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Find video protocols related to scientific articles indexed in Pubmed.
Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis.
Nucleic Acids Res.
PUBLISHED: 11-16-2014
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We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis.
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The feasibility of using simulated targets in the stomachs of live pigs for full endoscopic submucosal dissection training.
Gut Liver
PUBLISHED: 11-15-2014
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In endoscopic submucosal dissection (ESD) training, only a flat target lesion can usually be simulated in the normal mucosa. This study aimed to evaluate the feasibility of simulated targets in the stomachs of live pigs for complete training.
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Eyelid closure in embryogenesis is required for ocular adnexa development.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-08-2014
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Purpose: Mammalian eye development requires temporary fusion of the upper and lower eyelids in embryogenesis. Failure of lid closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid closure in eye development. Methods: Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective eyelid closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry. Results: Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses. Conclusions: In addition to providing a protective barrier for the ocular surface, eyelid closure in embryogenesis is required for the development of ocular adnexa, including eyelid and extraocular muscles.
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TGF? signaling inhibits goblet cell differentiation via SPDEF in conjunctival epithelium.
Development
PUBLISHED: 11-05-2014
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The ocular surface epithelia, including the stratified but non-keratinized corneal, limbal and conjunctival epithelium, in concert with the epidermal keratinized eyelid epithelium, function together to maintain eye health and vision. Abnormalities in cellular proliferation or differentiation in any of these surface epithelia are central in the pathogenesis of many ocular surface disorders. Goblet cells are important secretory cell components of various epithelia, including the conjunctiva; however, mechanisms that regulate goblet cell differentiation in the conjunctiva are not well understood. Herein, we report that conditional deletion of transforming growth factor ? receptor II (Tgfbr2) in keratin 14-positive stratified epithelia causes ocular surface epithelial hyperplasia and conjunctival goblet cell expansion that invaginates into the subconjunctival stroma in the mouse eye. We found that, in the absence of an external phenotype, the ocular surface epithelium develops properly, but young mice displayed conjunctival goblet cell expansion, demonstrating that TGF? signaling is required for normal restriction of goblet cells within the conjunctiva. We observed increased expression of SAM-pointed domain containing ETS transcription factor (SPDEF) in stratified conjunctival epithelial cells in Tgfbr2 cKO mice, suggesting that TGF? restricted goblet cell differentiation directly by repressing Spdef transcription. Gain of function of Spdef in keratin 14-positive epithelia resulted in the ectopic formation of goblet cells in the eyelid and peripheral cornea in adult mice. We found that Smad3 bound two distinct sites on the Spdef promoter and that treatment of keratin 14-positive cells with TGF? inhibited SPDEF activation, thereby identifying a novel mechanistic role for TGF? in regulating goblet cell differentiation.
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Review of enterovirus 71 vaccines.
Clin. Infect. Dis.
PUBLISHED: 10-28-2014
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Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD) outbreaks worldwide and have a significant socioeconomic impact in particular in Asia. Formalin-inactivated EV71 (FI-EV71) vaccines evaluated in human clinical trials in China, Taiwan and Singapore were found to be safe and to elicit strong neutralizing antibody responses against EV71 currently circulating in Asia. The results from 3 different phase III clinical trials performed in young children (6 to 60 months) indicate that the efficacy of FI-EV71 vaccines is >90% against EV71-related HFMD and >80% against EV71-associated serious diseases, but the vaccines did not protect against CVA16 infections. Here we discuss the critical factors affecting EV71 vaccine product registration, including clinical epidemiology, antigenic shift issues in cross-protection and vaccine strain selection, standardized animal models for potency test, and cost-effective manufacturing processes for potential incorporation of FI-EV71 vaccine into EPI vaccines.
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The association between prostate cancer and mood disorders: a nationwide population-based study in Taiwan.
Int Psychogeriatr
PUBLISHED: 10-23-2014
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ABSTRACT Background: This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients. Methods: From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status. Results: Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders. Conclusion: We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.
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Impact of hospital volume on long-term survival after resection for oesophageal cancer: a population-based study in Taiwan†.
Eur J Cardiothorac Surg
PUBLISHED: 10-03-2014
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Previous studies have shown that patients who undergo oesophageal cancer surgery in high-volume hospitals have lower postoperative mortality rates. However, the impact of hospital volume on long-term survival is controversial.
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The impacts of migraine and anxiety disorders on painful physical symptoms among patients with major depressive disorder.
J Headache Pain
PUBLISHED: 09-23-2014
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No study has simultaneously investigated the impacts of migraine and anxiety disorders on painful physical symptoms (PPS) among patients with major depressive disorder (MDD). The study aimed to investigate this issue.
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The novel Aryl hydrocarbon receptor inhibitor biseugenol inhibits gastric tumor growth and peritoneal dissemination.
Oncotarget
PUBLISHED: 09-17-2014
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Biseugenol (Eug) is known to antiproliferative of cancer cells; however, to date, the antiperitoneal dissemination effects have not been studied in any mouse cancer model. In this study, Aryl hydrocarbon receptor (AhR) expression was associated with lymph node and distant metastasis in patients with gastric cancer and was correlated with clinicolpathological pattern. We evaluated the antiperitoneal dissemination potential of knockdown AhR and Biseugenol in cancer mouse model and assessed mesenchymal characteristics. Our results demonstrate that tumor growth, peritoneal dissemination and peritoneum or organ metastasis implanted MKN45 cells were significantly decreased in shAhR and Biseugenol-treated mice and that endoplasmic reticulum (ER) stress was caused. Biseugenol-exposure tumors showed acquired epithelial features such as phosphorylation of E-cadherin, cytokeratin-18 and loss mesenchymal signature Snail, but not vimentin regulation. Snail expression, through AhR activation, is an epithelial-to-mesenchymal transition (EMT) determinant. Moreover, Biseugenol enhanced Calpain-10 (Calp-10) and AhR interaction results in Snail downregulation. The effect of shCalpain-10 in cancer cells was associated with inactivation of AhR/Snail promoter binding activity. Inhibition of Calpain-10 in gastric cancer cells by short hairpin RNA or pharmacological inhibitor was found to effectively reduced growth ability and vessel density in vivo. Importantly, knockdown of AhR completed abrogated peritoneal dissemination. Herein, Biseugenol targeting ER stress provokes Calpain-10 activity, sequentially induces reversal of EMT and apoptosis via AhR may involve the paralleling processes. Taken together, these data suggest that Calpain-10 activation and AhR inhibition by Biseugenol impedes both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.
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Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.
Support Care Cancer
PUBLISHED: 09-02-2014
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The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients.
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Respiratory perception measured by cortical neural activations in individuals with generalized anxiety disorder.
Respir Physiol Neurobiol
PUBLISHED: 08-18-2014
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There has been evidence for the effect of anxiety on the neural processing of respiratory sensation using the respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions. This study tested the RREP elicited by inspiratory occlusions in a group of outpatients with generalized anxiety disorder (GAD) and a group of healthy controls. We hypothesized that the RREP P3 peak would be modulated in the GAD patients. A RREP oddball paradigm of 150-ms inspiratory occlusion protocol was used in 15 GAD patients and 11 healthy adults with normal lung functions. The RREP was recorded with a 40-channel electroencephalography (EEG) system. A minimum of 100 occlusions was collected for data analysis. We found that the averaged P3 latency of the GAD patients was significantly longer than the P3 latency of the healthy controls. In addition, the GAD group showed significantly reduced P3 amplitudes compared to the control group. No group differences in latency and amplitudes were found for earlier RREP components. These results demonstrated that a delayed and reduced attention peak (P3) is present in patients with GAD. This suggests that GAD as a disease state modulates the higher order processing of respiratory perception.
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Precise and fast video assisted thoracoscopic bronchial sleeve resection.
J Thorac Dis
PUBLISHED: 08-07-2014
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Surgical management for lung cancer is basically a destructive one. The lung parenchyma removed is in the balance between the purpose of curative resection and the preservation of patient's lung function. Bronchial sleeve has been alternatively developed to achieve the same purpose, but through a different way-to save back healthy lung tissue through reconstruction of the central airway. Sleeve resection had been done with open technique for years, and just like the other thoracic operations, has continuously evolved into the era of minimally invasive surgery in spite of its difficulty. With rapid advancement and availability in technology-high resolution 3-D dynamic chest computed tomography (CT), PET-CT, and endobronchial ultrasound (EBUS), these tools are very helpful for us to have more precise tumor staging, and suitable for preoperative surgical planning. Under magnified 3-D endoscopic view and modified endoscopic suturing method, re-anastomosis of the airway could be easier and quicker, which would facilitate this innovative operation to accumulate experience in the not too distant future.
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Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.
J. Virol.
PUBLISHED: 07-30-2014
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Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-?/?]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-?), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-?), IFN-?, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. Importance: The host innate immune system is equipped with pattern recognition receptors (PRRs), which are useful for defending the host against invading pathogens. During enterovirus 71 (EV71) infection, the innate immune system is activated by pathogen-associated molecular patterns (PAMPs), which include viral RNA or DNA, and these PAMPs are recognized by PRRs. Toll-like receptor 3 (TLR3) and TLR7/8 recognize viral nucleic acids, and TLR9 senses unmethylated CpG DNA or pathogen-derived DNA. These PRRs stimulate the production of type I interferons (IFNs) to counteract viral infection, and they are the major source of antiviral alpha interferon (IFN-?) production in pDCs, which can produce 200- to 1,000-fold more IFN-? than any other immune cell type. In addition to PAMPs, danger-associated molecular patterns (DAMPs) are known to be potent activators of innate immune signaling, including TLR9. We found that EV71 induces cellular apoptosis, resulting in tissue damage; the endogenous DNA from dead cells may activate the innate immune system through TLR9. Therefore, our study provides new insights into EV71-induced apoptosis, which stimulates TLR9 in EV71-associated infections.
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Natural zwitterionic organosulfurs as surface ligands for antifouling and responsive properties.
Biointerphases
PUBLISHED: 07-03-2014
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Natural sulfur-containing zwitterionic compounds, l-cysteine (Cys), l-methionine, and glutathionine (GSH), have been employed as surface ligands to prevent protein nonspecific adsorption on planar substrates. These organosulfur compounds form self-assembled monolayers (SAMs) on gold substrates by gold-sulfur interaction. The chemical elements of SAMs were confirmed using x-ray photoelectron spectroscopy. The surface wetting tests for SAMs show that films prepared from Cys and GSH exhibited super-hydrophilicity (contact angles of ? = ~5°) due to their high coverage and strong hydration via ionic solvation and formation of hydrogen bonding. Quartz crystal microbalance with dissipation sensor was used to quantitatively and qualitatively monitor the adsorption of bovine serum albumin (BSA) from buffer onto these SAMs. It was found that the GSH film enables the resistance of BSA adsorption to the best extent at a physiological pH. Moreover, the surface charges of modified substrates were modulated by varying the pH value to control BSA adsorption. The effect of electrostatic repulsion on the antifouling behavior becomes prominent at a pH where the protein and the surface carry same charges. Consolidating the BSA adsorption measurements at different pH values, the antifouling properties of GSH-modified Au should be attributed to prevention of entropy gain and enthalpy loss, making BSA adsorption energetically unfavorable. It is believed that the surface modification with natural organosulfur ligands holds great potential in improving the biocompatibility of medical devices and in offering intelligent biointerfaces in response to environmental stimuli.
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Metabolic syndrome among psychiatric outpatients with mood and anxiety disorders.
BMC Psychiatry
PUBLISHED: 06-17-2014
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Few studies have simultaneously compared the impacts of pharmacotherapy and mental diagnoses on metabolic syndrome (MetS) among psychiatric outpatients with mood and anxiety disorders. This study aimed to investigate the impacts of pharmacotherapy and mental diagnoses on MetS and the prevalence of MetS among these patients.
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Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases.
Vaccine
PUBLISHED: 06-06-2014
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Enterovirus 71 (EV71), an emerging neurotropic virus and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD). These viruses have become a serious public health threat in the Asia Pacific region. Formalin-inactivated EV71 (FI-EV71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against EV71. Their failure to prevent CVA16 infections could compromise the acceptability of monovalent EV71 vaccines. Bivalent FI-EV71/FI-CVA16 vaccines have been found to elicit strong neutralizing antibody responses against both viruses in animal models but did not protect against CVA6 and CVA10 viral infections in cell culture neutralization assay. In this review, we discuss the critical bottlenecks in the development of multivalent HFMD vaccines, including the selection of vaccine strains, animal models to assess vaccine potency, the definition of end-points for efficacy trials, and the need for improved manufacturing processes to produce affordable vaccines.
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Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-27-2014
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Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain-domain interactions, stabilization in organic solvents, and crystallization.
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Single-Incision Versus Multiple-Incision Thoracoscopic Lobectomy and Segmentectomy: A Propensity-Matched Analysis.
Ann. Surg.
PUBLISHED: 05-20-2014
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To compare the perioperative outcomes of single-incision and multiple-incision thoracoscopic lobectomy and segmentectomy.
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Differences in psychiatric symptoms among Asian patients with depression: a multi-country cross-sectional study.
Psychiatry Clin. Neurosci.
PUBLISHED: 05-16-2014
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The aim of this study was to compare the symptomatic and clinical features of depression among five groups of patients with major depressive disorder (MDD) living in China, Korea, Malaysia/Singapore, Taiwan, and Thailand.
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Delivery of human EV71 receptors by adeno-associated virus increases EV71 infection-induced local inflammation in adult mice.
Biomed Res Int
PUBLISHED: 05-14-2014
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Enterovirus71 (EV71) is now recognized as an emerging neurotropic virus in Asia and one major causative agent of hand-foot-mouth diseases (HFMD). However potential animal models for vaccine development are limited to young mice. In this study, we used an adeno-associated virus (AAV) vector to introduce the human EV71 receptors P-selectin glycoprotein ligand-1 (hPSGL1) or a scavenger receptor class-B member-2 (hSCARB2) into adult ICR mice to change their susceptibility to EV71 infection. Mice were administered AAV-hSCARB2 or AAV-hPSGL1 through intravenous and oral routes. After three weeks, expression of human SCARB2 and PSGL1 was detected in various organs. After infection with EV71, we found that the EV71 viral load in AAV-hSCARB2- or AAV-hPSGL1-transduced mice was higher than that of the control mice in both the brain and intestines. The presence of EV71 viral particles in tissues was confirmed using immunohistochemistry analysis. Moreover, inflammatory cytokines were induced in the brain and intestines of AAV-hSCARB2- or AAV-hPSGL1-transduced mice after EV71 infection but not in wild-type mice. However, neurological disease was not observed in these animals. Taken together, we successfully infected adult mice with live EV71 and induced local inflammation using an AAV delivery system.
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Using the CHA2DS2-VASc Score for Refining Stroke Risk Stratification in 'Low-Risk' Asian Patients With Atrial Fibrillation.
J. Am. Coll. Cardiol.
PUBLISHED: 05-13-2014
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A new scoring system, the anticoagulation and risk factors in atrial fibrillation (ATRIA) score, was proposed for risk stratification in patients with atrial fibrillation (AF). Whether the ATRIA scheme can adequately identify patients who are at low risk of ischemic stroke remains unknown.
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Risk and impact of tuberculosis in patients with chronic myeloid leukemia: A nationwide population-based study in Taiwan.
Int. J. Cancer
PUBLISHED: 05-06-2014
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The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p?=?0.001) for both pulmonary (aHR 3.23, p?
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Development of a dietary induced metabolic syndrome model using miniature pigs-invovlement of ampk and sirt1.
Eur. J. Clin. Invest.
PUBLISHED: 04-09-2014
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During the progression of the metabolic syndrome (MetS), cardiovascular diseases (CVD) appear clinically in many individuals and cause death. As a result, it is essential to set-up an optimal animal model to study the mechanism of MetS leading to CVD. SIRT1 and AMPK are the master regulators of lipid and carbohydrate metabolism. The objective of this study was to establish a miniature pig model of Western diet-induced MetS and investigate the role of SIRT1/AMPK during MetS development.
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Safety of interventional bronchoscopy through complication review at a cancer center.
Clin Respir J
PUBLISHED: 03-10-2014
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There have been rapid advances in the area of interventional bronchoscopy over the past 15 years, but associated complications have been rarely discussed. A longitudinal evaluation of the same operator's performance at a cancer center is reported.
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A novel model for exploring the correlation between patterns and prescriptions in clinical practice of traditional Chinese medicine for systemic lupus erythematosus.
Complement Ther Med
PUBLISHED: 03-07-2014
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Traditional Chinese medicines in treating systemic lupus erythematosus are not uncommon. However, logic of pattern diagnosis and consensus on treating this disease is lacking. This study aimed to explore the correlation between the pattern diagnosis of and its corresponding prescription in systemic lupus erythematosus.
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Learning Thoracoscopic Lobectomy in Resident Training.
Thorac Cardiovasc Surg
PUBLISHED: 03-03-2014
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Background?Thoracoscopic lobectomy is a safe and effective procedure; however, the ways by which to incorporate this technically demanding procedure into residency training is still unknown. We reported on the outcomes of thoracoscopic lobectomies performed by a single thoracic resident, who was simultaneously undergoing training for both open and thoracoscopic lobectomies. Patients and Methods?Between January 2010, and May 2011, data from 87 consecutive thoracoscopic lobectomies that were performed by a trainee surgeon (B.-Y.W.) were prospectively obtained. Data were grouped into the first 30 and subsequent 57 cases. Patient characteristics, operative data, complications, and surgical pathology were analyzed. Results?The mean operating time in group 2 was significantly lower compared with group 1 (264.0?±?45.9?min in group 1 vs. 197.5?±?57.7?min in group 2; p?
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Immunogenicity studies of bivalent inactivated virions of EV71/CVA16 formulated with submicron emulsion systems.
Biomed Res Int
PUBLISHED: 02-18-2014
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We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 ?g) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.
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Long-term prognosis of patients older than ninety years after permanent pacemaker implantation: does the procedure save the patients?
Can J Cardiol
PUBLISHED: 02-13-2014
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The implantation of a permanent pacemaker (PPM) is life-saving for patients with life-threatening bradycardia. However, the effectiveness and prognosis of PPM implantations for extremely old patients (? 90 years old) have not been investigated.
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Clinical and sociodemographic correlates of suicidality in patients with major depressive disorder from six Asian countries.
BMC Psychiatry
PUBLISHED: 02-05-2014
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East Asian countries have high suicide rates. However, little is known about clinical and sociodemographic factors associated with suicidality in Asian populations. The aim of this study was to evaluate the factors associated with suicidality in patients with major depressive disorder (MDD) from six Asian countries.
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Spontaneous rupture of a cystic mediastinal teratoma complicated by superior vena cava syndrome.
Ann. Thorac. Surg.
PUBLISHED: 02-04-2014
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Spontaneous rupture of cystic mediastinal teratomas is rare but may cause serious complications. Here we report an unusual case of a cystic teratoma, which ruptured into the mediastinal and pleural cavities resulting in superior vena cava syndrome, acute mediastinitis, and pleural effusion. Early diagnosis and prompt surgical treatment of ruptured mediastinal teratomas are essential to preventing life-threatening complications.
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Using a questionnaire among patient, resident doctor and senior supervisor: Are their answers the same?
Complement Ther Med
PUBLISHED: 01-30-2014
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This study aims to contribute to the development of objective diagnostic standards in Traditional Chinese Medicine (TCM), in order to improve the training of physicians.
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Single-port video-assisted thoracoscopic surgery for lung cancer.
J Thorac Dis
PUBLISHED: 01-24-2014
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In 2004, novel results using pulmonary wedge resection executed through single-port video-assisted thoracoscopic surgery (VATS) was first described. Since that time, single-port VATS has been advocated for the treatment of a spectrum of thoracic diseases, especially lung cancer. Lung cancer remains one of the top three cancer-related deaths in Taiwan, and surgical resection remains the "gold standard" for early-stage lung cancer. Anatomical resections (including pneumonectomy, lobectomy, and segmentectomy) remain the primary types of lung cancer surgery, regardless of whether conventional open thoracotomy, or 4/3/2-ports VATS are used. In the past three years, several pioneers have reported their early experiences with single-port VATS lobectomy, segmentectomy, and pneumonectomy for lung cancer. Our goal was to appraise their findings and review the role of single-port VATS in the treatment of lung cancer. In addition, the current concept of mini-invasive surgery involves not only smaller resections (requiring only a few incisions), but also sub-lobar resection as segmentectomy. Therefore, our review will also address these issues.
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Structural insights into the catalytic mechanism of human squalene synthase.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 01-17-2014
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Squalene synthase (SQS) is a divalent metal-ion-dependent enzyme that catalyzes the two-step reductive `head-to-head' condensation of two molecules of farnesyl pyrophosphate to form squalene using presqualene diphosphate (PSPP) as an intermediate. In this paper, the structures of human SQS and its mutants in complex with several substrate analogues and intermediates coordinated with Mg2+ or Mn2+ are presented, which stepwise delineate the biosynthetic pathway. Extensive study of the SQS active site has identified several critical residues that are involved in binding reduced nicotinamide dinucleotide phosphate (NADPH). Based on mutagenesis data and a locally closed (JK loop-in) structure observed in the hSQS-(F288L)-PSPP complex, an NADPH-binding model is proposed for SQS. The results identified four major steps (substrate binding, condensation, intermediate formation and translocation) of the ordered sequential mechanisms involved in the `1'-1' isoprenoid biosynthetic pathway. These new findings clarify previous hypotheses based on site-directed mutagenesis and biochemical analysis.
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Does digoxin increase the risk of ischemic stroke and mortality in atrial fibrillation? A nationwide population-based cohort study.
Can J Cardiol
PUBLISHED: 01-10-2014
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Digoxin and related cardiac glycosides have been used for almost 100 years in atrial fibrillation (AF). However, 2 recent analyses of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial showed inconsistent results regarding the risk of mortality associated with digoxin use. The goal of the present study was to investigate the relationship between digoxin and the risk of ischemic stroke and mortality in Asians.
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Keratocytes derived from spheroid culture of corneal stromal cells resemble tissue resident keratocytes.
PLoS ONE
PUBLISHED: 01-01-2014
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Corneal stromal cells transform to precursor cells in spheroid culture. We determined whether keratocytes derived from spheroid culture of murine corneal stromal cells resemble tissue resident keratocytes.
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Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality.
PLoS ONE
PUBLISHED: 01-01-2014
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Some previous studies have identified bacteria in semen as being a potential factor in male infertility. However, only few types of bacteria were taken into consideration while using PCR-based or culturing methods. Here we present an analysis approach using next-generation sequencing technology and bioinformatics analysis to investigate the associations between bacterial communities and semen quality. Ninety-six semen samples collected were examined for bacterial communities, measuring seven clinical criteria for semen quality (semen volume, sperm concentration, motility, Kruger's strict morphology, antisperm antibody (IgA), Atypical, and leukocytes). Computer-assisted semen analysis (CASA) was also performed. Results showed that the most abundant genera among all samples were Lactobacillus (19.9%), Pseudomonas (9.85%), Prevotella (8.51%) and Gardnerella (4.21%). The proportion of Lactobacillus and Gardnerella was significantly higher in the normal samples, while that of Prevotella was significantly higher in the low quality samples. Unsupervised clustering analysis demonstrated that the seminal bacterial communities were clustered into three main groups: Lactobacillus, Pseudomonas, and Prevotella predominant group. Remarkably, most normal samples (80.6%) were clustered in Lactobacillus predominant group. The analysis results showed seminal bacteria community types were highly associated with semen health. Lactobacillus might not only be a potential probiotic for semen quality maintenance, but also might be helpful in countering the negative influence of Prevotella and Pseudomonas. In this study, we investigated whole seminal bacterial communities and provided the most comprehensive analysis of the association between bacterial community and semen quality. The study significantly contributes to the current understanding of the etiology of male fertility.
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Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized.
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Rheumatoid arthritis and the risk of bipolar disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately.
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Increased risk of acute angle closure in retinitis pigmentosa: a population-based case-control study.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the association between retinitis pigmentosa (RP) and acute angle closure during a 15-year follow-up period.
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Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt) was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-? and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.
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Integration of multidisciplinary technologies for real time target visualization and verification for radiotherapy.
Onco Targets Ther
PUBLISHED: 01-01-2014
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The current practice of radiotherapy examines target coverage solely from digitally reconstructed beam's eye view (BEV) in a way that is indirectly accessible and that is not in real time. We aimed to visualize treatment targets in real time from each BEV. The image data of phantom or patients from ultrasound (US) and computed tomography (CT) scans were captured to perform image registration. We integrated US, CT, US/CT image registration, robotic manipulation of US, a radiation treatment planning system, and a linear accelerator to constitute an innovative target visualization system. The performance of this algorithm segmented the target organ in CT images, transformed and reconstructed US images to match each orientation, and generated image registration in real time mode with acceptable accuracy. This image transformation allowed physicians to visualize the CT image-reconstructed target via a US probe outside the BEV that was non-coplanar to the beam's plane. It allowed the physicians to remotely control the US probe that was equipped on a robotic arm to dynamically trace and real time monitor the coverage of the target within the BEV during a simulated beam-on situation. This target visualization system may provide a direct remotely accessible and real time way to visualize, verify, and ensure tumor targeting during radiotherapy.
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Knockdown of zebrafish blood vessel epicardial substance results in incomplete retinal lamination.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Cell polarity during eye development determines the normal retinal lamination and differentiation of photoreceptor cells in the retina. In vertebrates, blood vessel epicardial substance (Bves) is known to play an important role in the formation and maintenance of the tight junctions essential for epithelial cell polarity. In the current study, we generated a transgenic zebrafish Bves (zbves) promoter-EGFP zebrafish line to investigate the expression pattern of Bves in the retina and to study the role of zbves in retinal lamination. Immunostaining with different specific antibodies from retinal cells and transmission electron microscopy were used to identify the morphological defects in normal and Bves knockdown zebrafish. In normal zebrafish, Bves is located at the apical junctions of embryonic retinal neuroepithelia during retinogenesis; later, it is strongly expressed around inner plexiform layer (IPL) and retinal pigment epithelium (RPE). In contrast, a loss of normal retinal lamination and cellular polarity was found with undifferentiated photoreceptor cells in Bves knockdown zebrafish. Herein, our results indicated that disruption of Bves will result in a loss of normal retinal lamination.
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Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: a randomized, double-blinded, and placebo-controlled trial.
PLoS ONE
PUBLISHED: 01-01-2014
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The aim of this study is to investigate the effect of green tea extract on patients with type 2 diabetes mellitus and lipid abnormalities on glycemic and lipid profiles, and hormone peptides by a double-blinded, randomized and placebo-controlled clinical trial. This trial enrolled 92 subjects with type 2 diabetes mellitus and lipid abnormalities randomized into 2 arms, each arm comprising 46 participants. Of the participants, 39 in therapeutic arm took 500 mg green tea extract, three times a day, while 38 in control arm took cellulose with the same dose and frequency to complete the 16-week study. Anthropometrics measurements, glycemic and lipid profiles, safety parameters, and obesity-related hormone peptides were analyzed at screening and after 16-week course. Within-group comparisons showed that green tea extract caused a significant decrease in triglyceride and homeostasis model assessment of insulin resistance index after 16 weeks. Green tea extract also increased significantly high density lipoprotein cholesterol. The HOMA-IR index decreased from 5.4±3.9 to 3.5±2.0 in therapeutic arm only. Adiponectin, apolipoprotein A1, and apolipoprotein B100 increased significantly in both arms, but only glucagon-like peptide 1 increased in the therapeutic arm. However, only decreasing trend in triglyceride was found in between-group comparison. Our study suggested that green tea extract significantly improved insulin resistance and increased glucagon-like peptide 1 only in within-group comparison. The potential effects of green tea extract on insulin resistance and glucagon-like peptide 1 warrant further investigation. Trial registration: ClinicalTrials.gov NCT01360567.
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Variant GADL1 and Response to Lithium Therapy in Bipolar I Disorder.
N. Engl. J. Med.
PUBLISHED: 12-25-2013
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Background Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. Methods We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. Results Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. Conclusions Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).
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Monoclonal antibodies for diagnosis of enterovirus 71.
Monoclon Antib Immunodiagn Immunother
PUBLISHED: 12-17-2013
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Enterovirus 71 (EV71), one of the major causative agents of hand, foot, and mouth disease (HFMD), is now recognized as an emerging neurotropic virus in Asia and may cause severe neurologic complications and mortalities. Laboratory diagnosis of EV71 infection must be efficient and accurate, which could be accomplished by various immunoassays. In this study we use a live EV71 isolate, Tainan/4643/98, with genotype C2 as an immunogen to sensitize BALB/c (H-2(d)) mice and then generate the EV71-specific murine monoclonal antibodies. Five hybridoma clones were established and their monoclonal antibodies were characterized. All five clones are applicable in immunofluorescence staining but with different sensitivities-that is, MAbs 22, 24, and 27 were sensitive in IFA detection, and MAbs 22 and 24 were also confirmed in flow cytometry. None of these cross-reacted with coxsackievirus A16 (CVA16) or Echovirus type 6 (ECHO6), but each varied in binding to different EV71 subgenogroups (B1, B4, B5, C2, and C4). Western blot analysis revealed that all of these MAbs reacted with EV71 VP1 capsid proteins, and in addition MAbs 22 and 24 exhibited potent neutralizing activities against EV71 and protected cells from infection. Further, mapping the epitopes for each MAb revealed that only MAb 27 showed positive for the linear epitope DVIESSIGDSVSRAL, which was located at the N-terminus (a.a. 6-20) of EV71 VP1 and highly conserved among all EV71 subgenotypes. Thus, these MAbs may provide valuable tools for the laboratory diagnosis of EV71 infection and for vaccine development.
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Impact of hypoalphalipoproteinemia on quality of life in Taiwanese women with central obesity.
Qual Life Res
PUBLISHED: 12-04-2013
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To investigate the relationship between health-related quality of life (HRQoL) and different cutoff value of low level of high-density lipoprotein cholesterol (HDL-C) in Taiwanese women with different definition of obesity.
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Role of SH2-Containing Tyrosine Phosphatase Shp2 in Mouse Corneal Epithelial Stratification.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 11-09-2013
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Shp2 protein tyrosine phosphatase mediates a wide variety of receptor tyrosine kinases (RTK) cell signaling. Herein, we investigate the role of Shp2 in corneal morphogenesis and homeostasis.
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Dexamethasone induces cross-linked actin networks in trabecular meshwork cells through noncanonical wnt signaling.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 08-22-2013
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Dexamethasone (DEX) regulates aqueous humor outflow by inducing a reorganization of the cytoskeleton to form cross-linked actin networks (CLANs) in trabecular meshwork (TM) cells. Rho-associated protein kinase (ROCK) has been demonstrated to have an important role in this process, but the upstream components leading to its activation remain elusive. The purpose of the study is to demonstrate that noncanonical Wnt signaling mediates the DEX-induced CLAN formation in TM cells.
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Risk of New-Onset Diabetes Mellitus Versus Reduction in Cardiovascular Events With Statin Therapy.
Am. J. Cardiol.
PUBLISHED: 08-07-2013
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The Food and Drug Administration recently updated the safety warning concerning the association between statin therapy and new-onset diabetes mellitus (NODM). For prediabetes, little information is available for statins on cardiovascular outcome reduction and diabetogenic consequences. This study aimed to examine the risk of NODM and the reduction of cardiovascular events and death (MACE) after statin therapy in the prediabetic subjects. The medical and pharmacy claims of the prediabetic beneficiaries were retrieved from Taiwan National Health Insurance research database. The occurrence of NODM, MACE, and morbidity indexed by hospitalizations and emergency visits was ascertained by ambulatory and inpatient database. A propensity score-matched model was constructed for statin users and nonusers. During follow-up (4.1 ± 2.5 years), NODM and MACE occurred in 23.5% and 16.7%, respectively, of nonusers and 28.5% and 12.0%, respectively, of users. Statin therapy was associated with a greater risk of NODM (hazard ratio 1.20, 95% confidence interval 1.08 to 1.32) and less risk of MACE (hazard ratio 0.70, 95% confidence interval 0.61 to 0.80), both in dose-dependent fashions. The earlier and more persistent use correlated with the greater increase in risk of NODM offset by the proportionally larger reduction in MACE. Furthermore, the early persistent users had the lowest rate of hospitalizations and emergency visits. In conclusion, our findings suggested that the relation between NODM and therapeutic advantages of statins was parallel in the prediabetic population. Treatment benefits outweighed diabetic consequences in subjects receiving the earlier and more persistent treatment.
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Antidepressant-like activity of turmerone in behavioral despair tests in mice.
BMC Complement Altern Med
PUBLISHED: 08-07-2013
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The present study was undertaken to evaluate the anti-depressive activity of turmerone after one-week administration by using a mouse forced swimming test (FST) and tail suspension test (TST).
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Comparison of escitalopram and paroxetine in the treatment of major depressive disorder.
Int Clin Psychopharmacol
PUBLISHED: 07-25-2013
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This is a single-blind, parallel, flexible-dose study to compare the efficacy and tolerability of escitalopram and paroxetine in the treatment of patients with major depressive disorder. We recruited 399 patients from the outpatient clinics of five hospitals in northern Taiwan. Patients were administered either escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of clinicians. These patients were assessed using the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4, 6, and 8. A total of 302 patients fulfilled the evaluation criteria and were included in a statistical analysis. We found that escitalopram induced more significant symptom reduction and response rate in terms of the mean HAM-D scores at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no significant differences between the two groups in the remission rate. Escitalopram induced significantly less frequency of adverse effects of weakness (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as somnolence (P<0.01) than paroxetine, although all these side effects were mild and tolerable. However for a more definitive result, future prospective trials with the inclusion of a placebo group and a double-blind design are needed. In patients who did not have severe depression (HAM-D score at baseline<21), but not in severely depressed patients, escitalopram was statistically superior to paroxetine, as shown by the mean change in the HAM-D score.
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Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection.
Pharm. Res.
PUBLISHED: 07-23-2013
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RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina.
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Clinical features of depression in Asia: Results of a large prospective, cross-sectional study.
Asia Pac Psychiatry
PUBLISHED: 07-23-2013
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The objective of this study was to investigate the clinical features of depression in Asian patients.
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CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions.
Pharmacogenomics
PUBLISHED: 07-18-2013
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The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT.
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A chinese medicine, kuan-sin-yin decoction, improves liver function in hepatitis B virus carriers: a randomized, controlled study.
J Altern Complement Med
PUBLISHED: 07-17-2013
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Abstract Objective: To examine the effects of a Chinese medical herb complex formula, Kuan-Sin-Yin (KSY) decoction, on hepatitis B virus (HBV) carriers. Methods: Of 86 HBV carriers, 57 who met the inclusion criteria completed this study from February 2011 to December 2011 in Taipei City Hospital, Taiwan. The participants were randomly assigned to one of two groups: the KSY group (n=29) and a control group (n=28) that received KSY diluted 16 times. The participants took one packet of decoction per day after dinner for 6 weeks. The major outcome measurements were the percentage reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the log of the HBV DNA level. The other measurements included seroconversion of hepatitis B e antigen and responses to the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF) and Short-Form-12. The measurements were collected before the first treatment and 6 weeks later. Results: In the KSY group, AST and ALT levels decreased significantly and the score on the physical component of WHOQOL-BREF increased significantly. However, in the control group, there was no significant change after 6 weeks of treatment. Only the KSY group had a significant percentage reduction in ALT (change, -25.2% versus -0.74% in the control group) after 6 weeks of treatment. No major adverse effects occurred after 6 weeks of treatment. Conclusions: KSY significantly improved ALT levels. The study suggests that a longer-term study testing the efficacy of KSY in a larger sample is warranted.
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Oral glutamine supplement inhibits ascites formation in peritoneal carcinomatosis mouse model.
Gastroenterol Res Pract
PUBLISHED: 07-12-2013
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Background. Peritoneal carcinomatosis (PC) accompanied with ascites formation causes several distressing symptoms, resulting in poor quality of life. Methods. Twenty BALB/c nude mice generated by direct orthotopic injection of human pancreatic cancer PANC-1 cells were randomized to receive either a stock laboratory diet or a stock diet supplemented with glutamine. Half of the mice were sacrificed at day 76 to measure the amount of ascitic fluid and pancreatic tumor volume. The remaining mice were subject to survival analysis. Serum albumin levels were estimated every 2 weeks. Results. At day 76, the average amount of ascitic fluid measured in the control group was 1.2 ± 0.3?mL compared to 0.5 ± 0.5?mL from the glutamine-supplemented mice (P = 0.045). The volume of pancreatic tumor was 2.60 ± 0.8?cm(3) in the control group and 1.98 ± 1.3?cm(3) in glutamine-supplemented mice (P = 0.39). The mean survival time of glutamine-supplemented mice was prolonged from 87 ± 4 to 101 ± 2 days (P = 0.0024). Mean serum albumin levels were higher in the glutamine-supplemented group. Conclusions. This preclinical study showed that oral supplementation of glutamine may provide ascites-reducing activity in pancreatic cancer patients with PC, via a cell-mediated immunity-independent mechanism.
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Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV.
Hum Vaccin Immunother
PUBLISHED: 07-11-2013
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Combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. Here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (H5N1/H1N1), enterovirus 71 (EV71), and/or Japanese encephalitis virus (JEV) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. We demonstrated that the antigenic competition happens between H5N1/H1N1 or H5N1/EV71 inactivated virions when the vaccine combinations either formulated with Alum suspensions or without adjuvant. In the presence of PELC emulsified particles, EV71-specific immune responses before and after incorporating H5N1 virus into EV71 vaccine were detected of no significant difference; in addition, H5N1- and EV71-specific immune responses were found at the same level when H5N1/EV71/JEV consolidating into combination vaccine. Emulsified vaccine formulation was represented as a potential tool that is found to reduce the number of injections required to prevent multiple infectious strains causing the same disease (H5N1/H1N1) and/or that protect against different diseases (H5N1/EV71). Combination vaccines can also include a third component to protect against H5N1/EV71/JEV at the same time.
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Caveolar endocytosis is required for human PSGL-1-mediated enterovirus 71 infection.
J. Virol.
PUBLISHED: 06-12-2013
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Enterovirus 71 (EV71) causes hand, foot, and mouth disease and severe neurological disorders in children. Human scavenger receptor class B member 2 (hSCARB2) and P-selectin glycoprotein ligand-1 (PSGL-1) are identified as receptors for EV71. The underling mechanism of PSGL-1-mediated EV71 entry remains unclear. The endocytosis required for EV71 entry were investigated in Jurkat T and mouse L929 cells constitutively expressing human PSGL-1 (PSGL-1-L929) or human rhabdomyosarcoma (RD) cells displaying high SCARB2 but no PSGL-1 by treatment of specific inhibitors or siRNA. We found that disruption of clathrin-dependent endocytosis prevented EV71 infection in RD cells, while there was no influence in Jurkat T and PSGL-1-L929 cells. Disturbing caveolar endocytosis by specific inhibitor or caveolin-1 siRNA in Jurkat T and PSGL-1-L929 cells significantly blocked EV71 infection, whereas it had no effect on EV71 infection in RD cells. Confocal immunofluorescence demonstrated caveola, and EV71 was directly colocalized. pH-dependent endosomal acidification and intact membrane cholesterol were important for EV71 infection, as judged by the pretreatment of inhibitors that abrogated the infection. A receptor-dominated endocytosis of EV71 infection was observed: PSGL-1 initiates caveola-dependent endocytosis and hSCARB2 activates clathrin-dependent endocytosis.
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Residual symptoms related to physical and panic symptoms at baseline predict remission of depression at follow-up.
Psychopathology
PUBLISHED: 05-03-2013
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Aims: The study aimed to investigate whether common residual symptoms at baseline were able to predict full remission of depression at 6-month and 2-year follow-up examinations in patients with major depressive disorder (MDD). Methods: This study enrolled 135 outpatients with MDD. The depression (DS) and somatic subscales (SS) of the Depression and Somatic Symptoms Scale and the depression and anxiety (HADS-A) subscales of the Hospital Anxiety and Depression Scale were used to investigate residual symptoms, which were divided into the common residual part (CRP) and the other residual part (ORP). Multivariate logistic regression was used to compare the ability to predict full remission between the CRP and ORP scores at baseline. Results: One hundred and nineteen and 106 outpatients completed the two follow-up examinations. The CRP of the DS and the ORP of the SS and HADS-A at baseline had a good ability to predict full remission among patients without pharmacotherapy. The three residual parts included physical and anxiety symptoms of depression and panic symptoms. Conclusions: Physicians should pay attention to physical, anxiety, and panic symptoms, because these symptoms are related to remission of depression. Future studies should explore how these symptoms affect the prognosis of depression.
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Application of the solvent extraction technique to investigation of the anti-inflammatory activity of adlay bran.
Food Chem
PUBLISHED: 04-11-2013
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The current study utilised a bioassay-directed chemical analysis scheme to screen the anti-inflammatory activity of fractions and compounds from adlay bran (AB). Liquid-liquid extraction couple with liquid chromatography-mass spectrometry (LC-MS) was applied to the isolation, analysis and identification of active components in AB samples. Ethanol extracts of AB (ABE) and ethyl acetate extracts AB (ABEa) were obtained and further partitioned with different solvents. The results showed that among all 16 kinds of fractions from ABE and ABEa, ABEa-Ea-B (80% Ea/n-hexane sub-fraction from ABE-Ea) had the most potent inhibitory effects on NO production, iNOS and COX-2 expressions, and proinflammatory IL-6 and TNF-? secretion in lipopolysaccharide-activated RAW264.7 cells system. Mechanistic data from luciferase reporter-gene assay revealed that the anti-inflammatory action of ABEa-Ea-B may be associated with inhibition of NF-kB transcriptional activity. Notably, tangeretin, nobiletin, and p-hydroxybenzoic acid were found to be the main active compounds for the anti-inflammatory properties in ABEa-Ea-B.
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Increased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients.
Asia Pac Psychiatry
PUBLISHED: 03-12-2013
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Schizophrenia is associated with the activation of the immune/inflammatory system. C-reactive protein (CRP), a positive acute phase protein, may be associated with schizophrenia and antipsychotic treatment.
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Use of antidepressants in the treatment of depression in Asia: Guidelines, clinical evidence, and experience revisited.
Asia Pac Psychiatry
PUBLISHED: 02-24-2013
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Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patients clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.
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Migraine predicts physical and pain symptoms among psychiatric outpatients.
J Headache Pain
PUBLISHED: 02-19-2013
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No study has been performed to compare the impacts of migraine and major depressive episode (MDE) on depression, anxiety and somatic symptoms, and health-related quality of life (HRQoL) among psychiatric outpatients. The aim of this study was to investigate the above issue.
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Targeted overexpression of TGF-? in the corneal epithelium of adult transgenic mice induces changes in anterior segment morphology and activates noncanonical Wnt signaling.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 02-16-2013
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Transforming growth factor-alpha (TGF-?) transduces its signal through the epidermal growth factor receptor and is essential for corneal epithelial homeostasis. Previous studies have demonstrated that overexpression of TGF-? in the developing eye leads to anterior segment dysgenesis. However, the underlying mechanisms remain unclear. Here we examined the effects of TGF-? overexpression on adult ocular surface homeostasis.
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Feasibility of combined paravertebral block and subcostal transversus abdominis plane block in postoperative pain control after minimally invasive esophagectomy.
Acta Anaesthesiol Taiwan
PUBLISHED: 01-31-2013
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Subcostal transversus abdominis plane (TAP) block and paravertebral block (PVB) offer postoperative analgesia for laparoscopic and thoracoscopic surgery, respectively. We investigated the early postoperative analgesic effects of PVB in combination with subcostal TAP block in patients undergoing minimally invasive esophagectomy (MIE) for esophageal cancer.
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Single-incision thoracoscopic lobectomy and segmentectomy with radical lymph node dissection.
Ann. Thorac. Surg.
PUBLISHED: 01-30-2013
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Reports of single-incision thoracoscopic lobectomy and segmentectomy are rare. In this article, we present our experience with single-incision thoracoscopic lobectomy and segmentectomy and radical mediastinal lymph node dissection.
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Caffeic Acid phenethyl ester inhibits epithelial-mesenchymal transition of human pancreatic cancer cells.
Evid Based Complement Alternat Med
PUBLISHED: 01-30-2013
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Background. This study aimed to investigate the effect of propolis component caffeic acid phenethyl ester (CAPE) on epithelial-mesenchymal transition (EMT) of human pancreatic cancer cells and the molecular mechanisms underlying these effects. Methods. The transforming growth factor ? (TGF-?-) induced EMT in human pancreatic PANC-1 cancer cells was characterized by observation of morphology and the expression of E-cadherin and vimentin by western blotting. The migration potential was estimated with wound closure assay. The expression of transcriptional factors was measured by quantitative RT-PCR and immunocytochemistry staining. The orthotopic pancreatic cancer xenograft model was used for in vivo assessment. Results. The overexpression of vimentin was attenuated by CAPE, and the alteration in morphology from polygonal to spindle shape was partially reversed by CAPE. Furthermore, CAPE delayed the TGF-?-stimulated migration potential. CAPE treatment did not reduce the expression levels of Smad 2/3, Snail 1, and Zeb 1 but inhibited the expression of transcriptional factor Twist 2. By using an orthotopic pancreatic cancer model, CAPE suppressed the expression of Twist 2 and growth of PANC-1 xenografts without significant toxicity. Conclusion. CAPE could inhibit the orthotopic growth and EMT of pancreatic cancer PANC-1 cells accompanied by downregulation of vimentin and Twist 2 expression.
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A Phase I, randomized, open-label study to evaluate the safety and immunogenicity of an enterovirus 71 vaccine.
Vaccine
PUBLISHED: 01-26-2013
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Large-scale outbreaks of enterovirus 71 (EV71) infections have occurred in Asia-Pacific regions. Severe complications include encephalitis and poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating an effective vaccine against EV71.
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Human SCARB2 transgenic mice as an infectious animal model for enterovirus 71.
PLoS ONE
PUBLISHED: 01-25-2013
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Enterovirus 71 (EV71) and coxsackievirus (CVA) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. Lack of a reliable animal model is an issue in investigating EV71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. We generated a novel EV71-infectious model with hSCARB2-transgenic mice expressing the discovered receptor human SCARB2 (hSCARB2). The challenge of hSCARB2-transgenic mice with clinical isolates of EV71 and CVA16 resulted in HFMD-like and neurological syndromes caused by E59 (B4) and N2838 (B5) strains, and lethal paralysis caused by 5746 (C2), N3340 (C4), and CVA16. EV71 viral loads were evident in the tissues and CNS accompanied the upregulated pro-inflammatory mediators (CXCL10, CCL3, TNF-?, and IL-6), correlating to recruitment of the infiltrated T lymphocytes that result in severe diseases. Transgenic mice pre-immunized with live E59 or the FI-E59 vaccine was able to resist the subsequent lethal challenge with EV71. These results indicate that hSCARB2-transgenic mice are a useful model for assessing anti-EV71 medications and for studying the pathogenesis induced by EV71.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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