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Find video protocols related to scientific articles indexed in Pubmed.
[Study on the molecular epidemiology and antibiotic resistance of Salmonella enterica serovar Pomona].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 10-09-2014
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To study the epidemiological characteristics and antibiotic resistance of Salmonella enterica serovar Pomona (S. Pomona).
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Integrative post-genome-wide association analysis of CDKN2A and TP53 SNPs and risk of esophageal adenocarcinoma.
Carcinogenesis
PUBLISHED: 10-03-2014
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Incidence of esophageal adenocarcinoma (EA) in Western countries has increased markedly in recent decades. Although several risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), including reflux, Caucasian race, male gender, obesity, and smoking, less is known about the role of inherited genetic variation. Frequent somatic mutations in the tumor suppressor genes CDKN2A and TP53 were recently reported in EA tumors, while somatic alterations at 9p (CDKN2A) and 17p (TP53) have been implicated as predictors of progression from BE to EA. Motivated by these findings, we used data from a genome-wide association study of 2515 EA cases and 3207 controls to analyze 37 germline single nucleotide polymorphisms at the CDKN2A and TP53 loci. Three CDKN2A polymorphisms were nominally associated (P < 0.05) with reduced risk of EA: rs2518720 C>T [intronic, odds ratio 0.90, P = 0.0121, q = 0.3059], rs3088440 G>A (3'UTR, odds ratio 0.84, P = 0.0186, q = 0.3059), and rs4074785 C>T (intronic, odds ratio 0.85, P = 0.0248, q = 0.3059). None of the TP53 single nucleotide polymorphisms reached nominal significance. Two of the CDKN2A variants identified were also associated with reduced risk of progression from BE to EA, when assessed in a prospective cohort of 408 BE patients: rs2518720 (hazard ratio 0.57, P = 0.0095, q = 0.0285) and rs3088440 (hazard ratio 0.34, P = 0.0368, q = 0.0552). In vitro functional studies of rs3088440, a single nucleotide polymorphism located in the seed sequence of a predicted miR-663b binding site, suggested a mechanism whereby the G>A substitution may attenuate miR-663b-mediated repression of the CDKN2A transcript. This study provides the first evidence that germline variation at the CDKN2A locus may influence EA susceptibility.
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Sulfur-doped graphene quantum dots as a novel fluorescent probe for highly selective and sensitive detection of fe(3+).
Anal. Chem.
PUBLISHED: 10-03-2014
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Sulfur-doped graphene quantum dots (S-GQDs) with stable blue-green fluorescence were synthesized by one-step electrolysis of graphite in sodium p-toluenesulfonate aqueous solution. Compared with GQDs, the S-GQDs drastically improved the electronic properties and surface chemical reactivities, which exhibited a sensitive response to Fe(3+). Therefore, the S-GQDs were used as an efficient fluorescent probe for highly selective detection of Fe(3+). Upon increasing of Fe(3+) concentration ranging from 0.01 to 0.70 ?M, the fluorescence intensity of S-GQDs gradually decreased and reached a plateau at 0.90 ?M. The difference in the fluorescence intensity of S-GQDs before and after adding Fe(3+) was proportional to the concentration of Fe(3+), and the calibration curve displayed linear regions over the range of 0-0.70 ?M. The detection limit was 4.2 nM. Finally, this novel fluorescent probe was successfully applied to the direct analysis of Fe(3+) in human serum, which presents potential applications in clinical diagnosis and may open a new way to the design of effective fluorescence probes for other biologically related targets.
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Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery.
Mol. Pharm.
PUBLISHED: 10-03-2014
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It is one of the challenges for a wide clinical application of polymer micelles to address the structure disintegration and premature drug release before reaching a pathological site. In the current study, folic acid (FA)-decorated polymer-drug conjugates (FSC) were synthesized with disulfide linkages between camptothecin (CPT) and amphiphilic poly(ethylene glycol)-b-poly(?-caprolactone) (PECL) copolymers. FSC conjugates were proposed to assemble into micelles with a hydrophobic core of PCL segments and CPT and a hydrophilic corona of PEG segments. The addition of hexadecanol during micelle formation (FSC-16) was proposed to modulate the interactions of hydrophobic segments in micelles and enhance the reductive sensitivity. FSC-16 micelles were obtained with critical micelle concentration of around 2 ?g/mL and an average size of around 200 nm, and the conjugated CPT was rapidly released out in response to glutathione. The reductive sensitivity was also demonstrated with respect to the changes of micelle size and morphologies as well as the fluorescent intensity of pyrene loaded in micelles. Benefiting from the FA receptor-mediated uptake and the reduction-sensitive release of CPT, significant cytotoxicity and cell apoptosis were identified for FSC-16 micelles against SKOV-3 cells with strong expressions of FA receptors. Flow cytometry and confocal laser scanning microscopy analyses demonstrated that CPT was distributed into nuclei after cellular uptake and intracellular release from FSC-16 micelles. Thus, the FA-decorated and reduction-sensitive micelles assembled from polymer-drug conjugates show advantages in inhibiting premature release during circulation, enhancing cellular uptake at the tumor tissues, and promoting intracellular release and nuclei location of the active moieties.
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[Magnetic resonance imaging study of disc low back pain].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 09-26-2014
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To study the diagnostic value of disc low back pain (DLBP) with lumbar disc high-intensity zone on magnetic resonance imaging (MRI) .
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Shear Stress in Atherosclerotic Plaque Determination.
DNA Cell Biol.
PUBLISHED: 08-28-2014
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Atherosclerosis initiates at predictable focal sites near arterial branches and curves, where blood flow is disturbed and shear stress is complex. Endothelial shear stress is the tangential stress derived from the friction of the flowing blood on the endothelial surface of the arterial wall. It is a key factor in modulating endothelial cell gene expression and vascular development and remodeling. Increasing evidences suggest that shear stress patterns have a strong relationship with atherosclerotic features. Moreover, variations in the local artery geometry during atherogenesis further modify flow shear stress characteristics, which contribute to the rupture site at the plaque upstream. In this study, we summarize the mechanistic evidences that associate shear stress patterns with determined atherosclerotic plaque features. An enhanced understanding of the relationship and pathophysiological function of shear stress patterns in atherosclerotic plaque features is essential, which may provide early prediction of clinical risk and guide individualized treatment strategies. In the current review, we analyzed the function of shear stress on the determination of atherosclerotic lesion and provided an update on the mechanotransduction of shear stress, gene expression regulation, and atherosclerotic plaque development and rupture.
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Supramolecular [60]Fullerene Liquid Crystals Formed By Self-Organized Two-Dimensional Crystals.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-21-2014
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Fullerene-based liquid crystalline materials have both the excellent optical and electrical properties of fullerene and the self-organization and external-field-responsive properties of liquid crystals (LCs). Herein, we demonstrate a new family of thermotropic [60]fullerene supramolecular LCs with hierarchical structures. The [60]fullerene dyads undergo self-organization driven by ?-? interactions to form triple-layer two-dimensional (2D) fullerene crystals sandwiched between layers of alkyl chains. The lamellar packing of 2D crystals gives rise to the formation of supramolecular LCs. This design strategy should be applicable to other molecules and lead to an enlarged family of 2D crystals and supramolecular liquid crystals.
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Correlation between Congenital Heart Defects and maternal copper and zinc concentrations.
Birth Defects Res. Part A Clin. Mol. Teratol.
PUBLISHED: 08-18-2014
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The aim of this study was to investigate the correlation between maternal concentrations of copper and zinc and the risk of having an infant with a congenital heart defect (CHD).
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Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous cell carcinoma.
Acta Otolaryngol.
PUBLISHED: 08-16-2014
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Increased expression of Dicer may be a prognostic biomarker for patients with laryngeal squamous cell carcinoma (LSCC).
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Baicalin attenuates Alzheimer-like pathological changes and memory deficits induced by amyloid ?1-42 protein.
Metab Brain Dis
PUBLISHED: 08-10-2014
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Baicalin is one bioactive flavone with anti-inflammatory and neuroprotective activities. The neuroprotective effects of baicalin on pathological changes and behavioral deficits were explored in a mouse model of amyloid ? (A?) 1-42 protein-induced Alzheimer's disease (AD). Mice received a bilateral injection of A?1-42 protein into the hippocampus, then they were treated with baicalin (30, 50 and 100 mg/kg body weight, orally) or Tween 80. The therapeutic effects of baicalin were monitored by Morris water maze trial and probe test. Then mice were sacrificed for immunohistochemistry and western blot analysis. After a relatively short-term treatment of 14 days, 100 mg/kg of baicalin significantly ameliorated memory impairment in the Morris water maze test and probe test, and also attenuated glial cell activations and increase of TNF-? and IL-6 expressions induced by A?1-42 protein. These results suggest that baicalin ameliorated A?1-42 protein-related pathology and cognitive dysfunction via its anti-neuroinflammatory activity, and may be a potential candidate for the treatment of AD.
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Micropatterned coculture of vascular endothelial and smooth muscle cells on layered electrospun fibrous mats toward blood vessel engineering.
J Biomed Mater Res A
PUBLISHED: 07-21-2014
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A major challenge in vascular engineering is the establishment of proper microenvironment to guide the spatial organization, growth, and extracellular matrix (ECM) productions of cells found in blood vessels. In the current study, micropatterned fibrous mats with distinct ridges and grooves of different width were created to load smooth muscle cells (SMCs), which were assembled by stacking on vascular endothelial cell (EC)-loaded flat fibrous mats to mimic the in vivo-like organized structure of blood vessels. SMCs were mainly distributed in the ridges, and aligned fibers in the patterned regions led to the formation of elongated cell bodies, intense actin filaments, and expressions of collagen I and ?-smooth muscle actin in a parallel direction with fibers. ECs spread over the flat fibrous mats and expressed collagen IV and laminin with a cobblestone-like feature. A z-stack scanning of fluorescently stained fibrous mats indicated that SMCs effectively infiltrated into fibrous scaffolds at the depth of around 200 ?m. Compared with SMCs cultured alone, the coculture with ECs enhanced the proliferation, infiltration, and cytoskeleton elongation of SMCs on patterned fibrous mats. Although the coculture of SMCs made no significant difference in the EC growth, the coculture system on patterned fibrous scaffolds promoted ECM productions of both ECs and SMCs. Thus, this patterned fibrous configuration not only offers a promising technology in the design of tissue engineering scaffolds to construct blood vessels with durable mechanical properties, but also provides a platform for patterned coculture to investigate cell-matrix and cell-cell interactions in highly organized tissues. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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From trigonal bipyramidal to platonic solids: self-assembly and self-sorting study of terpyridine-based 3D architectures.
J. Am. Chem. Soc.
PUBLISHED: 07-09-2014
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Using a series of tritopic 2,2':6',2?-terpyridine (tpy) ligands constructed on adamantane, three discrete 3D metallo-supramolecular architectures were assembled, i.e., trigonal bipyramidal, tetrahedron, and cube. The self-assembly used tritopic ligands as corner directing units and metal ions as glue units at the edge. The angles of the linkers between adamantane and tpy head play a critical role in guiding the assembled structures, which have the general formula of M3nL2n, where M denotes metal ion and L denotes ligand. All complexes were fully characterized by (1)H, (13)C NMR, diffusion-ordered NMR spectroscopy, ESI-MS, and traveling-wave ion mobility-mass spectrometry. The binary mixtures of LA and LC or LB and LC underwent a self-sorting process that led to the self-assembly of discrete 3D structures. The self-sorting behavior is solely based on the angles precoded within the arm of tritopic ligands. Moreover, kinetic study of preassembled cube and tetrahedron demonstrated a slow ligand exchange process toward a statistical mixture of hetero tetrahedrons with LA and LB.
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Prognostic significance of artemin and GFR?1 expression in laryngeal squamous cell carcinoma.
Exp Ther Med
PUBLISHED: 07-02-2014
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Artemin (ARTN) has been implicated in the development and progression of several human malignancies. However, the clinical and prognostic significance of ARTN and its receptors has not yet been investigated in human laryngeal squamous cell carcinoma (LSCC). Therefore, in the present study, the protein expression of ARTN and its receptor, namely GFR?1, was determined in 76 LSCC and 26 laryngeal polyp tissue samples using immunohistochemistry. Furthermore, the clinicopathological and prognostic significance of ARTN and GFR?1 expression was analyzed in patients with LSCC. The results revealed that the expression of ARTN and GFR?1 was significantly increased in LSCC compared with polyp tissue samples. Furthermore, the expression of ARTN and GFR?1 was positively associated with pTNM stage in LSCC. Kaplan-Meier survival analyses revealed a strong association between the expression of ARTN or GFR?1 and the survival of patients with LSCC. Correlation analysis demonstrated that the expression of ARTN was significantly correlated with the expression GFR?1. In conclusion, the results demonstrated that ARTN and GFR?1 may be useful predictors of disease progression and outcome in patients with LSCC.
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Cotransplantation of human umbilical cord mesenchymal and haplo-hematopoietic stem cells in patients with severe aplastic anemia.
Cytotechnology
PUBLISHED: 06-22-2014
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To evaluate the efficacy and safety of cotransplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) and haploidentical hematopoietic stem cells (HSCs) and to determine the correlation factors affecting incidence of graft versus host disease (GVHD) in patients with severe aplastic anemia (SAA), twenty-four SAA patients received haploidentical HSCs and UC-MSCs co-transplantation. Grafts came from a combination of granulocyte colony stimulating factor (G-CSF)-primed bone marrow and G-CSF mobilized peripheral blood stem cell of haploidentical donors, and in vitro expanded third-party donor derived UC-MSCs were employed as the cell graft. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide and fludarabine with or without busulfan. GVHD was prevented by using cyclosporine A (CSA), ATG, anti-CD25 monoclonal antibody and mycophenolate mofetil. All 24 patients achieved hematopoietic reconstitution. Median time to absolute neutrophil count >2 × 10(9)/L and platelet count >20 × 10(9)/L were 11 and 13 days, respectively. An incidence of 25 % on grade I-II acute GVHD was found while an incidence of 25 % of grade III-IV acute GVHD was seen. Blood type (r = 0.152, P = 0.043) and patient/donor pair (r = 0.541, P = 0.022) were significantly correlated with incidence of cGVHD. Transplantation related mortality was observed in 20.8 % of the cases. Co-transplantation of haploidentical HSCs and hUC-MSCs on SAA was an effective and safe approach in reducing GVHD and transplantation related mortality. The adequate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.
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Engineering blood vessels through micropatterned coculture of vascular endothelial and smooth muscle cells on bilayered electrospun fibrous mats with pDNA inoculations.
Acta Biomater
PUBLISHED: 06-16-2014
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Although engineered blood vessels have seen important advances during recent years, proper mechanical strength and vasoactivity remain unsolved problems. In the current study, micropatterned fibrous mats were created to load smooth muscle cells (SMCs), and a coculture with endothelial cells (ECs) was established through overlaying upon an EC-loaded flat fibrous mat to mimic the layered structure of a blood vessel. A preferential distribution of SMCs was determined in the patterned regions throughout the fibrous scaffolds, and aligned fibers in the patterned regions provided topological cues to guide the orientation of SMCs with intense actin filaments and extracellular matrix (ECM) productions in a circumferential direction. Plasmids DNA encoding basic fibroblast growth factors and vascular endothelial growth factor were integrated into electrospun fibers as biological cues to promote SMC infiltration into fibrous mats, the viability and ECM productions of both ECs and SMCs. The layered fibrous mats with loaded ECs and SMCs were wrapped into a cylinder, and engineered vessels were obtained with compact EC and SMC layers after coculture for 3 months. Randomly oriented ECM productions of ECs formed a continuous endothelium covering the entire lumenal surface, and a highly alignment of ECM was shown in the circumferential direction of SMC layers. The tensile strength, strain at failure and suture retention strength were higher than those of human femoral artery, and the burst pressure and radial compliance were in the same range of human saphenous vein, indicating potentials as blood vessel substitutes for transplantation in vivo. Thus, the establishment of topographical cues and biochemical signals into fibrous scaffolds demonstrates advantages in modulating cellular behaviors and organization found in complex multicellular tissues.
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Astrocyte-like cells differentiated from a novel population of CD45-positive cells in adult human peripheral blood.
Cell Biol. Int.
PUBLISHED: 06-11-2014
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We have previously reported a novel CD45-positive cell population called peripheral blood insulin-producing cells (PB-IPCs) and its unique potential for releasing insulin in vitro. Despite the CD45-positive phenotype and self-renewal ability, PB-IPCs are distinguished from hemopoietic and endothelial progenitor cells (EPCs) by some characteristics, such as a CD34-negative phenotype and different culture conditions. We have further identified the gene profiles of the embryonic and neural stem cells, and these profiles include Sox2, Nanog, c-Myc, Klf4, Notch1 and Mash1. After treatment with all-trans retinoic acid (ATRA) in vitro, most PB-IPCs exhibited morphological changes that included the development of elongated and branched cell processes. In the process of induction, the mRNA expression of Hes1 was robustly upregulated, and a majority of cells acquired some astrocyte-associated specific phenotypes including anti-glial fibrillary acidic protein (GFAP), CD44, Glutamate-aspartate transporter (GLAST) and S100?. In spite of the deficiency of glutamate uptaking, the differentiated cells significantly relaxed the regulation of the expression of brain-derived neurotrophic factor (BDNF) mRNA. This finding demonstrates that PB-IPCs could be induced into a population of astrocyte-like cells and enhanced the neurotrophic potential when the state of proliferation was limited by ATRA, which implies that this unique CD45+ cell pool may have a protective role in some degenerative diseases of the central nervous system (CNS).
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Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers.
Int J Pharm
PUBLISHED: 06-03-2014
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The vasculature in tumor microenvironment plays important roles in the tumor growth and metastasis, and the combination of vascular disrupting agents with chemotherapeutic drugs should be effective in inhibiting tumor progression. But the dosing schedules are essential to achieve a balance between vascular collapse and intratumoral uptake of chemotherapeutic agents. In the current study, emulsion and blend electrospinning were used to create compartmental fibers accommodating both combretastatin A-4 (CA4) and hydroxycamptothecin (HCPT). The release durations of CA4 and HCPT were modulated through the structure of fibers for dual drug loadings and the inoculation of 2-hydroxypropyl-?-cyclodextrin in fiber matrices. Under a noncontact cell coculture in Transwell, the sequential release of CA4 and HCPT indicated a sequential killing of endothelial and tumor cells. In an orthotopic breast tumor model, all the CA4/HCPT-loaded fibers showed superior antitumor efficacy and higher survival rate than fibers with loaded individual drug. Compared with fibrous mats with infiltrated free CA4 and fibers with extended release of CA4 for over 30 days, fibers with sustained release of CA4 for 3-7 days from CA4/HCPT-loaded fibers resulted in the most significant antitumor efficacy, tumor vasculature destruction, and the least tumor metastasis to lungs. A judicious selection of CA4 release durations in the combination therapy should be essential to enhance the tumor suppression efficacy and antimetastasis activity.
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DNA Molecular Beacon-Based Plastic Biochip: A Versatile and Sensitive Scanometric Detection Platform.
ACS Appl Mater Interfaces
PUBLISHED: 05-24-2014
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In this paper, we report a novel DNA molecular beacon (MB)-based plastic biochip platform for scanometric detection of a range of analytical targets. Hairpin DNA strands, which are dually modified with amino and biotin groups at their two ends are immobilized on a disposable plastic (polycarbonate) substrate as recognition element and gold nanoparticle-assisted silver-staining as signal reading protocol. Initially, the immobilized DNA probes are in their folded forms; upon target binding the hairpin secondary structure of the probe strand is "forced" open (i.e., converted to the unfolded state). Nanogold-streptavidin conjugates can then bind the terminal biotin groups and promote the deposition of rather large silver particles which can be either directly visualized or quantified with a standard flatbed scanner. We demonstrate that with properly designed probe sequences and optimized preparation conditions, a range of molecular targets, such as DNA strands, proteins (thrombin) and heavy metal ions (Hg(2+)), can be detected with high sensitivity and excellent selectivity. The detection can be done in both standard physiological buffers and real world samples. This constitutes a platform technology for performing rapid, sensitive, cost-effective, and point-of-care (POC) chemical analysis and medical diagnosis.
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Self-assembly of an azobenzene-containing polymer prepared by a multi-component reaction: supramolecular nanospheres with photo-induced deformation properties.
Soft Matter
PUBLISHED: 05-23-2014
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In this article, we have synthesized a polymer containing regulated azobenzene groups by one-pot multi-component polymerization (MCP) based on Passerini reaction, and investigated its self-assembly behavior and photo-induced deformation properties. We found that this molecule can form spherical structures with sizes ranging from hundreds of nanometers to several micrometers when dissolved in THF. NMR and FTIR studies indicate that there are associated hydrogen bonds among the molecules in the aggregates, which are responsible for the formation of the nanospheres. By controlling the stirring rate as the THF suspension is dropped into water, the nanospheres can be sorted according to their size. In this way, we have obtained nanospheres with relatively uniform diameter. When irradiated by UV light in the aqueous medium, the nanospheres tend to aggregate into large clusters, while in dry state they are ready to merge into island-like structures, showing a good photo-induced deformation property.
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The caspase-8 shRNA-modified mesenchymal stem cells improve the function of infarcted heart.
Mol. Cell. Biochem.
PUBLISHED: 05-17-2014
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The beneficial effects of mesenchymal stem cells (MSCs) in cardiac cell therapy are greatly limited due to poor survival after transplantation into ischemic hearts. Here, we investigated whether caspase 8 small hairpin RNA (shRNA) modification enhance human MSCs (hMSCs) survival and improve infarcted heart function. Recombinant adenovirus encoding pre-miRNA-155-designed caspase 8 shRNA was prepared to inhibit caspase 8 expression in hMSCs. The effect of caspase 8 shRNA modification on protecting hMSCs from apoptosis under the conditions of serum deprivation and hypoxia was tested by Annexin V/PI staining and caspase 8 activity assay. The caspase 8 shRNA-modified and superparamagnetic iron oxide (SPIO)-labeled hMSCs were injected into the border zone of the infarcted region of rat heart. Echocardiography and Masson trichrome staining were performed to assess heart function and cardiac fibrosis. Our results showed that adenovirus-mediated caspase 8 shRNA could efficiently inhibit caspase 8 expression in hMSCs. Knock-down of caspase 8 expression lead to inhibition of hMSCs apoptosis, reduction of caspase 8 activity and up-regulations of HGF, IGF-1 and Bcl-2. Transplantation of caspase 8 shRNA-modified hMSCs could significantly improve infracted heart function, attenuate cardiac fibrosis. Consistently, the rate of cardiomyocyte apoptosis and caspase 8 activity were significantly decreased, and the survival rate of transplanted hMSCs was markedly elevated in the myocardium receiving caspase 8 shRNA-modified hMSCs transplantation. Together, our findings implicated the therapeutic potential of caspase 8 shRNA-modified hMSCs in improving the infarcted heart function.
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Mesosilica-coated ultrafine fibers for highly efficient laccase encapsulation.
Nanoscale
PUBLISHED: 05-14-2014
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In this paper, we present a simple but efficient biomimetic method to encapsulate laccase on mesoporous silica-modified electrospun (ES) ultrafine fibers. Because of the mild immobilization conditions (room temperature, aqueous condition), the encapsulated laccase retained a high activity of 94%. Because of the protection from the silica layer, the laccase worked efficiently at 60 °C and retained a long-term activity in the presence of proteinase K. After recycling for 10 times the laccase still preserved 96% of its original reactivity. More remarkably, the immobilized laccase on fibers could completely recover its activity after thermal denature, while the free laccase permanently lost the activity. We also demonstrated that the laccase on silica-coated fibers exhibited an enhanced decolorization capability of Brilliant Blue KN-R (BBKN-R) as compared to the free laccase, showing its great potential for industrial applications.
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[Application of contrast-enhanced ultrasound in needle biopsy of tuberculous cervical lymph node].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 05-14-2014
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To study the value of contrast-enhanced ultrasound in tuberculous cervical lymph node biopsy.
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Autophagy regulates vascular endothelial cell eNOS and ET-1 expression induced by laminar shear stress in an ex vivo perfused system.
Ann Biomed Eng
PUBLISHED: 05-10-2014
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Vascular endothelial cell function responds to steady laminar shear stress; however, the underlying mechanisms are not fully elucidated. In the present study, we examined the effect of steady laminar shear stress on vascular endothelial cell autophagy and endothelial cell nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression using an ex vivo perfusion system. Human vascular endothelial cells and common arteries of New Zealand rabbits were pretreated with or without rapamycin or 3-MA for 30 min. These were then placed in an ex vivo cell perfusion system or an ex vivo organ perfusion system under static conditions (0 dynes/cm2) or steady laminar shear stress (5 or 15 dynes/cm2) for 1 h. In both ex vivo perfusion vascular endothelial cells and vascular vessel segment, steady laminar shear stress promoted autophagy and eNOS expression and inhibited ET-1 expression. Compared with steady laminar shear stress treatment alone, the pretreatment of autophagy inducer rapamycin obviously strengthened the expression of eNOS and decreased the expression of ET-1 in both the 5 and 15 dynes/cm2 treatment groups. Moreover, when pretreated with the autophagy inhibitor 3-MA, the eNOS expression was obviously inhibited and the ET-1 expression was reversed. These findings demonstrate that autophagy is upregulated under steady laminar shear stress, improving endothelial cell maintenance of vascular tone function.
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Acrolein decreases endothelial cell migration and insulin sensitivity through induction of let-7a.
Toxicol. Sci.
PUBLISHED: 05-08-2014
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Acrolein is a major reactive component of vehicle exhaust, and cigarette and wood smoke. It is also present in several food substances and is generated endogenously during inflammation and lipid peroxidation. Although previous studies have shown that dietary or inhalation exposure to acrolein results in endothelial activation, platelet activation, and accelerated atherogenesis, the basis for these effects is unknown. Moreover, the effects of acrolein on microRNA (miRNA) have not been studied. Using AGILENT miRNA microarray high-throughput technology, we found that treatment of cultured human umbilical vein endothelial cells with acrolein led to a significant (>1.5-fold) upregulation of 12, and downregulation of 15, miRNAs. Among the miRNAs upregulated were members of the let-7 family and this upregulation was associated with decreased expression of their protein targets, ?3 integrin, Cdc34, and K-Ras. Exposure to acrolein attenuated ?3 integrin-dependent migration and reduced Akt phosphorylation in response to insulin. These effects of acrolein on endothelial cell migration and insulin signaling were reversed by expression of a let-7a inhibitor. Also, inhalation exposure of mice to acrolein (1 ppm x 6 h/day x 4 days) upregulated let-7a and led to a decrease in insulin-stimulated Akt phosphorylation in the aorta. These results suggest that acrolein exposure has broad effects on endothelial miRNA repertoire and that attenuation of endothelial cell migration and insulin signaling by acrolein is mediated in part by the upregulation of let-7a. This mechanism may be a significant feature of vascular injury caused by inflammation, oxidized lipids, and exposure to environmental pollutants.
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Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-05-2014
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Sterile alpha motif domain containing protein 4 (Samd4) is an RNA binding protein that mediates translational repression. We identified a Samd4 missense mutation, designated supermodel, that caused leanness and kyphosis associated with myopathy and adipocyte defects in C57BL/6J mice. The supermodel mutation protected homozygous mice from high fat diet-induced obesity, likely by promoting enhanced energy expenditure through uncoupled mitochondrial respiration. Glucose tolerance was impaired due to diminished insulin release in homozygous mutant mice. The defects of metabolism in supermodel mice may be explained by dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling, evidenced by hypophosphorylation of 4E-BP1 and S6 in muscle and adipose tissues of homozygous mice. Samd4 may interface with mTORC1 signaling through an interaction with 14-3-3 proteins and with Akt, which phosphorylates Samd4 in vitro.
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Effect of acupotomy on nitric oxide synthase and beta-endorphin in third lumbar vertebrae transverse process syndrome model rats.
J Tradit Chin Med
PUBLISHED: 05-03-2014
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To explore the long-term effects and pain relief mechanism of acupotomy by observing changes in nitric oxide synthase (NOS) and beta-endorphin (beta-EP) in the hypothalamus, spinal cord, and peripheral blood of rats with third lumbar vertebrae (L3) transverse process syndrome.
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Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Nicholas J Kassebaum, Amelia Bertozzi-Villa, Megan S Coggeshall, Katya A Shackelford, Caitlyn Steiner, Kyle R Heuton, Diego Gonzalez-Medina, Ryan Barber, Chantal Huynh, Daniel Dicker, Tara Templin, Timothy M Wolock, Ayse Abbasoglu Ozgoren, Foad Abd-Allah, Semaw Ferede Abera, Ibrahim Abubakar, Tom Achoki, Ademola Adelekan, Zanfina Ademi, Arsène Kouablan Adou, José C Adsuar, Emilie E Agardh, Dickens Akena, Deena Alasfoor, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, Mazin J Al Kahbouri, François Alla, Peter J Allen, Mohammad A AlMazroa, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Carl A T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Majed Masoud Asad, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Arindam Basu, Sanjay Basu, Justin Beardsley, Neeraj Bedi, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku J Beyene, Zulfiqar Bhutta, Aref Bin Abdulhak, Jed D Blore, Berrak Bora Basara, Dipan Bose, Nicholas Breitborde, Rosario Cárdenas, Carlos A Castañeda-Orjuela, Ruben Estanislao Castro, Ferrán Catalá-López, Alanur Cavlin, Jung-Chen Chang, Xuan Che, Costas A Christophi, Sumeet S Chugh, Massimo Cirillo, Samantha M Colquhoun, Leslie Trumbull Cooper, Cyrus Cooper, Iuri da Costa Leite, Lalit Dandona, Rakhi Dandona, Adrian Davis, Anand Dayama, Louisa Degenhardt, Diego De Leo, Borja del Pozo-Cruz, Kebede Deribe, Muluken Dessalegn, Gabrielle A deVeber, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Rob E Dorrington, Tim R Driscoll, Sergei Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Manuela Mendonca Felicio, Seyed-Mohammad Fereshtehnejad, Graça Maria Ferreira De Lima, Mohammad H Forouzanfar, Elisabeth B França, Lynne Gaffikin, Ketevan Gambashidze, Fortuné Gbètoho Gankpé, Ana C Garcia, Johanna M Geleijnse, Katherine B Gibney, Maurice Giroud, Elizabeth L Glaser, Ketevan Goginashvili, Philimon Gona, Dinorah González-Castell, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rahul Gupta, Rajeev Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Rasmus Havmoeller, Simon I Hay, Ileana B Heredia Pi, Hans W Hoek, H Dean Hosgood, Damian G Hoy, Abdullatif Husseini, Bulat T Idrisov, Kaire Innos, Manami Inoue, Kathryn H Jacobsen, Eiman Jahangir, Sun Ha Jee, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Edmond Kato Kabagambe, Haidong Kan, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Konstantin Kazanjan, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Luke Knibbs, Yoshihiro Kokubo, Soewarta Kosen, Barthélemy Kuate Defo, Chanda Kulkarni, Veena S Kulkarni, G Anil Kumar, Kaushalendra Kumar, Ravi B Kumar, Gene Kwan, Taavi Lai, Ratilal Lalloo, Hilton Lam, Van C Lansingh, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Xiaohong Li, Yichong Li, Yongmei Li, Juan Liang, Xiaofeng Liang, Stephen S Lim, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Stephanie J London, Paulo A Lotufo, Jixiang Ma, Stefan Ma, Vasco Manuel Pedro Machado, Nana Kwaku Mainoo, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Amanda J Mason-Jones, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Jonathan de la Cruz Monis, Julio Cesar Montañez Hernandez, Ami R Moore, Maziar Moradi-Lakeh, Rintaro Mori, Ulrich O Mueller, Mitsuru Mukaigawara, Aliya Naheed, Kovin S Naidoo, Devina Nand, Vinay Nangia, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Mark J Nieuwenhuijsen, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Jae-Hyun Park, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Konrad Pesudovs, Max Petzold, Dan Poenaru, Guilherme V Polanczyk, Suzanne Polinder, Dan Pope, Farshad Pourmalek, Dima Qato, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Amany Refaat, Luca Ronfani, Nobhojit Roy, Tania Georgina Sánchez Pimienta, Mohammad Ali Sahraian, Joshua A Salomon, Uchechukwu Sampson, Itamar S Santos, Monika Sawhney, Felix Sayinzoga, Ione J C Schneider, Austin Schumacher, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Marina Shakh-Nazarova, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Sergey S Soshnikov, Luciano A Sposato, Chandrashekhar T Sreeramareddy, Konstantinos Stroumpoulis, Lela Sturua, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Feng Tan, Carolina Maria Teixeira, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Andrew L Thorne-Lyman, David L Tirschwell, Jeffrey A Towbin, Bach X Tran, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Eduardo A Undurraga, Selen Begüm Uzun, Andrew J Vallely, Coen H van Gool, Tommi J Vasankari, Monica S Vavilala, N Venketasubramanian, Salvador Villalpando, Francesco S Violante, Vasiliy Victorovich Vlassov, Theo Vos, Stephen Waller, Haidong Wang, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, James D Wilkinson, Solomon Meseret Woldeyohannes, John Q Wong, Muluemebet Abera Wordofa, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Z Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Mohsen Naghavi, Christopher J L Murray, Rafael Lozano.
Lancet
PUBLISHED: 05-02-2014
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The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
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Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I.
J. Med. Chem.
PUBLISHED: 04-25-2014
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Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In principle, it shows remarkable antibacterial activities against laboratory and clinically isolated Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further expanded its antibacterial spectrum into against Gram-negative bacteria with the assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate through the bacterial outer membrane. Finally, the therapeutic effect of haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit model. With distinctive structural difference from the antibiotics we used, the haloemodins are of value as promising antibacterial pharmacophore, especially for combat the infections caused by drug-resistant pathogens.
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Hexagon wreaths: self-assembly of discrete supramolecular fractal architectures using multitopic terpyridine ligands.
J. Am. Chem. Soc.
PUBLISHED: 04-23-2014
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In this study, we overcame a challenge in conventional self-assembly of macrocycles that uses ditopic 2,2':6',2?-terpyridine (tpy) building blocks with a 120° angle between two ligating moieties, which generally produces a mixture of multiple macrocycles instead of a single hexagon. Two supramolecular hexagon wreaths, [Zn9LA6] and [Zn12LB6], were designed and self-assembled from tritopic and tetratopic tpy ligands with Zn(II) ions, respectively. These multitopic ligands, bearing multiple binding sites, increased the total density of coordination sites and provided high geometric constraints to induce the formation of discrete structures. Such hexagon wreaths, which were constructed by simple recursion of small hexagons around a central hexagon, exhibit fractal geometry features with self-similarity at different levels. The shapes, sizes, and structures were fully characterized by NMR, ESI-MS, traveling-wave ion mobility mass spectrometry (TWIM-MS), and transmission electron microscopy. With diameters around 5.5 nm for [Zn9LA6] and 5.8 nm for [Zn12LB6], the remarkable rigidity of these fractal architectures was supported by TWIM-MS, in contrast to the high flexibility of macrocycles assembled by ditopic tpy ligands.
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Extracellular matrix protein 1 is correlated to carcinogenesis and lymphatic metastasis of human gastric cancer.
World J Surg Oncol
PUBLISHED: 04-20-2014
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Tumor-induced lymphangiogenesis is a crucial step in malignant invasion and metastasis. Extracellular matrix protein 1 (ECM1) was recently reported to play a role in lymphangiogenesis. In the present work, we aimed to evaluate the role of ECM1 in gastric cancer and examined whether aberrant expression of ECM1 increased the tumorigenic and metastatic potential of human gastric cancer.
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The apoptotic perspective of autism.
Int. J. Dev. Neurosci.
PUBLISHED: 04-05-2014
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Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and non-verbal communication, and repetitive behavior and restricted interests. The normal brain development during fetal brain development and the first year of life is critical to the behaviors and cognitions in adulthood. Programmed cell death (apoptosis) is an important mechanism that determines the size and shape of the brain and regulates the proper wiring of developing neuronal networks. Pathological activation of apoptotic death pathways under pathological conditions may lead to neuroanatomic abnormalities and possibly to developmental disabilities. It has been demonstrated a possible association between neural cell death and autism. Here, the abnormal apoptosis found in autism from postmortem and animal studies was reviewed and the possible mechanism was discussed.
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Effect of pretreatment with transdermal testosterone on poor ovarian responders undergoing IVF/ICSI: A meta-analysis.
Exp Ther Med
PUBLISHED: 04-01-2014
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In order to identify and describe the effectiveness of transdermal testosterone pretreatment on poor ovarian responders, MEDLINE, EMBASE, the Cochrane library and the Chinese biomedical database were searched for randomized controlled trials (RCTs). Three RCTs, which compared the outcomes of female pretreatment with transdermal testosterone prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with those of control groups, were included in the present review. The three RCTs enrolled a total of 221 randomized subjects. The meta-analysis revealed that females who received transdermal testosterone treatment prior to their IVF/ICSI cycle had a two-fold increase in live birth rate [risk ratio (RR)=2.01, 95% confidence interval (CI) 1.03-3.91], clinical pregnancy rate (RR=2.09, 95% CI 1.14-3.81) and a significantly more oocyte retrieved [mean difference (MD)=1.36, 95% CI 0.82-1.90]. The current findings provide evidence that pretreatment with transdermal testosterone may improve the clinical outcomes for poor ovarian responders undergoing IVF/ICSI. However, the results should be interpreted with caution due to the small sample size of the studies used and the heterogeneities. Further good quality RCTs would be needed to reach further conclusions.
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Inhibition of microRNA-21 upregulates the expression of programmed cell death 4 and phosphatase tensin homologue in the A431 squamous cell carcinoma cell line.
Oncol Lett
PUBLISHED: 03-11-2014
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microRNA-21 (miRNA/miR-21) is a well-known oncogenic miRNA that is overexpressed in various carcinomas. The tumor suppressor genes, programmed cell death 4 (PDCD4) and phosphatase tensin homologue (PTEN), which target miR-21, are underexpressed in several types of cancer. However, the expression of miR-21 and its target genes, PDCD4 and PTEN, has not yet been reported in skin squamous cell carcinoma (SCC). In the present study, anti-miR-21 was transfected into the A431 cell line, and the expression of miR-21, PDCD4 and PTEN and the level of cell apoptosis were detected by quantitative polymerase chain reaction, immunocytochemistry and western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. The expression levels of PDCD4 and PTEN in the A431 cell line transfected with anti-miR-21 were significantly increased (P<0.05) and the apoptotic ratio was significantly increased (P<0.05). The data indicate that miR-21 may play an oncogenic role in the cellular processes of SCC and represent a novel target for effective therapies.
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In vitro apatite formation on porous anodic alumina induced by a phosphorylation treatment.
J Biomater Appl
PUBLISHED: 03-05-2014
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In this study, a phosphorylation treatment of porous anodic alumina (PAA) was performed by wet impregnation in phosphoric acid and a subsequent heat treatment. The PAA and phosphorylated PAA specimens were analyzed using a field emission scanning electron microscope, an energy-dispersive X-ray spectrometer, and Fourier transform infrared spectroscopy. The apatite-forming ability of the phosphorylated PAA was evaluated by soaking the specimens in simulated body fluid for 1, 3, and 7 days. The surface microstructures and chemical property changes after soaking in simulated body fluid were again characterized by field emission scanning electron microscope, energy-dispersive X-ray spectrometer, and Fourier transform infrared spectroscopy. Results of this study demonstrated that the functional -PO4 groups introduced onto the PAA surface dramatically promoted the deposition of bone-like apatite on PAA. The results from this study indicated that the phosphorylation treatment of anodic alumina is an effective method for inducing bone-like apatite formation, and this phosphorylated PAA can be a promising candidate to be used as bioactive surface coatings on implant metals and alloys for orthopedic and dental applications.
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Hepatocyte cocultures with endothelial cells and fibroblasts on micropatterned fibrous mats to promote liver-specific functions and capillary formation capabilities.
Biomacromolecules
PUBLISHED: 02-25-2014
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The maintenance of hepatocyte phenotype and functions remains as a great challenge in the generation of functional liver tissue and in vitro model for drug metabolism studies. The use of hepatocyte coculture systems plays essential roles in the establishment of cell-cell and cell-extracellular matrix communications similar to native liver tissues. In the current study, micropatterned electrospun fibrous mats were created to load hepatocytes, fibroblasts, and endothelial cells (ECs), which were precisely assembled to establish their spatially controlled coculture for mimicking the in vivo structure of hepatic lobules. Hepatocytes formed compact polyhedral spheroids with an average diameter of 80-100 ?m, reorganized actin filaments in the cell-cell contact regions, and well-developed bile canaliculi. Compared with hepatocytes cultured alone, the coculture of hepatocytes with either fibroblasts or ECs led to significantly higher albumin secretion, urea synthesis and cytochrome P-450 expression, which were dramatically improved by the coculture of hepatocytes with both fibroblasts and ECs. The cocultured ECs well spread on patterned regions with little organized filamentous actin, and significantly higher densities and deeper penetration into patterned scaffolds were determined for ECs after coculture with fibroblasts and hepatocytes compared with those after cultured alone or coculture with either fibroblasts or hepatocytes. A Matrigel overlay assay showed that the capabilities of ECs to form capillary tubes were significantly enhanced by micropatterned coculture with fibroblasts and hepatocytes. Thus, the coculture of hepatocytes, fibroblasts, and ECs on micropatterned fibrous mats helps both hepatocytes in the maintenance of hepatic functions and ECs in the formation of capillary-like structures. It is suggested that the micropatterned coculture model described here not only provides functional hepatic tissues for predictions of drug metabolism profiles, but also will enable investigations on more complex and physiological cell-cell communications.
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Chronic kidney disease after autologous stem cell transplantation: analysis of a single center experience.
Int Urol Nephrol
PUBLISHED: 02-24-2014
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Chronic kidney disease (CKD) after allogeneic hematopoietic stem cell transplantation (HSCT) has increasingly been reported. However, CKD after autologous HSCT, especially changes in renal pathology, has rarely been reported. This study aimed to evaluate the frequency of CKD among patients who received autologous HSCT for hematological and nonhematological disorders, and analyze its clinical and pathological features.
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Electrochemical preparation of N-doped cobalt oxide nanoparticles with high electrocatalytic activity for the oxygen-reduction reaction.
Chemistry
PUBLISHED: 02-24-2014
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Nitrogen-doped CoO (N-CoO) nanoparticles with high electrocatalytic activity for the oxygen-reduction reaction (ORR) were fabricated by electrochemical reduction of CoCl2 in acetonitrile solution at cathodic potentials. The initially generated, highly reactive nitrogen-doped Co nanoparticles were readily oxidized to N-CoO nanoparticles in air. In contrast to their N-free counterparts (CoO or Co3 O4 ), N-CoO nanoparticles with a N content of about 4.6?% exhibit remarkable ORR electrocatalytic activity, stability, and immunity to methanol crossover in an alkaline medium. The Co?Nx active sites in the CoO nanoparticles are held responsible for the high ORR activity. This work opens a new path for the preparation of nitrogen-doped transition metal oxide nanomaterials, which are promising electrocatalysts for fuel cells.
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Quantification of population benefit in evaluation of biomarkers: practical implications for disease detection and prevention.
BMC Med Inform Decis Mak
PUBLISHED: 02-18-2014
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With the rapid development of "-omic" technologies, an increasing number of purported biomarkers have been identified for cancer and other diseases. The process of identifying those that are most promising and validating them for use at the population level for prevention and early detection is a critical next step in achieving significant health benefits.
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Accelerated removal of pyrene and benzo[a]pyrene in freshwater sediments with amendment of cyanobacteria-derived organic matter.
J. Hazard. Mater.
PUBLISHED: 02-02-2014
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The removal of pyrene and benzo[a]pyrene (BaP) were investigated in freshwater sediments with amendment of seven different organic matters including cyanobacteria-derived organic matter (COM), plant-derived organic matter (POM), and humic substances (HS). During the 210 days of experiments, the amendment of COM or HS enhanced significantly the removal of pyrene and BaP in sediments, especially with fresh COM (FCOM) treatment much superior to HS. On the contrary, degradation of these polycyclic aromatic hydrocarbons (PAHs) was not significantly improved and even inhibited in POM-amended sediments. The first-order rate constants of pyrene and BaP degradation in the FCOM-amended sediments reached 0.00540±0.00017d(-1) and 0.00517±0.00057d(-1), respectively, and were about three and five folds of those in the control treatment. The enhanced PAHs degradation in FCOM-amended sediments was related to higher PAH-degrading bacteria number and bioavailability with a result of biostimulation and priming effect by labile carbon and high-value nutrition in FCOM. Thus, this study improved our understanding about effects of settled biomass from cyanobacterial blooms, which occurred frequently in eutrophic aquatic ecosystems, on the natural attenuation of PAHs in sediments. Furthermore, this study would also help develop a new promising approach to remediate PAH-contaminated sediments through utilization of cyanobacterial bloom biomass.
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Acquired immunodeficiency syndrome/human immunodeficiency virus knowledge, attitudes, and practices, and use of healthcare services among rural migrants: a cross-sectional study in China.
BMC Public Health
PUBLISHED: 01-31-2014
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Today's rapid growth of migrant populations has been a major contributor to the human immunodeficiency virus (HIV) epidemic. However, relatively few studies have focused on HIV/acquired immunodeficiency syndrome (AIDS)-related knowledge, attitudes, and practice among rural-to-urban migrants in China. This cross-sectional study was to assess HIV/AIDS-related knowledge and perceptions, including knowledge about reducing high-risk sex.
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Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum disorders.
Int. J. Dev. Neurosci.
PUBLISHED: 01-28-2014
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The IGF-I/PI3K/AKT/mTOR signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, motility, survival, metabolism and protein synthesis. Insulin-like growth factor-I (IGF-I) is synthesized in the liver and fibroblasts, and its biological actions are mediated by the IGF-I receptor (IGF-IR). The binding of IGF-I to IGF-IR leads to the activation of phosphatidylinositol 3-kinase (PI3K). Activated PI3K stimulates the production of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3]. The PH domain of AKT (protein kinase B, PKB) (v-AKT murine thymoma viral oncogene homolog) binds to PI(4,5)P2 and PI(3,4,5)P3, followed by phosphorylation of the Thr308 and Ser473 regulatory sites. Tuberous sclerosis complex 1 (TSC1) and TSC2 are upstream regulators of mammalian target of rapamycin (mTOR) and downstream effectors of the PI3K/AKT signaling pathway. The activation of AKT suppresses the TSC1/TSC2 heterodimer, which is an upstream regulator of mTOR. Dysregulated IGF-I/PI3K/AKT/mTOR signaling has been shown to be associated with autism spectrum disorders (ASDs). In this review, we discuss the emerging evidence for a functional relationship between the IGF-I/PI3K/AKT/mTOR pathway and ASDs, as well as a possible role of this signaling pathway in the diagnosis and treatment of ASDs.
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MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell.
BMC Cancer
PUBLISHED: 01-27-2014
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Pancreatic cancer is one of the most aggressive cancers, and the aggressiveness of pancreatic cancer is in part due to its intrinsic and extrinsic drug resistance characteristics, which are also associated with the acquisition of epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells. And miR-200 has been identified as a powerful regulator of EMT.
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Understanding the shortage of village doctors in China and solutions under the policy of basic public health service equalization: evidence from Changzhou.
Int J Health Plann Manage
PUBLISHED: 01-26-2014
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As the most important public health service providers in rural China, village doctors are facing a new challenge of heavier workload resulting from the recent policy of public health service equalization. Studies on the shortage of village doctors, mainly based on the national statistics, have so far been very broad. This study conducted detailed field surveys to identify specific factors of and potential solutions to the shortage in village doctors. Eight hundred forty-four village doctors and 995 health decision makers and providers were surveyed through a questionnaire, and some of them were surveyed by in-depth face-to-face interviews and focus group interviews. Opinions on the shortage in village doctors and the potentially effective approaches to addressing the problem were sought. Some village doctors (51.3%) were at least 50?years old. Some village doctors (92.3%) did not want their children to become a village doctor, and the main reasons were "low salary" and "lack of social security". Village doctors felt that it was difficult to provide all the required public health services. Local residents indicated that they established good relationships with village doctors. Some health decision makers and providers (74.0%) thought that they needed more village doctors. The shortage in village doctors presents a major obstacle toward the realization of China's policy of public health service equalization. The aging of current village doctors exacerbates the problem. Policies and programs are needed to retain the current and attract new village doctors into the workforce. Separate measures are also needed to address disparities in socioeconomic circumstance from village to village. Copyright © 2014 John Wiley & Sons, Ltd.
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Expression of basic fibroblast growth factor, CD31, and ?-smooth muscle actin and esophageal cancer recurrence after definitive chemoradiation.
Tumour Biol.
PUBLISHED: 01-12-2014
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There is cumulative evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aims of this study were to analyze the expression of basic fibroblast growth factor (FGF-2), CD31, and ?-smooth muscle actin (SMA) in esophageal cancer patients and to establish their significance as indicators of disease recurrence after definitive chemoradiation (CRT). Protein expressions of FGF-2, CD31, and SMA were evaluated by immunohistochemistry and Western blot analysis in 70 patients, 20 with esophageal squamous cell carcinoma (ESCC) and 50 with locally recurrent ESCC after definitive CRT. Twenty matched normal esophageal squamous epithelium were also studied as controls. Esophageal cancer tissues showed positive expression of FGF-2, CD31, and SMA; in contrast, FGF-2 expression was not detected and only little staining for CD31 and SMA was noted in normal epithelium. Protein levels of FGF-2, CD31, and SMA were significantly elevated in recurrent ESCC. Among the patients with locally recurrent disease, expression of FGF-2 and SMA was notably high in whom the tumor recurred locally within 24 months after definitive CRT. The 2- and 5-year local recurrence-free survival rate was 15.4 % and 0 in patients with high FGF-2 expression, compared with 45.8 and 33.3 % in those who expressed low FGF-2, respectively (P = 0.005). Of patients who expressed high SMA, the 2- and 5-year local recurrence-free survival rate was 21.7 and 8.7 %, respectively, compared to those with low SMA expression which was 37.0 and 22.2 %, respectively (P = 0.016). Overexpression of FGF-2 and SMA is associated with local recurrence and reduced recurrence-free survival after definitive CRT for ESCC. The data also suggest that targeting stromal cells may be an attractive approach for esophageal cancer therapy strategies.
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In Silico Prediction of T and B Cell Epitopes of Der f 25 in Dermatophagoides farinae.
Int J Genomics
PUBLISHED: 01-09-2014
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The house dust mites are major sources of indoor allergens for humans, which induce asthma, rhinitis, dermatitis, and other allergic diseases. Der f 25 is a triosephosphate isomerase, representing the major allergen identified in Dermatophagoides farinae. The objective of this study was to predict the B and T cell epitopes of Der f 25. In the present study, we analyzed the physiochemical properties, function motifs and domains, and structural-based detailed features of Der f 25 and predicted the B cell linear epitopes of Der f 25 by DNAStar protean system, BPAP, and BepiPred 1.0 server and the T cell epitopes by NetMHCIIpan-3.0 and NetMHCII-2.2. As a result, the sequence and structure analysis identified that Der f 25 belongs to the triosephosphate isomerase family and exhibited a triosephosphate isomerase pattern (PS001371). Eight B cell epitopes (11-18, 30-35, 71-77, 99-107, 132-138, 173-187, 193-197, and 211-224) and five T cell epitopes including 26-34, 38-54, 66-74, 142-151, and 239-247 were predicted in this study. These results can be used to benefit allergen immunotherapies and reduce the frequency of mite allergic reactions.
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Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis.
J. Surg. Res.
PUBLISHED: 01-08-2014
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Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer.
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The effect of astragalus extractive on alveolar bone rebuilding progress of tooth extracted socket of ovariectomied rats.
Afr J Tradit Complement Altern Med
PUBLISHED: 01-01-2014
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Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition that causes severe loss of bone mass in the vertebrae and long bones. We explored the effect and the possible underlying mechanism of the extracts of Astragalus (AE) on the tooth alveolar bone rebuilding progress of postmenopausal osteoporosis of PMO animal models.
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Esophageal Adenocarcinoma and Its Rare Association with Barrett's Esophagus in Henan, China.
PLoS ONE
PUBLISHED: 01-01-2014
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Incidence of esophageal adenocarcinoma (EAC) has increased sharply in Western Europe and United States over the past three decades. Nearly all cases of EAC in the west are thought to be associated with Barrett's esophagus (BE) at the time of diagnosis. Regions in the Henan province of China have one of world's highest incidences of esophageal cancer, yet recent temporal trends in the relative rates of EAC with respect to esophageal squamous-cell carcinoma (ESCC), as well as its association with Barrett's esophagus (BE), have not been reported. In this report, we present large-scale longitudinal clinical and histological data on 5401 esophageal cancers (EC) patients diagnosed during the recent 10-year period (2002-2011) at Henan Cancer Hospital, China. All 217 esophageal adenocarcinoma (EAC) patients from these 5401 EC patients were examined to better understand the relationship between Barrett's esophagus (BE) and EAC. We found that EAC was relatively rare and accounted for approximately 5% of all esophageal cancers each year during 2002-2011. There is no evidence of significant temporal trends in the rate of EAC relative to ESCC. Only 10 out of 217 (4.6%) EAC cases were detected to have any evidence of Barrett's esophagus. This result raises the possibility of a different etiological basis for EAC in China motivating more detailed epidemiological, clinical and molecular characterization of EAC in China in order to better understand the neoplastic development of EAC.
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Synaptic proteins and receptors defects in autism spectrum disorders.
Front Cell Neurosci
PUBLISHED: 01-01-2014
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Recent studies have found that hundreds of genetic variants, including common and rare variants, rare and de novo mutations, and common polymorphisms contribute to the occurrence of autism spectrum disorders (ASDs). The mutations in a number of genes such as neurexin, neuroligin, postsynaptic density protein 95, SH3, and multiple ankyrin repeat domains 3 (SHANK3), synapsin, gephyrin, cadherin, and protocadherin, thousand-and-one-amino acid 2 kinase, and contactin, have been shown to play important roles in the development and function of synapses. In addition, synaptic receptors, such as gamma-aminobutyric acid receptors and glutamate receptors, have also been associated with ASDs. This review will primarily focus on the defects of synaptic proteins and receptors associated with ASDs and their roles in the pathogenesis of ASDs via synaptic pathways.
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Time-dependent Gene Profiling Indicates the Presence of Different Phases for Ischemia/Reperfusion Injury in Retina.
Ophthalmol Eye Dis
PUBLISHED: 01-01-2014
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Ischemia/reperfusion (IR) injury has been associated with several retinal pathologies, and a few genes/gene products have been linked to IR injury. However, the big picture of temporal changes, regarding the affected gene networks, pathways, and processes remains to be determined. The purpose of the present study was to investigate initial, intermediate, and later stages to characterize the etiology of IR injury in terms of the pathways affected over time. Analyses indicated that at the initial stage, 0-hour reperfusion following the ischemic period, the ischemia-associated genes were related to changes in metabolism. In contrast, at the 24-hour time point, the signature events in reperfusion injury include enhanced inflammatory and immune responses as well as cell death indicating that this would be a critical period for the development of any interventional therapeutic strategies. Genes in the signal transduction pathways, particularly transmitter receptors, are downregulated at this time. Activation of the complement system pathway clearly plays an important role in the later stages of reperfusion injury. Together, these results demonstrate that the etiology of injury related to IR is characterized by the appearance of specific patterns of gene expression at any given time point during retinal IR injury. These results indicate that evaluation of treatment strategies with respect to time is very critical.
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Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination cycles in women with polycystic ovary syndrome: a meta-analysis.
Gynecol. Endocrinol.
PUBLISHED: 12-03-2013
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Abstract Polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian stimulation and intrauterine insemination (COS/IUI) often face the risk of premature luteinization, which may result in lower pregnancy rate and higher miscarriage rate. This review was performed to identify if adjuvant treatment with GnRH antagonist (GnRH-ant) could effectively improve the clinical outcome of patients with PCOS undergoing COS/IUI. A literature search was conducted on the PubMed, EMBASE and Cochrane library databases. Two randomized controlled trials were included in this review, enrolling a total of 333 cycles. The patients who received GnRH-ant treatment had lower progesterone levels on the hCG day and a reduced premature luteinization rate. However, the rates of live birth, clinical pregnancy and miscarriage did not significantly differ between the GnRH-ant supplementation group and control group. In conclusion, although the existing randomized controlled trials indicate that GnRH-ant can effectively decrease the premature luteinizaton rate, evidence to support its use to improve clinical pregnancy outcomes in PCOS patients undergoing COS/IUI treatment is insufficient.
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Household catastrophic medical expenses in eastern China: determinants and policy implications.
BMC Health Serv Res
PUBLISHED: 11-27-2013
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Much of research on household catastrophic medical expenses in China has focused on less developed areas and little is known about this problem in more developed areas. This study aimed to analyse the incidence and determinants of catastrophic medical expenses in eastern China.
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Temporal and spatial evolution of somatic chromosomal alterations: A case-cohort study of Barretts esophagus.
Cancer Prev Res (Phila)
PUBLISHED: 11-19-2013
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All cancers are believed to arise by dynamic, stochastic somatic genomic evolution with genome instability, generation of diversity and selection of genomic alterations that underlie multi-stage progression to cancer. Advanced esophageal adenocarcinomas (EAs) have high levels of somatic copy number alterations. Barretts esophagus (BE) is a risk factor for developing EA, and somatic chromosomal alterations (SCAs) are known to occur in BE. The vast majority (~95%) of individuals with BE do not progress to EA during their lifetimes, but a small subset develop EA, many of which arise rapidly even in carefully monitored patients without visible endoscopic abnormalities at the index endoscopy. Using a well-designed, longitudinal case-cohort study, we characterized SCA as assessed by SNP arrays over space and time in 79 "progressors" with BE as they approach the diagnosis of cancer and 169 "nonprogressors" with BE who did not progress to EA over 20,425 person-months of follow-up. The genomes of nonprogressors typically had small localized deletions involving fragile sites and 9p loss/copy neutral LOH that generate little genetic diversity and remained relatively stable over prolonged follow-up. As progressors approach the diagnosis of cancer, their genomes developed chromosome instability with initial gains and losses, genomic diversity, and selection of SCAs followed by catastrophic genome doublings. Our results support a model of differential disease dynamics in which nonprogressor genomes largely remain stable over prolonged periods whereas progressor genomes evolve significantly increased SCA and diversity within four years of EA diagnosis, suggesting a window of opportunity for early detection.
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[Isolation, identification and characterization of 68 protease-producing bacterial strains from the Arctic].
Wei Sheng Wu Xue Bao
PUBLISHED: 11-08-2013
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We screened and identified protease-producing bacterial strains from the Arctic, the results would help find cold-adapted protease.
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Maternal influenza-like illness, medication use during pregnancy and risk of congenital heart defects in offspring.
J. Matern. Fetal. Neonatal. Med.
PUBLISHED: 09-27-2013
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Abstract Objective: To evaluate the association between maternal influenza and congenital heart defects (CHDs), and whether the use of traditional Chinese medicine (TCM) or Western medicine (antibiotics, antipyretic-analgesic drugs) modified this association. Method: We analysed 294 fetuses with CHDs and 416 control fetuses without any abnormalities identified from February 2010 through October 2011 in this hospital-based case-control study. Participating mothers were interviewed to determine whether they had been infected with "influenza" during the early pregnancy period or had used any medicine (TCM, Western medicine) to treat influenza. A logistic regression model was used to calculate ORs and 95% CIs while controlling for potential confounders. Results: There were significant associations between maternal influenza and CHDs in the aggregate (AOR, 1.60; 95%CI, 1.12 to 2.28) and specific subtypes, namely septal defects (AOR, 2.12; 95%CI, 1.38 to 3.26) and conotruncal defects (AOR, 1.60; 95%CI, 1.01 to 2.51). Maternal medication use (i.e. TCM or Western medicine) in the setting of influenza tended to decrease these associations. Conclusions: Maternal influenza during second-third months of pregnancy increased the risk for CHDs, with septal defects and conotruncal defects in particular being observed. The use of medication for influenza might attenuate such associations.
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Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: Successful engraftment and mild GVHD.
Stem Cell Res
PUBLISHED: 09-26-2013
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Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 21 young people with severe aplastic anemia (SAA) undergoing haplo-HSCT without T-cell-depleted. We observed that all patients had sustained hematopoietic engraftment without any adverse UC-MSC infusion-related events. Furthermore, we did not observe any increase in severe aGVHD. These data suggest that UC-MSCs, possibly thanks to their potent immunosuppressive effect on allo-reactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure and severe GVHD in haplo-HSCT.
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Expression and immune characterization of a novel enzyme, protein arginine methyltransferase 1, from Schistosoma japonicum.
Parasitol. Res.
PUBLISHED: 09-15-2013
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Protein arginine methyltransferase 1 (PRMT1) is an arginine-specific protein methyltransferase that methylates a number of proteins involved in transcription and RNA metabolism in all parasitic helminths, including the human blood fluke, Schistosoma japonicum. To characterize the role of PRMT1 in the development of S. japonicum and to investigate its influence on parasite-host interactions, we cloned and expressed the protein from an existing cDNA library. We report that the clone encoded a polypeptide comprising 360 amino acids with a predictive Mr of 42 kDa. Bioinformatic analyses predicted that there were many potential B cell epitopes and T cell epitopes associated with SjcPRMT1, suggesting it is a potential candidate molecule for vaccine development. The purified recombinant protein of S. japonicum (Chinese strain) (rSjcPRMT1) was found to be immunogenic, eliciting a high antibody titer in mice. Moreover, Western blot analysis revealed that the protein could be recognized by the sera of infected mice. Using flow cytometry, we showed that rSjcPRMT1 slightly upregulated the expression of CD40, CD80, CD86, and MHC-II molecules of mouse bone marrow-derived dendritic cell (BMDC), indicating that rSjcPRMT1 could induce mouse BMDC to mature and, therefore, activate their immune response. Overall, our findings provide evidence that rSjcPRMT1 could serve as an effective candidate molecule for the development of a vaccine against infection with S. japonicum.
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Targeted deletion and inversion of tandemly arrayed genes in Arabidopsis thaliana using zinc finger nucleases.
G3 (Bethesda)
PUBLISHED: 08-28-2013
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Tandemly arrayed genes (TAGs) or gene clusters are prevalent in higher eukaryotic genomes. For example, approximately 17% of genes are organized in tandem in the model plant Arabidopsis thaliana. The genetic redundancy created by TAGs presents a challenge for reverse genetics. As molecular scissors, engineered zinc finger nucleases (ZFNs) make DNA double-strand breaks in a sequence-specific manner. ZFNs thus provide a means to delete TAGs by creating two double-strand breaks in the gene cluster. Using engineered ZFNs, we successfully targeted seven genes from three TAGs on two Arabidopsis chromosomes, including the well-known RPP4 gene cluster, which contains eight resistance (R) genes. The resulting gene cluster deletions ranged from a few kb to 55 kb with frequencies approximating 1% in somatic cells. We also obtained large chromosomal deletions of ~9 Mb at approximately one tenth the frequency, and gene cluster inversions and duplications also were achieved. This study demonstrates the ability to use sequence-specific nucleases in plants to make targeted chromosome rearrangements and create novel chimeric genes for reverse genetics and biotechnology.
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Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases.
Physiol Rep
PUBLISHED: 08-06-2013
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Engineered cardiac tissues (ECTs) are platforms to investigate cardiomyocyte maturation and functional integration, the feasibility of generating tissues for cardiac repair, and as models for pharmacology and toxicology bioassays. ECTs rapidly mature in vitro to acquire the features of functional cardiac muscle and respond to mechanical load with increased proliferation and maturation. ECTs are now being investigated as platforms for in vitro models for human diseases and for pharmacologic screening for drug toxicities. We tested the hypothesis that global ECT gene expression patterns are complex and sensitive to mechanical loading and tyrosine kinase inhibitors similar to the maturing myocardium. We generated ECTs from day 14.5 rat embryo ventricular cells, as previously published, and then conditioned constructs after 5 days in culture for 48 h with mechanical stretch (5%, 0.5 Hz) and/or the p38 MAPK (p38 mitogen-activated protein kinase) inhibitor BIRB796. RNA was isolated from individual ECTs and assayed using a standard Agilent rat 4 × 44k V3 microarray and Pathway Analysis software for transcript expression fold changes and changes in regulatory molecules and networks. Changes in expression were confirmed by quantitative-polymerase chain reaction (q-PCR) for selected regulatory molecules. At the threshold of a 1.5-fold change in expression, stretch altered 1559 transcripts, versus 1411 for BIRB796, and 1846 for stretch plus BIRB796. As anticipated, top pathways altered in response to these stimuli include cellular development, cellular growth and proliferation; tissue development; cell death, cell signaling, and small molecule biochemistry as well as numerous other pathways. Thus, ECTs display a broad spectrum of altered gene expression in response to mechanical load and/or tyrosine kinase inhibition, reflecting a complex regulation of proliferation, differentiation, and architectural alignment of cardiomyocytes and noncardiomyocytes within ECT.
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Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in neurofibromin-deficient mice.
Hum. Mol. Genet.
PUBLISHED: 07-17-2013
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Neurofibromatosis type 1 (NF1) is a common genetic disorder affecting 1 in 3500 individuals. Patients with NF1 are predisposed to debilitating skeletal manifestations, including osteopenia/osteoporosis and long bone pseudarthrosis (nonunion fracture). Hyperactivation of the Ras/mitogen-activated protein kinase (MAPK) pathway in NF1 is known to underlie aberrant proliferation and differentiation in cell lineages, including osteoclast progenitors and mesenchymal stem cells (MSCs) also known as osteoblast progenitors (pro-OBLs). Our current study demonstrates the hyper Ras/MAPK as a critical pathway underlying the pathogenesis of NF1-associated fracture repair deficits. Nf1-deficient pro-OBLs exhibit Ras/MAPK hyperactivation. Introduction of the NF1 GTPase activating-related domain (NF1 GAP-related domain) in vitro is sufficient to rescue hyper Ras activity and enhance osteoblast (OBL) differentiation in Nf1(-/-) pro-OBLs and NF1 human (h) MSCs cultured from NF1 patients with skeletal abnormalities, including pseudarthrosis or scoliosis. Pharmacologic inhibition of mitogen-activated protein kinase kinase (MEK) signaling with PD98059 partially rescues aberrant Erk activation while enhancing OBL differentiation and expression of OBL markers, osterix and osteocalcin, in Nf1-deficient murine pro-OBLs. Similarly, MEK inhibition enhances OBL differentiation of hMSCs. In addition, PD98059 rescues aberrant osteoclast maturation in Nf1 haploinsufficient bone marrow mononuclear cells (BMMNCs). Importantly, MEK inhibitor significantly improves fracture healing in an NF1 murine model, Col2.3Cre;Nf1(flox/-). Collectively, these data indicate the Ras/MAPK cascade as a critical pathway in the pathogenesis of bone loss and pseudarthrosis related to NF1 mutations. These studies provide evidence for targeting the MAPK pathway to improve bone mass and treat pseudarthrosis in NF1.
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Quantitative assessment of the association between TP53 Arg72Pro polymorphism and risk of glioma.
Tumour Biol.
PUBLISHED: 07-16-2013
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Many studies have investigated on the association between TP53 Arg72Pro polymorphism and risk of glioma, but the impact of TP53 Arg72Pro polymorphism on glioma risk is unclear owing to the obvious inconsistence among those studies. To shed light on these inconclusive findings and get a quantitative assessment of the association between the TP53 Arg72Pro polymorphism and risk of glioma, we conducted a meta-analysis of eligible studies. We searched PubMed and Embase databases for studies investigating on the association between the TP53 Arg72Pro polymorphism and risk of glioma. The pooled odds ratios (OR) with their 95 % confidence intervals (95 % CI) was calculated to assess the association between the TP53 Arg72Pro polymorphism and risk of glioma. A total of 12 studies were finally included into the meta-analysis. Meta-analysis of the 12 studies showed that TP53 Arg72Pro polymorphism was not associated with the risk of glioma (ORPro vs. Arg?=?1.07, 95 % CI 0.93?1.22; ORProPro vs. ArgArg?=?1.02, 95 % CI 0.85?1.22; ORProPro/ArgPro vs. ArgArg?=?1.06, 95 % CI 0.85?1.34; and ORProPro vs. ArgArg/ArgPro?=?1.07, 95 % CI 0.91?1.27). Subgroup analyses by ethnicity further identified that TP53 Arg72Pro polymorphism was not associated with the risk of glioma in Caucasians. However, there was a mild association between the TP53 Arg72Pro polymorphism and risk of glioma in Asians (ORProPro vs. ArgArg/ArgPro?=?1.42, 95 % CI 1.00?2.02). Thus, there is limited evidence for the association between the TP53 Arg72Pro polymorphism and risk of glioma, and more studies are needed to provide a more comprehensive assessment of the association in Asians.
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Promoting antitumor activities of hydroxycamptothecin by encapsulation into Acid-labile nanoparticles using electrospraying.
Pharm. Res.
PUBLISHED: 06-24-2013
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Acid-labile nanoparticles are proposed to enhance the tumor targeting and anti-tumor therapy of hydroxycamptothecin (HCPT) in response to the acidic microenvironment within cells and tumor tissues.
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[Determination of metabolite residues of nitrofuran antibiotics in aquatic products by liquid chromatography-tandem mass spectrometry].
Se Pu
PUBLISHED: 06-22-2013
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A method was developed for simultaneous qualitative and quantitative analysis of five metabolites of nitrofuran antibiotics, including 3-amino-2-oxazolidinone (AOZ), 5-morpholino-methyl-3-amino-2-oxazolidinone ( AMOZ ), semicarbazide ( SEM ), 1-aminohydantoin (AHD) and 3, 5-dinitrosalicylic acid hydrazide (DNSH) in aquatic products by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were hydrolyzed with HCl, and derivatized with 2-nitrobenzaldehyde at 37 degre C for 16 hours. The derivative solutions were adjusted to pH 7.0 -7. 5, and the analytes were extracted by ethyl acetate. The separation was based on Thermo Aquasil C18 column (150 mm x 4.6 mm, 3.01 micro m). The analytes were detected by tandem mass spectrometry with electrospray ionization source with multiple reaction monitoring (MRM) mode. The developed method showed good linear correlation between the peak area ratios of the analyte and the internal standard and the concentration of the analyte with the correlation coefficients all above 0. 99 over the dynamic range of 0.5 - 10 micro g/kg. The limits of quantitation (LOQs) of AOZ, AMOZ, SEM, AHD and DNSH were 0.5 micro g/kg. The average recoveries of all the compounds at four spiked levels of 0.5, 1.0, 2.0 and 4. 0 micro g/kg ranged from 81.3% to 100.5% with the RSDs between 3.4% and 10.0% (n =6). The method is proved to be fast and effective for simultaneous qualitative and quantitative analysis of the metabolites of the nitrofuran antibiotics in aquatic products.
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Thioglucose-bound gold nanoparticles increase the radiosensitivity of a triple-negative breast cancer cell line (MDA-MB-231).
Breast Cancer
PUBLISHED: 06-19-2013
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Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16?nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays.
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Multimeric immobilization of alcohol oxidase on electrospun fibers for valid tests of alcoholic saliva.
J. Biotechnol.
PUBLISHED: 06-18-2013
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An accurate quantitation of ethanol is of great importance in clinical and forensic analyses. In the current study, alcohol oxidase (AOX) from Pichia pastoris, a multimeric enzyme consisting of eight identical subunits, was immobilized on electrospun polystyrene-co-maleic anhydride (PSMA) fibers for valid tests of alcoholic saliva. Branched polyethyleneimine (PEI) was grafted on PSMA fibers with a density of 0.15 nmol/cm(2) as tethers to allow multipoint covalent binding of enzyme molecules through glutaraldehyde activation, and the secondary and tertiary amino groups of PEI could intensify the interactions with AOX subunits to stabilize the quaternary structure. PSMA-PEI-AOX fibers were less sensitive than free AOX to the incubation temperature and pH, and indicated no detectable subunit release from the immobilized AOX after boiling in the presence of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol. Color strips were established on PSMA-PEI-AOX fibrous mats dyed with indigo Carmine after incubation into ethanol solutions of different concentrations. The color fading ratio remained no significant change after repeat tests for 9 cycles after immersion in 0.2 and 0.8 mg/mL of alcoholic saliva. It was indicated that multipoint immobilization of the multimeric enzyme was essential to improve the enzyme stability by stabilizing both the quaternary structure of the enzyme and the structure of each individual subunit.
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Electrosprayed Microparticles with Loaded pDNA-Calcium Phosphate Nanoparticles to Promote the Regeneration of Mature Blood Vessels.
Pharm. Res.
PUBLISHED: 06-13-2013
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The lack of control over microvasculature formation remains a key roadblock to the therapeutic vascularization and regeneration of functional tissues. In the current study, the integration of plasmid DNA (pDNA) condensation and electrospraying technologies was proposed to promote the regeneration of mature blood vessels through injectable or infusible administration of microparticles.
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Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy.
Ann. Hematol.
PUBLISHED: 06-13-2013
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Human leukocyte antigen haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 50 people with refractory/relapsed hematologic malignancy undergoing haplo-HSCT with myeloablative conditioning. We observed that all patients given MSCs showed sustained hematopoietic engraftment without any adverse UC-MSC infusion-related reaction. The median times to neutrophil >0.50 × 10(9)/L and platelet >20 × 10(9)/L engraftment were 12.0 and 15.0 days, respectively. We did not observe an increase in severe acute GVHD (aGVHD) and extensive chronic GVHD (cGVHD), too. Grade II-IV aGVHD was observed in 12 of 50 (24.0 %) patients. cGVHD was observed in 17 of 45 (37.7 %) patients and was extensive in 3 patients. Additionally, only five patients (10.0 %) experienced relapse at a median time to progression of 192 days. The probability that patients would attain progression-free survival at 2 years was 66.0 %. The results indicate that this new strategy is effective in improving donor engraftment and reducing severe GVHD, which will provide a feasible option for the therapy of high-risk hematologic malignancy.
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Chalcogen-based aerogels as sorbents for radionuclide remediation.
Environ. Sci. Technol.
PUBLISHED: 06-13-2013
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The efficient capture of radionuclides with long half-lives such as technetium-99 ((99)Tc), uranium-238 ((238)U), and iodine-129 ((129)I) is pivotal to prevent their transport into groundwater and/or release into the atmosphere. While different sorbents have been considered for capturing each of them, in the current work, nanostructured chalcogen-based aerogels called chalcogels are shown to be very effective at capturing ionic forms of (99)Tc and (238)U, as well as nonradioactive gaseous iodine (i.e., a surrogate for (129)I2), irrespective of the sorbent polarity. The chalcogel chemistries studied were Co0.7Bi0.3MoS4, Co0.7Cr0.3MoS4, Co0.5Ni0.5MoS4, PtGe2S5, and Sn2S3. The PtGe2S5 sorbent performed the best overall with capture efficiencies of 98.0% and 99.4% for (99)Tc and (238)U, respectively, and >99.0% for I2(g) over the duration of the experiment. The capture efficiencies for (99)Tc and (238)U varied between the different sorbents, ranging from 57.3-98.0% and 68.1-99.4%, respectively. All chalcogels showed >99.0% capture efficiency for iodine over the test duration. This versatile nature of chalcogels can provide an attractive option for the environmental remediation of the radionuclides associated with legacy wastes from nuclear weapons production as well as wastes generated during nuclear power production or nuclear fuel reprocessing.
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A novel porous bioceramics scaffold by accumulating hydroxyapatite spherulites for large bone tissue engineering in vivo. II. Construct large volume of bone grafts.
J Biomed Mater Res A
PUBLISHED: 06-05-2013
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In vivo engineering of bone autografts using bioceramic scaffolds with appropriate porous structures is a potential approach to prepare autologous bone grafts for the repair of critical-sized bone defects. This study investigated the evolutionary process of osteogenesis, angiogenesis, and compressive strength of bioceramic scaffolds implanted in two non-osseous sites of dogs: the abdominal cavity and the dorsal muscle. Hydroxyapatite (HA) sphere-accumulated scaffolds with controlled porous structures were prepared and placed in the two sites for up to 6 months. Analyses of retrieved scaffolds found that osteogenesis and angiogenesis were faster in scaffolds implanted in dorsal muscles compared with those placed in abdominal cavities. The abdominal cavity, however, can accommodate larger bone grafts with designed shape. Analyses of scaffolds implanted in abdominal cavities [an environment of a low mesenchymal stem cell (MSC) density] further demonstrated that angiogenesis play critical roles during osteogenesis in the scaffolds, presumably by supplying progenitor cells and/or MSCs as seed cells. This study also examined the relationship between the volume of bone grafts and the physiological environment of in vivo bioreactor. These results provide basic information for the selection of appropriate implanting sites and culture time required to engineer autologous bone grafts for the clinical bone defect repair. Based on these positive results, a pilot study has applied the grafts constructed in canine abdominal cavity to repair segmental bone defect in load-bearing sites (limbs). © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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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.