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Find video protocols related to scientific articles indexed in Pubmed.
Postprandial glucose, insulin and incretin responses to different carbohydrate tolerance tests.
J Diabetes
PUBLISHED: 11-06-2014
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Few studies focused on postprandial incretin responses to different carbohydrate meals. Therefore, we designed a study to compare the different effects of two carbohydrates (75g oral glucose, a monosaccharide and 100g standard noodle, a polysaccharide, with 75g carbohydrates equivalently) on postprandial glucose, insulin and incretin responses in different glucose tolerance groups.
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The immunologic and hematopoietic profiles of mesenchymal stem cells derived from different sections of human umbilical cord.
Acta Biochim. Biophys. Sin. (Shanghai)
PUBLISHED: 11-05-2014
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Mesenchymal stem cells (MSCs) have been widely used in allogeneic stem cell transplantation. We compared immunologic and hematopoietic characteristics of MSCs derived from whole human umbilical cord (UC), as well as from different sections of UCs, including the amniotic membrane (AM), Wharton's jelly (WJ), and umbilical vessel (UV). Cell phenotypes were examined by flow cytometry. Lymphocyte transformation test and mixed lymphocyte reaction were performed to evaluate the immuno-modulatory activity of MSCs derived from UCs. The mRNA expression of cytokines was detected by real-time polymerase chain reaction. Hematopoietic function was studied by co-culturing MSCs with CD34(+) cells isolated from cord blood. Our results showed that MSCs separated from these four different sections including UC, WJ, UV, and AM had similar biological characteristics. All of the MSCs had multi-lineage differentiation ability and were able to differentiate into osteoblasts, adipocytes, and chondrocytes. The MSCs also inhibited the proliferation of allogeneic T cells in a dose-dependent manner. The relative mRNA expression of cytokines was examined, and the results showed that UCMSCs had higher interleukin-6 (IL6), IL11, stem cell factor, and FLT3 expression than MSCs derived from specific sections of UCs. CD34(+) cells had high propagation efficiencies when co-cultured with MSCs derived from different sections of UCs, among which UCMSCs are the most efficient feeding layer. Our study demonstrated that MSCs could be isolated from whole UC or specific sections of UC with similar immunomodulation and hematopoiesis supporting characteristics.
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High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial.
Radiology
PUBLISHED: 11-05-2014
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Purpose To determine the association between nonalcoholic fatty liver disease ( NAFLD nonalcoholic fatty liver disease ) and the presence of high-risk coronary atherosclerotic plaque as assessed with coronary computed tomographic (CT) angiography. Materials and Methods This study was approved by the local ethics committees; informed consent was obtained. Patients randomized to the coronary CT angiography arm of the Rule Out Myocardial Infarction using Computer Assisted Tomography, or ROMICAT Rule Out Myocardial Infarction using Computer Assisted Tomography , II trial who underwent both nonenhanced CT to assess calcium score and contrast material-enhanced coronary CT angiography were included. Readers assessed coronary CT angiography images for the presence of coronary plaque, significant stenosis (?50%), and high-risk plaque features (positive remodeling, CT attenuation < 30 HU, napkin-ring sign, spotty calcium). NAFLD nonalcoholic fatty liver disease was defined as hepatic steatosis at nonenhanced CT (liver minus spleen CT attenuation < 1 HU) without evidence of clinical liver disease, liver cirrhosis, or alcohol abuse. To determine the association between high-risk plaque and NAFLD nonalcoholic fatty liver disease , univariable and multivariable logistic regression analyses were performed, with high-risk plaque as a dependent variable and NAFLD nonalcoholic fatty liver disease , traditional risk factors, and extent of coronary atherosclerosis as independent variables. Results Overall, 182 (40.9%) of 445 patients had CT evidence of NAFLD nonalcoholic fatty liver disease . High-risk plaque was more frequent in patients with NAFLD nonalcoholic fatty liver disease than in patients without NAFLD nonalcoholic fatty liver disease (59.3% vs 19.0%, respectively; P < .001). The association between NAFLD nonalcoholic fatty liver disease and high-risk plaque (odds ratio, 2.13; 95% confidence interval: 1.18, 3.85) persisted after adjusting for the extent and severity of coronary atherosclerosis and traditional risk factors. Conclusion NAFLD nonalcoholic fatty liver disease is associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease. © RSNA, 2014.
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Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis.
Leuk. Lymphoma
PUBLISHED: 10-16-2014
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Myelofibrosis is characterized by progressive cytopenias, bone marrow fibrosis, splenomegaly and severe constitutional symptoms. In the phase 3 Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies, ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, provided substantial improvements in splenomegaly, symptoms, quality-of-life measures and overall survival compared with placebo or best available therapy. No assessments of the efficacy and safety of ruxolitinib have been conducted in Asian patients. Here, we describe results from an open-label, single-arm, phase 2 trial evaluating ruxolitinib in Asian patients with myelofibrosis (n = 120). The primary endpoint was met, with 31.7% of patients achieving a ? 35% reduction from baseline spleen volume at week 24. As measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0, 49% of patients achieved a ? 50% reduction from baseline in total symptom score. Adverse events were consistent with those seen in the COMFORT studies. Ruxolitinib was well tolerated in Asian patients with myelofibrosis and provided substantial reductions in splenomegaly and improvements in symptoms.
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[Comparing BFA with BuCyA as a myeloablative conditioning regimen for allogeneic stem cell transplantation in acute leukemias].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To compare BFA (busulfan, fludarabine plus cytarabine) with BuCyA (busulfan, cyclophoshpamide plus cytarabine) as the conditioning regimens in allogeneic stem cell transplantation for acute leukemias.
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[Efficacy of tyrosine kinase inhibitor in treatment of chronic myeloid leukemia patients].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To evaluate the effects of tyrosine kinase inhibitors (TKI) in the treatment of chronic myeloid leukemia.
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[Advances in the target therapy of hematological malignancies].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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With the rapid development of modern bio-medical technology, the pathogenesis of hematological malignancies including leukemia, lymphoma, myeloma has been illustrated with more and more attractive details. The diagnosis of hematological malignancies now becomes more precisely and clarified based on the progress than ever before, and the treatments of hematological malignancies keep the evolution in the way of integrating the novel molecular target drugs with conventional chemotherapy, radiotherapy, hematopoietic stem cell transplantation. The pivotal progress in the target therapy of hematological malignancies includes tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, CD20 monoclonal antibody treatment of B-cell lymphoma and CD20 positive leukemia, FLT3 inhibitors fo the treatment of FLT3 mutation positive high-risk acute myelogenous leukemia. The topics of this issue focus on the advances in this field, which reflects the new achievements in the research of hematological malignancies, and the trends of precise and stratified diagnosis as well as tailored target therapy in the future.
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[Effect of total flavones of Epimedium leptorrhizum on osteoporosis in ovariectomized rats].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-07-2014
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To observe the effect of total flavones of Epimedium leptorrhizum (YYH-C) on osteoporosis in ovariectomized rats.
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Solid-to-fluid-like DNA transition in viruses facilitates infection.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2014
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Releasing the packaged viral DNA into the host cell is an essential process to initiate viral infection. In many double-stranded DNA bacterial viruses and herpesviruses, the tightly packaged genome is hexagonally ordered and stressed in the protein shell, called the capsid. DNA condensed in this state inside viral capsids has been shown to be trapped in a glassy state, with restricted molecular motion in vitro. This limited intracapsid DNA mobility is caused by the sliding friction between closely packaged DNA strands, as a result of the repulsive interactions between the negative charges on the DNA helices. It had been unclear how this rigid crystalline structure of the viral genome rapidly ejects from the capsid, reaching rates of 60,000 bp/s. Through a combination of single-molecule and bulk techniques, we determined how the structure and energy of the encapsidated DNA in phage ? regulates the mobility required for its ejection. Our data show that packaged ?-DNA undergoes a solid-to-fluid-like disordering transition as a function of temperature, resulting locally in less densely packed DNA, reducing DNA-DNA repulsions. This process leads to a significant increase in genome mobility or fluidity, which facilitates genome release at temperatures close to that of viral infection (37 °C), suggesting a remarkable physical adaptation of bacterial viruses to the environment of Escherichia coli cells in a human host.
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Ginsenoside 20(S)?Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells.
Int. J. Oncol.
PUBLISHED: 09-24-2014
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Cancer cells prefer to metabolize glucose through aerobic glycolysis, known as the Warburg effect. It plays a crucial role in proliferation and progression of cancer cells. However, the complete mechanism remains elusive. In recent studies, the signal transducer and activator of transcription 3 (STAT3) signaling has been discovered to have roles in cancer?associated changes in metabolism. In this study, we find that the ginsenoside 20(S)?Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, inhibits glycolysis in ovarian cancer cells by regulating hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). We also show that 20(S)?Rg3 regulates HK2 through downregulation of p?STAT3 (Tyr705). Furthermore, overexpression of STAT3 in ovarian cancer cells weakened the suppression of Warburg effect induced by 20(S)?Rg3. Importantly, 20(S)?Rg3 treatment represses HK2 expression in nude mouse xenograft models of ovarian cancer. Taken together, our results show that 20(S)?Rg3 inhibits the Warburg effect by targeting STAT3/HK2 pathway in ovarian cancer cells, highlighting the potentiality of 20(S)?Rg3 to be used as a therapeutic agent for ovarian cancer.
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Activation of a Novel c-Myc-miR27-Prohibitin 1 Circuitry in Cholestatic Liver Injury Inhibits Glutathione Synthesis in Mice.
Antioxid. Redox Signal.
PUBLISHED: 09-17-2014
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Abstract Aims: We showed that chronic cholestatic liver injury induced the expression of c-Myc but suppressed that of glutamate-cysteine ligase (GCL, composed of catalytic and modifier subunits GCLC and GCLM, respectively). This was associated with reduced nuclear antioxidant response element (ARE) binding by nuclear factor-erythroid 2 related factor 2 (Nrf2). Here, we examined whether c-Myc is involved in this process. Results: Similar to bile duct ligation (BDL), lithocholic acid (LCA) treatment in vivo induced c-Myc but suppressed GCL subunits expression at day 14. Nrf2 expression and Nrf2 ARE binding fell markedly. However, Nrf2 heterodimerization with MafG was enhanced by LCA, which prompted us to examine whether LCA treatment in vivo altered proteins that bind to ARE using biotinylated ARE in pull-down assay followed by proteomics. LCA treatment enhanced c-Myc but lowered prohibitin 1 (PHB1) binding to ARE. This was a result of c-Myc-mediated induction of microRNA 27a/b (miR27a/b), which target both PHB1 and Nrf2 to reduce their expression. Knockdown of c-Myc or miR27a/b attenuated LCA-mediated suppression of Nrf2, PHB1, and GCL subunit expression, whereas overexpression of PHB1 protected against the fall in Nrf2 and GCL subunits. Both c-Myc and PHB1 directly interact with Nrf2 but c-Myc lowers Nrf2 binding to ARE while PHB1 enhances it. Innovation: This is the first work that shows how activation of this circuit in cholestatic liver injury inhibits GCL expression. Conclusions: LCA feeding and BDL activate c-Myc-miR27a/b-PHB1 circuit, with the consequence of inhibiting Nrf2 expression and ARE binding, resulting in decreased reduced glutathione synthesis and antioxidant capacity. Antioxid. Redox Signal. 00, 000-000.
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Paenibacillus guangzhouensis sp. nov., an Fe(III)- and humus-reducing bacterium from a forest soil.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 09-01-2014
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A Gram-reaction-variable, rod-shaped, motile, facultatively aerobic and endospore-forming bacterium, designated strain GSS02(T), was isolated from a forest soil. Strain GSS02(T) was capable of reducing humic substances and Fe(III) oxides. Strain GSS02(T) grew optimally at 35 °C, at pH 78 and in the presence of 1?% NaCl. The predominant menaquinone was MK-7. The major cellular fatty acids were anteiso-C15?:?0 and iso-C16?:?0 and the polar lipid profile contained mainly phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol, with moderate amounts of two unknown aminophospholipids and a minor amount of one unknown lipid. The DNA G+C content was 53.4 mol%. Comparative 16S rRNA gene sequence analysis showed that strain GSS02(T) was related most closely to Paenibacillus terrigena JCM 21741(T) (98.1?% similarity). Mean DNA-DNA relatedness between strain GSS02(T) and P. terrigena JCM 21741(T) was 58.8±0.5?%. The phylogenetic, chemotaxonomic and phenotypic results clearly demonstrated that strain GSS02(T) belongs to the genus Paenibacillus and represents a novel species, for which the name Paenibacillus guangzhouensis sp. nov. is proposed. The type strain is GSS02(T) (?=?KCTC 33171(T)?=?CCTCC AB 2013236(T)).
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Tetrandrine induces G1/S cell cycle arrest through the ROS/Akt pathway in EOMA cells and inhibits angiogenesis in vivo.
Int. J. Oncol.
PUBLISHED: 08-29-2014
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Tetrandrine, a bisbenzylisoquinoline alkaloid, is known to inhibit tumor cell proliferation and induce apoptosis in cancer models in vitro and in vivo. In the present study, tetrandrine significantly inhibited the proliferation of mouse endothelial cells (EOMA cell) and induced G1/S arrest in EOMA cells, in which the expressions of cyclin D and cyclin E and CDKs were downregulated. Tetrandrine treatment also caused intracellular accumulation of reactive oxygen species (ROS). Pretreatment with NAC, which is a ROS inhibitor, blocked G1/S cell arrest and cyclin regulation induced by tetrandrine, implying that ROS generation plays an important role in tetrandrine-induced cell cycle arrest. Furthermore, a decreased phospho-Akt protein level after tetrandrine treatment was reversible with the removal of the intracellular ROS by NAC. Notably, overexpression of Akt decreased tetrandrine-induced G1/S arrest. Finally, we verified the antiangiogenic effects of tetrandrine in vivo in a liver cancer xenograft model in nude mice. In conclusion, tetrandrine inhibits EOMA cell growth through the ROS/Akt pathway, and it could be a promising compound for cancer therapy as an inhibitor of tumor vascular growth.
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Plasmon-driven surface catalysis in hybridized plasmonic gap modes.
Sci Rep
PUBLISHED: 08-28-2014
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Plasmon-driven surface catalytic (PDSC) reaction in Ag/Au nanoparticle monomer or dimer-film gaps are experimentally and theoretically investigated, using surface enhanced Raman scattering (SERS) and finite element method. The variation of SERS spectra in different nano gaps of nanoparticle-film systems indicated the PDSC reaction was largely depended on the number of nanoparticles. The higher Raman intensity of p,p'-dimercaptoazobenzene (DMAB) in dimer-film nanogap was because effective coupling of induced image charge on metal film in hybridized plasmonic gap mode, which was confirmed by the electric field distribution. Furthermore, the influence of material and wavelength was also studied to obtain the optimal experimental condition for best surface catalysis in hybridized plasmonic gap mode. Our studies in this common configuration of plasmonic nanostructure are of great significance not only in the field of catalysis on metal surface but also in other surface plasmon fields such as senor, photon detection, water splitting, etc.
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The human SRCAP chromatin remodeling complex promotes DNA-end resection.
Curr. Biol.
PUBLISHED: 08-28-2014
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Repair of DNA double-strand breaks (DSBs) by homologous recombination requires 5'-3' resection of the DSB ends. In vertebrates, DSB resection is initiated by the collaborative action of CtIP and the MRE11-RAD50-NBS1 (MRN) complex. However, how this process occurs within the context of chromatin is still not well understood.
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Estimated rates of retinal ganglion cell loss in glaucomatous eyes with and without optic disc hemorrhages.
PLoS ONE
PUBLISHED: 08-26-2014
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To evaluate whether optic disc hemorrhages are associated with faster rates of estimated retinal ganglion cell (RGC) loss in glaucoma.
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?-Opioid Receptor Attenuates A? Oligomers-Induced Neurotoxicity Through mTOR Signaling.
CNS Neurosci Ther
PUBLISHED: 08-21-2014
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?-opioid receptor (OPRM1) exerts many functions such as antinociception, neuroprotection, and hippocampal plasticity. A body of evidence has shown that OPRM1 activation could stimulate downstream effectors of mechanistic/mammalian target of rapamycin (mTOR). However, it is not clear whether OPRM1 protects neurons against ?-amyloid peptide (A?) neurotoxicity through mTOR signaling.
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Tunable SERS-Tags-Hidden Gold Nanorattles for Theranosis of Cancer Cells with Single Laser Beam.
Sci Rep
PUBLISHED: 08-19-2014
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With the use of gold nanostructures, photothermal therapy (PTT) of cancer has great advantages compared to conventional methods, such as noninvasive targeted destruction and easily operation. Generally speaking, respective diagnosis and therapy of tumor require at least two instruments, leading to incongruence of tumor borders between diagnosis and therapy. To tackle this problem, tunable SERS-tags-hidden gold nanorattles (STHGNRs) have been designed and developed here for theranosis of cancer with single laser beam. The surface plasma resonance peak of STHGNRs can be tuned from visible region to near-infrared region by controlling the cavity size and shell thickness. The outer shells not only improve the stability of the SERS reporters but also enhance the brightness by more than two order magnitude compared to gold nanoparticles. In vitro study, immuno STHGNRs can serve as theranosis agents simultaneously for sensitive and efficient theranosis of cancer cells.
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[Clinical analysis of 202 cases of extranodal NK/T-cell lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 08-19-2014
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This study was purposed to explore the therapeutic strategy and factors influencing prognosis through the analysis of clinical characteristics, genetic aberrations, treatment and prognosis of the patients with extranodal NK/T cell lymphoma (ENKTL). A total of 202 patients with ENKL from 2005-2013 were analyzed retrospectively in term of Ann Arbor stage, B symptoms, lactate dehydrogenase (LDH), international prognostic index (IPI), ?2-microglobulin and the expression of MYC,HXO11,BCL-2. The survival was analyzed using Kaplan-Meier method, and the COX regression model was employed for multivariate analysis. The results showed that the 5 year overall survival (OS) rate and event-free survival (EFS) rate were 61.9% and 53.9% respectively; chemoradiotherapy was apparently better than chemotherapy alone for OS and EFS; OS and EFS of the patients with BCL-2 expression were apparently better than patients without BCL-2 expression; multivariant analysis by COX regression showed that Ann Arbor stage and BCL-2 expression were independent prognostic factors for EFS/OS. It is concluded that chemoradiotherapy is better than chemotherapy alone for treatment of ENKL. Ann Arbor stage and BCL-2 expression are independent prognostic factors.
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Segmentation and quantification of blood vessels for OCT-based micro-angiograms using hybrid shape/intensity compounding.
Microvasc. Res.
PUBLISHED: 08-17-2014
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Optical coherence tomography (OCT) based microangiography is capable of visualizing 3D functional blood vessel networks within microcirculatory tissue beds in vivo. To provide the quantitative information of vasculature from the microangiograms such as vessel diameter and morphology, it is necessary to develop efficient vessel segmentation algorithms. In this paper, we propose to develop a hybrid Hessian/intensity based method to segment and quantify shape and diameter of the blood vessels innervating capillary beds that are imaged by functional OCT in vivo. The proposed method utilizes multi-scale Hessian filters to segment tubular structures such as blood vessels, but compounded by the intensity-based segmentation method to mitigate the limitations of Hessian filters' sensitivity to the selection of scale parameters. Such compounding segmentation scheme takes advantage of the morphological nature of Hessian filters while correcting for the scale parameter selection by intensity-based segmentation. The proposed algorithm is tested on a wound healing model and its performance of segmentation vessels is quantified by a publicly available manual segmentation dataset. We believe that this method will play an important role in the quantification of micro-angiograms for microcirculation research in ophthalmology and diagnosing retinal eye diseases involved with microcirculation.
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A cross-sectional analysis of the relationship between uric acid and coronary atherosclerosis in patients with suspected coronary artery disease in China.
BMC Cardiovasc Disord
PUBLISHED: 08-16-2014
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Although many studies have examined the relationship between uric acid (UA) and coronary artery disease (CAD), whether UA is an independent risk factor contributing to progression of CAD is still controversial. Whether UA plays a different role in different sexes is also unclear.
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Gracilaria lemaneiformis polysaccharide as integrin-targeting surface decorator of selenium nanoparticles to achieve enhanced anticancer efficacy.
ACS Appl Mater Interfaces
PUBLISHED: 08-08-2014
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The poor permeability of glioma parenchyma represents a major limit for antiglioblastoma drug delivery. Gracilaria lemaneiformis polysaccharide (GLP), which has a high binding affinity to ?v?3 integrin overexpressed in glioma cells, was employed in the present study to functionalize selenium nanoparticles (SeNPs) to achieve antiglioblastoma efficacy. GLP-SeNPs showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. In U87 glioma cell membrane, which has a high integrin expression level, GLP-SeNPs exhibited significantly higher cellular uptake than unmodified SeNPs. As expected, U87 cells exhibited a greater uptake of GLP-SeNPs than C6 cells with low integrin expression level. Furthermore, the internalization of GLP-SeNPs was inhibited by cyclo-(Arg-Gly-Asp-Phe-Lys) peptides, suggesting that cellular uptake into U87 cells and C6 cells occurred via ?v?3 integrin-mediated endocytosis. For U87 cells, the cytotoxicity of SeNPs decorated by GLP was enhanced significantly because of the induction of various apoptosis signaling pathways. Internalized GLP-SeNPs triggered intracellular reactive oxygen species downregulation. Therefore, p53, MAPKs, and AKT pathways were activated to advance cell apoptosis. These findings suggest that surface decoration of nanomaterials with GLP could be an efficient strategy for design and preparation of glioblastoma targeting nanodrugs.
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Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response.
Cell Rep
PUBLISHED: 08-07-2014
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Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1? (IL-1?). Although the dynamics of caspase-1 activation, IL-1? secretion, and cell death have been examined with bulk assays in population-level studies, they remain poorly understood at the single-cell level. In this study, we conducted single-cell imaging using a genetic fluorescence resonance energy transfer sensor that detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none (digital) activation at the single-cell level, with similar activation kinetics irrespective of the type of inflammasome or the intensity of the stimulus. Real-time concurrent detection of caspase-1 activation and IL-1? release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1? in a digital manner, which identified these macrophages as the main source of IL-1? within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases.
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Anti-TROP2 conjugated hollow gold nanospheres as a novel nanostructure for targeted photothermal destruction of cervical cancer cells.
Nanotechnology
PUBLISHED: 08-07-2014
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Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L(-1)) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). ?H2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.
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Treatment with lutein provides neuroprotection in mice subjected to transient cerebral ischemia.
J Asian Nat Prod Res
PUBLISHED: 08-01-2014
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Lutein is known to be a nonprovitamin A carotenoid found in broccoli and spinach. The aim of present study was to investigate whether lutein can protect brain against ischemic injury by reducing oxidative stress. Male ICR mice were randomly divided into five experimental groups: model group, sham group, lutein high, middle, and low-dose groups (30, 15, and 7.5 mg/kg). Mice were subjected to a 2-h middle cerebral artery occlusion followed by reperfusion for 22 h. The reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, antioxidant enzyme activities, malondialdehyde (MDA), and the carbonyl content in oxidatively modified proteins in brain tissue were determined with colorimetric method. The 8-hydroxy deoxyguanosine (8-OHdG) expression was measured by immunohistochemistry assay, and the neuron apoptosis was detected by TdT-mediated dUTP nick end labeling assay. Then, the neurological deficit scores were measured at last. Treatment of lutein significantly elevated the ratio of GSH/GSSG as well as activities of superoxide dismutase, glutathione peroxidase, and catalase and obviously decreased the contents of MDA, brain carbonyl, the expression of 8-OHdG, the number of apoptotic cells, and neurological deficit scores. Our results demonstrate that administration of lutein affords strong neuroprotective effect against transient cerebral ischemic injury and that the effect might be associated with its antioxidant property.
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Unusual presentation of duodenal plasmablastic lymphoma in an immunocompetent patient: A case report and literature review.
Oncol Lett
PUBLISHED: 07-25-2014
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Plasmablastic lymphoma (PBL) is a rare and recently described entity of large B-cell lymphoma. It predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients and exhibits a highly aggressive clinical behavior without effective treatment. Recently, sporadic cases describing PBL in extraoral locations of HIV-negative patients have been reported; frequently in patients with underlying immunosuppressive states. To develop the understanding of PBL, the current study reports the unusual presentation of duodenal PBL and reviews the pathogenesis, immunohistochemical features, clinical and differential diagnoses, as well as the treatment of PBL as described in previous studies. The case of a 75-year-old female with duodenal PBL without definite immunosuppression is presented in the current report. The tumor was composed of large B-cell-like cells, and was positive for cluster of differentiation 138 and melanoma ubiquitous mutated-1, with ~80% of the tumor cells positive for Ki-67. The features of the tumor were as follows: Extraoral location, HIV-negative, immunoglobulin M ?-type M protein expression, light chain restriction (monoclonal) and Epstein-Barr virus-encoded small RNA-negative, which are considered to be unusual for PBL. These unusual features complicate the differentiation of PBL from other plasma cell diseases. To the best of our knowledge, this is the first study to report a case of duodenal PBL in an immunocompetent patient. To date, the standard treatment of PBL remains elusive, however, the most commonly administered chemotherapy treatments are CHOP [intravenous cyclophosphamide (750 mg/m(2), day 1), intravenous doxorubicin (50 mg/m(2), day 1), intravenous vincristine (1.4 mg/m(2), day 1) and prednisone (100 mg, days 1-50)]-like regimens. The patient was administered two cycles of CHOP chemotherapy for 56 days, however, ultimately succumbed as a result of disease progression. Therefore, PBL represents a diagnostic and therapeutic challenge. PBL must be considered in the differential diagnosis of gastrointestinal tumors in daily practice, even in immunocompetent patients. Furthermore, CHOP does not appear to be an optimal treatment regimen and more intensive regimens are required.
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Major capsid reinforcement by a minor protein in herpesviruses and phage.
Nucleic Acids Res.
PUBLISHED: 07-22-2014
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Herpes simplex type 1 virus (HSV-1) and bacteriophage ? capsids undergo considerable structural changes during self-assembly and DNA packaging. The initial steps of viral capsid self-assembly require weak, non-covalent interactions between the capsid subunits to ensure free energy minimization and error-free assembly. In the final stages of DNA packaging, however, the internal genome pressure dramatically increases, requiring significant capsid strength to withstand high internal genome pressures of tens of atmospheres. Our data reveal that the loosely formed capsid structure is reinforced post-assembly by the minor capsid protein UL25 in HSV-1 and gpD in bacteriophage ?. Using atomic force microscopy nano-indentation analysis, we show that the capsid becomes stiffer upon binding of UL25 and gpD due to increased structural stability. At the same time the force required to break the capsid increases by ?70% for both herpes and phage. This demonstrates a universal and evolutionarily conserved function of the minor capsid protein: facilitating the retention of the pressurized viral genome in the capsid. Since all eight human herpesviruses have UL25 orthologs, this discovery offers new opportunities to interfere with herpes replication by disrupting the precise force balance between the encapsidated DNA and the capsid proteins crucial for viral replication.
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Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial.
Lancet Oncol.
PUBLISHED: 07-17-2014
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Multicentric Castleman's disease is a rare lymphoproliferative disorder driven by dysregulated production of interleukin 6. No randomised trials have been done to establish the best treatment for the disease. We assessed the safety and efficacy of siltuximab-a chimeric monoclonal antibody against interleukin 6-in HIV-negative patients with multicentric Castleman's disease.
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Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma.
Oncol. Rep.
PUBLISHED: 07-16-2014
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Progestin and adipoQ receptor family member III (PAQR3) is a regulator that negatively modulates the Ras/Raf/MEK/ERK signaling cascade and the GPCR G?? subunit signaling pathway. The role of PAQR3 in hepatocellular carcinoma (HCC) has not been elucidated. The present study investigated the expression of PAQR3 and its prognostic value in primary HCC patients. Furthermore, the functional aspects of PAQR3 were also studied using an in vitro cell model. PAQR3 expression was examined in paired HCC and adjacent noncancerous tissues using real-time quantitative RT-PCR (62 pairs) and western blotting (26 pairs). We also analyzed PAQR3 expression in 132 additional HCC samples by immunohistochemistry. The functional impact of PAQR3 on the proliferation and colony formation of an HCC cell line was analyzed by transfecting cells with a full-length PAQR3 expression vector or siRNA targeting PAQR3. The expression of PAQR3 was significantly decreased in the cancer tissues. Clinicopathological analyses showed that the expression of PAQR3 was significantly correlated with expression of serum ?-fetoprotein (AFP), mitotic count, tumor size, histological grade and recurrence. Notably, Kaplan-Meier survival curves revealed a correlation between decreased expression of PAQR3 and the poor prognosis of HCC patients. Multivariate analyses showed that PAQR3 expression is an independent prognostic marker for overall and disease-free survival of HCC patients. Furthermore, restoring PAQR3 expression in HCC cells significantly diminished Hep3B cell proliferation and colony formation. Silencing PAQR3 expression in hepatic normal cell line LO2 significantly enhanced cell growth. PAQR3 may play an important role in the progression of HCC and serve as a potential candidate for the targeted therapy of HCC.
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Comparative study of corneal endothelial cell damage after femtosecond laser assisted deep stromal dissection.
Biomed Res Int
PUBLISHED: 07-10-2014
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To find a relatively safe designed stromal bed thickness to avoid endothelial damage for lamellar keratoplasty with an Allegretto Wavelight FS200 femtosecond laser.
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Laboratory analyses of two explanted hydrophobic acrylic intraocular lenses.
Indian J Ophthalmol
PUBLISHED: 07-10-2014
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Two three-piece hydrophobic acrylic intraocular lenses (IOLs) were explanted from two patients at 7 and 9 years, respectively, after implantation, because of poor fundus visualisation and/or a clinically significant decrease in visual acuity related to their opacified IOLs. In addition to light microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy, confocal laser scanning microscopy was used for the first time to observe the explanted IOLs. The clinical aspect seemed to correspond to the phenomenon of surface light scattering, while laboratory analyses showed dense glistenings in the central layer of the IOL optic, which had no change next to the surface. Further studies on these phenomena are needed.
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Minimal incision access for pediatric and adult cochlear implantation.
Chin. Med. J.
PUBLISHED: 07-03-2014
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Cochlear implant surgery is widely practiced. Minimal incision cochlear implant surgery has been developed with the aims of reducing the impact of surgery on the patient and improving cosmesis while maintaining the low morbidity of conventional wider access approaches. This study aimed to assess the surgical technique and complication rate of minimal incision cochlear implantation (MICI) for children and adults.
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Clinical and pathological features of microscopic polyangiitis in 20 children.
J. Rheumatol.
PUBLISHED: 07-01-2014
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To explore the clinical and pathological features of microscopic polyangiitis (MPA) in children.
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SIVA1 directs the E3 ubiquitin ligase RAD18 for PCNA monoubiquitination.
J. Cell Biol.
PUBLISHED: 06-25-2014
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Translesion DNA synthesis (TLS) is a universal DNA damage tolerance mechanism conserved from yeast to mammals. A key event in the regulation of TLS is the monoubiquitination of proliferating cell nuclear antigen (PCNA). Extensive evidence indicates that the RAD6-RAD18 ubiquitin-conjugating/ligase complex specifically monoubiquitinates PCNA and regulates TLS repair. However, the mechanism by which the RAD6-RAD18 complex is targeted to PCNA has remained elusive. In this study, we used an affinity purification approach to isolate the PCNA-containing complex and have identified SIVA1 as a critical regulator of PCNA monoubiquitination. We show that SIVA1 constitutively interacts with PCNA via a highly conserved PCNA-interacting peptide motif. Knockdown of SIVA1 compromised RAD18-dependent PCNA monoubiquitination and Pol? focus formation, leading to elevated ultraviolet sensitivity and mutation. Furthermore, we demonstrate that SIVA1 interacts with RAD18 and serves as a molecular bridge between RAD18 and PCNA, thus targeting the E3 ligase activity of RAD18 onto PCNA. Collectively, our results provide evidence that the RAD18 E3 ligase requires an accessory protein for binding to its substrate PCNA.
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[Optimal cut-off value of phalangeal radiographic absorptiometry to identify osteoporosis in postmenopausal women].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 06-20-2014
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To study the optimal cut-off value of phalangeal radiographic absorptiometry (RA) to identify osteoporosis in postmenopausal women.
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Identi?cation of Multiple Constituents in Chinese Medicinal Prescription Shensong Yangxin Capsule by Ultra-Fast Liquid Chromatography Combined with Quadrupole Time-of-Flight Mass Spectrometry.
J Chromatogr Sci
PUBLISHED: 05-30-2014
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A practical method using ultra-fast liquid chromatography in tandem with quadrupole time-of-?ight mass spectrometry combined with dynamic background subtraction technology was developed for the rapid separation and identi?cation of the complicated constituents in the Shensong Yangxin capsule (SSYX). The chromatographic separation was performed on a C18 column (2.1 × 100 mm, 2.6 ?m) with a gradient elution program using methanol and 0.1% formic acid aqueous solution as the mobile phase at a ?ow rate of 0.4 mL min(-1). Accurate mass measurements of the molecular ions in the full scan and the characteristic fragment ions triggered by information-dependent acquisition provided reliable identi?cation criteria. Thus, 99 compounds, including saponins, phenolic acids, tanshinones, lignans, terpenoids, alkaloids and flavonoids, were unambiguously or tentatively identi?ed in 40 min by comparing their retention times and accurate mass measurements for each molecular ion and its subsequent fragment ions with those of authentic standards or literature data. Simultaneously, all the compounds were further assigned to the individual raw materials. In conclusion, these results will provide a basis for quality control and further study of SSYX, and the proposed technique based on high-resolution mass spectrometry would be expected to be adaptable to the analysis of complicated constituents in various complex matrices.
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Analysis of CEA expression and EGFR mutation status in non-small cell lung cancers.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-30-2014
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The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21 may have an important relationship with tumor cell sensitivity to EGFR -TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC).
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Methionine Oxidation Accelerates the Aggregation and Enhances the Neurotoxicity of the D178N Variant of the Human Prion Protein.
Biochim. Biophys. Acta
PUBLISHED: 05-27-2014
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The D178N mutation of the prion protein (PrP) results in the hereditary prion disease fatal familial insomnia (FFI). Little is known regarding the effects of methionine oxidation on the pathogenesis of D178N-associated FFI. In the present study, we found that the D178N variant was more susceptible to oxidation than wild-type PrP, as indicated by reverse-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry (MS) analysis. Circular dichroism (CD), differential scanning calorimetry (DSC), thioflavin T (ThT) binding assay studies demonstrated that methionine oxidation decreased the structural stability of the D178N variant, and the oxidized D178N variant exhibited a greater propensity to form ?-sheet-rich oligomers and aggregates. Moreover, these aggregates of oxidized D178N PrP were more resistant to proteinase K (PK) digestion. Additionally, using fluorescence confocal microscopy, we detected a high degree of aggregation in D178N-transfected Neuro-2a (N2a) cells after treatment with hydrogen peroxide (H2O2). Furthermore, the oxidation and consequent aggregation of the D178N variant induced greater apoptosis of N2a cells, as monitored using flow cytometry. Collectively, these observations suggest that methionine oxidation accelerates the aggregation and enhances the neurotoxicity of the D178N variant, possibly providing direct evidence to link the pathogenesis of D178N-associated FFI with methionine oxidation.
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C1q nephropathy in an old woman with acute renal failure: a case report and literature review.
Ren Fail
PUBLISHED: 05-21-2014
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Reports on the clinical entity of C1q nephropathy have focused on older children and young adult, data on old people are rare. In this report, we would introduce a 77-year-old woman who was diagnosed as C1q nephropathy by means of electron microscopic and immunofluorescence examination. Facial and lower extremity edema was the main reason for her to go for medical treatment, and she developed into acute renal failure within 5 d. Complete remission was observed after hemodialysis and steroid drugs treatments.
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Effect of Antiviral Prophylaxis Strategy for Chemotherapy-Associated Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients with Hepatitis B Virus Infection: A Retrospective Cohort Study.
Indian J Hematol Blood Transfus
PUBLISHED: 05-20-2014
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Recent data indicates that nucleoside/nucleotide analogue (NUC) is effective in preventing and controlling hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the ideal antiviral agent and optimal application protocol still needs to be determined. Meanwhile, it is uncertain whether those with past HBV infection require antiviral prophylaxis during chemotherapy. This report retrospectively analyzed non-Hodgkin's lymphoma (NHL) patients seen from January, 2004 to June, 2009 in West China Hospital. We found that the prevalence of chronic HBV infection in our NHL patients was 20.7 % while that of past HBV infection was 21.05 %. Compared with the high rate (25.6 %) of HBV reactivation in patients with chronic HBV infection, none of those with past HBV infection in fact had occult HBV infection thus none experienced reactivation. Of the 82 patients with chronic HBV infection who received chemotherapy, antiviral prophylaxis could significantly reduce the incidence of HBV reactivation (5.0 vs. 45.2 % in the control group) and the incidence of liver function damage (32.5 vs. 73.8 % in the control group). The results of the current study confirmed previous reports that prophylactic NUCs administration can effectively prevent HBV reactivation and significantly reduce the incidence of HBV reactivation especially for patients receiving rituximab-containing regimens. Due to the fact that none of individuals who had past HBV infection developed HBV reactivation reported in our study, antiviral prophylaxis may not be required for patients with past HBV infection. Close observation of alanine aminotransferase and HBV-DNA contributes to early diagnosis and timely treatment of HBV reactivation.
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The Genomic DNA Immobilization on Microcrystalline Cellulose and its Application to Separate DNA-Binding Proteins from Kumquat (Fortunella margarita Swingle).
Protein Pept. Lett.
PUBLISHED: 05-15-2014
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A method of immobilizing genomic DNA on microcrystalline cellulose was described to isolate DNA-binding proteins. At first, DNA fragments were prepared by sonication and immobilized on cellulose phase. After the immobilization, DNA duplex formation was done. Using this microcrystalline cellulose affinity chromatography technique, DNA-binding proteins from kumquat (Fortunella margarita Swingle) leaf samples were isolated and then analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS). LC-MS/MS analysis showed that twenty-eight kinds of protein mainly including histones, protein-synthetic proteins and other DNA-binding proteins were identified. The identification list consists with the results in previous research on DNA-binding proteins isolation. It further suggests that the technique developed in this study can be applied to the effective isolation of DNA-binding proteins.
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Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors.
ACS Med Chem Lett
PUBLISHED: 05-08-2014
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Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that 14c was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-?, and RET. Furthermore, 14c effectively blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a promising candidate for the treatment of cancer.
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Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix.
J. Mol. Cell. Cardiol.
PUBLISHED: 04-23-2014
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The translation of cell-based therapies for ischemic tissue repair remains limited by several factors, including poor cell survival and limited target site retention. Advances in nanotechnology enable the development of specifically designed delivery matrices to address these limitations and thereby improve the efficacy of cell-based therapies. Given the relevance of integrin signaling for cellular homeostasis, we developed an injectable, bioactive peptide-based nanofiber matrix that presents an integrin-binding epitope derived from fibronectin, and evaluated its feasibility as a supportive artificial matrix for bone marrow-derived pro-angiogenic cells (BMPACs) used as a therapy in ischemic tissue repair. Incubation of BMPACs with these peptide nanofibers in vitro significantly attenuated apoptosis while enhancing proliferation and adhesion. Pro-angiogenic function was enhanced, as cells readily formed tubes. These effects were, in part, mediated via p38, and p44/p42 MAP kinases, which are downstream pathways of focal adhesion kinase. In a murine model of hind limb ischemia, an intramuscular injection of BMPACs within this bioactive peptide nanofiber matrix resulted in greater retention of cells, enhanced capillary density, increased limb perfusion, reduced necrosis/amputation, and preserved function of the ischemic limb compared to treatment with cells alone. This self-assembling, bioactive peptide nanofiber matrix presenting an integrin-binding domain of fibronectin improves regenerative efficacy of cell-based strategies in ischemic tissue by enhancing cell survival, retention, and reparative functions.
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Novel Mutation of OCRL1 in Lowe Syndrome.
Indian J Pediatr
PUBLISHED: 04-04-2014
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Lowe syndrome is a rare, X-linked recessive genetic disease with multi-organ involvement. The pathogenic gene is OCRL1. The authors analyzed the OCRL1 mutation and summarized the clinical features of a Chinese child with Lowe syndrome. The patient is a 3 year 7 mo-old boy. He presented with hypotonia at birth and gradually presented with bilateral congenital cataracts, psychomotor retardation, hypophosphatemic rickets and renal tubular function disorder. Sequence analysis of OCRL1 revealed a novel insertion mutation, c.2367insA (p. Ala813X), in exon 22. This mutation was suspected to cause a premature stop codon of OCRL1 and truncation of the OCRL1 protein. His mother, who carried a heterozygous mutation, had no sign of abnormality.
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A MicroRNA Profile in Fmr1 Knockout Mice Reveals MicroRNA Expression Alterations with Possible Roles in Fragile X Syndrome.
Mol. Neurobiol.
PUBLISHED: 03-25-2014
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Fragile X syndrome (FXS), a common form of inherited mental retardation, is caused by a loss of expression of the fragile X mental retardation protein (FMRP). FMRP is involved in brain functions by interacting with mRNAs and microRNAs (miRNAs) that selectively control gene expression at translational level. However, little is known about the role of FMRP in regulating miRNA expression. Here, we found a development-dependant dynamic expression of Fmr1 gene (encoding FMRP) in mouse hippocampus with a small peak at postnatal day 7 (P7). MiRNA microarray analysis showed that the levels of 38 miRNAs showed a significant increase with about 15?~?250-folds and the levels of 26 miRNAs showed a significant decrease with only about 2?~?4-folds in the hippocampus of P7 Fmr1 knockout (KO) mice. The qRT-PCR assay showed that nine of the most increased miRNAs (>100-folds in microarrays) increased about 40?~?70-folds and their pre-miRNAs increased about 5?~?10-folds, but no significant difference in their pri-miRNA levels was observed, suggesting that the alterations of partial miRNAs are an indirect consequence of FMRP lacking. We further demonstrated that a set of protein-coding mRNAs, potentially targeted by the nine miRNAs, were down-regulated in the hippocampus of Fmr1 KO mice. Finally, luciferase assays demonstrated that miR-34b, miR-340, and miR-148a could down-regulate the reporter gene expression by interacting with the Met 3' UTR. Taken together, these findings suggest that the miRNA expression alterations resulted from the absence of FMRP might contribute to molecular pathology of FXS.
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Hyperpolization-activated Ca(2+) channels in guard cell plasma membrane are involved in extracellular ATP-promoted stomatal opening in Vicia faba.
J. Plant Physiol.
PUBLISHED: 03-07-2014
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Extracellular ATP (eATP) plays essential roles in plant growth, development, and stress tolerance. Extracellular ATP-regulated stomatal movement of Arabidopsis thaliana has been reported. Here, ATP was found to promote stomatal opening of Vicia faba in a dose-dependent manner. Three weakly hydrolysable ATP analogs (adenosine 5'-O-(3-thio) triphosphate (ATP?S), 3'-O-(4-benzoyl) benzoyl adenosine 5'-triphosphate (Bz-ATP) and 2-methylthio-adenosine 5'-triphosphate (2meATP)) showed similar effects, indicating that ATP acts as a signal molecule rather than an energy charger. ADP promoted stomatal opening, while AMP and adenosine did not affect stomatal movement. An ATP-promoted stomatal opening was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI), the reductant dithiothreitol (DTT) or the Ca(2+) channel blockers GdCl3 and LaCl3. A hyperpolarization-activated Ca(2+) channel was detected in plasma membrane of guard cell protoplast. Extracellular ATP and weakly hydrolyzable ATP analogs activated this Ca(2+) channel significantly. Extracellular ATP-promoted Ca(2+) channel activation was markedly inhibited by DPI or DTT. These results indicated that eATP may promote stomatal opening via reactive oxygen species that regulate guard cell plasma membrane Ca(2+) channels.
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Effects of phenanthrene on seed germination and some physiological activities of wheat seedling.
C. R. Biol.
PUBLISHED: 03-04-2014
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Polycyclic aromatic hydrocarbons (PAHs) are one of the highly persistent organic pollutants, and they are toxic to plants and other living organisms, including human beings. To analyze the response of higher plant to PAHs, we investigated the effects of phenanthrene (PHE) on seed germination and various physiological changes of wheat seedlings. Specifically, we investigated growth, chlorophyll content, lipid peroxidation (LPO), activities of antioxidant enzymes and H2O2 accumulation. The results showed that PHE inhibited seed germination, affected the growth and chlorophyll level of wheat seedlings. Furthermore, PHE elevated the levels of LPO and induced H2O2 accumulation in leaf tissues in a dose-dependent manner, accompanied by the changes in the antioxidant status. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), displayed a decreasing trend with the increasing of PHE concentration. The results indicated that PHE could exert oxidative damages in the early development stage of wheat and the harmfulness occurred mainly in samples with higher concentrations of PHE.
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Quality control of homologous recombination.
Cell. Mol. Life Sci.
PUBLISHED: 02-28-2014
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Exogenous and endogenous genotoxic agents, such as ionizing radiation and numerous chemical agents, cause DNA double-strand breaks (DSBs), which are highly toxic and lead to genomic instability or tumorigenesis if not repaired accurately and efficiently. Cells have over evolutionary time developed certain repair mechanisms in response to DSBs to maintain genomic integrity. Major DSB repair mechanisms include non-homologous end joining and homologous recombination (HR). Using sister homologues as templates, HR is a high-fidelity repair pathway that can rejoin DSBs without introducing mutations. However, HR execution without appropriate guarding may lead to more severe gross genome rearrangements. Here we review current knowledge regarding the factors and mechanisms required for accomplishment of accurate HR.
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Ethylparaben affects lifespan, fecundity, and the expression levels of ERR, EcR and YPR in Drosophila melanogaster.
J. Insect Physiol.
PUBLISHED: 02-26-2014
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Parabens, which mainly include methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), are widely used as cosmetic and food preservatives. Although these chemicals, when used as preservatives, are thought to be safe for humans, many studies have demonstrated that they have estrogenic effects, and can affect the normal development and functions of the reproductive systems in a number of animal species. By treating fruit flies (Drosophila melanogaster) with EP, here we show that lower concentration of EP (0.02%) enhanced fertility while higher concentration of EP (0.10% and 0.20%) shortened the lifespan and reduced the fecundity of fruit flies. When we analyzed the expression levels of the estrogen-related receptor gene (ERR), ecdysone receptor gene (EcR) and Yolk protein receptor gene (YPR) from control and EP-treated fruit flies by using quantitative real-time PCR, we found that the expression levels of all three genes were significantly changed by EP treatment, and that female fruit flies are more sensitive to EP than males. Our data suggests that the estrogenic and the toxic effects of EP to fruit flies may have a molecular basis through the hormonal effect of EP.
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A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas.
Neoplasia
PUBLISHED: 02-24-2014
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The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM) kinases (PIM-1, PIM-2, and PIM-3) are serine/threonine kinases that are involved in a number of signaling pathways important to cancer cells. PIM kinases act in downstream effector functions as inhibitors of apoptosis and as positive regulators of G1-S phase progression through the cell cycle. PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. Overexpression of one or more PIM family members in patient tumors frequently correlates with poor prognosis. The aim of this investigation was to evaluate PIM expression in low- and high-grade urothelial carcinoma and to assess the role PIM function in disease progression and their potential to serve as molecular targets for therapy. One hundred thirty-seven cases of urothelial carcinoma were included in this study of surgical biopsy and resection specimens. High levels of expression of all three PIM family members were observed in both noninvasive and invasive urothelial carcinomas. The second-generation PIM inhibitor, TP-3654, displays submicromolar activity in pharmacodynamic biomarker modulation, cell proliferation studies, and colony formation assays using the UM-UC-3 bladder cancer cell line. TP-3654 displays favorable human ether-à-go-go-related gene and cytochrome P450 inhibition profiles compared with the first-generation PIM inhibitor, SGI-1776, and exhibits oral bioavailability. In vivo xenograft studies using a bladder cancer cell line show that PIM kinase inhibition can reduce tumor growth, suggesting that PIM kinase inhibitors may be active in human urothelial carcinomas.
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Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease.
J. Clin. Invest.
PUBLISHED: 02-14-2014
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Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2-/- mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease.
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pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate.
Carbohydr Polym
PUBLISHED: 02-13-2014
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A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160 nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 ?M GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%.
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Elucidation and biological activities of a new polysaccharide from cultured Cordyceps militaris.
Carbohydr Polym
PUBLISHED: 02-11-2014
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A novel low-molecular-weight polysaccharide (CMP-1) with antioxidant, immunostimulatory and antitumor activities was isolated from the cultured Cordyceps militaris. The structure of CMP-1 was elucidated by a combination of physicochemical and instrumental analyses, and its average molecular weight was 4.3 kDa. The backbone of CMP-1 was composed of (1 ? 4)-linked ?-D-glucopyranosyl, (1 ? 6)-linked ?-D-glucopyranosyl and (1 ? 4)-linked ?-D-glucopyranosyl residues which branched at O-6. The branches consisted of (1 ? 3)-linked ?-L-rhamnopyranosyl terminated with (1 ? )-linked ?-D-glucopyranosyl residues. The ultrastructure of CMP-1 was further investigated by scanning electron microscope (SEM). The antioxidant assays showed that CMP-1 exhibited free radical-scavenging effects, ferrous ions-chelating ability and reducing power. In vitro test revealed that CMP-1 could significantly stimulate the mouse splenocyte proliferation. The cytotoxicity assay showed that CMP-1 inhibited the proliferation of HT-29, HeLa, HepG2 and K562 cells, with the IC50 values of 137.66, 162.59, 176.29 and 364.01 ?g/mL, respectively.
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Effect of the 2010 task force criteria on reclassification of cardiovascular magnetic resonance criteria for arrhythmogenic right ventricular cardiomyopathy.
J Cardiovasc Magn Reson
PUBLISHED: 02-10-2014
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We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation.
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Human Organic Cation Transporter 1 Protein Levels of Granulocytes Can Optimize Imatinib Therapy in Patients with Chronic Myeloid Leukemia.
Acta Haematol.
PUBLISHED: 02-05-2014
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The human organic cation transporter 1 (hOCT1) is the major active influx protein responsible for the transport of imatinib mesylate (IM) into cells. Previous studies have used (14)C-labeled IM to demonstrate a link between chronic myeloid leukemia (CML) molecular response and hOCT1 activity. However, this method is not convenient in routine clinical practice. Hence, we detected hOCT1 protein expression levels (Choct1) of peripheral blood in CML patients and evaluated the relationship between Choct1 and IM response. A total of 83 patients who were diagnosed with Philadelphia chromosome (Ph)-positive CML with IM therapy and 31 heathy donors were collected. Choct1 were detected by indirect immunofluorescent flow cytometry. The study showed that Choct1 expression was higher in healthy donors than in CML patients (n = 31, 9.11 ± 6.04; n = 35, 5.60 ± 3.74; p = 0.005). Both Choct1 and plasma IM trough concentration (Cmin, n = 83) were significantly higher in patients with major molecular response (MMR) than those without (p = 0.011; p = 0.001, respectively), and patients with Choct1 ?4.745 and Cmin ?1,385 ng/ml were more likely to achieve MMR. hOCT1 expression levels measured using flow cytometry is a convenient and clinically available technique. The hOCT1 expression level can be an important predictor in CML patients treated with IM. © 2014 S. Karger AG, Basel.
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A novel transgenic mouse model of Chinese Charcot-Marie-Tooth disease type 2L.
Neural Regen Res
PUBLISHED: 01-20-2014
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We previously found that the K141N mutation in heat shock protein B8 (HSPB8) was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this (K141N)HSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing (K141N)HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the (K141N)HSPB8 gene and widespread expression in tissues of the transgenic mice. The (K141N)HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in (K141N)HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the (K141N)HSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.
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High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial.
J. Am. Coll. Cardiol.
PUBLISHED: 01-12-2014
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It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain.
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Recombinant adenovirus-mediated overexpression of 3?-hydroxysteroid-?24 reductase.
Neural Regen Res
PUBLISHED: 01-10-2014
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3?-Hydroxysteroid-?24 reductase (DHCR24) is a multifunctional enzyme that localizes to the endoplasmic reticulum and has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid ? deposition. The present study aimed to construct two recombinant adenoviruses driving DHCR24 expression specifically in neurons. Two SYN1 promoter DNA fragments were obtained from human (h) and rat (r). Recombinant Ad-r(h)SYN1-DHCR24 was transfected into AD-293, N2A (mouse neuroblastoma), and MIN6 (mouse pancreatic carcinoma) cells. Western blot analysis showed DHCR24 was specially expressed in 293 and N2A cells, but no specific band was found in MIN6 cells. This demonstrates that the recombinant adenoviruses successfully express DHCR24, and no expression is observed in non-neuronal cells. TUNEL assay results showed apoptosis was inhibited in adenovirus-transfected neurons. Detecting reactive oxygen species by immunofluorescence, we found that adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species. Our findings show that the recombinant DHCR24 adenoviruses induce neuron-specific DHCR24 expression, and thereby lay the foundation for further studies on DHCR24 gene therapy for Alzheimer's disease.
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A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3).
Bone
PUBLISHED: 01-09-2014
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MicroRNAs (miRNAs) involve in the regulation of a wide range of physiological processes. Recent studies suggested that miRNAs might play a role in osteoclast differentiation. Here, we identify a new miRNA (miR-9718) in primary mouse osteoclasts that promotes osteoclast differentiation by repressing protein inhibitor of activated STAT3 (PIAS3) at the post-transcriptional level. MiR-9718 was found to be transcribed during osteoclastogenesis, which was induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-?B ligand (RANKL). Overexpression of miR-9718 in RAW 264.7 cells promoted M-CSF and RANKL-induced osteoclastogenesis, whereas inhibition of miR-9718 attenuated it. PIAS3 was predicted to be a target of miR-9718. Luciferase reporter gene validated the prediction. Transfection of pre-miR-9718 in RAW 264.7 cells induced by both M-CSF and RANKL inhibited expression of PIAS3 protein, while the mRNA levels of PIAS3 were not attenuated. In vivo, our study showed that silencing of miR-9718 using a specific antagomir inhibited bone resorption and increased bone mass in mice receiving ovariectomy (OVX) and in sham-operated control mice. Thus, our study showed that miR-9718 played an important role in osteoclast differentiation via targeting PIAS3 both in vitro and in vivo.
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Ginsenoside 20(S)-Rg3 targets HIF-1? to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT) is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S)-Rg3, which reduces the expression of hypoxia-inducible factor 1? (HIF-1?) by activating the ubiquitin-proteasome pathway to promote HIF-1? degradation. A decrease in HIF-1? in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S)-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy.
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Quantitative evaluation of the reticuloendothelial system function with dynamic MRI.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the reticuloendothelial system (RES) function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO) using dynamic magnetic resonance imaging (MRI) with two-compartment pharmacokinetic modeling.
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CD271+ osteosarcoma cells display stem-like properties.
PLoS ONE
PUBLISHED: 01-01-2014
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Cancer stem cell (CSC) theory has been proposed and verified in many cancers. The existence of osteosarcoma CSCs has been confirmed for many years and multiple surface markers have been employed to identify them. In this study, we identified CD271(+) subpopulation of osteosarcoma displaying stem-like properties. CD271, known as the neural crest nerve growth factor receptor, is the marker of bone marrow mesenchymal stem cells (MSCs) and human melanoma-initiating cells. We discovered that CD271 was expressed differentially in diverse types of human osteosarcoma and stabilized cell lines. CD271(+) osteosarcoma cells displayed most of the properties of CSC, such as self-renewal, differentiation, drug resistance and tumorigenicity in vivo. Nanog, Oct3/4, STAT3, DNA-PKcs, Bcl-2 and ABCG2 were more expressed in CD271(+) cells compared with CD271- cells. Our study supported the osteosarcoma CSC hypothesis and, to a certain extent, revealed one of the possible mechanisms involved in maintaining CSCs properties.
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[Analysis on characteristics of meridians and acupoints of acupuncture and moxibustion for diarrhea in ancient based on data mining].
Zhongguo Zhen Jiu
PUBLISHED: 12-31-2013
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The data in literature of acupuncture and moxibustion on treatment of diarrhea from pre-Qin period to Qing dynasty was collected to establish prescription database and characteristics and rules of ancient acupuncture and moxibustion for diarrhea were analyzed with data mining technology. Totally 235 papers were collected and 76 acupoints were involved with 439 times of selection. The number and times of special acupoints were 72.37% (55/76) and 76.99% (338/439), respectively, which was more seen in front-mu acupoint and back-shu acupoint. The acupoints were distributed among 11 meridians. Moxibustion was applied in 53 papers while combination of acupuncture and moxibustion was used in 1 literature. As a result, acupuncture and moxibustion for diarrhea in ancient pay much attention on acupoint in back and abdomen, in which Tianshu (ST 25), Shen-que (CV 8), Guanyuan (CV 4) and Dachangshu (BL 25) were the most frequently used. The compatibility of front-mu acupoint and back-shu acupoint was very common. Selection of special acupoint was dominant. Besides crossing points that has the most intersection of meridian qi in the back and abdomen, acupoints below the elbow and knee joints, such as five-shu points, source point, luo-connecting point, eight confluence point and lower he-sea point were also taken into account. As for compatibility of special acupoints, the supportive degree between back-shu acupoint and confluence points or front-mu acupoint was the highest; the selections of meridians mainly were Bladder Meridian, Conception Vessel and Spleen Meridian; and application of moxibustion was highly valued. In conclusion, it is feasible to apply data mining technology to the clinical literature research of ancient acupuncture and moxibustion, which can provide evidence for summary of the traditional classical theory.
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Zinc Finger Protein 451 is a novel Smad corepressor in Transforming Growth Factor-? signaling.
J. Biol. Chem.
PUBLISHED: 12-09-2013
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Zinc Figure Protein 451 (ZNF451) is a transcriptional cofactor localized to promyelocytic leukemia (PML) bodies. Here, we present evidence demonstrating that ZNF451 physically interacts with Smad3/4 and functionally inhibits TGF-? signaling. Increased expression of ZNF451 attenuates TGF-?-induced growth inhibitory and gene transcriptional responses, whereas depletion of ZNF451 enhances TGF-? responses. Mechanistically, ZNF451 blocks the ability of Smad3/4 to recruit p300 in response to TGF-?, which causes reduction of histone H3K9 acetylation on the promoters of TGF-? target genes. Taken together, ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-? signaling.
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[Quality improvement on acupuncture intervention report: application and perfection of STRICTA].
Zhongguo Zhen Jiu
PUBLISHED: 12-05-2013
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ABSTRACT Clinical application of standards for reporting interventions in clinical trials of acupuncture (STRICTA) is introduced in this article, and improving opinions are proposed as well. STRICTA has already been extensively applied in designation of acupuncture clinical trials, composition of articles and quality assessment of acupuncture literature. According to the present version of STRICTA, it is suggested that items such as "standards and methods on acupoint selection and location", "angle and direction of needle insertion" and "whether the subjects ever have been acupunctured" should be further perfected. Individuated treat protocols which is highlighted on treatment according to differentiation of syndromes according to different opportunities and stages of diseases should be promoted so as to give better expression to the characteristics of Chinese medicine and enhance the clinical value of the relative literature.
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Using (15)n, (17)o, and (18)o to determine nitrate sources in the yellow river, china.
Environ. Sci. Technol.
PUBLISHED: 11-19-2013
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Many previous studies have used ?(15)N and ?(18)O of nitrate (?(15)NNO3 and ?(18)ONO3) to determine the nitrate sources in rivers but were subject to substantial uncertainties and limitations, especially associated with evaluating the atmospheric contribution. The ?(17)O of nitrate (?(17)ONO3) has been suggested as an unambiguous tracer of atmospheric NO3(-) and may serve as an additional nitrate source constraint. In the present study, triple nitrate isotopes (?(15)NNO3, ?(17)ONO3, and ?(18)ONO3) were used for the first time to assess the sources and sinks of nitrate in the Yellow River (YR) basin, which is the second longest river in China. Results showed that the ?(17)ONO3 of the water from the YR ranged from 0‰ to 1.6‰ during two normal-water seasons. This suggested that unprocessed atmospheric nitrate accounted for 0-7% of the total nitrate in the YR. The corrected ?(15)NNO3 and ?(18)ONO3 values with atmospheric imprints being removed indicated that the main terrestrial sources of nitrate were sewage/manure effluents in the upstream of the YR and manure/sewage effluents and ammonium/urea-containing fertilizer in the middle and lower reaches which made comparable contributions to the nitrate. In addition, there was a significant positive relationship between ?(15)NNO3 and ?(18)ONO3 values of river water (p < 0.01) which may signal the presence of denitrification. This study indicates that the triple nitrate isotope method is useful for assessing the nitrate sources in rivers, especially for the measurements of atmospheric nitrate contribution.
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[Effects of genetic variations of cholesteryl ester transfer protein on atorvastatin treatment efficacy and clinical outcomes in patients with coronary artery disease].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-31-2013
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To explore the polymorphism of cholesteryl ester transfer protein (CETP) gene -629C/A among the coronary heart disease (CHD) Han population of Tianjin area and evaluate the influences of genetic factors on atorvastatin therapeutic effects and clinical outcomes in pharmacogenomics and provide theoretical rationales for individualized treatment.
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Genetic association between p53 codon 72 polymorphism and risk of cutaneous squamous cell carcinoma.
Tumour Biol.
PUBLISHED: 10-23-2013
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This study was designed to obtain a conclusive result about the relevance of p53 codon 72 polymorphism to the risk of cutaneous squamous cell carcinoma (SCC). We performed an updated meta-analysis of 3,792 subjects (1,349 cancer cases and 2,443 controls) to summarize the data available for p53 codon 72 polymorphism and SCC risk. The association was estimated by odds ratios (ORs) with 95 % confidence intervals (CIs). The meta-analysis showed no statistical significance for SCC risk associated with any of the genetic models of p53 codon 72 polymorphism. The analyses by ethnic subgroup also failed to produce significant associations. This study suggests that p53 codon 72 polymorphism does not appear to represent a significant susceptibility factor for SCC in Caucasians.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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