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Find video protocols related to scientific articles indexed in Pubmed.
Rationalizing Inter- and Intracrystal Heterogeneities in Dealuminated Acid Mordenite Zeolites by Stimulated Raman Scattering Microscopy Correlated with Super-Resolution Fluorescence Microscopy.
ACS Nano
PUBLISHED: 11-18-2014
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Dealuminated zeolites are widely used acid catalysts in research and chemical industry. Bulk-level studies have revealed that the improved catalytic performance results from an enhanced molecular transport as well as from changes in the active sites. However, fully exploiting this information in rational catalysts design still requires insight in the intricate interplay between both. Here we introduce fluorescence and stimulated Raman scattering microscopy to quantify sub-crystal reactivity as well as acid site distribution, and to probe site accessibility in the set of individual mordenite zeolites. Dealumination effectively introduces significant heterogeneities between different particles and even within individual crystals. Besides enabling direct rationalization of the nanoscale catalytic performance these observations reveal valuable information on the industrial dealumination process itself.
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Point spread function analysis with saturable and reverse saturable scattering.
Opt Express
PUBLISHED: 11-18-2014
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Nonlinear plasmonics has attracted a lot of interests due to its wide applications. Recently, we demonstrated saturation and reverse saturation of scattering from a single plasmonic nanoparticle, which exhibits extremely narrow side lobes and central peaks in scattering images [ACS Photonics 1(1), 32 (2014)]. It is desirable to extract the reversed saturated part to further enhance optical resolution. However, such separation is not possible with conventional confocal microscope. Here we combine reverse saturable scattering and saturated excitation (SAX) microscopy. With quantitative analyses of amplitude and phase of SAX signals, unexpectedly high-order nonlinearities are revealed. Our result provides greatly reduced width in point spread function of scattering-based optical microscopy. It will find applications in not only nonlinear material analysis, but also high-resolution biomedical microscopy.
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Disruption of the Nuclear Membrane by Perinuclear Inclusions of Mutant Huntingtin Causes Cell-Cycle Re-entry and Striatal Cell Death in Mouse and Cell Models of Huntington's Disease.
Hum. Mol. Genet.
PUBLISHED: 11-16-2014
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Accumulation of N-terminal fragments of mutant huntingtin (mHTT) in the cytoplasm, nuclei, and axons of neurons is a hallmark of Huntington's disease (HD), although how these fragments negatively impact neurons remains unclear. We followed the distribution of mHTT in the striata of transgenic R6/2-J2 HD mice as their motor function declined. The fraction of cells with diffuse, perinuclear or intranuclear mHTT changed in parallel with decreasing motor function. In transgenic mice, medium spiny neurons (MSNs) that exhibited perinuclear inclusions expressed cell cycle markers typically not seen in the striata of normal mice and these cells are preferentially lost as disease progresses. Electron microscopy reveals that perinuclear inclusions disrupt the nuclear envelope. The progression of perinuclear inclusions being accompanied by cell cycle activation and culminating in cell death was also observed in 1° cortical neurons. These observations provide a strong correlation between the subcellular location of mHTT, disruption of the nucleus, reentry into the cell cycle and eventual neuronal death. They also highlight the fact that the subcellular distribution of mHTT is highly dynamic such that the distribution of mHTT observed depends greatly on the stage of the disease being examined.
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Diastereoselective Synthesis of 2-Arylmethylene-6-hydroxyspiro[4.5]deca-7-ones via FeCl3.6H2O-Catalyzed Spiroannulation/Hydride Transfer of 6-(5-Arylpent-4-yn-1-yl)-7-oxabicyclo[4.1.0]heptan-2-ols.
J. Org. Chem.
PUBLISHED: 11-15-2014
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In the presence of a catalytic amount of FeCl3.6H2O, 6-(5-arylpent-4-yn-1-yl)-7-oxabicyclo[4.1.0]heptan-2-ols underwent attack of the pendant acetylene at the iron-activated oxirane to give a vinylic carbonium ion. Hydride transfer from the carbinol carbon to the newly formed cation center furnished 2-arylmethylene-6-hydroxyspiro[4.5]deca-7-ones in excellent stereoselectivity and good yields.
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Solar nebula magnetic fields recorded in the Semarkona meteorite.
Science
PUBLISHED: 11-15-2014
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Magnetic fields are proposed to have played a critical role in some of the most enigmatic processes of planetary formation by mediating the rapid accretion of disk material onto the central star and the formation of the first solids. However, there have been no experimental constraints on the intensity of these fields. Here we show that dusty olivine-bearing chondrules from the Semarkona meteorite were magnetized in a nebular field of 54 ± 21 ?T. This intensity supports chondrule formation by nebular shocks or planetesimal collisions rather than by electric currents, the x-wind, or other mechanisms near the sun. This implies that background magnetic fields in the terrestrial planet-forming region were likely 5-54 ?T, which is sufficient to account for measured rates of mass and angular momentum transport in protoplanetary disks.
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Establishment of a New Ovarian Cancer Cell Line CA5171.
Reprod Sci
PUBLISHED: 11-15-2014
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A new cell line, CA5171, derived from a chemotherapy-naive, high-grade undifferentiated ovarian carcinoma was established and characterized. The CA5171 cells presented with cobblestone morphology and a doubling time of 24 hours. Gene mutation analysis showed that the cells belonged to the type II ovarian cancer pathway with mutations of PIK3CA, PTEN, and TP53. Single-nucleotide polymorphism array analysis showed no homozygous gene deletion; however, several loci of gene copy number gains were noted in chromosome 1, 2, 5, 9, 10, 12, 15, 16, 20, and X. The in vitro and in vivo experiments showed that the cells were sensitive to paclitaxel and doxorubicin, but resistant to cisplatin. The cells also presented epithelial-mesenchymal transition properties that may have been related to their invasion and migration potential. The CA5171 cells show the potential as a new cell line for studies on epithelial ovarian carcinoma.
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Laparoendoscopic single-site herniorrhaphy after gynecologic surgery.
JSLS
PUBLISHED: 11-14-2014
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Increased interest in laparoendoscopic single-site surgery has instigated research into trials of novel techniques. The procedure we propose may potentially improve patient satisfaction and cosmetic results while diminishing the incidence of trocar-site herniation. We report our initial experience with laparoendoscopic single-site totally extraperitoneal herniorrhaphy for postoperative incisional hernia to determine the procedure's feasibility and safety.
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Advanced Hepatic Fibrosis and Steatosis Are Associated with Persistently Alanine Aminotransferase Elevation in Chronic Hepatitis C Patients Negative for HCV RNA During Pegylated Interferon Plus Ribavirin Therapy.
J. Infect. Dis.
PUBLISHED: 11-13-2014
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?Clinical implications of persistently alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy remain unknown.
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EFFECT OF THE RECREATIONAL LIFE REVIEW PROGRAM ON PATIENTS WITH DEMENTIA IN AN OUTPATIENT CLINIC: A PRELIMINARY STUDY (.)
Percept Mot Skills
PUBLISHED: 11-07-2014
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Summary.-The purpose of this study is to investigate the effect of the Life Review Program-Taiwan (LRP-TW) on outpatients with mild to moderate dementia. Ten individuals were selected through purposive sampling and tested using a single group pretest-posttest design. The Mini-Mental State Examination (MMSE), the Loewenstein Occupational Therapy Cognitive Assessment-Geriatric (LOTCA-G) and the Geriatric Depression Scale-Short Form (GDS-SF) were used as outcome measures. The total scores and three subtests of the LOTCA-G revealed significant differences after the intervention. Affective function remained stable through the experiment. The LRP-TW may offer a clinical intervention program for supporting cognitive and mental performance in individuals with dementia.
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[Imaging study of paravertebral muscle degeneration in degenerative lumbar instability].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 11-06-2014
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To compare the paravertebral muscle (such as multifidus, erector spinae, psoas muscle) changes between the patients with degenerative lumbar instability and normal person by MRI and to observe the degeneration of paravertebral muscles. To analyze the relationship between paravertebral muscle degeneration and lumbar curvature of degenerative lumbar instability.
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SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-05-2014
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Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and ?-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.
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Effect of surface Si redistribution on the alignment of Ge dots grown on pit-patterned Si(001) substrates.
Nanotechnology
PUBLISHED: 11-05-2014
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Thermally activated redistribution of Si surface atoms is found to be a crucial factor for the growth of aligned Ge dots on pit-patterned Si(001) substrates. A phenomenon of Si accumulation around the edge of pits significantly alters the substrate surface morphology. As the pit spacing is reduced to below 100 nm, a convex morphology developed between adjacent pits causes a chemical potential distribution that drives the Ge dots into the pits. In addition, the pits of an etching depth greater than 60 nm will evolve into truncated inverted pyramids with sharp base corners that provide deep potential wells for the confinement of Ge dots. Perfectly aligned Ge dots are obtained on pit-patterned Si substrates with this range of pit spacing and etching depth. We also find that the initial geometric shape of the pits does not affect the spatial arrangement of Ge dots.
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Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.
J. Oral Pathol. Med.
PUBLISHED: 10-21-2014
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Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms.
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Psychosocial adjustments in patients with prostate cancer from pre-diagnosis to 6 months post-treatment.
Int J Nurs Pract
PUBLISHED: 10-14-2014
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We evaluated changes in psychosocial adjustment over time and its associated factors in prostate cancer patients. A total of 69 patients with prostate cancer were surveyed at pre-diagnosis, 1 month and 6 months post-treatment. The questionnaires distributed to the patients consisted of the Psychosocial Adjustment to Illness Scale and the UCLA Prostate Cancer Index. The generalized estimating equations were used to analyse the collected data. The results of adjustments to psychological distress, the domestic environment and the social environment worsened post-treatment. However, the adjustment to health-care orientation was worst at the time of pre-diagnosis and improved during post-treatment. Patients who perceived an unfavourable health status reported poor adjustment in psychological distress. Patients exhibiting poor urinary function poorly adjusted to the domestic environment. Patients with sexual dysfunction exhibited poor adjustment to the social environment. Patients with low education demonstrated poor adjustment to health-care orientation. Further studies should assess the psychosocial adjustment among prostate cancer patients and provide interventions following pre-diagnosis.
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Term delivery of a complete hydatidiform mole with a coexisting living fetus followed by successful treatment of maternal metastatic gestational trophoblastic disease.
Taiwan J Obstet Gynecol
PUBLISHED: 10-08-2014
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A twin pregnancy consisting of a complete hydatidiform mole with a coexisting normal fetus is extremely rare with an incidence of 1/22,000 to 1/100,000. The incidence of preterm delivery is high and few pregnancies reach near term with a viable fetus.
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Electronic Structure of Open-Shell Tetrahedral {Fe(NO)2}(9) Dinitrosyliron Complexes.
Inorg Chem
PUBLISHED: 10-03-2014
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High-level ab initio excited-state theory is employed to investigate the electronic structure of doublet {Fe(NO)2}(9) species in the ground state and compared with the results obtained by density functional theory. Both of the approaches consistently suggest that the linear NO ligands in dinitrosyliron complexes (DNICs) feature a radical character. Theoretical calculations also predict that the cyanide-supported DNIC anion of [(NC)2Fe(NO)2](-) features C2v symmetry with a Fe-C-N bonding motif, and multireference theories suggest a minimal active space of CAS(9,9) to describe these {Fe(NO)2}(9) compounds, while larger CAS(13,13) calculations do not tend to significantly improve the geometries. Experimental vibration modes of NO ligands are also accurately assigned due to second-order n-electron valence state perturbation theory.
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The complete mitochondrial genome of the small Indian civet, Viverricula indica taivana - the first complete representation of the genus Viverricula.
Mitochondrial DNA
PUBLISHED: 09-18-2014
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Abstract The complete mitochondrial genome of Viverricula indica taivana, exclusive of tandem repeats within the control region, is 16,583?bp in length, with a total base composition of: 33.18% A, 28.93% T, 24.88% C, and 13.00% G in H-strand. The genome contains 37 genes, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region.
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Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression and ARID1A expression.
Histopathology
PUBLISHED: 09-09-2014
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We aimed to understand the role and difference in molecular alterations between endometrial and ovarian endometrioid adenocarcinomas.
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Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia.
PLoS ONE
PUBLISHED: 09-03-2014
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The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV-infected Taiwanese patients who received TMP/SMX for pneumocystosis. Concomitant use of fluconazole was associated with decreased risk for TMP/SMX-related hepatotoxicity.
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Increasing Biopsy Number and Sampling from Gastric Body Improve the Sensitivity of Rapid Urease Test in Patients with Peptic Ulcer Bleeding.
Dig. Dis. Sci.
PUBLISHED: 09-01-2014
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Previous studies demonstrated that the sensitivity of rapid urease test (RUT) for diagnosis of Helicobacter pylori infection decreased during peptic ulcer bleeding.
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Multimodality treatment for cardiac angiosarcoma.
Intern. Med.
PUBLISHED: 09-01-2014
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Primary cardiac angiosarcoma is a rare and highly malignant condition. Besides performing complete surgical excision, it remains controversial as to whether survival can be improved with additional treatment. We herein describe a 30-year-old man with a right atrial angiosarcoma. He underwent two operations for the resection of the primary lesion, and the patient's metastatic lesions involved an intestinal segment. With chemotherapy, radiotherapy, and molecular targeted therapy, he survived for 33 months. The literature describing adjuvant therapy for cardiac angiosarcoma, which is mostly case reports, is also reviewed. In conclusion, the limited evidence suggests that multimodality treatment for cardiac angiosarcoma is a beacon of hope to improve the survival of such patients.
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Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.
J Int AIDS Soc
PUBLISHED: 08-28-2014
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The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated.
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Expansive open-door laminoplasty secured with titanium miniplates is a good surgical method for multiple-level cervical stenosis.
J Orthop Surg Res
PUBLISHED: 08-21-2014
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Laminoplasty is an effective procedure for treating cervical spondylotic myelopathy (CSM). Little information is available regarding the surgical outcomes of expansive open-door laminoplasty (EOLP) when securing with titanium miniplates without bone grafting. This study is aimed to elucidate the efficacy of and problems associated with EOLP secured with titanium miniplates without bone grafting, thereby enhancing future surgical outcomes.
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Unusual branch of external iliac artery.
J Minim Invasive Gynecol
PUBLISHED: 08-19-2014
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We report first time in English literature, case of an unusual branch of right external iliac artery in a 75 year old patient during laparoscopic staging for endometrial adenocarcinoma. Awareness of this variation in branching might be useful during pelvic lymphadenectomy.
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Dynamics of structural relaxation of stilbene 3 in solution, cetyltrimethylammonium bromide micelle, and bis(2-ethylhexyl) sulfosuccinate reverse micelle.
J Phys Chem B
PUBLISHED: 08-15-2014
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The relaxation dynamics of the excited states of stilbene 3 in various solvents, confined environment cetyltrimethylammonium bromide (CTAB) micelle, and water/bis(2-ethylhexyl) sulfosuccinate (AOT)/hexane reverse micelle are investigated. In the time-resolved decay curves of fluorescence measured in solution at excitation wavelength 256 or 266 nm, stilbene 3 underwent initially an ultrafast internal conversion to the S2 state or was directly excited at the S2 then via a conformational relaxation with time constant 1.1-4.6 ps. This relaxation process displays a linear dependence on solvent viscosity. Slow relaxation in deuterated methanol and water is explained that the vibrational energy is efficiently coupled to the librational modes of solvent. The conformational relaxation rate decreases slightly in the CTAB micelle but is greatly hindered in the AOT reverse micelle with small cavities. According to the results of anisotropy measurements, in both CTAB and AOT reverse micelles with a cavity diameter as large as ?7 nm, the dynamics of molecular rotation remain significantly hindered.
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Comorbidities among the HIV-infected patients aged 40 years or older in Taiwan.
PLoS ONE
PUBLISHED: 08-13-2014
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With the widespread use of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients has significantly prolonged. An increasing number of HIV-infected patients are aging and concurrent use of medications are not uncommon for management of metabolic complications and cardiovascular diseases related to aging and prolonged exposure to cART.
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An increased risk of epithelial ovarian cancer in Taiwanese women with a new surgico-pathological diagnosis of endometriosis.
BMC Cancer
PUBLISHED: 08-10-2014
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Epidemiological evidence of relationships between endometriosis and epithelial ovarian cancer (EOC) has been obtained mainly from Western countries. Our goal was to determine the risk of EOC due to endometriosis in Taiwanese women.
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Pterostilbene suppresses oral cancer cell invasion by inhibiting MMP-2 expression.
Expert Opin. Ther. Targets
PUBLISHED: 08-09-2014
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Polyphenol compounds, present in a wide variety of natural plants, exhibit antioxidant and free radical scavenging ability and induce apoptosis in various cancer cells. However, the effect of pterostilbene on oral cancer cell metastasis has not been clarified.
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Engineering Organic Macrocycles and Cages: Versatile Bonding Approaches.
Chem Asian J
PUBLISHED: 08-06-2014
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The emergence of supramolecular chemistry has led to the discovery of a rising number of macrocycles and cages with a range of functionalities. Most of these supramolecular aggregates are metal coordination networks, whereas pure organic assemblies are less developed. Organic macrocycles and cages have the advantages of chemical robustness, processability in organic solvents, and suitability for pilot-scale applications. They are constructed primarily from covalent bonds, with irreversible and reversible bond types. We herein highlight the use of different versatile bonding approaches in engineering these soft materials, as well as their emerging applications, such as gas storage, thin films, liquid crystals, and catalysis.
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Characteristic Tandem Mass Spectral Features Under Various Collision Chemistries for Site-Specific Identification of Protein S-Glutathionylation.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 07-29-2014
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Protein S-glutathionylation is a reversible post-translational modification widely implicated in redox regulated biological functions. Conventional biochemical methods, however, often do not allow such a mixed disulfide modification to be reliably identified on specific cysteine residues or be distinguished from other related oxidized forms. To develop more efficient mass spectrometry (MS)-based analytical strategies for this purpose, we first investigated the MS/MS fragmentation pattern of S-glutathionylated peptides under various dissociation modes, including collision-induced dissociation (CID), higher-energy C-trap dissociation (HCD), and electron transfer dissociation (ETD), using synthetic peptides derived from protein tyrosine phosphatase as models. Our results indicate that a MALDI-based high energy CID MS/MS on a TOF/TOF affords the most distinctive spectral features that would facilitate rapid and unambiguous identification of site-specific S-glutathionylation. For more complex proteomic samples best tackled by LC-MS/MS approach, we demonstrate that HCD performed on an LTQ-Orbitrap hybrid instrument fairs better than trap-based CID and ETD in allowing more protein site-specific S-glutathionylation to be confidently identified by direct database searching of the generated MS/MS dataset using Mascot. Overall, HCD afforded more peptide sequence-informative fragment ions retaining the glutathionyl modification with less neutral losses of side chains to compromise scoring. In conjunction with our recently developed chemo-enzymatic tagging strategy, our nanoLC-HCD-MS/MS approach is sufficiently sensitive to identify endogenous S-glutathionylated peptides prepared from non-stressed cells. It is anticipated that future applications to global scale analysis of protein S-glutathionylation will benefit further from current advances in both speed and mass accuracy afforded by HCD MS/MS mode on the Orbitrap series.
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Novel multipotent AChEI-CCB attenuates hyperhomocysteinemia-induced memory deficits and Neuropathologies in rats.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
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Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3?. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
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A meta-learning approach for B-cell conformational epitope prediction.
BMC Bioinformatics
PUBLISHED: 07-11-2014
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BackgroundOne of the major challenges in the field of vaccine design is identifying B-cell epitopes in continuously evolving viruses. Various tools have been developed to predict linear or conformational epitopes, each relying on different physicochemical properties and adopting distinct search strategies. We propose a meta-learning approach for epitope prediction based on stacked and cascade generalizations. Through meta learning, we expect a meta learner to be able integrate multiple prediction models, and outperform the single best-performing model. The objective of this study is twofold: (1) to analyze the complementary predictive strengths in different prediction tools, and (2) to introduce a generic computational model to exploit the synergy among various prediction tools. Our primary goal is not to develop any particular classifier for B-cell epitope prediction, but to advocate the feasibility of meta learning to epitope prediction. With the flexibility of meta learning, the researcher can construct various meta classification hierarchies that are applicable to epitope prediction in different protein domains.ResultsWe developed the hierarchical meta-learning architectures based on stacked and cascade generalizations. The bottom level of the hierarchy consisted of four conformational and four linear epitope prediction tools that served as the base learners. To perform consistent and unbiased comparisons, we tested the meta-learning method on an independent set of antigen proteins that were not used previously to train the base epitope prediction tools. In addition, we conducted correlation and ablation studies of the base learners in the meta-learning model. Low correlation among the predictions of the base learners suggested that the eight base learners had complementary predictive capabilities. The ablation analysis indicated that the eight base learners differentially interacted and contributed to the final meta model. The results of the independent test demonstrated that the meta-learning approach markedly outperformed the single best-performing epitope predictor.ConclusionsComputational B-cell epitope prediction tools exhibit several differences that affect their performances when predicting epitopic regions in protein antigens. The proposed meta-learning approach for epitope prediction combines multiple prediction tools by integrating their complementary predictive strengths. Our experimental results demonstrate the superior performance of the combined approach in comparison with single epitope predictors.
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Cotton-based Diagnostic Devices.
Sci Rep
PUBLISHED: 06-30-2014
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A good diagnostic procedure avoids wasting medical resources, is easy to use, resists contamination, and provides accurate information quickly to allow for rapid follow-up therapies. We developed a novel diagnostic procedure using a "cotton-based diagnostic device" capable of real-time detection, i.e., in vitro diagnostics (IVD), which avoids reagent contamination problems common to existing biomedical devices and achieves the abovementioned goals of economy, efficiency, ease of use, and speed. Our research reinforces the advantages of an easy-to-use, highly accurate diagnostic device created from an inexpensive and readily available U.S. FDA-approved material (i.e., cotton as flow channel and chromatography paper as reaction zone) that adopts a standard calibration curve method in a buffer system (i.e., nitrite, BSA, urobilinogen and uric acid assays) to accurately obtain semi-quantitative information and limit the cross-contamination common to multiple-use tools. Our system, which specifically targets urinalysis diagnostics and employs a multiple biomarker approach, requires no electricity, no professional training, and is exceptionally portable for use in remote or home settings. This could be particularly useful in less industrialized areas.
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Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations.
Hum. Pathol.
PUBLISHED: 05-31-2014
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This study aims to evaluate the relationships between chromosome 20q13.2 zinc finger protein 217 (ZNF217) locus amplification, ZNF217 expression, E-cadherin expression, and PI3K-Akt pathway alterations (activating PIK3CA mutations or loss of phosphatase and tensin homolog [PTEN] expression), and whether these molecular alterations can predict the clinical survival data in ovarian clear cell carcinoma (OCCC) patients. Samples and clinical data of 72 OCCC patients were collected. Chromosome 20q13.2 ZNF217 locus amplification was detected by fluorescence in situ hybridization. ZNF217, E-cadherin and PTEN expression were assessed using immunohistochemical stain. PIK3CA mutation was identified by PCR-amplified gene sequencing. Cox proportional hazard regression model was used to estimate the adjusted hazard ratios of survival. Chromosome 20q13.2 ZNF217 locus amplification was detected in 31% (22/72) of cases, and ZNF217 expression was increased in 40% (27/68) of cases. E-cadherin and PTEN expressions were decreased or lost in 44% (32/72) and 14% (10/72) of cases, respectively. Activating PIK3CA mutations were present in 35% (25/72) of cases. Thirty-three OCCC patients (46%) showed activating PI3K-Akt pathway alterations. Chromosome 20q13.2 ZNF217 locus amplification was significantly associated with decreased E-cadherin expression (P = .001). In contrast, ZNF217 expression was not related to ZNF217 amplification or E-cadherin expression. In OCCC patients with activating PI3k-Akt pathway, decreased E-cadherin expression (P = .033) and advanced Federation of Gynecology and Obstetrics stage (P = .014) predicted shorter overall survival. Two conclusions were raised in our study. First, ZNF217 plays a role in down-regulating E-cadherin expression and is a potential therapeutic target for OCCC patients. Second, E-cadherin expression is a prognostic marker for OCCC patients with activating PI3K-Akt pathway.
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Efficiency of three-dimensional Doppler ultrasonography in assessing nodal metastasis of head and neck cancer.
Eur Arch Otorhinolaryngol
PUBLISHED: 05-31-2014
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The aim of this study was to assess the clinical usefulness of three-dimensional (3D) color Doppler ultrasonography with a novel predictive model in the detection of cervical metastasis of untreated head and neck squamous cell carcinoma patients. We assessed cervical lymph node metastasis in 52 head and neck squamous cell carcinoma patients by 3D color Doppler ultrasonography, magnetic resonance imaging, and [(18)F] fluorodeoxyglucose positron emission tomography with computed tomography. Pathologic analysis was used as the gold standard for evaluation of these imaging modalities. The rate of correct N staging was 84.6 % on ultrasonography, 55.8 % on magnetic resonance imaging, and 71.2 % on positron emission tomography/computed tomography. On a level-by-level basis, the ultrasonography had 78.9 % sensitivity, 99.0 % specificity, 93.8 % positive predictive value, 96.0 % negative predictive value, and 95.7 % accuracy. It also showed the highest agreement to histology results as compared with magnetic resonance imaging and positron emission tomography/computed tomography (kappa value = 0.832, 0.506, and 0.537, respectively). 3D Doppler ultrasonography with our prediction model provides a rapid, low-cost, noninvasive, and reliable method with low inter-observation variations for detecting neck metastasis of head and neck squamous cell carcinoma patients.
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Long-term survival outcome of laparoscopic staging surgery for endometrial cancer in Taiwanese experience.
Taiwan J Obstet Gynecol
PUBLISHED: 04-29-2014
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This study aims to evaluate the long-term safety and efficacy of laparoscopic staging surgery (LSS) for endometrial cancer in Taiwanese women.
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Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review.
World J. Gastroenterol.
PUBLISHED: 04-27-2014
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Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to the shared modes of transmission, coinfection with HBV and human immunodeficiency virus (HIV) is not uncommon. It is estimated that 10% of HIV-infected patients worldwide are coinfected with HBV. In areas where an HBV vaccination program is implemented, the HBV seroprevalence has declined significantly. In HIV/HBV-coinfected patients, HBV coinfection accelerates immunologic and clinical progression of HIV infection and increases the risk of hepatotoxicity when combination antiretroviral therapy (cART) is initiated, while HIV infection increases the risk of hepatitis events, cirrhosis, and end-stage liver disease related to chronic HBV infection. With the advances in antiviral therapy, concurrent, successful long-term suppression of HIV and HBV replication can be achieved in the cART era. To reduce the disease burden of HBV infection among HIV-infected patients, adoption of safe sex practices, avoidance of sharing needles and diluent, HBV vaccination and use of cART containing tenofovir disoproxil fumarate plus emtricitabine or lamivudine are the most effective approaches. However, due to HIV-related immunosuppression, using increased doses of HBV vaccine and novel approaches to HBV vaccination are needed to improve the immunogenicity of HBV vaccine among HIV-infected patients.
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The impact of climate factors on the prevalence of urolithiasis in Northern Taiwan.
Biomed J
PUBLISHED: 03-27-2014
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Urolithiasis is a common disease with high prevalence and recurrence. Its incidence varies in different geographic locations, and there are evidences that meteorological factors also affect urinary stone formation. The aim of this study is to analyze the effects of climate parameters on the numbers of shockwave treatments for urinary stones in our hospital, in order to understand the effects of these parameters on the prevalence of urolithiasis in northern Taiwan.
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Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection.
Clin. Infect. Dis.
PUBLISHED: 03-05-2014
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Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV.
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Nemonoxacin (TG-873870) for treatment of community-acquired pneumonia.
Expert Rev Anti Infect Ther
PUBLISHED: 03-03-2014
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With a broad-spectrum of activity, fluoroquinolones have been widely and successfully used for decades for the treatment of and prophylaxis against various bacterial infections, including community-acquired pneumonia (CAP). However, the use of fluoroquinolones has been compromised by the emergence and spreading of bacterial resistance and the potential for adverse effects. Therefore, there is an unmet need for newer compounds that have a broader spectrum of activity to overcome existing bacterial resistance as well as the potential to minimize the risk of adverse effects. Nemonoxacin (TG-873870), a newly developed quinolone, has demonstrated broad-spectrum activity against Gram-positive, Gram-negative and atypical pathogens, including drug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. Results from Phases I and II studies of treatment of CAP are encouraging. This article reviews the updated data on nemonoxacin, including the bacterial susceptibility, the pharmacologic characteristics, and toxicities, and clinical trials using nemonoxacin for treatment of CAP.
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TERT promoter mutation is uncommon in acral lentiginous melanoma.
J. Cutan. Pathol.
PUBLISHED: 02-28-2014
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Melanoma is a heterogeneous group of diseases with distinct sets of genetic changes. Recurrent and mutually exclusive C>T or CC>TT transition mutations were identified in the promoter region of the reverse transcriptase catalytic subunit of the telomerase gene (TERT) in melanoma recently, and it was suggested that they enhanced the expression of TERT gene and played important roles in the melanoma pathogenesis. These mono or di-nucleotide transitions were ultraviolet (UV)-signature mutations.
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Tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway.
Biomed Res Int
PUBLISHED: 02-26-2014
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Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.
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Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.
Mod. Pathol.
PUBLISHED: 02-24-2014
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Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.Modern Pathology advance online publication, 1 August 2014; doi:10.1038/modpathol.2014.93.
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Identification of genes with consistent methylation levels across different human tissues.
Sci Rep
PUBLISHED: 02-17-2014
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DNA methylation plays an important role in regulating cell growth and disease development. Methylation profiles are examined by bisulfite conversion; however, the lack of markers for bisulfite conversion efficiency and appropriate internal control genes remains a major challenge. To address these issues, we utilized two bioinformatics approaches, coefficients of variances and resampling tests, to identify probes showing stable methylation levels from several independent microarray datasets. Mass spectrometry validated the consistently high methylation levels of the five probes (N4BP2, EGFL8, CTRB1, TSPAN3, and ZNF690) in 13 human tissue types from 24 cell lines. Linear associations between detected methylation levels and methyl concentrations of DNA samples were further demonstrated in three genes (N4BP2, EGFL8, and CTRB1). To summarize, we identified five genes which may serve as internal controls for methylation studies by analyzing large-scale microarray data, and three of them can be used as markers for evaluating the efficiency of bisulfite conversion.
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Increased expression of carbonic anhydrase IX in oral submucous fibrosis and oral squamous cell carcinoma.
Clin. Chem. Lab. Med.
PUBLISHED: 02-07-2014
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Cumulative evidence has demonstrated that carbonic anhydrase IX (CAIX) is upregulated in many types of human cancers. We attempted to evaluate plasma levels of CAIX in patients with oral cancer and investigated whether plasma CAIX is correlated with the progression of this disease.
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Novel Au/La-SrTiO3 microspheres: superimposed effect of gold nanoparticles and lanthanum doping in photocatalysis.
Chem Asian J
PUBLISHED: 02-03-2014
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Novel multielement Au/La-SrTiO(3) microspheres were synthesized by a solvothermal method using monodisperse gold and La-SrTiO(3) nanocrystals as building blocks. The porous Au/La-SrTiO(3) microspheres had a large surface area of 94.6?m(2) ?g(-1). The stable confined Au nanoparticles demonstrated strong surface plasmon resonance effect, leading to enhanced absorption in a broad UV/Vis/NIR range. Doping of rare-earth metal La also broadened the absorption band to the visible region. Both the conduction and valence bands of Au/La-SrTiO(3) microspheres thus show favorable potential for proton reduction under visible light. The superimposed effect of Au nanoparticles and La doping in Au/La-SrTiO(3) microspheres led to high photocurrent density in photoelectrochemical water splitting and good photocatalytic activity in photodegradation of rhodamine?B. The photocatalytic activities are in the order of the following: Au/La-SrTiO(3) microspheres>Au/SrTiO(3) microspheres>La-SrTiO(3) microspheres>SrTiO(3) microspheres.
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Endoscopic resection of intranasal meningo-encephalocele accompanying meningioma.
Auris Nasus Larynx
PUBLISHED: 02-03-2014
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This paper aims to present the case of a 43-year-old woman diagnosed with a rare condition of meningoencephalocele that arose from a meningioma, and treated with endoscope-assisted transnasal tumor extirpation and repair of the skull base defect with tensor fascia lata flap. Endoscope-assisted operation is a viable and minimally invasive alternative to traditional craniotomy. With improved endoscopic equipment and operative technique, we can perform more reliable surgery and provide better quality of life for these patients.
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Extraocular well-differentiated sebaceous tumors with overlying cutaneous horns: four tumors in three patients.
J. Cutan. Pathol.
PUBLISHED: 02-03-2014
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Sebaceous tumors are adnexal neoplasms showing sebocytic differentiation. They range from benign to malignant and are associated with Muir-Torre syndrome (MTS). Several clinical and histopathological features associated with MTS have been described. Sebaceous tumors with an overlying cutaneous horn are extremely rare.
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Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-?B and AP-1 activity in human liver cancer cells.
Br. J. Pharmacol.
PUBLISHED: 01-27-2014
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High mortality and morbidity rates for hepatocellular carcinoma in Taiwan primarily result from uncontrolled tumour metastasis. Glabridin, a prenylated isoflavonoid of licorice (Glycyrrhiza?glabra) roots, is associated with a wide range of biological properties, such as regulation of energy metabolism, oestrogenic, neuroprotective, anti-osteoporotic and skin whitening. However, the effect of glabridin on the metastasis of tumour cells has not been clarified.
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Losartan-induced hypotension leads to tau hyperphosphorylation and memory deficit.
J. Alzheimers Dis.
PUBLISHED: 01-23-2014
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Recent studies have reported a correlation between dementia and low blood pressure. How hypotension is associated with the increased risk of Alzheimer's disease (AD) remains unclear. Here we show that one month treatment of losartan, an angiotensin II type 1 (AT1) receptor antagonist, causes chronic and sustained hypotension, along with oxidative stress in adult male Sprague-Dawley rats. Furthermore, we show that losartan treatment increases the level of inactivated protein phosphatase 2A (PP2A) and the hyperphosphorylation of tau at Ser 199 and Ser 396. Rats treated with losartan present memory deficits and decreases in spine-density. These findings suggest that losartan-induced hypotension may increase the risk of AD-like pathological alteration and behavioral impairment through oxidative stress which leads to tau hyperphosphorylation and loss of dendritic spines.
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Hypermethylation of the CDKN2A gene promoter is a frequent epigenetic change in periocular sebaceous carcinoma and is associated with younger patient age.
Hum. Pathol.
PUBLISHED: 01-21-2014
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Periocular sebaceous carcinoma is an aggressive neoplasm with significant morbidity and mortality. Its pathogenesis is poorly understood. It is only rarely associated with Muir-Torre syndrome. Previous studies from Asian countries, have suggested that human papillomavirus (HPV) infection plays a role in the pathogenesis and overexpression of p16(INK4a), a surrogate marker of HPV infection, have also been reported. However, data from western countries seem contradictory. In order to clarify and explore the molecular and epigenetic basis of HPV, CDKN2A status and role of microsatellite instability in the development of periocular sebaceous carcinoma, 24 cases of periocular sebaceous carcinoma were analyzed for the expression of p16(INK4a) and mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) via immunohistochemistry. Nested polymerase chain reaction (PCR) and genechip HPV typing were used to detect HPV infection and decide its genotype when present. PCR amplification using a consensus primer pair was also performed to detect ?-HPV. The methylation status of CDKN2A promoter region was studied by methylation-specific polymerase chain reaction. HPV-positivity was demonstrated in only one of our cases (HPV 16), while another case showed p16(INK4a) overexpression. All cases showed preserved expression of mismatch repair proteins. CDKN2A promoter hypermethylation was noted in nearly half of our cases (11/24) and was associated with younger patient age (P = .013). Our results showed that periocular sebaceous carcinoma is rarely associated with HPV and microsatellite instability. Higher frequency of CDKN2A promoter hypermethylation in younger patients implies a significant epigenetic role in tumor development in this age group.
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Psoralen reverses docetaxel-induced multidrug resistance in A549/D16 human lung cancer cells lines.
Phytomedicine
PUBLISHED: 01-18-2014
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Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs.
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Lipid droplet pattern and nondroplet-like structure in two fat mutants of Caenorhabditis elegans revealed by coherent anti-Stokes Raman scattering microscopy.
J Biomed Opt
PUBLISHED: 01-15-2014
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Lipid is an important energy source and essential component for plasma and organelle membranes in all kinds of cells. Coherent anti-Stokes Raman scattering (CARS) microscopy is a label-free and nonlinear optical technique that can be used to monitor the lipid distribution in live organisms. Here, we utilize CARS microscopy to investigate the pattern of lipid droplets in two live Caenorhabditis elegans mutants (fat-2 and fat-3). The CARS images showed a striking decrease in the size, number, and content of lipid droplets in the fat-2 mutant but a slight difference in the fat-3 mutant as compared with the wild-type worm. Moreover, a nondroplet-like structure with enhanced CARS signal was detected for the first time in the uterus of fat-2 and fat-3 mutants. In addition, transgenic fat-2 mutant expressing a GFP fusion protein of vitellogenin-2 (a yolk lipoprotein) revealed that the enhanced CARS signal colocalized with the GFP signal, which suggests that the nondroplet-like structure is primarily due to the accumulation of yolk lipoproteins. Together, this study implies that CARS microscopy is a potential tool to study the distribution of yolk lipoproteins, in addition to lipid droplets, in live animals.
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A single poly-Si gate-all-around junctionless fin field-effect transistor for use in one-time programming nonvolatile memory.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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This work demonstrates a feasible single poly-Si gate-all-around (GAA) junctionless fin field-effect transistor (JL-FinFET) for use in one-time programming (OTP) nonvolatile memory (NVM) applications. The advantages of this device include the simplicity of its use and the ease with which it can be embedded in Si wafer, glass, and flexible substrates. This device exhibits excellent retention, with a memory window maintained 2 V after 10(4) s. By extrapolation, 95% of the original charge can be stored for 10 years. In the future, this device will be applied to multi-layer Si ICs in fully functional systems on panels, active-matrix liquid-crystal displays, and three-dimensional (3D) stacked flash memory.
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Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Wide inter-patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients.
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Influence of patterned sapphire substrates with different symmetry on the light output power of InGaN-based LEDs.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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This paper aims to investigate the light output power (LOP) of InGaN-based light-emitting diodes (LEDs) grown on patterned sapphire substrates (PSSs) with different symmetry. The GaN epitaxial layers grown on the hexagonal lattice arrangement PSS (HLAPSS) have a lower compressive strain than the ones grown on the square lattice arrangement PSS (SLAPSS). The quantum-confined Stark effect (QCSE) is also affected by the residual compressive strain. Based on the experimentally measured data and the ray tracing simulation results, the InGaN-based LED with the HLAPSS has a higher LOP than the one with the SLAPSS due to the weaker QCSE within multiple-quantum wells (MQWs).
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Association studies with imputed variants using expectation-maximization likelihood-ratio tests.
PLoS ONE
PUBLISHED: 01-01-2014
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Genotype imputation has become standard practice in modern genetic studies. As sequencing-based reference panels continue to grow, increasingly more markers are being well or better imputed but at the same time, even more markers with relatively low minor allele frequency are being imputed with low imputation quality. Here, we propose new methods that incorporate imputation uncertainty for downstream association analysis, with improved power and/or computational efficiency. We consider two scenarios: I) when posterior probabilities of all potential genotypes are estimated; and II) when only the one-dimensional summary statistic, imputed dosage, is available. For scenario I, we have developed an expectation-maximization likelihood-ratio test for association based on posterior probabilities. When only imputed dosages are available (scenario II), we first sample the genotype probabilities from its posterior distribution given the dosages, and then apply the EM-LRT on the sampled probabilities. Our simulations show that type I error of the proposed EM-LRT methods under both scenarios are protected. Compared with existing methods, EM-LRT-Prob (for scenario I) offers optimal statistical power across a wide spectrum of MAF and imputation quality. EM-LRT-Dose (for scenario II) achieves a similar level of statistical power as EM-LRT-Prob and, outperforms the standard Dosage method, especially for markers with relatively low MAF or imputation quality. Applications to two real data sets, the Cebu Longitudinal Health and Nutrition Survey study and the Women's Health Initiative Study, provide further support to the validity and efficiency of our proposed methods.
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Clinical evaluation of motion and position sense in the upper extremities of the elderly using motion analysis system.
Clin Interv Aging
PUBLISHED: 01-01-2014
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The purpose of this study was to measure kinesthetic accuracy in healthy older adults by using arm position and motion matching tests. We investigated the effect of task type, joint angle, and matching arm results on kinesthetic accuracy in the upper extremities of 17 healthy right-handed older adults. Blinded subjects were asked to match positions and motions at four reference joint angles: 1) shoulder flexion, 0°-60°; 2) elbow flexion, 90°-135°; 3) wrist extension, 0°-50° in the sagittal plane; and 4) shoulder abduction, 0°-60° in the frontal plane. The absolute difference in angular displacement between the reference and matching arms was calculated to determine kinesthetic accuracy. Results showed that subjects were more accurate at matching motion than position tasks (P=0.03). Shoulder and elbow joints were more sensitive than wrist joints in perceiving passive positions and motions (P<0.05). The effect of the matching arm was found only when matching the joint angles of shoulder abduction and wrist extension (P<0.01). These results are comparable to findings of other studies that used machine-generated kinesthetic stimuli. The manual measurement of kinesthetic accuracy could be effective as a preliminary screening tool for therapists in clinical settings.
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Progesterone receptor expression in sinonasal leiomyoma: a case report and review of the literature.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Leiomyomas are benign myogenic tumors that seldom occur in the sinonasal cavity. They were commonly found in middle-aged adults with a female predominance. Clinical symptoms include nasal obstruction with discharge, nasal bleeding and pain. We describe the case of a 48 year-old woman with a leiomyoma arising from right inferior nasal turbinate. Transnasal endoscopic excision was performed with satisfied result. The tumor was found to be progesterone receptor positive on immunohistochemical analysis. The clinical findings are addressed with a review of the literature. To the best of our knowledge, this is the third reported case that supports the growth of the tumor may be hormone-dependent.
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Therapeutic drug monitoring and pharmacogenetic study of HIV-infected ethnic Chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.
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Exclusively endoscopic resection of nasopharyngeal adenocarcinoma.
Clin Exp Otorhinolaryngol
PUBLISHED: 11-29-2013
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We reported two patients with nasopharyngeal adenocarcinoma resected by using the exclusively endoscopic approach. Case reports and a review of the world literature concerning nasopharyngeal adenocarcinoma. The tumors were resected successfully via the exclusively endoscopic approach and no conversions to the conventional approach were necessary. The two patients were followed up for 26 and 18 months respectively, and no recurrence was noted without postoperative chemotherapy or radiotherapy. To the best of our knowledge, this is the first report of endoscopic resection of nasopharyngeal adenocarcinoma. Our experience revealed that not only for the early recurrent nasopharyngeal carcinoma, the exclusively endoscopic nasopharyngectomy can be expanded for the resection of selected nasopharyngeal adenocarcinoma.
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Improved CCT uniformity of white LED using remote phosphor with patterned sapphire substrate.
Appl Opt
PUBLISHED: 11-13-2013
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The light distribution of a light-emitting diode (LED), using remote phosphor with a patterned sapphire substrate, is evaluated in this study. Three kinds of substrates of the remote phosphors, including planar sapphire (PS), partially patterned sapphire (PPS), and fully patterned sapphire (FPS) are prepared. The LED with the remote phosphor of FPS delivers much better uniformity of the correlated color temperature (CCT) in a far-field pattern than the CCT obtained in the cases of PS and PPS. The results are majorly attributed to the improvement in the scattering ability of the blue light in the FPS; thereby increasing the excitation of the phosphor particles in comparison to the ability of the device assembled with the remote phosphor of PS or PPS.
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A combination of pterostilbene with autophagy inhibitors exerts efficient apoptotic characteristics in both chemosensitive and chemoresistant lung cancer cells.
Toxicol. Sci.
PUBLISHED: 10-23-2013
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The emergence of multidrug resistance (MDR), meaning that cancer cells develop simultaneous resistance to different drugs, has limited the clinical efficacy and application of chemotherapy. Pterostilbene, a naturally occurring phytoalexin exerts a variety of pharmacologic activities, including cancer prevention, cytotoxicity, and antioxidant activity. In this study, results proved the capability of pterostilbene to effectively inhibit the cell viability of docetaxel-induced MDR human lung cancer cell lines through cell cycle arrest and apoptosis. Meanwhile, the observation of LC3-II production and formation of acidic vesicular organelles revealed an induction of autophagy at an early stage by pterostilbene, which was triggered by an inhibition of the AKT and JNK pathways and activation of ERK1/2. Furthermore, pretreatment with the autophagy inhibitors 3-methyladenine and bafilomycin A1 or with beclin-1 small interfering RNA was able to enhance pterostilbene-triggered apoptosis. In conclusion, this study demonstrated that pterostilbene causes autophagy and apoptosis in lung cancer cells. Furthermore, pterostilbene in combination with autophagy inhibitors may strengthen the efficiency of chemotherapeutic strategies in both chemosensitive and chemoresistant lung cancer cells, which may be of immense value for the clinical management of lung cancer patients with MDR.
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Mass Spectrometry-Based Quantitative Proteomics for Dissecting Multiplexed Redox Cysteine Modifications in Nitric Oxide-Protected Cardiomyocyte Under Hypoxia.
Antioxid. Redox Signal.
PUBLISHED: 10-23-2013
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Abstract Aims: Distinctive states of redox-dependent cysteine (Cys) modifications are known to regulate signaling homeostasis under various pathophysiological conditions, including myocardial injury or protection in response to ischemic stress. Recent evidence further implicates a dynamic interplay among these modified forms following changes in cellular redox environment. However, a precise delineation of multiplexed Cys modifications in a cellular context remains technically challenging. To this end, we have now developed a mass spectrometry (MS)-based quantitative approach using a set of novel iodoacetyl-based Cys-reactive isobaric tags (irreversible isobaric iodoacetyl Cys-reactive tandem mass tag [iodoTMT]) endowed with unique irreversible Cys-reactivities. Results: We have established a sequential iodoTMT-switch procedure coupled with efficient immunoenrichment and advanced shotgun liquid chromatography-MS/MS analysis. This workflow allows us to differentially quantify the multiple redox-modified forms of a Cys site in the original cellular context. In one single analysis, we have identified over 260 Cys sites showing quantitative differences in multiplexed redox modifications from the total lysates of H9c2 cardiomyocytes experiencing hypoxia in the absence and presence of S-nitrosoglutathione (GSNO), indicative of a distinct pattern of individual susceptibility to S-nitrosylation or S-glutathionylation. Among those most significantly affected are proteins functionally implicated in hypoxic damage from which we showed that GSNO would protect. Innovation: We demonstrate for the first time how quantitative analysis of various Cys-redox modifications occurring in biological samples can be performed precisely and simultaneously at proteomic levels. Conclusion: We have not only developed a new approach to map global Cys-redoxomic regulation in vivo, but also provided new evidences implicating Cys-redox modifications of key molecules in NO-mediated ischemic cardioprotection. Antioxid. Redox Signal. 00, 000-000.
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Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma.
Am. J. Surg. Pathol.
PUBLISHED: 10-01-2013
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ARID1A is a recently identified tumor suppressor that functions in chromatin remodeling. Inactivating mutations of ARID1A and loss of its expression most frequently occur in ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. In this study, we performed a detailed immunostaining analysis of ARID1A in 246 cases including benign endometrium and endometrioid carcinoma at different stages of progression. Special attention was paid to recording intratumoral heterogeneity of clonal loss of ARID1A immunoreactivity. All normal endometria (n=51) and endometrial polyps (n=14) retained ARID1A expression. Among complex atypical hyperplasias (n=38), 16% exhibited clonal loss of ARID1A, but none showed complete loss. Among low-grade endometrioid carcinomas (n=88), 25% exhibited complete loss and 24% exhibited clonal loss. In contrast, 44% of high-grade endometrioid carcinomas (n=55) showed complete loss of ARID1A, and 9% exhibited clonal loss. We found that 19 high-grade carcinomas also contained concurrent low-grade carcinomas. In the high-grade areas, 63% exhibited complete loss and 11% exhibited clonal loss, whereas in the low-grade areas, 37% exhibited complete loss and 42% clonal loss. In 5 of these 19 cases, progressive loss of ARID1A from retention or clonal loss to complete loss was observed between the low-grade and high-grade areas. Overall, the percentage of complete ARID1A loss increased from 0% in complex atypical hyperplasia, to 25% in low-grade endometrioid carcinoma, to 44% in high-grade endometrioid carcinoma. These findings suggest that loss of ARID1A expression, presumably due to mutation, plays an important role in tumor progression of uterine endometrioid carcinoma.
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Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma.
Mod. Pathol.
PUBLISHED: 08-14-2013
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AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P=0.048), PI3K-Akt pathway activation (P=0.046) and ZNF217 amplification (P=0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P=0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.Modern Pathology advance online publication, 13 December 2013; doi:10.1038/modpathol.2013.216.
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Changes in decisional conflict and decisional regret in patients with localised prostate cancer.
J Clin Nurs
PUBLISHED: 08-04-2013
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To identify the changes and associated factors in decisional conflict and regret in patients with localised prostate cancer up to six months postprimary treatment.
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Inhibition of apoptosis by knockdown of caspase-3 with siRNA in rat bone marrow mesenchymal stem cells.
Exp. Biol. Med. (Maywood)
PUBLISHED: 07-30-2013
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Transplantation of bone marrow mesenchymal stem cells is a promising new strategy for the repair of infarcted cardiac tissue. However, the majority of transplanted bone marrow mesenchymal stem cells (BMSCs) die soon after transplantation, due in part to oxidative stress in the ischemic region. Oxidative stress is known to induce apoptosis through the activation of caspase-3. The aim of this study is to determine whether small interfering RNA targeting caspase-3 can inhibit the apoptosis of rat BMSCs in vitro. Caspase-3 siRNA expression vectors were prepared and transfected into rat BMSCs in the presence of liposomes. Western blot assay and real-time polymerase chain reaction (RT-PCR) were performed to detect caspase-3 expression. A retrovirus packaging system was employed to package 293FT cells producing caspase-3 siRNA virus, which were transfected into rat BMSCs. Those stably expressing caspase-3 siRNA were screened by Western blot assay and RT-PCR to determine caspase-3 expression levels. Stable transfection of caspase-3 siRNA significantly decreased caspase-3 protein (0.26?±?0.001 vs. 0.42?±?0.004, P?
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Ethanol Extracts of Fresh Davallia formosana (WL1101) Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor- ? B Activation.
Evid Based Complement Alternat Med
PUBLISHED: 06-24-2013
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The rhizome of Davallia formosana is commonly used to treat bone disease including bone fracture, arthritis, and osteoporosis in Chinese herbal medicine. Here, we report the effects of WL1101, the ethanol extracts of fresh rhizomes of Davallia formosana on ovariectomy-induced osteoporosis. In addition, excess activated bone-resorbing osteoclasts play crucial roles in inflammation-induced bone loss diseases, including rheumatoid arthritis and osteoporosis. In this study, we examined the effects of WL1101 on receptor activator of nuclear factor- ? B ligand (RANKL)-induced osteoclastogenesis. Treatment with WL1101 significantly inhibited RANKL-stimulated osteoclastogenesis. Two isolated active compounds, ((-)-epicatechin) or WL14 (4-hydroxy-3-aminobenzoic acid) could also inhibit RANKL-induced osteoclastogenesis. WL1101 suppressed the RANKL-induced nuclear factor- ? B (NF- ? B) activation and nuclear translocation, which is the key process during osteoclastogenesis, by inhibiting the activation of I ? B kinase (IKK) and I ? B ? . In animal model, oral administration of WL1101 (50 or 200?mg/kg/day) effectively decreased the excess bone resorption and significantly antagonized the trabecular bone loss in ovariectomized rats. Our results demonstrate that the ethanol extracts of fresh rhizomes of Davallia formosana inhibit osteoclast differentiation via the inhibition of NF- ? B activation and effectively ameliorate ovariectomy-induced osteoporosis. WL1101 may thus have therapeutic potential for the treatment of diseases associated with excessive osteoclastic activity.
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