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Find video protocols related to scientific articles indexed in Pubmed.
Downregulated miR-329 and miR-410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b.
Cancer Res.
PUBLISHED: 10-30-2014
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MicroRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR-329 and miR-410, which could potentially target Wnt-7b, an activator of the Wnt/?-catenin pathway, thereby attenuating the Wnt/?-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR-329 or miR-410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to re-express miR-329, miR-410 and Meg3 consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR-329, miR-410 and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contribute to oral carcinogenesis through epigenetic silencing of tumor suppressor miRNA which target Wnt/?-catenin signaling.
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Asymmetrical dual tapered fiber Mach-Zehnder interferometer for fiber-optic directional tilt sensor.
Opt Express
PUBLISHED: 10-17-2014
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This work proposes a novel, highly sensitive and directional fiber tilt sensor that is based on an asymmetrical dual tapered fiber Mach-Zehnder interferometer (ADTFMZI). The fiber-optic tilt sensor consists of two abrupt tapers with different tapered waists into which are incorporated a set of iron spheres to generate an asymmetrical strain in the ADTFMZI that is correlated with the tilt angle and the direction of inclination. Owing to the asymmetrical structure of the dual tapers, the proposed sensor can detect the non-horizontal/horizontal state of a structure and whether the test structure is tilted to clockwise or counterclockwise by measuring the spectral responses. Experimental results show that the spectral wavelengths are blue-shifted and red-shifted when the sensor tilts to clockwise (-?) and counterclockwise ( + ?), respectively. Tilt angle sensitivities of about 335pm/deg. and 125pm/deg. are achieved in the -? and + ? directions, respectively, when the proposed sensing scheme is utilized.
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Identification of trans,trans-2,4-Decadienal Metabolites in Mouse and Human Cells Using Liquid Chromatography-Mass Spectrometry.
Chem. Res. Toxicol.
PUBLISHED: 10-07-2014
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trans,trans-2,4-Decadienal (tt-DDE), a lipid peroxidation product of linolieic acid, is the most abundant aldehyde identified in cooking oil fumes and is readily detectable in food products as well as in restaurant emissions. Previously, we have reported the toxicological effects of tt-DDE in vitro and in vivo. However, the metabolic pathways of tt-DDE in vivo remain unclear. In our present study, we combined liquid chromatography-mass spectrometry with triple quadrupole and time-of-flight to identify tt-DDE metabolites in the urine of mice orally administered tt-DDE. We identified two tt-DDE metabolites, 2,4-decadienoic acid and cysteine-conjugated 2,4-decadien-1-ol, in the urine of mice gavaged with tt-DDE and in human hepatoma cell cultures. The structure of 2,4-decadienoic acid was confirmed upon comparison of its tandem mass spectrometry (MS/MS) spectrum and retention time with those of synthetic standards. The moieties of cysteine and alcohol on cysteine-conjugated 2,4-decadien-1-ol were validated by treating cell cultures with stable-isotope-labeled cysteine and 4-methylpyrazole, an alcohol dehydrogenase inhibitor. The MS/MS spectra of a cysteine standard and ionized cysteine detached from cysteine-conjugated 2,4-decadien-1-ol were identical. Two metabolic pathways for the biotransformation of tt-DDE in vivo are proposed: (i) the oxidation of tt-DDE to the corresponding carboxylic acid, 2,4-decadienoic acid, in liver cells and (ii) glutathione (GHS) conjugation, GSH breakdown, and aldehyde reduction, which generate cysteine-conjugated 2,4-decadien-1-ol in both liver and lung cells. In conclusion, this platform can be used to identify tt-DDE metabolites, and cysteine-conjugated 2,4-decadien-1-ol can serve as a biomarker for assessing exposure to tt-DDE.
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Damage to dorsolateral prefrontal cortex affects tradeoffs between honesty and self-interest.
Nat. Neurosci.
PUBLISHED: 08-31-2014
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Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior.
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The prognostic value of lymph node status among breast cancer subtypes.
Am. J. Surg.
PUBLISHED: 08-05-2014
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Breast cancer subtypes (BCSs) are predictive of responses to specific therapies and of prognostic value for clinical outcomes. This study aimed to evaluate the relative 5-year overall survival (OS) and recurrence-free survival rates (RFS) based on lymph node (LN) status among BCSs.
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GALNT2 suppresses malignant phenotypes through IGF-1 receptor and predicts favorable prognosis in neuroblastoma.
Oncotarget
PUBLISHED: 07-31-2014
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Aberrant expression of the simple mucin-type carbohydrate antigens such as Tn antigen is associated with malignant transformation and cancer progression. N-acetylgalactosaminyltransferase 2 (GALNT2), one of the enzymes that mediate the initial step of mucin-type O-glycosylation, is responsible for forming Tn antigen. GALNT2 is expressed differentially in nervous tissues during mouse embryogenesis; however, the role of GALNT2 in neuroblastoma (NB) remains unclear. Here we showed that increased GALNT2 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as younger age at diagnosis, early clinical stage, primary tumor originated from the extra-adrenal site, favorable INPC histology, and MYCN non-amplification. Multivariate analysis showed that GALNT2 expression is an independent prognostic factor for better survival for NB patients. GALNT2 overexpression suppressed IGF-1-induced cell growth, migration, and invasion of NB cells, whereas GALNT2 knockdown enhanced these NB phenotypes. Mechanistic investigations demonstrated that GALNT2 overexpression modified O-glycans on IGF-1R, which suppressed IGF-1-triggered IGF-1R dimerization and subsequent downstream signaling events. Conversely, these properties were reversed by GALNT2 knockdown in NB cells. Our findings suggest that GALNT2 regulates malignant phenotypes of NB cells through the IGF-1R signaling pathway, suggesting a critical role for GALNT2 in the pathogenesis of NB.
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Clinical and biochemical characteristics of women with menstrual disturbance.
Taiwan J Obstet Gynecol
PUBLISHED: 07-15-2014
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Menstrual irregularity is one of the major complaints in women of reproductive age. The aim of this study was to evaluate the complications in women with different menstrual disturbances.
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A higher anti-Müllerian hormone level is associated with an increased chance of pregnancy in patients undergoing controlled ovarian stimulation and intrauterine insemination.
J Obstet Gynaecol
PUBLISHED: 07-11-2014
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Anti-Müllerian hormone (AMH) level has been found to be a useful marker of ovarian reserve, and a predictor of poor and hyper-responses in patients undergoing controlled ovarian stimulation (COS). The study aimed to determine the association of serum AMH level with achieving pregnancy in patients undergoing COS with intrauterine insemination. The cross-sectional study investigated 204 patients who underwent COS with intrauterine insemination at the Obstetrics and Gynecology Department of Taipei Medical University Hospital, from January 2011 to March 2012. The medical records of these patients were reviewed, and serum AMH levels were evaluated for association with successful clinical pregnancy. The AMH level in the patients who achieved clinical pregnancy was significantly higher than in patients who did not (median 2.7 vs 2.0 ng/ml, p = 0.005). Controlling for factors affecting infertility, AMH level had a significant independent influence on outcome; a higher AMH level was associated with a decreased risk of a non-pregnant outcome (odds ratio, OR = 0.895, p = 0.026). In patients undergoing COS and intrauterine insemination, a low AMH level is associated with a decreased chance of a clinical pregnancy, and this association remains irrespective of the presence or absence of endometriosis.
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Andrographolide inhibits nuclear factor-?B activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-?-stimulated vascular smooth muscle cells.
ScientificWorldJournal
PUBLISHED: 07-10-2014
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Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-? (TNF-?). Treating TNF-?-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-?-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither I?B? degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-?B activity in TNF-?-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an I?B?-independent mechanism.
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?1, 4-N-acetylgalactosaminyltransferase III modulates cancer stemness through EGFR signaling pathway in colon cancer cells.
Oncotarget
PUBLISHED: 07-09-2014
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Cancer stem cells are cancer cells characterized with tumor initiating capacity. ?1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) synthesizes GalNAc?1-4GlcNAc (LacdiNAc) which contributes to self-renewal of mouse embryonic stem cells. We previously showed that B4GALNT3 overexpression enhances colon cancer cell malignant phenotypes in vitro and in vivo. However, the role of B4GALNT3 in cancer stemness remains unclear. We found that B4GALNT3 expression was positively correlated with advanced stages and poor survival in colorectal cancer patients. Knockdown of B4GALNT3 using small interfering (si) RNAs in colon cancer cell lines (HCT116, SW480, HCT15, and HT29 cells) decreased sphere formation and the expression of stem cell markers, OCT4 and NANOG. The expression of B4GALNT3 was upregulated in colonospheres. Interestingly, we found that B4GALNT3 primarily modified N-glycans of EGFR with LacdiNAc by Wisteria floribunda agglutinin (WFA) pull down assays. B4GALNT3 knockdown suppressed EGF-induced phosphorylation of EGFR and its downstream signaling molecules. Furthermore, EGF-induced degradation of EGFR was facilitated. In addition, EGF-induced migration and invasion were significantly suppressed by B4GALNT3 knockdown. Taken together, these data suggest B4GALNT3 regulates cancer stemness and the invasive properties of colon cancer cells through modifying EGFR glycosylation and signaling. Our results provide novel insights into the role of LacdiNAc in colorectal cancer development.
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Rapid Increase in the Height and Width of the Upper Chest in Adolescents with Primary Spontaneous Pneumothorax.
Pediatr Neonatol
PUBLISHED: 06-30-2014
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We determined the chest height in a cohort of patients with primary spontaneous pneumothorax (PSP) who had received chest radiographic examinations prior to the attack. The aim of this study was to determine when their chest height began to change and how this was related to the PSP.
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A peripheral ameloblastic fibro-odontoma in a 3-year-old girl: case report, immunohistochemical analysis, and literature review.
Case Rep Dent
PUBLISHED: 06-30-2014
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Ameloblastic fibro-odontoma (AFO) predominantly occurs in the jaw bones of children and young adults. Extraosseous AFO is extremely rare. We describe a peripheral ameloblastic fibro-odontoma in the maxillary gingiva of a 3-year-old girl. The clinical appearance resembled fiery red reactive gingival lesions. The histopathological examination of the excised lesion showed small islands and cords of odontogenic epithelium with cellular myxoid stroma in the subepithelial tissue. The mass contained calcified material and an enamel-like deposit. Many small blood vessels appeared in the connective tissue surrounding the odontogenic epithelium. The immunohistochemical assays showed strong reactivity for amelogenin, ?-catenin, CD44, and CD31 in the tissue sections. There was no recurrence after the 1-year follow-up. Because this lesion clinically resembles other nonneoplastic lesions and is very rare in gingiva, establishing a correct diagnosis is achieved only based on specific histological characteristics. Conservative excision of the tumor is the treatment of choice.
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Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade.
Sci Rep
PUBLISHED: 06-24-2014
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The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-?B dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-?B inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.
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Calreticulin Regulates VEGF-A in Neuroblastoma Cells.
Mol. Neurobiol.
PUBLISHED: 06-18-2014
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Calreticulin (CRT) has been previously correlated with the differentiation of neuroblastoma (NB), implying a favorable prognostic factor. Vascular endothelial growth factor (VEGF) has been reported to participate in the behavior of NB. This study investigated the association of CRT and VEGF-A in NB cells. The expressions of VEGF-A and HIF-1?, with overexpression or knockdown of CRT, were measured in three NB cells (SH-SY5Y, SK-N-DZ, and stNB-V1). An inducible CRT NB cell line and knockdown CRT stable cell lines were also established. The impacts of CRT overexpression on NB cell apoptosis, proliferation, and differentiation were also evaluated. We further examined the role of VEGF-A in the NB cell differentiation via VEGF receptor blockade. Constitutive overexpression of CRT led to NB cell differentiation without proliferation. Thus, an inducible CRT stNB-V1 cell line was generated by a tetracycline-regulated gene system. CRT overexpression increased VEGF-A and HIF-1? messenger RNA (mRNA) expressions in SH-SY5Y, SK-N-DZ, and stNB-V1 cells. CRT overexpression also enhanced VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. Knockdown of CRT decreased VEGF-A and HIF-1? mRNA expressions and lowered VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. We further demonstrated that NB cell apoptosis was not affected by CRT overexpression in stNB-V1 cells. Nevertheless, overexpression of CRT suppressed cell proliferation and enhanced cell differentiation in stNB-V1 cells, whereas blockage of VEGFR-1 markedly suppressed the expression of neuron-specific markers including GAP43, NSE2, and NFH, as well as TrkA, a molecular marker indicative of NB cell differentiation. Our findings suggest that VEGF-A is involved in CRT-related neuronal differentiation in NB. Our work may provide important information for developing a new therapeutic strategy to improve the outcome of NB patients.
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Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-16-2014
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Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance--catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase--modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function--dopamine transporter and D2 receptors--was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.
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Ophthalmic plastic and orbital surgery in Taiwan.
J Chin Med Assoc
PUBLISHED: 06-02-2014
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We describe in this paper the current status of ophthalmic plastic and orbital surgery in Taiwan. Data were collected from the Bureau of National Health Insurance of Taiwan, the Bulletin of the Taiwan Ophthalmic Plastic and Reconstructive Society, and the Statistics Yearbook of Practicing Physicians and Health Care Organizations in Taiwan by the Taiwan Medical Association. We ascertained that 94 ophthalmologists were oculoplastic surgeons and accounted for 5.8% of 1621 ophthalmologists in Taiwan. They had their fellowship training abroad (most ophthalmologists trained in the United States of America) or in Taiwan. All ophthalmologists were well trained and capable of performing major oculoplastic surgeries. The payment rates by our National Health Insurance for oculoplastic and orbital surgeries are relatively low, compared to Medicare payments in the United States. Ophthalmologists should promote the concept that oculoplastic surgeons specialize in periorbital plastic and aesthetic surgeries. However, general ophthalmologists should receive more educational courses on oculoplastic and cosmetic surgery.
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Functional variants at the 21q22.3 locus involved in breast cancer progression identified by screening of genome-wide estrogen response elements.
Breast Cancer Res.
PUBLISHED: 05-27-2014
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IntroductionEstrogen forms a complex with the estrogen receptor (ER) that binds to estrogen response elements (EREs) in the regulatory region of estrogen-responsive genes, and regulates their transcription. Since sequence variants in the regulatory regions have the potential to affect the transcription factor-regulatory sequence interaction, resulting in altered expression of target genes, this study explored the association between single-nucleotide-polymorphisms (SNPs) within the ERE-associated sequences and breast cancer progression.MethodsThe ERE-associated sequences throughout the whole genome, demonstrated to bind ER¿ in vivo, were blasted against online information from SNP datasets, and 54 SNPs located adjacent to estrogen-responsive genes were selected for genotyping in two independent cohorts of breast cancer patients, 779 in the initial screening stage and another 888 in the validation stage. The death from breast cancer or recurrence of breast cancer were defined as the respective event of interest, and the hazard ratios of individual SNPs were estimated based on the Cox proportional hazard model. Furthermore, functional assays were performed and information from publicly available genomic data and bioinformatic platforms were used to provide additional evidence for the association identified in the association analysis.ResultsThe SNPs at 21q22.3 ERE were significantly associated with overall survival and disease-free survival of patients. Furthermore, these 21q22.3 SNPs (rs2839494 and rs1078272) could affect the binding of this ERE-associated sequence to ER¿ or Rad21 (an ER¿ coactivator), respectively, resulting in a difference in ER¿-activated expression of the reporter gene.ConclusionThese findings support the idea that functional variants in the ER¿-regulating sequence at 21q22.3 is important in determining breast cancer progression.
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Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice.
Arch. Toxicol.
PUBLISHED: 05-19-2014
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Di-(2-ethylhexyl) phthalate (DEHP) is associated with atherosclerosis-related cardiovascular disease complications, but we lack direct evidence of its unfavorable effect on atherogenesis. In this study, we aimed to clarify in vivo and in vitro the contribution of DEHP to the development of atherosclerosis and its underlying mechanisms. Apolipoprotein E-deficient (apoE(-/-)) mice chronically treated with DEHP for 4 weeks showed exacerbated hyperlipidemia, systemic inflammation, and atherosclerosis. In addition, DEHP promoted low-density lipoprotein (LDL) oxidation, which led to inflammation in endothelial cells as evidenced by increased protein expression of pro-inflammatory mediators. Furthermore, chronic DEHP treatment increased hepatic cholesterol accumulation by downregulating the protein expression of key regulators in cholesterol clearance including LDL receptor, cholesterol 7?-hydrolase, ATP-binding cassette transporter G5 and G8, and liver X receptor ?. Moreover, the adiposity and inflammation of white adipose tissues were promoted in DEHP-treated apoE(-/-) mice. In conclusion, DEHP may disturb cholesterol homeostasis and deregulate the inflammatory response, thus leading to accelerated atherosclerosis.
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Using volume index and lateral hepatic angle to differentiate biliary atresia from TPN-associated cholestasis.
J. Pediatr. Gastroenterol. Nutr.
PUBLISHED: 05-14-2014
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Differential diagnosis between biliary atresia (BA) and total parenteral nutrition-associated cholestasis (TPN-AC) and early treatment for cholestatic infants are challenges for evaluating neonatal or infantile cholestasis. The aim of our retrospective study was to apply noninvasive indices of magnetic resonance images to differentiate BA from TPN-AC.
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1,25-dihydroxyvitamin D3 increases testosterone-induced 17beta-estradiol secretion and reverses testosterone-reduced connexin 43 in rat granulosa cells.
Reprod. Biol. Endocrinol.
PUBLISHED: 05-08-2014
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Aromatase converts testosterone into 17beta-estradiol in granulosa cells, and the converted 17beta-estradiol contributes to follicular maturation. Additionally, excessive testosterone inhibits aromatase activity, which can lead to concerns regarding polycystic ovary syndrome (PCOS). Generally, 1,25-dihydroxyvitamin D3 (1,25D3) supplements help to improve the symptoms of PCOS patients who exhibit low blood levels of 1,25D3. Therefore, this study investigated the interaction effects of 1,25D3 and testosterone on estrogenesis and intercellular connections in rat granulosa cells.
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Directly thiolated modification onto the surface of detonation nanodiamonds.
ACS Appl Mater Interfaces
PUBLISHED: 05-06-2014
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An efficient method for modifying the surface of detonation nanodiamonds (5 and 100 nm) with thiol groups (-SH) by using an organic chemistry strategy is presented herein. Thiolated nanodiamonds were characterized by spectroscopic techniques, and the atomic percentage of sulfur was analyzed by elemental analysis and X-ray photoelectron spectroscopy. The conjugation between thiolated nanodiamonds and gold nanoparticles was elucidated by transmission electron microscopy and UV-vis spectrometry. Moreover, the material did not show significant cytotoxicity to the human lung carcinoma cell line and may prospectively be applied in bioconjugated technology. The new method that we elucidated may significantly improve the approach to surface modification of detonation nanodiamonds and build up a new platform for the application of nanodiamonds.
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Calreticulin activates ?1 integrin via fucosylation by fucosyltransferase 1 in J82 human bladder cancer cells.
Biochem. J.
PUBLISHED: 03-06-2014
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Fucosylation regulates various pathological events in cells. We reported that different levels of CRT (calreticulin) affect the cell adhesion and metastasis of bladder cancer. However, the precise mechanism of tumour metastasis regulated by CRT remains unclear. Using a DNA array, we identified FUT1 (fucosyltransferase 1) as a gene regulated by CRT expression levels. CRT regulated cell adhesion through ?1,2-linked fucosylation of ?1 integrin and this modification was catalysed by FUT1. To clarify the roles for FUT1 in bladder cancer, we transfected the human FUT1 gene into CRT-RNAi stable cell lines. FUT1 overexpression in CRT-RNAi cells resulted in increased levels of ?1 integrin fucosylation and rescued cell adhesion to type-I collagen. Treatment with UEA-1 (Ulex europaeus agglutinin-1), a lectin that recognizes FUT1-modified glycosylation structures, did not affect cell adhesion. In contrast, a FUT1-specific fucosidase diminished the activation of ?1 integrin. These results indicated that ?1,2-fucosylation of ?1 integrin was not involved in integrin-collagen interaction, but promoted ?1 integrin activation. Moreover, we demonstrated that CRT regulated FUT1 mRNA degradation at the 3'-UTR. In conclusion, the results of the present study suggest that CRT stabilized FUT1 mRNA, thereby leading to an increase in fucosylation of ?1 integrin. Furthermore, increased fucosylation levels activate ?1 integrin, rather than directly modifying the integrin-binding sites.
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Finite element analysis of helical flows in human aortic arch: a novel index.
Biomicrofluidics
PUBLISHED: 03-01-2014
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This study investigates the helical secondary flows in the aortic arch using finite element analysis. The relationship between helical flow and the configuration of the aorta in patients of whose three-dimensional images constructed from computed tomography scans was examined. A finite element model of the pressurized root, arch, and supra-aortic vessels was developed to simulate the pattern of helical secondary flows. Calculations indicate that most of the helical secondary flow was formed in the ascending aorta. Angle ? between the zero reference point and the aortic ostium (correlation coefficient (r)?=?-0.851, P?=?0.001), the dispersion index of the cross section of the ascending (r?=?0.683, P?=?0.021) and descending aorta (r?=?0.732, P?=?0.010), all correlated closely with the presence of helical flow (P?
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Daptomycin-loaded polymethylmethacrylate bone cement for joint arthroplasty surgery.
Artif Organs
PUBLISHED: 02-28-2014
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Antibiotic-loaded acrylic bone cement has been frequently used as an infection prophylaxis or antibiotic-loaded spacer in infected arthroplasty. In addition, daptomycin has been used recently against broad spectrum Gram-positive organisms. The goal of this in vitro study is to investigate the bacteriacidal and mechanical properties of daptomycin-incorporated polymethylmethacrylate (PMMA) bone cement and evaluate its feasibility for clinical use. Daptomycin (0.5, 1, or 2?g) was premixed with 40?g of PMMA bone cement powder before curing. The mechanical properties of the daptomycin-loaded acrylic bone cement (DLABC) were estimated following standard guidance, and the release profile and kinetics of daptomycin from PMMA were analyzed. The antimicrobial efficacy of DLABC was determined with a zone of inhibition (ZOI) assay against Staphylococcus aureus, Staphylococcus epidermis, Enterococcus faecalis, and Enterococcus faecium, respectively. The results showed that the compressive strength, of PMMA bone cement, which was higher than 100 MPa in all groups, was sufficient according to ISO 5833 after incorporation of daptomycin. The encapsulated daptomycin was released for 2 weeks with a 9.59?±?0.85%, 15.25?±?0.69%, and 20.64?±?20.33% released percentage on the first day in the low, mid, and high groups, respectively. According to the calculated release kinetics, incorporated daptomycin should be 3.3 times the original dose to double its release. Although all recipes of DLABC had a microbial inhibitory effect, the effect with a higher encapsulated amount of daptomycin was more significant. Therefore, we believe that daptomycin can be locally delivered from PMMA bone cement at the surgical site as a prophylactic or treatment for osteomyelitis against Gram-positive organisms with intact cement function.
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Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity.
Reprod. Biomed. Online
PUBLISHED: 02-23-2014
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Chemotherapy damages the reproductive system by enhancing apoptosis, and evidence suggests that targeted anti-apoptotic therapy may preserve fertility in patients receiving chemotherapy. To investigate the protective effect of sphingosine-1-phosphate (S1P) on chemotherapeutic agent-induced ovarian gonadotoxicity, busulfan-treated female mice were pre-treated with low (0.5?mM) and high (2.0?mM) doses of S1P or vehicle 1?h before busulfan injection. In the S1P groups, each mouse was injected with low-dose S1P in one ovary and high-dose S1P in the contralateral ovary. Four weeks later, the ovaries were removed for histological and biochemical examinations. Caspase 3 immunoreactivity was greater in mice treated with busulfan compared with mice pre-treated with S1P, in which more primordial follicles were observed (P < 0.05). The mRNA level of anti-Müllerian hormone was higher in mice pre-treated with S1P than those that received busulfan only, indicating a better ovarian function in mice pre-treated with S1P. No difference was observed in the levels of growth differentiation factor-9 among all groups. In conclusion, S1P protects primordial follicles from chemotherapy-induced gonadotoxicity, and may partially preserve ovarian function.
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Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.
ChemMedChem
PUBLISHED: 02-23-2014
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It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.
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Hepatocellular carcinoma targeting agents: conjugates of nitroimidazoles with trimethyl nordihydroguaiaretic Acid.
ChemMedChem
PUBLISHED: 02-21-2014
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Cancer has been a primary global health issue for decades, with hepatocellular carcinoma (HCC) resulting in more than half a million new cases annually. With survival rates as low as <5% after five years, it remains a poorly treated cancer. Nordihydroguaiaretic acid (NDGA), an antioxidant, was previously proven effective against cancer cells. Nitroimidazole derivatives convert into reactive compounds under hypoxic conditions. In this study, eight methylated NDGAs containing a 2- or 4-nitroimidazole moiety were synthesized as leads against HCC. Four of these conjugates, possessing a poly(ethylene glycol) tether, had superior aqueous solubility. These four NDGA-nitroimidazole conjugates were found to inhibit the proliferation HCC Hep3B cells with IC50 values between 10 and 15 ?M. Furthermore, nitroimidazole-conjugated NDGA derivatives exhibit better antiproliferative activity under hypoxic conditions.
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[Exploring medical futility].
Hu Li Za Zhi
PUBLISHED: 02-13-2014
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Although able to extend the life of some critical patients, advanced medical technology is limited in terms of scope and extent of effectiveness. Some patients die despite the best efforts of medical teams. Medical futility describes treatments that are both extremely unlikely to benefit a patient and costly to provide. Clearly defining futile treatments and considering this concept in patient care strategies is important to provide quality patient care. Taiwan is currently formulating a policy on medical futility. While accepting that the term "futile" is used in many different ways and that this term is difficult to define in clinical practice, this article discusses the various ethical views on medical futility and its definition, the debate among these different views, and related research. We hope this article may help medical care staff better understand the importance of medical futility.
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PMC, a potent hydrophilic ?-tocopherol derivative, inhibits NF-?B activation via PP2A but not I?B?-dependent signals in vascular smooth muscle cells.
J. Cell. Mol. Med.
PUBLISHED: 02-11-2014
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The hydrophilic ?-tocopherol derivative, 2,2,5,7,8-pentamethyl-6-hydroxychromane (PMC), is a promising alternative to vitamin E in clinical applications. Critical vascular inflammation leads to vascular dysfunction and vascular diseases, including atherosclerosis, hypertension and abdominal aortic aneurysms. In this study, we investigated the mechanisms of the inhibitory effects of PMC in vascular smooth muscle cells (VSMCs) exposed to pro-inflammatory stimuli, lipopolysaccharide (LPS) combined with interferon (IFN)-?. Treatment of LPS/IFN-?-stimulated VSMCs with PMC suppressed the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 in a concentration-dependent manner. A reduction in LPS/IFN-?-induced nuclear factor (NF)-?B activation was also observed in PMC-treated VSMCs. The translocation and phosphorylation of p65, protein phosphatase 2A (PP2A) inactivation and the formation of reactive oxygen species (ROS) were significantly inhibited by PMC in LPS/IFN-?-activated VSMCs. However, neither I?B? degradation nor I?B kinase (IKK) or ribosomal s6 kinase-1 phosphorylation was affected by PMC under these conditions. Both treatments with okadaic acid, a PP2A-selective inhibitor, and transfection with PP2A siRNA markedly reversed the PMC-mediated inhibition of iNOS expression, NF-?B-promoter activity and p65 phosphorylation. Immunoprecipitation analysis of the cellular extracts of LPS/IFN-?-stimulated VSMCs revealed that p65 colocalizes with PP2A. In addition, p65 phosphorylation and PP2A inactivation were induced in VSMCs by treatment with H(2)O(2), but neither I?B? degradation nor IKK phosphorylation was observed. These results collectively indicate that the PMC-mediated inhibition of NF-?B activity in LPS/IFN-?-stimulated VSMCs occurs through the ROS-PP2A-p65 signalling cascade, an IKK-I?B?-independent mechanism. Therapeutic interventions using PMC may therefore be beneficial for the treatment of vascular inflammatory diseases.
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Acceleration of re-endothelialization and inhibition of neointimal formation using hybrid biodegradable nanofibrous rosuvastatin-loaded stents.
Biomaterials
PUBLISHED: 02-09-2014
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Incomplete endothelialization and neointimal hyperplasia of injured arteries can cause acute and late stent thromboses. This work develops hybrid stent/biodegradable nanofibers for the local and sustained delivery of rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of rosuvastatin for four weeks. The effectiveness of the local delivery of rosuvastatin in reducing platelets was studied. The tissue inflammatory reaction caused by the hybrid stents that were used to treat diseased arteries was also documented. The proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. The results of this work provide insight into how patients with a high risk of stent restenosis should be treated for accelerating re-endothelialization and inhibiting neointimal hyperplasia.
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Valproic acid suppresses lipopolysaccharide-induced cyclooxygenase-2 expression via MKP-1 in murine brain microvascular endothelial cells.
Biochem. Pharmacol.
PUBLISHED: 02-07-2014
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Inflammation and vascular perturbations are increasingly implicated in the pathogenesis of neurodegenerative diseases. Prevailing evidence suggests that valproic acid (VPA), an antiepileptic and mood stabilizer, exhibits not only neuro-protective effects, but also anti-inflammatory effects in neurodegenerative diseases. However, the underlying mechanism contributing to VPA's suppression of inflammatory responses remains unclear. In this study, we explored the inhibitory action of VPA on cyclooxygenase (COX)-2 expression in bEnd.3 mouse brain microvascular endothelial cells exposed to lipopolysaccharide (LPS), a pro-inflammatory stimulus. The LPS-induced increases in COX-2 protein level and COX-2 promoter-luciferase activity were significantly suppressed by VPA. VPA inhibited p38MAPK and JNK phosphorylation in LPS-stimulated bEnd.3 cells. Treatment of cells with a p38MAPK inhibitor (p38MAPK inhibitor III) or a JNK signaling inhibitor (JNK inhibitor II) significantly inhibited LPS-induced COX-2 expression. VPA inhibited LPS-induced NF-?B subunit p65 phosphorylation and ?B-luciferase activity. LPS-increased p65 and C/EBP? binding to the COX-2 promoter region was attenuated in the presence of VPA. In addition, VPA suppression of p38MAPK, JNK and p65 phosphorylation, and subsequent COX-2 expression was restored in cells transfected with mitogen-activated protein kinase phosphatase-1 (MKP-1) dominant negative (DN) mutant. VPA also caused increases in MKP-1 acetylation and MKP-1 phosphatase activity in bEnd.3 cells. In conclusion, VPA may cause MKP-1 activation to dephosphorylate p38MAPK and JNK, leading to decrease in p65 and C/EBP? binding to the COX-2 promoter region and COX-2 down-regulation in LPS-stimulated bEnd.3 cells. The present study therefore supports the therapeutic value of VPA in alleviating brain inflammatory processes.
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Proliferative effects of melatonin on Schwann cells: implication for nerve regeneration following peripheral nerve injury.
J. Pineal Res.
PUBLISHED: 01-31-2014
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Activation of proliferation of Schwann cells is crucial for axonal guidance and successful nerve regeneration following peripheral nerve injury (PNI). Considering melatonin plays an important role in proliferative regulation of central glial cells, the present study determined whether melatonin can effectively promote Schwann cell proliferation and improve nerve regeneration after PNI. The spontaneous immortalized rat Schwann cell line (RSC 96 cells) was first analyzed by quantitative polymerase chain reaction (QPCR) to detect the potential existence of melatonin receptors. The melatonin receptor-mediated signaling responsible for proliferation was examined by measuring the phosphorylation of extracellular signal-regulated kinases (ERK1/2) pathway. The in vivo model of PNI was performed by the end-to-side neurorrhaphy. The quantity of Schwann cells as well as the number of re-innervated motor end plates (MEP) on target muscles was examined to represent the functional recovery of injured nerves. QPCR results indicated that MT1 is the dominant receptor in Schwann cells. Immunoblotting and proliferation assay revealed an enhanced phosphorylation of ERK1/2 and increased number of RSC 96 cells following melatonin administration. Nonselective melatonin receptor antagonist (luzindole) treatment significantly suppressed all the above findings, suggesting that the proliferative effects of melatonin were mediated by a receptor-dependent pathway. In vivo results corresponded well with in vitro findings in which melatonin effectively increased the amount of proliferated Schwann cells and re-innervated MEP on target muscles following PNI. As melatonin successfully improves nerve regeneration by promoting Schwann cell proliferation, therapeutic use of melatonin may thus serve as a promising strategy to counteract the PNI-induced neuronal disability.
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Microwave assistance of labeling hippuric acid by I-131.
Appl Radiat Isot
PUBLISHED: 01-28-2014
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This work presents a novel approach for labeling hippuric acid with I-131 using microwaves. It utilizes copper(II) acetate as a catalyst of the labeling. The process involves the use of this catalytic copper(II) acetate at low dilutions that were nevertheless sufficient to produce labeled hippuric acid with high radiochemical purity in a short time. Therefore, the novel technique overcomes the limitations of previously reported conventional methods that involve heating.
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Drug delivery system design and development for boron neutron capture therapy on cancer treatment.
Appl Radiat Isot
PUBLISHED: 01-23-2014
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We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content.
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Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age.
Fertil. Steril.
PUBLISHED: 01-15-2014
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To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care.
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Reciprocal regulation of microRNA-99a and insulin-like growth factor I receptor signaling in oral squamous cell carcinoma cells.
Mol. Cancer
PUBLISHED: 01-06-2014
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MicroRNAs (miRNAs), small noncoding RNA molecules can function as oncogenes or tumor suppressors in tumorigenesis. Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with a 5-year survival rate of approximately 50%.
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Behavioral variant frontotemporal dementia patients do not succumb to the Allais paradox.
Front Neurosci
PUBLISHED: 01-01-2014
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The Allais Paradox represents one of the earliest empirical challenges to normative models of decision-making, and suggests that choices in one part of a gamble may depend on the possible outcome in another, independent, part of the gamble-a violation of the so-called "independence axiom." To account for Allaisian behavior, one well-known class of models propose that individuals' choices are influenced not only by possible outcomes resulting from one's choices, but also the anticipation of regret for foregone options. Here we test the regret hypothesis using a population of patients with behavioral variant frontotemporal dementia (bvFTD), a clinical population known to present ventromedial prefrontal cortex dysfunctions and associated with impaired regret processing in previous studies of decision-making. Compared to matched controls and Alzheimer's disease (AD) patients, we found a striking diminution of Allaisian behavior among bvFTD patients. These results are consistent with the regret hypothesis and furthermore suggest a crucial role for prefrontal regions in choices that typically stands in contradiction with a basic axiom of rational decision-making.
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Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.
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Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.
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Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.
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Relationship between structure of conjugated oxime esters and their ability to cleave DNA.
Bioconjug. Chem.
PUBLISHED: 10-30-2013
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The size and geometry of polycycles are critical to intercalation into DNA. This work involves the establishment of a new compound library that includes 35 O-benzoyl oxime esters with intercalators of five types. These conjugated compounds were synthesized by the condensation of substituted benzoyl chlorides (XC6H4COCl; X = H, Me, CN, F, and NO2) or naphthoyl chlorides with oximes of fluoren-9-one, 9,10-anthraquinone, xanthen-9-one, thioxanthen-9-one, and 9H-thioxanthen-9-one 10,10-dioxide to give the corresponding esters in 80-99% yields. All of these compounds could cleave DNA when photolyzed by UV light. Of these conjugates, 9,10-anthraquinone-O-9-(4-fluorobenzoyl)oxime with a binding constant of 4.49 × 10(4) M(-1) cleaved DNA most efficiently. Examination of the structure-activity relationship supports a conclusion that two factors affect DNA-cleaving potency. These are (1) the planarity of the intercalating moiety, and (2) the size and substituents of the benzoyl ring. The DNA-cleaving ability followed the order 9,10-anthraquinone > fluoren-9-one ? xanthen-9-one ? thioxanthen-9-one > 9H-thioxanthen-9-one 10,10-dioxide. The benzoyl-containing oxime ester conjugates were more active than the corresponding naphthoyl-containing conjugates. The potency that was associated with the different substituents on the benzoyl ring followed the order F > CN ? NO2 > Me ? H.
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Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells.
Angiogenesis
PUBLISHED: 09-12-2013
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Formation of lymphatic capillaries by lymphatic endothelial cells (LECs) occurs both in normal tissues as well as in pathological processes including tumor metastasis. Interleukin-6 (IL-6), a potent pro-inflammatory cytokine, has been shown to be highly elevated in various cancers. IL-6 has also been shown to increase tumor lymphangiogenesis through vascular endothelial growth factor-C (VEGF-C) induction in tumor cells. Although lymphangiogenesis is associated with lymph node metastasis and also resistance to conventional therapy in various cancers, the precise mechanisms of lymphangiogenesis in LECs remain unclear. This study aimed to investigate the signaling cascade involved in IL-6-induced VEGF-C expression in murine LECs (SV-LEC). The VEGF-C mRNA and protein levels were increased in SV-LECs exposed to IL-6. IL-6 time-dependently induced Src phosphorylation and downstream phosphorylation of ERK1/2 and p38MAPK. In contrast, PP2, an inhibitor of Src signaling, abrogated IL-6s effects on ERK1/2 and p38MAPK phosphorylation. IL-6 exposure also led to increase in VEGF-C promoter-luciferase activity as well as C/EBP?- and ?B-luciferase activities. VEGF-C promoter-, C/EBP?- and ?B-luciferase activities were all suppressed by Src, ERK1/2 or p38MAPK signaling blockades despite presence of IL-6. Finally, C/EBP? and p65 binding to the VEGF-C promoter region were increased after IL-6 exposure in SV-LECs. Taken together, we report a Src-mediated ERK1/2 and p38MAPK activation resulting in C/EBP? and p65 binding to the promoter region of VEGF-C, leading to VEGF-C expression in IL-6-exposed SV-LECs.
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Ligand-Dependent Activation of EphA4 Signaling Regulates the Proteolysis of Amyloid Precursor Protein Through a Lyn-Mediated Pathway.
Mol. Neurobiol.
PUBLISHED: 09-06-2013
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Alzheimers disease is the most common dementia afflicting the elderly in modern society. This disease arises from the neurotoxicity elicited by abnormal aggregates of amyloid-? (A?) protein. Such aggregates form through the cleavage of amyloid precursor protein (APP) by ?-secretase and the subsequent proteolysis of the APP C-terminal fragment (APP-?CTF or C99) by ?-secretase to yield A? and APP intracellular domain (AICD). Recent evidence suggests that C99 and AICD may exert harmful effects on cells, suggesting that the proteolytic products of APP, including A?, C99, and AICD, could play a pivotal role in neuronal viability. Here, we demonstrate that ligand-activated EphA4 signaling governs the proteostasis of C99, AICD, and A?, without significantly affecting ?-secretase activity. EphA4 induced accumulation of C99 and AICD through a Lyn-dependent pathway; activation of this pathway triggered phosphorylation of EphA4, resulting in positive feedback of C99 and AICD proteostasis. Inhibition of EphA4 by dasatinib, a receptor tyrosine kinase inhibitor, effectively suppressed C99 and AICD accumulation. Furthermore, EphA4 signaling controlled C99 and AICD proteolysis through the ubiquitin-proteasome system. In conclusion, we have identified an EphA4-Lyn pathway that is essential for the metabolism of APP and its proteolytic derivatives, thereby providing novel pharmacological targets for the development of anti-A? therapeutics for AD.
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A novel estrogen receptor-microRNA 190a-PAR-1-pathway regulates breast cancer progression, a finding initially suggested by genome-wide analysis of loci associated with lymph-node metastasis.
Hum. Mol. Genet.
PUBLISHED: 09-05-2013
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To identify microRNAs that are important in regulating breast cancer progression, the present study used data for the 199 961 single-nucleotide polymorphisms (SNPs) in 837 breast cancer patients genotyped in a recent genome-wide association study to identify loci associated with lymph node metastasis (LNM). SNPs tagging the 15q22.2 locus showed a significant association with LNM and miR-190a was found to be the only microRNA in this region. The role of miR-190a in LNM was supported by the findings that increased miR-190a expression inhibited cell migration and invasiveness and that the target of miR-190a was protease-activated-receptor 1 (PAR-1), which is a metastasis promoting protein in several cancers. In addition, the promoter region of miR-190a was defined and found to contain half of an estrogen response element, suggesting that miR-190a is regulated by estrogen receptor (ER) signaling. This was confirmed by the findings that miR-190a expression was activated by 17?-estradiol and that ER? bound directly to this promoter. The importance of this ER?-miR190a-PAR-1 link in breast tumorigenesis is suggested by the findings of (i) an association between genetic polymorphism of the miR-190a-containing region and LNM that is modified by SNPs of PAR-1 and is particularly significant in ER?-positive patients and (ii) a combined effect of ER? and miR-190a expression on tumor grade/cancer stage. More importantly, the level of miR-190a expression in primary breast carcinomas correlated with overall survival. These findings suggest a novel pathway in which ER? signaling regulates miR-190a expression, causing inhibition of PAR-1 expression, correlated with inhibition of cancer metastasis.
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Adenocarcinoma arising from tubulovillous adenoma in a native bladder following gastrocystoplasty.
Pediatr. Surg. Int.
PUBLISHED: 09-02-2013
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Gastrocystoplasty is a surgical form of bladder augmentation which improves bladder capacity and compliance. Patients who undergo bladder augmentation with a gastric remnant are at increased risk for malignancy. The most common types of tumors in this situation were adenocarcinoma and urothelial carcinoma. Most of the adenocarcinomas arise in the gastric remnant or anastomotic site, and adenocarcinomas arising in the residual native bladder are extremely rare. We report on a patient who received gastrocystoplasty 16 years ago. She suffered from recurrent urinary tract infections for a year and cystoscopy showed a tumor in the bladder trigone. Pathologic examination showed tubulovillous adenoma with malignant transformation to adenocarcinoma. The tumor consisted of intact adenomatous architecture from low-grade dysplastic gland to adenocarcinoma, which suggested that the pathogenesis might be related to intestinal metaplasia and dysplasia. The unique location and immunohistologic findings of the tumor suggested that it originated in the bladder mucosa.
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Anti-inflammatory effects of hydrophilic and lipophilic statins with hyaluronic acid against LPS-induced inflammation in porcine articular chondrocytes.
J. Orthop. Res.
PUBLISHED: 07-29-2013
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The objective of the study is to understand the therapeutic effects of lipophilic (simvastatin) and hydrophilic statins (pravastatin) combined with/without hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model of articular chondrocytes. HA in combination with different doses of simvastatin or pravastatin were used. Beside cytotoxicity, the influence of statins on NO production, pro-inflammatory cytokine, inflammatory mediators, and NF-?B p50 protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand breakage. Two statins were less able to lower NF-?B activity when they were administrated along without HA. The gene expression demonstrates that simvastatin and pravastatin had the ability to decrease pro-inflammatory and inflammatory mediator levels. High dose simvastatin with or without HA down regulated inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms the regulatory effect of statins with or without HA over the apoptosis of chondrocytes, especially in hydrophilic statins. The significant down-regulation of inflammatory mediators suggests that intra-articular injection of HA in combination with statins might feasibly slow the progress of osteoarthritis. Administration of simvastatin or pravastatin with hyaluronic acid may produce beneficial effects for OA treatment, but with better results when hydrophilic statin was used. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Calnexin is required for zebrafish posterior lateral line development.
Int. J. Dev. Biol.
PUBLISHED: 07-23-2013
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The lateral line is a mechanosensory system in fish and amphibians to detect local water flow and pressure. Development of the posterior lateral line (PLL) originates from the migrating PLL primordium (PLLP). The PLLP deposits neuromasts on the trunk during migration to the tail. Molecular dissection revealed that PLL development is associated with genes mediating cell adhesion, morphogenesis, neurogenesis and development, but the regulatory signaling network is far from completion. To further investigate candidate regulatory genes for lateral line development, we found using whole-mount in situ hybridization that calnexin, an endoplasmic reticular (ER) calcium-binding protein gene, is expressed in PLL neuromasts. Knockdown of calnexin using antisense morpholino oligonucleotides resulted in a dose-dependent reduction in neuromasts and hair cells of the PLL. Using a transgenic claudin b:gfp line, we observed a notably reduced PLLP size, but no significant migration defect in calnexin morphants. Finally, we discovered that the reduced PLLP is associated with a reduction in cell proliferation and an increase in ER stress-dependent apoptosis. These results suggest that calnexin is essential for neuromast formation during lateral line development in the zebrafish.
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Synthesis of apolipoprotein B lipoparticles to deliver hydrophobic/amphiphilic materials.
ACS Appl Mater Interfaces
PUBLISHED: 07-19-2013
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To develop a drug delivery system (DDS), it is critical to address challenging tasks such as the delivery of hydrophobic and amphiphilic compounds, cell uptake, and the metabolic fate of the drug delivery carrier. Low-density lipoprotein (LDL) has been acknowledged as the human serum transporter of natively abundant lipoparticles such as cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo B) is the only protein contained in LDL, and possesses a binding moiety for the LDL receptor that can be internalized and degraded naturally by the cell. Therefore, synthetic/reconstituting apoB lipoparticle (rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic materials. Here, we synthesized rABL in vitro, using full-length apoB through a five-step solvent exchange method, and addressed its potential as a DDS. Our rABL exhibited good biocompatibility when evaluated with cytotoxicity and cell metabolic response assays, and was stable during storage in phosphate-buffered saline at 4 °C for several months. Furthermore, hydrophobic superparamagnetic iron oxide nanoparticles (SPIONPs) and the anticancer drug M4N (tetra-O-methyl nordihydroguaiaretic acid), used as an imaging enhancer and lipophilic drug model, respectively, were incorporated into the rABL, leading to the formation of SPIONPs- and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier transform infrared spectroscopy suggested that rABL has a similar composition to that of LDL, and successfully incorporated SPIONPs or M4N. SPIO@rABL presented significant hepatic contrast enhancement in T2-weighted magnetic resonance imaging in BALB/c mice, suggesting its potential application as a medical imaging contrast agent. M4N@rABL could reduce the viability of the cancer cell line A549. Interestingly, we developed solution-phase high-resolution transmission electron microscopy to observe both LDL and SPIO@rABL in the liquid state. In summary, our LDL-based DDS, rABL, has significant potential as a novel DDS for hydrophobic and amphiphilic materials, with good cell internalization properties and metabolicity.
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Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-08-2013
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The circadian clock gene Period2 (PER2) has been suggested to be a tumor suppressor. However, detailed mechanistic evidence has not been provided to support this hypothesis. We found that loss of PER2 enhanced invasion and activated expression of epithelial-mesenchymal transition (EMT) genes including TWIST1, SLUG, and SNAIL. This finding was corroborated by clinical observation that PER2 down-regulation was associated with poor prognosis in breast cancer patients. We further demonstrated that PER2 served as a transcriptional corepressor, which recruited polycomb proteins EZH2 and SUZ12 as well as HDAC2 to octamer transcription factor 1 (OCT1) (POU2F1) binding sites of the TWIST1 and SLUG promoters to repress expression of these EMT genes. Hypoxia, a condition commonly observed in tumors, caused PER2 degradation and disrupted the PER2 repressor complex, leading to activation of EMT gene expression. This result was further supported by clinical data showing a significant negative correlation between hypoxia and PER2. Thus, our findings clearly demonstrate the tumor suppression function of PER2 and elucidate a pathway by which hypoxia promotes EMT via degradation of PER2.
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Human acellular cartilage matrix powders as a biological scaffold for cartilage tissue engineering with synovium-derived mesenchymal stem cells.
J Biomed Mater Res A
PUBLISHED: 06-24-2013
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In our previous study, we found that cartilage fragments from osteoarthritic knee promoted chondrogenesis of mesenchymal stem cells. In this study, we further transformed the cartilage tissues into acellular cartilage matrix (ACM) and explored the feasibility of using ACM as a biological scaffold. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery and were successfully fabricated into ACM powders. The ACM powders and human synovium-derived mesenchymal stem cells (SMSCs) were mixed into collagen gel for in vitro culture. Histological results showed a synergistic effect of ACM powders and chondrogenic growth factors in the formation of engineered cartilage. The findings of real-time polymerase chain reaction (PCR) suggested that ACM powders had the potential of promoting type II collagen gene expression in the growth factors-absent environment. Moreover, with growth factors induction, the ACM powders could reduce the hypertrophy in chondrogenesis of SMSCs. In summary, ACM powders could serve as a functional scaffold that benefited the chondrogenesis of SMSCs for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Antiapoptotic Agent Sphingosine-1-Phosphate Protects Vitrified Murine Ovarian Grafts.
Reprod Sci
PUBLISHED: 06-21-2013
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Significant follicle loss from frozen ovarian grafts is unavoidable. The authors evaluated the protective effects of the antiapoptotic agent sphingosine-1-phosphate (S1P) on vitrified ovarian grafts. Three-week-old sexually immature female FVB mice were divided into 4 groups, fresh, control without S1P, 0.5 mmol/L S1P, and 2 mmol/L S1P. The ovaries were pretreated with S1P for 1 hour and then cryopreserved by modified vitrification. The frozen-thawed ovaries were autotransplanted under the back muscles of mice for 10 days. Expression of apoptosis-related genes encoding caspase 3 and c-Myc was analyzed in the vitrified ovaries and 10 days after transplantation using real-time quantitative polymerase chain reaction. To quantify the ovarian reserve, anti-Müllerian hormone (AMH) levels and follicles were measured in the 10-day vitrified ovarian grafts. Caspase 3 and c-Myc messenger RNA did not differ significantly in the 4 groups after vitrification but was significantly upregulated in the control group after transplantation. The AMH levels and primordial follicle pool were significantly higher in the S1P-treated groups than in the control group but lower than that in the fresh group. The S1P protects vitrified ovarian grafts from ischemic reperfusion injury rather than from vitrification-associated process.
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Emphysematous Pyelonephritis: Patient Characteristics and Management Approach.
Urol. Int.
PUBLISHED: 06-14-2013
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Introduction: Emphysematous pyelonephritis (EPN) is an acute, severe, necrotizing infection of the renal parenchyma and perirenal tissue that requires immediate treatment. However, the ideal approach to its management remains controversial. We conducted this study to determine the appropriate treatment modalities. Materials and Methods: A retrospective review of EPN cases revealed 10 consecutive cases from July 2003 to June 2012. Clinical and demographic data were collected from each patient. Results: All patients had diabetes mellitus, 5 presented with urinary tract obstruction by urolithiasis. Seven patients had type I disease and 3 had type II disease. Six of the type I patients underwent emergent nephrectomy and 1 of these died, the remaining patient refused surgical intervention and died after receiving medical management only. The type II patients underwent percutaneous drainage, and 2 of them subsequently underwent elective nephrectomy; all 3 survived. Conclusion: Our results suggest that emergency nephrectomy may be considered the initial management for type I EPN, while percutaneous drainage may be an effective initial treatment option for type II EPN. © 2013 S. Karger AG, Basel.
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Low-tube-voltage (80 kVp) CT aortography using 320-row volume CT with adaptive iterative reconstruction: lower contrast medium and radiation dose.
Eur Radiol
PUBLISHED: 05-08-2013
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To evaluate CT aortography at reduced tube voltage and contrast medium dose while maintaining image quality through iterative reconstruction (IR).
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Acute transverse myelitis after thoracic epidural anesthesia and analgesia: should anesthesia and analgesia be blamed?
Acta Anaesthesiol Taiwan
PUBLISHED: 04-28-2013
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A 63-year-old man developed acute transverse myelitis (ATM) with a rapid progression of sensory and motor deficits and autonomic dysfunction 2 days after chest surgery. Thoracic epidural anesthesia/analgesia (TEA) had been administered in this case. Since the temporal and spatial relationships between TEA and ATM are so close, one may easily mistake the TEA as the cause. Therefore, we discuss here the differential diagnoses for cord damage after TEA and the characteristics of ATM, and suggest that it is unlikely that TEA is the cause of ATM in this case.
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Long-term biometric optic components of diode laser-treated threshold retinopathy of prematurity at 9 years of age.
Acta Ophthalmol
PUBLISHED: 04-20-2013
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To assess quantitatively the biometric optic components and its relationship with refractive status in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP).
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B3GNT3 expression suppresses cell migration and invasion and predicts favorable outcomes in neuroblastoma.
Cancer Sci.
PUBLISHED: 04-19-2013
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Aberrant expression of the simple mucin-type carbohydrate antigens such as T, Tn, sialyl-T and sialyl-Tn is associated with poor prognosis in several cancers. ?1,3-N-acetylglucosaminyltransferase-3 (B3GNT3), a member of the ?3GlcNAcT family, is responsible for forming extended core 1 (T antigen) oligosaccharides. The role of B3GNT3, which is expressed in various tissues including human fetal brain, in regulating neuroblastoma (NB) formation and cell behaviors remains unclear. Here, we showed that increased B3GNT3 expression evaluated using immunohistochemistry in NB tumor tissues correlated well with the histological grade of differentiation as well as a favorable Shimadas subset of pathology. Univariate and multivariate analyses revealed that positive B3GNT3 expression in tumor tissues predicted a favorable prognosis in NB patients independent of other prognostic markers. B3GNT3 overexpression suppresses T antigen formation and malignant phenotypes including migration and invasion of SK-N-SH cells, whereas B3GNT3 knockdown enhances these phenotypes of SK-N-SH cells. Moreover, B3GNT3 expression decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt and ERK1/2. We conclude that B3GNT3 predicts a favorable cancer behavior of NB and suppresses malignant phenotypes by modulating mucin-type O-glycosylation and signaling in NB cells.
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[Patient safety and nursing staff allocation].
Hu Li Za Zhi
PUBLISHED: 04-17-2013
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This article aims to explore three main concepts related to the professional development of nursing professionals. This paper first critically reviews and reinterprets scientific evidence on the relationship between nurse staff allocation and healthcare outcomes and then challenges some of the common interpretations of this evidence in the professional literature. Secondly, in the absence of solid empirical evidence provided by sophisticated datasets in this field, we consider how Communitarianism may provide a well-defined, highly appropriate ethical framework for further developing and improving the nursing profession and healthcare outcomes. Thirdly, this article examines the role of Communitarian ethics in setting Taiwans healthcare priorities and promotion nursings core professional values. In conclusion, we recommend several conceptual health policy frameworks to ensure patient safety.
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Retinoic acid-elicited RAR?/RXR? signaling attenuates A? production by directly inhibiting ?-secretase-mediated cleavage of amyloid precursor protein.
ACS Chem Neurosci
PUBLISHED: 04-15-2013
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Retinoic acid (RA)-elicited signaling has been shown to play critical roles in development, organogenesis, and the immune response. RA regulates expression of Alzheimers disease (AD)-related genes and attenuates amyloid pathology in a transgenic mouse model. In this study, we investigated whether RA can suppress the production of amyloid-? (A?) through direct inhibition of ?-secretase activity. We report that RA treatment of cells results in significant inhibition of ?-secretase-mediated processing of the amyloid precursor protein C-terminal fragment APP-C99, compared with DMSO-treated controls. RA-elicited signaling was found to significantly increase accumulation of APP-C99 and decrease production of secreted A?40. In addition, RA-induced inhibition of ?-secretase activity was found to be mediated through significant activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells with the specific ERK inhibitor PD98059 completely abolished RA-mediated inhibition of ?-secretase. Consistent with these findings, RA was observed to inhibit secretase-mediated proteolysis of full-length APP. Finally, we have established that RA inhibits ?-secretase through nuclear retinoic acid receptor-? (RAR?) and retinoid X receptor-? (RXR?). Our findings provide a new mechanistic explanation for the neuroprotective role of RA in AD pathology and add to the previous data showing the importance of RA signaling as a target for AD therapy.
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Financial errors in dementia: Testing a neuroeconomic conceptual framework.
Neurocase
PUBLISHED: 04-03-2013
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Financial errors by patients with dementia can have devastating personal and family consequences. We developed and evaluated a neuroeconomic conceptual framework for understanding financial errors across different dementia syndromes, using a systematic, retrospective, blinded chart review of demographically-balanced cohorts of patients with Alzheimers disease (AD, n=100) and behavioral variant frontotemporal dementia (bvFTD, n=50). Reviewers recorded specific reports of financial errors according to a conceptual framework identifying patient cognitive and affective characteristics, and contextual influences, conferring susceptibility to each error. Specific financial errors were reported for 49% of AD and 70% of bvFTD patients (p?=?0.012). AD patients were more likely than bvFTD patients to make amnestic errors (p < 0.001), while bvFTD patients were more likely to spend excessively (p?=?0.004) and to exhibit other behaviors consistent with diminished sensitivity to losses and other negative outcomes (p < 0.001). Exploratory factor analysis identified a social/affective vulnerability factor associated with errors in bvFTD, and a cognitive vulnerability factor associated with errors in AD. Our findings highlight the frequency and functional importance of financial errors as symptoms of AD and bvFTD. A conceptual model derived from neuroeconomic literature identifies factors that influence vulnerability to different types of financial error in different dementia syndromes, with implications for early diagnosis and subsequent risk prevention.
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Simvastatin induced HCT116 colorectal cancer cell apoptosis through p38MAPK-p53-survivin signaling cascade.
Biochim. Biophys. Acta
PUBLISHED: 04-02-2013
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Statins, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors with cholesterol-lowering properties, were recently shown to exhibit anti-cancer effects. However, the molecular mechanism underlying statin-induced cancer cell death remains to be elucidated. Elevated level of survivin is often found over-expressed in human cancers and has been implicated in the progression of tumorigenesis. Given its central role in cell division and action as an apoptosis suppressor, survivin represents a potential molecular target in cancer management.
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Changes in the PCOS phenotype with age.
Steroids
PUBLISHED: 03-21-2013
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Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women. The diagnosis of PCOS is mainly based on the following three components: (1) hyperandrogenism, (2) oligo-amenorrhea, and (3) the observation of polycystic ovaries on a sonogram. The comorbidities may include insulin resistance, type II diabetes mellitus, hypertension and cardiovascular disease. Importantly, the diagnostic criteria and complications related to PCOS are age-dependent. Androgen production in women may decrease because of ovarian aging or decreased production by the adrenal glands over time. The prevalence of hirsutism and acne decreases with age. Ovarian volume and follicle number also decrease with age, with the age-related decrease in follicle number seemingly greater than that of ovarian volume. Aging may also be associated with increased risk of insulin resistance and metabolic disturbances. Therefore, these age-related changes may affect the observed incidence and complications of PCOS. In adolescent patients, the criteria described above pose particular diagnostic problems because the characteristics of normal puberty often overlap with the signs and symptoms of PCOS. Hyperandrogenism and chronic anovulation are the primary disturbances in younger women with PCOS; whereas, obesity, insulin resistance, and metabolic disturbances are predominant in older women with PCOS. The deterioration of insulin resistance during the reproductive life of women with PCOS appears to be mainly attributable to the increase in obesity. Therefore, if body weight could be controlled properly, younger hyperandrogenic PCOS women might reduce their risk of insulin resistance and metabolic disturbances later in life.
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Intravitreal bevacizumab (Avastin) and panretinal photocoagulation in the treatment of high-risk proliferative diabetic retinopathy.
J Ocul Pharmacol Ther
PUBLISHED: 03-15-2013
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To report the short-term efficacy and safety of intravitreal bevacizumab (Avastin) injection with panretinal laser photocoagulation (PRP) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria.
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?-1,4-Galactosyltransferase III enhances invasive phenotypes via ?1-integrin and predicts poor prognosis in neuroblastoma.
Clin. Cancer Res.
PUBLISHED: 02-26-2013
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Neuroblastoma (NB) is a neural crest-derived tumor that commonly occurs in childhood. ?-1,4-Galactosyltransferase III (B4GALT3) is highly expressed in human fetal brain and is responsible for the generation of poly-N-acetyllactosamine, which plays a critical role in tumor progression. We therefore investigated the expression and role of B4GALT3 in NB.
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Presenilin-1 Regulates the Expression of p62 to Govern p62-dependent Tau Degradation.
Mol. Neurobiol.
PUBLISHED: 02-22-2013
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Mutations in presenilin-1 (PS1) are tightly associated with early-onset familial Alzheimers disease (FAD), which is characterized by extracellular amyloid plaques and the accumulation of intracellular Tau. In addition to being the catalytic subunit of ?-secretase, PS1 has been shown to regulate diverse cellular functions independent of its proteolytic activity. We found that cells deficient in PS1 exhibit reduced levels of p62 protein, a cargo-receptor shuttling Tau for degradation. The downregulation of PS1 led to a significant decrease in both the protein and mRNA transcript of p62, concomitant with attenuated p62 promoter activity. This PS1-dependent regulation of p62 expression was mediated through an Akt/AP-1 pathway independent of the proteolytic activity of PS1/?-secretase. This p62-mediated Tau degradation was significantly impaired in PS1-deficient cells, which can be rescued by ectopic expression of either p62 or wild-type PS1 but not mutant PS1 containing FAD-linked mutations. Our study suggests a novel function for PS1 in modulating p62 expression to control the proteostasis of Tau.
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Hyperhomocysteinaemia is associated with biochemical hyperandrogenaemia in women with reproductive age.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 02-21-2013
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Hyperhomocysteinaemia is a well-established risk factor for cardiovascular disease. This study investigated the relationship between hyperhomocysteinaemia and factors related to polycystic ovary syndrome (PCOS).
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Competitive bond rupture in the photodissociation of bromoacetyl chloride and 2- and 3-bromopropionyl chloride: adiabatic versus diabatic dissociation.
Chemphyschem
PUBLISHED: 02-10-2013
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Competitive bond dissociation mechanisms for bromoacetyl chloride and 2- and 3-bromopropionyl chloride following the (1) [n(O)??*(C=O)] transition at 234-235 nm are investigated. Branching ratios for C?Br/C?Cl bond fission are found by using the (2+1) resonance-enhanced multiphoton ionization (REMPI) technique coupled with velocity ion imaging. The fragment branching ratios depend mainly on the dissociation pathways and the distances between the orbitals of Br and the C=O chromophore. C?Cl bond fission is anticipated to follow an adiabatic potential surface for a strong diabatic coupling between the n(O)?*(C=O) and np (Cl)?*(C?Cl) bands. In contrast, C?Br bond fission is subject to much weaker coupling between n(O)?*(C=O) and np (Br)?*(C?Br). Thus, a diabatic pathway is preferred for bromoacetyl chloride and 2-bromopropionyl chloride, which leads to excited-state products. For 3-bromopropionyl chloride, the available energy is not high enough to reach the excited-state products such that C?Br bond fission must proceed through an adiabatic pathway with severe suppression by nonadiabatic coupling. The fragment translational energies and anisotropy parameters for the three molecules are also analyzed and appropriately interpreted.
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A bioconjugated design for amino acid-modified mesoporous silicas as effective adsorbents for toxic chemicals.
J. Hazard. Mater.
PUBLISHED: 02-09-2013
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A general synthetic method for functionalization of mesoporous silica with amino acid has been developed. The carboxylic acid functionalized SBA-15 was conjugated with l-phenylalanine (Phe) and l-tryptophan (Trp) to obtain nontoxic amino acid-conjugated functionalized mesoporous silica materials. The materials were used as adsorbents for the removal of the herbicide Paraquat (PQ) and its analog, ethyl viologen dibromide (EVB) from aqueous solutions. In comparison to the commercially available activated carbon adsorbents, the silica-based adsorbents prepared in this study exhibited relatively higher PQ removal efficiency in aqueous solutions at room temperature and pH 7.0. The silica-based adsorbents, pendant with amino acid moieties exhibited greater adsorption capacities toward PQ and EVB than the analogs but without the amino acid moiety, suggesting that there is a benefit for the enhanced ?-? interaction between the aromatic groups of the conjugated amino acid moieties and the adsorbate. This bioconjugated method developed here provides a promising new tool to synthesize new materials for detoxification of herbicides in clinical trials.
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Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus.
Eur J Med Chem
PUBLISHED: 02-05-2013
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A new compound library that contained 20 hinged benzimidazole-coumarin hybrids and their ?-d-ribofuranosides was established. The anti-hepatitis C virus (HCV) activity of all novel coumarin derivatives, which were obtained by use of organic synthetic methods, was tested. Two of these hybrids exhibited appealing EC50 values of as low as 3.0 and 5.5 ?M. The best selectivity index was 14. The incorporation of a d-ribofuranose into the hinged hybrids provided the corresponding nucleosides with the ? configuration, one of which inhibited HCV replication with an EC50 value of 20 ?M. Additionally, the structure-activity relationship is elucidated on the basis of the functional groups that were attached to the nuclei of benzimidazole, coumarin, and ribofuranose of the hybrids.
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Caffeic Acid phenethyl ester as a potential treatment for advanced prostate cancer targeting akt signaling.
Int J Mol Sci
PUBLISHED: 01-30-2013
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Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1-3 years after treatment. The median overall survival time is 1-2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-?B inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.