis has not been accurately predicted by the current risk stratification guidelines, National Institutes of Health classification. In this study, we evaluated the predictive factors for GIST prognosis in a retrospective analysis of 332 patients. The data collected included tumor sites, including the esophagus, stomach, duodenum, small intestine, and extragastrointestinal sites; tumor size; microscopic indicators for malignant tumor behavior, such as the number of dividing cells, cell necrosis, atypical morphology, and invasion into the muscular or mucous layer; and previously established immunohistochemical indicators, CD117, CD34, and discovered on GIST-1 (DOG-1). No single occurrence of any microscopic indicators correlated with the prognosis of GIST; however, the total number of microscopic indicators was a significant prognostic factor of GIST (P < 0.001). Regarding the tumor sites, the order of prognostic risk (from the lowest to the highest) was as follows: the esophagus, stomach, duodenum, small intestine, extragastrointestinal sites, and colorectum. The association between tumor sites and prognosis was significant (P < 0.001). On the other hand, the expression of CD117 or CD34 was not associated with the risk of GIST. Importantly, 91% of the patients (302/332) showed the expression of DOG-1, and the lack of DOG-1 expression was associated with poor prognosis (P < 0.05). In conclusion, both tumor sites and total number of microscopic indicators are independent risk factors associated with the prognosis of GIST. The lack of DOG-1 expression may be predictive of malignant outcome.
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One-pot and one-step synthesis of bioactive urease/ZnFe?O? nanocomposites and their application in detection of urea.
Dalton Trans
PUBLISHED: 05-14-2014
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This communication describes a novel environmentally friendly method to prepare bioactive urease/ZnFe2O4 nanocomposites through a one-pot and one-step process. The synthetic procedure is triggered through a biological mineralization process of decomposition of urea catalyzed by urease. During the growth of ZnFe2O4, urease molecules are immobilized by original ZnFe2O4 nanoparticles. As a consequence, the bioactive urease/ZnFe2O4 nanoparticle composites are assembled. This simple route is expected to endow the bioactive nanocomposites with new properties for various interesting fields.
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Evaluation of hydrophobic polyvinyl-alcohol formaldehyde sponges as absorbents for oil spill.
ACS Appl Mater Interfaces
PUBLISHED: 05-13-2014
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Macroporous materials are a class of absorbents used for oil spill cleanup. In this article, novel macroporous and hydrophobic polyvinyl formaldehyde (PVF-H) sponges were prepared by the reaction of stearoyl chloride with hydroxyl groups of hydrophilic PVF sponge at different temperatures. Attenuated total reflectance-infrared (ATR-IR) spectroscopy confirmed the successfully anchoring of hydrophobic stearoyl groups on the PVF networks. Scanning electron microscopy (SEM) images demonstrated that the as-prepared PVF-H had interconnected open-cell structures, and mercury intrusion porosimetry indicated that the average pore size ranged from 60 to 90 ?m and porosity was greater than 94.8%. Such PVF-H sponges can absorb oil products effectively, such as toluene, n-hexane, kerosene, soybean oil, hydraulic oil, and crude oil up to 13.7 g·g(-1) to 56.6 g·g(-1), and this level of absorption was approximately 2-4 times higher than that absorbed by commercial polypropylene nonwoven mat. In low-viscosity oils, the samples can reach the saturated absorption amount only in 1 min, but in higher-viscosity oils, absorption equilibrium can be reached in 10 min. In a simulated oil slick system, these macroporous and hydrophobic sponges can still maintain high oil absorption capacities within the range of 14.4 g·g(-1) to 57.6 g·g(-1), whereas a relatively low absorption rate (approximately 20 min) indicated high absorption performance and excellent selectivity in the oil-water mixture. In addition, the absorbed oils were collected effectively only through a simple squeeze. The PVF-H sponges were subjected to 35 absorption-squeeze cycles and exhibited good reusability and 90% recovery for oils. The samples prepared at different temperatures differed in their absorption capacities to some extent. However, this new kind of macroporous and PVF-H sponges had excellent absorption performance on oil products.
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Pedestrian gestures increase driver yielding at uncontrolled mid-block road crossings.
Accid Anal Prev
PUBLISHED: 05-10-2014
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To protect pedestrians, many countries give them priority at uncontrolled mid-block crosswalks or pedestrian crossings. However, the actual driver yielding rate is not always satisfactory (only 3.5% in this study). To increase the yielding rate, this study proposed eleven pedestrian gestures to inform drivers of their intent to cross. The gestures were evaluated based on the process of human interaction with environment. Four gestures were selected as candidates to test in field experiments based on scores for visibility, clarity, familiarity and courtesy (see illustration in Fig. 2): (1) right elbow bent with hands erect and palm facing left (R-bent-erect), (2) left elbow bent with hands level and palm facing left (L-bent-level), (3) left arm extended straight to left side with palm erect facing left (L-straight-erect), and (4) a 'T' gesture for "Time-out". In the experiment, confederate pedestrians waiting at the roadside displayed the gestures (baseline: no gesture) to 420 vehicles at 5 sites in Beijing, China. When pedestrians used the L-bent-level gesture, the vehicle yielding rate more than tripled of that in the baseline condition. The L-bent-level gesture also resulted in a significant decrease in driving with unchanged speed (63.5-38.8%) and had no significant side effects in terms of drivers' horn use or lane changing. The effects of such gestures in other contexts such as when pedestrians are in the crosswalk and when they are interacting with turning vehicles are discussed, together with the applications in training vulnerable pedestrian groups (children or elderly) and facilitating pedestrian detection by drivers.
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[Clinical research of no use of antibiotics in patients undergoing tension-free repair with incarcerated inguinal hernia].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-16-2014
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To explore the safety in inguinal incarcerated hernia repair without use of antibiotics.
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Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice.
J. Exp. Bot.
PUBLISHED: 04-10-2014
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The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3(?NLS)) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3(?NLS) affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency.
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Differential protein accumulations in isolates of the strawberry wilt pathogen Fusarium oxysporum f. sp. fragariae differing in virulence.
J Proteomics
PUBLISHED: 04-02-2014
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This study was conducted to define differences in Fusarium oxysporum f. sp. fragariae (Fof) isolates with different virulence efficiency to strawberry at the proteome level, in combination with their differences in mycelial growth, conidial production and germination. Comparative proteome analyses revealed substantial differences in mycelial proteomes between Fof isolates, where the 54 differentially accumulated protein spots were consistently over-accumulated or exclusively in the highly virulent isolate. These protein spots were identified through MALDI-TOF/TOF mass spectrometry analyses, and the identified proteins were mainly related to primary and protein metabolism, antioxidation, electron transport, cell cycle and transcription based on their putative functions. Proteins of great potential as Fof virulence factors were those involved in ubiquitin/proteasome-mediated protein degradation and reactive oxygen species detoxification; the hydrolysis-related protein haloacid dehalogenase superfamily hydrolase; 3,4-dihydroxy-2-butanone 4-phosphate synthase associated with riboflavin biosynthesis; and those exclusive to the highly virulent isolate. In addition, post-translational modifications may also make an important contribution to Fof virulence.
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Development of a neutralizing mouse-pig chimeric antibody with therapeutic potential against Haemophilus parasuis in Pichia pastoris.
FEMS Microbiol. Lett.
PUBLISHED: 03-02-2014
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Haemophilus parasuis is one of the most important bacterial diseases of pigs worldwide. The lack of a vaccine against a broad spectrum of strains and the limitation of antimicrobial susceptibility hamper the control of disease. In this study, we cloned the constant regions of gamma heavy chains and kappa light chain of pig lymphocytes in frame with the variable regions of heavy and light chains of mouse monoclonal antibody 1D8, which reacts with all 15 serotypes of H. parasuis and has neutralizing activity. The constructed mouse-pig chimeric antibody was expressed in Pichia pastoris. Results demonstrated that the expressed chimeric antibody inhibited the growth of H. parasuis in vitro. Furthermore, the experiments in mice showed that chimeric antibody increased survival rate of the mice compared with that of the control group (P < 0.05). Importantly, the chimeric antibody partially protected piglets against H. parasuis infection according to the clinical lesion scores and PCR results of H. parasuis in the tissues from piglets of the chimeric antibody-inoculated group and the PBS group. In summary, our results demonstrated that the mouse-pig chimeric antibody could be a therapeutic candidate to prevent the H. parasuis infection and control the prevalence of disease.
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Genome-wide analysis reveals divergent patterns of gene expression during zygotic and somatic embryo maturation of Theobroma cacao L., the chocolate tree.
BMC Plant Biol.
PUBLISHED: 02-28-2014
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Theobroma cacao L. is a tropical fruit tree, the seeds of which are used to create chocolate. In vitro somatic embryogenesis (SE) of cacao is a propagation system useful for rapid mass-multiplication to accelerate breeding programs and to provide plants directly to farmers. Two major limitations of cacao SE remain: the efficiency of embryo production is highly genotype dependent and the lack of full cotyledon development results in low embryo to plant conversion rates. With the goal to better understand SE development and to improve the efficiency of SE conversion we examined gene expression differences between zygotic and somatic embryos using a whole genome microarray.
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Novel de novo heterozygous FGFR1 mutation in two siblings with Hartsfield syndrome: a case of gonadal mosaicism.
Am. J. Med. Genet. A
PUBLISHED: 02-26-2014
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Hartsfield syndrome has been recently reported to be associated with mutations in FGFR1 however, to this date; no familial cases have been reported. In this report, we describe two siblings with Hartsfield syndrome and a novel de novo FGFR1 mutation suggesting gonadal mosaicism. The proband presented at our institution at age 6 years with a clinical diagnosis of Hartsfield syndrome and requesting further genetic evaluation. Previous studies included a normal karyotype, oligonucleotide array, and single gene testing for nonsyndromic holoprosencephaly (SHH, SIX3, ZIC2, TGIF). At the age of 6 years, exome sequencing was performed and a de novo novel missense variant was identified in FGFR1 (coding for fibroblast growth factor-1) on chromosome 8p12: c.1880G>C (p.R627T). Subsequently, a younger sibling was born with the same phenotype (holoprosencephaly, ectrodactyly of bilateral hands and feet and bilateral cleft lip and palate). Targeted sequencing of FGFR1 revealed the identical variant that was previously identified in the proband. To our knowledge this observation is the first documentation of familial recurrence of Hartsfield syndrome. As both parents were negative for the sequence variant in FGFR1 gene by testing peripheral blood samples, this suggests gonadal mosaicism. The frequency of gonadal mosaicism in Hartsfield syndrome is not known however given our case, this possibility should be taken in to consideration for recurrence risk estimation in children of clinically unaffected parents.
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Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta.
Sci Rep
PUBLISHED: 02-18-2014
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Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000??g/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application.
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The impact of CDA A79C gene polymorphisms on the response and hematologic toxicity in gemcitabine-treated patients: A meta-analysis.
Int. J. Biol. Markers
PUBLISHED: 02-13-2014
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To investigate the impact of the cytidine deaminase (CDA) A79C polymorphism on both the response to gemcitabine in non-small cell lung cancer (NSCLC) patients and the risk of hematologic toxicities in patients bearing any kind of cancer taking gemcitabine.
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Synthesis of ultra-stable fluorescent carbon dots from polyvinylpyrrolidone and their application in the detection of hydroxyl radicals.
Chem Asian J
PUBLISHED: 02-12-2014
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Highly biocompatible and highly photostable fluorescent carbon dots (C dots) were obtained through a simple and nontoxic one-pot hydrothermal method. Polyvinylpyrrolidone, a common and low-cost biocompatibility reagent, was used as the only carbon source for the first time. The resulting water-soluble C dots showed a quantum yield of up to 23.58% with low cytotoxicity, favorable photoluminescent properties, and good photostability. Importantly, the fluorescence intensities of the C dots were quite stable in high-salt conditions and over a broad pH range (3.0-10.5). The as-prepared C dots have been demonstrated to be an excellent probe for hydroxyl radicals sensing based on the fluorescence quenching with great sensitivity and specificity. This opens up a new application field for C dots.
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Purification of endothelial cells from rat brain.
Methods Mol. Biol.
PUBLISHED: 02-11-2014
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Endothelial cells make up a minor population of cells in a tissue, but play a major role in tissue homeostasis, as well as in diverse pathologies. To understand the biology of cerebral endothelium, purification and characterization of the cerebrocortical endothelial cell population is highly desirable. For this purpose, rat brains are mechanically minced and subsequently digested enzymatically with collagenase. In this protocol, the capillary fraction (microvessels) and the fraction enriched in small arterioles and arteries (resistance vessels) are separated. Each produces its own homogenous endothelial culture, namely, MV-EC and RV-EC. The endothelial origin of these cells is identified by positive immunofluorescent staining for the endothelial cell surface antigen Factor VIII. Unlike MV-EC, RV-EC cultures are capable of serial cultivation for up to 15 passages. Primary MV-ECs are able to retain their characteristic endothelial morphology for 6-8 weeks.
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A new paradigm for the treatment of Alzheimer's disease: targeting vascular activation.
J. Alzheimers Dis.
PUBLISHED: 02-08-2014
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No disease-modifying therapies are currently available for Alzheimer's disease (AD), a neurodegenerative disorder that affects more than 36 million people worldwide. Although cardiovascular risk factors such as hypertension and diabetes are increasingly implicated as contributing to the development of AD, the mechanisms whereby these factors influence pathological processes in the AD brain have not been defined. Here we propose, for the first time, vascular activation as a relevant mechanism in AD pathogenesis. We explore this hypothesis in two transgenic AD animal models: AD2576APPSwe (AD2576) and LaFerla 3xTg (3xTgAD) mice using the vascular activation inhibitor sunitinib. Our data show that in both AD animal models, the cerebrovasculature is activated and overexpresses amyloid beta, thrombin, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and matrix metalloproteinase 9. Oral administration of sunitinib significantly reduces vascular expression of these proteins. Furthermore, sunitinib improves cognitive function, as assessed by several behavioral paradigms, in both AD animal models. Finally, oxidant injury of brain endothelial cells in culture, resulting in expression of inflammatory proteins, is mitigated by sunitinib. The current data, as well as published studies showing cerebrovascular activation in human AD, support further exploration of vascular-based mechanisms in AD pathogenesis. New thinking about AD pathogenesis and novel, effective treatments are urgently needed. Identification of "vascular activation" as a heretofore unexplored target could stimulate translational investigations in this newly defined area, leading to innovative therapeutic approaches for the treatment of this devastating disease.
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Alcohol and mortality in Russia: prospective observational study of 151,000 adults.
Lancet
PUBLISHED: 01-31-2014
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Russian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50,000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations.
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Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers.
Neurology
PUBLISHED: 01-29-2014
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To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging ((1)H MRSI) and to assess their potential as prognostic biomarkers.
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Sex differences in cerebral energy metabolism in Parkinson's disease: a phosphorus magnetic resonance spectroscopic imaging study.
Parkinsonism Relat. Disord.
PUBLISHED: 01-27-2014
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To test the hypothesis that there are sex differences in cerebral energy metabolism in Parkinson's disease (PD).
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Progression of IgA nephropathy under current therapy regimen in a Chinese population.
Clin J Am Soc Nephrol
PUBLISHED: 01-09-2014
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Current therapy for IgA nephropathy mainly includes renin-angiotensin system inhibitors and adding steroids for patients with persistent proteinuria. This study aimed to evaluate kidney disease progression and its risk factors in a Chinese cohort under current therapy.
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The pseudogene TUSC2P promotes TUSC2 function by binding multiple microRNAs.
Nat Commun
PUBLISHED: 01-08-2014
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Various non-coding regions of the genome, once presumed to be 'junk' DNA, have recently been found to be transcriptionally active. In particular, pseudogenes are now known to have important biological roles. Here we report that transcripts of the two tumour suppressor candidate-2 pseudogenes (TUSC2P), found on chromosomes X and Y, are homologous to the 3'-UTR of their corresponding protein coding transcript, TUSC2. TUSC2P and the TUSC2 3'-UTR share many common miRNA-binding sites, including miR-17, miR-93, miR-299-3p, miR-520a, miR-608 and miR-661. We find that ectopic expression of TUSC2P and the TUSC2 3'-UTR inhibits cell proliferation, survival, migration, invasion and colony formation, and increases tumour cell death. By interacting with endogenous miRNAs, TUSC2P and TUSC2 3'-UTR arrest the functions of these miRNAs, resulting in increased translation of TUSC2. The TUSC2P and TUSC2 3'-UTR could thus be used as combinatorial miRNA inhibitors and might have clinical applications.
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In vivo (1)H MRS study of potential associations between glutathione, oxidative stress and anhedonia in major depressive disorder.
Neurosci. Lett.
PUBLISHED: 01-06-2014
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Inflammation and oxidative stress are important mechanisms that have been implicated in the pathophysiology of major depressive disorder (MDD). Glutathione (GSH) is the most abundant antioxidant in human tissue, and a key index of antioxidant capacity and, hence, of oxidative stress. The aims of this investigation were to examine possible relationships between occipital GSH and dimensional measures of depressive symptom severity, including anhedonia - the reduced capacity to experience pleasure - and fatigue. We hypothesized that the magnitude of anhedonia and fatigue will be negatively correlated with occipital GSH levels in subjects with MDD and healthy controls (HC). Data for eleven adults with MDD and ten age- and sex-matched HC subjects were included in this secondary analysis of data from a previously published study. In vivo levels of GSH in a 3cm×3cm×2cm voxel of occipital cortex were obtained by proton magnetic resonance spectroscopy ((1)H MRS) on a 3T MR system, using the standard J-edited spin-echo difference technique. Anhedonia was assessed by combining interest items from depression and fatigue rating scales, and fatigue by use of the multidimensional fatigue inventory. Across the full sample of participants, anhedonia severity and occipital GSH levels were negatively correlated (r=-0.55, p=0.01). No associations were found between fatigue severity and GSH in this sample. These preliminary findings are potentially consistent with a pathophysiological role for GSH and oxidative stress in anhedonia and MDD. Larger studies in anhedonic depressed patients are indicated.
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GABA level, gamma oscillation, and working memory performance in schizophrenia.
Neuroimage Clin
PUBLISHED: 01-01-2014
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A relationship between working memory impairment, disordered neuronal oscillations, and abnormal prefrontal GABA function has been hypothesized in schizophrenia; however, in vivo GABA measurements and gamma band neural synchrony have not yet been compared in schizophrenia. This case-control pilot study (N = 24) compared baseline and working memory task-induced neuronal oscillations acquired with high-density electroencephalograms (EEGs) to GABA levels measured in vivo with magnetic resonance spectroscopy. Working memory performance, baseline GABA level in the left dorsolateral prefrontal cortex (DLPFC), and measures of gamma oscillations from EEGs at baseline and during a working memory task were obtained. A major limitation of this study is a relatively small sample size for several analyses due to the integration of diverse methodologies and participant compliance. Working memory performance was significantly lower for patients than for controls. During the working memory task, patients (n = 7) had significantly lower amplitudes in gamma oscillations than controls (n = 9). However, both at rest and across working memory stages, there were significant correlations between gamma oscillation amplitude and left DLPFC GABA level. Peak gamma frequency during the encoding stage of the working memory task (n = 16) significantly correlated with GABA level and working memory performance. Despite gamma band amplitude deficits in patients across working memory stages, both baseline and working memory-induced gamma oscillations showed strong dependence on baseline GABA levels in patients and controls. These findings suggest a critical role for GABA function in gamma band oscillations, even under conditions of system and cognitive impairments as seen in schizophrenia.
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Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight.
Neuroimage Clin
PUBLISHED: 01-01-2014
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We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS).
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Identification of a novel Haemophilus parasuis-specific B cell epitope using monoclonal antibody against the OppA protein.
PLoS ONE
PUBLISHED: 01-01-2014
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Monoclonal antibody (MAb) 1B3 against Haemophilus parasuis (H. parasuis) was generated by fusing SP2/0 murine myeloma cells and spleen cells from BALB/c mice immunized with the whole-bacterial-cell suspension of H. parasuis HS80 (serotype 5). The MAb 1B3 showed strong reactivity with 15 serotype reference strains of H. parasuis using Dot blot and Western blot analysis. Immunoprecipitation and protein spectral analysis indicated that MAb 1B3 recognized by Oligopeptide permease A (OppA) belongs to the ATP binding cassette transporter family. In addition, a linear B-cell epitope recognized by MAb 1B3 was identified by the screening of a phage-displayed 12-mer random peptide library. Sequence analysis showed that MAb 1B3 was recognized by phages-displaying peptides with the consensus motif KTPSEXR (X means variable amino acids). Its amino acid sequence matched (469)KTPAEAR(475) of H. parasuis OppA protein. A series of progressively truncated peptides were synthesized to define the minimal region that was required for MAb 1B3 binding. The epitope was highly conserved in OppA protein sequences from the isolated H. parasuis strains, which was confirmed by alignment analysis. Furthermore, the minimal linear epitope was highly specific among 75 different bacterial strains as shown in sequence alignments. These results indicated MAb 1B3 might be potentially used to develop serological diagnostic tools for H. parasuis.
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Glycogen synthase kinase 3 promotes p53 mRNA translation via phosphorylation of RNPC1.
Genes Dev.
PUBLISHED: 10-22-2013
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The RNPC1 RNA-binding protein, also called Rbm38, is a target of p53 and a repressor of p53 mRNA translation. Thus, the p53-RNPC1 loop is critical for modulating p53 tumor suppression, but it is not clear how the loop is regulated. Here, we showed that RNPC1 is phosphorylated at Ser195 by glycogen synthase kinase 3 (GSK3). We also showed that GSK3 promotes p53 mRNA translation through phosphorylation of RNPC1. Interestingly, we found that the phosphor-mimetic mutant S195D and the deletion mutant ?189-204, which lacks the GSK3 phosphorylation site, are unable to repress p53 mRNA translation due to loss of interaction with eukaryotic translation factor eIF4E on p53 mRNA. Additionally, we found that phosphorylated RNPC1, RNPC1-S195D, and RNPC1(?189-204) promote p53 mRNA translation through interaction with eukaryotic translation factor eIF4G, which then facilitates the assembly of the eIF4F complex on p53 mRNA. Furthermore, we showed that upon inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, GSK3 is activated, leading to increased RNPC1 phosphorylation and increased p53 expression in a RNPC1-dependent manner. Together, we postulate that the p53-RNPC1 loop can be explored to increase or decrease p53 activity for cancer therapy.
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Sensitive and selective detection of Hg2+ and Cu2+ ions by fluorescent Ag nanoclusters synthesized via a hydrothermal method.
Nanoscale
PUBLISHED: 09-24-2013
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An easily prepared fluorescent Ag nanoclusters (Ag NCs) probe for the sensitive and selective detection of Hg(2+) and Cu(2+) ions was developed here. The Ag NCs were synthesized by using polymethacrylic acid sodium salt as a template via a convenient hydrothermal process. The as-prepared fluorescent Ag NCs were monodispersed, uniform and less than 2 nm in diameter, and can be quenched in the presence of mercury (Hg(2+)) or copper (Cu(2+)) ions. Excellent linear relationships existed between the quenching degree of the Ag NCs and the concentrations of Hg(2+) or Cu(2+) ions in the range of 10 nM to 20 ?M or 10 nM to 30 ?M, respectively. By using ethylenediaminetetraacetate (EDTA) as the masking agent of Cu(2+), Hg(2+) was exclusively detected in coexistence with Cu(2+) with high sensitivity (LOD = 10 nM), which also provided a reusable detection method for Cu(2+). Furthermore, the different quenching phenomena caused by the two metals ions such as changes in visible colour, shifts of UV absorbance peaks and changes in size of Ag NCs make it easy to distinguish between them. Therefore the easily synthesized fluorescent Ag NCs may have great potential as Hg(2+) and Cu(2+) ions sensors.
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A new amperometric glucose biosensor based on one-step electrospun poly(vinyl alcohol)/chitosan nanofibers.
J Biomed Nanotechnol
PUBLISHED: 09-11-2013
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In this work, a new glucose amperometric biosensor was developed by directly electrospinning poly(vinyl alcohol)/chitostan nanofibers on the surface of the platinum electrode, in which glucose oxidase (GOD) was effectively immobilized in nanofibers by encapsulation. After been cross-linked in glutaraldehyde vapor and modified with a thin nafion film, the nanofibers (PVA/chitosan/GOD)/nafion electrode was used for glucose amperometric measurements. The electrospun nanofibrous enzyme membrane served as a better sensing element than the casing one due to the unique properties of nanofibers such as the special three-dimensional network structure, large pores, high porosity, and large surface to volume ratios. The as-prepared biosensor showed a wide linear calibration range, low detection limit, and low apparent Michaelis-Menten constant in the glucose determination. The stability, reproducibility and anti-interference capability of biosensor were also presented. Furthermore, the new biosensor was successfully applied to detect glucose in human serum samples.
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Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion.
Nucleic Acids Res.
PUBLISHED: 08-28-2013
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MicroRNAs (miRNA) precursor (pre-miRNA) molecules can be processed to release a miRNA/miRNA* duplex. In the canonical model of miRNA biogenesis, one strand of the duplex is thought to be the biologically active miRNA, whereas the other strand is thought to be inactive and degraded as a carrier or passenger strand called miRNA* (miRNA star). However, recent studies have revealed that miRNA* strands frequently play roles in the regulatory networks of miRNA target molecules. Our recent study indicated that miR-17 transgenic mice could abundantly express both the mature miR-17-5p and the passenger strand miR-17-3p. Here, we showed that miR-17 enhanced prostate tumor growth and invasion by increasing tumor cell proliferation, colony formation, cell survival and invasion. miRNA target analysis showed that both miR-17-5p and miR-17-3p repressed TIMP metallopeptidase inhibitor 3 (TIMP3) expression. Silencing with small interfering RNA against TIMP3 promoted cell survival and invasion. Ectopic expression of TIMP3 decreased cell invasion and cell survival. Our results demonstrated that mature miRNA can function coordinately with its passenger strand, enhancing the repressive ability of a miRNA by binding the same target. Within an intricate regulatory network, this may be among the mechanisms by which miRNA can augment their regulatory capacity.
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MiR-200, a new star miRNA in human cancer.
Cancer Lett.
PUBLISHED: 08-22-2013
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MicroRNAs (miRNAs) are a set of non-coding small RNA molecules in control of gene expression at posttranscriptional/translational level. They not only play crucial roles in normal developmental progress, but also are commonly dysregulated in human diseases, including cancer. MiR-200 is a family of tumor suppressor miRNAs consisting of five members, which are significantly involved in inhibition of epithelial-to-mesenchymal transition (EMT), repression of cancer stem cells (CSCs) self-renewal and differentiation, modulation of cell division and apoptosis, and reversal of chemoresistance. In this article, we summarize the latest findings with regard to the tumor suppressor signatures of miR-200 and the regulatory mechanisms of miR-200 expression. The collected evidence supports that miR-200 is becoming a new star miRNA in study of human cancer.
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Reversing Multidrug-Resistant by RNA Interference Through Silencing MDR1 Gene in Human Hepatocellular Carcinoma Cells Subline Bel-7402/ADM.
Pathol. Oncol. Res.
PUBLISHED: 08-06-2013
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Multidrug resistance (MDR) in hepatocellular carcinoma (HC) significantly impedes the effect of chemotherapy and is considered as a primary reason leading to its recurrences and metastasis. The aim of present study was to explore new molecular targets for the reversal of MDR in HC by screening the adriamycin (ADM)-induced, human MDR-resistant HC cell subline Bel-7402/ADM. Small interfering RNAs (siRNAs) of four (MDR1si326, MDR1si1513, MDR1si2631 and MDR1si3071) targeting MDR1 were designed and transfected into Bel-7402/ADM cell strains. The experiments involved the following: mRNA expression of MDR1 gene by RT-PCR, P-glycoprotein (P-gp) expression by Western blot, intracellular ADM accumulation flow cytometry, and IC50 of ADM by a cytotoxic MTT assay. Four siRNAs reversed MDR in HC mediated by MDR1 to varying degrees. The expression level of MDR1 mRNA in cells of MDR1si326 or MDR1si2631 group (0.190?±?0.038 or 0.171?±?0.011) was more decreased. The expression level of P-gp in cells of MDR1si326 group was the lowest. The accumulation of ADM in cells of MDR1si326 or MDR1si2631 group (77.0?±?3.5 or 75.4?±?2.9) was more increased. The IC50 of cells to ADM was lowest in MDR1si326 group (11.32?±?0.69 mg/L). Compared with other three siRNAs, MDR1si326 performed the optimal reversal effect of drug resistance in human HC Bel-7402/ADM.
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Brittle Culm1, a COBRA-like protein, functions in cellulose assembly through binding cellulose microfibrils.
PLoS Genet.
PUBLISHED: 08-01-2013
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Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity.
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An eco-friendly, simple, and sensitive fluorescence biosensor for the detection of choline and acetylcholine based on C-dots and the Fenton reaction.
Biosens Bioelectron
PUBLISHED: 07-31-2013
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A simple and novel method is proposed for the preparation of Carbon dots (C-dots) with excellent properties. We firstly demonstrated that the fluorescence of C-dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this finding, C-dots are successfully adopted as probes for the detection of H2O2. After the experimental conditions are optimized, the limit of detection (LOD) for H2O2 is found to be 0.1 ?M. Furthermore, we established an eco-friendly, simple and sensitive biosensor for the detection of choline and acetylcholine (ACh) based on the detection of H2O2 using C-dots as probes. The detection limit for choline is 0.1 ?M and the linear range is 0.1-40 ?M. The detection limit for ACh is found to be 0.5 ?M and the linear range is 0.5-60 ?M. The excellent performance of the proposed biosensor shows that this method possesses the potential for practical application.
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Preparation of magnetic rattle-type silica through a general and facile pre-shell-post-core process for simultaneous cancer imaging and therapy.
Chem. Commun. (Camb.)
PUBLISHED: 07-30-2013
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Here we report a novel pre-shell-post-core method for the fabrication of monodispersed magnetic rattle-type silica (MRS) through an entrapment process, which could be used as a promising theranostic agent for simultaneous magnetic resonance imaging and drug delivery.
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Association between elevated visfatin and carotid atherosclerosis in patients with chronic kidney disease.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 07-06-2013
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To determine the levels of visfatin in patients with chronic kidney disease (CKD) and to explore the relationship between visfatin levels and caroid atherosclerosis in CKD patients.
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Cyclic AMP-Dependent Protein Kinase Enhances SC35-Promoted Tau Exon 10 Inclusion.
Mol. Neurobiol.
PUBLISHED: 06-25-2013
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Alternative splicing of tau exon 10 generates tau with three or four microtubule-binding repeats (3R-tau or 4R-tau). The ratio of 3R-tau to 4R-tau is approximately 1:1 in the adult normal human brain. Disturbances in the ratio result in neurodegenerative tauopathies. Splicing factor SC35 acts on a SC35-like element located at the 5 end of tau exon 10 and promotes tau exon 10 inclusion. Here, we report that protein kinase (PKA) was able to interact and phosphorylate SC35. Activation or overexpression of PKA catalytic subunits promoted SC35-mediated tau exon 10 inclusion. Four PKA catalytic subunits, ?1, ?2, ?1, and ?2, all enhanced SC35-promoted tau exon 10 inclusion. SC35 has four putative PKA phosphorylation sites, Ser121, Ser128, Ser130, and Ser171. Pseudophosphorylation (SC354E) and blockage (SC354A) of phosphorylation of SC35 at these four sites increased and decreased, respectively, SC35s ability to promote tau exon 10 inclusion. Moreover, PKA catalytic subunits no longer further enhanced tau exon 10 inclusion when these four were mutated to either alanine or glutamate. These results suggest that PKA interacts with and phosphorylates SC35 and enhances SC35-promoted tau exon 10 inclusion. In Alzheimers brain, down-regulation of the PKA pathway could lead to dysregulation of tau exon 10, contributing to tau pathogenesis.
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Modifying cellular properties using artificial aptamer-lipid receptors.
Sci Rep
PUBLISHED: 06-21-2013
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We demonstrate that artificial aptamer-lipid receptors (AR), which anchor on the surface of cells, can modify important cellular functions, including protein binding, enzymatic activity, and intercellular interactions. Streptavidin (SA)-AR-modified CEM cells captured the tetravalent SA with one biotin binding site. The remaining biotin sites captured biotinylated TDO5 aptamers, which target IgM on Ramos cells, to form CEM-Ramos cell assemblies. In another design, thrombin, an enzyme involved in blood clotting, was captured by thrombin-AR-modified cells and clot formation was visualized. Lastly, hematopoietic stem cell (HSC) mimics were modified with a tenascin-C-AR to improve the homing of HSC after an autologous bone marrow transplant. Tenascin-C-AR modified cells aggregated to cells in a tenascin-C expressing stem cell niche model better than library-AR modified cells. Modification of cellular properties using ARs is a one-step, dosable, nontoxic, and reversible method, which can be applied to any cell-type with any protein that has a known aptamer.
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Engineering of switchable aptamer micelle flares for molecular imaging in living cells.
ACS Nano
PUBLISHED: 06-14-2013
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Simultaneous monitoring of the expression, distribution, and dynamics of biological molecules in living cells is one of the most challenging tasks in the analytical sciences. The key to effective and successful intracellular imaging is the development of delivery platforms with high efficiency and ultrasensitive molecular probes for specific targets of interest. To achieve these goals, many nanomaterials are widely used as carriers to introduce nucleic acid probes into living cells for real-time imaging of biomolecules. However, limitations on their use include issues of cytotoxicity and delivery efficiency. Herein, we propose a switchable aptamer micelle flare (SAMF), formed by self-assembly of an aptamer switch probe-diacyllipid chimera, to monitor ATP molecules inside living cells. Similarity of hydrophobic composition between diacyllipids in the micelle flares and phospholipid bilayers in the dynamic membranes of living cells allows SAMFs to be uptaken by living cells more efficiently than aptamer switch probes without external auxiliary. Switchable aptamers were found to bind target ATP molecules with high selectivity and specificity, resulting in restoration of the fluorescence signal from "OFF" to "ON" state, thus indicating the presence of the analyte. These switchable aptamer micelle flares, which exhibit cell permeability and nanoscale controllability, show exceptional promise for molecular imaging in bioanalysis, disease diagnosis, and drug delivery.
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Aortic cholesterol accumulation correlates with systemic inflammation but not hepatic and gonadal adipose tissue inflammation in low-density lipoprotein receptor null mice.
Nutr Res
PUBLISHED: 06-13-2013
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Inflammation is a major contributor to the development of atherosclerotic plaque, yet the involvement of liver and visceral adipose tissue inflammatory status in atherosclerotic lesion development has yet to be fully elucidated. We hypothesized that an atherogenic diet would increase inflammatory response and lipid accumulation in the liver and gonadal adipose tissue (GAT) and would correlate with systemic inflammation and aortic lesion formation in low-density lipoprotein (LDL) receptor null (LDLr-/-) mice. For 32 weeks, LDLr-/- mice (n = 10/group) were fed either an atherogenic (high saturated fat and cholesterol) or control (low fat and cholesterol) diet. Hepatic and GAT lipid content and expression of inflammatory factors were measured using standard procedures. Compared with the control diet, the atherogenic diet significantly increased hepatic triglyceride and total cholesterol (TC), primarily esterified cholesterol, and GAT triglyceride content. These changes were accompanied by increased expression of acyl-CoA synthetase long-chain family member 5, CD36, ATP-binding cassette, subfamily A, member 1 and scavenger receptor B class 1, and they decreased the expression of cytochrome P450, family 7 and subfamily a, polypeptide 1 in GAT. Aortic TC content was positively associated with hepatic TC, triglyceride, and GAT triglyceride contents as well as plasma interleukin 6 and monocyte chemoattractant protein-1 concentrations. Although when compared with the control diet, the atherogenic diet increased hepatic tumor necrosis factor ? production, they were not associated with aortic TC content. These data suggest that the LDLr-/- mice responded to the atherogenic diet by increasing lipid accumulation in the liver and GAT, which may have increased inflammatory response. Aortic TC content was positively associated with systemic inflammation but not hepatic and GAT inflammatory status.
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Sunitinib enhances neuronal survival in vitro via NF-?B-mediated signaling and expression of cyclooxygenase-2 and inducible nitric oxide synthase.
J Neuroinflammation
PUBLISHED: 06-07-2013
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Angiogenesis is tightly linked to inflammation and cancer. Regulation of angiogenesis is mediated primarily through activation of receptor tyrosine kinases, thus kinase inhibitors represent a new paradigm in anti-cancer therapy. However, these inhibitors have broad effects on inflammatory processes and multiple cell types. Sunitinib is a multitarget receptor tyrosine kinase inhibitor, which has shown promise for the treatment of glioblastoma, a highly vascularized tumor. However, there is little information as to the direct effects of sunitinib on brain-derived neurons. The objective of this study is to explore the effects of sunitinib on neuronal survival as well as on the expression of inflammatory protein mediators in primary cerebral neuronal cultures.
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Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma.
Mol. Cancer
PUBLISHED: 05-31-2013
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Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and Southeast Asia, but its molecular mechanisms of pathogenesis are poorly understood. Our previous work has demonstrated that BCAT1 mRNA is over expressed in NPC and knocking down its expression in 5-8F NPC cell line can potently inhibit cell cycle progression and cell proliferation. However, the mechanism of BCAT1 up-regulation and its functional role in NPC development remain to be elucidated yet.
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Usefulness of Proton and Phosphorus MR Spectroscopic Imaging for Early Diagnosis of Parkinsons Disease.
J Neuroimaging
PUBLISHED: 05-26-2013
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Cerebral mitochondrial dysfunction has been observed in Parkinsons disease (PD). If mitochondrial dysfunction is an early event contributing to PD development, then noninvasive techniques that detect disturbed energy metabolism in vivo might be useful tools for early diagnosis and treatment monitoring. In the present study, we tested the hypothesis that proton ((1) H) and phosphorus ((31) P) magnetic resonance spectroscopy (MRS) measures of brain metabolites are able to differentiate between individuals with early PD and healthy volunteers (HVs).
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Plasma proteins adsorption mechanism on polyethylene-grafted poly(ethylene glycol) surface by quartz crystal microbalance with dissipation.
Langmuir
PUBLISHED: 05-23-2013
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Protein adsorption has a vital role in biomaterial surface science because it is directly related to the hemocompatibility of blood-contacting materials. In this study, monomethoxy poly(ethylene glycol) (mPEG) with two different molecular weights was grafted on polyethylene as a model to elucidate the adsorption mechanisms of plasma protein through quartz crystal microbalance with dissipation (QCM-D). Combined with data from platelet adhesion, whole blood clotting time, and hemolysis rate, the blood compatibility of PE-g-mPEG film was found to have significantly improved. Two adsorption schemes were developed for real-time monitoring of protein adsorption. Results showed that the preadsorbed bovine serum albumin (BSA) on the surfaces of PE-g-mPEG films could effectively inhibit subsequent adsorption of fibrinogen (Fib). Nonspecific protein adsorption of BSA was determined by surface coverage, not by the chain length of PEG. Dense PEG brush could release more trapped water molecules to resist BSA adsorption. Moreover, the preadsorbed Fib could be gradually displaced by high-concentration BSA. However, the adsorption and displacement of Fib was determined by surface hydrophilicity.
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Responsive DNA-based hydrogels and their applications.
Macromol Rapid Commun
PUBLISHED: 05-17-2013
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The term hydrogel describes a type of soft and wet material formed by cross-linked hydrophilic polymers. The distinct feature of hydrogels is their ability to absorb a large amount of water and swell. The properties of a hydrogel are usually determined by the chemical properties of their constituent polymer(s). However, a group of hydrogels, called "smart hydrogels," changes properties in response to environmental changes or external stimuli. Recently, DNA or DNA-inspired responsive hydrogels have attracted considerable attention in construction of smart hydrogels because of the intrinsic advantages of DNA. As a biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by Watson-Crick base pairing. DNA can form a hydrogel by itself under certain conditions, and it can also be incorporated into synthetic polymers to form DNA-hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide additional molecular recognition capabilities and versatility. In this Review, DNA-based hydrogels are discussed in terms of their stimulus response, as well as their applications.
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DNA branch migration reactions through photocontrollable toehold formation.
J. Am. Chem. Soc.
PUBLISHED: 05-16-2013
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Strand displacement cascades are commonly used to make dynamically assembled structures. Particularly, the concept of "toehold-mediated DNA branch migration reactions" has attracted considerable attention in relation to dynamic DNA nanostructures. However, it is a challenge to obtain and control the formation of pure 1:1 ratio DNA duplexes with toehold structures. Here, for the first time, we report a photocontrolled toehold formation method, which is based on the photocleavage of 2-nitrobenzyl linker-embedded DNA hairpin precursor structures. UV light irradiation (? ? 365 nm) of solutions containing these DNA hairpin structures causes the complete cleavage of the nitrobenzyl linker, and pure 1:1 DNA duplexes with toehold structures are easily formed. Our experimental results indicate that the amount of toehold can be controlled by simply changing the dose of UV irradiation and that the resulting toehold structures can be used for subsequent toehold-mediated DNA branch migration reactions, e.g., DNA hybridization chain reactions. This newly established method will find broad application in the construction of light-powered, controllable, and dynamic DNA nanostructures or large-scale DNA circuits.
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Specificity of miR-378a-5p targeting rodent fibronectin.
Biochim. Biophys. Acta
PUBLISHED: 05-13-2013
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One criterion for microRNA identification is based on their conservation across species, and prediction of miRNA targets by empirical approaches using computational analysis relies on the presence of conservative mRNA 3UTR. Because most miRNA target sites identified are highly conserved across different species, it is not clear whether miRNA targeting is species-specific. To predict miRNA targeting, we aligned all available fibronectin 3UTRs and observed significant conservation of all 20 species. Twelve miRNAs were predicted to target most fibronectin 3UTRs, but rodent fibronectin showed potential binding sites specific for five different miRNAs. One of them, the miR-378a-5p, contained a complete matching seed-region for all rodent fibronectin, which could not be found in any other species. We designed experiments to test whether the species-specific targeting possessed biological function and found that expression of miR-378a-5p decreased cancer cell proliferation, migration, and invasion, resulting in inhibition of tumor growth. Silencing fibronectin expression produced similar effects as miR-378a-5p, while transfection with a construct targeting miR-378-5p produced opposite results. Tumor formation assay showed that enhanced expression of fibronectin in the stromal tissues as a background environment suppressed tumor growth, while increased fibronectin expression inside the tumor cells promoted tumor growth. This was likely due to the different signaling direction, either inside-out or outside-in signal. Our results demonstrated that species-specific targeting by miRNA could also exert functional effects. Thus, one layer of regulation has been added to the complex network of miRNA signaling.
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Wnt signaling pathways participate in Astragalus injection-induced differentiation of bone marrow mesenchymal stem cells.
Neurosci. Lett.
PUBLISHED: 05-06-2013
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Bone marrow mesenchymal stem cells (MSCs) have the capacity for self-renewal and multi-directional differentiation, and MSCs can differentiate into neuron-like cells under certain conditions. In this study, we used the traditional Chinese medicine Astragalus as an inducer. After 7 days of induction, the expression of specific markers was detected in each induced group by immunocytochemical staining. The results of real-time quantitative PCR and Western blot confirmed the immunocytochemistry analysis. We also tested some key genes and proteins of the Wnt signaling pathway, and found that they were increased in Astragalus-treated groups. After treatment with lithium chloride (LiCl), the protein expression of phospho GSK-3? and ?-catenin was increased in each group compared to the corresponding group without LiCl. These findings demonstrate that Astragalus injection can induce differentiation of MSCs into neuron-like cells and suggest that the process of differentiation might be mediated by activation of Wnt signaling pathways.
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Highly H2O2-sensitive electrospun quantum dots nanocomposite films for fluorescent biosensor.
J Biomed Nanotechnol
PUBLISHED: 05-01-2013
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Bright CdSe quantum dots (QDs)/polycaprolactone (PCL) nanocomposite fluorescent films were fabricated by electronspinning. By using chloroform and N,N-dimethylformamide as electronspinning solvent, the oil-soluble CdSe QDs were uniformly distributed in PCL fibers, and were directly employed as optical probe without any modification processing. The fluorescences of CdSe QDs/PCL nanocomposite films were quickly quenched when the films were contacted with H2O2, solution. In the presence of glucose oxidase (GOD), the fluorescence intensities of these fluorescent films exhibit a liner change with the concentrations of glucose. The H2O2-sensitive electrospun QDs nanocomposite films are highly uniform and repeatable, demonstrating the potential to fabricate stable, sensitive and recyclable fluorescent biosensor for the detection different H2O2-generating oxidases and their substrates.
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Advanced glycation endproducts induce fibrogenic activity in nonalcoholic steatohepatitis by modulating TNF-?-converting enzyme activity in mice.
Hepatology
PUBLISHED: 04-23-2013
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Advanced glycation endproducts (AGEs) accumulate in patients with diabetes, yet the link between AGEs and inflammatory and fibrogenic activity in nonalcoholic steatohepatitis (NASH) has not been explored. Tumor necrosis factor alpha (TNF-?)-converting enzyme (TACE) is at the center of inflammatory processes. Because the main natural regulator of TACE activity is the tissue inhibitor of metalloproteinase 3 (Timp3), we hypothesized that AGEs induce TACE through nicotinamide adenine dinucleotide phosphate reduced oxidase 2 (NOX2); and the down-regulation of Sirtuin 1 (Sirt1)/Timp3 pathways mediate fibrogenic activity in NASH. The role of NOX2, Sirt1, Timp3, and TACE was evaluated in choline-deficient L-amino acid defined (CDAA) or Western diet (WD)-fed wild-type (WT) and NOX2(-/-) mice. To restore Timp3, mice were injected with adenovirus (Ad)-Timp3. Sirt1 and Timp3 expressions were studied in livers from NASH patients, and we found that their levels were significantly lower than in healthy controls. In WT mice on the CDAA or WD, Sirt1 and Timp3 expressions were lower, whereas production of reactive oxidative species and TACE activity significantly increased with an increase in active TNF-? production as well as induction of fibrogenic transcripts. Ad-Timp3 injection resulted in a significant decline in TACE activity, procollagen ?1 (I), alpha smooth muscle actin (?-SMA) and transforming growth factor beta (TGF-?) expression. NOX2(-/-) mice on the CDAA or WD had no significant change in Sirt1, Timp3, and TACE activity or the fibrosis markers assessed. In vitro, AGE exposure decreased Sirt1 and Timp3 in hepatic stellate cells by a NOX2-dependent pathway, and TACE was induced after exposure to AGEs. Conclusion: TACE activation is central to the pathogenesis of NASH and is mediated by AGEs through NOX2 induction and down-regulation of Sirt1/Timp3 pathways.
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Identification, expression and subcellular localization of ESRG.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-16-2013
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ESRG (embryonic stem cell related gene, also known as HESRG), is a novel human gene first cloned and identified by our group with microarray analysis. Interestingly, it is expressed specifically in undifferentiated human embryonic stem cells (hESCs), while its expression pattern and its role in hESCs remain unclear. Here, full-length 3151nt ESRG cDNA was further identified by RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) technique. Meanwhile, an alternatively splicing ESRG transcript (ESRG-B) of 2837nt in length was also found. Surprisingly, bioinformatics analyses showed that the open reading frames (ORFs) of ESRG and ESRG-B were identical. Both of them consist of 669nt and encode a 222aa protein with a predicted molecular size of 24 kDa. The ESRG protein was located in the nuclei of hESCs as demonstrated by immunocytochemical staining and Western blotting using ESRG specific antibody generated by us. In contrast, ESRG located in the cytoplasm of COS7 cells when it was forced to be expressed in these cells by gene transfection strategy, suggesting there may be some special proteins present only in hESCs which can help ESRG protein transport into the nuclei of hESCs. By spatial expression analysis, we further discovered that ESRG only expressed in the ovary tissue and hESCs instead of other tissues or cell lines. Our current data provide us with an important basis for conducting further studies on the functions and regulatory mechanisms underlying the role of ESRG in hESCs.
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Fe3O4-Au@mesoporous SiO2 microspheres: an ideal artificial enzymatic cascade system.
Chem. Commun. (Camb.)
PUBLISHED: 04-12-2013
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An artificial enzymatic cascade system with high activity and stability is engineered based on Fe3O4-Au@mesoporous SiO2 (MS) microspheres, which possess both intrinsic glucose oxidase (GOx)- and peroxidase-mimic activities.
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Misprocessing and functional arrest of microRNAs by miR-Pirate: roles of miR-378 and miR-17.
Biochem. J.
PUBLISHED: 04-12-2013
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miRNAs (microRNAs) are short non-coding RNAs that can regulate gene expression in cancer development, which makes them valuable targets for therapeutic intervention. In the present study we report on an approach that can not only arrest the functions of mature miRNAs by binding to them, but it can also induce the mis-processing of the target miRNA, producing a non-functional truncated miRNA. This approach involves generating an expression construct that produces an RNA fragment with 16 repeat sequences. The construct is named miR-Pirate (miRNA-interacting RNA-producing imperfect RNA and tangling endogenous miRNA). The transcript of the construct contained mismatches to the seed region, and thus it would not target the potential targets of the miRNA under study. The homology of the construct is sufficiently high, allowing the transcript to block miRNA functions. The functions of the construct were validated in cell cultures, in tumour formation assays and in transgenic mice stably expressing this construct. To explore the possibility of adopting this approach in gene therapy, we transfected cells with synthetic miR-Pirate and obtained the results we expected. The miR-Pirate, expressed by the construct or synthesized chemically, was found to be able to specifically pirate and silence a mature miRNA through its dual roles and thus could be clinically applied for miRNA intervention.
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Promoter Hypermethylation Along With LOH, But Not Mutation, Contributes to Inactivation of DLC-1 in Nasopharyngeal Carcinoma.
Mol. Carcinog.
PUBLISHED: 04-08-2013
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Previous studies have shown that promoter hypermethylation plays a key role in DLC-1 inactivation in nasopharyngeal carcinoma (NPC). However, DLC-1 mutation in NPC has not been reported, and there remain some discrepancies in methods and results between different groups. Here, we examined the mRNA and protein expression of DLC-1 in chronic nasopharyngitis (CN) and NPC tissues by reverse transcription-polymerase chain reaction/qPCR and immunohistochemistry, respectively. DLC-1 mRNA was undetectable in all the seven widely used NPC cell lines and absent or significantly down-regulated in 70% of NPC tissues. DLC-1 protein level was reduced in 74.3% of NPCs when compared with CN tissues, and significantly lower in NPC samples at advanced clinical stages than that at early stages. Then, we purified the same batch of specimens by microdissection and analyzed the possible mechanisms of DLC-1 downregulation with mutation and allelic loss analysis, methylation-specific PCR and bisulfite genomic sequencing. Only one mutation was detected at codon 693 of exon 8 in 3.3% of NPCs and five single nucleotide polymorphisms (SNPs) were identified. Loss of DLC-1 was detected in 23.3% of NPC tissues. The 100% of NPC cell lines, 80% of primary NPC and 22.2% of CN tissues showed methylation in DLC-1 promoter, while DLC-1 expression was recovered in seven NPC cell lines after 5-aza-dC treatment. Patched methylation assay confirmed that promoter methylation could repress DLC-1 expression. This report demonstrates that DLC-1 is negatively associated with NPC carcinogenesis, and promoter hypermethylation along with loss of heterozygosity, but not mutation, contributes to inactivation of DLC-1 in NPC. © 2013 Wiley Periodicals, Inc.
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Enhanced power conversion efficiencies in bulk heterojunction solar cells based on conjugated polymer with isoindigo side chain.
Chem. Commun. (Camb.)
PUBLISHED: 04-03-2013
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A novel conjugated side-chain polymer (PBDT-TID), based on benzo[1,2-b:4,5-b]dithiophene (BDT) and isoindigo (ID) moieties, was designed and synthesized. The new polymer exhibited excellent microphase separation in active layers. Bulk heterojunction polymer solar cells fabricated from PBDT-TID and PC61BM showed promising power conversion efficiencies of 5.25% and 6.51% using conventional and inverted device structures, respectively.
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Comparative Proteome Analysis of the Strawberry-Fusarium oxysporum f. sp. fragariae Pathosystem Reveals Early Activation of Defense Responses as a Crucial Determinant of Host Resistance.
J. Proteome Res.
PUBLISHED: 03-28-2013
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Fusarium wilt on strawberry caused by Fusarium oxysporum f. sp. fragariae (Fof) is a serious threat to commercial strawberry production worldwide. However, resistance mechanisms of strawberry against Fof remain unknown. To reveal the defense responses of strawberry against Fof, comparative proteome analyses were conducted to determine temporal changes in root proteomes of the resistant cv. Festival and susceptible cv. Camarosa from 4 to 72 h post inoculation with Fof. Analysis of proteins separated by two-dimensional gel electrophoresis revealed 79 Fof-responsive proteins with significant differences in abundance (P < 0.05 and greater than 2-fold) in the resistant and/or susceptible cultivar. The 79 proteins were identified through MALDI-TOF/TOF MS/MS analysis, and were mainly involved in primary, secondary and protein metabolism, stress and defense responses, antioxidant and detoxification mechanisms, and hormone biosynthesis. Among these, pathogenesis-related proteins and proteins involved in reactive oxygen species detoxification, ethylene/jasmonic acid signaling pathways, secondary metabolite biosynthesis, glycolysis and/or ubiquitin/26S proteasome-mediated protein degradation have great potential in mediating strawberry resistance against Fof. Protein modification may also have an important contribution. This study provides the first insights into strawberry resistance mechanisms against Fof, opening novel avenues to engineer new strawberry cultivars with improved disease resistance and to develop more effective and sustainable disease management strategies.
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Semaphorin 5A promotes gastric cancer invasion/metastasis via urokinase-type plasminogen activator/phosphoinositide 3-kinase/protein kinase B.
Dig. Dis. Sci.
PUBLISHED: 03-27-2013
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Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is currently available as to the involvement of uPA in the semaphorin 5A-induced metastasis and invasion of gastric cancer cells.
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Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney.
Kidney Int.
PUBLISHED: 03-20-2013
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The kidney atrophies in patients with advanced chronic kidney disease (CKD) but factors influencing kidney size in normal adults are less clear. To help define this, we measured kidney volumes on contrast-enhanced computed tomographic images from 1344 potential kidney donors (aged 18-75 years). Cortical volume per body surface area progressively declined in both genders with increased age. Statistically, this was primarily dependent on the age-related decline in glomerular filtration rate (GFR). Independent predictors of increased cortical volume per body surface area were male gender, increased GFR, increased 24-h urine albumin, current smoker, and decreased high-density lipid cholesterol. Medullary volume per body surface area increased with age in men, while it increased with age in women until the age of 50 years followed by a subsequent decline. Independent predictors of increased medullary volume per body surface area were older age, male gender, increased GFR, increased 24-h urine albumin, increased serum glucose, and decreased serum uric acid. Thus, while cortical volume declines with age along the same biological pathway as the age-related decline in GFR, albuminuria and some risk factors are actually associated with increased cortical or medullary volume among relatively healthy adults. Underlying hypertrophy or atrophy of different nephron regions may explain these findings.Kidney International advance online publication, 25 September 2013; doi:10.1038/ki.2013.359.
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A simple and sensitive fluorescence biosensor for detection of organophosphorus pesticides using H2O2-sensitive quantum dots/bi-enzyme.
Biosens Bioelectron
PUBLISHED: 03-16-2013
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In this paper, we have developed a simple, fast, convenient and sensitive method for determination of organophosphorus pesticides in real samples based on inhibition mechanism of acetylcholinesterase (AChE). The biosensor is composed of enzymes (AChE and ChOx (choline oxidase)), QDs and acetylcholine (ACh), without any complex process of assembly for biosensor. After the experimental conditions are optimized, the limit of detection (LOD) for dichlorvos (DDVP) is found to be 4.49nM. Two linear ranges allow a wide determination of DDVP concentration from 4.49nM to 6780nM. Furthermore, a possible mechanism is put forward to explain the fluorescence quenching of CdTe QDs in the presence of H2O2. More importantly, the obtained biosensor is proven to be suitable for the detection of residues of organophosphorus pesticides (OPs) in real examples. The excellent performance of this biosensor will facilitate future development of rapid and high-throughput detection of organophosphorus pesticides.
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Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [(11)C]ABP688 and Magnetic Resonance Spectroscopy.
Biol. Psychiatry
PUBLISHED: 03-04-2013
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Preclinical studies demonstrate that glutamate homeostasis in the striatum is disrupted following cocaine exposure, including a decrease in metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate turnover. The goal of this study was to use imaging of the human brain to investigate alterations in the glutamate signaling in cocaine addiction.
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The role of versican in modulating breast cancer cell self-renewal.
Mol. Cancer Res.
PUBLISHED: 02-28-2013
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Versican is highly expressed during the early stages of tissue development and its expression is elevated during wound repair and tumor growth. There is little literature on the potential role of breast cancer stem cells on the cellular-extracellular matrix interactions involving versican. An anti-versican short hairpin RNA (shRNA) was used to observe the effect of reduction of versican on breast cancer self-renewal. A versican G3 construct was exogenously expressed in breast cancer cell lines. Colony formation and mammosphere formation assays were conducted; flow cytometry was applied to analyze the prevalence of side population cells. The versican G3- and vector-transfected 66c14 cells were injected transdermally into BALB/c mice as a 10-fold dilution series from 1 × 10(5) to 1 × 10(2) cells per mouse. Versican G3 domain enhanced breast cancer self-renewal in both experimental in vitro and in vivo models. Versican G3-transfected cells contained high levels of side population cells, formed more mammospheres when cultured in the serum-free medium, and formed a greater number and larger colonies. Reduction of versicans functionality through anti-versican shRNA or knocking out the EGF-like motifs reduced the effect of versican on enhancing mammosphere and colony formation. Versican-enhanced self-renewal played a role in enhanced chemotherapeutic drug resistance, relating partly to the upregulated expression of EGF receptor (EGFR) signaling. Versican is highly expressed in breast cancer progenitor cells and was maintained at high levels before cell differentiation. Overexpression of versican enhanced breast cancer self-renewal through EGFR/AKT/GSK-3? (S9P) signaling and conferred resistant to chemotherapeutic drugs tested.
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Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios.
Clin Nutr
PUBLISHED: 02-26-2013
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BACKGROUND & AIMS: Diets with low omega (?)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT) in mediating these effects is not well understood. LDL receptor null mice were used to assess the effect of an atherogenic diet with different ?-6:EPA+DHA ratios on weight gain, hepatic and GAT lipid accumulation, and their relationship to atherosclerosis. METHODS: Four groups of mice were fed a high saturated fat and cholesterol diet (HSF ?-6) alone, or with ?-6 PUFA to EPA+DHA ratios up to 1:1 for 32 weeks. Liver and GAT were collected for lipid and gene expression analysis. RESULTS: The fatty acid profile of liver and GAT reflected the diets. All diets resulted in similar weight gains. Compared to HSF ?-6 diet, the 1:1 ratio diet resulted in lower hepatic total cholesterol (TC) content. Aortic TC was positively correlated with hepatic and GAT TC and triglyceride. These differences were accompanied by significantly lower expression of CD36, ATP-transporter cassette A1, scavenger receptor B class 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 5, and stearoyl-coenzyme A desaturase 1 (SCD1) in GAT, and HMGCR, SCD1 and cytochrome P450 7A1 in liver. CONCLUSIONS: Dietary ?-6:EPA+DHA ratios did not affect body weight, but lower ?-6:EPA+DHA ratio diets decreased liver lipid accumulation, which possibly contributed to the lower aortic cholesterol accumulation.
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DLC-1, a candidate tumor suppressor gene, inhibits the proliferation, migration and tumorigenicity of human nasopharyngeal carcinoma cells.
Int. J. Oncol.
PUBLISHED: 02-25-2013
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In our previous study we demonstrated the downregulation or loss of deleted in liver cancer?1 (DLC-1) gene expression in nasopharyngeal carcinoma (NPC). In this study, we report the effects of the DLC-1 gene on NPC cells and its mechanisms of action. DLC-1 expression was restored in the 5-8F NPC cell line, which lacks DLC-1 expression, and the biological characteristics of 5-8F-DLC?1 cells were analyzed by MTT assay, colony formation assay, flow cytometry (FCM), tumorigenesis analysis in nude mice, as well as invasion and migration assay. Differentially expressed genes in response to DLC-1 expression were screened using microarray analysis and identified by RT-PCR. The re-expression of DLC-1 in the NPC cells attenuated the proliferation and colony formation ability of the cells in vitro, blocked NPC cells at the G0/G1 phase, reduced tumorigenicity potential in vivo, inhibited the invasion and migration ability of NPC cells and resulted in the reorganization of the actin cytoskeleton. DLC-1 altered the gene expression profile in 5-8F cells. Some tumor suppressor genes (TSGs) were upregulated and some oncogenes were downregulated. These results demonstrate that DLC-1 gene can partially reverse the malignant phenotype of NPC cells by changing the tumor-related gene expression profile, and may be a candidate tumor suppressor gene and a promising diagnostic and therapeutic target in NPC.
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