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Find video protocols related to scientific articles indexed in Pubmed.
RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 - insensitive Brown Norway rat.
J. Physiol. (Lond.)
PUBLISHED: 11-12-2014
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Raphe-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems like breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphe gene expression and the consequent deficiencies in raphe-derived neuromodulators such as TRH. Medullary raphe transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl Salt-sensitive (SS) rats, predictive of reduced CNS monoamines by bioinformatics analyses and confirmed by HPLC measurements. In particular, raphe Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analog Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague Dawley (SD) rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control SD rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signaling in the mammalian CO2 chemoreflex. This article is protected by copyright. All rights reserved.
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[Research progress of chemical composition of taxane in Taxus canadensis and medicine source crisis solution].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
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Diagnostic value of surfactant protein-a in severe acute pancreatitis-induced acute respiratory distress syndrome.
Med. Sci. Monit.
PUBLISHED: 09-27-2014
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The complexity of multiple-item criteria in acute respiratory distress syndrome (ARDS) often causes inconvenience for physicians in the management of patients with severe acute pancreatitis (SAP). We evaluated whether serum SP-A levels in the presence of diffuse alveolar damage (DAD) can be qualitatively assessed for diagnosis of SAP-induced ARDS.
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Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize metastatic castration-resistant prostate cancer cells to cabazitaxel chemotherapy.
Tumour Biol.
PUBLISHED: 09-12-2014
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Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that can stabilize some proteins by inhibiting degradation mediated by protein phosphatase 2A (PP2A), and its level in cancer is associated with resistance to chemotherapy. However, whether CIP2A could increase chemoresistance of prostate cancer (PCa) cells to chemotherapeutic agent cabazitaxel remains unclear. To determine whether CIP2A serves as a potential therapeutic target of human PCa, we utilized small interference RNA (siRNA) to knock down CIP2A expression in human PCa cells and analyzed their phenotypic changes. The data demonstrated that CIP2A was significantly elevated in mCRPC cell lines C4-2 and ARCaPM at both the mRNA and protein levels. CIP2A silencing led to decreased proliferation and enhanced chemosensitivity and apoptosis to cabazitaxel in human PCa cells, as well as reduced Akt phosphorylation. Our data suggesting critical roles of CIP2A in PCa cells chemoresistance to cabazitaxel and raising the possibility of CIP2A inhibition as a promising approach for chemosensitization of metastatic castration-resistant prostate cancer (mCRPC).
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Improved rat genome gene prediction by integration of ESTs with RNA-Seq information.
Bioinformatics
PUBLISHED: 09-12-2014
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RNA-Seq (also called whole-transcriptome sequencing) is an emerging technology that uses the capabilities of next-generation sequencing to detect and quantify entire transcripts. One of its important applications is the improvement of existing genome annotations. RNA-Seq provides rapid, comprehensive and cost-effective tools for the discovery of novel genes and transcripts compared with expressed sequence tag (EST), which is instrumental in gene discovery and gene sequence determination. The rat is widely used as a laboratory disease model, but has a less well-annotated genome as compared with humans and mice. In this study, we incorporated deep RNA-Seq data from three rat tissues-bone marrow, brain and kidney-with EST data to improve the annotation of the rat genome.
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Lipid rafts participate in aberrant degradative autophagic-lysosomal pathway of amyloid-beta peptide in Alzheimer's disease.
Neural Regen Res
PUBLISHED: 09-11-2014
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Amyloid-beta peptide is the main component of amyloid plaques, which are found in Alzheimer's disease. The generation and deposition of amyloid-beta is one of the crucial factors for the onset and progression of Alzheimer's disease. Lipid rafts are glycolipid-rich liquid domains of the plasma membrane, where certain types of protein tend to aggregate and intercalate. Lipid rafts are involved in the generation of amyloid-beta oligomers and the formation of amyloid-beta peptides. In this paper, we review the mechanism by which lipid rafts disturb the aberrant degradative autophagic-lysosomal pathway of amyloid-beta, which plays an important role in the pathological process of Alzheimer's disease. Moreover, we describe this mechanism from the view of the Two-system Theory of fasciology and thus, suggest that lipid rafts may be a new target of Alzheimer's disease treatment.
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[Multiple factors quantitative analysis on middle ear function in primarily diagnosed patients with nasopharyngeal carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To explore the ways of quantitative and objective evaluation for analyzing the multiple influence factors on middle ear function in the patients with primarily diagnosed NPC, and to analyze the influence factors of middle ear function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC).
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[Prevalence of HIV and sexually transmitted diseases as well as related associated risk factors among middle/low level female sex workers in a city in Guangdong province].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 07-26-2014
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To explore the prevalence of HIV, sexually transmitted diseases (STDs) and associated factors among medium/low level female sex workers (FSWs) in an under-developed city in Guangdong province.
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[Element distribution analysis of welded fusion zone by laser-induced breakdown spectroscopy].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 07-11-2014
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Over the past decade there has been intense activity in the study and development of laser-induced breakdown spectroscopy (LIBS). As a new tool for surface microanalysis, it caused widespread in materials science because of the advantage of rapid and high sensitivity. In the present paper, the distribution of Ni, Mn, C and Si near weld fusion line was analyzed on two kinds of weld sample. Line scanning mode analysis was carried out by three different kinds of methods, namely laser-induced breakdown spectroscopy (LIBS), scanning electron microscope/energy dispersive spectrometer (SEM/EDS) and electron probe X-ray microanalyser (EPMA). The concentration variation trend of Ni and Mn acquired by LIBS is coincident with SEM/EDS and EPMA. The result shows that the content of Ni and Mn was significantly different between weld seam and base metal on both the samples. The content of Ni and Mn was much higher in weld seam than in base metal, and a sharp concentration gradient was analyzed in the fusion zone. According to the distribution of Ni and Mn, all the three methods got a similar value of welded fusion zone width. The concentration variation trend of C and Si acquired by LIBS is not coincident with SEM/EDS and EPMA. The concentration difference between weld seam and base metal was analyzed by LIBS, but had not by SEM/EDS and EPMA, because of the low concentration and slight difference. The concentration gradient of C and Si in fusion zone was shows clearly by LIBS. For higher sensitivity performance, LIBS is much more adapted to analyze low content element than SEM/EDS and EPMA.
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[Expressions and significance of TLR2 and TLR4 in Kupffer cells of tree shrews chronically infected with hepatitis B virus].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 07-09-2014
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To investigate the mRNA expression levels of Toll-like receptors 2 (TLR2) and TLR4 in Kupffer cells of tree shrews that were chronically infected with hepatitis B virus (HBV), and the effects of these receptors on the function of Kupffer cells.
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miR-101 regulates expression of EZH2 and contributes to progression of and cisplatin resistance in epithelial ovarian cancer.
Tumour Biol.
PUBLISHED: 07-07-2014
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In order to determine the expression pattern of miR-101 in epithelial ovarian neoplasms and assess the functions and mechanism of miR-101 in tumorigenesis, we detected the expression of miR-101 and zeste homolog 2 (EZH2) in normal, benign, and malignant ovarian tissues and used miR-101 lentivirus infection to increase miR-101 expression in ovarian cancer cells and drug-resistant cancer cells. We found that miR-101 was underexpressed in epithelial ovarian cancer tissues, which significantly correlated with poor cell differentiation, advanced International Federation of Gynecology and Obstetrics (FIGO) stages, and ovarian cancer cell cisplatin resistance. miR-101 overexpression decreased the expression of EZH2, reduced proliferation and migration of ovarian cancer cells, and resensitized drug-resistant cancer cells to cisplatin-induced cytotoxicity, suggesting the important role miR-101 plays in ovarian cancer that may be associated with its function as a regulator targeting EZH2. Our findings show the potential of miR-101 as a diagnostic marker and new therapeutic target for patients with epithelial ovarian cancer.
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[Construction and identification of a prokaryotic expression vector for Zmp1 gene from Mycobacterium tuberculosis].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 06-10-2014
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To construct a prokaryotic expression plasmid for zinc-dependent metalloprotease-1 (Zmp1) gene from Mycobacterium tuberculosis and express the plasmid in E.coli.
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Leptin: new hope for the treatment of post-operative cognitive dysfunction?
Med. Sci. Monit.
PUBLISHED: 05-27-2014
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Leptin plays a critical role in neuronal development and also promotes structural and functional activities in the central nervous system. Recent studies have demonstrated that leptin could produce therapeutic effects for cognitive impairments of patients with Alzheimer's disease (AD). Post-operative cognitive dysfunction (POCD), defined as a significant dysfunction in cognitive performance for several weeks after surgery, probably has a pathogenesis similar to that of AD. Specifically, they are both characterized by cognitive impairment. In this regard, we hypothesized that leptin probably has a therapeutic benefit of alleviating symptoms of patients with POCD, and the leptin signaling pathway may be involved in the pathogenesis of POCD.
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Intrastriatal GDNF gene transfer by inducible lentivirus vectors protects dopaminergic neurons in a rat model of parkinsonism.
Exp. Neurol.
PUBLISHED: 05-09-2014
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Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective effects on dopaminergic (DA) neurons both in vivo and in vitro. However, substantial evidence has shown that a long-term overexpression of GDNF gene is often associated with side effects. We previously improved tetracycline (Tet)-On lentivirus system carrying human GDNF (hGDNF) gene, and demonstrated that hGDNF gene expression was tightly regulated and functional in vitro. Here we further examined the efficiency and neuroprotection of Tet-On lentivirus-mediated hGDNF gene regulation in neural progenitor cells (NPCs) and a rat model of parkinsonism. The results showed that hGDNF gene expression was tightly regulated in transduced NPCs. Doxycycline (Dox)-induced hGDNF protected DA neurons from 6-hydroxydopamine (6-OHDA)-induced toxicity in vitro. Intrastriatal injections of Tet-On lentivirus vectors resulted in dramatically increased levels of hGDNF protein in the striatum of rats with Dox-drinking water, when compared to lentivirus-injected and saline-injected rats with normal drinking water, respectively. In addition, hGDNF protected nigral DA neurons and striatal DA fibers, and attenuated d-amphetamine-induced rotational asymmetry in the 6-OHDA lesioned rats. To the best of our knowledge, this is the first report that hGDNF gene transfer by Tet-On lentivirus vectors is tightly regulated in rat brain, and Dox-induced hGDNF is functional in neuroprotection of nigral DA neurons in a rat model of parkinsonism.
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Lymphocyte-derived microparticles induce apoptosis of airway epithelial cells through activation of p38 MAPK and production of arachidonic acid.
Apoptosis
PUBLISHED: 04-30-2014
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The airway epithelium is critical for the normal integrity and function of the respiratory system. Excessive epithelial cell apoptosis contributes to cell damage and airway inflammation. We previously demonstrated that lymphocyte-derived microparticles (LMPs) induce apoptosis of human bronchial epithelial cells. However, the underlying mechanisms contributing to LMPs-evoked epithelial cell death are largely unknown. Here we used bronchial and lung tissue cultures to confirm the pro-apoptotic effects of LMPs. In cell culture experiments, we found that LMPs induced human airway epithelial cell apoptosis with associated increases in caspase-3 activity. In addition, LMPs treatment triggered oxidative stress in epithelial cells by enhancing production of malondialdehyde, superoxide, and reactive oxygen species (ROS), and by inhibiting production of the antioxidant glutathione. Moreover, decreasing cellular ROS with the antioxidant N-acetylcysteine rescued epithelial cell viability. Together, these results demonstrate an important role for oxidative stress in LMPs-induced cell death. In epithelial cells, LMPs treatment induced phosphorylation of p38 MAPK and arachidonic acid accumulation. Moreover, arachidonic acid was significantly cytotoxic towards LMPs-treated epithelial cells, whereas inhibition of p38 MAPK was protective against these cytotoxic effects. Similarly, inhibition of arachidonic acid production led to decreased caspase-3 activity, thus rescuing airway epithelial cells from LMPs-induced cell death. In conclusion, our results show that LMPs induce airway epithelial cell apoptosis by activating p38 MAPK signaling and stimulating production of arachidonic acid, with consequent increases in oxidative stress and caspase-3 activity. As such, LMPs may be regarded as deleterious markers of epithelial cell damage in respiratory diseases.
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IVUS-Based FSI Models for Human Coronary Plaque Progression Study: Components, Correlation and Predictive Analysis.
Ann Biomed Eng
PUBLISHED: 04-27-2014
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Atherosclerotic plaque progression is believed to be associated with mechanical stress conditions. Patient follow-up in vivo intravascular ultrasound coronary plaque data were acquired to construct fluid-structure interaction (FSI) models with cyclic bending to obtain flow wall shear stress (WSS), plaque wall stress (PWS) and strain (PWSn) data and investigate correlations between plaque progression measured by wall thickness increase (WTI), cap thickness increase (CTI), lipid depth increase (LDI) and risk factors including wall thickness (WT), WSS, PWS, and PWSn. Quarter average values (n = 178-1016) of morphological and mechanical factors from all slices were obtained for analysis. A predictive method was introduced to assess prediction accuracy of risk factors and identify the optimal predictor(s) for plaque progression. A combination of WT and PWS was identified as the best predictor for plaque progression measured by WTI. Plaque WT had best overall correlation with WTI (r = -0.7363, p < 1E-10), cap thickness (r = 0.4541, p < 1E-10), CTI (r = -0.4217, p < 1E-8), LD (r = 0.4160, p < 1E-10), and LDI (r = -0.4491, p < 1E-10), followed by PWS (with WTI: (r = -0.3208, p < 1E-10); cap thickness: (r = 0.4541, p < 1E-10); CTI: (r = -0.1719, p = 0.0190); LD: (r = -0.2206, p < 1E-10); LDI: r = 0.1775, p < 0.0001). WSS had mixed correlation results.
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Stress fiber response to mechanics: a free energy dependent statistical model.
Soft Matter
PUBLISHED: 04-26-2014
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An experimental observation has been puzzling scientists for years: cells tend to align perpendicular to cyclic uniaxial strain, but parallel to external static strain. Recent experimental results demonstrate that both the magnitude of the external strain and the cell contractility manipulate the cells' orientation under cyclic uniaxial strain. In light of these reports, we introduce a minimum free energy model to explain the different orientation tendencies of cells subjected to external strain, and elucidate the significant role of cell contractility in this issue. With the present model, we successfully explain a series of well-documented phenomena: (1) cells orient nearly parallel to static uniaxial strain; (2) cell alignment depends on the magnitude of the cyclic uniaxial strain; (3) under cyclic uniaxial stretch, a tensioned contractility results in a strengthened perpendicular alignment of the cells, whereas a contractility relaxation results in a nearly parallel alignment. In addition, this model also successfully describes the functional relationship between cell contractility and substrate stiffness.
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Hepatocellular carcinoma in Budd-Chiari syndrome: enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging.
Cell Biochem. Biophys.
PUBLISHED: 04-25-2014
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The objective of this study was to analyze the enhancement patterns at dynamic gadolinium-enhanced T1-weighted MR imaging in patients of Hepatocellular Carcinoma (HCC) with associated Budd-Chiari syndrome (BCS). The MR imaging findings in 10 patients of HCC with associated BCS were compared to those of 32 other patients of HCC without BCS. During the arterial phase, significantly more lesions with BCS were hyperintense than lesions without BCS; during the equilibrium phase, significantly more lesions with BCS were slightly hyperintense or isointense than lesions without BCS (P < 0.05 for both). For HCC, contrast enhancement on MRI shows different enhancement patterns between patients of HCC with associated BCS and those without BCS.
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Characterization of biological pathways associated with a 1.37 Mbp genomic region protective of hypertension in Dahl S rats.
Physiol. Genomics
PUBLISHED: 04-08-2014
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The goal of the present study was to narrow a region of chromosome 13 to only several genes and then apply unbiased statistical approaches to identify molecular networks and biological pathways relevant to blood-pressure salt sensitivity in Dahl salt-sensitive (SS) rats. The analysis of 13 overlapping subcongenic strains identified a 1.37 Mbp region on chromosome 13 that influenced the mean arterial blood pressure by at least 25 mmHg in SS rats fed a high-salt diet. DNA sequencing and analysis filled genomic gaps and provided identification of five genes in this region, Rfwd2, Fam5b, Astn1, Pappa2, and Tnr. A cross-platform normalization of transcriptome data sets obtained from our previously published Affymetrix GeneChip dataset and newly acquired RNA-seq data from renal outer medullary tissue provided 90 observations for each gene. Two Bayesian methods were used to analyze the data: 1) a linear model analysis to assess 243 biological pathways for their likelihood to discriminate blood pressure levels across experimental groups and 2) a Bayesian graphical modeling of pathways to discover genes with potential relationships to the candidate genes in this region. As none of these five genes are known to be involved in hypertension, this unbiased approach has provided useful clues to be experimentally explored. Of these five genes, Rfwd2, the gene most strongly expressed in the renal outer medulla, was notably associated with pathways that can affect blood pressure via renal transcellular Na(+) and K(+) electrochemical gradients and tubular Na(+) transport, mitochondrial TCA cycle and cell energetics, and circadian rhythms.
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Synthesis and insecticidal activity of novel hydrazone compounds derived from a naturally occurring lignan podophyllotoxin against Mythimna separata (Walker).
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-20-2014
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In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, a series of novel hydrazone derivatives of podophyllotoxin, which is a naturally occurring aryltetralin lignan and isolated as the main secondary metabolite from the roots and rhizomes of Podophyllum species, were synthesized and evaluated as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1mg/mL. Especially compounds 8i, 8j, 8t, and 8u showed the more potent insecticidal activity with the final mortality rates greater than 60%.
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Treatment of hemolymphangioma of the spleen by laparoscopic partial splenectomy: a case report.
World J Surg Oncol
PUBLISHED: 03-14-2014
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Hemolymphangioma is a malformation of both lymphatic and blood vessels. The incidence of splenic hemolymphangioma is extremely rare. Laparoscopic partial splenectomy is feasible, reproducible, and safe in children with focal splenic tumors. We report on the case of a 12-year-old male with a large splenic hemolymphangioma successfully managed by laparoscopic partial splenectomy. The patient recovered well after operation. Laparoscopic partial splenectomy is a safe and minimally invasive technique for treatment of splenic hemolymphangioma located in the pole of the spleen.
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Human coronary plaque wall thickness correlated positively with flow shear stress and negatively with plaque wall stress: an IVUS-based fluid-structure interaction multi-patient study.
Biomed Eng Online
PUBLISHED: 03-07-2014
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Atherosclerotic plaque progression and rupture are believed to be associated with mechanical stress conditions. In this paper, patient-specific in vivo intravascular ultrasound (IVUS) coronary plaque image data were used to construct computational models with fluid-structure interaction (FSI) and cyclic bending to investigate correlations between plaque wall thickness and both flow shear stress and plaque wall stress conditions.
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Downregulation of neuregulin 1-ErbB4 signaling in parvalbumin interneurons in the rat brain may contribute to the antidepressant properties of ketamine.
J. Mol. Neurosci.
PUBLISHED: 02-27-2014
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Increasing evidence underscores the strong, rapid, and sustained antidepressant properties of ketamine with a good tolerability profile in patients with depression; however, the underlying mechanisms are not fully elucidated. Neuregulin 1 (NRG1) is a bipolar disorder susceptibility gene and a biomarker of major depressive disorder, which regulates pyramidal neuron activity via ErbB4 in parvalbumin interneurons. Moreover, NRG1-ErbB4 signaling is reported to play a key role in the modulation of synaptic plasticity through regulating the neurotransmission. We therefore hypothesized that hypofunction of NRG1-ErbB4 signaling in parvalbumin interneurons is involved in the process of ketamine exerting rapid antidepressant actions in rats subjected to the forced swimming test (FST). The results showed that ketamine reduced the immobility time and latency to feed of rats receiving the FST, downregulated the levels of NRG1, phosphorylated ErbB4 (p-ErbB4), parvalbumin, 67-kDA isoform of glutamic acid decarboxylase (GAD67), gamma-aminobutyric acid (GABA), and upregulated the levels of glutamate in the rat prefrontal cortex and hippocampus. Pretreatment with NRG1 abolished both ketamine's antidepressant effects and ketamine-induced reduction in p-ErbB4, parvalbumin, GAD67, and GABA levels and increase in glutamate levels. These results suggest that the downregulation of NRG1-ErbB4 signaling in parvalbumin interneurons in the rat brain may be a mechanism underlying ketamine's antidepressant properties.
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The Effects of Fludarabine on Rat Cerebral Ischemia.
J. Mol. Neurosci.
PUBLISHED: 02-26-2014
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Cerebral ischemic injury involves a variety of cellular and molecular events. Signal transducers and activators of transcription-1 (STAT-1) activation is associated with neuronal cell death and contributes to ischemic injury. The effects of fludarabine, a specific inhibitor of STAT1 protein, on cerebral ischemic/reperfusion (I/R) injury were studied in a rat model. Rats subjected to I/R injury were either treated with intra-cerebroventricular injection of fludarabine (5,000 ?M, 10 ?l) or saline 20 min before middle cerebral artery occlusion (MCAO). MR examinations including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI) were performed after I/R period. Then rat brains were sectioned for triphenyltetrazolium chloride (TTC) stains, analyzed by Western blot and TUNEL staining of apoptosis. It was found that fludarabine treatment decreased the infarct volume of the cerebrum and the number of apoptotic neural cells in the ischemic brain. Compared to saline-treated group, the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) in the ischemic region were greater, and the mean transit time (MTT) was shortened in the fludarabine-treated group. Moreover, fludarabine inhibited the expression level of phosphorylated STAT1 (P-STAT1) in neural cells after I/R injury, whereas the expression of phosphorylated STAT3 (P-STAT3) was increased. Therefore, we concluded that fludarabine administrated in early stage of cerebral ischemia had neuroprotective effects, and the underlying mechanism could be mediated through inhibiting STAT1 phosphorylation and activating the cross regulation between STAT1 and STAT3 in neural cells.
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Cholinergic neurons excite cortically projecting basal forebrain GABAergic neurons.
J. Neurosci.
PUBLISHED: 02-21-2014
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The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. In GAD67-GFP knock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP(+)) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices from GAD67-GFP knock-in or PV-tdTomato mice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 ?m diameter) BF GFP(+) and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1 and M3 muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and small Ih, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically projecting GABAergic/PV neurons.
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miR-335 represents an independent prognostic marker in epithelial ovarian cancer.
Am. J. Clin. Pathol.
PUBLISHED: 02-12-2014
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To investigate the clinical significance of miR-335 expression in epithelial ovarian cancer (EOC).
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[Association of 15 short tandem repeats loci with aggressive behavior].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 02-11-2014
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To assess the association between aggressive behaviors and 15 short tandem repeats (STRs) loci.
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Coexpression of SFRP1 and WIF1 as a prognostic predictor of favorable outcomes in patients with colorectal carcinoma.
Biomed Res Int
PUBLISHED: 02-10-2014
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Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1-, WIF-/SFRP1+, and WIF-/SFRP1-) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC.
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Genome-wide methylation changes are associated with muscle fiber density and drip loss in male three-yellow chickens.
Mol. Biol. Rep.
PUBLISHED: 01-28-2014
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In eukaryotes, DNA methylation is an important epigenetic modification involved in gene expression regulation. Meat quality traits are complicated traits that are controlled by many genes. Changes in the methylation levels of certain genes controlling meat quality traits will inevitably affect their expression levels, thereby affecting meat quality. The objectives of this study were to investigate the differences in the DNA methylation level in pectoral muscle tissues using fluorescent-labeled methylation sensitive amplified polymorphism and their relationships with meat quality traits in three-yellow chickens. The results showed that the differences in the DNA methylation level had a highly significant effect on muscle fiber density and drip loss (P<0.01). However, no significant correlations were found between the DNA methylation levels and the other investigated traits (P>0.05).
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Metabolomic evaluation of the response to endocrine therapy in patients with prostate cancer.
Eur. J. Pharmacol.
PUBLISHED: 01-22-2014
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Timely evaluation of the response to endocrine therapy in patients with prostate cancer (PCa) may optimize treatment regimens and improve long-term prognosis. We used the liquid chromatography-mass spectrometry (LC-MS)-based metabolomic technique to identify serum biomarkers indicative of disease progression and therapeutic benefit. The mean serum levels of seven metabolites, including deoxycholic acid (DCA), glycochenodeoxycholate (GCDC), l-tryptophan, docosapentaenoic acid (DPA), arachidonic acid, deoxycytidine triphosphate, and pyridinoline, differed significantly between untreated PCa patients and healthy controls. In patients who did not develop castration-resistant prostate cancer (CRPC) for at least 2 years (good responders), these metabolite levels reverted to near healthy control levels during endocrine therapy. In contrast, the metabolite levels remained abnormal in patients who developed CRPC within 1 year (poorly responsive patients). Three of these biomarkers (DCA, GCDC, and DPA) are mainly involved in cholesterol metabolism, underscoring the importance of elevated cholesterol to PCa progression. These metabolites may serve as predictive biomarkers for assessing the therapeutic response of PCa patients to endocrine therapy.
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Mechanical memory and dosing influence stem cell fate.
Nat Mater
PUBLISHED: 01-21-2014
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We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young's modulus E ~ 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E ~ 10 kPa) and then soft (E ~ 2 kPa) phototunable PEG hydrogels resulted in either reversible or--above a threshold mechanical dose--irreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memory--with YAP/TAZ acting as an intracellular mechanical rheostat--that stores information from past physical environments and influences the cells' fate.
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Integrin activation and internalization mediated by extracellular matrix elasticity: a biomechanical model.
J Biomech
PUBLISHED: 01-15-2014
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Cells sense and respond to the elasticity of extracellular matrix (ECM) via integrin-mediated adhesion. As a class of well-documented mechanosenors in cells, integrins switch among inactive, bound, and dissociated states, depending upon the variation of forces acting on them. However, it remains unclear how the ECM elasticity directs and affects the states of integrins and, in turn, their cellular functions. On the basis of our recent experiments, a biomechanical model is proposed to reveal the role of ECM elasticity in the state-switching of integrins. It is demonstrated that a soft ECM can increase the activation level of integrins while a stiff ECM has a tendency to prevent the dissociation and internalization of bound integrins. In addition, it is found that more stable focal adhesions can form on stiffer and thinner ECMs. The theoretical results agree well with relevant experiments and shed light on the ECM elasticity-sensing mechanisms of cells.
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Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy.
Int J Endocrinol
PUBLISHED: 01-10-2014
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Background. The purpose of the present study was to assess the feasibility of using miR-126 in the urine as a biomarker for diabetic nephropathy. Methods. miRNAs were extracted from the urine samples of T2DM patients with diabetic nephropathy (DN; n = 92), T2DM without DN (n = 86), and 85 healthy volunteers using quantitative reverse transcriptase polymerase chain reaction (real-time polymerase chain reaction) analysis. Stability of urinary miR-126 and factors that affected the stability were assessed. A subgroup analysis was also carried out to compare the urinary miR-126 level in T2DM patients well controlled by the treatment versus those who were not well controlled. Results. Urinary miR-126 was stable when the urine samples were kept at room temperature for extended period of time, 4°C, -20°C, and -80°C for up to 12 hours or subjected to 10 freeze-and-thaw cycle. Urinary miR-126 was significantly higher in T2DM patients with DN (5.76 ± 0.33 versus 3.25 ± 0.45 in T2DM patients without DN). Successful treatment significantly reduced urinary miR-126 in T2DM patients with DN to 3.89 ± 0.52 (P < 0.05). Conclusion. miR-126 in the urine is stable and it could be used as a biomarker of DN and to monitor the treatment response.
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Primary application of PPE68 of Mycobacterium tuberculosis.
Hum. Immunol.
PUBLISHED: 01-03-2014
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PPE68 protein is absent from BCG and the attenuated strains of Mycobacterium tuberculosis (MTB). In this study, the shuttle plasmid pBudCE4.1/PPE68/OriM was constructed and transformed into BCG to obtain PPE68 recombination BCG (PPE68-rBCG), and BALB/c mice were immunized with PPE68-rBCG to evaluate the immunological characterization of PPE68-rBCG. The level of lgG2a, IFN-?, IL-12 and IL-4 in serum of immunized mice were detected, the proliferation response of spleen lymphocyte were measured, the frequency of CD4(+), CD8(+) and CD4(+)/CD8(+) were determined, and the spleen and lung tissue were prepared for pathological analysis. PPE68-rBCG was constructed successfully and could induce powerful Th1 immune response in mice. Besides, we took the purified recombination PPE68 (rPPE68) protein as diagnostic antigen to detect pulmonary tuberculosis patients (n=252) and extrapulmonary tuberculosis patients (n=66). We also used anti-PPE68 polyclonal antibody as coating antibody to detect specific antigen in the same serum samples. Our data provide an experimental basis for potential application of rPPE68 in the diagnosis of tuberculosis, especially for extrapulmonary tuberculosis.
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The role of circulating microRNA-126 (miR-126): a novel biomarker for screening prediabetes and newly diagnosed type 2 diabetes mellitus.
Int J Mol Sci
PUBLISHED: 01-02-2014
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Recent studies suggested an association of endothelial microRNA-126 (miR-126) with type 2 diabetes mellitus (T2DM). In the current study, we examined whether circulating miR-126 is associated with T2DM and pre-diabetic syndrome. The study included 82 subjects with impaired glucose tolerance (IGT), 75 subjects with impaired fasting glucose (IFG), 160 patients with newly diagnosed T2DM, and 138 healthy individuals. Quantitative polymerase chain reaction (qPCR) was used to examine serum miR-126. Serum miR-126 was significantly lower in IGT/IFG subjects and T2DM patients than in healthy controls (p<0.05). After six months of treatment (diet control and exercise in IGT/IFG subjects, insulin plus diet control and exercise in T2DM patients), serum miR-126 increased significantly (p<0.05). An analysis based on serum miR-126 in the sample revealed a significantly higher odds ratio (OR) for the subjects with the lowest 1/3 of serum miR-126 for T2DM (OR: 3.500, 95% confidence interval: 1.901-6.445, p<0.05) than subjects within the highest 1/3 of serum miR-126. Such an association was still apparent after adjusting for other major risk factors. The area under the curve (AUC) for the receiver-operating characteristic (ROC) analysis was 0.792 (95% confidence interval: 0.707-0.877, p<0.001). These results encourage the use of serum miR-126 as a biomarker for pre-diabetes and diabetes mellitus, as well as therapeutic response.
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Chronic lipopolysaccharide exposure induces cognitive dysfunction without affecting BDNF expression in the rat hippocampus.
Exp Ther Med
PUBLISHED: 01-02-2014
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Previous studies have shown that lipopolysaccharide (LPS) has the potential to cause cognitive dysfunction. However, the underlying pathogenesis has yet to be fully elucidated. Increasing attention is being focused on infection in the central nervous system. Therefore, the present study aimed to investigate the behavioral performance of rats receiving intraperitoneal injections of LPS and to determine the expression levels of amyloid-? (A?), brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines in the hippocampus. In total, 30 male Wistar rats were randomly divided into 3 groups (each n=10): Control and 3 and 7 day LPS administration groups. The rats were intraperitoneally injected with saline or LPS for 3 or 7 days. Following this, rats performed the Morris water maze test, in which the latency to the platform and proportion of time spent in the target quadrant were recorded. Rats were then sacrificed and the hippocampi were harvested for determination of interleukin (IL)-1?, IL-6, tumor necrosis factor-? (TNF-?), A? and BDNF expression levels. LPS administration for 3 and 7 days significantly increased the latency to the platform and decreased the proportion of time spent in the target quadrant compared with those in the control group, (P<0.05). Administration of LPS for 3 and 7 days induced statistically significant increases in the expression levels of IL-1?, IL-6 and TNF-? in the hippocampus, compared with those in the control group (P<0.05). Additionally, the administration of LPS for 7 days induced a statistically significant increase in the expression level of A? in the hippocampus, compared with that in the control group (P<0.05). However, the administration of LPS did not elicit a statistically significant change in the expression level of BDNF in the hippocampus, compared with that in the control group (P>0.05). The results indicate that LPS induces cognitive dysfunction, which is associated with increased expression levels of pro-inflammatory cytokines and A?, but does not affect the expression of BDNF in the hippocampus.
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Leptin deficiency is involved in the cognitive impairment of streptozocin-induced diabetic rats undergoing cardiopulmonary bypass.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Several lines of evidence have demonstrated that leptin is probably involved in the cognitive impairment which induced by a single injection of streptozocin (STZ). However, there is little literature reporting the relationship between cognitive impairment and cardiopulmonary bypass (CPB). This study aimed to investigate the role of leptin in the cognitive impairment of STZ-induced diabetic rats undergoing CPB. Wistar rats received 2 h of CPB exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. Behavioral results of rats in Morris water maze were recorded. After that, rat hippocampi were harvested for measuring leptin, tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?). Besides, we observed intracerebroventricular injection of leptin on the cognitive impairment of diabetic-rats undergoing CPB and measured behavioral performance and hippocampal TNF-? and IL-1? levels. Rats undergoing CPB significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. Additionally, the expression of leptin significantly decreased, while TNF-? and IL-1? levels significantly increased. Moreover, intracerebroventricular injection of leptin has a therapeutic effect for cognitive impairment of diabetic rats undergoing CPB. Leptin deficiency in hippocampus is probably involved in the cognitive impairment of streptozocin-induced diabetic rats undergoing cardiopulmonary bypass.
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Cloning and characterization of Clp protease proteolytic subunit 2 and its implication in clinical diagnosis of tuberculosis.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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To clone, express, and characterize Mycobacterium tuberculosis (Mtb) ClpP2, and evaluated the potential usage of ClpP2 in clinical diagnosis of tuberculosis.
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Fabrication of mAb G250-SPIO molecular magnetic resonance imaging nanoprobe for the specific detection of renal cell carcinoma in vitro.
PLoS ONE
PUBLISHED: 01-01-2014
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Molecular magnetic resonance imaging (mMRI) has been paid more and more attention for early diagnosis of cancer. A sensitive and specific mMRI probe plays the most important role in this technique. In this study, superparamagnetic iron oxide (SPIO) nanoparticles and mAb G250 were conjugated as mMRI probe for the detection of clear cell renal cell carcinoma (ccRCC) using 3.0-Tesla MRI in vitro. mAb G250 could specifically recognize carbonic anhydrase IX (CAIX) antigen overexpressed in ccRCC and the SPIO nanoparticles as MRI contrast agent presented excellent MRI response and good biocompatibility. The successful assembly of this nanoprobe was confirmed by UV-vis spectrum, FT-IR spectroscopy and DLS analysis. In vitro MRI study on ccRCC cells and control cells indicated that our fabricated mAb G250-SPIO nanoprobe could be used in the specific labeling of clear cell renal carcinoma cells successfully.
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Isoflurane anesthesia aggravates cognitive impairment in streptozotocin-induced diabetic rats.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Several lines of evidence demonstrate that isoflurane anesthesia would be a great risk factor for the patients undergoing surgeries to suffer from postoperative cognitive dysfunction (POCD). Additionally, diabetes is also an important pathogenic factor for the emergence of cognitive dysfunction. If patient is suffering from diabetes, the incidence of cognitive dysfunction greatly increased. We therefore aimed to investigate the effects of isoflurane anesthesia on cognitive dysfunction in a diabetic rat model induced by a single injection of streptozotocin (STZ). Wistar rats received 2 h of 2% isoflurane or oxygen exposure 1 month after a single intraperitoneal injection of 60 mg/kg of STZ or the vehicle. The results showed that isoflurane anesthesia significantly aggravates STZ-induced an increase of the latency to the platform and a decrease of the proportion of time spent in the target quadrant of rats in Morris water maze test. In addition to the expression of amyloid-? (A?), superoxide dismutase (SOD), malonyldialdehyde (MDA), tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), isoflurane anesthesia significantly increased as compared with a single injection of STZ. However, isoflurane anesthesia had no effect on the blood glucose and leptin. In conclusion, our results suggested that isoflurane anesthesia aggravating cognitive impairment induced by STZ is probably related to the activation of oxidative stress and inflammatory response in rat hippocampus.
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Anti-proliferative and anti-tumour effects of lymphocyte-derived microparticles are neither species- nor tumour-type specific.
J Extracell Vesicles
PUBLISHED: 01-01-2014
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Unregulated cell proliferation or growth is a prominent characteristic of cancer. We have previously demonstrated that LMPs (cell membrane microparticles derived from apoptotic human CEM T lymphoma cells stimulated with actinomycin D) strongly suppress the proliferation of not only human endothelial cells but also mouse Lewis lung carcinoma cells.
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Semisynthesis and Insecticidal Activity of Some Fraxinellone Derivatives Modified in the B Ring.
J. Agric. Food Chem.
PUBLISHED: 11-25-2013
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A series of novel fraxinellone derivatives modified at the C-1 or C-8 position in the B ring were prepared as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata Walker at 1 mg/mL. Five key steric configurations of compounds 2, 3, and 8f,g,j were further determined by single-crystal X-ray diffraction. It was found that the kinds and the amount of the reduction products of fraxinellone were related to the molar ratio between the reduction agent Red-Al and the substrate fraxinellone. Among all of the derivatives, compounds 2 and 8i,j,o displayed more promising insecticidal activity than their precursors fraxinellone and toosendanin. The preliminary structure-activity relationships revealed that the lactone (B-ring) of fraxinellone contributed to the observed insecticidal activity; the double bond at the C-2 position of fraxinellone was not necessary for the insecticidal activity; conversion of the oxygen atom of carbonyl group on the lactone of fraxinellone to a sulfur one does not improve the insecticidal activity; introduction of electron-withdrawing groups on the phenyl ring of 8f, to the benzoyloxy series, could result in more potent compounds.
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[Expression of choline acetyltransferase in the rat barrel cortex by electrical stimulation].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 11-02-2013
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To observe a turning performance in the rats excited by using a proper electrical stimuli of the barrel cortex region (BC), and the expression of choline acetyltransferase (ChAT) in the BC regions after electoral stimulation.
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Transcystic Approach with Micro-incision of the Cystic Duct and Its Confluence Part in Laparoscopic Common Bile Duct Exploration.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 10-18-2013
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Abstract Background: Laparoscopic transcystic common bile duct exploration has become a safe and ideal treatment of common bile duct stones. This study was designed to explore the clinical value of modified laparoscopic transcystic common bile duct exploration as a first line of treatment for patients with common bile duct stones. Patients and Methods: A retrospective, case-control study of clinically comparable groups of patients who underwent the laparoscopic transcystic approach with micro-incision of the cystic duct and its confluence part in common bile duct exploration (LTM-CBD) (n=110) and laparoscopic common bile duct exploration (LCBD) (n=100) under the care of one surgeon was performed. All clinical data were analyzed retrospectively. Results: There was no significant difference in terms of operation time between the two groups (P>.05). Postoperative hospital stay and abdominal drainage time were shorter in the LTM-CBD group than in the LCBD group (P<.05). Postoperative bile leakage was seen in 1 case (1 of 110) in the LTM-CBD group and 10 cases (10 of 100) in the LCBD group (P<.05). Twenty patients underwent T-tube drainage in the LCBD group, and primary closure was performed in the other patients; however, all cases in the LTM-CBD group underwent primary closure. The median follow-up was 12 months; 2 patients in the LCBD group who suffered from bile leakage presented with obstructive jaundice due to bile duct stenosis 6 months postoperatively. Conclusions: LTM-CBD, which can avoid postoperative T-tube drainage, decrease complications, shorten hospitalization time, and enhance the existing quality, is a minimally invasive, safe, and effective treatment.
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Ultrashort single-walled carbon nanotubes in a lipid bilayer as a new nanopore sensor.
Nat Commun
PUBLISHED: 10-11-2013
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An important issue in nanopore sensing is to construct stable and versatile sensors that can discriminate analytes with minute differences. Here we report a means of creating nanopores that comprise ultrashort single-walled carbon nanotubes inserted into a lipid bilayer. We investigate the ion transport and DNA translocation through single-walled carbon nanotube nanopores and find that our results are fundamentally different from previous studies using much longer single-walled carbon nanotubes. Furthermore, we utilize the new single-walled carbon nanotube nanopores to selectively detect modified 5-hydroxymethylcytosine in single-stranded DNA, which may have implications in screening specific genomic DNA sequences. This new nanopore platform can be integrated with many unique properties of carbon nanotubes and might be useful in molecular sensing such as DNA-damage detection, nanopore DNA sequencing and other nanopore-based applications.
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[Th17 cells and IL-17 are increased in patients with brain metastases from the primary lung cancer].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 09-17-2013
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Th17 cells are important T helper cells, which are characterized by their production of IL-17. Th17 cells play an important role in host defense against microbial infections, autoimmune diseases and cancer. The aim of this study is to investigate the percentage of Th17 in peripheral blood lymphocyte and the level of IL-17 in serum and cerebrospinal fluid (CSF) in patients with brain metastases from lung cancer.
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[Effects of cyclic stretch on the induction of the transdifferentiation in human lung epithelial cells].
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 09-12-2013
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To investigate the effect of mechanical stretch induced epithelial-mesenchymal transition in human lung epithelial cells BEAS-2B in vitro.
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Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus.
Virol. J.
PUBLISHED: 08-22-2013
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An animal model for HBV that more closely approximates the disease in humans is needed. The tree shrew (Tupaia belangeri) is closely related to primates and susceptible to HBV. We previously established that neonatal tree shrews can be persistently infected with HBV in vivo, and here present a six year follow-up histopathological study of these animals.
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Correlations between carotid plaque progression and mechanical stresses change sign over time: a patient follow up study using MRI and 3D FSI models.
Biomed Eng Online
PUBLISHED: 08-18-2013
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Increasing evidence suggests that mechanisms governing advanced plaque progression may be different from those for early progression and require further investigation. Serial MRI data and 3D fluid-structure interaction (FSI) models were employed to identify possible correlations between mechanical stresses and advanced plaque progression measured by vessel wall thickness increase (WTI). Long-term patient follow up was used to gather data and investigate if the correlations identified above were reproducible.
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p75 neurotrophin receptor participates in the choroidal antiangiogenic and apoptotic effects of T-lymphocyte-derived microparticles.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 08-08-2013
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Choroidal neovascularization (CNV) is a major cause of vision loss in which choroidal vessels penetrate the RPE-an important source of growth factors, including nerve growth factor (NGF), whose activation via the p75NTR receptor promotes apoptosis and inhibits angiogenesis. We demonstrated previously that human T-lymphocyte-derived microparticles (LMPs) significantly inhibit angiogenesis in several models of ocular neovascularization. We investigated how LMPs modulate pro- and antiangiogenic microenvironments during choroidal angiogenesis.
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Highly sensitive simultaneous detection of lead(II) and barium(II) with G-quadruplex DNA in ?-hemolysin nanopore.
Anal. Chem.
PUBLISHED: 07-29-2013
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Both Pb(2+) and Ba(2+) can bind with high affinity to some specific DNA sequences, inducing the formation of unimolecular G-quadruplex structures. Translocation of a DNA probe containing such sequences through an ?-hemolysin nanopore in the presence of Pb(2+) or Ba(2+) would result in much prolonged DNA translocation events. Quantification of these events can reveal the concentrations of Pb(2+) or Ba(2+) at as low as 0.8 nM. Besides, Pb(2+) and Ba(2+) in the solution can be simultaneously detected and individually identified. Furthermore, the probe is highly selective for Pb(2+) and Ba(2+) detection without interference from other metal ions. This sensing strategy can be extended to many other analytes which can bind to DNA molecules with high affinity.
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Method development for forensic identification of biodiesel based on chemical fingerprints and corresponding diagnostic ratios.
Forensic Sci. Int.
PUBLISHED: 07-12-2013
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A forensic identification method based on the chemical fingerprinting of the first generation of biodiesel (fatty acid alkyl esters as effective components), and several corresponding diagnostic ratios was developed and validated. The distribution of major fatty acid methyl esters (FAMEs) and polar compounds (free fatty acids, glycerol, monoacylglycerides, and free sterols) in several representative above biodiesel products commercially available in Canada were positively quantified and compared, a number of cross-plots of diagnostic ratios of target FAMEs and sterols were developed for biofuel correlation and differentiation. It was found that the cross-plots of FAME ratios, for example, the sum of the di-unsaturated relative to saturated homologues of FAMEs (D/S) versus the sum of the mono-saturated to saturated FAMEs (M/S), and the sum of di-unsaturated to mono-saturated FAMEs (D/M) versus the sum of the mono-saturated to saturated FAMEs (M/S), could cluster samples clearly into their individual feedstock. The cross-plots of diagnostic ratios of individual major sterols (cholesterol, brassicasterol, campesterol, ?-stiosterol and stigmasterol) to the total sterols were also developed and proved to be effective in identifying biodiesel sources due to their self-normalizing effect on sterol data. The case study of a mystery biodiesel spill using this method showed that the two real samples can be tightly clustered into biodiesel from animal fat (Ban) group. However, the significant discrepancy of free fatty acids, glycerol, monoacylglycerides and sterol concentrations between the two real samples indicated their different producing batches.
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Higher critical plaque wall stress in patients who died of coronary artery disease compared with those who died of other causes: A 3D FSI study based on ex vivo MRI of coronary plaques.
J Biomech
PUBLISHED: 07-12-2013
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Mechanical forces play an important role in the rupture of vulnerable plaques. This process is often associated with cardiovascular syndromes, such as heart attack and stroke. In this study, magnetic resonance imaging (MRI)-based models were used to investigate the association between plaque wall stress (PWS) and coronary artery disease (CAD). Ex vivo MRI data of coronary plaques from 12 patients were used to construct 12 three-dimensional (3D) fluid-structure interaction (FSI) computational models. Six of the patients had died from CAD and six had died from non-CAD causes. PWS was assessed using all nodal points on the lumen surface of each plaque. The maximum PWS from all possible vulnerable sites of each plaque was defined as the 3D critical plaque wall stress (CPWS). Mean 3D CPWS in the CAD group was 94.3% higher than that in the non-CAD group (265.6 vs. 136.7kPa, P=0.0029). There was no statistically significant difference in global maximum plaque wall stress (GMPWS) between the two groups (P=0.347). There was also no statistically significant difference in plaque burden between the CAD group (84.4±5%) and the non-CAD group (82.0±8%, P=0.552). The results indicate that plaques from patients who died from CAD were associated with higher CPWS compared with those from patients who died from non-CAD causes. With further validation, analysis of CPWS may prove to be an important component in assessment of plaque vulnerability.
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Cooperative techniques for surgical assistants in laparoscopy-assisted radical distal gastrectomy for gastric cancer.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 06-12-2013
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Laparoscopy-assisted radical distal gastrectomy for gastric cancer is challenging to perform, particularly when conducted with D2 lymph node dissection. Successful completion of this procedure requires collaboration among all members of the surgical team. On the basis of the clinical data of 52 patients undergone laparoscopy-assisted radical distal surgery for gastric cancer from September 2009 to October 2010, we describe cooperative techniques for first and laparoscopic-holder assistants that are required to ensure successful outcomes. Precautions for surgical assistants are also described.
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Semisynthesis and quantitative structure-activity relationship (QSAR) study of some cholesterol-based hydrazone derivatives as insecticidal agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-24-2013
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In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, four series of novel cholesterol-based hydrazone derivatives were synthesized, and their insecticidal activity was tested against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1mg/mL. All the derivatives showed the better insecticidal activity than their precursor cholesterol. Quantitative structure-activity relationship (QSAR) model demonstrated that six descriptors such as RDF085v, Mor06u, Mor11u, Dv, HATS0v and H-046, are likely to influence the insecticidal activity of these compounds. Among them, two important ones are the Mor06u and RDF085v.
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A Multiphysics Modeling Approach to Develop Right Ventricle Pulmonary Valve Replacement Surgical Procedures with a Contracting Band to Improve Ventricle Ejection Fraction.
Comput Struct
PUBLISHED: 05-14-2013
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Patients with repaired tetralogy of Fallot account for the majority of cases with late onset right ventricle (RV) failure. A new surgical procedure placing an elastic band in the right ventricle is proposed to improve RV function measured by ejection fraction. A multiphysics modeling approach is developed to combine cardiac magnetic resonance imaging, modeling, tissue engineering and mechanical testing to demonstrate feasibility of the new surgical procedure. Our modeling results indicated that the new surgical procedure has the potential to improve right ventricle ejection fraction by 2-7% which compared favorably with recently published drug trials to treat LV heart failure.
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Application of a high performance liquid chromatography-tandem mass spectrometry method for determination of buflomedil in human plasma for a bioequivalence study.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 05-02-2013
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A rapid, simple and sensitive method based on ultra fast liquid chromatography-tandem spectrometry for the determination of buflomedil in human plasma has been developed and validated using carbamazepine as internal standard. After the precipitation of plasma sample with methanol, the analyte and IS were separated on an Ultimate C18 column (5?m, 2.1mm×50mm, MD, USA) with an isocratic mobile phase composed of acetonitrile and 5mM ammonium acetate in water (60:40, v/v) at a flow rate of 0.25ml/min. The analyte and IS were detected with proton adducts at m/z 308.3-237.1 and m/z 237.2-194.2 in positive ion electrospray ionization and multiple reaction monitoring acquisition mode, respectively. The lower limit of quantification of the method was 23.64ng/ml with a linear dynamic range of 23.64-1182ng/ml for buflomedil. The intra- and inter-batch precisions were less than 5.8%. The developed method was successfully applied to a bioequivalence study of two buflomedil hydrochloride preparations (150mg) in 22 healthy Chinese male volunteers.
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Overexpression of CPE-?N predicts poor prognosis in colorectal cancer patients.
Tumour Biol.
PUBLISHED: 04-29-2013
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Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-?N) has been detected and the mechanism of CPE-?N action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-?N expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-?N isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-?N mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan-Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-?N is overexpressed in colorectal tumor tissue and that high CPE-?N mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis (P?=?0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-?N expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-?N expression had a significantly shorter survival (P?
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Effects of ketamine on lipopolysaccharide-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex.
Mol Med Rep
PUBLISHED: 03-06-2013
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The present study was designed to investigate the effects of ketamine on lipopolysaccharide (LPS)-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex. Thirty male Wistar rats were randomly divided into 3 groups (n=10): saline group (S group), LPS only group (L group) and LPS plus ketamine group (LK group). A forced swimming test (FST) was performed. On the first day, rats were placed into water for 15 min. Twenty-four hours later, rats were treated again as in the first test for a 5 min session, and the immobility time was recorded. The prefrontal cortex was harvested for the determination of the interleukin (IL)?1?, IL-6 and IL-10 levels. Compared with the S group, rats in the L group had significantly increased immobility time in the FST and expression of IL-1? and IL-6, and significantly decreased expression of IL-10 in the prefrontal cortex (P<0.05). However, rats in the LK group had significantly decreased immobility times in the FST and expression of IL-1? and IL-6, and significantly increased expression of IL-10 in the prefrontal cortex compared with the L group (P<0.05). Ketamine can alleviate LPS-induced depressive-like behavior, and its effect is likely associated with changes in the expression of inflammatory cytokines in the rat prefrontal cortex.
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Differential expression of ISG20 in chronic hepatitis B patients and relation to interferon-alpha therapy response.
J. Med. Virol.
PUBLISHED: 03-06-2013
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The 20 kDa exonuclease encoded by the interferon-stimulated gene, ISG20, can inhibit the replication of hepatitis B virus (HBV), and may represent a clinically useful prognostic marker for response to interferon-alpha (IFN-?) antiviral therapy. The present study was designed to investigate the differential expression patterns of ISG20 in liver biopsy samples from treatment-naive patients with chronic hepatitis B and non-HBV infected controls and to determine the relation between the differential expression and IFN-? treatment outcome (responders vs. non-responders). HBV infection status was determined by measuring levels of hepatitis B surface antigen (HBsAg) by chemoluminescence immunoassay and of HBV DNA by real-time quantitative (q)PCR. ISG20 protein and mRNA expressions were assessed by immunohistochemistry and qPCR, respectively. Chronic hepatitis B responders showed significantly higher levels of ISG20 protein and mRNA expressions than either the chronic hepatitis B non-responders or the controls. Moreover, increased expression of ISG20 in both the nucleus and cytoplasm was correlated with positive response to IFN-? treatment. Thus, active transcription and translation of ISG20 may represent a marker to identify chronic hepatitis B patients likely to respond to IFN-? therapy. Prognostic clinical strategies based upon this marker may include genomic screening methods and immunohistochemical staining of liver biopsies.
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Electrokinetics of non-Newtonian fluids: a review.
Adv Colloid Interface Sci
PUBLISHED: 03-03-2013
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This work presents a comprehensive review of electrokinetics pertaining to non-Newtonian fluids. The topic covers a broad range of non-Newtonian effects in electrokinetics, including electroosmosis of non-Newtonian fluids, electrophoresis of particles in non-Newtonian fluids, streaming potential effect of non-Newtonian fluids and other related non-Newtonian effects in electrokinetics. Generally, the coupling between non-Newtonian hydrodynamics and electrostatics not only complicates the electrokinetics but also causes the fluid/particle velocity to be nonlinearly dependent on the strength of external electric field and/or the zeta potential. Shear-thinning nature of liquids tends to enhance electrokinetic phenomena, while shear-thickening nature of liquids leads to the reduction of electrokinetic effects. In addition, directions for the future studies are suggested and several theoretical issues in non-Newtonian electrokinetics are highlighted.
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Determination of trace amounts of Se(IV) by hydride generation atomic fluorescence spectrometry after solid-phase extraction using magnetic multi-walled carbon nanotubes.
Talanta
PUBLISHED: 03-03-2013
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A sensitive and simple method using magnetic multi-walled carbon nanotubes, as an adsorbent, has been successfully developed for extraction and preconcentration trace amounts of Se(IV) with detection by hydride generation atomic fluorescence spectrometry. The prepared nanoparticles were confirmed by Fourier transform infrared spectra, X-ray diffraction spectrometry, vibrating sample magnetometry, and transmission electron microscopy. These magnetic nanocomposites can be easily dispersed in aqueous samples and retrieved by the application of external magnetic field via a piece of permanent magnet. The main factors affecting the signal intensity such as sample pH value, adsorbent amount, eluent concentration and volume, sample volume, and coexisting ions have been investigated and established. The absorbent could be repeatedly used at least 100 times. The enhancement factor of the proposed method for Se(IV) was 100. The method had a linear calibration plot in the range from 0.05 to 10.0 ?g L(-1) with a standard deviation of 2.3% at 0.5 ?g L(-1) (n=11). The limit of detection was as low as 0.013 ?g L(-1). Accuracy of the method was evaluated by the analysis of water samples and certified reference materials.
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Dynamic contact angle of water-based titanium oxide nanofluid.
Nanoscale Res Lett
PUBLISHED: 02-27-2013
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This paper presents an investigation into spreading dynamics and dynamic contact angle of TiO2-deionized water nanofluids. Two mechanisms of energy dissipation, (1) contact line friction and (2) wedge film viscosity, govern the dynamics of contact line motion. The primary stage of spreading has the contact line friction as the dominant dissipative mechanism. At the secondary stage of spreading, the wedge film viscosity is the dominant dissipative mechanism. A theoretical model based on combination of molecular kinetic theory and hydrodynamic theory which incorporates non-Newtonian viscosity of solutions is used. The model agreement with experimental data is reasonable. Complex interparticle interactions, local pinning of the contact line, and variations in solid-liquid interfacial tension are attributed to errors.
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Rapamycin and mTOR inhibitors probably have therapeutic effects for post-operative cognitive dysfunction.
Med. Hypotheses
PUBLISHED: 02-17-2013
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Several lines of evidence have indicated that rapamycin acts as an inhibitor of mammalian target of rapamycin (mTOR) and this produces therapeutic benefits as a treatment for Alzheimers disease (AD) by activating an autophagic pathway. Similarly, postoperative cognitive dysfunction (POCD) is a decline in cognitive function for weeks or months after surgery. POCD and AD are both characterized by cognitive dysfunction, and more importantly, are both related to aging. We therefore hypothesized that rapamycin may have a therapeutic effect to relieve POCD. Inhibition of mTOR induces autophagic effect, thereby leading to a slower aging process, so this would be a novel target for the prevention and treatment of POCD.
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Mutant spectrum of dengue type 1 virus in the plasma of patients from the 2006 epidemic in South China.
Int. J. Infect. Dis.
PUBLISHED: 01-21-2013
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The aim of the present study was to explore the mutant spectrum of dengue type 1 virus (DENV-1) within individuals during the 2006 dengue epidemic in South China. A 513-bp fragment including most of domain III of the envelope (E) gene was amplified directly from clinical samples, then cloned and sequenced. A total of 89 clones from six patients (range 11-17 clones per patient) were sequenced. Genetic diversity was calculated using MEGA 4 package. The total number of nucleotide mutations was 113 (3.7%) within the sequenced 513-bp E gene, with a range of 15 (3%) to 24 (4.7%) within individual viral populations, harboring more non-synonymous than synonymous mutations. The extent of sequence diversity varied among patients, with the mean diversity ranging from 0.19% to 0.32%, and the mean pairwise p-distance ranging from 0.34% to 0.65%. No genome-defective virus was detected in any clone in this study. Purifying selection may be the main driving force for the intrahost evolution: the mean dN/dS ratio was 0.532. Our findings contribute to the understanding of the genetic variation of DENV-1 in South China.
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Ketamine attenuates the lipopolysaccharide-induced inflammatory response in cultured N2a cells.
Mol Med Rep
PUBLISHED: 01-20-2013
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The use of ketamine is recommended in patients with sepsis undergoing surgery due to its anti-inflammatory effects. However, a paucity of data exists with regard to the anti-inflammatory effects of ketamine in the central nervous system. Therefore, the present study aimed to investigate the effect of ketamine on lipopolysaccharide (LPS)?induced inflammatory responses in cultured Neuro2a (N2a) cells and to elucidate its potential mechanism of action. N2a cells were randomly divided into the following 3 groups (n=6): The DMEM culture solution administration alone group, the 0.5 µmol/l LPS administration alone group and the 1 µmol/l ketamine plus 0.5 µmol/l LPS administration group. The expression levels of interleukin (IL)-1?, IL-6, tumor necrosis factor (TNF)-?, nuclear factor (NF)-?B and inducible nitric oxide synthase (iNOS) were determined. LPS-treated N2a cells exhibited a significant increase in the expression levels of IL-1?, IL-6, TNF-?, NF-?B and iNOS, while the administration of ketamine eliminated the LPS-induced production of IL-1?, IL-6, TNF-?, NF-?B and iNOS. Based on our data, we hypothesized that the anti-inflammatory effect exerted by ketamine on N2a cells was potentially due to the inhibition of NF-?B and iNOS.
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Dishevelled-2 silencing reduces androgen-dependent prostate tumor cell proliferation and migration and expression of Wnt-3a and matrix metalloproteinases.
Mol. Biol. Rep.
PUBLISHED: 01-19-2013
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To identify Dishevelled-2 (Dvl2) is a prostate cancer-associated gene and analyze the effects on the growth and invasive capacity of human prostate cancer (PCa) cells. Dvl2 mRNA expression was measured in PCa cell lines and tissue samples, by real-time reverse transcription PCR (qRT-PCR). Immunohistochemistry was used to examine the distribution of Dvl2 in PCa specimens. Silencing Dvl2 in LNCaP cells, proliferation was measured by the CCK-8 assay, cell motility and invasiveness by scratch wound and transwell migration assays, and Wnt-3a, AR, and matrix metalloproteinase (MMP) expression by western blotting. Dvl2 was overexpressed in LNCaP cells compared with the AI PCa lines DU-145 and PC-3, as well as in the majority of PCa tissue specimens examined by qRT-PCR (14/27, 51.9 %). Dvl2 expression was low in all 10 BPH specimens, weakly positive in 26/104 AD PCa specimens (23.8 %), positive in 60/104 AD PCa specimens (55 %), and strongly positive in all 5 AI PCa specimens. Dvl2 expression was significantly correlated with combined Gleason score (p = 0.02), lymph node metastasis (p = 0.005), and TNM stage (p = 0.015). Silencing of Dvl2 mRNA expression significantly reduced LNCaP cell proliferation, motility, invasiveness and Wnt-3a, AR, MMP-2, and MMP-9 expression. Dvl2 may increase PCa growth and metastasis potential, possibly by upregulating Wnt-3a, AR, and MMP expression. Silencing Dvl2 expression may be an effective treatment strategy for PCa.
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Adenosine inhibits the excitatory synaptic inputs to Basal forebrain cholinergic, GABAergic, and parvalbumin neurons in mice.
Front Neurol
PUBLISHED: 01-01-2013
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Coffee and tea contain the stimulants caffeine and theophylline. These compounds act as antagonists of adenosine receptors. Adenosine promotes sleep and its extracellular concentration rises in association with prolonged wakefulness, particularly in the basal forebrain (BF) region involved in activating the cerebral cortex. However, the effect of adenosine on identified BF neurons, especially non-cholinergic neurons, is incompletely understood. Here we used whole-cell patch-clamp recordings in mouse brain slices prepared from two validated transgenic mouse lines with fluorescent proteins expressed in GABAergic or parvalbumin (PV) neurons to determine the effect of adenosine. Whole-cell recordings were made from BF cholinergic neurons and from BF GABAergic and PV neurons with the size (>20??m) and intrinsic membrane properties (prominent H-currents) corresponding to cortically projecting neurons. A brief (2?min) bath application of adenosine (100??M) decreased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in all groups of BF cholinergic, GABAergic, and PV neurons we recorded. In addition, adenosine decreased the frequency of miniature EPSCs in BF cholinergic neurons. Adenosine had no effect on the frequency of spontaneous inhibitory postsynaptic currents in cholinergic neurons or GABAergic neurons with large H-currents but reduced them in a group of GABAergic neurons with smaller H-currents. All effects of adenosine were blocked by a selective, adenosine A1 receptor antagonist, cyclopentyltheophylline (CPT, 1??M). Adenosine had no postsynaptic effects. Taken together, our work suggests that adenosine promotes sleep by an A1 receptor-mediated inhibition of glutamatergic inputs to cortically projecting cholinergic and GABA/PV neurons. Conversely, caffeine and theophylline promote attentive wakefulness by inhibiting these A1 receptors in BF thereby promoting the high-frequency oscillations in the cortex required for attention and cognition.
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Regulated expression of lentivirus-mediated GDNF in human bone marrow-derived mesenchymal stem cells and its neuroprotection on dopaminergic cells in vitro.
PLoS ONE
PUBLISHED: 01-01-2013
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Gene regulation remains one of the major challenges for gene therapy in clinical trials. In the present study, we first generated a binary tetracycline-on (Tet-On) system based on two lentivirus vectors, one expressing both human glial cell line-derived neurotrophic factor (hGDNF) and humanized recombinant green fluorescent protein (hrGFP) genes under second-generation tetracycline response element (TRE), and the other expressing the advanced reverse tetracycline-controlled transactivator--rtTA2S-M2 under a human minimal cytomegalovirus immediate early (CMV-IE) promoter. This system allows simultaneous expression of hGDNF and hrGFP genes in the presence of doxycycline (Dox). Human bone marrow-derived mesenchymal stem cells (hMSCs) were transduced with the binary Tet-On lentivirus vectors and characterized in vitro in the presence (On) or absence (Off) of Dox. The expression of hGDNF and hrGFP transgenes in transduced hMSCs was tightly regulated as determined by flow cytometry (FCM), GDNF enzyme-linked immunosorbent assay (ELISA) and quantitative real time-polymerase chain reaction (qRT-PCR). There was a dose-dependent regulation for hrGFP transgene expression. The levels of hGDNF protein in culture medium were correlated with the mean fluorescence intensity (MFI) units of hrGFP. The levels of transgene background expression were very low in the absence of Dox. The treatment of the conditioned medium from cultures of transduced hMSCs in the presence of Dox protected SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) toxicity as determined by cell viability using 3, [4,5-dimethylthiazol-2-yl]-diphenyltetrazolium bromide (MTT) assay. The treatment of the conditioned medium was also found to improve the survival of dopaminergic (DA) neurons of ventral mesencephalic (VM) tissue in serum-free culture conditions as assessed by cell body area, the number of neurites and dendrite branching points, and proportion of tyrosine hydroxylase (TH)-immunoreactive (IR) cells. Our inducible lentivirus-mediated hGDNF gene delivery system may provide useful tools for basic research on gene therapy for chronic neurological disorders such as Parkinsons disease (PD).
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