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Find video protocols related to scientific articles indexed in Pubmed.
Status and Determinants of Health Literacy among Adolescents in Guangdong, China.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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Previous studies for non-communicable disease cotrol, including cancer, have mostly relied on health literacy in adults. However, limited studies are available for adolescents. This study aimed to assess the status and determinants of health literacy in in-school adolescents in Guangdong, China.
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Macular Measurements Using Spectral-Domain Optical Coherence Tomography in Chinese Myopic Children.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 10-16-2014
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To evaluate the macular thickness/volume in Chinese myopic children using spectral-domain optical coherence tomography (SD-OCT) and assess its correlation with spherical equivalent refraction (SER), axial length (AL), sex, and age.
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Investigation of the therapeutic effectiveness of active components in Sini decoction by a comprehensive GC/LC-MS based metabolomics and network pharmacology approaches.
Mol Biosyst
PUBLISHED: 10-16-2014
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As a classical formula, Sini decoction (SND) has been fully proved to be clinically effective in treating doxorubicin (DOX)-induced cardiomyopathy. Current chemomics and pharmacology proved that the total alkaloids (TA), total gingerols (TG), total flavones and total saponins (TFS) are the major active ingredients of Aconitum carmichaelii, Zingiber officinale and Glycyrrhiza uralensis in SND respectively. Our animal experiments in this study demonstrated that the above active ingredients (TAGFS) were more effective than formulas formed by any one or two of the three individual components and nearly the same as SND. However, very little is known about the action mechanisms of TAGFS. Thus, this study aimed to use for the first time the combination of GC/LC-MS based metabolomics and network pharmacology for solving this problem. By metabolomics, it was found that TAGFS worked by regulating six primary pathways. Then, network pharmacology was applied to search for specific targets. 17 potential cardiovascular related targets were found through molecular docking, 11 of which were identified by references, which demonstrated the therapeutic effectiveness of TAGFS using network pharmacology. Among these targets, four targets, including phosphoinositide 3-kinase gamma, insulin receptor, ornithine aminotransferase and glucokinase, were involved in the TAGFS regulated pathways. Moreover, phosphoinositide 3-kinase gamma, insulin receptor and glucokinase were proved to be targets of active components in SND. In addition, our data indicated TA as the principal ingredient in the SND formula, whereas TG and TFS served as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae with the combination use of metabolomics and network pharmacology may be a good strategy.
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Similarity Learning of Manifold Data.
IEEE Trans Cybern
PUBLISHED: 10-15-2014
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Without constructing adjacency graph for neighborhood, we propose a method to learn similarity among sample points of manifold in Laplacian embedding (LE) based on adding constraints of linear reconstruction and least absolute shrinkage and selection operator type minimization. Two algorithms and corresponding analyses are presented to learn similarity for mixsignedand nonnegative data respectively. The similarity learning method is further extended to kernel spaces. The experiments on both synthetic and real world benchmark data sets demonstrate that the proposed LE with new similarity has better visualization and achieves higher accuracy in classification.
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[Macular thickness in unilateral amblyopia as measured by optical coherence tomography: a meta analysis].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 10-15-2014
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To offer a clue for the etiology of amblyopia by systematically comparing the macular thickness measured by optical coherence tomography (OCT) between the amblyopic eye and the fellow normal eye in patients with unilateral amblyopia.
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Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.
Medicine (Baltimore)
PUBLISHED: 10-14-2014
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Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children.This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding.We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives.Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.
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Effects of crystal orientation on cellulose nanocrystals-cellulose acetate nanocomposite fibers prepared by dry spinning.
Biomacromolecules
PUBLISHED: 09-30-2014
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This work presents the development of dry spun cellulose acetate (CA) fibers using cellulose nanocrystals (CNCs) as reinforcements. Increasing amounts of CNCs were dispersed into CA fibers in efforts to improve the tensile strength and elastic modulus of the fiber. A systematic characterization of dispersion of CNCs in the polymer fiber and their effect on the nanocomposites' mechanical properties is described. The birefringence, thermal properties, and degree of CNC orientation of the fibers are discussed. 2D X-ray diffraction was used to quantify the degree of CNC alignment within the fibers. It is shown that the CNC alignment directly correlates to the mechanical properties of the composite. Maximum improvements of 137% in tensile strength and 637% in elastic modulus were achieved. Empirical micromechanical models Halpin-Tsai equation and an orientation modified Cox model were used to predict the fiber performance and compared with experimental results.
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[Adeno-associated vector mediated intracellular biological activity of human Kallistatin].
Yao Xue Xue Bao
PUBLISHED: 09-20-2014
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Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
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Epigenetic control of dendritic cell development and fate determination of common myeloid progenitor by Mysm1.
Blood
PUBLISHED: 09-12-2014
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The mechanisms controlling the development of dendritic cells (DCs) remain incompletely understood. Using an Mysm1 knockout (Mysm1(-/-)) mouse model, we identified the histone H2A deubiquitinase Mysm1, as a critical regulator in DC differentiation. Mysm1(-/-) mice showed a global reduction of DCs in lymphoid organs, whereas development of granulocytes and macrophages were not severely affected. Hematopoietic progenitors and DC precursors were significantly decreased in Mysm1(-/-) mice and defective in Fms-like tyrosine kinase-3(Flt3) ligand-induced, but not in granulocyte macrophage-colony-stimulating factor (GM-CSF)-induced DC differentiation in vitro. Molecular studies demonstrated that the developmental defect of DCs from common myeloid progenitor (CMP) in Mysm1(-/-) mice is associated with decreased Flt3 expression and that Mysm1 derepresses transcription of the Flt3 gene by directing histone modifications at the Flt3 promoter region. Two molecular mechanisms were found to be responsible for the selective role of Mysm1 in lineage determination of DCs from CMPs: the selective expression of Mysm1 in a subset of CMPs and the different requirement of Mysm1 for PU.1 recruitment to the Flt3 locus vs GM-CSF-? and macrophage-colony-stimulating factor receptor loci. In conclusion, this study reveals an essential role of Mysm1 in epigenetic regulation of Flt3 transcription and DC development, and it provides a novel mechanism for lineage determination from CMP.
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Psychological distress, burnout level and job satisfaction in emergency medicine: A cross-sectional study of physicians in China.
Emerg Med Australas
PUBLISHED: 09-07-2014
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Chinese physicians are not only facing heavy work overloads, but also abuse and injury because of patient mistrust of physicians. The primary objective of the present study was to measure psychological distress, burnout levels and job satisfaction among Chinese emergency physicians.
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The role of autophagy in usnic Acid-induced toxicity in hepatic cells.
Toxicol. Sci.
PUBLISHED: 07-30-2014
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The use of usnic acid and usnic acid-containing products is associated with acute liver failure; however, mechanistic studies of hepatotoxicity caused by usnic acid are limited. In this study, we investigated and characterized the possible mechanisms, especially the role of autophagy in usnic acid's toxicity in human HepG2 cells. Usnic acid caused apoptosis as demonstrated by an increased caspase-3/7 activity and an increased subdiploid nucleus formation. Usnic acid-induced autophagy as demonstrated by the conversion of LC3B-I to LC3B-II, degradation of P62, and an increased number of puncta. Inhibition of autophagy by treating cells with autophagy inhibitors (3-methyladenine or chloroquine) or by small interfering RNA against Atg7 aggravated usnic acid-induced apoptosis and decreased cell viability, indicating that autophagy plays a protective role against usnic acid-induced toxicity. Moreover, usnic acid activated the MAPK signaling pathway. Usnic acid-elicited apoptosis was enhanced and autophagy was decreased when JNK was suppressed by a specific inhibitor. Additionally, inhibition of autophagy decreased the activity of JNK. Taken together, our results suggest that usnic acid perturbs various interrelated signaling pathways and that autophagy induction is a defensive mechanism against usnic acid-induced cytotoxicity.
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DNA phosphorothioate modifications influence the global transcriptional response and protect DNA from double-stranded breaks.
Sci Rep
PUBLISHED: 07-18-2014
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The modification of DNA by phosphorothioate (PT) occurs when the non-bridging oxygen in the sugar-phosphate backbone of DNA is replaced with sulfur. This DNA backbone modification was recently discovered and is governed by the dndABCDE genes in a diverse group of bacteria and archaea. However, the biological function of DNA PT modifications is poorly understood. In this study, we employed the RNA-seq analysis to characterize the global transcriptional changes in response to PT modifications. Our results show that DNA without PT protection is susceptible to DNA damage caused by the dndFGHI gene products. The DNA double-stranded breaks then trigger the SOS response, cell filamentation and prophage induction. Heterologous expression of dndBCDE conferring DNA PT modifications at GPSA and GPST prevented the damage in Salmonella enterica. Our data provide insights into the physiological role of the DNA PT system.
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Accuracy of computer-guided implant surgery by a CAD/CAM and laser scanning technique.
Chin J Dent Res
PUBLISHED: 07-17-2014
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Objectives: To explore the method of manufacturing an implant surgery template with a computer-aided design/computer-aided manufacturing (CAD/CAM) technique and evaluate its precision in clinical cases. Methods: Patients referred to the 2nd Dental Center of Peking University who were partially edentulous, were enrolled and scanned with cone beam computed tomography (CBCT). Diagnostic casts were laser scanned to record the configuration of the patients' dentition and mucosae. CBCT and laser scanning data were subsequently loaded into Simplant software. Implant positions were planned in the software with a computer-aided design technique, and surgical templates were fabricated with a rapid prototyping technique. These templates were used to guide implant placement surgery. Results: The mean value of linear deviation was 1.00 mm (range 0 to 2.16 mm) for implant shoulder and 1.26 mm (range 0.51 to 2.86 mm) for the implant apex. The mean angular deviation was 4.74 degress (0.37 to 10.28 degrees). Deviations were higher in the posterior region than anterior. The tooth-supported template provided higher precision than did the tooth/ mucosa-supported template, but no statistically significant difference was found. Conclusion: Computer-guided implant surgery with the CAD/CAM technique provides dentists with a good platform for preoperative planning, precise implant insertion, and ideal rehabilitation. The protocol of this three-dimensional laser scanning technique can provide precision comparable to that of double-scanning.
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The transcriptional regulation of SOX2 on FOXA1 gene and its application in diagnosis of human breast and lung cancers.
Clin. Lab.
PUBLISHED: 07-15-2014
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Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2.
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Developmental and adaptive functioning in children with retinoblastoma: a longitudinal investigation.
J. Clin. Oncol.
PUBLISHED: 07-14-2014
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To determine the developmental trajectory of early cognitive and adaptive skills in young children with retinoblastoma from diagnosis to 5 years of age.
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New strategies for developing cardiovascular stent surfaces with novel functions (Review).
Biointerphases
PUBLISHED: 07-03-2014
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In this review, the authors summarize the developments in surface modification of cardiovascular materials especially in author's laboratory. The authors focus on three different strategies to construct multifunctional surfaces including coimmobilization of various biomolecules on stent surfaces, stem cell based therapy systems, and a single-molecule multipurpose modification strategy in vascular interventional therapy. The roles of various molecules like heparin, gallic acid, various aptamers, and nitric oxide are highlighted in the new strategies for developing cardiovascular stent surfaces with novel functions including excellent hemocompatibility, inhibiting smooth muscle cells proliferation, and native endothelium regeneration. The success of these multifunctional surfaces provides the tremendous potential in designing the next generation of vascular stents.
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Extracellular signal-regulated kinases 1/2 and Akt contribute to triclosan-stimulated proliferation of JB6 Cl 41-5a cells.
Arch. Toxicol.
PUBLISHED: 07-01-2014
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Triclosan is a broad spectrum anti-bacterial agent widely used in many personal care products, household items, medical devices, and clinical settings. Human exposure to triclosan is mainly through oral and dermal routes. In previous studies, we found that sub-chronic dermal exposure of B6C3F1 mice to triclosan induced epidermal hyperplasia and focal necrosis; however, the mechanisms for these responses remain elusive. In this study, using mouse epidermis-derived JB6 Cl 41-5a cells, we found that triclosan stimulated cell growth in a concentration- and time-dependent manner. Enhanced cell proliferation was demonstrated by a substantial increase in the percentage of BrdU-positive cells, an elevation in the protein levels of cyclin D1 and cyclin A, and a reduction in the protein level of p27(Kip1). Western blotting analysis revealed that triclosan induced the activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), p38, and Akt. Pre-treatment of the cells with PD184352, an inhibitor of the upstream kinase MEK1/2, or with wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked triclosan-mediated phosphorylation of ERK1/2 and Akt, respectively, and substantially suppressed triclosan-stimulated cell proliferation, whereas the JNK inhibitor SP600125 or the p38 inhibitor SB203580 had little to no effect on triclosan-stimulated cell proliferation. The phosphorylation activation of ERK1/2 and Akt was further confirmed on the skin of mice dermally administered triclosan. These data suggest that the activation of ERK1/2 and Akt is involved in triclosan-stimulated proliferation of JB6 Cl 41-5a cells.
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Effect of Nd:YAG laser-nitriding-treated titanium nitride surface over Ti6Al4V substrate on the activity of MC3T3-E1 cells.
Biomed Mater Eng
PUBLISHED: 06-24-2014
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Ti6Al4V discs with a thickness of 2.5 mm and dimensions of 15 × 15 mm2 were fabricated. The titanium nitride (TiN) surface was formed via Nd:YAG laser-nitriding. A sandblast acid-etched (SA) surface was used as a control. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and surface roughness tests were conducted to study the surface and cross-section morphologies as well as the properties of TiN and SA surfaces. MC3T3-E1 osteoblast-like cells were cultured on the TiN and SA surfaces to evaluate the effect of TiN surface on cellular behaviors, including attachment, proliferation and differentiation. Morphological testing results revealed that the cross-section of TiN exhibited dendritic crystallization without cracking. The proliferation and differentiation of MC3T3-E1 cells on the laser-nitriding TiN surface were significantly increased compared to those cultured on SA surface. These findings suggested that the TiN surface generated from Nd:YAG laser-nitriding were favorable for the proliferation and differentiation of MC3T3-E1 cells, which is significant for implant surface modification.
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Core-shell nanoreactors for efficient aqueous biphasic catalysis.
Chemistry
PUBLISHED: 06-04-2014
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Water-borne phosphine-functionalized core-cross-linked micelles (CCM) consisting of a hydrophobic core and a hydrophilic shell were obtained as stable latexes by reversible addition-fragmentation chain transfer (RAFT) in water in a one-pot, three-step process. Initial homogeneous aqueous-phase copolymerization of methacrylic acid (MAA) and poly(ethylene oxide) methyl ether methacrylate (PEOMA) is followed by copolymerization of styrene (S) and 4-diphenylphosphinostyrene (DPPS), yielding P(MAA-co-PEOMA)-b-P(S-co-DPPS) amphiphilic block copolymer micelles (M) by polymerization-induced self-assembly (PISA), and final micellar cross-linking with a mixture of S and diethylene glycol dimethacrylate. The CCM were characterized by dynamic light scattering and NMR spectroscopy to evaluate size, dispersity, stability, and the swelling ability of various organic substrates. Coordination of [Rh(acac)(CO)2 ] (acac=acetylacetonate) to the core-confined phosphine groups was rapid and quantitative. The CCM and M latexes were then used, in combination with [Rh(acac)(CO)2 ], to catalyze the aqueous biphasic hydroformylation of 1-octene, in which they showed high activity, recyclability, protection of the activated Rh center by the polymer scaffold, and low Rh leaching. The CCM latex gave slightly lower catalytic activity but significantly less Rh leaching than the M latex. A control experiment conducted in the presence of the sulfoxantphos ligand pointed to the action of the CCM as catalytic nanoreactors with substrate and product transport into and out of the polymer core, rather than as a surfactant in interfacial catalysis.
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MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1?.
J. Mol. Cell. Cardiol.
PUBLISHED: 05-28-2014
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It is well known that menopause could worsen age-related ventricular concentric remodeling following estrogen (E2) deficiency. However the underlying mechanisms of such phenomena are not fully understood. Mitochondria, as the 'cellular power station' of hearts, play an important role in maintaining normal cardiac function and structure. Therefore, the present study aims to investigate whether mitochondrial compromise is responsible for E2 deficiency associated concentric remodeling and, if so, what is its underlying molecular mechanism. We found evident concentric remodeling pattern in both postmenopausal and ovariectomized (OVX) mice, which could be attenuated by E2 replacement. Further study showed mitochondrial structural damages and respiratory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mitochondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the heart. Then, peroxisome proliferator-activated receptor-? co-activator 1-? (PGC-1?), a key mitochondrial function and biology regulator, was found significantly reduced in both postmenopausal and OVX mice. The reduction of PGC-1? protein level in OVX mice could be rescued by E2 delivery, indicating that E2 could positively regulate PGC-1? expression. Next, we found that microRNA-23a (miR-23a) could be negatively regulated by E2 in both myocardium and cultured cardiomyocytes. Moreover, miR-23a could directly downregulate PGC-1? expression in cardiomyocytes via binding to its 3'UTR which implied that miR-23a could be critical for the downregulation of PGC-1? under E2 deficiency. Overexpression of miR-23a was also found to damage mitochondria in cultured cardiomyocytes, ascribed to PGC-1? downregulation. Taken together, E2 deficiency may cause mitochondrial compromise through miR-23a-mediated PGC-1? downregulation, which may subsequently lead to the menopause-associated concentric remodeling.
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Loofah-like gel network formed by the self-assembly of a 3D radially symmetrical organic-inorganic hybrid gelator.
Chem. Commun. (Camb.)
PUBLISHED: 05-24-2014
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We report a unique loofah-like gel network that is supported by the sectional type hexagonal columnar assembly of flexuous furcate fibers, which are constructed by plane-to-plane stacking of a novel 3D radially symmetrical gelator with POSS as the core and L-lysine as the arm.
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Mouse dead end 1-? interacts with c-Jun and stimulates activator protein 1 transactivation.
Mol Med Rep
PUBLISHED: 05-16-2014
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Dead end 1 (Dnd1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with dnd1-?. The interaction between Dnd1-? and c-Jun was demonstrated to occur by glutathione S?transferase pull?down and co-immunoprecipitation. Using confocal microscopy, Dnd1-? was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, Dnd1-? and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with Dnd1-? and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with dnd1-? facilitates the investigation of the functions and molecular mechanisms of Dnd1.
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Three new phenylpropanoids from the roots of Piper taiwanense and their inhibitory activities on platelet aggregation and Mycobacterium tuberculosis.
Chem. Biodivers.
PUBLISHED: 05-16-2014
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Bioassay-guided fractionation of the active AcOEt-soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B (1 and 2, resp.), a new natural product, taiwanensol C (3), and 3-acetoxy-4-hydroxy-1-allylbenzene (4). The compounds were obtained as two isomer mixtures (1/2 and 3/4, resp.). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1-4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1/2 and 3/4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC50 values of 35.2 and 8.8 ?M, respectively. In addition, 1/2 and 3/4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 ?g/ml, respectively.
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Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis.
BMC Cancer
PUBLISHED: 05-14-2014
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Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis.
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Frequent KIT mutations in human gastrointestinal stromal tumors.
Sci Rep
PUBLISHED: 05-07-2014
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Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.
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Effect of oridonin-mediated hallmark changes on inflammatory pathways in human pancreatic cancer (BxPC-3) cells.
World J. Gastroenterol.
PUBLISHED: 05-02-2014
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To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells.
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Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.
J Am Heart Assoc
PUBLISHED: 04-12-2014
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Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF.
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Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma.
Respir. Res.
PUBLISHED: 04-03-2014
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Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16?V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma.
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Human intestinal microbial metabolism of naringin.
Eur J Drug Metab Pharmacokinet
PUBLISHED: 03-24-2014
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Naringin, a major flavonoid in citrus fruits, has been proved to be a promising antitussive candidate. It undertakes complicated metabolism. In this study, human intestinal microbial metabolism of naringin was studied in vitro. Six persons' fecal water, which have intestinal microbial enzyme, were used in the first experiment. Naringin was metabolized by fecal water into naringenin. Subsequently, 3-(4-hydroxyphenyl)propionic acid (4-HPPA) was produced with naringenin degradation by a person's fecal water. However, 4-HPPA was not detected after naringenin degradation by the other 5 subjects' fecal water and the reason might be that the degrading velocity of 4-HPPA exceeded the producing velocity. To confirm the difference in degrading 4-HPPA among human feces, 22 healthy persons' feces were used for incubation. In this second experiment, 15 persons' feces could degrade 4-HPPA, but the other 7 subjects' could not. Human feces showed different ability of degrading 4-HPPA, and there are no gender differences. These results may be helpful for explaining findings in pharmacological and toxicological studies and are groundwork for clinical studies.
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Sertraline induces endoplasmic reticulum stress in hepatic cells.
Toxicology
PUBLISHED: 03-18-2014
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Sertraline is used for the treatment of depression, and is also used for the treatment of panic, obsessive-compulsive, and post-traumatic stress disorders. Previously, we have demonstrated that sertraline caused hepatic cytotoxicity, with mitochondrial dysfunction and apoptosis being underlying mechanisms. In this study, we used microarray and other biochemical and molecular analyses to identify endoplasmic reticulum (ER) stress as a novel molecular mechanism. HepG2 cells were exposed to sertraline and subjected to whole genome gene expression microarray analysis. Pathway analysis revealed that ER stress is among the significantly affected biological changes. We confirmed the increased expression of ER stress makers by real-time PCR and Western blots. The expression of typical ER stress markers such as PERK, IRE1?, and CHOP was significantly increased. To study better ER stress-mediated drug-induced liver toxicity; we established in vitro systems for monitoring ER stress quantitatively and efficiently, using Gaussia luciferase (Gluc) and secreted alkaline phosphatase (SEAP) as ER stress reporters. These in vitro systems were validated using well-known ER stress inducers. In these two reporter assays, sertraline inhibited the secretion of Gluc and SEAP. Moreover, we demonstrated that sertraline-induced apoptosis was coupled to ER stress and that the apoptotic effect was attenuated by 4-phenylbutyrate, a potent ER stress inhibitor. In addition, we showed that the MAP4K4-JNK signaling pathway contributed to the process of sertraline-induced ER stress. In summary, we demonstrated that ER stress is a mechanism of sertraline-induced liver toxicity.
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Endoplasmic reticulum stress in drug- and environmental toxicant-induced liver toxicity.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev
PUBLISHED: 03-07-2014
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Liver injury resulting from exposure to drugs and environmental chemicals is a major health problem. Endoplasmic reticulum stress (ER stress) is considered to be an important factor in a wide range of diseases, such as cancer, neurological and cardiovascular disease, diabetes, and inflammatory diseases. The role of ER stress in drug-induced and environmental toxicant-induced liver toxicity has been underestimated in the past; emerging evidence indicates that ER stress makes a substantial contribution to the pathogenesis of drug-induced liver toxicity. In this review, we summarize current knowledge on drugs and environmental toxicants that trigger ER stress in liver and on the underlying molecular mechanisms. We also discuss experimental approaches for ER stress studies.
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Strigolactones are involved in phosphate- and nitrate-deficiency-induced root development and auxin transport in rice.
J. Exp. Bot.
PUBLISHED: 03-06-2014
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Strigolactones (SLs) or their derivatives have recently been defined as novel phytohormones that regulate root development. However, it remains unclear whether SLs mediate root growth in response to phosphorus (P) and nitrogen (N) deficiency. In this study, the responses of root development in rice (Oryza sativa L.) to different levels of phosphate and nitrate supply were investigated using wild type (WT) and mutants defective in SL synthesis (d10 and d27) or insensitive to SL (d3). Reduced concentration of either phosphate or nitrate led to increased seminal root length and decreased lateral root density in WT. Limitation of either P or N stimulated SL production and enhanced expression of D10, D17, and D27 and suppressed expression of D3 and D14 in WT roots. Mutation of D10, D27, or D3 caused loss of sensitivity of root response to P and N deficiency. Application of the SL analogue GR24 restored seminal root length and lateral root density in WT and d10 and d27 mutants but not in the d3 mutant, suggesting that SLs were induced by nutrient-limiting conditions and led to changes in rice root growth via D3. Moreover, P or N deficiency or GR24 application reduced the transport of radiolabelled indole-3-acetic acid and the activity of DR5::GUS auxin reporter in WT and d10 and d27 mutants. These findings highlight the role of SLs in regulating rice root development under phosphate and nitrate limitation. The mechanisms underlying this regulatory role involve D3 and modulation of auxin transport from shoots to roots.
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Association between VDR polymorphisms and breast cancer: an updated and comparative meta-analysis of crude and adjusted odd ratios.
Asian Pac. J. Cancer Prev.
PUBLISHED: 02-27-2014
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There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta- analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case- control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.
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Effects of partial deletion of the wzm and wzt genes on lipopolysaccharide synthesis and virulence of Brucella abortus S19.
Mol Med Rep
PUBLISHED: 02-21-2014
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Brucellosis is a worldwide human and animal infectious disease, and the effective methods of its control are immunisation of animals by vaccination and elimination. Brucella abortus S19 is one of the popular vaccines with virulence in the control of cattle Brucellosis. In the present study, allelic exchange plasmids of wzm and wzt genes and partial knockout mutants of wzm and wzt were constructed to evaluate the resulting difference in virulence of B. abortus S19. PCR analysis revealed that the target genes were knocked out. The mutants were rough mutants and they could be differentiated from natural infection by the Rose Bengal plate and standard agglutination tests. The molecular weights of lipopolysaccharides of the ?wzm and ?wzt mutants were clustered between 25 and 40 kDa, and 30 and 35 kDa separately, and were markedly different from those in B. abortus S19. The virulence of B. abortus ?wzm and ?wzt was decreased compared with that of B. abortus S19 in mice. All these results identified that there were several differences between the wzm and wzt genes on lipopolysaccharide synthesis and on the virulence of B. abortus.
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Enantioseparation of new triadimenol antifungal active compounds by electrokinetic chromatography and molecular modeling study of chiral recognition mechanisms.
Electrophoresis
PUBLISHED: 02-18-2014
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Chiral separation of 12 new triadimenol antifungal active compounds by electrokinetic chromatography and chiral recognition mechanisms by computer-aided molecular modeling techniques were studied. Seven neutral cyclodextrins were used as chiral selectors. Heptakis-(2,3,6-tri-O-methyl)-?-cyclodextrin (TM-?-CD) exhibited a very high enantioselectivity power to 12 active compounds compared to the other tested CDs. The influences of the concentration of TM-?-CD, buffer pH, buffer concentration, applied voltage, and temperature were investigated, respectively. Under the optimum separation conditions, all the 12 active compounds were baseline separated and the resolutions of most compounds were beyond 2.50. The study of the analyte structure-enantioseparation relationships showed that substitutions in the side chains played important roles on enantiomeric separation. By means of computer-aided molecular modeling software Discovery Studio 2.5/Sybyl 7.0/Gold 3.0.1, inclusion process between TM-?-CD and these enantiomers was investigated and their binding energies were calculated. The results suggested that the enantioseparation result related to the difference in binding energy. And the good separation obtained in the presence of the TM-?-CD chiral selector was due to the big binding energy difference of two enantiomers with the chiral selector.
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Differential requirement of GRP94 and GRP78 in mammary gland development.
Sci Rep
PUBLISHED: 02-07-2014
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Glucose Regulated Protein (GRP) 94 and GRP78 are critical molecular chaperones and regulators of signaling. Conditional knockout mouse models have revealed tissue specific requirements for GRP94 and GRP78, including selection for allele retention in specific cell types. Here we report the consequences of mammary-targeted knockout of these GRPs. Our studies revealed that MMTV-Cre, Grp94(f/f) mammary glands, despite GRP94 deficiency, exhibited normal proliferation and ductal morphogenesis. Interestingly, MMTV-Cre, Grp78(f/f) mammary glands displayed only slightly reduced GRP78 protein levels, associating with the retention of the non-recombined Grp78 floxed alleles in isolated mammary epithelial cells and displayed phenotypes comparable to wild-type glands. In contrast, transduction of isolated Grp78(f/f) mammary epithelial stem/progenitor cells with adenovirus expressing GFP and Cre-recombinase was successful in GRP78 ablation, and the GFP sorted cells failed to give rise to repopulated mammary glands in de-epithelialized recipient mice. These studies imply GRP78, but not GRP94, is required for mammary gland development.
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The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats.
Behav. Brain Res.
PUBLISHED: 02-04-2014
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In this study, the motor deficit, cognition impairment and the vulnerability of different striatal interneurons to the 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in unilateral medial forebrain bundle (MFB) lesion rats were analyzed by employing behavioral test, immunohistochemistry and Western blot methods. The apomorphine-induced rotation after MFB lesion was used as a valid criterion of motor deficit. The 6-OHDA damaged rats had limb rigidity with longer hang time compared to the controls in the grip strength test. Cognitive and mnemonic deficits of rats with unilateral MFB lesion were observed by the water maze task. The MFB lesion resulted in a significant loss of tyrosine hydroxylase (TH)+ cells in the contralateral striatum or substantia nigra. After dopaminergic depletion, the numbers of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ interneurons were notably reduced while these of neuropeptide Y (NPY)+ were markedly increased in the striatum. No noticeable change in the number of parvalbumin (Parv)+ interneurons was found in 6-OHDA rats. In addition, the fiber densities for each individual interneuron were increased after 6-OHDA treatment, especially for the fiber densities of Parv+ and Cr+ interneurons. The Western blot analysis further confirmed the results described above. In conclusion, the MFB lesion model is suitable to mimic Parkinson's disease (PD), and our results are helpful for further understanding the underlying mechanism and the specific functions of various striatal interneurons in the pathological process of PD.
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Examination of risk factors for intellectual and academic outcomes following treatment for pediatric medulloblastoma.
Neuro-oncology
PUBLISHED: 02-03-2014
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The aim of this study was to prospectively examine the effects of hearing loss and posterior fossa syndrome (PFS), in addition to age at diagnosis and disease risk status, on change in intellectual and academic outcomes following diagnosis and treatment in a large sample of medulloblastoma patients.
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Alphavbeta6 is required in maintaining the intestinal epithelial barrier function.
Cell Biol. Int.
PUBLISHED: 01-27-2014
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Epithelial barrier dysfunction is involved in a large number of diseases, but the pathogenesis is unclear. Integrin alphavbeta6 (avb6) in involved in the maintenance of the mucosal homeostasis. We have investigated the role of avb6 in maintaining the epithelial barrier function. Using T84 monolayers cultures, transepithelial electric resistance (TER) and permeability to ovalbumin (OVA) were measured as indicators of functioning. The antigenicity of OVA collected from the Transwell basal chambers was assessed using OVA-specific T cell proliferation. Knockdown of the avb6 genes increased the permeability of T84 monolayers to OVA, but did not affect TER. The deficiency of avb6-related hyperpermeability in T84 monolayers could be compensated by adding exogenous avb6 to the culture. The OVA samples collected from the basal chambers had strong antigenicity as it markedly induced the antigen specific T cell proliferation. Addition of recombinant avb6 blocked increases in permeability of T84 monolayers to OVA induced by tumor necrosis factor-?.
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PTPN2 rs1893217 single-nucleotide polymorphism is associated with risk of Behçet's disease in a Chinese Han population.
Clin. Exp. Rheumatol.
PUBLISHED: 01-24-2014
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Behçet's disease (BD) is a rare, chronic, relapsing, systemic, immune-mediated vasculitis and the etiology remains to be defined. This study investigated single-nucleotide polymorphisms (SNP) of tyrosine-protein phosphatase non-receptor type 2 (PTPN2) and inducible T-cell co-stimulator-ligand gene (ICOSLG) in Chinese Han BD patients and healthy controls because SNPs of these two genes are associated with risk of developing other auto-inflammation diseases.
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miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition.
Exp. Cell Res.
PUBLISHED: 01-19-2014
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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs.
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Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice.
Oxid Med Cell Longev
PUBLISHED: 01-18-2014
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The exact pathophysiological change concerning mitochondrial injury and oligodendrocyte apoptosis in MS and EAE model is still unknown. Whether curcumin is able to inhibit mitochondrial injury and suppress the apoptosis in the early stages of MS/EAE is still unclear. We first explored mitochondrial injury and apoptosis at different time points p.i. in C57 BL/6 EAE mice. We then explored the effects of curcumin on mitochondria and apoptosis. Results showed that mitochondrial injury can be observed 3 days p.i. Apoptosis in the spinal cord occurred 3 days p.i. and the apoptotic cells were shown to be oligodendrocytes and neuronal cells. Curcumin significantly reduced the number of apoptotic cells and inhibited the upregulation of cyt-c, caspase-9, and caspase-3 at 7 days p.i. in the EAE mice. These observations demonstrate that mitochondrial injury and oligodendrocyte/neuronal apoptosis occur in the early stages of EAE. Curcumin can inhibit apoptosis in EAE mice which maybe act through protection of mitochondrial injury and inhibition of the intrinsic apoptotic pathway.
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Melatonin reduces projection neuronal injury induced by 3-nitropropionic Acid in the rat striatum.
Neurodegener Dis
PUBLISHED: 01-14-2014
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Melatonin has shown a protective effect against various oxidative damages in the nervous system. Our previous studies have also confirmed its effect on behavioral dysfunction of experimental rats and injury of striatal interneurons induced by 3-nitropropionic acid. The present study aimed to further determine the effect of melatonin on the injury of striatal projection neurons induced by 3-nitropropionic acid.
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Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk.
Tumour Biol.
PUBLISHED: 01-08-2014
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Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. As in many other diseases, environment and genetic factors are believed to be involved in the pathogenesis of HCC. Numerous epidemiologic investigations including case-control and cohort studies have suggested the association of glutathione S-transferase (GST) genetic polymorphisms and HCC risk. However, some studies have produced conflicting results. Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility. We searched PubMed, Embase, ISI Web of Science, and CNKI databases to identify eligible studies meeting the inclusion criteria up to August 30, 2013. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association. Finally, there were a total of 33 studies with 4,232 cases and 6,601 controls included in this meta-analysis. In the pooled analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR?=?1.31, 95% CI?=?1.07-1.61, P?=?0.010, P heterogeneity?
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Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes through phosphorylation of troponin I.
Life Sci.
PUBLISHED: 01-06-2014
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The specific role of AMPK?1 or AMPK?2 in mediating cardiomyocyte contractile function remains elusive. The present study investigated how AMPK activation modulates the contractility of isolated cardiomyocytes.
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Protective role of the cholinergic anti-inflammatory pathway in a mouse model of viral myocarditis.
PLoS ONE
PUBLISHED: 01-01-2014
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Activation of the cholinergic anti-inflammatory pathway, which relies on the ?7nAchR (alpha 7 nicotinic acetylcholine receptor), has been shown to decrease proinflammatory cytokines. This relieves inflammatory responses and improves the prognosis of patients with experimental sepsis, endotoxemia, ischemia/reperfusion injury, hemorrhagic shock, pancreatitis, arthritis and other inflammatory syndromes. However, whether the cholinergic anti-inflammatory pathway has an effect on acute viral myocarditis has not been investigated. Here, we studied the effects of the cholinergic anti-inflammatory pathway on acute viral myocarditis.
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Stabilization of collagen nanofibers with l-lysine improves the ability of carbodiimide cross-linked amniotic membranes to preserve limbal epithelial progenitor cells.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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To overcome the drawbacks associated with limited cross-linking efficiency of carbodiimide modified amniotic membrane, this study investigated the use of l-lysine as an additional amino acid bridge to enhance the stability of a nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results of ninhydrin assays and zeta potential measurements showed that the amount of positively charged amino acid residues incorporated into the tissue collagen chains is highly correlated with the l-lysine-pretreated concentration. The cross-linked structure and hydrophilicity of amniotic membrane scaffolding materials affected by the lysine molecular bridging effects were determined. With an increase in the l-lysine-pretreated concentration from 1 to 30 mM, the cross-linking density was significantly increased and water content was markedly decreased. The variations in resistance to thermal denaturation and enzymatic degradation were in accordance with the number of cross-links per unit mass of amniotic membrane, indicating l-lysine-modulated stabilization of collagen molecules. It was also noteworthy that the carbodiimide cross-linked tissue samples prepared using a relatively high l-lysine-pretreated concentration (ie, 30 mM) appeared to have decreased light transmittance and biocompatibility, probably due to the influence of a large nanofiber size and a high charge density. The rise in stemness gene and protein expression levels was dependent on improved cross-link formation, suggesting the crucial role of amino acid bridges in constructing suitable scaffolds to preserve limbal progenitor cells. It is concluded that mild to moderate pretreatment conditions (ie, 3-10 mM l-lysine) can provide a useful strategy to assist in the development of carbodiimide cross-linked amniotic membrane as a stable stem cell niche for corneal epithelial tissue engineering.
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The use of google trends in health care research: a systematic review.
PLoS ONE
PUBLISHED: 01-01-2014
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Google Trends is a novel, freely accessible tool that allows users to interact with Internet search data, which may provide deep insights into population behavior and health-related phenomena. However, there is limited knowledge about its potential uses and limitations. We therefore systematically reviewed health care literature using Google Trends to classify articles by topic and study aim; evaluate the methodology and validation of the tool; and address limitations for its use in research.
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Genetic Association Study of TNFAIP3, IFIH1, IRF5 Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population.
PLoS ONE
PUBLISHED: 01-01-2014
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Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.
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Systematic review of clinical practice guidelines related to multiple sclerosis.
PLoS ONE
PUBLISHED: 01-01-2014
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High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated.
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Associations between TNF-?-308A/G polymorphism and susceptibility with dermatomyositis: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Some surveys had inspected the effects of the tumor necrosis factor-? (TNF-?)-308A/G polymorphism on susceptibility to dermatomyositis (DM), and showed mixed results. To briefly review these consequences, a comprehensive meta-analysis was carried out to estimate the relationship between them much more accurately.
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Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.
PLoS ONE
PUBLISHED: 01-01-2014
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Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7%) in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.
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Dynamic transcription of long non-coding RNA genes during CD4+ T cell development and activation.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent evidence shows that long non-coding RNA (LncRNA) play important regulatory roles in many biology process, including cell development, activation and oncogenesis. However, the roles of these LncRNAs in the development and activation of CD4+ T cells, which is an important component of immune response, remain unknown.
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PIK3CA and TP53 gene mutations in human breast cancer tumors frequently detected by ion torrent DNA sequencing.
PLoS ONE
PUBLISHED: 01-01-2014
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Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5-10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.
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Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Huntington's disease (HD) is a neurological degenerative disease and quinolinic acid (QA) has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD) rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv)+ and neuropeptide Y (NPY)+ interneurons were both significantly reduced while those of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD.
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A novel mutation of Hyaluronan synthase 2 gene in Chinese children with ventricular septal defect.
PLoS ONE
PUBLISHED: 01-01-2014
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As a major product of extracellular matrix (ECM), Hyaluronic acid (HA) is involved in early cardiac development and mainly synthesized by Hyaluronan synthase 2 (HAS2) during embryogenesis. Targeted deletion of HAS2 gene in mice led to obvious cardiac and vascular defects. To clarify the potential association of the mutation in HAS2 with the development of congenital heart disease (CHD), in this study, we sequenced the coding region of HAS2 and identified a novel non-synonymous variant c.A1496T (p.Glu499Val) in one of 100 non-syndromic Ventricular Septal Defect (VSD) patients. The variant was not observed in 250 controls. In addition, to determine the contribution of HAS2 variant in VSD, we compared HA content in supernatant using HA quantitative analysis and found that the mutation obviously affected the HA synthetic activity of HAS2. To our knowledge, this is the first time that the mutation in HAS2 was found in Chinese VSD patients, which suggested that HAS2 may be involved in the etiology of non-syndromic VSD and have the vital function in the development of heart septum.
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Epidermal Growth Factor Receptor Targeted Nuclear Delivery and High-Resolution Whole Cell X-ray Imaging of Fe3O4@TiO2 Nanoparticles in Cancer Cells.
ACS Nano
PUBLISHED: 11-27-2013
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Sequestration within the cytoplasm often limits the efficacy of therapeutic nanoparticles that have specific subcellular targets. To allow for both cellular and subcellular nanoparticle delivery, we have created epidermal growth factor receptor (EGFR)-targeted Fe3O4@TiO2 nanoparticles that use the native intracellular trafficking of EGFR to improve internalization and nuclear translocation in EGFR-expressing HeLa cells. While bound to EGFR, these nanoparticles do not interfere with the interaction between EGFR and karyopherin-?, a protein that is critical for the translocation of ligand-bound EGFR to the nucleus. Thus, a portion of the EGFR-targeted nanoparticles taken up by the cells also reaches cell nuclei. We were able to track nanoparticle accumulation in cells by flow cytometry and nanoparticle subcellular distribution by confocal fluorescent microscopy indirectly, using fluorescently labeled nanoparticles. More importantly, we imaged and quantified intracellular nanoparticles directly, by their elemental signatures, using X-ray fluorescence microscopy at the Bionanoprobe, the first instrument of its kind in the world. The Bionanoprobe can focus hard X-rays down to a 30 nm spot size to map the positions of chemical elements tomographically within whole frozen-hydrated cells. Finally, we show that photoactivation of targeted nanoparticles in cell nuclei, dependent on successful EGFR nuclear accumulation, induces significantly more double-stranded DNA breaks than photoactivation of nanoparticles that remain exclusively in the cytoplasm.
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A coumarin derivative as a fluorogenic glycoproteomic probe for biological imaging.
Chem. Commun. (Camb.)
PUBLISHED: 11-26-2013
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Fluorescence imaging in living cells is typically carried out using a functionalized fluorescent dye. But it often causes strong background noise under many conditions where washing is not applicable. Here, we report on a coumarin based fluorogenic probe, which can be used as a bioorthogonal-labeling tool for glycoproteins. The results indicated that the probe was able to image glycoproteins in living cells and it may also be suitable for intracellular imaging.
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SOX2 regulates apoptosis through MAP4K4-Survivin signaling pathway in human lung cancer cells.
Carcinogenesis
PUBLISHED: 11-14-2013
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Previous studies have implicated cancer stem cells in tumor recurrence and revealed that the stem cell gene SOX2 plays an important role in the tumor cell resistance to apoptosis. Nonetheless, the mechanism by which SOX2 regulates apoptosis signals remained undefined. Here, we demonstrated the surprising finding that silencing of the SOX2 gene effectively induces apoptosis via the activation of death receptor and mitochondrial signaling pathways in human non-small cell lung cancer cells. Unexpectedly, reverse transcription-PCR analysis suggested that downregulation of SOX2 leads to activation of MAP4K4, previously implicated in cell survival. Evaluation of the apoptotic pathways revealed an increased expression of key inducers of apoptosis, including tumor necrosis factor-? and p53, with concurrent attenuation of Survivin. Although p53 appeared dispensable for this pathway, the loss of Survivin in SOX2-deficient cells appeared critical for the observed MAP4K4 induced cell death. Rescue experiments revealed that SOX2-silencing-mediated killing was blocked by ectopic expression of Survivin, or by reduction of MAP4K4 expression. Clinically, expressions of Survivin and SOX2 were highly correlated with each other. The results reveal a key target of SOX2 expression and highlight the unexpected context-dependent role for MAP4K4, a pluripotent activator of several mitogen-activated protein kinase pathways, in regulating tumor cell survival.
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Aberrant methylation of the Ras-related associated with diabetes gene in human primary esophageal cancer.
Anticancer Res.
PUBLISHED: 11-14-2013
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Ras-related associated with diabetes (RRAD), a member of the Ras-related GTPase superfamily, is frequently methylated in several human cancers, though its methylation profile remains unclear in esophageal cancer.
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Sertraline, an Antidepressant, Induces Apoptosis in Hepatic Cells Through the Mitogen-Activated Protein Kinase Pathway.
Toxicol. Sci.
PUBLISHED: 11-05-2013
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Sertraline is generally used for the treatment of depression and is also approved for the treatment of panic, obsessive-compulsive, and posttraumatic stress disorders. Previously, using rat primary hepatocytes and isolated mitochondria, we demonstrated that sertraline caused hepatic cytotoxicity and mitochondrial impairment. In the current study, we investigated and characterized molecular mechanisms of sertraline toxicity in human hepatoma HepG2 cells. Sertraline decreased cell viability and induced apoptosis in a dose- and time-dependent manner. Sertraline activated the intrinsic checkpoint protein caspase-9 and caused the release of cytochrome c from mitochondria to cytosol; this process was Bcl-2 family dependent because antiapoptotic Bcl-2 family proteins were decreased. Pretreatment of the HepG2 cells with caspase-3, caspase-8, and caspase-9 inhibitors partially but significantly reduced the release of lactate dehydrogenase, indicating that sertraline-induced apoptosis is mediated by both intrinsic and extrinsic apoptotic pathways. Moreover, sertraline markedly increased the expression of tumor necrosis factor (TNF) and the phosphorylation of JNK, extracellular signal-regulated kinase (ERK1/2), and p38. In sertraline-treated cells, the induction of apoptosis and cell death was shown to be the result of activation of JNK, but not ERK1/2 or p38 in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, silencing MAP4K4, the upstream kinase of JNK, attenuated both apoptosis and cell death caused by sertraline. Taken together, our findings suggest that sertraline induced apoptosis in HepG2 cells at least partially via activation of the TNF-MAP4K4-JNK cascade signaling pathway.
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Epigenetic control of natural killer cell maturation by histone H2A deubiquitinase, MYSM1.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-23-2013
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Histone modifications play critical roles in regulating immunity; however, little is known about the epigenetic control of natural killer (NK) cell development. Here, we found that NK cell development is severely impaired in mice deficient in the histone H2A deubiquitinase MYSM1. We demonstrated that MYSM1 is required for NK cell maturation but not for NK lineage specification and commitment. We also found that MYSM1 intrinsically controls this NK cell maturation. Mechanistic studies revealed that the expression of transcription factor, inhibitor of DNA-binding protein (ID2), a critical factor for NK cell development, is impaired in Mysm1(-/-) NK cells. MYSM1 interacts with nuclear factor IL-3 (NFIL3, also known as E4BP4), a critical factor for mouse NK cell development, and the recruitment of nuclear factor Il-3 to the ID2 locus is dependent on MYSM1. Further, we observed that MYSM1 is involved in maintaining an active chromatin at the ID2 locus to promote NK cell development. Hence this study demonstrates the critical epigenetic regulation of NK cell development by the histone H2A deubiquitinase MYSM1 through the transcriptional control of transcription factors important for NK cell development.
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Plasmon-enhanced enzyme-linked immunosorbent assay on large arrays of individual particles made by electron beam lithography.
ACS Nano
PUBLISHED: 09-18-2013
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Ultrasensitive biosensing is one of the main driving forces behind the dynamic research field of plasmonics. We have previously demonstrated that the sensitivity of single nanoparticle plasmon spectroscopy can be greatly enhanced by enzymatic amplification of the refractive index footprint of individual protein molecules, so-called plasmon-enhanced enzyme-linked immunosorbent assay (ELISA). The technique, which is based on generation of an optically dense precipitate catalyzed by horseradish peroxidase at the metal surface, allowed for colorimetric analysis of ultralow molecular surface coverages with a limit of detection approaching the single molecule limit. However, the plasmonic response induced by a single enzyme can be expected to vary for a number of reasons, including inhomogeneous broadening of the sensing properties of individual particles, variation in electric field enhancement over the surface of a single particle and variation in size and morphology of the enzymatic precipitate. In this report, we discuss how such inhomogeneities affect the possibility to quantify the number of molecules bound to a single nanoparticle. The discussion is based on simulations and measurements of large arrays of well-separated gold nanoparticles fabricated by electron beam lithography (EBL). The new data confirms the intrinsic single-molecule sensitivity of the technique but we were not able to clearly resolve the exact number of adsorbed molecules per single particle. The results indicate that the main sources of uncertainty come from variations in sensitivity across the surface of individual particles and between different particles. There is also a considerable uncertainty in the actual precipitate morphology produced by individual enzyme molecules. Possible routes toward further improvements of the methodology are discussed.
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Fabrication of Novel Reduction-Sensitive Gene Vectors Based on Three-Armed Peptides.
Macromol Biosci
PUBLISHED: 09-16-2013
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To address the inherent barriers of gene transfection, two reduction-sensitive branched polypeptides (RBPs) are synthesized and explored as novel non-viral gene vectors. The introduced disulfide linkages in RBPs facilitate glutathione-triggered intracellular gene release and reduce polymer degradation-induced cytotoxicity. Furthermore, the highly branched architecture concurrently realizes multivalency for strong DNA binding and elicits conformational flexibility for tight DNA compacting, which are beneficial for cellular entry. To increase the endosomal escape of plasmid DNA, pH-sensitive histidyl residues are incorporated into RBPs to improve buffer capacity in an acidic environment. In vitro study demonstrates that RBPs can efficiently mediate the DNA transfection and avoid apparent cytotoxicity in HeLa and COS7. The present gene delivery system offers a simple and flexible approach to fabricate microenvironment-specific branched gene vectors for gene therapy.
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Morphological Diversity of GABAergic and Cholinergic Interneurons in the Striatal Dorsolateral and Ventromedial Regions of Rats.
Cell. Mol. Neurobiol.
PUBLISHED: 09-12-2013
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The striatum plays a fundamental role in sensorimotor and cognitive functions of the body, and different sub-regions control different physiological functions. The striatal interneurons play important roles in the striatal function, yet their specific functions are not clearly elucidated so far. The present study aimed to investigate the morphological properties of the GABAergic interneurons expressing neuropeptide Y (NPY), calretinin (Cr), and parvalbumin (Parv) as well as the cholinergic interneurons expressing choline acetyltransferase (ChAT) in the striatal dorsolateral (DL) and ventromedial (VM) regions of rats using immunohistochemistry and Western blot. The present results showed that the somatic size of Cr+ was the smallest, while ChAT+ was the largest among the four types of interneurons. There was no regional difference in neuronal somatic size of all types of interneurons. Cr+ and Parv+ neurons were differentially distributed in the striatum. Moreover, Parv+ had the longest primary dendrites in the DL region, while NPY+ had the longest ones in the VM region of striatum. But there was regional difference in the length of primary dendrites of Parv. The numbers of primary dendrites of Parv+ were the largest in both DL and VM regions of striatum. Both Cr+ and Parv+ primary dendrites displayed regional difference in the striatum. Western blot further confirmed the regional differences in the protein expression level of Cr and Parv. Hence, the present study indicates that GABAergic and cholinergic interneurons might be involved in different physiological functions based on their morphological and distributional diversity in different regions of the rat striatum.
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The control of hematopoietic stem cell maintenance, self-renewal, and differentiation by Mysm1-mediated epigenetic regulation.
Blood
PUBLISHED: 09-06-2013
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Epigenetic histone modifications play critical roles in the control of self-renewal and differentiation of hematopoietic stem cells (HSCs). Mysm1 is a recently identified histone H2A deubiquitinase with essential and intrinsic roles for maintaining functional HSCs. In this study, in addition to confirming this function of Mysm1, by using Mysm1-deficient (Mysm1(-/-)) mice, we provide more evidence for how Mysm1 controls HSC homeostasis. Mysm1 deletion drives HSCs from quiescence into rapid cycling and increases their apoptotic rate, resulting in an exhaustion of the stem cell pool, which leads to an impaired self-renewal and lineage reconstituting abilities in the Mysm1-deficient mice. Our study identified Gfi1 as one of the candidate genes responsible for the HSC defect in Mysm1-deficient mice. Mechanistic studies revealed that Mysm1 modulates histone modifications and directs the recruitment of key transcriptional factors such as Gata2 and Runx1 to the Gfi1 locus in HSCs. We found that Mysm1 directly associates with the Gfi1 enhancer element and promotes its transcription through Gata2 and Runx1 transactivation. Thus, our study not only elaborates on the initial reports of Mysm1 association with HSC homeostasis but also delineates a possible epigenetic mechanism through which Mysm1 carries out this function in the HSCs.
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Office removal of a subglottic bread clip.
Case Rep Otolaryngol
PUBLISHED: 09-05-2013
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Objective. The presence of an upper airway foreign body is an emergent, potentially life-threatening situation that requires careful but rapid evaluation and management. Organic or nonorganic material may typically be found in the pyriform sinuses or tongue base or may be aspirated directly into the tracheobronchial tree. We present here an unusual case report of a patient who accidentally ingested a plastic bread clip that was lodged in his subglottis for 15 months and report successful removal in the office under local anesthesia. Methods. Mucosal anesthesia was achieved with inhaled 4% lidocaine spray. Flexible laryngoscopic removal of the foreign body was then successfully accomplished. Results. The patients symptoms resolved completely following removal, with no sequelae. Conclusions. Office removal of airway foreign bodies is feasible and can be safely done with adequate topical anesthesia, but great caution and emergency planning must be exercised.
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Hydroxide-initiated conversion of aromatic nitriles to imidazolines: fullerenes vs TCNE.
Org. Lett.
PUBLISHED: 09-04-2013
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Transformation of aromatic nitriles to imidazolines has been achieved under basic conditions with the electron-deficient C60 and C70 fullerenes, but not with the electron-deficient olefin of tetracyanoethylene (TCNE). In situ UV-vis-NIR indicates that the ability of RC60(-) to undergo single-electron transfer (SET) to C60 is crucial for the reaction.
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Lose dose genistein inhibits glucocorticoid receptor and ischemic brain injury in female rats.
Neurochem. Int.
PUBLISHED: 08-23-2013
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Although acute bolus of genistein treatment has been shown to protect against neuronal damage in experimental brain injury animal models, chronic continuous low dose treatment of genistein on ischemic brain injury has not been well elucidated. In the present study, female rats were received either pure genistein (0.1mg/kg/day via osmotic minipumps) or placebo at the time of ovariectomy, and transient forebrain ischemia was induced 7days later. Results demonstrated that genistein treatment for 14days significantly improved ischemic neuronal survival in hippocampal CA1 region of ovariectomized rats. Glucocorticoid receptor (GR) is a member of the adrenal steroid hormone receptor, which is highly expressed in the rat hippocampus. Activation of the GR plays a critical role in the neuronal stress responses, including ischemic brain damage. This study therefore examined the potential mechanisms by which genistein regulates GR signaling, including the protein distribution and receptor activation in hippocampus following ischemic reperfusion (I/R). Results showed that GR expression in the ovariectomized rats was excessively increased both in neurons (I/R 6h) and activated microglial cells (I/R 7d) in hippocampal CA1 region. Genistein treatment significantly attenuated GR induction and the enhanced GR nuclear translocation and DNA-binding capacity. The effects of genistein on the GR levels was accompanied with decreased blood plasma levels of corticosterone (primary glucocorticoid in rodents) and coupled to an E3 ubiquitin ligase Mdm2 targeted proteasomal degradation of GR, because genistein treatment could enhance the GR-Mdm2 interaction and the ubiquitination level of GR protein. In addition, our results indicated that genistein markedly prevented the excessive activation of microglia in CA1 sector. These results demonstrate the neuroprotective action of chronic low dose genistein replacement against ischemic brain damage, and a potential mechanism associated with the inhibition of both neuronal and microglial GR signaling following ischemic stress.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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