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Find video protocols related to scientific articles indexed in Pubmed.
Supramolecular polymeric vesicles formed by p-sulfonatocalix[4]arene and chitosan with multistimuli responses.
Soft Matter
PUBLISHED: 11-20-2014
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Supramolecular polymeric vesicles are constructed by the complexation of p-sulfonatocalix[4]arene and chitosan, where the multivalent electrostatic interactions between the anionic sulfonate tetramer and cationic polyammoniums served as the dominant driving force. The supra-amphiphilic assemblies are disassembled upon exposure to a pH stimulus since the partial deprotonation of chitosan accompanied by a pH increase. Adding a competitive guest can also disrupt the assembly, representing the host-guest inclusion response. Interestingly, an abnormal temperature-response is observed, possibly as a result of the temperature-directed fusion process.
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[Clinical efficacy of CCG7942/POG9354 protocol in treatment of peripheral primitive neuroectodermal tumor in children.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To investigate the clinical manifestations, diagnosis, and treatment of peripheral primitive neuroectodermal tumor (pPNET) in children and the survival of patients treated with the CCG7942/POG9354 protocol.
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Ischemic Stroke and Intracranial Hemorrhage With Aspirin, Dabigatran, and Warfarin: Impact of Quality of Anticoagulation Control.
Stroke
PUBLISHED: 11-20-2014
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Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy.
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Acousto-optical interaction of surface acoustic and optical waves in a two-dimensional phoxonic crystal hetero-structure cavity.
Opt Express
PUBLISHED: 11-18-2014
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Phoxonic crystal is a promising material for manipulating sound and light simultaneously. In this paper, we theoretically demonstrate the propagation of acoustic and optical waves along the truncated surface of a two-dimensional square-latticed phoxonic crystal. Further, a phoxonic crystal hetero-structure cavity is proposed, which can simultaneously confine surface acoustic and optical waves. The interface motion and photoelastic effects are taken into account in the acousto-optical coupling. The results show obvious shifts in eigenfrequencies of the photonic cavity modes induced by different phononic cavity modes. The symmetry of the phononic cavity modes plays a more important role in the single-phonon exchange process than in the case of the multi-phonon exchange. Under the same deformation, the frequency shift of the photonic transverse electric mode is larger than that of the transverse magnetic mode.
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Mediterranean-Style Diet Is Associated With Reduced Blood Pressure Variability and Subsequent Stroke Risk in Patients With Coronary Artery Disease.
Am. J. Hypertens.
PUBLISHED: 10-30-2014
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The Mediterranean-style diet is widely advocated for the prevention of cardiovascular diseases (CVD). Meanwhile, blood pressure variability (BPV) is a novel risk factor for CVD. It is unknown whether dietary pattern plays a role in modulating BPV.
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Redox-responsive magnetic nanoparticle for targeted convection-enhanced delivery of o(6)-benzylguanine to brain tumors.
ACS Nano
PUBLISHED: 09-29-2014
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Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes.
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A composite cathode based on scandium doped titanate with enhanced electrocatalytic activity towards direct carbon dioxide electrolysis.
Phys Chem Chem Phys
PUBLISHED: 09-03-2014
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A composite cathode based on redox-stable La0.2Sr0.8TiO(3+?) (LSTO) can perform direct carbon dioxide electrolysis; however, the insufficient electro-catalytic activity limits the electrode performances and current efficiencies. In this work, catalytically active scandium is doped into LSTO to enhance the electro-catalytic activity for CO2 electrolysis. The structures, electronic conductivities and ionic conductivities of La0.2Sr0.8Ti(1-x)Sc(x)O (LSTS(x)O) (x = 0, 0.05, 0.1, 0.15 and 0.2) are systematically studied and further correlated with electrode performances. The ionic conductivities of single-phase LSTS(x)O (x = 0, 0.05, 0.1 and 0.15) remarkably improve versus the scandium doping contents though the electrical conductivities gradually change in an adverse trend. Electrochemical measurements demonstrate promising electrode polarisation of LSTS(x)O electrodes and increasing scandium doping contents accordingly improve electrode performances. The Faradic efficiencies of carbon dioxide electrolysis are enhanced by 20% with LSTS0.15O in contrast to bare LSTO electrodes in a solid oxide electrolyser at 800 °C.
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Redox Regulation of Inflammation: Old Elements, a New Story.
Med Res Rev
PUBLISHED: 08-29-2014
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Inflammation is an essential immune response characterized by pain, swelling, redness, heat, and impaired function. A controlled acute inflammatory response is necessary to fight off infection and overcome injury. However, if the inflammatory process persists and enters into the chronic state, it can lead to local and systemic deleterious effects counterproductive to healing and instead constitutes a new pathology. Typically, inflamed tissues are associated with an elevated level of reactive species (reactive oxygen species (ROS)/reactive nitrogen species (RNS)). These ROS/RNS are generated during the respiratory burst of immune cells and are important factors in defense against invading pathogens. Additionally, reactive species are now known to trigger oxidative/nitrosative modifications of biomolecules. While most of these modifications lead to irreparable damage, some are subtle and fully reversible. The reversible modifications can initiate signaling cascades known as "redox signaling." This redox signaling tightly modulates the inflammatory response. Thus, understanding the complex role of ROS/RNS-induced redox signaling in inflammation will assist in the design of relevant therapeutic intervention strategies for inflammation-associated diseases. This review will highlight the impact of oxidative stress and redox signaling on inflammation and inflammation-associated diseases, with a focus on redox modifications of inflammation-related proteins.
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Human structural proteome-wide characterization of Cyclosporine A targets.
Bioinformatics
PUBLISHED: 08-28-2014
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Off-target interactions of a popular immunosuppressant Cyclosporine A (CSA) with several proteins besides its molecular target, cyclophilin A, are implicated in the activation of signaling pathways that lead to numerous side effects of this drug.
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Highly sensitive naphthalene-based two-photon fluorescent probe for in situ real-time bioimaging of ultratrace cyclooxygenase-2 in living biosystems.
Anal. Chem.
PUBLISHED: 08-27-2014
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Detecting and imaging of ultratrace cyclooxygenase-2 in living biosystems could provide much important valuable information for the diagnosis and intervention of cancer. Molecular probes, whose fluorescent signals are generated by cyclooxygenase-2, hold great potential for identification and enumeration of cyclooxygenase-2 in living biosystems. Although quite a few fluorescent probes have been reported for cyclooxygenase-2, the use fluorogenic probe with the excellent two-photon properties for the determination of ultratrace cyclooxygenase-2 has been scarce. Herein, an "off-on" fluorescence probe (BTDAN-COX-2), able to report and image the presence of ultratrace cyclooxygenase-2 in living biosystems, has been designed and evaluated. In order to improve sensitivity and specific selectivity of probe for ultratrace cyclooxygenase-2, BTDAN-COX-2 employed cyclooxygenase-2's inhibitor as recognition group, because it is a classical and efficient recognition group for cyclooxygenase-2. A polarity-sensitive naphthalene derivative (BTDAN) as fluorophore was introduced into the molecule to enhance two-photon properties of BTDAN-COX-2. In the absent of cyclooxygenase-2, BTDAN-COX-2 mainly exists in a folded conformation where probe fluorescence is quenched through photoinduced electron transfer between the fluorophore and the recognition group. Under the condition of existence of cyclooxygenase-2, fluorescence of probe is turned on, because photoinduced electron transfer between the fluorophore and the recognition group is restrained. BTDAN-COX-2 provides high signal-to-background staining for the ultratrace cyclooxygenase-2 and has been successfully used to rapidly detect and image ultratrace cyclooxygenase-2 in living biosystems.
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Epstein-Barr virus latent membrane protein 2A suppresses the expression of HER2 via a pathway involving TWIST and YB-1 in Epstein-Barr virus-associated gastric carcinomas.
Oncotarget
PUBLISHED: 08-20-2014
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To explore HER2 expression in Epstein-Barr virus-associated gastric carcinoma (EBVaGC) and the possible mechanisms causing down-regulation of HER2 expression in EBVaGC, we first evaluated HER2 and LMP2A expression on a clinicopathological-features matched cohort including 78 EBVaGC and 216 EBV-negative gastric carcinoma (EBVnGC) cases by immunohistochemistry. Cases with high HER2 expression in EBVaGC were significantly less than in EBVnGC (5.1% versus 23.7%; p<0.001), and none of the 34 LMP2A+ EBVaGC showed high HER2 expression. Further, overexpressing LMP2A in EBV-negative SGC7901 cells significantly decreased HER2, TWIST and YB-1 mRNA by 36.1%±8.1%, 87.6%±14.0% and 83.8%±5.7%, and protein by 44%, 57% and 49%, respectively. Additionally, the nucleus/cytoplasm ratios of TWIST and YB-1 were also decreased by 85% and 80%, respectively. Silencing LMP2A by siRNA in EBV-positive SNU719 cells for 48 h significantly increased HER2, TWIST and YB-1 mRNA to 276.7%±14.6%, 1284.8%±38.2% and 332.0%±15.5% and protein to 212%, 457% and 232%, respectively. The nucleus/cytoplasm ratios of TWIST and YB-1 were up-regulated by 4.00- and 3.57-fold, respectively, following LMP2A down-regulation. Moreover, LMP2A+/HER2low EBVaGC cases presented the best overall survival compared with LMP2A-/HER2low and LMP2A-/HER2high cases (p=0.003, log-rank test). These results suggest that LMP2A may suppress the HER2 expression through the TWIST/YB-1 axis in EBVaGC.
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Redox-reversible niobium-doped strontium titanate decorated with in situ grown nickel nanocatalyst for high-temperature direct steam electrolysis.
Dalton Trans
PUBLISHED: 08-19-2014
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Composite cathodes based on Sr0.94Ti0.9Nb0.1O3 (STNO) can be utilized for direct steam electrolysis; however, the insufficient electrocatalytic activity limits electrode performance and current efficiency. In this work, redox-reversible (Sr0.94)0.9(Ti0.9Nb0.1)0.9Ni0.1O3 (STNNO) with A-site deficiency and B-site excess has been designed as a cathode material in an oxide-ion-conducting solid oxide electrolyzer for direct steam electrolysis. The XRD, TEM, SEM, EDS, TGA and XPS results together confirm that the exsolution or dissolution of Ni nanoparticles anchored on the STNO surface is completely reversible in the redox cycles. The electrical properties of STNO and STNNO are investigated and correlated to electrode performances. The current efficiency with an STNNO cathode is enhanced by about 20% compared to the values with a bare STNO cathode in 5% H2O/H2/Ar or 5% H2O/Ar at 800 °C. The synergetic effect of catalytically active nickel nanoparticles and the redox-stable STNO skeleton contributes to the improved performance and excellent stability of the cathode for steam electrolysis.
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Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds.
Biomaterials
PUBLISHED: 08-07-2014
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Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.
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In situ formation of oxygen vacancy in perovskite Sr0.95Ti0.8Nb0.1M0.1O3 (M = Mn, Cr) toward efficient carbon dioxide electrolysis.
Sci Rep
PUBLISHED: 07-11-2014
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In this work, redox-active Mn or Cr is introduced to the B site of redox stable perovskite Sr0.95Ti0.9Nb0.1O3.00 to create oxygen vacancies in situ after reduction for high-temperature CO2 electrolysis. Combined analysis using X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy and thermogravimetric analysis confirms the change of the chemical formula from oxidized Sr0.95Ti0.9Nb0.1O3.00 to reduced Sr0.95Ti0.9Nb0.1O2.90 for the bare sample. By contrast, a significant concentration of oxygen vacancy is additionally formed in situ for Mn- or Cr-doped samples by reducing the oxidized Sr0.95Ti0.8Nb0.1M0.1O3.00 (M = Mn, Cr) to Sr0.95Ti0.8Nb0.1M0.1O2.85. The ionic conductivities of the Mn- and Cr-doped titanate improve by approximately 2 times higher than bare titanate in an oxidizing atmosphere and 3-6 times higher in a reducing atmosphere at intermediate temperatures. A remarkable chemical accommodation of CO2 molecules is achieved on the surface of the reduced and doped titanate, and the chemical desorption temperature reaches a common carbonate decomposition temperature. The electrical properties of the cathode materials are investigated and correlated with the electrochemical performance of the composite electrodes. Direct CO2 electrolysis at composite cathodes is investigated in solid-oxide electrolyzers. The electrode polarizations and current efficiencies are observed to be significantly improved with the Mn- or Cr-doped titanate cathodes.
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Inference on differences between classes using cluster-specific contrasts of mixed effects.
Biostatistics
PUBLISHED: 06-26-2014
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The detection of differentially expressed (DE) genes, that is, genes whose expression levels vary between two or more classes representing different experimental conditions (say, diseases), is one of the most commonly studied problems in bioinformatics. For example, the identification of DE genes between distinct disease phenotypes is an important first step in understanding and developing treatment drugs for the disease. We present a novel approach to the problem of detecting DE genes that is based on a test statistic formed as a weighted (normalized) cluster-specific contrast in the mixed effects of the mixture model used in the first instance to cluster the gene profiles into a manageable number of clusters. The key factor in the formation of our test statistic is the use of gene-specific mixed effects in the cluster-specific contrast. It thus means that the (soft) assignment of a given gene to a cluster is not crucial. This is because in addition to class differences between the (estimated) fixed effects terms for a cluster, gene-specific class differences also contribute to the cluster-specific contributions to the final form of the test statistic. The proposed test statistic can be used where the primary aim is to rank the genes in order of evidence against the null hypothesis of no DE. We also show how a [Formula: see text]-value can be calculated for each gene for use in multiple hypothesis testing where the intent is to control the false discovery rate (FDR) at some desired level. With the use of publicly available and simulated datasets, we show that the proposed contrast-based approach outperforms other methods commonly used for the detection of DE genes both in a ranking context with lower proportion of false discoveries and in a multiple hypothesis testing context with higher power for a specified level of the FDR.
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Submucosal small-cell neuroendocrine carcinoma of the larynx detected using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report and review of the literature.
Oncol Lett
PUBLISHED: 06-12-2014
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A 67-year-old male presented with a metastatic carcinoma in the right side of the neck from an unknown primary site. (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed increased (18)F-FDG uptake in the right larynx and right neck lymph nodes. A smooth lesion was identified in the submucosa of the right supraglottic region via a suspension laryngoscopy under general anaesthesia. A biopsy was performed and a frozen section revealed a small-cell (SC) carcinoma. A total laryngectomy and bilateral neck dissection were performed simultaneously, and the pathological results demonstrated a SC neuroendocrine carcinoma. The patient received chemo-radiotherapy postoperatively, however, succumbed due to distant metastasis one year following surgery.
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Cultural differences in sensitivity to the relationship between objects and contexts: evidence from P3.
Neuroreport
PUBLISHED: 05-30-2014
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Cross-cultural differences in Easterners and Westerners have been observed in different cognitive domains. Differential sensitivity to the relationship between objects and contexts might be an underlying cognitive mechanism for these differences. Twenty-one Chinese and 22 Germans participated in a three-stimulus event-related potential oddball task. They were instructed to monitor geometrical forms filled in black (targets) that were presented among a series of blank geometrical forms (standards). Novel stimuli were colored images of common objects. Robust novelty P3 and target P3 over the entire scalp were observed in both groups. As compared with the German group, Chinese participants showed larger amplitudes of novelty P3 and target P3 over frontal regions and earlier peak latency for target P3. This indicates a higher sensitivity to the relationship between contexts and objects in the Chinese as compared with the German group, which might be an underlying mechanism for cross-cultural differences reported in many cognitive domains.
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Recent advances in proteomics: towards the human proteome.
Biomed. Chromatogr.
PUBLISHED: 05-28-2014
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After the successful completion of the Human Genome project in 2003, the next major challenge was to understand when and where the encoded proteins were expressed, and to generate a map of the complex, interconnected pathways, networks and molecular systems (the human proteome) that, taken together, control the workings of all cells, tissues, organs and organisms. Proteomics will be fundamental for such studies. This review summarizes the key discoveries that laid down the foundations for proteomics as we now know it, and describes key recent technological advances that will undoubtedly contribute to achieving the initial goal of the Human Proteome Organization of identifying and characterizing at least one protein product and representative post-translational modifications, single amino acid polymorphisms and splice variant isoforms from the 20,300 human protein-coding genes within the next 10 years. Successful unraveling of the human proteome will undoubtedly improve our understanding of human biology at the cellular level and lay the foundations for improved diagnostic, prognostic, therapeutic and preventive medical outcomes as we enter the era of personalized medicine.
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Long-Term Prognostic Implications of Visit-to-Visit Blood Pressure Variability in Patients With Ischemic Stroke.
Am. J. Hypertens.
PUBLISHED: 05-18-2014
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Blood pressure (BP) variability (BPV) is a novel risk factor for the development of atherosclerotic diseases. High BPV has recently been shown to predict all-cause and cardiovascular mortality in patients with lacunar infarct. Whether BPV has prognostic implications in patients with ischemic stroke subtypes, other than those due to small-vessel occlusion, remains uncertain.
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Itraconazole suppresses the growth of glioblastoma through induction of autophagy: involvement of abnormal cholesterol trafficking.
Autophagy
PUBLISHED: 05-15-2014
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Glioblastoma is one of the most aggressive human cancers with poor prognosis, and therefore a critical need exists for novel therapeutic strategies for management of glioblastoma patients. Itraconazole, a traditional antifungal drug, has been identified as a novel potential anticancer agent due to its inhibitory effects on cell proliferation and tumor angiogenesis; however, the molecular mechanisms involved are still unclear. Here, we show that itraconazole inhibits the proliferation of glioblastoma cells both in vitro and in vivo. Notably, we demonstrate that treatment with itraconazole induces autophagic progression in glioblastoma cells, while blockage of autophagy markedly reverses the antiproliferative activities of itraconazole, suggesting an antitumor effect of autophagy in response to itraconazole treatment. Functional studies revealed that itraconazole retarded the trafficking of cholesterol from late endosomes and lysosomes to the plasma membrane by reducing the levels of SCP2, resulting in repression of AKT1-MTOR signaling, induction of autophagy, and finally inhibition of cell proliferation. Together, our studies provide new insights into the molecular mechanisms regarding the antitumor activities of itraconazole, and may further assist both the pharmacological investigation and rational use of itraconazole in potential clinical applications.
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Chitosan-based thermoreversible hydrogel as an in vitro tumor microenvironment for testing breast cancer therapies.
Mol. Pharm.
PUBLISHED: 05-15-2014
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Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment. Here, we report the use of a thermoreversible poly(ethylene glycol)-g-chitosan hydrogel (PCgel) as an in vitro breast cancer model. We hypothesized that PCgel could provide a tumor microenvironment that promotes cultured cancer cells to a more malignant phenotype with drug and immune resistance. Traditional tissue culture plates and Matrigel were applied as controls in our studies. In vitro cellular proliferation and morphology, the secretion of angiogenesis-related growth factors and cytokines, and drug and immune resistance were assessed. Our results show that PCgel cultures promoted tumor aggregate formation, increased secretion of various angiogenesis- and metastasis-related growth factors and cytokines, and increased tumor cell resistance to chemotherapeutic drugs and immunotherapeutic T cells. This PCgel platform may offer a valuable strategy to bridge the gap between standard in vitro and costly animal studies for a wide variety of experimental designs.
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A Prognostic Scoring System for Patients with Multiple Hepatocellular Carcinomas Treated by Hepatectomy.
Ann. Surg. Oncol.
PUBLISHED: 04-28-2014
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The selection criteria of hepatectomy for patients with multiple hepatocellular carcinomas (HCCs) remain controversial.
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Identification of membrane proteins associated with phenylpropanoid tolerance and transport in Escherichia coli BL21.
J Proteomics
PUBLISHED: 04-08-2014
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Phenylpropanoids are phytochemicals produced by some plants and possess a wide variety of biological activities. These compounds exist in plants in low amounts. Production of them in genetically engineered microorganisms has many advantages. A majority of functional phenylpropanoids are toxic to microbial hosts. Export of these compounds may relieve the cellular toxicity and increase the yield. However, proteins and mechanisms involved in phenylpropanoids transport and tolerance remain poorly understood. In this study, 16 membrane proteins that were differentially expressed in Escherichia coli in response to three typical phenylpropanoids (resveratrol, naringenin and rutin) were identified using a membrane proteomics approach. These proteins included outer membrane proteins OmpA, OmpF, OmpW, FadL, TolC, LamB, and YaeT, peripheral membrane proteins AtpD, AtpH, YgaU, OppA, MalK, and MalE, and cytoplasmic membrane proteins OppD, PotG, and ManX. Functions of these proteins were determined by using gene overexpression and silencing. The results suggest that OmpA and FadL may play important roles in the transmembrane export of phenylpropanoids in E. coli. LamB, MalE, MalK and ManX may participate in phenylpropanoid uptake. The role of YgaU in enhancing the tolerance to phenylpropanoids remains to be determined. These results may assist the engineering of microorganisms with enhanced phenylpropanoid producing capabilities.
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Exceptionally abundant exceptions: comprehensive characterization of intrinsic disorder in all domains of life.
Cell. Mol. Life Sci.
PUBLISHED: 04-04-2014
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Recent years witnessed increased interest in intrinsically disordered proteins and regions. These proteins and regions are abundant and possess unique structural features and a broad functional repertoire that complements ordered proteins. However, modern studies on the abundance and functions of intrinsically disordered proteins and regions are relatively limited in size and scope of their analysis. To fill this gap, we performed a broad and detailed computational analysis of over 6 million proteins from 59 archaea, 471 bacterial, 110 eukaryotic and 325 viral proteomes. We used arguably more accurate consensus-based disorder predictions, and for the first time comprehensively characterized intrinsic disorder at proteomic and protein levels from all significant perspectives, including abundance, cellular localization, functional roles, evolution, and impact on structural coverage. We show that intrinsic disorder is more abundant and has a unique profile in eukaryotes. We map disorder into archaea, bacterial and eukaryotic cells, and demonstrate that it is preferentially located in some cellular compartments. Functional analysis that considers over 1,200 annotations shows that certain functions are exclusively implemented by intrinsically disordered proteins and regions, and that some of them are specific to certain domains of life. We reveal that disordered regions are often targets for various post-translational modifications, but primarily in the eukaryotes and viruses. Using a phylogenetic tree for 14 eukaryotic and 112 bacterial species, we analyzed relations between disorder, sequence conservation and evolutionary speed. We provide a complete analysis that clearly shows that intrinsic disorder is exceptionally and uniquely abundant in each domain of life.
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Differentiation-stimulating potency of differentiated HL60 cells after drug treatment.
Biomed. Pharmacother.
PUBLISHED: 04-03-2014
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Differentiation therapy in the treatment of leukemia is often hampered by limitations on using certain pharmaceutical regents or on the required doses due to various reasons, such as drug-resistance and retinoic acid syndrome. To circumvent these problems, a strategy might be developed on the basis of the ability of drug-differentiated cells to stimulate differentiation in leukemia cells. Using the promyelocytic leukemia cell line HL60 as a cell model, we assessed the differentiation-stimulating potency of differentiated granulocytes and monocytes/macrophages after treatments with all-trans retinoic acid (ATRA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), respectively. ATRA- and TPA-differentiated cells were able to stimulate differentiation in fresh HL60 cells, accompanied by inhibition on cell growth to various extents. The differentiated cells of the second generation, especially those originated from TPA treatment, were as potent as the drugs themselves in stimulating differentiation in fresh HL60 cells. On the basis of "differentiation induced by differentiated cells", we explored the feasibility of ex vivo therapy.
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In situ growth of Ni(x)Cu(1-x) alloy nanocatalysts on redox-reversible rutile (Nb,Ti)O? towards high-temperature carbon dioxide electrolysis.
Sci Rep
PUBLISHED: 03-28-2014
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In this paper, we report the in situ growth of Ni(x)Cu(1-x) (x = 0, 0.25, 0.50, 0.75 and 1.0) alloy catalysts to anchor and decorate a redox-reversible Nb1.33Ti0.67O4 ceramic substrate with the aim of tailoring the electrocatalytic activity of the composite materials through direct exsolution of metal particles from the crystal lattice of a ceramic oxide in a reducing atmosphere at high temperatures. Combined analysis using XRD, SEM, EDS, TGA, TEM and XPS confirmed the completely reversible exsolution/dissolution of the Ni(x)Cu(1-x) alloy particles during the redox cycling treatments. TEM results revealed that the alloy particles were exsolved to anchor onto the surface of highly electronically conducting Nb1.33Ti0.67O4 in the form of heterojunctions. The electrical properties of the nanosized Ni(x)Cu(1-x)/Nb1.33Ti0.67O4 were systematically investigated and correlated to the electrochemical performance of the composite electrodes. A strong dependence of the improved electrode activity on the alloy compositions was observed in reducing atmospheres at high temperatures. Direct electrolysis of CO2 at the Ni(x)Cu(1-x)/Nb1.33Ti0.67O4 composite cathodes was investigated in solid-oxide electrolysers. The CO2 splitting rates were observed to be positively correlated with the Ni composition; however, the Ni0.75Cu0.25 combined the advantages of metallic nickel and copper and therefore maximised the current efficiencies.
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Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms.
Gastric Cancer
PUBLISHED: 03-28-2014
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Gastric lymphoepithelioma-like carcinoma (LELC) is a rare entity that is closely associated with Epstein-Barr virus (EBV). However, the EBV latency pattern and genome polymorphisms in gastric LELC have not been systematically explored.
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Proteomics, genomics and transcriptomics: their emerging roles in the discovery and validation of colorectal cancer biomarkers.
Expert Rev Proteomics
PUBLISHED: 03-10-2014
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Colorectal cancer (CRC) is the second most common cancer in females and the third in males. Since CRC is often diagnosed at an advanced stage when prognosis is poor, identification of biomarkers for early diagnosis is urgently required. Recent advances in proteomics, genomics and transcriptomics have facilitated high-throughput profiling of data generated from CRC-related genes and proteins, providing a window of information for biomarker discovery and validation. However, transfer of candidate biomarkers from bench to bedside remains a dilemma. In this review, we will discuss emerging proteomic technologies and highlight various sample types utilized for proteomics-based identification of CRC biomarkers. Moreover, recent breakthroughs in genomics and transcriptomics for the identification of CRC biomarkers, with particular emphasis on the merits of emerging methylomic and miRNAomic strategies, will be discussed. Integration of proteomics, genomics and transcriptomics will facilitate the discovery and validation of CRC biomarkers leading to the emergence of personalized medicine.
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A Supramolecular Vesicle Based on the Complexation of p-Sulfonatocalixarene with Protamine and its Trypsin-Triggered Controllable-Release Properties.
Chemistry
PUBLISHED: 03-06-2014
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Enzyme-responsive assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites at which the target enzymes are located. In this work, based on the concept of host-guest chemistry, a trypsin-responsive supramolecular vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural serine protease trypsin-cleavable cationic protein protamine as the guest molecule, is reported. The complexation of p-sulfonatocalix[4]arene with protamine directs the formation of a supramolecular binary vesicle, which is dissipated by trypsin with high selectivity. Therefore, the present system represents a principle-of-concept to build a controlled-release carrier at trypsin-overexpressed sites.
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Reexpression of Let-7g microRNA inhibits the proliferation and migration via K-Ras/HMGA2/snail axis in hepatocellular carcinoma.
Biomed Res Int
PUBLISHED: 01-16-2014
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Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.
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Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus.
Cardiovasc Diabetol
PUBLISHED: 01-15-2014
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High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients.
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Intestinal obstruction caused by extramedullary hematopoiesis and ascites in primary myelofibrosis.
World J. Gastroenterol.
PUBLISHED: 01-14-2014
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Primary myelofibrosis (PMF) is a clonal hematopoietic stem cell disorder. It is characterized by bone marrow fibrosis, extramedullary hematopoiesis with hepatosplenomegaly and leukoerythroblastosis in the peripheral blood. The main clinical manifestations of PMF are anemia, bleeding, hepatosplenomegaly, fatigue, and fever. Here we report a rare case of PMF with anemia, small bowel obstruction and ascites due to extramedullary hematopoiesis and portal hypertension. The diagnosis was difficult to establish before surgery and the differential diagnosis is discussed.
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Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions.
Fitoterapia
PUBLISHED: 01-14-2014
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Licorice and its components have been reported to posses various anti-tumor activities, but its active ingredients and underlying mechanisms are not well understood yet. In the present study, a group of representative licorice-derived compounds that could be detected in rat plasma or urine were screened for anti-tumor activity. Among these compounds, isoangustone A (IAA) was found to promptly inhibit the viability of SW480 human colorectal adenocarcinoma cells in a time- and concentration-dependent manner. Further analyses indicate that IAA activated caspase-dependent pro-apoptotic signaling and induced significant apoptosis, while had little effect on cell cycle. IAA strongly inhibited Akt phosphorylation within 5 min; however, overexpression of constitutively activated Akt could not rescue IAA-mediated inhibition, indicating that inhibition of Akt was not involved in IAA-induced apoptosis. Further examinations show that IAA induced dissipation of mitochondria membrane potential and release of cytochrome C within 1h, accompanied by swelling of mitochondrial matrix and disrupting of mitochondrial outer membrane, and followed by decreasing of cellular ATP. The above results suggest that IAA induced apoptosis in colorectal cancer cells principally by inducing mitochondrial outer membrane permeabilization, and deserves further investigations as a novel anti-colorectal cancer agent.
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Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.
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F-18 FDG hypermetabolism in mass-forming focal pancreatitis and old hepatic schistosomiasis with granulomatous inflammation misdiagnosed by PET/CT imaging.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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We report the case of a 59-year-old male patient who presented with space-occupying lesions in the pancreas and liver suggestive of metastatic pancreatic cancer.
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Joint modeling and registration of cell populations in cohorts of high-dimensional flow cytometric data.
PLoS ONE
PUBLISHED: 01-01-2014
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In biomedical applications, an experimenter encounters different potential sources of variation in data such as individual samples, multiple experimental conditions, and multivariate responses of a panel of markers such as from a signaling network. In multiparametric cytometry, which is often used for analyzing patient samples, such issues are critical. While computational methods can identify cell populations in individual samples, without the ability to automatically match them across samples, it is difficult to compare and characterize the populations in typical experiments, such as those responding to various stimulations or distinctive of particular patients or time-points, especially when there are many samples. Joint Clustering and Matching (JCM) is a multi-level framework for simultaneous modeling and registration of populations across a cohort. JCM models every population with a robust multivariate probability distribution. Simultaneously, JCM fits a random-effects model to construct an overall batch template--used for registering populations across samples, and classifying new samples. By tackling systems-level variation, JCM supports practical biomedical applications involving large cohorts. Software for fitting the JCM models have been implemented in an R package EMMIX-JCM, available from http://www.maths.uq.edu.au/~gjm/mix_soft/EMMIX-JCM/.
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Stroke patients with a past history of cancer are at increased risk of recurrent stroke and cardiovascular mortality.
PLoS ONE
PUBLISHED: 01-01-2014
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Cancer patients are at increased risk of cardiovascular and cerebrovascular events. It is unclear whether cancer confers any additional risk for recurrent stroke or cardiovascular mortality after stroke.
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[Correlation of single nucleotide polymorphisms of X-ray repair cross complementing group 1 gene to hereditary susceptibility of colorectal cancer].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 12-27-2013
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To investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer.
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A new anastomosis method for choledochojejunostomy by the way behind antrue pyloricum.
Chin. Med. J.
PUBLISHED: 12-18-2013
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Reflux cholangitis has been the most common complication after Roux-en-Y choledochojejunostomy. In this study we intended to evaluate the perioperative and long-term efficacy of a new anastomosis method for choledochojejunostomy.
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Perovskite chromates cathode with exsolved iron nanoparticles for direct high-temperature steam electrolysis.
ACS Appl Mater Interfaces
PUBLISHED: 08-23-2013
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Recently, composite cathodes based on doped lanthanum chromates have been widely employed for direct steam electrolysis. However, this approach limits the electrode performances and Faraday efficiency due to insufficient electrocatalytic activity. This study addresses the drawbacks and reports an improved electrocatalytic activity and Faraday efficiency of composite cathode with a reversibly exsolved iron nanoparticles anchored on the surface of doped lanthanum chromates. A-site deficient and B-site excess (La0.75Sr0.25)0.85(Cr0.5Fe0.5)0.85Fe0.15O3-? (LSCrFF) was designed as the parent material to anchor the exsolved iron nanoparticles on the surface of perovskite chromate (La0.75Sr0.25)(Cr0.5Fe0.5)O3-? (LSCrF) via high-temperature reduction. The electrical properties of LSCrF and Fe/LSCrF were systematically investigated and correlated with electrochemical performance of the composite electrodes in symmetrical cells and electrolysis cells. The iron nanoparticles significantly improve the electrical conductivity of LSCrF from 1.80 to 6.35 S cm(-1) for Fe/LSCrF at 800 °C and Po2 of 10(-15) atm. The polarization resistance, Rp, of the symmetrical cells was accordingly enhanced from 4.26 ? cm2 with LSCrF to 2.58 ? cm2 with Fe/LSCrF in hydrogen atmosphere at 800 °C. The Faraday efficiency for the direct steam electrolysis showed a marked increase of 89.3% with LSCrFF cathode at 800 °C and 1.8 V as opposed to 76.7% with the cathodes based on LSCrF. The synergetic effect of catalytic-active iron nanoparticles and redox-stable LSCrF substrate produced improved performances and excellent stability for the direct steam electrolysis without a flow of reducing gas over the composite cathodes.
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FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer.
Cancer Res.
PUBLISHED: 08-13-2013
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Tumor cells evolve by interacting with the local microenvironment; however, the tumor-stroma interactions that govern tumor metastasis are poorly understood. In this study, proteomic analyses reveal that coculture with tumor-associated fibroblasts (TAF) induces significant overexpression of FGFR4, but not other FGFRs, in colorectal cancer cell lines. Mechanistic study shows that FGFR4 plays crucial roles in TAF-induced epithelial-to-mesenchymal transition (EMT) in colorectal cancer cell lines. Accumulated FGFR4 in cell membrane phosphorylates ?-catenin, leading to translocation of ?-catenin into the nucleus. Further, TAF-derived CCL2 and its downstream transcription factor, Ets-1, are prerequisites for TAF-induced FGFR4 upregulation. Furthermore, FGFR4-associated pathways are shown to be preferentially activated in colorectal tumor samples, and direct tumor metastasis in a mouse metastasis model. Our study shows a pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis, and suggests novel therapeutic opportunities for the treatment of colorectal cancer.
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Ag-Promoted Azido-Carbocyclization of Activated Alkenes via C?H Bond Cleavage.
Chem Asian J
PUBLISHED: 07-19-2013
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A sliver of silver: An efficient silver-promoted azido-carbocyclization of activated alkenes via a radical pathway has been developed. Azido oxindoles, which hold great potential for subsequent transformation of the azido unit, are efficiently constructed by this protocol. Radical addition and C?H functionalization processes are involved in this transformation with the formation of C?N and C?C bonds. Silver is observed to promote the single-electron oxidation process.
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Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM.
Biomaterials
PUBLISHED: 07-15-2013
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Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties. Chitosan-HA (C-HA) scaffolds had a highly porous network. C-HA scaffolds were compared to 2D surfaces for in vitro culture of U-118 MG human glioblastoma (GBM) cells. C-HA scaffold cultures promoted tumor spheroid formation and increased stem-like properties of GBM cells as evidenced by the upregulation of CD44, Nestin, Musashi-1, GFAP, and HIF-1? as compared with 2D cultures. Additionally, the invasiveness of GBM cells cultured in C-HA scaffolds was significantly enhanced compared to those grown in 2D cultures. C-HA scaffold cultures were also more resistant to chemotherapy drugs, which corresponded to the increased expression of ABCG2 drug efflux transporter. These findings suggest that C-HA scaffolds offer promise as an in vitro GBM platform for study and screening of novel cancer therapeutics.
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HIV Infection in gastric epithelial cells.
J. Infect. Dis.
PUBLISHED: 07-11-2013
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Many chronic human immunodeficiency virus (HIV) patients suffer from gastric complaints, including gastric tuberculosis and coinfection of other pathogens. Recent work has demonstrated that a variety of nonimmune cells can act as viral reservoirs, even at the early stage of HIV infection. In this study, we detect HIV viral particles, proteins, and nucleic acids in gastric epithelial cells using clinical samples. These observations are further supported by a simian immunodeficiency virus-infected macaque model. Further, the number of HIV-infected gastric epithelial cells is positively associated with blood viral load, and is negatively correlated with CD4 lymphocyte cell counts. We also demonstrate that HIV infection is accompanied by severe inflammatory response in gastric mucosa. Additionally, HIV infection activates signal transducer and activator of transcription 3 and RelA, and enhances the production of interleukin 6 and tumor necrosis factor ? in gastric epithelial cells. The present data suggest that the gastric epithelial cells are natural targets of HIV infection, and HIV infection in epithelial cells contributes to HIV-induced gastric mucosal inflammation.
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Salt ions and related parameters affect PEI-DNA particle size and transfection efficiency in Chinese hamster ovary cells.
Cytotechnology
PUBLISHED: 06-18-2013
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Transfection efficiency is directly associated with the expression level and quantity of recombinant protein after the transient transfection of animal cells. The transfection process can be influenced by many still-unknown factors, so it is valuable to study the precise mechanism and explore these factors in gene delivery. Polyethylenimine (PEI) is considered to have high transfection efficiency and endosome-disrupting capacity. Here we aimed to investigate optimal conditions for transfection efficiency by setting different parameters, including salt ion concentration, DNA/PEI ratio, and incubation time. We examined the PEI-DNA particle size using a Malvern particle size analyzer and assessed the transfection efficiency using flow cytometry in Chinese hamster ovary-S cells. Salt ions, higher amounts of PEI tended to improve the aggregation of PEI-DNA particles and the particle size of PEI-DNA complexes and the transfection efficiency were increased. Besides, the particle size was also found to benefit from longer incubation time. However, the transfection efficiency increased to maximum of 68.92 % at an incubation time of 10 min, but decreased significantly thereafter to 23.71 %, when incubating for 120 min (P < 0.05). Besides, PEI-DNA complexes formed in salt-free condition were unstable. Our results suggest DNA and PEI incubated in 300 mM NaCl at a ratio of 1:4 for 10 min could achieve the optimal transfection efficiency. Our results might provide guidance for the optimization of transfection efficiency and the industrial production of recombinant proteins.
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An accurate method for prediction of protein-ligand binding site on protein surface using SVM and statistical depth function.
Biomed Res Int
PUBLISHED: 05-17-2013
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Since proteins carry out their functions through interactions with other molecules, accurately identifying the protein-ligand binding site plays an important role in protein functional annotation and rational drug discovery. In the past two decades, a lot of algorithms were present to predict the protein-ligand binding site. In this paper, we introduce statistical depth function to define negative samples and propose an SVM-based method which integrates sequence and structural information to predict binding site. The results show that the present method performs better than the existent ones. The accuracy, sensitivity, and specificity on training set are 77.55%, 56.15%, and 87.96%, respectively; on the independent test set, the accuracy, sensitivity, and specificity are 80.36%, 53.53%, and 92.38%, respectively.
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[Application of modified plaster material and device in acupoint plaster therapy].
Zhongguo Zhen Jiu
PUBLISHED: 04-30-2013
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Through the analysis on the methods of medicinal paste preparation, the irritation of skin to medicine and the plaster materials adopted in acupoint plaster therapy for the prevention of winter-attacked disease in summer, the acupoint plaster materials and devices were improved. According to the differences in age, illness condition, acupoint and medicinal irritation of patients, the high-dosage, moderate-dosage and low-dosage series of medicine were prepared in proportion; 2. 5 mL and 5 mL syringes were manually reconstructed as the pushers for the delivery of the medicine paste of different specifications. The new-type materials such as spun-bonded non-woven fabrics, transparent dressing film and spun-laced non-woven skin-color stick plaster were adopted. In the operation, the medicine was classified and prepared more specifically. The dedicated acupoint plaster was characterized as less in skin irritation, breathable in property, convenient in practice and proper in stickiness. The plastic anti-seepage film in the middle and the medicine storage pool for stabilizing medicinal paste could avoid drug leakage. The medicinal paste pusher could achieve the even size, proper thickness and precise dosage of the paste. The new-type plaster material and the self-prepared innovated plaster device contribute to the development of acupoint plaster therapy in clinical application.
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Lanthanides inhibit adipogenesis with promotion of cell proliferation in 3T3-L1 preadipocytes.
Metallomics
PUBLISHED: 04-23-2013
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Lanthanides are widely used in various fields for industrial, agricultural and medical purposes. They have also been used in Chinese agriculture either as fertilizers in plant production or as performance-enhancers in animal nutrition for many years. In view of their possible application for growth enhancing purposes and new medical applications, detailed information on how lanthanides influence physiological processes in biological systems is indispensable. In the present work, the effects of lanthanides (LaCl3, CeCl3 and GdCl3) on cell proliferation and adipogenesis in 3T3-L1 preadipocytes were evaluated. The results demonstrate that lanthanides inhibit adipogenesis in 3T3-L1 preadipocytes, evidenced by decreased triglyceride content and expression of C/EBP? and PPAR?. Simultaneously, the results show that lanthanides can promote cell proliferation during the different stages of differentiation. Firstly, prior to the addition of differentiation inducers (MDI), all the three types of lanthanides resulted in a significant increase of cell growth. Secondly, during the mitotic clonal expansion (MCE) process, GdCl3, as a representative compound, is able to promote cell-cycle entry into the S phase and levels of cell cycle-regulating proteins. Third, at the late stage of the terminal differentiation, on day 8, in the presence of GdCl3, cells exhibited higher levels of G1/S regulatory proteins and proliferating cell nuclear antigen (PCNA). In addition, GdCl3 caused stronger sustained ERK activation during the differentiation process of 3T3-L1 cells. The present study demonstrates that lanthanides may modulate lipid metabolism by inhibition of adipocyte differentiation. The sustained activation of the ERK pathway might be responsible for their inhibition of differentiation and a possible link between their pro-proliferative ability and inhibition of the differentiation process is indicated.
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Identification of dicalcium phosphate dihydrate deposited during osteoblast mineralization in vitro.
J. Inorg. Biochem.
PUBLISHED: 04-20-2013
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The hydroxyapatite (HAP) with variable chemical substitutions has been considered as the major component in the mineralized part of bones. Various metastable crystalline phases have been suggested as transitory precursors of HAP in bone, but there are no consensuses as to the nature of these phases and their temporal evolution. In the present study, we cultured rat calvarial osteoblasts with ascorbate and ?-glycerophosphate to explore which calcium phosphate precursor phases comprise the initial mineral in the process of osteoblast mineralization in vitro. At the indicated time points, the deposited calcium phosphate was analyzed after removing organic substances from the extracellular matrix with hydrazine. The features comparable to dicalcium phosphate dihydrate (DCPD) and octacalcium phosphate (OCP), in addition to HAP, were detected in the mineral phases by high resolution transmission electron microscopy. And there was a trend of conversion from DCPD- and OCP-like phases to HAP in the course of mineralization, as indicated by Fourier-transform infrared microspectroscopy, energy-dispersive X-ray spectroscopy and synchrotron X-ray powder diffraction analyses. Besides, biochemical assay showed a progressive decrease in the ratio of mineral-associated proteins to calcium with time. These findings suggest that DCPD- and OCP-like phases are likely to occur on the course of osteoblast mineralization, and the mineral-associated proteins might be involved in modulating the mineral phase transformation.
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Bis(acetylacetonato)-oxovanadium(iv), bis(maltolato)-oxovanadium(iv) and sodium metavanadate induce antilipolytic effects by regulating hormone-sensitive lipase and perilipin via activation of Akt.
Metallomics
PUBLISHED: 04-10-2013
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The increased plasma free fatty acid levels due to the deregulated lipolysis in adipocytes are considered as one of the major risk factors for developing type II diabetes. Vanadium compounds are well-known for their antidiabetic effects both on glucose and lipid metabolism, but the mechanisms are still not completely understood. The present study suggests a mechanism for how vanadium compounds exert antilipolytic effects. It demonstrates that all the three vanadium compounds, bis(acetylacetonato)-oxovanadium(iv) (VO(acac)2), bis(maltolato)-oxovanadium(iv) (VO(ma)2) and sodium metavanadate (NaVO3), attenuated basal lipolysis in 3T3L1 adipocytes in a dose- (from 100 to 400 ?M for VO(acac)2 and VO(ma)2, 1.0 to 4.0 mM for vanadate) and time-dependent (from 0.5 to 4 h) manner using the glycerol release as a marker of lipolysis. In addition, the three compounds inhibited lipolysis to a different extent. Among them, VO(acac)2 (from 100 to 400 ?M) exerted the most potent effect and reduced the lipolysis to ?60-20% of control after 4 h treatment. The antilipolytic effects of vanadium compounds were further evidenced by a decrease of the levels of phosphorylated HSL at Ser660 and phosphorylated perilipin, which were counteracted by inhibitors of PI3K or Akt but not by an MEK inhibitor. This indicates that though both Akt and ERK pathways are activated by the vanadium compounds, only Akt activation contributes to the antilipolytic effect of the vanadium compounds, without the involvement of ERK activation. We previously demonstrated that VO(acac)2 can block cell cycle progression at the G1/S phase via a highly activated ERK signal in human hepatoma HepG2 cells. Together with this study, we show that similar activated pathways may lead to differential biological consequences for cancer cells and adipocytes, indicating that vanadium compounds may be used in the prevention and treatment of both diabetes and cancer.
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Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells.
Biomacromolecules
PUBLISHED: 04-03-2013
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In the tumor microenvironment, the signals from tumor-associated fibroblasts (TAF) that suppress antitumor immunity remain unclear. Here, we develop and investigate an in vitro three-dimensional (3D) scaffold model for the novel evaluation of TAF interaction with breast tumor cells and breast specific, neu antigen (p98) reactive T cells. Breast cancer cells seeded on 3D chitosan-alginate (CA) scaffolds showed productive growth and formed distinct tumor spheroids. Antigen specific p98 T cells, but not naïve T cells, bound significantly better to tumor cells on scaffolds. The p98 T cells induced potent tumor cell killing but T helper cell cytokine function was impaired in the presence of TAF coseeding on scaffolds. We found that the immunosuppression was mediated, in part, by transforming growth factor beta (TGF-b) and interleukin-10 (IL-10). Therefore, TAF appear capable of inducing potent T cell suppression. CA scaffolds can provide clinically relevant findings prior to preclinical testing of novel immunotherapies.
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Redox homeostasis: the linchpin in stem cell self-renewal and differentiation.
Cell Death Dis
PUBLISHED: 03-16-2013
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Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as redox sensors by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology.
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Bipolar disorder and schizophrenia share a similar deficit in semantic inhibition: a meta-analysis based on Hayling Sentence Completion Test performance.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 03-15-2013
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Bipolar disorder (BD) is associated with deficits in executive function similar to that found in schizophrenia (SZ). However, very few studies have examined whether a specific component of executive function, namely, semantic inhibition, is differentially impaired in BD and SZ. The present study reports the results of a meta-analysis of performance on a theory-driven test of semantic inhibition, namely, the Hayling Sentence Completion Test (HSCT), in patients with BD and SZ, and to examine differential group impairments. The Comprehensive Meta-Analysis Software package was used to calculate the mean effect sizes for group differences on different measures of HSCT. A total of 13 studies were included in the meta-analysis. Effect sizes for six HSCT measures were calculated. These included: Total Latency of Task A, Total Latency of Task B, Suppression Time, Total Error of Task B, Type A Error of Task B, and Type B Error of Task B. When compared with healthy controls, medium-to-large effect sizes were observed in both groups for each HSCT measure. Interestingly, the effect sizes for BD and SZ groups were comparable. These results suggest that patients with SZ and patients with BD are impaired in both task initiation and task inhibition of executive function and these impairments are similar in magnitude for both disorders.
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Aligned chitosan-polycaprolactone polyblend nanofibers promote the migration of glioblastoma cells.
Adv Healthc Mater
PUBLISHED: 03-13-2013
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In vitro models that accurately mimic the microenvironment of invading glioblastoma multiform (GBM) cells will provide a high-throughput system for testing potential anti-invasion therapies. Here, the ability of chitosan-polycaprolactone polyblend nanofibers to promote a migratory phenotype in human GBM cells by altering the nanotopography of the nanofiber membranes is investigated. Fibers are prepared with diameters of 200 nm, 400 nm, and 1.1 ?m, and are either randomly oriented or aligned to produce six distinct nanotopographies. Human U-87 MG GBM cells, a model cell line commonly used for invasion assays, are cultured on the various nanofibrous substrates. Cells show elongation and alignment along the orientation of aligned fibers as early as 24 h and up to 120 h of culture. After 24 h of culture, human GBM cells cultured on aligned 200 nm and 400 nm fibers show marked upregulation of invasion-related genes including ?-catenin, Snail, STAT3, TGF-?, and Twist, suggesting a mesenchymal change in these migrating cells. Additionally, cells cultured on 400 nm aligned fibers show similar migration profiles as those reported in vivo, and thus these nanofibers should provide a unique high-throughput in vitro culture substrate for developing anti-migration therapies for the treatment of GBM.
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Association of subclinical myocardial injury with arterial stiffness in patients with type 2 diabetes mellitus.
Cardiovasc Diabetol
PUBLISHED: 03-06-2013
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Type 2 diabetes mellitus (T2DM) is associated with subclinical myocardial injury although the underlying mechanism is uncertain. We postulated that arterial stiffness, endothelial dysfunction and subclinical atherosclerosis may contribute to subclinical myocardial injury in patients with T2DM.
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Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report.
Iran J Radiol
PUBLISHED: 02-20-2013
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Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for only 0.8% of all tonsillar tumors, with only 100 cases reported in the English-language literature. Various malignant lung carcinomas may metastasize to the tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma have been reported. A 67-year-old female underwent a right tonsillectomy because of a sore throat and an enlarged right tonsil. The postoperative pathology showed right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated metabolic activity in the lower lobe of the right lung. In addition, hypermetabolic foci were noted in the lymph nodes of the right neck and mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient received chemotherapy and died of multiple distant metastases after 6 months. This is the first report using PET/CT to evaluate tonsillar metastasis from lung SCNC.
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Angioimmunoblastic T-cell lymphoma-associated pure red cell aplasia with abdominal pain.
World J Clin Oncol
PUBLISHED: 02-19-2013
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Angioimmunoblastic T-cell lymphoma (AITL) is a unique type of peripheral T-cell lymphoma with a constellation of clinical symptoms and signs, including weight loss, fever, chills, anemia, skin rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and polyclonal hypergammaglobulinemia. The histological features of AITL are also distinctive. Pure red cell aplasia is a bone marrow failure characterized by progressive normocytic anemia and reticulocytopenia without leucopenia or thrombocytopenia. However, AITL with abdominal pain and pure red cell aplasia has rarely been reported. Here, we report a rare case of AITL-associated pure red cell aplasia with abdominal pain. The diagnosis was verified by a biopsy of the enlarged abdominal lymph nodes with immunohistochemical staining.
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Predictive Value of the HAS-BLED Score for the Risk of Recurrent Intracranial Hemorrhage After First Spontaneous Intracranial Hemorrhage.
World Neurosurg
PUBLISHED: 02-18-2013
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BACKGROUND: Patients who survive intracranial hemorrhage (ICH) are at high risk of recurrence. The Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly (Age >65 years), Drugs/Alcohol Concomitantly (HAS-BLED) score has recently been developed to assess bleeding risk. METHODS: This observational study was aimed to investigate the prognostic performance of the HAS-BLED score in predicting recurrent ICH. Consecutive patients (434) with a first spontaneous ICH who were not prescribed antiplatelet or anticoagulation therapy (59.8 ± 15.3 years; men, 62.3%) were recruited. RESULTS: Most patients (71.6%) had a HAS-BLED score of >1. After a follow-up of 52.7 months, there were 42 ICH recurrences (2.25 per 100 patient-years). The risk of ICH recurrence increased with HAS-BLED score. Specifically, the risk of ICH recurrence with HAS-BLED score of 1, 2, 3, and 4 were 1.37, 2.38, 3.39, and 2.90 per 100 patient-years, respectively. The sensitivity and specificity of HAS-BLED was 79.1% and 29.2%, respectively, with C-statistic of 0.54 (0.50-0.59). CONCLUSION: This study provided data on the risk of ICH recurrence stratified using the HAS-BLED score in patients after an ICH.
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Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients.
J Interv Card Electrophysiol
PUBLISHED: 02-07-2013
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Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms.
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The CHADS2 and CHA 2DS 2-VASc scores predict new occurrence of atrial fibrillation and ischemic stroke.
J Interv Card Electrophysiol
PUBLISHED: 02-07-2013
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Early identification of individuals who are at risk of developing atrial fibrillation (AF) and ischemic stroke may enable a closer surveillance and thus prompt initiation of oral anticoagulation for stroke prevention.
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Cinnabar is different from mercuric chloride in mercury absorption and influence on the brain serotonin level.
Basic Clin. Pharmacol. Toxicol.
PUBLISHED: 02-07-2013
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The toxicity of cinnabar, a naturally occurring mercury sulphide (HgS), has long been referred to soluble mercury chloride (HgCl2 ). To investigate whether the speciation of mercury plays a role in its disposition and toxicity, we hereby investigated and compared cinnabar with soluble HgCl2 and pure insoluble HgS in mice on mercury absorption, tissue distribution and in relation to the biological effects. The male C57BL/6J mice were treated by oral administration of various doses of cinnabar, with 0.01 g/kg of HgCl2 for comparison, or the same dose of cinnabar or pure HgS (0.1 g/kg), once a day for 10 consecutive days. The total mercury contents in serum and tissue (brain, kidney, liver) were measured by atomic fluorescence spectrometer (AFS). The biological effects investigated involved monoamine neurotransmitters (serotonin, 5-HT) in brain as an indicator of therapeutic function, and serum alanine transaminase (ALT) as a marker of hepatic damage, blood urea nitrogen (BUN) and serum creatinine as markers for renal function. The mercury absorption of cinnabar or HgS was much less than that of HgCl2 . The mercury levels in brains of the cinnabar group were only slightly changed and kept in a steady-state with the dose elevated. Cinnabar or HgS suppressed brain 5-HT levels. HgCl2 could not cause any changes in brain 5-HT although the mercury level increased considerably. The results revealed that cinnabar or HgS is markedly different from HgCl2 in mercury absorption, tissue distribution and influence on brain 5-HT levels, which suggests that the pharmacological and/or toxicological effects of cinnabar undertake other pathways from mercuric ions.
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Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy.
J. Clin. Oncol.
PUBLISHED: 01-28-2013
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This study aimed to establish an effective prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy.
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Treatment of glioblastoma multiforme using a combination of small interfering RNA targeting epidermal growth factor receptor and ?-catenin.
J Gene Med
PUBLISHED: 01-16-2013
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Epidermal growth factor receptor (EGFR) and ?-catenin are two key mediators of cell signal transduction implicated in the pathogenesis of a variety of tumors. There is emerging evidence indicating that they are overexpressed in glioblastoma multiforme (GBM) and both play significant roles in GBM carcinogenesis. Moreover, down-regulating EGFR individually only provides limited therapeutic efficacy. Therefore, we aimed to determine the feasibility and efficacy of gene therapy of GBM using combinatorial inhibition of EGFR and ?-catenin in view of the cross-talk between these two signaling pathways.
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Genome sequences of siphoviruses infecting marine Synechococcus unveil a diverse cyanophage group and extensive phage-host genetic exchanges.
Environ. Microbiol.
PUBLISHED: 12-22-2011
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Investigating the interactions between marine cyanobacteria and their viruses (phages) is important towards understanding the dynamic of oceans primary productivity. Genome sequencing of marine cyanophages has greatly advanced our understanding about their ecology and evolution. Among 24 reported genomes of cyanophages that infect marine picocyanobacteria, 17 are from cyanomyoviruses and six from cyanopodoviruses, and only one from cyanosiphovirus (Prochlorococcus phage P-SS2). Here we present four complete genome sequences of siphoviruses (S-CBS1, S-CBS2, S-CBS3 and S-CBS4) that infect four different marine Synechococcus strains. Three distinct subtypes were recognized among the five known marine siphoviruses (including P-SS2) in terms of morphology, genome architecture, gene content and sequence similarity. Our study revealed that cyanosiphoviruses are genetically diverse with polyphyletic origin. No core genes were found across these five cyanosiphovirus genomes, and this is in contrast to the fact that many core genes have been found in cyanomyovirus or cyanopodovirus genomes. Interestingly, genes encoding three structural proteins and a lysozyme of S-CBS1 and S-CBS3 showed homology to a prophage-like genetic element in two freshwater Synechococcus elongatus genomes. Re-annotation of the prophage-like genomic region suggests that S.?elongatus may contain an intact prophage. Cyanosiphovirus genes involved in DNA metabolism and replication share high sequence homology with those in cyanobacteria, and further phylogenetic analysis based on these genes suggests that ancient and selective genetic exchanges occurred, possibly due to past prophage integration. Metagenomic analysis based on the Global Ocean Sampling database showed that cyanosiphoviruses are present in relatively low abundance in the ocean surface water compared to cyanomyoviruses and cyanopodoviruses.
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Protein expression and significance of VEGF, EGFR and MMP-9 in non-small cell lung carcinomas.
Asian Pac. J. Cancer Prev.
PUBLISHED: 12-01-2011
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This study was designed to detect the protein expression of VEGF, EGFR and MMP-9, to investigate the potential roles they might play in the pathogenesis of NSCLC and to discuss their relationship and their clinical significance.
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[Effects of damage-regulated autophagy modulator on the radiosensitivity of SGC7901 cell xenografts in nude mice].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 11-26-2011
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To investigate the effects of damage-regulated autophagy modulator (DRAM) on radiosensitivity and the related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.
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[Impact of stromal interaction molecule 1 silencing on cell cycle of endothelial progenitor cells].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-18-2011
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To investigate the effect of stromal interaction molecule 1 (STIM1) silencing on EPCs cell cycle.
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Abnormal vascular function in PR-interval prolongation.
Clin Cardiol
PUBLISHED: 10-14-2011
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Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function.
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Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus.
Cardiovasc Diabetol
PUBLISHED: 09-24-2011
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Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.
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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.

Video X seems to be unrelated to Abstract Y...

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.