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Find video protocols related to scientific articles indexed in Pubmed.
Tunable-Color Luminescence via Energy Transfer in NaCa13/18Mg5/18PO4:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) Phosphors for Solid State Lighting.
Inorg Chem
PUBLISHED: 11-06-2014
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A series of NaCa13/18Mg5/18PO4(NCMPO):A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) phosphors have been prepared by the high-temperature solid-state reaction method. The X-ray diffraction (XRD) and Rietveld refinement, X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), cathodoluminescence (CL), decay lifetimes, and PL quantum yields (QYs) were utilized to characterize the phosphors. The pure crystalline phase of as-prepared samples has been demonstrated via XRD measurement and Rietveld refinements. XPS reveals that the Eu(2+)/Tb(3+)/Mn(2+) can be efficiently doped into the crystal lattice. NCMPO:Eu(2+)/Tb(3+)/Mn(2+) phosphors can be effectively excited under UV radiation, which show tunable color from purple-blue to red including white emission based on energy transfer from Eu(2+) to Tb(3+)/Mn(2+) ions. Under low-voltage electron beam bombardment, the NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) display their, respectively, characteristic emissions with different colors, and the CL spectrum of NCMPO:0.04Tb(3+) has the comparable intensity to the ZnO:Zn commercial product. In addition, the calculated CIE coordinate of NCMPO:0.04Tb(3+) (0.252, 0.432) is more saturated than it (0.195, 0.417). These results reveal that NCMPO:A (A = Eu(2+)/Tb(3+)/Mn(2+), Dy(3+)) may be potential candidate phosphors for WLEDs and FEDs.
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[Efficacy of CO2 laser in the treatment of precancerous laryngeal lesions under phonomicrosurgery and its relative factors].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-18-2014
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To investigate the efficacy of CO2 laser treatment for patients with precancerous laryngeal lesions under phonomicrosurgery and to explore the points for attention in operation.
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Challenges and opportunities for next-generation sequencing in companion diagnostics.
Expert Rev. Mol. Diagn.
PUBLISHED: 09-25-2014
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The rapid decline in sequencing costs has allowed next-generation sequencing (NGS) assays, previously ubiquitous only in research laboratories, to begin making inroads into molecular diagnostics. Genotypic assays - DNA sequencing - include whole genome sequencing, whole exome sequencing, focused assays that target only a handful of genes. Phenotypic assays comprise a broader spectrum of options and can query a variety of epigenetic modifications of DNA (such as ChIP-seq, bisulfite sequencing, DNase-I hypersensitivity site-sequencing, Formaldehyde-Assisted Isolation of Regulatory Elements-sequencing, etc.) that regulate gene expression-related processes or gene expression (RNA-sequencing) itself. To date, the US FDA has only cleared 12 DNA-based companion diagnostic tests, all in cancer. Although challenges exist for NGS in companion diagnostics, the wide-ranging capabilities of NGS offer extraordinary opportunities for the development and implementation of NGS-based companion diagnostics to probe oncogenes, tumor suppressor genes and cancer-enabling genes.
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Application of a low cost array-based technique - TAB-Array - for quantifying and mapping both 5mC and 5hmC at single base resolution in human pluripotent stem cells.
Genomics
PUBLISHED: 08-29-2014
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5-hydroxymethylcytosine (5hmC), an oxidized derivative of 5-methylcytosine (5mC), has been implicated as an important epigenetic regulator of mammalian development. Current procedures use DNA sequencing methods to discriminate 5hmC from 5mC, limiting their accessibility to the scientific community. Here we report a method that combines TET-assisted bisulfite conversion with Illumina 450K DNA methylation arrays for a low-cost high-throughput approach that distinguishes 5hmC and 5mC signals at base resolution. Implementing this approach, termed "TAB-array", we assessed DNA methylation dynamics in the differentiation of human pluripotent stem cells into cardiovascular progenitors and neural precursor cells. With the ability to discriminate 5mC and 5hmC, we identified a large number of novel dynamically methylated genomic regions that are implicated in the development of these lineages. The increased resolution and accuracy afforded by this approach provides a powerful means to investigate the distinct contributions of 5mC and 5hmC in human development and disease.
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The global burden of liver disease: The major impact of China.
Hepatology
PUBLISHED: 08-28-2014
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Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. (Hepatology 2014).
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Effect of fixing distal radius fracture with volar locking palmar plates while preserving pronator quadratus.
Chin. Med. J.
PUBLISHED: 08-19-2014
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L-shaped incision of pronator quadratus (PQ) muscle along its radial and distal borders was always taken for distal radius fractures reduction and internal fixation. Repair of the PQ muscle was always recommended at the end of operation for some instructive reasons. But repair of PQ is not satisfied because of poor quality of muscle and fascial tissues which may cause pain or impede forearm pronation and supination for post-operative scarring around PQ. Inserting the locking palmar plate to pass under the pronator quadratus muscle and the locking screws are inserted through mini-incisions in pronator quadratus in some patients with distal radius fractures is a reasonable technique which can preserve the pronator quadratus. The purpose of this study was to evaluate and compare the clinical effects after volar plating of the distal radius fractures while preserving the pronator quadratus and pronator quadratus repair.
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Randomized, vitamin E-controlled trial of bicyclol plus metformin in non-alcoholic fatty liver disease patients with impaired fasting glucose.
Clin Drug Investig
PUBLISHED: 08-19-2014
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Non-alcoholic fatty liver disease (NAFLD) is associated with a high morbidity in patients with impaired fasting glucose (IFG). Bicyclol is a synthetic compound known to protect the liver against oxidation and lipid injuries.
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Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest.
Tumour Biol.
PUBLISHED: 08-17-2014
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Histone deacetylases (HDACs) play a critical role in the proliferation, differentiation, and apoptosis of cancer cells. An obstacle for the application of HDAC inhibitors as effective anti-cancer therapeutics is that our current knowledge on the contributions of different HDACs in various cancer types remains scarce. The present study reported that the mRNA and protein levels of HDAC5 were up-regulated in human hepatocellular carcinoma (HCC) tissues and cells as shown by quantitative real-time PCR and Western blot. MTT assay and BrdU incorporation assay showed that the down-regulation of HDAC5 inhibited cell proliferation in HepG2, Hep3B, and Huh7 cell lines. Data from in vivo xenograft tumorigenesis model also demonstrated the anti-proliferative effect of HDAC5 depletion on tumor cell growth. Furthermore, the suppression of HDAC5 promoted cell apoptosis and induced G1-phase cell cycle arrest in HCC cells. On the molecular level, we observed altered expression of apoptosis-related proteins such as p53, bax, bcl-2, cyto C, and caspase 3 in HDAC5-shRNA-transfected cells. Knockdown of HDAC5 led to a significant up-regulation of p21 and down-regulation of cyclin D1 and CDK2/4/6. We also found that the down-regulation of HDAC5 substantially increased p53 stability and promoted its nuclear localization and transcriptional activity. Our study suggested that knockdown of HDAC5 could inhibit cancer cell proliferation by the induction of cell cycle arrest and apoptosis; thus, suppression of HDAC5 may be a viable option for treating HCC patients.
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EGFR-AKT-mTOR activation mediates epiregulin-induced pleiotropic functions in cultured osteoblasts.
Mol. Cell. Biochem.
PUBLISHED: 07-10-2014
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Epidermal growth factor (EGF) receptor (EGFR) emerges as an essential molecule for the regulating of osteoblast cellular functions. In the current study, we explored the effect of epiregulin, a new EGFR ligand, on osteoblast functions in vitro, and studied the underlying mechanisms. We found that epiregulin-induced EGFR activation in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, epiregulin activated AKT-mammalian target of rapamycin (mTOR) and Erk-mitogen-activated protein kinase (MAPK) signalings in cultured osteoblasts, which were blocked by EGFR inhibitor AG1478 or monoclonal antibody against EGFR (anti-EGFR). Further, in primary and MC3T3-E1 osteoblasts, epiregulin promoted cell proliferation and increased alkaline phosphatase activity, while inhibiting dexamethasone (Dex)-induced cell death. Such effects by epiregulin were largely inhibited by AG1478 or anti-EGFR. Notably, AKT-mTOR inhibitors, but not Erk inhibitors, alleviated epiregulin-induced above pleiotropic functions in osteoblasts. Meanwhile, siRNA depletion of Sin1, a key component of mTOR complex 2 (mTORC2), also suppressed epiregulin-exerted effects in MC3T3-E1 cells. Together, these results suggest that epiregulin-induced pleiotropic functions in cultured osteoblasts are mediated through EGFR-AKT-mTOR signalings.
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A double substitution of Mg2+-Si4+/Ge4+ for Al(1)(3+)-Al(2)3+ in Ce3+-doped garnet phosphor for white LEDs.
Inorg Chem
PUBLISHED: 06-27-2014
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The influence of Mg(2+)-Si(4+)/Ge(4+) incorporation into Ce(3+)-doped Y3Al5O12 garnet phosphors on the crystal structure and luminescence properties is described in this work. X-ray diffraction with Rietveld refinements, photoluminescence spectra, absolute quantum yield, thermal quenching behavior, and lifetimes were utilized to characterize samples. The introduction of Mg(2+)-Si(4+)/Ge(4+) leads to an obvious red shift of emission wavelength under the excitation of blue light, especially for the series of Mg(2+)-Si(4+) substitutions, which is suited for white light-emitting diodes (LEDs) with low color temperatures and good color rendering using only a single phosphor. More interestingly, an additional emission band locating at high-energy was observed with ultraviolet excitation, which is different than previous literature. Under the excitation of ultraviolet, the emission color for the Mg(2+)-Si(4+) substitutions can be tuned from yellow-green to blue, which is expected to obtain single-phased phosphors with white emission excited with UV-LED chip. The usual Ce(3+) emission band at low energy has stronger quenching at high temperatures. The mechanisms for the observed phenomena are discussed.
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Synthesis, luminescence, and energy-transfer properties of ?-Na2Ca4(PO4)2(SiO4):A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors.
Inorg Chem
PUBLISHED: 06-06-2014
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A series of ?-Na2Ca4(PO4)2(SiO4) (?-NCPS):A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors were prepared via a high-temperature solid-state reaction route. The X-ray diffraction, Fourier transform infrared, photoluminescence (PL), cathodoluminescence (CL) properties, fluorescent lifetimes, and absolute quantum yield were exploited to characterize the samples. Under UV radiation, the ?-NCPS:Eu(2+) phosphors present bright green emissions, and the ?-NCPS:Ce(3+) phosphors show strong blue emissions, which are attributed to their 4f(6)5d(1) ? 4f(7) and 5d-4f allowed transitions, respectively. The ?-NCPS:Ce(3+), Tb(3+) phosphors display intense tunable color from blue to green and high absolute quantum yields (81% for ?-NCPS:0.12Ce(3+) and 83% for ?-NCPS:0.12Ce(3+), 0.08Tb(3+)) when excited at 365 nm. Simultaneously, the energy transfer from Ce(3+) to Tb(3+) ions is deduced from the spectral overlap between Ce(3+) emission and Tb(3+) excitation spectra and demonstrated by the change of emission spectra and decay lifetimes. Moreover, the energy-transfer mechanism from Ce(3+) to Tb(3+) ions is confirmed to be exchange interaction according to the discussion of expression from Dexter and Reisfeld. Under a low-voltage electron-beam excitation, the ?-NCPS:A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors exhibit their characteristic emissions, and the emission profiles of ?-NCPS:Ce(3+),Tb(3+) phosphors are obviously different from those of the PL spectra; this difference might be ascribed to their different luminescence mechanisms. These results in PL and CL properties suggest that ?-NCPS:A (A = Eu(2+), Dy(3+), Ce(3+)/Tb(3+)) phosphors are potential candidates for solid-state lighting and field-emission displays.
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[Combined stress of enhanced UV-B radiation and 1,2,4-trichlorobenzene contamination on the growth of green vegetable].
Huan Jing Ke Xue
PUBLISHED: 06-03-2014
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A pot experiment was conducted to study the effects of UV-B radiation enhancement alone, 1,2,4-trichlorobenzene (TCB) contamination soil alone, and the combined stress on the growing process, stomatal resistance and leaf structure of green vegetable. The results showed that 1,2,4-TCB contamination alone had more significant inhibitory effect on the growth of green vegetable than the combined stress. Both UV-B radiation enhancement and 1,2,4-TCB contamination reduced the stomatal resistance of front and reverse leaves. Enhanced UV-B radiation resulted in the albino of leaves. 1,2,4-TCB contamination resulted in the fading of leaf color and the appearing of black spots on leaf surfaces, and the enhanced UV-B radiation strengthened the black-spot symptom. In conclusion, the effects of UV-B radiation enhancement alone, 1,2,4-trichlorobenzene (TCB) contamination soil alone and the combined stress on the growth indicators of green vegetable were different.
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Understanding the effects of the number of pyrazines and their positions on charge-transport properties in silylethynylated N-heteropentacenes.
J Mol Model
PUBLISHED: 05-14-2014
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The charge-transport properties of a series of silylethynylated N-heteropentacenes (TIPS-PEN-xN; x = 2, 4) were systematically investigated using Marcus electron-transfer theory coupled with kinetic Monte Carlo simulations. Electronic structure calculations showed that introducing more pyrazine rings decreases the energy levels of the lowest unoccupied molecular orbitals (LUMOs) and should aid electron transfer. The number and the positions of the pyrazine rings greatly influence the molecular packing in crystals and hence the intermolecular electronic coupling. Furthermore, the introduction of internal (rather than external) pyrazine rings leads to a better charge-transport network. Transport parameters evaluated from the hopping and band-like models both demonstrate that, among the TIPS-PEN-xN molecules, B-TIPS-PEN-4N-which has two internal pyrazine rings-is the most promising n-type material.
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Controlled Attenuation Parameter for Noninvasive Assessment of Hepatic Steatosis Using Fibroscan(®): Validation in Chronic Hepatitis B.
Dig. Dis. Sci.
PUBLISHED: 05-14-2014
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The controlled attenuation parameter (CAP) using transient elastography (TE) was validated in chronic hepatitis C to evaluate hepatic steatosis; however, limited data are available on chronic hepatitis B (CHB). Therefore, we assessed the accuracy and the efficacy of CAP for the detection of steatosis in CHB.
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Weak evidence supports the short-term benefits of orthopaedic treatment for Class III malocclusion in children.
Evid Based Dent
PUBLISHED: 04-26-2014
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Data sources The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase.
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Sphincter electromyography in diabetes mellitus and multiple system atrophy.
Neurourol. Urodyn.
PUBLISHED: 04-24-2014
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Abnormalities of external anal sphincter electromyography (EAS-EMG) characterize multiple system atrophy (MSA) and focal cauda equina or conus medullaris lesions. This study is designed to determine whether and how diabetic polyneuropathy (DPN) affects EAS as compared to the abnormalities seen in MSA.
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Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors.
Dig. Dis. Sci.
PUBLISHED: 04-20-2014
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The interaction between hepatitis B virus (HBV) infection and hepatic steatosis remains unclear. We aimed to explore the trend of prevalence of hepatic steatosis and its relationship with virological factors in HBV infected patients.
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Tumor hypomethylation at 6p21.3 associates with longer time to recurrence of high-grade serous epithelial ovarian cancer.
Cancer Res.
PUBLISHED: 04-11-2014
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To reveal biologic mechanisms underlying clinical outcome of high-grade serous (HGS) epithelial ovarian carcinomas (EOC), we evaluated the association between tumor epigenetic changes and time to recurrence (TTR). We assessed methylation at approximately 450,000 genome-wide CpGs in tumors of 337 Mayo Clinic (Rochester, MN) patients. Semi-supervised clustering of discovery (n=168) and validation (n=169) sets was used to determine clinically relevant methylation classes. Clustering identified two methylation classes based on 60 informative CpGs, which differed in TTR in the validation set [R vs. L class, P=2.9×10(-3), HR=0.52; 95% confidence interval (CI), 0.34-0.80]. Follow-up analyses considered genome-wide tumor mRNA expression (n=104) and CD8 T-cell infiltration (n=89) in patient subsets. Hypomethylation of CpGs located in 6p21.3 in the R class associated with cis upregulation of genes enriched in immune response processes (TAP1, PSMB8, PSMB9, HLA-DQB1, HLA-DQB2, HLA-DMA, and HLA-DOA), increased CD8 T-cell tumor infiltration (P=7.6×10(-5)), and trans-regulation of genes in immune-related pathways (P=1.6×10(-32)). This is the most comprehensive assessment of clinical outcomes with regard to epithelial ovarian carcinoma tumor methylation to date. Collectively, these results suggest that an epigenetically mediated immune response is a predictor of recurrence and, possibly, treatment response for HGS EOC.
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Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-09-2014
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One challenge in prostate cancer is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in prostate cancer, but few studies of DNA methylation in relation to features of more aggressive tumors or prostate cancer recurrence have been completed.
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Identification of p.Gln858* in ATP13A2 in two EOPD patients and presentation of their clinical features.
Neurosci. Lett.
PUBLISHED: 03-26-2014
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We present results of homozygosity mapping in two siblings affected with early onset Parkinson's disease (EOPD) and mutation screening of ATP13A2 in these and other Iranian EOPD patients. Genome-wide SNP homozygosity analysis revealed linkage to a locus that included ATP13A2, and sequencing of the gene revealed a novel p.Gln858*-causing mutation in the homozygous state in the siblings. Sequencing of the gene in seven other unrelated EOPD patients previously shown not to have mutations in PRKN, DJ-1, PINK1, and LRRK2 identified the same homozygous p. Gln858*-causing mutation in another patient. Haplotype analysis revealed that two alleles harboring the mutation were not identical by decent. The variation identified represents the 13th known disease causing mutation in ATP13A2. The clinical features of the patients who harbored the mutation are compared to those of previously reported patients with mutations in ATP13A2. Bradykinesia and rigidity, but not tremor, were reported in nearly all the patients. l-dopa administration, though initially effective, usually caused dyskinesia upon prolonged usage. Eye movement abnormalities including saccades and supranuclear gaze palsy, were almost always observed. Dystonia and bulbar anomalies were common but more variable manifestations. Although a degree of cognitive decline was found in most of the patients, the decline was often mild and absent in one patient. Age at onset of symptoms was usually in the second decade of life, and sometimes in the third decade.
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EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-26-2014
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Pleiotrophin (Ptn) plays an important role in bone growth through regulating osteoblasts' functions. The underlying signaling mechanisms are not fully understood. In the current study, we found that Ptn induced heparin-binding epidermal growth factor (HB-EGF) release to trans-activate EGF-receptor (EGFR) in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, Ptn activated Akt and Erk signalings in cultured osteoblasts. The EGFR inhibitor AG1478 as well as the monoclonal antibody against HB-EGF (anti-HB-EGF) significantly inhibited Ptn-induced EGFR activation and Akt and Erk phosphorylations in MC3T3-E1 cells and primary osteoblasts. Further, EGFR siRNA depletion or dominant negative mutation suppressed also Akt and Erk activation in MC3T3-E1 cells. Finally, we observed that Ptn increased alkaline phosphatase (ALP) activity and inhibited dexamethasone (Dex)-induced cell death in both MC3T3-E1 cells and primary osteoblasts, such effects were alleviated by AG1478 or anti-HB-EGF. Together, these results suggest that Ptn-induced Akt/Erk activation and some of its pleiotropic functions are mediated by EGFR trans-activation in cultured osteoblasts.
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Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step real-time RT-PCR assay.
BMC Infect. Dis.
PUBLISHED: 03-18-2014
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A novel avian influenza A (H7N9) virus emerged in eastern China in February 2013. 413 confirmed human cases, including 157 deaths, have been recorded as of July 31, 2014.
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Are triphenylamine-functionalized or carbazole-functionalized iridium complexes the more effective phosphorescent materials? A theoretical perspective.
Chemistry
PUBLISHED: 03-05-2014
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The ground and excited states, charge injection/transport, and phosphorescence properties of eleven carbazole- and triphenylamine-functionalized Ir(III) complexes were investigated by using the DFT method. By analyzing the spin-orbit coupling (SOC) matrix elements, radiative decay rate constants k(r), and the electronic structures and energies at the S?(opt) and T?(opt) states, it was possible to rationalize the order of the experimental phosphorescence quantum yields of a series of Ir(III) complexes and to predict that [Ir(Nph-2-Cz-tz)3] has a higher phosphorescence quantum yield than [Ir(TPA-tz)3] (TPA=triphenylamine, tz=thiazolyl, Cz=carbazole, Nph=N-phenyl). Carbazole-functionalized Ir(III) complexes were shown to be efficient phosphorescent materials that have not only fast but also balanced electron/hole-transport performance as well as high phosphorescence quantum yields. The phosphorescence emission spectra can be modulated by modifying or replacing a pyridyl substituent.
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?-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/?-catenin signaling inhibits hepatic stellate cell activation.
Mol Med Rep
PUBLISHED: 03-03-2014
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?-catenin, a core component of Wnt/?-catenin signaling, has been shown to be an important regulator of cellular proliferation and differentiation. Abnormal activation of Wnt/?-catenin signaling promotes tissue fibrogenesis. In the present study, the role of ?-catenin during liver fibrogenesis was analyzed and the functional effects of ?-catenin gene silencing in hepatic stellate cells (HSCs) using small interfering (si)RNA were investigated. The expression of ?-catenin in human hepatic fibrosis tissues of different grades and normal human hepatic tissues was examined using immunohistochemistry. To inhibit the Wnt/?-catenin signaling pathway, siRNA for ?-catenin was developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000. ?-catenin expression was evaluated by quantitative polymerase chain reaction (qPCR) and western blot analysis. The expression of collagen types ? and ? was evaluated by qPCR and immunofluorescent staining. Cellular proliferation and the cell cycle were analyzed using a methyl thiazolyl tetrazolium assay. Apoptosis was assessed by Annexin V staining. A higher expression level of ?-catenin was identified in the patients with high-grade hepatic fibrosis in comparison with that of the normal controls. Additionally, ?-catenin siRNA molecules were successfully transfected into HSCs and induced inhibition of ?-catenin expression in a time-dependent manner. ?-catenin siRNA treatment also inhibited synthesis of collagen types ? and ? in transfected HSCs. Furthermore, compared with those of the control group, siRNA-mediated knockdown of ?-catenin in HSC-T6 cells inhibited cell proliferation and resulted in cell apoptosis. This study suggests a significant functional role for ?-catenin in the development of liver fibrosis and demonstrates that downregulation of the Wnt/?-catenin signaling pathway inhibits HSC activation. Thus, this study provides a novel strategy for the treatment of hepatic fibrosis.
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Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients.
World J. Gastroenterol.
PUBLISHED: 02-26-2014
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To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis.
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Negative elongation factor controls energy homeostasis in cardiomyocytes.
Cell Rep
PUBLISHED: 01-23-2014
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Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor ? (PPAR?), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPAR?-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes.
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In vitro response of human osteoblasts to multi-step sol-gel derived bioactive glass nanoparticles for bone tissue engineering.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-18-2014
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A multi-step sol-gel process was employed to synthesize bioactive glass (BG) nanoparticles. Transmission electron microscopy (TEM) revealed that the BG nanoparticles were spherical and ranged from 30 to 60 nm in diameter. In vitro reactivity of the BG nanoparticles was tested in phosphate buffer saline (PBS), Tris-buffer (TRIS), simulated body fluid (SBF), and Dulbecco's modified Eagle's medium (DMEM), in comparison with similar sized hydroxyapatite (HA) and silicon substituted HA (SiHA) nanoparticles. Bioactivity of the BG nanoparticles was confirmed through Fourier transform infrared spectroscopy (FTIR) analysis. It was found that bone-like apatite was formed after immersion in SBF at 7 days. Solutions containing BG nanoparticles were slightly more alkaline than HA and SiHA, suggesting that a more rapid apatite formation on BG was related to solution-mediated dissolution. Primary human osteoblast (HOB) cell model was used to evaluate biological responses to BG nanoparticles. Lactate dehydrogenase (LDH) cytotoxicity assay showed that HOB cells were not adversely affected by the BG nanoparticles throughout the 7day test period. Interestingly, MTS assay results showed an enhancement in cell proliferation in the presence of BG when compared to HA and SiHA nanoparticles. Particularly, statistically significant (p<0.05) alkaline phosphatase (ALP) activity of HOB cells was found on the culture containing BG nanoparticles, suggesting that the cell differentiation might be promoted by BG. Real-time quantitative PCR analysis (qPCR) further confirmed this finding, as a significantly higher level of RUNX2 gene expression was recorded on the cells cultured in the presence of BG nanoparticles when compared to those with HA and SiHA.
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A panel of CpG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.
Stem Cell Reports
PUBLISHED: 01-14-2014
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Whether human induced pluripotent stem cells (hiPSCs) are epigenetically identical to human embryonic stem cells (hESCs) has been debated in the stem cell field. In this study, we analyzed DNA methylation patterns in a large number of hiPSCs (n = 114) and hESCs (n = 155), and identified a panel of 82 CpG methylation sites that can distinguish hiPSCs from hESCs with high accuracy. We show that 12 out of the 82 CpG sites were subject to hypermethylation in part by DNMT3B. Notably, DNMT3B contributes directly to aberrant hypermethylation and silencing of the signature gene, TCERG1L. Overall, we conclude that DNMT3B is involved in a wave of de novo methylation during reprogramming, a portion of which contributes to the unique hiPSC methylation signature. These 82 CpG methylation sites may be useful as biomarkers to distinguish between hiPSCs and hESCs.
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Mutation in ST6GALNAC5 identified in family with coronary artery disease.
Sci Rep
PUBLISHED: 01-09-2014
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We aimed to identify the genetic cause of coronary artery disease (CAD) in an Iranian pedigree. Genetic linkage analysis identified three loci with an LOD score of 2.2. Twelve sequence variations identified by exome sequencing were tested for segregation with disease. A p.Val99Met causing mutation in ST6GALNAC5 was considered the likely cause of CAD. ST6GALNAC5 encodes sialyltransferase 7e. The variation affects a highly conserved amino acid, was absent in 800 controls, and was predicted to damage protein function. ST6GALNAC5 is positioned within loci previously linked to CAD-associated parameters. While hypercholesterolemia was a prominent feature in the family, clinical and genetic data suggest that this condition is not caused by the mutation in ST6GALNAC5. Sequencing of ST6GALNAC5 in 160 Iranian patients revealed a candidate causative stop-loss mutation in two other patients. The p.Val99Met and stop-loss mutations both caused increased sialyltransferase activity. Sequence data from combined Iranian and US controls and CAD affected individuals provided evidence consistent with potential role of ST6GALNAC5 in CAD. We conclude that ST6GALNAC5 mutations can cause CAD. There is substantial literature suggesting a relation between sialyltransferase and sialic acid levels and coronary disease. Our findings provide strong evidence for the existence of this relation.
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Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion.
Cell Stem Cell
PUBLISHED: 01-07-2014
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The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs. We found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation. Conversely, reducing ID2 expression levels increases lymphoid potential. Mechanistically, ID2 inhibits the transcription factor E47 to attenuate B-lymphoid priming in HSCs and progenitors. Strikingly, ID2 overexpression also results in a 10-fold expansion of HSCs in serial limiting dilution assays, indicating that early lymphoid transcription factors antagonize human HSC self-renewal. The relationship between lineage priming and self-renewal can be exploited to increase expansion of transplantable human HSCs and points to broader implications for other stem cell populations.
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Garlic-derived allyl sulfides in cancer therapy.
Anticancer Agents Med Chem
PUBLISHED: 01-05-2014
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Garlic (Allium sativam L.) is widely used in traditional herbal remedies and alternative medicine. The potential health benefits of garlic are largely attributed to its metabolic byproducts. Extensive in vivo and in vitro studies has demonstrated that the garlic derivatives possess anti-cancer effects, but the underlying mechanisms are not completely understood. In this mini-review, we aim to summarize the reported biological effects of garlic products as anti-tumor agents, and present the possible molecular mechanisms responsible for the anti-carcinogenesis effects of garlic and its derivatives.
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Angular velocity affects trunk muscle strength and EMG activation during isokinetic axial rotation.
Biomed Res Int
PUBLISHED: 01-03-2014
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To evaluate trunk muscle strength and EMG activation during isokinetic axial rotation at different angular velocities.
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RNAi screening with shRNAs against histone methylation-related genes reveals determinants of sorafenib sensitivity in hepatocellular carcinoma cells.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Sorafenib is the first drug currently approved to treat advanced hepatocellular carcinoma (HCC). However, very low response rate and acquired drug resistance makes rare patients benefit from sorafenib therapy, therefore it is urgent to find biomarkers for sorafenib sensitivity. Histone modifications, including histone methylation, have been demonstrated to influence the initiation and progression of HCC. It is of great interest to elicit the possibility whether histone methylation plays a role in regulation of sorafenib sensitivity. In present work, a high throughput RNAi screening with 176 shRNA pools against 88 histone methyltransferases (HMTs) and histone demethyltransferases genes was applied to HepG2 cells. Silencing of 3 genes (ASH1L, C17ORF49 and SETD4) was validated to specifically promote HepG2 cells sensitivity to sorafenib. Western blotting results showed that those 3 HMT genes knockdown alone or sorafenib treatments alone both induce AKT/ERK activation. However, combination treatment with sorafenib and silencing of C17ORF49 or SETD4 downregulated AKT phosphorylation and hence induced HCC cells death. Our work may provide potential biomarkers for sorafenib sensitivity and therapeutic combination for sorafenib treatment in HCC patients.
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Transcriptome profiling of archived sectioned formalin-fixed paraffin-embedded (AS-FFPE) tissue for disease classification.
PLoS ONE
PUBLISHED: 01-01-2014
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Archived tissues from previously completed prospective trials represent invaluable resource for biomarker development. However, such specimens are often stored as sections on glass slides, in which RNA is severely degraded due to prolonged air exposure. We evaluated whether a proportion of archived sectioned formalin-fixed paraffin-embedded (AS-FFPE) tissues yield transcriptome profiles comparable to freshly cut (FC) FFPE tissues, which can be used for retrospective class prediction analysis.
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Nanohydroxyapatite shape and its potential role in bone formation: an analytical study.
J R Soc Interface
PUBLISHED: 01-01-2014
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Bone cells (osteoblasts) produce a collagen-rich matrix called osteoid, which is mineralized extracellularly by nanosized calcium phosphate (CaP). Synthetically produced CaP nanoparticles (NPs) have great potential for clinical application. However few studies have compared the effect of CaP NPs with different properties, such as shape and aspect ratio, on the survival and behaviour of active bone-producing cells, such as primary human osteoblasts (HOBs). This study aimed to investigate the biocompatibility and ultrastructural effects of two differently shaped hydroxyapatite [Ca10(PO4)6(OH)2] nanoparticles (HA NPs), round- (aspect ratio 2.12, AR2) and rice-shaped (aspect ratio 3.79, AR4). The ultrastructural response and initial extracellular matrix (ECM) formation of HOBs to HA NPs were observed, as well as matrix vesicle release. A transmission electron microscopy (TEM)-based X-ray microanalytical technique was used to measure cytoplasmic ion levels, including calcium (Ca), phosphorus (P), sodium (Na) and potassium (K). K/Na ratios were used as a measure of cell viability. Following HA NP stimulation, all measured cytoplasmic ion levels increased. AR2 NPs had a greater osteogenic effect on osteoblasts compared with AR4 NPs, including alkaline phosphatase activity and matrix vesicle release. However, they produced only a moderate increase in intracellular Ca and P levels compared with AR4. This suggests that particular Ca and P concentrations may be required for, or indicative of, optimal osteoblast activity. Cell viability, as measured by Na and K microanalysis, was best maintained in AR2. Initial formation of osteoblast ECM was altered in the presence of either HA NP, and immuno-TEM identified fibronectin and matrilin-3 as two ECM proteins affected. Matrilin-3 is here described for the first time as being expressed by cultured osteoblasts. In summary, this novel and in-depth study has demonstrated that HA NP shape can influence a range of different parameters related to osteoblast viability and activity.
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[Study of RON mediated invasion of Raji cell line and drug-target effects].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 12-04-2013
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To study the proto-oncogene RON mediated aggression of Raji cells and the inhibitory effects by monoclonal antibody Zt/f2 (2f2).
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[Effectiveness of open reduction and internal fixation for Bosworth fracture].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 11-28-2013
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To explore the operative methods and effectiveness of open reduction and internal fixation for Bosworth fracture.
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APOBEC3B Upregulation and Genomic Mutation Patterns in Serous Ovarian Carcinoma.
Cancer Res.
PUBLISHED: 10-23-2013
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Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in the majority of ovarian cancer cell lines (three SDs above the mean of normal ovarian surface epithelial cells) and high-grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5-TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5-TC dinucleotide motifs in early-stage high-grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA "repair" enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. Cancer Res; 73(24); 7222-31. ©2013 AACR.
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The effectiveness of low-level laser therapy in accelerating orthodontic tooth movement: a meta-analysis.
Lasers Med Sci
PUBLISHED: 08-21-2013
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Low-level laser therapy is claimed to accelerate bone remodeling. The aim of this meta-analysis was to critically appraise current evidence and to determine the effectiveness of low-level laser therapy in accelerating orthodontic tooth movement. PubMed, Web of Knowledge, Embase, CENTRAL, ProQuest Dissertations &Theses, and SIGLE were electronically searched from Jan 1990 to Jun 2013. Article screening, data extraction, assessment of risk of bias and evaluation of evidence quality through GRADE were conducted independently and in duplicate by two reviewer authors. Outcome of interest in this meta-analysis was accumulative moved distance (AMD). Meta-analyses were performed in Comprehensive Meta-Analysis Version 2.2.064 (Biostat, Englewood, NJ, USA). Finally, five studies were included in this meta-analysis. The meta-analysis revealed that the pooled difference in mean (DM) was 0.33 [95 % CI: (0.03-0.64)], 0.76 [95 % CI: (-0.14, 1.65)] and 0.43 [95 % CI: (-0.05, 0.91)] for AMD within 1 month, AMD within 2 months and AMD within 3 months, respectively. However, significant heterogeneities and instability of the pooled results were detected. Moreover, publication bias was found for AMD within 3 months. The subgroup analysis on the wavelength of 780 nm revealed that the pooled DM of AMD were 0.54 (95 % CI?=?0.18-0.91), 1.11 (95 % CI?=?0.91-1.31) and 1.25 (95 % CI?=?0.68-1.82) for 1, 2, and 3 months, respectively. For the output power of 20 mW, the subgroup analysis showed that the pooled DM of AMD was 0.45 (95 % CI?=?0.26-0.64), 1.11 (95 % CI?=?0.91-1.31), and 1.25 (95 % CI?=?0.68-1.82) for 1, 2, and 3 months, respectively. Weak evidence suggests that low-level laser irradiations at the wavelength of 780 nm, at the fluence of 5 J/cm(2) and/or the output power of 20 mW could accelerate orthodontic tooth movement within 2 months and 3 months. However, we cannot determine its effectiveness within 1 month due to potential measurement errors.
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[Surveillance of schistosome antibodies in population in mountainous schistosomiasis endemic regions in China].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 07-31-2013
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To understand the dynamics of schistosome antibodies in population in mountainous schistosomiasis low endemic regions, China, so as to provide the evaluation reference for immunodiagnosis.
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A phenanthroline-terpyridine hybrid as a chameleon-type ligand in a reversible metallosupramolecular rearrangement.
Dalton Trans
PUBLISHED: 07-30-2013
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Phenanthroline-terpyridine hybrid 1 was designed as a chameleon-type ligand to satisfy both HETPHEN and HETTAP coordination modes. In the presence of Cu(+), 1 exclusively self-assembled to triangle T1, whereas Zn(2+) addition produced a 2:1 mixture of triangle T2 and square S2. Interconversion between T1 and (T2 + S2) states was triggered by the addition of Zn(2+) and reversed by selectively removing Zn(2+) with ligand 7.
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Diagnostic accuracy of CBCT for tooth fractures: A meta-analysis.
J Dent
PUBLISHED: 07-17-2013
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The objective of this meta-analysis was to determine the diagnostic accuracy of cone-beam computed tomography (CBCT) for tooth fractures in vivo.
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Mutation in CYP27A1 identified in family with coronary artery disease.
Eur J Med Genet
PUBLISHED: 05-18-2013
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Coronary artery disease (CAD) is a leading cause of death worldwide. Myocardial infarction is the most severe outcome of CAD. Despite extensive efforts, the genetics of CAD is poorly understood. We aimed to identify the genetic cause of CAD in a pedigree with several affected individuals. Exome sequencing led to identification of a mutation in CYP27A1 that causes p.Arg225His in the encoded protein sterol 27-hydroxylase as the likely cause of CAD in the pedigree. The enzyme is multifunctional, and several of its functions including its functions in vitamin D metabolism and reverse cholesterol transport (RCT) are relevant to the CAD phenotype. Measurements of vitamin D levels suggested that the mutation does not affect CAD by affecting this parameter. We suggest that the mutation may cause CAD by affecting RCT. Screening of all coding regions of the CYP27A1 in 100 additional patients led to finding four variations (p.Arg14Gly, p.Arg26Lys, p.Ala27Arg, and p.Val86Met) in seven patients that may contribute to their CAD status. CYP27A1 is the known causative gene of cerebrotendinous xanthomatosis, a disorder which is sometimes accompanied by early onset atherosclerosis. This and the observation of potentially harmful variations in unrelated CAD patients provide additional evidence for the suggested causative role of the p.Arg225His mutation in CAD.
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[Clinical and laboratory features of four cases with IgM multiple myeloma].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-15-2013
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Objective To improve the understanding of the clinical and laboratory features of the IgM multiple myeloma (MM). Methods The clinical data of four cases of IgM MM patients were collected, their clinical and laboratory features were summarized and analyzed. Results Four patients met the criteria of IgM MM. They were all male. The age at the diagnosis ranged from 54 to 69 years. The primary symptoms included bone pain, hyperviscosity and bleeding. Three cases had ?-chain and only one case had ?-chain. They were all staged ?A according to the Durie-Salmon staging system (DSS). One case staged ?and three cases staged ? according to the international staging system (ISS). The average value of IgM, hemoglobin, serum calcium, creatinine and the proportion of bone marrow plasma cells were 83.6 (52.9-111.0) g/L, 79.5? (61.0-105.0) g/L, 3.20(2.11-6.00) mmol/L, 104.3 (56.0-171.0) ?mol/L and 0.558 (0.290-0.775), respectively. Bone destruction was found in 3 cases. Immunophenotypes of bone marrow plasma cells were analyzed in 3 patients. Results showed that these cells expressed CD38 and CD138, and did not express CD19, CD20 and CD117. Chromosome and fluorescence in situ hybridization (FISH) analysis were carried out in 4 cases and found that all of them had IgH translocations and 1q21 amplification, 2 cases had 13q and 17p deletion, and 3 cases had t(11;14). Three patients received bortezomib-based regimens as induction therapy and reached partial response (PR) - very good partial response (VGPR). Followed up to November 30, 2012, the median progress-free survival (PFS) and overall survival (OS) of the 4 cases were only 6.0 (2.5-7.0) months and 17.5 (2.5-27.0) months, respectively. Conclusions IgM MM is very rare and is no more than 0.5% in all types of MM. IgM MM have frequent t(11;14) and amp(1q21). Bortezomib-based regimens are effective for it, however, the disease progresses rapidly and has poor prognosis.
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[Busulfan, cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-15-2013
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To evaluate the efficacy and safety of dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) as conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM).
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[The efficacy and safety analysis of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-15-2013
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To evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.
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Initial arch wires for tooth alignment during orthodontic treatment with fixed appliances.
Cochrane Database Syst Rev
PUBLISHED: 05-02-2013
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Initial arch wires are the first arch wires to be inserted into the fixed appliance at the beginning of orthodontic treatment and are used mainly for the alignment of teeth by correcting crowding and rotations. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which wire is most efficient, as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is an update of the review Initial arch wires for alignment of crooked teeth with ?xed orthodontic braces first published in the Cochrane Database of Systematic Reviews 2010, Issue 4.
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The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.
Nat. Immunol.
PUBLISHED: 04-16-2013
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Understanding how differentiation programs originate from the gene-expression landscape of hematopoietic stem cells (HSCs) is crucial for the development of new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSCs and eight early progenitor populations. We found that transcriptional programs were extensively shared, extended across lineage-potential boundaries and were not strictly lineage affiliated. Elements of stem, lymphoid and myeloid programs were retained in multilymphoid progenitors (MLPs), which reflected a hybrid transcriptional state. By functional single cell analysis, we found that the transcription factors Bcl-11A, Sox4 and TEAD1 (TEF1) governed transcriptional networks in MLPs, which led to B cell specification. Overall, we found that integrated transcriptome approaches can be used to identify previously unknown regulators of multipotency and show additional complexity in lymphoid commitment.
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Translational utility of next-generation sequencing.
Genomics
PUBLISHED: 04-15-2013
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The development of next-generation sequencing (NGS) technology has made DNA sequencing not only rapid and cost-effective, but also highly accurate and reproducible. The translational utility of genomic sequencing is clear, from understanding of human genetic variation and its association with disease risk and individual response to treatment, to the interpretation and translation of the data for clinical decision making. It will be a critical technology for disease characterization and monitoring in molecular pathology and is expected to become a central piece of routine healthcare management which will result in accurate and reliable reporting, a prerequisite for physicians to practice genomic medicine.
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Comparison of adverse effects between lingual and labial orthodontic treatment.
Angle Orthod
PUBLISHED: 04-12-2013
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To compare adverse effects between labial and lingual orthodontic treatments through a systematic review of the literature.
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Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel.
Hum. Mol. Genet.
PUBLISHED: 04-09-2013
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Ovarian cancer remains the leading cause of death in women with gynecologic malignancies, despite surgical advances and the development of more effective chemotherapeutics. As increasing evidence indicates that clear-cell ovarian cancer may have unique pathogenesis, further understanding of molecular features may enable us to begin to understand the underlying biology and histology-specific information for improved outcomes. To study epigenetics in clear-cell ovarian cancer, fresh frozen tumor DNA (n = 485) was assayed on Illumina Infinium HumanMethylation450 BeadChips. We identified a clear-cell ovarian cancer tumor methylation profile (n = 163) which we validated in two independent replication sets (set 1, n = 163; set 2, n = 159), highlighting 22 CpG loci associated with nine genes (VWA1, FOXP1, FGFRL1, LINC00340, KCNH2, ANK1, ATXN2, NDRG21 and SLC16A11). Nearly all of the differentially methylated CpGs showed a propensity toward hypermethylation among clear-cell cases. Several loci methylation inversely correlated with tumor gene expression, most notably KCNH2 (HERG, a potassium channel) (P = 9.5 × 10(-7)), indicating epigenetic silencing. In addition, a predicted methylation class mainly represented by the clear-cell cases (20 clear cell out of 23 cases) had improved survival time. Although these analyses included only 30 clear-cell carcinomas, results suggest that loss of expression of KCNH2 (HERG) by methylation could be a good prognostic marker, given that overexpression of the potassium (K(+)) channel Eag family members promotes increased proliferation and results in poor prognosis. Validation in a bigger cohort of clear-cell tumors of the ovary is warranted.
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Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.
Cancer Discov
PUBLISHED: 04-02-2013
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Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
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Role of diet and nutritional management in non-alcoholic fatty liver disease.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-27-2013
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Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis, which causes an increased risk of cirrhosis, type 2 diabetes, and cardiovascular complications. With the worldwide growing incidence of obesity, sedentary lifestyle, and unhealthy dietary pattern, NAFLD has currently been recognized as a major health burden. Dietary patterns and nutrients are the important contributors to the development, progression, and treatment of NAFLD and associated metabolic comorbidities. Generally, hypercaloric diet, especially rich in trans/saturated fat and cholesterol, and fructose-sweetened beverages seem to increase visceral adiposity and stimulate hepatic lipid accumulation and progression into non-alcoholic steatohepatitis, whereas reducing caloric intake, increasing soy protein and whey consumption, and supplement of monounsaturated fatty acids, omega-3 fatty acids, and probiotics have preventive and therapeutic effects. In addition, choline, fiber, coffee, green tea, and light alcohol drinking might be protective factors for NAFLD. Based on available data, at least 3-5% of weight loss, achieved by hypocaloric diet alone or in conjunction with exercise and behavioral modification, generally reduces hepatic steatosis, and up to 10% weight loss may be needed to improve hepatic necroinflammation. A sustained adherence to diet rather than the actual diet type is a major predictor of successful weight loss. Moreover, a healthy diet has benefits beyond weight reduction on NAFLD patients whether obese or of normal weight. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation.
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NAFLD leads to liver cancer: Do we have sufficient evidence?
Cancer Lett.
PUBLISHED: 03-26-2013
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Primary liver cancer has several well-recognized risk factors, such as HBV and HCV infection, alcohol abuse and aflatoxin. Recent studies show that nonalcoholic fatty liver disease (NAFLD), especially its aggressive form nonalcoholic steatohepatitis (NASH) is associated with an increased risk of liver cancer, mainly hepatocellular carcinoma (HCC). On the other hand, clinical and epidemiological data have showed that HCC has rarely been found in a "pure" fatty liver in human. Thus, the question we need to ask is do we have sufficient evidence to support a causative role of NAFLD in liver cancer? Furthermore, if NAFLD is indeed a causative factor for liver cancer, what is the mechanism? Perhaps at this stage, fatty liver and NASH can be regarded as a definite risk factor for liver cancer, but to conclude that NAFLD induces HCC requires more robust in vitro and in vivo data.
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CD59 is overexpressed in human lung cancer and regulates apoptosis of human lung cancer cells.
Int. J. Oncol.
PUBLISHED: 03-21-2013
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CD59, belonging to membrane complement regulatory proteins (mCRPs), inhibits the cytolytic activity of complement and is overexpressed in many types of solid cancers. The aim of the present study was to detect the expression of CD59 in non-small cell lung cancer (NSCLC) and to investigate the relationship between decreased CD59 expression and tumorigenesis of NSCLC by transfecting recombinant retrovirus encoding shRNA targeting human CD59 into the human NSCLC cell line NCI-H157. CD59 expression in NSCLC was detected by immunocytochemistry (IHC). In the human NSCLC cell line NCI-H157, CD59 mRNA and protein expression suppressed with lentivirus-mediated RNAi was confirmed by using RT-PCR and western blotting, respectively. The proliferation and apoptosis of NCI-H157 cells was measured by using MTT assay and FACS. The resistance to complement cracking ability was detected by LDH assay. Caspase-3 expression in cells was assessed by IHC. Bcl-2 and Fas protein was determined by western blotting both in vitro and in vivo. CD59 is overexpressed in human NLCLC cancer. In NCI-H157 cells, lentivirus-mediated RNAi significantly reduced both CD59 mRNA and protein expression, which resulted in suppressing cell proliferation and increasing cell apoptosis. When incubated with fresh normal human serum (8%, v/v) for 1 h at 37?C, the cell viability was decreased and cell apoptosis was increased in siCD59-infected NCI-H157 cells compared to siCD59-C-infected cells. Reduced CD59 expression led to increased expression of caspase-3 and Fas and decreased expression of Bcl-2. Furthermore, the nude mouse tumor graft weight was significantly decreased and survival rate was significantly increased in the siCD59 group. CD59 is overexpressed in human NLCLC. CD59 silencing in NSCLC cancer cells via retrovirus-mediated RNAi can enhance complement-mediated cell apoptosis, inhibiting the growth of NSCLC. CD59 may serve as a potential target for gene therapy in NSCLC.
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Whole-genome haplotyping by dilution, amplification, and sequencing.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-18-2013
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Standard whole-genome genotyping technologies are unable to determine haplotypes. Here we describe a method for rapid and cost-effective long-range haplotyping. Genomic DNA is diluted and distributed into multiple aliquots such that each aliquot receives a fraction of a haploid copy. The DNA template in each aliquot is amplified by multiple displacement amplification, converted into barcoded sequencing libraries using Nextera technology, and sequenced in multiplexed pools. To assess the performance of our method, we combined two male genomic DNA samples at equal ratios, resulting in a sample with diploid X chromosomes with known haplotypes. Pools of the multiplexed sequencing libraries were subjected to targeted pull-down of a 1-Mb contiguous region of the X-chromosome Duchenne muscular dystrophy gene. We were able to phase the Duchenne muscular dystrophy region into two contiguous haplotype blocks with a mean length of 494 kb. The haplotypes showed 99% agreement with the consensus base calls made by sequencing the individual DNAs. We subsequently used the strategy to haplotype two human genomes. Standard genomic sequencing to identify all heterozygous SNPs in the sample was combined with dilution-amplification-based sequencing data to resolve the phase of identified heterozygous SNPs. Using this procedure, we were able to phase >95% of the heterozygous SNPs from the diploid sequence data. The N50 for a Yoruba male DNA was 702 kb whereas the N50 for a European female DNA was 358 kb. Therefore, the strategy described here is suitable for haplotyping of a set of targeted regions as well as of the entire genome.
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Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology.
J Diabetes
PUBLISHED: 03-17-2013
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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, affecting 20%-33% of the general population. Large population-based surveys in China indicate a prevalence of approximately 15%-30%. Worldwide, including in China, the prevalence of NAFLD has increased rapidly in parallel with regional trends of obesity, type 2 diabetes and metabolic syndrome. In addition, NAFLD has contributed significantly to increased overall, as well as cardiovascular and liver-related, mortality in the general population. In view of rapid advances in research into NAFLD in recent years, this consensus statement provides a brief update on the progress in the field and suggests preferred approaches for the comprehensive management of NAFLD and its related metabolic diseases.
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N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of doxorubicin by inhibiting activation of eukaryotic translation initiation factor 5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in hepatocellular carcinoma cells.
Exp. Cell Res.
PUBLISHED: 03-13-2013
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Hepatocellular carcinoma (HCC) cells undergo the epithelial-mesenchymal transition (EMT) during chemotherapy, which reduces the efficacy of doxorubicin-based chemotherapy. We investigated N1-guanyl-1,7-diaminoheptane (GC7) which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation; eIF5A2 is associated with chemoresistance. GC7 enhanced doxorubicin cytotoxicity in epithelial HCC cells (Huh7, Hep3B and HepG2) but had little effect in mesenchymal HCC cells (SNU387, SNU449). GC7 suppressed the doxorubicin-induced EMT in epithelial HCC cells; knockdown of eIF5A2 inhibited the doxorubicin-induced EMT and enhanced doxorubicin cytotoxicity. GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in HCC by inhibiting eIF5A2 activation and preventing the EMT.
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An integrative analysis of four CESA isoforms specific for fiber cellulose production between Gossypium hirsutum and Gossypium barbadense.
Planta
PUBLISHED: 03-04-2013
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Cotton fiber is an excellent model system of cellulose biosynthesis; however, it has not been widely studied due to the lack of information about the cellulose synthase (CESA) family of genes in cotton. In this study, we initially identified six full-length CESA genes designated as GhCESA5-GhCESA10. Phylogenetic analysis and gene co-expression profiling revealed that CESA1, CESA2, CESA7, and CESA8 were the major isoforms for secondary cell wall biosynthesis, whereas CESA3, CESA5, CESA6, CESA9, and CESA10 should involve in primary cell wall formation for cotton fiber initiation and elongation. Using integrative analysis of gene expression patterns, CESA protein levels, and cellulose biosynthesis in vivo, we detected that CESA8 could play an enhancing role for rapid and massive cellulose accumulation in Gossypium hirsutum and Gossypium barbadense. We found that CESA2 displayed a major expression in non-fiber tissues and that CESA1, a housekeeping gene like, was predominantly expressed in all tissues. Further, a dynamic alteration was observed in cell wall composition and a significant discrepancy was observed between the cotton species during fiber elongation, suggesting that pectin accumulation and xyloglucan reduction might contribute to cell wall transition. In addition, we discussed that callose synthesis might be regulated in vivo for massive cellulose production during active secondary cell wall biosynthesis in cotton fibers.
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Epidemiology of alcoholic and nonalcoholic fatty liver disease in China.
J. Gastroenterol. Hepatol.
PUBLISHED: 02-20-2013
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The prevalence of patients presenting with fatty liver disease (FLD) in China has approximately doubled over the past two decades. At present, FLD, which is typically diagnosed by imaging, is highly prevalent (? 27% urban population) in China and is mainly related to obesity and metabolic syndrome (MetS). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, China is likely to harbor an increasing reservoir of patients with FLD. The risk factors for FLD resemble to those of Caucasian counterparts, but the ethnic-specific definitions of obesity and MetS are more useful in assessment of Chinese people. Therefore, FLD/NAFLD has become a most common chronic liver disease in China. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.
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Investigation of water-soluble inclusion complex of hypericin with ?-cyclodextrin polymer.
Carbohydr Polym
PUBLISHED: 02-13-2013
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A water-soluble inclusion complex of hypericin (HY) with ?-cyclodextrin polymer (CDP) was achieved by supramolecular interactions between HY and CDP. The inclusion complex (HY-CDP) was characterized by (1)H NMR, FTIR, and UV-vis spectroscopies. Compared with HY, the water-solubility of HY-CDP was greatly enhanced because of the water-soluble CDP host. The mole ratio of ?-cyclodextrin (?-CD) unit in CDP to HY was determined as 2:1. At 25 °C, the dissociated constant of HY-CDP was measured as 1.47×10(-7) mol L(-1) by UV-vis spectroscopy. In the formation of inclusion complexes, CDP could overcome the ?-CD drawbacks - such as the poor water-solubility and the restriction of single cavity size, indicating it was able to use as a universal solubilizer for pharmaceutical application.
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FOXC1 in human trabecular meshwork cells is involved in regulatory pathway that includes miR-204, MEIS2, and ITG?1.
Exp. Eye Res.
PUBLISHED: 02-13-2013
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Forkhead box C1 (FOXC1) is a transcription factor that affects eye development. FOXC1 is implicated in the etiology of glaucoma because mutations in the gene are among the causes of Axenfeld-Rieger syndrome which is often accompanied by glaucoma. Glaucoma is the second leading cause of blindness. It is a complex disorder whose genetic basis in most patients remains unknown. Microarrays expression analysis was performed to identify genes in human trabecular meshwork (TM) primary cultures that are affected by FOXC1 and genes that may have roles in glaucoma. This represents the first genome wide analysis of FOXC1 target genes in any tissue. FOXC1 knock down by siRNAs affected the expression of 849 genes. Results on selected genes were confirmed by real time PCR, immunoblotting, and dual luciferase reporter assays. Observation of MEIS2 as a FOXC1 target and consideration of FOXC1 as a potential target of miR-204 prompted testing the effect of this micro RNA on expression of FOXC1 and several genes identified by array analysis as FOXC1 target genes. It was observed that miR-204 caused decreased expression of FOXC1 and the FOXC1 target genes CLOCK, PLEKHG5, ITG?1, and MEIS2 in the TM cultures. Expression of CLOCK, PLEKHG5, ITG?1 has not previously been reported to be affected by miR-204. The data suggest existence of a complex regulatory pathway in the TM part of which includes interactions between FOXC1, miR-204, MEIS2, and ITG?1. All these molecules are known to have TM relevant functions, and the TM is strongly implicated in the etiology of glaucoma.
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Regulation of adipose oestrogen output by mechanical stress.
Nat Commun
PUBLISHED: 02-02-2013
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Adipose stromal cells are the primary source of local oestrogens in adipose tissue, aberrant production of which promotes oestrogen receptor-positive breast cancer. Here we show that extracellular matrix compliance and cell contractility are two opposing determinants for oestrogen output of adipose stromal cells. Using synthetic extracellular matrix and elastomeric micropost arrays with tunable rigidity, we find that increasing matrix compliance induces transcription of aromatase, a rate-limiting enzyme in oestrogen biosynthesis. This mechanical cue is transduced sequentially by discoidin domain receptor 1, c-Jun N-terminal kinase 1, and phosphorylated JunB, which binds to and activates two breast cancer-associated aromatase promoters. In contrast, elevated cell contractility due to actin stress fibre formation dampens aromatase transcription. Mechanically stimulated stromal oestrogen production enhances oestrogen-dependent transcription in oestrogen receptor-positive tumour cells and promotes their growth. This novel mechanotransduction pathway underlies communications between extracellular matrix, stromal hormone output, and cancer cell growth within the same microenvironment.
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The RON receptor tyrosine kinase is a potential therapeutic target in Burkitt lymphoma.
Cancer Biol. Ther.
PUBLISHED: 01-29-2013
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Aberrant expression of the RON receptor tyrosine kinase is associated with tumor progression and carcinogenesis. The aims of this study were to determine the role and functional mechanisms of RON in Burkitt lymphoma (BL) and to document its potential as a therapeutic target.
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Effects of collagen and collagen hydrolysate from jellyfish umbrella on histological and immunity changes of mice photoaging.
Nutrients
PUBLISHED: 01-04-2013
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Jellyfish collagen (JC) was extracted from jellyfish umbrella and hydrolyzed to prepare jellyfish collagen hydrolysate (JCH). The effects of JC and JCH on UV-induced skin damage of mice were evaluated by the skin moisture, microscopic analyses of skin and immunity indexes. The skin moisture analyses showed that moisture retention ability of UV-induced mice skin was increased by JC and JCH. Further histological analysis showed that JC and JCH could repair the endogenous collagen and elastin protein fibers, and could maintain the natural ratio of type I to type III collagen. The immunity indexes showed that JC and JCH play a role in enhancing immunity of photoaging mice in vivo. JCH showed much higher protective ability than JC. These results suggest that JCH as a potential novel antiphotoaging agent from natural resources.
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A genome-wide survey of highly expressed non-coding RNAs and biological validation of selected candidates in Agrobacterium tumefaciens.
PLoS ONE
PUBLISHED: 01-01-2013
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Agrobacterium tumefaciens is a plant pathogen that has the natural ability of delivering and integrating a piece of its own DNA into plant genome. Although bacterial non-coding RNAs (ncRNAs) have been shown to regulate various biological processes including virulence, we have limited knowledge of how Agrobacterium ncRNAs regulate this unique inter-Kingdom gene transfer. Using whole transcriptome sequencing and an ncRNA search algorithm developed for this work, we identified 475 highly expressed candidate ncRNAs from A. tumefaciens C58, including 101 trans-encoded small RNAs (sRNAs), 354 antisense RNAs (asRNAs), 20 5 untranslated region (UTR) leaders including a RNA thermosensor and 6 riboswitches. Moreover, transcription start site (TSS) mapping analysis revealed that about 51% of the mapped mRNAs have 5 UTRs longer than 60 nt, suggesting that numerous cis-acting regulatory elements might be encoded in the A. tumefaciens genome. Eighteen asRNAs were found on the complementary strands of virA, virB, virC, virD, and virE operons. Fifteen ncRNAs were induced and 7 were suppressed by the Agrobacterium virulence (vir) gene inducer acetosyringone (AS), a phenolic compound secreted by the plants. Interestingly, fourteen of the AS-induced ncRNAs have putative vir box sequences in the upstream regions. We experimentally validated expression of 36 ncRNAs using Northern blot and Rapid Amplification of cDNA Ends analyses. We show functional relevance of two 5 UTR elements: a RNA thermonsensor (C1_109596F) that may regulate translation of the major cold shock protein cspA, and a thi-box riboswitch (C1_2541934R) that may transcriptionally regulate a thiamine biosynthesis operon, thiCOGG. Further studies on ncRNAs functions in this bacterium may provide insights and strategies that can be used to better manage pathogenic bacteria for plants and to improve Agrobacterum-mediated plant transformation.
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MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32.
Genome Med
PUBLISHED: 01-01-2013
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BACKGROUND: Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. METHODS: We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. RESULTS: Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. CONCLUSIONS: Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis supports a possible role of the 14q32 locus in osteosarcoma progression and outcome. Our study creates a paradigm for formalin-fixed, paraffin-embedded-based miRNA biomarker studies in cancer.
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Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes.
Gastroenterology
PUBLISHED: 01-01-2013
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Cholangiocarcinoma, the second most common liver cancer, can be classified as intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma. We performed an integrative genomic analysis of ICC samples from a large series of patients.
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Protective effects of two constituents of Chinese herbs on spinal motor neurons from embryonic rats with hypoxia injury.
Afr J Tradit Complement Altern Med
PUBLISHED: 12-29-2011
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Neuroprotective agents are becoming significant tools in the repair of central nervous system injuries. In this study, we determined whether ginkgolides (Gin, extract of GinkgoBiloba) and Acanthopanax senticosus saponins (ASS, flavonoids extracted from Acanthopanax herbal preparations) have protective effects on rat spinal cords exposed to anoxia and we explored the mechanisms that underlie the protective effects. Spinal motor neurons (SMNs) from rat spinal cords were obtained and divided into five groups with 10 wells in each group. In control group, SMNs suffered no injury under normal oxygen; in hypoxia- inducible (HI) group, SMNs suffered injury from hypoxia; in Gin group, 37.5µg/ml Gin were used before 24 hrs of hypoxia; in ASS group, 50µg/ml ASS were used before 24 hrs of hypoxia;in glial cell-lined derived neurotrophic factor (GDNF) group, 0.1µg/ml GDNF were used before 24 hrs of hypoxia. Changes in morphology, neuron viability, and lactate dehydrogenase (LDH) release were observed. In addition, the expression of HIF-1? induced by hypoxia was measured. The neuronal viability in the Gin, ASS, and GDNF pretreated groups was higher than that in the HI group (P<0.05). The viability in the Gin group was better than that in the ASS group (P<0.05), but there was no significant difference between the ASS and GDNF groups (P>0.05). The quantity of LDH released in the three pretreated groups was lower than that in the HI group (P<0.05). The expression of HIF-1? in the HI group was greater than that in the control group (P<0.05), and the expression in the three pretreated groups was greater than that in the HI and the control groups (P<0.05). Our results indicate that Gin and ASS which was not as effective as Gin, but its effects were similar to those of GNDF could all enhance the viability of SMNs and have protective effects on hypoxic neurons.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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