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Find video protocols related to scientific articles indexed in Pubmed.
Synthesis of 2-Pyridyl-benzimidazole Iridium(III), Ruthenium(II), and Platinum(II) Complexes. Study of the Activity as Inhibitors of Amyloid-? Aggregation and Neurotoxicity Evaluation.
Inorg Chem
PUBLISHED: 11-20-2014
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The design of small molecules that can target the aggregation of A? as potential therapeutic agents for Alzheimer's disease is an area of study that has attracted a lot of attention recently. The novel ligand methyl 1-butyl-2-pyridyl-benzimidazole carboxylate was prepared for the synthesis of a series of new iridium(III), ruthenium(II), and platinum(II) 2-pyridyl-benzimidazole complexes. The crystal structure of the half-sandwich iridium(III) complex was established by X-ray diffraction. An arrangement of two cationic complexes in the unit cell is observed, and it seems to be organized by weak ?···? interactions that are taking place between two symmetry-related benzimidazole ring systems. All new compounds inhibited aggregation of A?1-42 in vitro as shown by both thioflavin T fluorescence assay and transmission electron microscopy. Among them the Ir compound rescued the toxicity of A?1-42 in primary cortical neurons effectively.
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Molecular dynamics reveal a novel kinase-substrate interface that regulates protein translation.
J Mol Cell Biol
PUBLISHED: 11-19-2014
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A key control point in gene expression is the initiation of protein translation, with a universal stress response being constituted by inhibitory phosphorylation of the eukaryotic initiation factor 2? (eIF2?). In humans, four kinases sense diverse physiological stresses to regulate eIF2? to control cell differentiation, adaptation, and survival. Here we develop a computational molecular model of eIF2? and one of its kinases, the protein kinase R, to simulate the dynamics of their interaction. Predictions generated by coarse-grained dynamics simulations suggest a novel mode of action. Experimentation substantiates these predictions, identifying a previously unrecognized interface in the protein complex, which is constituted by dynamic residues in both eIF2? and its kinases that are crucial to regulate protein translation. These findings call for a reinterpretation of the current mechanism of action of the eIF2? kinases and demonstrate the value of conducting computational analysis to evaluate protein function.
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Effectiveness and Safety of Lower Doses of Mifepristone Combined With Misoprostol for the Termination of Ultra-Early Pregnancy: A Dose-Ranging Randomized Controlled Trial.
Reprod Sci
PUBLISHED: 11-15-2014
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This study aimed to investigate the effectiveness and safety of lower doses of mifepristone combined with misoprostol for the termination of ultra-early pregnancy. A total of 2500 women with ultra-early pregnancy (amenorrhea ? 35 days) were randomly divided into 5 groups with gradually decreased dose of oral mifepristone from 150 to 50 mg followed by 200 µg of oral misoprostol 24 hours later. The primary end point was complete abortion without surgical intervention. Secondary end points were vaginal bleeding, return of menses, and side effects. Rates of complete abortion were high in all groups. Moreover, the lower doses of mifepristone led to shorter vaginal bleeding period, the return of menses on the expected date, and fewer side effects. Lower doses of mifepristone combined with 200 µg of misoprostol are as effective and safe as higher doses of this combination for the termination of ultra-early pregnancy with lower possibility of vaginal bleeding and side effects.
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EVpedia: A Community Web Portal for Extracellular Vesicles Research.
Dae-Kyum Kim, Jaewook Lee, Sae Rom Kim, Dong-Sic Choi, Yae Jin Yoon, Ji Hyun Kim, Gyeongyun Go, Dinh Nhung, Kahye Hong, Su Chul Jang, Si-Hyun Kim, Kyong-Su Park, Oh Youn Kim, Hyun Taek Park, Ji Hye Seo, Elena Aikawa, Monika Baj-Krzyworzeka, Bas W M van Balkom, Mattias Belting, Lionel Blanc, Vincent Bond, Antonella Bongiovanni, Francesc E Borràs, Luc Buée, Edit I Buzás, Lesley Cheng, Aled Clayton, Emanuele Cocucci, Charles S Dela Cruz, Dominic M Desiderio, Dolores Di Vizio, Karin Ekström, Juan M Falcon-Perez, Chris Gardiner, Bernd Giebel, David W Greening, Julia Christina Gross, Dwijendra Gupta, An Hendrix, Andrew F Hill, Michelle M Hill, Esther Nolte-'t Hoen, Do Won Hwang, Jameel Inal, Medicharla V Jagannadham, Muthuvel Jayachandran, Young-Koo Jee, Malene Jørgensen, Kwang Pyo Kim, Yoon-Keun Kim, Thomas Kislinger, Cecilia Lässer, Dong Soo Lee, Hakmo Lee, Johannes van Leeuwen, Thomas Lener, Ming-Lin Liu, Jan Lötvall, Antonio Marcilla, Suresh Mathivanan, Andreas Möller, Jess Morhayim, François Mullier, Irina Nazarenko, Rienk Nieuwland, Diana N Nunes, Ken Pang, Jaesung Park, Tushar Patel, Gabriella Pocsfalvi, Hernando Del Portillo, Ulrich Putz, Marcel I Ramirez, Marcio L Rodrigues, Tae-Young Roh, Felix Royo, Susmita Sahoo, Raymond Schiffelers, Shivani Sharma, Pia Siljander, Richard J Simpson, Carolina Soekmadji, Philip Stahl, Allan Stensballe, Ewa Stępień, Hidetoshi Tahara, Arne Trummer, Hadi Valadi, Laura J Vella, Sun Nyunt Wai, Kenneth Witwer, María Yáñez-Mó, Hyewon Youn, Reinhard Zeidler, Yong Song Gho.
Bioinformatics
PUBLISHED: 11-13-2014
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Extracellular vesicles are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for extracellular vesicle-related publications and vesicular components are currently challenging.
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Insecticidal Activities of Chiral N-Trifluoroacetyl Sulfilimines as Potential Ryanodine Receptor Modulators.
J. Agric. Food Chem.
PUBLISHED: 11-07-2014
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This is the first report of novel chiral N-trifluoroacetyl sulfilimines during research for new environmentally benign and ecologically safe novel insecticides with new modes of action. Four series of phthalamides containing 20 new structures were designed, synthesized, and evaluated against oriental armyworm (Pseudaletia separata Walker) and diamondback moth (Plutella xylostella (L.)) for their insecticidal activities. The target compounds were established by corresponding (1)H NMR, HRMS (or elemental analysis), X-ray diffraction analysis, and optical polarimetry. Introduction of chiral N-trifluoroacetyl sulfiliminyl moieties into the new scaffolds showed that some target compounds possessed impressive activities as commercial flubendiamide. These N-trifluoroacetyl sulfilimines exhibited the sequence of activity against oriental armyworm as (Sc, Ss) ? (Sc, Rs) ? (Rc, Rs) > (Rc, Ss), in which the chiral carbon influenced the activities stronger than sulfur. For diamondback moth, compounds If, IIa, and IIc exhibited even stronger activity than flubendiamide; especially If displayed a death rate of 100% at 10(-6) mg L(-1), much better than that of flubendiamide (0% at 10(-4) mg L(-1)). Comparative molecular field analysis calculation indicated that stereoisomers with Sc configurations containing more electronegative group as COCF3 are favorable to the insecticidal activity. The present work demonstrated that chiral N-trifluoroacetyl sulfilimines can be considered as potential insect ryanodine receptor modulators. From the standpoint of molecular design, it was concluded that the conventional second methyl group in the aliphatic amido side chain of dicarboxamide might not be a requisite in our research on novel sulfiliminyl insecticides.
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Neuroprotection of nalmefene for postoperative patients with spontaneous intracerebral hemorrhage.
Int. J. Neurosci.
PUBLISHED: 11-07-2014
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Abstract Background: Endogenous opiates play an important role in the secondary injury of brain tissue after central nervous system injury. It was confirmed that nalmefene, an opiates receptor antagonist, has neuroprotective efficacy in animal models. However, evidence of nalmefene treatment for surgical patients with spontaneous intracerebral hemorrhage is insufficient. Methods: Outcomes of patients treated with nalmefene were retrospectively compared with that of patients without any anti-opiate treatment. The primary outcome was functional outcome at 6 months post ictus, which was assessed using modified Rankin Scales. Secondary outcomes included mortality in 30 days post ictus, state of consciousness evaluated using Glasgow Coma Scale at 1,3,7 days post operation and complications. Results: Of 79 patients in the nalmefene treatment group, 22 (27.85%) had a favorable functional outcome at 6 months, while in the control group, 12 of 72 (16.67%) had the same result (p = 0.273). A significantly better outcome was observed in the surgical group during only one subgroup analyses which was Glasgow Coma Scale (GCS) between 3 and 8 (32.26% vs 6.45%, p = 0.006). Conclusions: Nalmefene treatment was safe for patients with spontaneous intracerebral hemorrhage but could not improve the outcome of either short-term consciousness or long-term functional outcome.
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Mesomeric betaine - N-heterocyclic carbene interconversions of 1,2,4-triazolium-phenolates. Sulfur, selenium, and borane adduct formation.
Chem. Commun. (Camb.)
PUBLISHED: 11-01-2014
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The conjugated mesomeric betaines 2-(1-phenyl-4H-1,2,4-triazolium-4-yl)phenolates are masked N-heterocyclic carbenes of 1,2,4-triazole which can be trapped as thiones and selenones. Reaction with triethylborane and triphenylborane resulted in the formation of first representatives of a new zwitterionic heterocyclic ring system, benzo[e]1,2,4-triazolo[3,4-c][1,4,2]oxazaborinium-4-ide, as a formal trapping product of an anionic N-heterocyclic carbene.
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[Influence of different processing methods and mature stages on 3,29-dibenzoyl rarounitriol of Trichosanthes kirilowii seeds].
Zhong Yao Cai
PUBLISHED: 10-28-2014
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To study the different mature stages and the best processing methods on the quality of Trichosanthes kirilowii seeds.
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Nosocomial neonatal legionellosis associated with water in infant formula, taiwan.
Emerging Infect. Dis.
PUBLISHED: 10-24-2014
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We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.
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8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations.
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[Economic burden and economic risk of five major chronic diseases among Chinese urban residents].
Beijing Da Xue Xue Bao
PUBLISHED: 10-22-2014
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To provide scientific evidence for medical insurance and health policies allocating the limited health resources in China.
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[Relationship between genetic polymorphism of MTHFR C677T and nonsyndromic cleft lip with or without cleft palate in Shanxi Province of China].
Zhonghua Zheng Xing Wai Ke Za Zhi
PUBLISHED: 10-18-2014
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To assess the association between polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T locus and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Shanxi Province of China.
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NADPH Oxidase in the Renal Microvasculature Is a Primary Target for Blood Pressure-Lowering Effects by Inorganic Nitrate and Nitrite.
Hypertension
PUBLISHED: 10-15-2014
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Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood pressure responses to angiotensin II (ANG II) by modulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NO bioavailability. Nitrite in the physiological range (10(-7)-10(-5) mol/L) dilated isolated perfused renal afferent arterioles, which were associated with increased NO. Contractions to ANG II (34%) and simultaneous NO synthase inhibition (56%) were attenuated by nitrite (18% and 26%). In a model of oxidative stress (superoxide dismutase-1 knockouts), abnormal ANG II-mediated arteriolar contractions (90%) were normalized by nitrite (44%). Mechanistically, effects of nitrite were abolished by NO scavenger and xanthine oxidase inhibitor, but only partially attenuated by inhibiting soluble guanylyl cyclase. Inhibition of NADPH oxidase with apocynin attenuated ANG II-induced contractility (35%) similar to that of nitrite. In the presence of nitrite, no further effect of apocynin was observed, suggesting NADPH oxidase as a possible target. In preglomerular vascular smooth muscle cells and kidney cortex, nitrite reduced both basal and ANG II-induced NADPH oxidase activity. These effects of nitrite were also abolished by xanthine oxidase inhibition. Moreover, supplementation with dietary nitrate (10(-2) mol/L) reduced renal NADPH oxidase activity and attenuated ANG II-mediated arteriolar contractions and hypertension (99±2-146±2 mm Hg) compared with placebo (100±3-168±3 mm Hg). In conclusion, these novel findings position NADPH oxidase in the renal microvasculature as a prime target for blood pressure-lowering effects of inorganic nitrate and nitrite.
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Mussel-inspired polydopamine coated hollow carbon microspheres, a novel versatile filler for fabrication of high performance syntactic foams.
ACS Appl Mater Interfaces
PUBLISHED: 10-15-2014
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Syntactic foams, which can be synthesized by mechanical mixing of hollow microspheres with a matrix material, are a special class of lightweight composite materials. Developing of high-performance syntactic foams remains challenges. In this work, a facile and environmentally friendly surface modification method employing polydopamine (PDA) as a surface treatment agent for hollow carbon microspheres (HCMs) was used, aiming to extend the application of syntactic foams to seldom touched areas. The PDA coating was used as a strategy for interfacial interaction enhancement and also as a platform for further metal coating meant for electromagnetic interference (EMI) shielding. The stronger interfacial interaction between microspheres and polymer matrix provided effective interfacial stress transfer, as a result of the syntactic foams with high strength to weight ratio. Furthermore, the PDA coating on HCMs served as a versatile platform for the growth of noble metals on the surface of PDA-HCMs. Silver nanoparticles was grown by PDA medium. The silver coated HCMs (Ag-PDA-HCMs) impacted the complex permittivity of the syntactic foams leading to high EMI shielding effectiveness (SE). The specific EMI SE reached up to 46.3 dB·cm(3)/g, demonstrated the Ag-PDA-HCMs/epoxy syntactic foam as a promising candidate for lightweight high-performance EMI shielding material.
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Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 10-10-2014
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Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently we found a thienoquinolin UT inhibitor, PU-14, which exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition rate was 69.5% with an IC50 of 0.32 ?M. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl- levels, or non-urea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics.
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Coculture of Peripheral Blood-Derived Mesenchymal Stem Cells and Endothelial Progenitor Cells on Strontium-Doped Calcium Polyphosphate Scaffolds to Generate Vascularized Engineered Bone.
Tissue Eng Part A
PUBLISHED: 10-10-2014
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Vascularization of engineered bone tissue is critical for ensuring its survival after implantation and it is the primary factor limiting its clinical use. A promising approach is to prevascularize bone grafts in vitro using endothelial progenitor cells (EPC) derived from peripheral blood. Typically, EPC are added together with mesenchymal stem cells (MSC) that differentiate into osteoblasts. One problem with this approach is how to promote traditional tissue engineering bone survival with a minimally invasive method. In this study, we examined the effectiveness of administering to stimulate the release of peripheral blood stem cells and their co-culturing system for generating prevascularized engineered bone. Cells were isolated by Ficoll density gradient centrifugation and identified as EPC and MSC based on morphology, surface markers, and functional analysis. EPC and MSC were cocultured in several different ratios, and cell morphology and tube formation were assessed by microscopy. Expression of osteogenesis and vascularization markers was quantified by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction, and histochemical and immunofluorescence staining. Increasing the proportion of EPC in the coculture system led to greater tube formation and greater expression of the endothelial cell marker CD31. An EPC:MSC ratio of 75:25 gave the highest expression of osteogenesis and angiogenesis markers. Cocultures adhered to a three-dimensional scaffold of strontium-doped calcium polyphosphate and proliferated well. Our findings show that coculturing peripheral blood-derived EPC and MSC may prove useful for generating prevascularized bone tissue for clinical use.
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VSARICHS: a simple grading scale for vascular structural abnormality-related intracerebral haemorrhage.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 10-05-2014
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Vascular structural abnormality-related intracerebral haemorrhage (VSARICH) accounts for 10-20% of cases of intracerebral haemorrhage (ICH), but none of the grading scales for primary ICH are reliable for VSARICH. This study aimed to propose a grading scale based on clinical and anatomical parameters to predict short-term clinical outcome.
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Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells.
J Nanobiotechnology
PUBLISHED: 09-17-2014
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BackgroundActive targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-ß-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells.ResultsWe prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-ß-cyclodextrin (CM-ß-CD) nanoparticles (FA-BSA-CM-ß-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of ¿18.6 mV. FA-BSA-CM-ß-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-ß-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs.ConclusionsThese results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-ß-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.
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Angiotensin-(1-7) upregulates expression of ABCA1 and ABCG1 through the Mas receptor via the liver X receptor alpha signaling pathway in THP-1 macrophages treated with Angiotensin II.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 09-17-2014
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ATP-binding cassette transporter A1 (ABCA1) and ABCG1 play crucial roles in reverse cholesterol transport and has anti-atherosclerosis effects, and liver X receptor alpha (LXR?) can stimulate cholesterol efflux through these transporters. Angiotensin (Ang)-(1-7) can protect endothelial cells, inhibit smooth muscle cell growth, ameliorate inflammation, and exert anti-atherosclerotic effects. In this study, we attempted to clarify the effect of Ang-(1-7) on expression of ABCA1 and ABCG1, and explored the role of LXR? in the regulation of ABCA1 and ABCG1 in THP-1 macrophages that had been incubated with angiotensin II (AngII). Ang-(1-7) increased ABCA1 and ABCG1 expression in a concentration-dependent manner at both the mRNA and protein levels, promoted cholesterol efflux, and decreased cholesterol content in THP-1 macrophages treated with AngII. Moreover, Ang-(1-7) upregulated the expression of LXR? in a concentration-dependent manner in these cells. LXR? small interfering RNA, as well as the Mas receptor antagonist A-779, completely abolished these effects of Ang-(1-7). In summary, Ang-(1-7) upregulates ABCA1 and ABCG1 expression in THP-1 macrophages treated with AngII through the Mas receptor, via the LXR? pathway. This novel insight into the molecular mechanism underlying Ang-(1-7) and AngII interaction could prove useful for developing new strategies for treatment of cardiovascular diseases. This article is protected by copyright. All rights reserved.
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Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
Nat. Genet.
PUBLISHED: 09-07-2014
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To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10(-5)) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68-0.78; P = 1.00 × 10(-20)), 0.78 (0.72-0.84; P = 2.43 × 10(-15)) and 0.71 (0.65-0.77; P = 4.48 × 10(-14)), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC.
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Synthesis of hollow hydroxyapatite nanospheres by the control of nucleation and growth in a two phase system.
Chem. Commun. (Camb.)
PUBLISHED: 09-06-2014
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Hollow hydroxyapatite nanospheres were prepared by a two-phase approach by controlling nucleation and crystal growth processes. The cavities of hollow HA provide potential applications as new kinds of containers for carrying, filling in, or encapsulating other materials, thus constructing a multifunctional system with good biocompatibility.
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Complete Genome Sequence of Feline Calicivirus Strain HRB-SS from a Cat in Heilongjiang Province, Northeastern China.
Genome Announc
PUBLISHED: 09-04-2014
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Here, we report the complete genome sequence of feline calicivirus (FCV) strain HRB-SS isolated in 2014 from a cat in Heilongjiang Province of northeastern China. The virus genome is 7,705 bases, excluding the poly(A) tail. This analysis will help to understand the genetic characteristics and evolution of FCV in China.
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Isolation and characterization of a radiation-resistant bacterium from Taklamakan Desert showing potent ability to accumulate Lead (II) and considerable potential for bioremediation of radioactive wastes.
Ecotoxicology
PUBLISHED: 09-03-2014
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Radioactive wastes always contain radioactive substances and a lot of Pb compound and other heavy metals, which severely contaminate soils and groundwater. Thus, search for radiation-resistant microorganisms that are capable of sequestering Pb contaminants from the contaminated sites is urgently needed. However, very few such microorganisms have been found so far. In the present study, we discovered a novel Gram-negative bacterium from the arid Taklamakan desert, which can strongly resist both radiation and Pb(2+). Phylogenetic and phenotypic analysis indicated that this bacterial strain is closely affiliated with Microvirga aerilata, and was thus referred to as Microvirga aerilata LM (=CCTCC AB 208311). We found that M. aerilata LM can effectively accumulate Pb and form intracellular precipitations. It also keeps similar ability to remove Pb(2+) under radioactive stress. Our data suggest that M. aerilata LM may offer an effective and eco-friendly in situ approach to remove soluble Pb contaminants from radioactive wastes.
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Maternal diet-induced microRNAs and mTOR underlie ? cell dysfunction in offspring.
J. Clin. Invest.
PUBLISHED: 09-02-2014
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A maternal diet that is low in protein increases the susceptibility of offspring to type 2 diabetes by inducing long-term alterations in ? cell mass and function. Nutrients and growth factor signaling converge through mTOR, suggesting that this pathway participates in ? cell programming during fetal development. Here, we revealed that newborns of dams exposed to low-protein diet (LP0.5) throughout pregnancy exhibited decreased insulin levels, a lower ? cell fraction, and reduced mTOR signaling. Adult offspring of LP0.5-exposed mothers exhibited glucose intolerance as a result of an insulin secretory defect and not ? cell mass reduction. The ? cell insulin secretory defect was distal to glucose-dependent Ca2+ influx and resulted from reduced proinsulin biosynthesis and insulin content. Islets from offspring of LP0.5-fed dams exhibited reduced mTOR and increased expression of a subset of microRNAs, and blockade of microRNA-199a-3p and -342 in these islets restored mTOR and insulin secretion to normal. Finally, transient ? cell activation of mTORC1 signaling in offspring during the last week of pregnancy of mothers fed a LP0.5 rescued the defect in the neonatal ? cell fraction and metabolic abnormalities in the adult. Together, these findings indicate that a maternal low-protein diet alters microRNA and mTOR expression in the offspring, influencing insulin secretion and glucose homeostasis.
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[P38 MAPK signaling pathway regulates nuclear factor-?B and inducible nitric oxide synthase expressions in the substantia nigra in a mouse model of Parkinson's disease].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-02-2014
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To investigate the role of P38 mitogen-activated protein kinase (P38 MAPK) signaling pathway in regulating the expression of nuclear factor-?B (NF-?B) and inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of a mouse model of Parkinson's disease (PD).
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Decreased expression of mucin-1 in endometriosis endometrium correlated with progesterone receptor B involved in infertility.
Arch. Gynecol. Obstet.
PUBLISHED: 08-26-2014
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Mucin-1(MUC1), a type of glucoprotein, has various expression statuses on the endometrium at different menstrual phases. Normal expression of MCU1 is closely related to successful blastocyst implantation. MUC1 was synthesized and secreted by the glandular epithelium of the endometrium, which acts as a barrier to foreign bodies. The endometrium was able to recognize and accept the blastocyst implantation. Endometriosis has lower rates of successful implantation with in vitro fertilization and embryo transfer, which may involve the altered expression of MUC1 on eutopic endometrium. In vitro studies demonstrated that progesterone and its receptors affected MUC1 expression under different physiopathology conditions. Our study was designed to explore whether progesterone receptors alteration contributed to MUC1 varied expression on endometriosis endometrium.
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Microparticles: new light shed on the understanding of venous thromboembolism.
Acta Pharmacol. Sin.
PUBLISHED: 08-25-2014
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Microparticles are small membrane fragments shed primarily from blood and endothelial cells during either activation or apoptosis. There is mounting evidence suggesting that microparticles perform a large array of biological functions and contribute to various diseases. Of these disease processes, a significant link has been established between microparticles and venous thromboembolism. Advances in research on the role of microparticles in thrombosis have yielded crucial insights into possible mechanisms, diagnoses and therapeutic targets of venous thromboembolism. In this review, we discuss the definition and properties of microparticles and venous thromboembolism, provide a synopsis of the evidence detailing the contributions of microparticles to venous thromboembolism, and propose potential mechanisms, by which venous thromboembolism occurs. Moreover, we illustrate a possible role of microparticles in cancer-related venous thromboembolism.
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Brain spontaneous fluctuations in sensorimotor regions were directly related to eyes open and eyes closed: evidences from a machine learning approach.
Front Hum Neurosci
PUBLISHED: 08-20-2014
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Previous studies have demonstrated that the difference between resting-state brain activations depends on whether the subject was eyes open (EO) or eyes closed (EC). However, whether the spontaneous fluctuations are directly related to these two different resting states are still largely unclear. In the present study, we acquired resting-state functional magnetic resonance imaging data from 24 healthy subjects (11 males, 20.17 ± 2.74 years) under the EO and EC states. The amplitude of the spontaneous brain activity in low-frequency band was subsequently investigated by using the metric of fractional amplitude of low frequency fluctuation (fALFF) for each subject under each state. A support vector machine (SVM) analysis was then applied to evaluate whether the category of resting states could be determined from the brain spontaneous fluctuations. We demonstrated that these two resting states could be decoded from the identified pattern of brain spontaneous fluctuations, predominantly based on fALFF in the sensorimotor module. Specifically, we observed prominent relationships between increased fALFF for EC and decreased fALFF for EO in sensorimotor regions. Overall, the present results indicate that a SVM performs well in the discrimination between the brain spontaneous fluctuations of distinct resting states and provide new insight into the neural substrate of the resting states during EC and EO.
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Thermoelectric Seebeck effect in oxide-based resistive switching memory.
Nat Commun
PUBLISHED: 08-20-2014
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Reversible resistive switching induced by an electric field in oxide-based resistive switching memory shows a promising application in future information storage and processing. It is believed that there are some local conductive filaments formed and ruptured in the resistive switching process. However, as a fundamental question, how electron transports in the formed conductive filament is still under debate due to the difficulty to directly characterize its physical and electrical properties. Here we investigate the intrinsic electronic transport mechanism in such conductive filament by measuring thermoelectric Seebeck effects. We show that the small-polaron hopping model can well describe the electronic transport process for all resistance states, although the corresponding temperature-dependent resistance behaviours are contrary. Moreover, at low resistance states, we observe a clear semiconductor-metal transition around 150?K. These results provide insight in understanding resistive switching process and establish a basic framework for modelling resistive switching behaviour.
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The influence of Chinese one-child family status on Developmental Coordination Disorder status.
Res Dev Disabil
PUBLISHED: 08-17-2014
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We conducted a population-based study on Developmental Coordination Disorder (DCD) in mainland China to explore the influence of one-child status in Chinese families on DCD. A total of 4001 children selected from 160 classes in 15 public nursery schools. The Movement Assessment Battery for Children assessed motor function. The prevalence of DCD in Chinese one-child families (8.7%) was higher than that in multi-child families (5.9%). Chinese one-child family status (compared with younger children in multi-child families) were negatively related with total score (-1.793), Manual dexterity (-0.228), Aiming and catching (-1.145), Balance (-0.433) of MABC-2 and DCD (OR=2.294) when adjusted for the children's and family's characteristics, and perinatal factors (each p<0.05). As one of the studies in this Chinese context, it provides a platform for future intervention programs in one-child families in preventing children's developmental disorders.
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Surgical treatment of metachronous second primary lung cancer.
Ann. Thorac. Surg.
PUBLISHED: 08-16-2014
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Many studies have demonstrated that patients with metachronous second primary lung cancer (MSPLC) benefit from surgery. Owing to the lack of uniform criteria and prospective randomized trials, the extent of resection remains controversial, and prognostic factors are still not fully clear. The present study aimed to assess surgical treatment of MSPLC and identify prognostic factors of outcome.
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A pilot study of angiogenin in heart failure with preserved ejection fraction: a novel potential biomarker for diagnosis and prognosis?
J. Cell. Mol. Med.
PUBLISHED: 08-15-2014
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Characteristics of heart failure with preserved ejection fraction (HFPEF) have not yet been fully understood. The objectives of this pilot study are to detect protein expression profile in the sera of HFPEF patients, and to identify potential biomarkers for the disease. Five hundred and seven proteins were detected in the sera of healthy volunteers and patients with either HFPEF or hypertension using antibody microarrays (three in each group). The results showed that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive patients and healthy controls), while a protein expression pattern distinct from that in non-HFPEF patients was associated with HFPEF patients. The up-regulation of angiogenin in both HFPEF patients with LVEF ?50% (P = 0.004) and a subset of HFPEF patients with LVEF = 41-49% (P < 0.001) was further validated in 16 HFPEF patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF patients from controls with a mean area under the receiver operating characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426 ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P < 0.001). In addition, high angiogenin level (?426 ng/ml) was a predictor of all-cause death within a short-term follow-up duration, but not in the longer term of 36 months. This pilot study indicates that the aforementioned 17 potential biomarkers, such as angiogenin, may hold great promise for both diagnosis and prognosis assessment of HFPEF.
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The association between testicular microlithiasis and semen parameters in Chinese adult men with fertility intention: experience of 226 cases.
Urology
PUBLISHED: 08-14-2014
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To investigate the association between testicular microlithiasis (TM) and semen parameters in Chinese adult men with fertility intention.
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Characterization of Drug-Resistant Influenza A(H7N9) Variants Isolated From an Oseltamivir-Treated Patient in Taiwan.
J. Infect. Dis.
PUBLISHED: 08-14-2014
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?Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited.
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Delayed relief of hemifacial spasm after microvascular decompression: can it be avoided?
Acta Neurochir (Wien)
PUBLISHED: 08-13-2014
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Although microvascular decompression (MVD) surgery has been widely accepted as an effective treatment for hemifacial spasm (HFS), delayed relief cases have been frequently reported. Therefore, the value of an immediate redo MVD should be discussed.
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Novel multiferroicity in GdMnO3 thin films with self-assembled nano-twinned domains.
Sci Rep
PUBLISHED: 08-11-2014
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There have been many interests in exploring multiferroic materials with superior ferroelectric and magnetic properties for the purpose of developing multifunctional devices. Fabrication of thin films plays an important role in achieving this purpose, since the multiferroicity can be tuned via strain, dimensionality, and size effect, without varying the chemical composition. Here, we report exotic multiferroic behaviors, including high-TC (~75?K) ferroelectric state, a large spontaneous polarization (~4900??C/m(2)) and relatively strong ferromagnetism emerging at ~105?K, in orthorhombic GdMnO3/SrTiO3 (001) thin films with self-assembled nano-scale twin-like domains. We propose a possible ab-plane spiral-spin-order phase to be responsible for the large spontaneous polarization in the films, which can only be stabilized by relatively high magnetic field H > 6 T in the bulk crystals. It is suggested that the nano-scale twin-like domain structure is essential for the high temperature ferroelectricity and ferromagnetism of the thin films.
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Aortic arch atheroma and the risk of stroke: a meta-analysis.
J Evid Based Med
PUBLISHED: 08-08-2014
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Epidemiological studies have suggested that aortic atheroma may play a role in cerebral embolization; however, no meta-analysis was conducted to evaluate the relationship between aortic atheroma and risk of stroke. The aim of this study was to investigate the association between the presence of aortic atheroma and risk of stroke.
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Large and fast single-crystal resistive humidity sensitivity of metal pnictide halides containing van der Waals host-guest interactions.
Chem Asian J
PUBLISHED: 08-08-2014
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Two new metal pnictide halides, (Hg(9.75)As(5.5))(GaCl4)3 and (Hg13Sb8)(ZnBr4)4, have been prepared by solid-state reactions. Their structures feature 3D cationic host frameworks built of mercury pnictide polyhedra and form 1D tunnels filled with discrete guest halide polyanions; the guests and hosts are assembled by van der Waals interactions. Both complexes exhibit good single-crystal humidity sensitivity, with a humidity sensitivity factor as big as three orders of magnitude, a quick resistance response, fast recovery, and good reproducibility. This study provide a new way to design promising resistive humidity detectors by introducing van der Waals host-guest interactions into their structures.
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Minimally invasive surgery treatment for the patients with spontaneous supratentorial intracerebral hemorrhage (MISTICH): protocol of a multi-center randomized controlled trial.
BMC Neurol
PUBLISHED: 08-05-2014
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The choice of surgical or conservative treatment for patients with spontaneous intracerebral hemorrhage is controversial. Some minimally invasive treatments have been applied to hematoma evacuation and could improve prognosis to some extent. Up to now, studies on minimally invasive surgery for patients with spontaneous intracerebral hemorrhage are still insufficient.
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Brachial-ankle pulse wave velocity as a predictor of mortality in elderly chinese.
Hypertension
PUBLISHED: 08-04-2014
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Pulse wave velocity (PWV) is a measure of arterial stiffness and predicts cardiovascular events and mortality in the general population and various patient populations. In the present study, we investigated the predictive value of brachial-ankle PWV for mortality in an elderly Chinese population. Our study subjects were older (?60 years) persons living in a suburban town of Shanghai. We measured brachial-ankle PWV using an automated cuff device at baseline and collected vital information till June 30, 2013, during follow-up. The 3876 participants (1713 [44.2%] men; mean [±SD] age, 68.1±7.3 years) included 2292 (59.1%) hypertensive patients. PWV was on average 17.8 (±4.0) m/s and was significantly (P<0.0001) associated with age (r=0.48) and in unadjusted analysis with all-cause (n=316), cardiovascular (n=148), stroke (n=46), and noncardiovascular mortality (n=168) during a median follow-up of 5.9 years. In further adjusted analysis, we studied the risk of mortality according to the decile distributions of PWV. Only the subjects in the top decile (23.3-39.3 m/s) had a significantly (P?0.003) higher risk of all-cause mortality (hazard ratio relative to the whole study population, 1.56; 95% confidence interval, 1.16-2.08), especially in hypertensive patients (hazard ratio, 1.86; 95% confidence interval, 1.31-2.64; P=0.02 for the interaction between PWV and hypertension). Similar trends were observed for cardiovascular, stroke, and noncardiovascular mortality, although statistical significance was not reached (P?0.08). In conclusion, brachial-ankle PWV predicts mortality in elderly Chinese on the conditions of markedly increased PWV and hypertension.
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Neurotrophic Signaling Factors in Brain Ischemia/Reperfusion Rats: Differential Modulation Pattern between Single-Time and Multiple Electroacupuncture Stimulation.
Evid Based Complement Alternat Med
PUBLISHED: 07-14-2014
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Electroacupuncture (EA) treatment has been widely used for stroke-like disorders in traditional Chinese medicine. However, the underlying mechanisms remain unclear. Our previous studies showed that single-time EA stimulation at "Baihui" (GV 20) and "Shuigou" (GV 26) after the onset of ischemia can protect the brain against ischemic injury in rats with middle cerebral artery occlusion (MCAO). Here, we further investigated the differential effects between multiple EA and single-time EA stimulation on ischemic injury. In the present study, we found that both single-time EA and multiple EA stimulation significantly reduced MCAO-induced ischemic infarction, while only multiple EA attenuated sensorimotor dysfunctions. Also, with PCR array screening and ingenuity gene analysis, we revealed that multiple EA and single-time EA stimulation could differentially induce expression changes in neurotrophic signaling related genes. Meanwhile, with western blotting, we demonstrated that the level of glia maturation factor ? (GMF?) increased in the early stage (day 1) of reperfusion, and this upregulation was suppressed only by single-time EA stimulation. These findings suggest that the short-term effect of single-time EA stimulation differs from the cumulative effect of multiple EA, which possibly depends on their differential modulation on neurotrophic signaling molecules expression.
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Knockdown of PPP5C Inhibits Growth of Hepatocellular Carcinoma Cells In Vitro.
Appl. Biochem. Biotechnol.
PUBLISHED: 07-02-2014
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Ser/Thr protein phosphatase 5 (PPP5C) has been reported to participate in tumor progression. However, its functional role in hepatocellular carcinoma (HCC) remains unknown yet. In this study, we firstly evaluated the expression levels of PPP5C in six HCC cell lines by real-time PCR and found that PPP5C was widely expressed in HCC cells. To explore the role of PPP5C in HCC cell growth, lentivirus-mediated short hairpin RNA (shRNA) was employed to silence PPP5C expression in HepG2 and Bel-7404 cells. The expression of PPP5C was significantly downregulated in PPP5C knockdown cells. Knockdown of PPP5C markedly suppressed the proliferation and colony formation ability of HCC cells. Moreover, cell cycle analysis showed that PPP5C depletion in HepG2 cells led to G0/G1 phase and G2/M phase arrest. We demonstrate for the first time that PPP5C is essential for growth of HCC cells, which suggests that inhibition of PPP5C by RNAi may be a potential therapeutic strategy for the treatment of HCC.
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Downregulation of GSK3? by miR-544a to maintain self-renewal ability of lung caner stem cells.
Oncol Lett
PUBLISHED: 07-01-2014
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In order to study the influence and mechanism of miR-544a on the self-renewal ability of lung cancer stem cells, TargetScan was used to predict the target gene of miR-544a. A luciferase reporter system and western blotting were used to validate the target genes identified by TargetScan. 95C and 95D low and high metastatic human lung cancer cells were transfected with miR-544a, and quantitative polymerase chain reaction (qPCR) was used to verify the miR-544a expression in these two cell lines. Tumor ball (spheroid) suspension culture was use to study the effects of miR-544a on lung cancer stem cells. TargetScan predicted that miR-544a interacted with GSK3?. A luciferase reporter system (F=201.37, P<0.01) and western blot analysis was used to validate that miR-544a could inhibit the expression of GSK3?, while ?-catenin and CD133 were significantly increased in miR-544a-overexpressing 95C and 95D cells (F=9.43, 7.73 and 3.37, respectively; P<0.01). qPCR revealed that miR-544a was overexpressed in transfected 95C and 95D cells (20.51±0.97 and 15.16±1.38, respectively; F=418.05; P<0.01). miR-544a-overexpressing cells formed spheroids in suspension cultures of spheroid single cells. miR-544a was shown to reduce the expression of GSK3? and activate the Wnt signaling pathway to maintain the self-renewal ability of lung caner stem cells.
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Effectiveness and safety of microvascular decompression surgery for treatment of trigeminal neuralgia: a systematic review.
J Craniofac Surg
PUBLISHED: 07-01-2014
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Microvascular decompression has been now accepted worldwide as a reasonable treatment for trigeminal neuralgia, yet, as a functional operation in the cerebellopontine angle, this process may be risky and the postoperative outcomes might not be good enough sometimes. To assess the effectiveness and safety of microvascular decompression for treatment of trigeminal neuralgia, we conducted a systematic review. Using the keywords "trigeminal neuralgia", "microvascular decompression", or "neurovascular conflict", manuscripts published in English-language journals and indexed in PubMed between January 1, 2000 and June 1, 2013 on the treatment of trigeminal neuralgia (TN) with microvascular decompression were considered for this study. The success and complications were analyzed. The success in this investigation was defined as complete pain free. Continuous outcomes were summarized using means or medians, and dichotomous outcomes were presented as percentage associated with 95% confidence interval. Twenty-six papers with 6,847 patients were finally enrolled in this review. Among them, the male-to-female ratio was 1:1.4, the left-to-right ratio was 1:1.6, and the pain was located in the innervation of V3 and/or V2 in most of the cases with only 2.3% (0.1-4.7) of V1 exclusively. The average age at surgery was 60.9 years (52.5-64.1) with TN symptoms duration of 24.7 months (6.1-42.1) before microvascular decompression (MVD). Operative findings confirmed the superior cerebellar artery, anterior inferior cerebellar artery, posterior inferior cerebellar artery, and multiple vascular contacts (including veins) as the most common sources of nerve compression. The average follow-up duration was 35.8 months (26.2-56.6). The success rate was 83.5% (79.6-89.1). Complications included incisional infection in 1.3% (0.1-2.5), facial palsy 2.9% (0.5-6.2), facial numbness 9.1% (1.3-19.6), cerebrospinal fluid leak 1.6% (0.7-2.5), and hearing deficit 1.9% (0.2-3.9). The postoperative mortality was 0.1% (0.02-0.2). Accordingly, MVD is the most effective treatment for patients with trigeminal neuralgia. An immediate pain free can be achieved by an experienced neurosurgeon with good knowledge of the regional anatomy. To avoid complications, each single step of the process cannot be overemphasized.
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Identification and characterisation of tobacco microRNA transcriptome using high-throughput sequencing.
Plant Biol (Stuttg)
PUBLISHED: 06-28-2014
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MicroRNAs (miRNAs) are post-transcriptional regulators that are involved in numerous biological processes in plants. In this study, we investigate miRNAs in Honghua Dajinyuan, an agronomically important species of tobacco in China. Here, we report a comprehensive analysis of miRNA expression profiles in the leaf, stem and root using a high-throughput sequencing approach. A total of 165 miRNAs, representing 55 conserved families, and 50 novel miRNAs, representing 19 families, were identified in three libraries. In addition, 12 miRNAs were randomly selected from a differentially expressed conserved miRNA family in three libraries with expression alterations and subjected to qRT-PCR validation. Of these, the expression level of nta-miR167d is highly enriched in the leaf tissue. In addition, the expression level of nta-miR319a is prominently enriched in the stem, while nta-miR160c is highly enriched in the root. Moreover, the target prediction showed that most of the targets coded for transcription factors that are involved in cellular and metabolic processes. GO analysis showed that most of the targets were involved in organelle function, served binding functions, and take part in cellular and metabolic processes. This study helps shed new light on understanding the role of miRNAs in different parts of the tobacco plant and adds a significant number of novel miRNAs to the tobacco miRNA transcriptome. This article is protected by copyright. All rights reserved.
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Ectopic thyroid papillary carcinoma of nasopharynx associated with adenoid hypertrophy: an unusual presentation.
Head Face Med
PUBLISHED: 06-25-2014
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Ectopic thyroid tissue of nasopharynx is an uncommon phenomenon and papillary thyroid carcinoma arising from the tissue is extremely rare. The authors report a rare case of 16-year-old girl with papillary thyroid carcinoma of nasopharynx. Clinicians were ever confused by adenoid hypertrophy and solved the diagnostic dilemma by adequate examinations. In the case, we mainly emphasize that surgeons should be aware of and actively consider such a possibility of ectopic papillary thyroid carcinoma of nasopharynx in children and adolescents with long-term nasal obstruction, even if thyroid carcinoma is a rare tumor.
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Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1? protein.
Mol Med Rep
PUBLISHED: 06-16-2014
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Resveratrol has been shown to have antineoplastic effects in vivo and in vitro. However, the effect of resveratrol on the hypoxia-enhanced proliferation and invasion of osteosarcoma cells remains unclear. In this study, we investigated the role of resveratrol on regulating proliferation and invasion of osteosarcoma cells under hypoxic conditions. Saos-2 cells were cultured under controlled hypoxic conditions (3% O2) or normoxic conditions. Resveratrol (50 µM) was added in the medium, and hypoxia inducible factor-1? (HIF-1?) siRNA was used to inhibit HIF-1? transcription. Proliferation of Saos-2 cells was evaluated by the methabenzthiazuron (MTT) assay. The invasive ability of Saos-2 cells was determined by a Transwell assay. HIF-1?, E-cadherin and vimentin protein levels were detected by western blot analysis. HIF-1?, E-cadherin and vimentin mRNA levels were assessed by RT-PCR. Compared to the control group, hypoxia significantly increased the proliferation rate and invasive ability of Saos-2 cells. Moreover, hypoxia markedly increased the E-cadherin level and decreased vimentin expression. However, resveratrol or HIF-1? silencing reverted all the above effects of hypoxia in Saos-2 cells. Moreover, resveratrol inhibited HIF-1? protein accumulation without affecting the HIF-1? mRNA level. These data suggest that resveratrol can inhibit the hypoxia?enhanced proliferation, invasion and epithelial to mesenchymal transition process in osteosarcoma via downregulation of the HIF-1? protein. Thus, HIF-1? may be a promising drug target of resveratrol in the context of development of anticancer therapy for human osteosarcoma.
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Cholesteatoma of cerebellopontine angle presented as trigeminal neuralgia.
J Craniofac Surg
PUBLISHED: 06-11-2014
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Cholesteatoma in the cerebellopontine angle presented as trigeminal neuralgia are not common. Between 2010 and 2013, 12 such patients were operated on in our department. Those patients included 8 females and 4 males with an average age of 47.8 years. One patient was combined with the ipsilateral hemifacial spasm. Five patients had hypesthesia in the ipsilateral side of the face. During the surgery, a pearly sheen mass with boundary was found in the cerebellopontine angle, and the trigeminal root was buried in the tumor. The tumor was removed totally in all the cases. Afterwards, the trigeminal root was observed distorted in 5 and the offending vessel was finally distinguished in 9. Postoperatively, the symptoms were relieved in all the cases and no recurrence was found up to the 36-month period of follow-up. We believed that the etiology of secondary trigeminal neuralgia caused by cholesteatoma is still the neurovascular confliction; the only difference is that the offending vessel was pushed by the tumor instead of idiopathically. Sometimes, the offending artery may not be found after the tumor resection for it may have been transposed off while the tumor is being removed.
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P-Akt/miR?200 signaling regulates epithelial-mesenchymal transition, migration and invasion in circulating gastric tumor cells.
Int. J. Oncol.
PUBLISHED: 06-10-2014
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Both circulating tumor cells (CTCs) and epithelial-mesenchymal transition (EMT) play an important role in invasion, migration and chemoresistant in tumor development. This study aimed to detect whether EMT occurred in human gastric CTCs and to explore the mechanism of EMT in human gastric CTCs. We analysed epithelial markers (pan-CK, E-cadherin), mesenchymal markers (N-cadherin, vimentin) EMT related miR?200s, and Akt in gastric CTCs. The impact of miR?200s on EMT, migration and invasion in CTCs was tested. We found that epithelial markers pan-CK, E-cadherin were decreased, and mesenchymal markers N-cadherin, vimentin were overexpressed in gastric CTCs. Expression of EMT related transcriptors, snail1, zeb1, twist1, were reversely correlated with miR?200s, and were positively correlated with phospho-Akt. Upregulated of miR?200s downregulated twist1 and zeb1 mRNA expression, and resulted in the supression of EMT, and impaired migration and invasion in gastric CTCs. Inhibition of p-Akt led to upregulation of miR?200s. In conclusion, gastric CTCs exhibited remarkable EMT process, and p-Akt/miR?200s signaling regulates EMT, migration and invasion in gastric CTCs.
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Upregulation of Nav1.8 in demyelinated facial nerves might be relevant to the generation of hemifacial spasm.
J Craniofac Surg
PUBLISHED: 06-04-2014
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Our previous studies demonstrated that the abnormal muscle response could vanish when the ipsilateral superior cervical ganglion was removed and reappear when norepinephrine was dripped at the neurovascular conflict site. Evidentially, we believed that the mechanism of hemifacial spasm should involve emersion of ectopical action potential in the compressed facial nerve fibers. As the action potential is ignited by ion channel opening, we focused on Nav1.8 that has been found overexpressed in peripheral nerve while damaged. In this study, Moller model was adopted, 20 Sprague-Dawley rats underwent drip of norepinephrine, and the abnormal muscle response wave was monitored in 14 rats. Antibodies against unique epitopes of the ? subunit of sodium channel isoforms were used to detect the Nav1.8 neuronal isoforms, and the immunohistochemistry showed strong staining in 13 rats, which were all in the abnormal muscle response positive group (P < 0.05). Accordingly, we concluded that the substance of hemifacial spasm is an ectopic action potential that emerged on the damaged facial nerve, which might be coupled by Nav1.8.
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Asymptomatic Hemorrhagic Transformation after Acute Ischemic Stroke: Is It Clinically Innocuous?
J Stroke Cerebrovasc Dis
PUBLISHED: 05-28-2014
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Whether asymptomatic hemorrhagic transformation (HT) is clinically innocuous, that is, unassociated with clinically detectable neurologic deterioration, remains an open question. To explore this, we examined whether asymptomatic HT affects long-term poor outcome and risk of stroke recurrence.
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Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization.
Sci Rep
PUBLISHED: 04-28-2014
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Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-?, and interferon-? onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance.
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Influenza A(H5N2) virus antibodies in humans after contact with infected poultry, Taiwan, 2012.
Emerging Infect. Dis.
PUBLISHED: 04-23-2014
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Six persons in Taiwan who had contact with poultry infected with influenza A(H5N2) showed seroconversion for the virus by hemagglutinin inhibition or microneutralization testing. We developed an ELISA based on nonstructural protein 1 of the virus to differentiate natural infection from cross-reactivity after vaccination; 2 persons also showed seroconversion by this test.
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Isolation and characterization of circulating tumor cells from human gastric cancer patients.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-16-2014
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Circulating tumor cells (CTCs) have been proved to be responsible for tumor metastasis and resistant to anticancer therapies. This study aims to isolate and characterize circulating tumor cells from human gastric cancer patients, and investigate characteristic differences between gastric CTCs and gastric cancer cell lines.
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High magnetic field phase diagram in electron-doped manganites La(0.4)Ca(0.6)Mn(1-y)Cr(y)O3.
Sci Rep
PUBLISHED: 04-10-2014
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We report the charge-order to ferromagnetic phase transition induced by pulsed high magnetic field and impurity doping effects in manganites La(0.4)Ca(0.6)(Mn(1-y)Cr(y))O3 (0 ? y ? 0.2). Significant charge-order suppression and ferromagnetic tendency upon the Cr(3+)-doping are evidenced, and three different ground states are identified, namely the charge-order state, the phase separated state, and the spin-glass like state. Phase diagram in the H-y plane at 4.2 K is determined by the high magnetic field study, in which the charge-order and ferromagnetic phase boundary is clearly figured out. The critical magnetic field for melting the charge-order phase of La(0.4)Ca(0.6)MnO3 is revealed to reach up to 46 T at 4.2 K. Interestingly, distinct responses of the three states to the high magnetic field are observed, indicating the special physics regarding the charge order melting process in each state. The mechanism of the doping induced charge-order suppression and ferromagnetism promotion can be understood by the competition between the antiferromagnetic interaction of Cr-Mn and local enhancement of electron hopping by Cr(3+).
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Mg²? coordinating dynamics in Mg:ATP fueled motor proteins.
J Chem Phys
PUBLISHED: 03-25-2014
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The coordination of Mg(2+) with the triphosphate group of adenosine triphosphate (ATP) in motor proteins is investigated using data mining and molecular dynamics. The possible coordination structures available from crystal data for actin, myosin, RNA polymerase, DNA polymerase, DNA helicase, and F1-ATPase are verified and investigated further by molecular dynamics. Coordination states are evaluated using structural analysis and quantified by radial distribution functions, coordination numbers, and pair interaction energy calculations. The results reveal a diverse range of both transitory and stable coordination arrangements between Mg(2+) and ATP. The two most stable coordinating states occur when Mg(2+) coordinates two or three oxygens from the triphosphate group of ATP. Evidence for five-site coordination is also reported involving water in addition to the triphosphate group. The stable states correspond to a pair interaction energy of either ?-2750 kJ/mol or -3500 kJ/mol. The role of water molecules in the hydration shell surrounding Mg(2+) is also reported.
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Effect of salidroside on lung injury by upregulating peroxisome proliferator-activated receptor ? expression in septic rats.
Exp Ther Med
PUBLISHED: 03-11-2014
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Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. Thus, the aim of the present study was to investigate the beneficial effects of salidroside on ameliorating cecal ligation and puncture (CLP)-induced lung inflammation. Rats underwent CLP surgery to induce ALI and 800 mg/kg salidroside (i.v.) was administered 24 h after the CLP challenge. Subsequently, biochemical changes in the blood and lung tissues, as well as morphological and histological alterations in the lungs, that were associated with inflammation and injury were analysed. CLP was shown to significantly increase the serum levels of plasma tumour necrosis factor-? and interleukin-6, -1? and-10. In addition, CLP increased pulmonary oedema, thickened the alveolar septa and caused inflammation in the lung cells. These changes were ameliorated by the administration of 800 mg/kg salidroside (i.v.) 24 h after the CLP challenge. This post-treatment drug administration also significantly attenuated the lipopolysaccharide-induced activation of nuclear factor-?? and increased the release of peroxisome proliferator-activated receptor ? in the lung tissue. Therefore, salidroside administered following the induction of ALI by CLP significantly prevented and reversed lung tissue injuries. The positive post-treatment effects of salidroside administration indicated that salidroside may be a potential candidate for the management of lung inflammation in CLP-induced endotoxemia and septic shock.
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Microvesicles and diabetic complications--novel mediators, potential biomarkers and therapeutic targets.
Acta Pharmacol. Sin.
PUBLISHED: 03-10-2014
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Microvesicles (MVs), also known as microparticles, are small membrane vesicles released from different cell types under different conditions. MVs have been detected in the circulation and in organs/tissues in various diseases, including diabetes. Patients with different types of diabetes and complications have different cellular MV patterns. Studies have shown that MVs may mediate vascular thrombosis, vascular inflammation, angiogenesis, and other pathological processes of the disease through their procoagulant, pro-inflammatory, pro-angiogenic, proteolytic, and other properties. Therefore, MVs contribute to the development of diabetic macrovascular and microvascular complications. In addition, clinical studies have indicated that changes in MV number and composition may reflect the pathophysiological conditions of disease, and therefore, may serve as potential biomarkers for diagnostic and prognostic use. Understanding MVs' involvement in the pathophysiological conditions may provide insight into disease mechanisms and would also be helpful for the development of novel therapeutic strategies in the future. Here, we review the latest publications from our group and other groups and focus on the involvement of MVs in diabetic complications.
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Effect of melilotus extract on lung injury by upregulating the expression of cannabinoid CB2 receptors in septic rats.
BMC Complement Altern Med
PUBLISHED: 02-24-2014
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M. Suaveolens Ledeb has long been used in China to treat inflammatory infectious diseases. Melilotus is extracted from Melilotus Suaveolens Ledeb and its therapeutic potential is associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of melilotus extract in a rat cecal ligation and puncture (CLP)-induced animal model of acute lung injury (ALI).
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Xuebijing exerts protective effects on lung permeability leakage and lung injury by upregulating Toll-interacting protein expression in rats with sepsis.
Int. J. Mol. Med.
PUBLISHED: 02-23-2014
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Xuebijing (XBJ) is a type of traditional Tibetan medicine, and previous pharmacological studies have shown that the ethanol extract is derived from Chuanxiong, Chishao, Danshen and Honghua. Chuanxiong, Chishao, Danshen and Honghua possesses potent anti-inflammatory activity, and has been used in the treatment of inflammatory infectious diseases. In the present study, we investigated the effects of XBJ on pulmonary permeability and lung injury in cecal ligation and puncture (CLP)?induced sepsis in rats. A CLP sepsis model was established for the control and treatment groups, respectively. Approximately 2 h prior to surgery, an amount of 100 mg/kg XBJ injection was administered to the treatment group. Reverse transcription polymerase chain reaction (PT-PCR) and western blot analysis were used to examine the expression of Toll?interacting protein (Tollip), interleukin-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), nuclear factor-?B65 (NF-?B65) and TNF receptor?associated factor 6 (TRAF6) in lung tissue. ELISA was applied to detect changes of tumor necrosis factor-? (TNF??), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels in bronchoalveolar lavage (BAL) fluid, and intercellular adhesion molecule 1 (ICAM-1) and von wille-brand factor (vWF) in serum. The number of neutrophils, albumin and total cells in the BAL fluid were measured. For histological analysis, hematoxylin and eosin (H&E) stains were evaluated. Lung permeability, the wet/dry weight ratio (W/D) and the lung pathology score were determined following the induction of ALI by CLP for 24 h. The results demonstrated that XBJ upregulated Tollip expression and blocked the activity of IRAK1, TLR4, NF-??65 and TRAF6. Additionally, the number of neutrophils and total cells were significantly decreased in the XBJ group compared to that in the control group. Lung permeability, the wet/dry weight ratio (W/D) and the lung pathology score were significantly decreased in the XBJ group. The histological results also demonstrated the attenuation effect of XBJ on CLP-induced lung inflammation. The results of the present study indicated that XBJ has a significantly reduced CLP-induced lung permeability by upregulating Tollip expression. The protective effects of XBJ suggest its therapeutic potential in CLP?induced acute lung injury treatment.
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The role of STAT-6 as a key transcription regulator in HeLa cell death induced by IFN-?/TNF-? co-immobilized on nanoparticles.
Biomaterials
PUBLISHED: 02-16-2014
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Based on the fact that the transcription of STAT-1 plus its Serine 727 and Tyrosine 701 phosphorylation is not the pre-requisite for the cell death signal transduction in the IFN-? signaling pathway induced by co-immobilized IFN-?/TNF-?, we investigate both in vitro and in vivo the key transcription regulators to promote the signal transduction of HeLa cells. It is found that IFN-? R2 is the important death signal receptor in the HeLa cell death by RNA interference. Checking the expression of the whole transcription (STAT) protein family reveals that STAT-6 is highly expressed in comparison with the other STAT proteins. The gene silence of IFN-? R2 leads to the down-regulation of STAT-6 and phosphorylation-STAT-6 (p-STAT-6) expressions. The successful gene silence of STAT-6 results in the reduction of HeLa cell programmed death and the expression of several important key factors related to programmed cell death (p53, Bcl-2, and Bax). More importantly, our in vivo experiments by injecting nanoparticle drug carriers with the co-immobilized IFN-?/TNF-? into nude mice model confirm the high expression of STAT-6 and p-STAT-6. It is thus concluded that, in response to IFN-?, the co-immobilized IFN-?/TNF-? unusually promotes the activation of STAT-6 rather than STAT-1, resulting in the enhanced cell programmed death in HeLa. The present work reveals the gene-level molecular mechanism of IFN-?/TNF-? co-immobilized on biomaterials as a potentially effective therapy against cancer cells.
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Targeted Activation of Human V?9V?2-T Cells Controls Epstein-Barr Virus-Induced B Cell Lymphoproliferative Disease.
Cancer Cell
PUBLISHED: 02-14-2014
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Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) after transplantation remains a serious and life-threatening complication. Herein we showed that the aminobisphosphonate pamidronate-expanded human V?9V?2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through ?/?-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2(-/-)?c(-/-) mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded V?9V?2-T cells alone effectively prevented EBV-LPD in Rag2(-/-)?c(-/-) mice and induced EBV-LPD regression in EBV(+) tumor-bearing Rag2(-/-)?c(-/-) mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of V?9V?2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through V?9V?2-T cell targeting.
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Comparison between autologous blood transfusion drainage and no drainage/closed-suction drainage in primary total hip arthroplasty: a meta-analysis.
Arch Orthop Trauma Surg
PUBLISHED: 02-12-2014
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Primary aim of this meta-analysis of randomized controlled trials (RCTs) was to compare blood loss, transfusion rate and postoperative hemoglobin levels at 24-48 h after primary total hip arthroplasty (THA) between autologous blood transfusion (ABT) drainage and no drainage/closed-suction drainage and to obtain a powerful conclusion which way of drainage had the best clinical efficacy. Secondary aim was to compare the postoperative complication rates during the first year to indentify which way of drainage was safest.
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Effect of Melilotus extract on lung injury via the upregulation of tumor necrosis factor-?-induced protein-8-like 2 in septic mice.
Mol Med Rep
PUBLISHED: 02-06-2014
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As a Traditional Chinese Medicine, Melilotus extracts have been reported to function as an anti?inflammatory agent, antioxidant and inhibitor of capillary permeability. The present study aimed to identify the mechanisms by which Melilotus interferes with inflammation?associated and oxidative stress pathways during sepsis. An animal model of cecal ligation?perforation (CLP)?induced sepsis was established. Two hours prior to surgery, animals in the treatment group were administered 25 mg/kg Melilotus extract tablets and subsequently every 8 h. At 24 h post?administration, pathological modifications in lung tissue and expression levels of tumor necrosis factor???induced protein?8?like 2 (TIPE2) expression, nuclear factor (NF)??B, toll?like receptor 4 (TLR4), heme oxygenase?1 (HO?1), inhibitor of ?B kinase (I?B), pro?inflammatory mediators (interleukin?6 and tumor necrosis factor??), myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), were examined. The results showed that Melilotus extract had a marked effect on the pathological manifestation of lung tissue and lung inflammatory response, the upregulation of TIPE2, HO?1 and I?B expression, and the inhibition of TLR4 and NF??B activities. In addition, following treatment with Melilotus extract, the model animals demonstrated decreased levels of MPO and MDA as well as increased levels of SOD. In conclusion, these results indicated that Melilotus extract may be a potential therapeutic agent for the treatment of CLP?induced lung injury, the mechanism of which proceeded via inflammation? and oxidation?associated pathways by increasing TIPE2 expression.
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Physiological evidence that anthropogenic woodlots can substitute for native riparian woodlands as stopover habitat for migrant birds.
Physiol. Biochem. Zool.
PUBLISHED: 01-25-2014
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The ability to find sufficient high-quality stopover habitat is a crucial factor for successful migration for woodland migrant birds. Woodland habitats are scarce in the Northern Prairie region of North America, and natural woodlands have been greatly reduced concurrent with the appearance of small anthropogenic woodlands on the landscape. Landbird migrants use both natural and anthropogenic woodlands in this region as stopover habitats, but the relative quality of these two habitats is unknown. We assessed the relative habitat quality of the two habitats by comparing body mass (Mb) and plasma metabolites associated with fattening (triglycerides [TRIG]) or fat catabolism (?-hydroxybutyrate [BUTY], glycerol [GLYC]) in individual species, taxa, and foraging guilds of migrating woodland birds during both spring and fall migrations. The only significant difference in Mb between birds in the two habitats occurred for fall yellow-rumped warblers (Setophaga coronata), where Mb was 8% greater in corridors than in woodlots. No significant between-habitat differences occurred for plasma TRIG at either season. Significant between-habitat differences for plasma BUTY occurred only for ruby-crowned kinglets (Regulus calendula; 61% higher in corridors) in fall. Plasma GLYC differed significantly between habitats for a few groups, including vireos (190% higher in woodlots), warbling vireos (Vireo gilvus; 263% higher in woodlots), and Nashville warblers (Oreothlypis ruficapilla; 226% higher in woodlots) in fall. The few significant differences and absence of a consistent direction of variation in Mb and plasma metabolites suggests similar stopover habitat quality in these two habitat types. Thus, during migration through the Northern Prairie region anthropogenic woodlots can, at least partially, substitute as stopover habitat for lost and degraded native riparian habitats for woodland birds.
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Effects of long-term wearing of high-heeled shoes on the control of the body's center of mass motion in relation to the center of pressure during walking.
Gait Posture
PUBLISHED: 01-12-2014
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High-heeled shoes are associated with instability and falling, leading to injuries such as fracture and ankle sprain. This study investigated the effects of habitual wearing of high-heeled shoes on the body's center of mass (COM) motion relative to the center of pressure (COP) during gait. Fifteen female experienced wearers and 15 matched controls walked with high-heeled shoes (7.3cm) while kinematic and ground reaction force data were measured and used to calculate temporal-distance parameters, joint moments, COM-COP inclination angles (IA) and the rate of IA changes (RCIA). Compared with inexperienced wearers, experienced subjects showed significantly reduced frontal IA with increased ankle pronator moments during single-limb support (p<0.05). During double-limb support (DLS), they showed significantly increased magnitudes of the frontal RCIA at toe-off and contralateral heel-strike, and reduced DLS time (p<0.05) but unaltered mean RCIA over DLS. In the sagittal plane experienced wearers showed significantly increased mean RCIA (p<0.05) and significant differences in the RCIA at toe-off and contralateral heel-strike (p<0.05). Significantly increased hip flexor moments and knee extensor moments at toe-off (p<0.05) were needed for forward motion of the trailing limb. The current results identified the change in the balance control in females after long-term use of high-heeled shoes, providing a basis for future design of strategies to minimize the risk of falling during high-heeled gait.
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The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines: an observational study.
BMC Infect. Dis.
PUBLISHED: 01-09-2014
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BackgroundWorld Health Organization (WHO) has recommended individuals with increased risk of contracting influenza A H5N1 infection to be immunized against the virus during the inter-pandemic period. Safety and immunogenicity of H5N1 vaccine among participants primed with homologous or heterologous H5N1 vaccines produced by diverse manufactures have not been reported.MethodsHealthy individuals aged 20 to 60 years old were recruited and stratified into three groups: participants without priming (control group), participants primed with A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59-adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were recorded by vaccine recipients. Blood samples were obtained for hemagglutination inhibition test.ResultsA total of 131 participants were enrolled. No significant adverse events were recorded. Tenderness, fatigue and general muscle ache were the most common solicited reactions which alleviated within one week of immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88% were in seroprotective status in the control group, A/Indonesia/05/2005 primed group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high immune response after booster with one dose of the study vaccine.ConclusionThe study vaccine did not cause severe adverse events. It elicited mostly mild to moderate reactions among participants. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response than those without priming or primed with A/Indonesia/05/2005 vaccine. The report suggested those with an increased risk of influenza A H5N1 virus exposure may benefit from receiving influenza A H5N1 priming during the inter-pandemic period if the antigenicity of the pandemic influenza strain is similar to that of the priming strain.
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Atorvastatin increases lipopolysaccharide-induced expression of tumour necrosis factor-?-induced protein 8-like 2 in RAW264.7 cells.
Exp Ther Med
PUBLISHED: 01-04-2014
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RAW264.7 cells are one of the major sources of productive inflammatory biomediators, including tumour necrosis factor-? (TNF-?) and interleukin (IL)-6. TNF-?-induced protein 8-like 2 (TIPE2) is an essential negative regulator of Toll-like and T-cell receptors, and the selective expression in the immune system prevents hyper-responsiveness and maintains immune homeostasis. The aim of the present study was to investigate whether atorvastatin upregulates the expression of TIPE2 and further regulates the inflammatory response and oxidation emergency response in RAW264.7 cells. RAW264.7 cells were incubated in Dulbecco's modified Eagle's medium containing lipopolysaccharide (LPS) in the presence or absence of atorvastatin. Following incubation, the medium was collected and the levels of TNF-? and IL-6 were measured using an enzyme-linked immunosorbent assay. The cells were harvested, and the mRNA and protein expression levels of TIPE2, macrophage migration inhibitory factor (MIF), I?B and nuclear factor (NF-?B)-?B were analysed using quantitative polymerase chain reaction and western blotting analysis, respectively, the expression of NOS, COX-2 and HO-1 protein were essayed by western blotting analysis, NO and ROS activities were determined. The results revealed that LPS increased the mRNA and protein expression levels of TIPE2, MIF and NF-?B, as well as the production of IL-6 and TNF-?, in a dose and time dependent manner in RAW264.7 cells. Meanwhile, LPS enhanced the expression of NOS and COX-2 protein, blocked HO-1 protein expression, increased NO and PGE2 production and ROS activity in a dose dependent manner in RAW264.7 cells. Atorvastatin significantly increased LPS induced expression of TIPE2, downregulated the expression of NOS, COX-2, MIF and NF-?B and the production of PGE2, NO, IL-6 and TNF-? in a time and dose dependent manner, and increased HO-1 protein expression, reduced ROS production in a dose dependent manner. The observations indicated that atorvastatin upregulated LPS induced expression of TIPE2 and consequently inhibited MIF, NF-?B, NOS and COX-2 expression and the production of NO, PGE2, TNF-? and IL-6, increased HO-1 expression, and inhibited ROS activity in cultured RAW264.7 cells.
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Operating Mechanism and Molecular Dynamics of Pheromone-Binding Protein ASP1 as Influenced by pH.
PLoS ONE
PUBLISHED: 01-01-2014
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Odorant binding protein (OBP) is a vital component of the olfactory sensation system. It performs the specific role of ferrying odorant molecules to odorant receptors. OBP helps insects and types of animal to sense and transport stimuli molecules. However, the molecular details about how OBPs bind or release its odorant ligands are unclear. For some OBPs, the systems' pH level is reported to impact on the ligands' binding or unbinding capability. In this work we investigated the operating mechanism and molecular dynamics in bee antennal pheromone-binding protein ASP1 under varying pH conditions. We found that conformational flexibility is the key factor for regulating the interaction of ASP1 and its ligands, and the odorant binds to ASP1 at low pH conditions. Dynamics, once triggered by pH changes, play the key roles in coupling the global conformational changes with the odorant release. In ASP1, the C-terminus, the N-terminus, helix ?2 and the region ranging from helices ?4 to ?5 form a cavity with a novel 'entrance' of binding. These are the major regions that respond to pH change and regulate the ligand release. Clearly there are processes of dynamics and hydrogen bond network propagation in ASP1 in response to pH stimuli. These findings lead to an understanding of the mechanism and dynamics of odorant-OBP interaction in OBP, and will benefit chemsensory-related biotech and agriculture research and development.
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