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Find video protocols related to scientific articles indexed in Pubmed.
[Nutrient accumulation and cycling in pure and mixed plantations of Azadirachta indica and Acacia auriculiformis in a dry-hot valley, Yunnan Province, southwest China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 10-28-2014
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To ease the implementation of effective nutrient management for plantations with different vegetation restoration patterns and to assist in the selection of appropriate species and forestation patterns, nutrient (N, P, K, Ca and Mg) accumulation and cycling were investigated and compared in three plantations (10-year-old Azadirachta indica, Acacia auriculiformis and mixed A. indica--A. auriculiformis plantations) in Yuanmou Valley, a dry-hot valley of Yunnan Province, Southwestern China. The result showed that total nutrient accumulations were 333.05, 725.61 and 533.85 kg x hm(-2) in pure plantations of A. indica and A. auriculiformis, and in A. indica--A. auriculiformis mixed plantation, respectively. The nutrient accumulation of various organs was ranked as branches > stems > roots > leaves > bark in the A. indica plantation and branches > stems > leaves > roots > bark both in the A. auriculiformis plantation and in the mixed plantation. Changes in accumulation of various nutrients in the mixed plantation were similar to that in the A. auriculiformis plantation (Ca > N > K > Mg > P), which were different from the A. indica plantation (Ca > K > N > Mg > P). Annual net nutrient accumulation, return and absorption in these plantations ranged from 62.72 to 162.19 kg x hm(-2) x a(-1), 48.82 to 88.86 kg x hm-2 a-1 and 111.54 to 251.05 kg x hm(-2) x a(-1), respectively, which were all the highest in the A. auriculiformis planta- tion, followed by the mixed plantation, and were the lowest in the A. indica plantation. The nutrient utilization coefficient, the cycling coefficient and the recycling period were estimated to be from 0.34 to 0.39, 0.35 to 0.44, and 6.54 to 8.17 a, respectively. The lower nutrient return and circulation rate of N or P in the A. indica plantation showed that this plantation had a poor ability to maintain soil fertility, while the highest nutrient circulation rate of N or P was observed in the A. auriculiformis plantation that displayed the advantage in maintaining soil nutrients and stand productivity. The nutrient return and nutrient absorption in the mixed plantation were 167.2% and 186.2%, of those in the A. indica plantation, and the circulation rate of N, P and K were higher than those in the A. indica plantation, while the recycling period of Ca in mixed plantation was 50% shorter than that in A. auriculiformis plantation. Soil fertility and nutrient supply were improved in the A. indica and A. auriculiformis mixed plantation.
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Multicomponent Reactions of Phosphines, Diynedioates, and Aryl Aldehydes Generated Furans Appending Reactive Phosphorus Ylides through Cumulated Trienoates as Key Intermediates: A Phosphine ?-Addition-?-Evolvement of an Anion Pathway.
Org. Lett.
PUBLISHED: 10-22-2014
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Multicomponent reactions of phosphines, diynedioates, and aryl aldehydes have been demonstrated, providing trisubstituted furans appending reactive phosphorus ylides, through cumulated trienoates as key intermediates. The proposed trienoate intermediates, 1,5-dipolar species formed via nucleophilic ?-attack of phosphines toward diynedioates (?-addition-?-evolvement of an anion, abbreviated ?A?E), undergo addition to aryl aldehydes followed by 5-endo-dig cyclization, proton transfer, and resonance to give trisubstituted furans. Furthermore, the phosphorus ylides are oxidized to ?-keto ester furans and utilized as Wittig reagents.
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Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium-Induced Colon Cancer.
J. Pharmacol. Exp. Ther.
PUBLISHED: 10-02-2014
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The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR-dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor ?-light-chain-enhancer of activated B cells-mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events.
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The early stage of the atrial electroanatomic remodeling as substrates for atrial fibrillation in hypertensive patients.
J Am Heart Assoc
PUBLISHED: 09-20-2014
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Hypertension is one of the most important risk factors for atrial fibrillation (AF). Recent studies suggest right atrial remodeling in hypertensive patients may be associated with increased inducibility of AF. This study sought to characterize the electroanatomic features of left and right atria and pulmonary veins (PVs) in hypertensive patients.
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Roles of SATB2 in Site-Specific Stemness, Autophagy and Senescence of Bone Marrow Mesenchymal Stem Cells.
J. Cell. Physiol.
PUBLISHED: 09-09-2014
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Craniofacial bone marrow mesenchymal stem cells (BMSCs) display some site-specific properties that differ from those of BMSCs derived from the trunk and appendicular skeleton, but the characteristics of craniofacial BMSCs and the mechanisms that underlie their properties are not completely understood. Previous studies indicated that special AT-rich binding protein 2 (SATB2) may be a potential regulator of craniofacial skeletal patterning and site-specific osteogenic capacity. Here, we investigated the stemness, autophagy, and anti-aging capacity of mandible-derived BMSCs (M-BMSCs) and tibia-derived BMSCs (T-BMSCs) and explored the role of SATB2 in regulating these properties. M-BMSCs not only possessed stronger expression of SATB2 and stemness markers (pluripotency genes, such as Nanog, OCT-4, Sox2, and Nestin) but also exhibited stronger autophagy and anti-aging capacities under normal or hypoxia/serum deprivation conditions compared to T-BMSCs. Exogenous expression of SATB2 in T-BMSCs significantly enhanced the expression of pluripotency genes as well as autophagy and anti-aging capacity. Moreover, SATB2 markedly enhanced osteogenic differentiation of BMSCs in vitro, and promoted bone defect regeneration and the survival of BMSCs that were transplanted into mandibles with critical size defects. Mechanistically, SATB2 upregulates pluripotency genes and autophagy-related genes, which in turn activate the mechanistic target of rapamycin signaling pathway. Collectively, our results provide novel evidence that site-specific BMSCs have distinct biological properties and suggest that SATB2 plays a potential role in regulating the stemness, autophagy, and anti-aging properties of craniofacial BMSCs. The application of SATB2 to manipulate stem cells for the reconstruction of bone defects might represent a new approach. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
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An 8-GW long-pulse generator based on Tesla transformer and pulse forming network.
Rev Sci Instrum
PUBLISHED: 07-03-2014
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A long-pulse generator TPG700L based on a Tesla transformer and a series pulse forming network (PFN) is constructed to generate intense electron beams for the purpose of high power microwave (HPM) generation. The TPG700L mainly consists of a 12-stage PFN, a built-in Tesla transformer in a pulse forming line, a three-electrode gas switch, a transmission line with a trigger, and a load. The Tesla transformer and the compact PFN are the key technologies for the development of the TPG700L. This generator can output electrical pulses with a width as long as 200 ns at a level of 8 GW and a repetition rate of 50 Hz. When used to drive a relative backward wave oscillator for HPM generation, the electrical pulse width is about 100 ns on a voltage level of 520 kV. Factors affecting the pulse waveform of the TPG700L are also discussed. At present, the TPG700L performs well for long-pulse HPM generation in our laboratory.
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A novel method for the sensitive detection of mutant proteins using a covalent-bonding tube-based proximity ligation assay.
Anal. Chim. Acta
PUBLISHED: 06-27-2014
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Tumorigenesis is the cumulative result of multiple gene mutations. The mutant proteins that are expressed by mutant genes in cancer cells are secreted into the blood and are useful biomarkers for the early diagnosis of cancer. However, some difficulties exist; for example, the same gene will express different protein mutants in different patients, and early tumors secrete only small amounts of mutant protein. Thus, the presence of mutant proteins in plasma has not previously been exploited for the early diagnosis of cancer. Proximity ligation assay is a protein-detection method that has been developed in recent years and has been widely used because of its high sensitivity. However, this approach still suffers from some shortcomings that should be addressed. In this paper, we develop a covalent-bonding tube-based proximity ligation assay (TB-PLA). The limit of detection of TB-PLA for 0.001pM, and the method exhibited a broad dynamic range of up to seven orders of magnitude. Furthermore, we coupled the conformation-specific antibody PAb240 of p53 mutants to PCR tubes for TB-PLA. The assay was capable of detecting an approximately 500-fold lower concentration of mutant p53 in serum compared with sandwich ELISA. Thus, we demonstrate TB-PLA to be a highly sensitive and effective approach that is suitable for the early clinical diagnosis of cancer using the conformation-specific antibodies of protein mutants.
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Nucleophilic conjugate 1,3-addition of phosphines to oligoynoates.
Chem. Commun. (Camb.)
PUBLISHED: 06-20-2014
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Herein we have elucidated unusual and unique nucleophilic conjugate 1,3-addition reactions of surveyed oligoynoates toward phosphines through spectroscopic and single crystal X-ray diffraction analyses of three-component reaction products of oligoynoates, phosphines and aldehydes.
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Evaluation of different obesity indices as predictors of type 2 diabetes mellitus in a Chinese population.
J Diabetes
PUBLISHED: 06-17-2014
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The aim of the present study was to compare correlation coefficients between anthropometric indices and blood glucose level, and to determine optimal cutoff points of obesity indices in a Chinese population.
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Nano-sized titanium dioxide-induced splenic toxicity: a biological pathway explored using microarray technology.
J. Hazard. Mater.
PUBLISHED: 06-01-2014
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Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.5, 5, or 10mg/kg body weight TiO2 NPs were administered to the mice by intragastric administration for 90 consecutive days, their immune capacity in the spleen as well as the gene-expressed characteristics in the mouse damaged spleen were investigated using microarray assay. The findings showed that with increased dose, TiO2 NP exposure resulted in the increases of spleen indices, immune dysfunction, and severe macrophage infiltration as well as apoptosis in the spleen. Importantly, microarray data showed significant alterations in the expressions of 1041 genes involved in immune/inflammatory responses, apoptosis, oxidative stress, stress responses, metabolic processes, ion transport, signal transduction, cell proliferation/division, cytoskeleton and translation in the 10 mg/kg TiO2 NP-exposed spleen. Specifically, Cyp2e1, Sod3, Mt1, Mt2, Atf4, Chac1, H2-k1, Cxcl13, Ccl24, Cd14, Lbp, Cd80, Cd86, Cd28, Il7r, Il12a, Cfd, and Fcnb may be potential biomarkers of spleen toxicity following exposure to TiO2 NPs.
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High expression of the histone demethylase LSD1 associates with cancer cell proliferation and unfavorable prognosis in tongue cancer.
J. Oral Pathol. Med.
PUBLISHED: 05-15-2014
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The histone lysine-specific demethylase (LSD1) is a key chromatin modifier mediating the demethylation of both H3K4me1/me2 and H3K9 me1/me2. Recently, its deregulation has been implicated in the initiation and progression of various cancers. The aim of this study was to investigate the expression pattern of LSD1 in tongue squamous cell carcinoma (SCC) and determine its prognostic significance in predicting patients' prognosis.
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Phenotypic characterization of craniofacial bone marrow stromal cells: unique properties of enhanced osteogenesis, cell recruitment, autophagy, and apoptosis resistance.
Cell Tissue Res.
PUBLISHED: 05-15-2014
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Previous studies have shown that craniofacial bone marrow stromal cells (MSCs) have greater osteogenic potential than appendicular bone MSCs. However, detailed phenotypic characterization of MSCs from bone marrow in the different sites remains unclear. To investigate bone repair and regeneration of craniofacial MSCs and the regulatory mechanisms underlying their unique properties, we compared osteogenesis, cell recruitment, autophagy, and apoptosis resistance of MSCs from the mandible (M-MSCs) to those from tibia (T-MSCs) in vitro and in vivo. Compared with T-MSCs, M-MSCs formed more colonies, possessed stronger proliferation activity, exhibited higher expression of pluripotency genes such as Oct4 and Nanog, and held stronger osteogenic differentiation in osteogenic medium. Moreover, M-MSCs had greater autophagy and anti-apoptotic capacities than T-MSCs under hypoxia and serum deprivation conditions. M-MSCs were found to be more capable of recruiting more MSCs than T-MSCs. When these MSCs were transplanted into mandible critical-sized defects, more bone formed in the M-MSC-treated animals than in their T-MSC counterparts. Collectively, these findings reveal that MSCs have unique characteristics and bone-repairing properties from the mandible as compared with those from tibia, presumably by enhanced osteogenic potential, cell recruitment, autophagy and apoptosis resistance.
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Mis-regulation of mammalian target of rapamycin (mTOR) complexes induced by albuminuria in proximal tubules.
J. Biol. Chem.
PUBLISHED: 05-01-2014
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High albumin concentrations in the proximal tubule of the kidney causes tubulointerstitial injury, but how this process occurs is not completely known. To address the signal transduction pathways mis-regulated in renal injury, we studied the modulation of mammalian target of rapamycin (mTOR) complexes by physiologic and pathophysiologic albumin concentrations in proximal tubule cells. Physiologic albumin concentrations activated the PI3K/mTORC2/PKB/mTORC1/S6 kinase (S6K) pathway, but pathophysiologically high albumin concentrations overactivated mTORC1 and inhibited mTORC2 activity. This control process involved the activation of ERK1/2, which promoted the inhibition of TSC2 and activation of S6K. Furthermore, S6K was crucial to promoting the over activation of mTORC1 and inhibition of mTORC2. Megalin expression at the luminal membrane is reduced by high concentrations of albumin. In addition, knockdown of megalin mimicked all the effects of pathophysiologic albumin concentrations, which disrupt normal signal transduction pathways and lead to an overactivation of mTORC1 and inhibition of mTORC2. These data provide new perspectives for understanding the molecular mechanisms behind the effects of albumin on the progression of renal disease.
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Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer.
Histopathology
PUBLISHED: 04-21-2014
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Pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) are two metabolic and oncogenic markers of cancer. In this study, we sought to investigate their expression patterns and prognostic value in tongue squamous cell carcinoma (TSCC).
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Visualizing the kinetic power stroke that drives proton-coupled zinc(II) transport.
Nature
PUBLISHED: 04-14-2014
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The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of Escherichia coli. Its transport site receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux. This membrane protein is a well-characterized member of the family of cation diffusion facilitators that occurs at all phylogenetic levels. Here we show, using X-ray-mediated hydroxyl radical labelling of YiiP and mass spectrometry, that Zn(II) binding triggers a highly localized, all-or-nothing change of water accessibility to the transport site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics reveal a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical re-orientation linked to Zn(II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport site enables a stationary proton gradient to facilitate the conversion of zinc-binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active-transport reaction.
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The LRP6 rs2302685 polymorphism is associated with increased risk of myocardial infarction.
Lipids Health Dis
PUBLISHED: 04-12-2014
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Abnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI.
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Access to Healthy Food Stores Modifies Effect of a Dietary Intervention.
Am J Prev Med
PUBLISHED: 04-04-2014
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Recent evidence suggests that opening a grocery store in a food desert does not translate to better diet quality among community residents.
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Evaluation of a Brucella melitensis mutant deficient in O-polysaccharide export system ATP-binding protein as a rough vaccine candidate.
Microbes Infect.
PUBLISHED: 04-02-2014
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Rough Brucella mutants have been sought as vaccine candidates that do not interfere with the conventional serological diagnosis of brucellosis. In this study, a rough mutant of Brucella melitensis was generated by the disruption of the wzt gene, which encodes the O-polysaccharide (O-PS) export system ATP-binding protein. In vivo, the mutant 16M?wzt was attenuated and conferred a level of protection against B. melitensis 16M challenge similar to that conferred by the vaccine strain B. melitensis M5 in mice. In pregnant sheep, the mutant 16M?wzt did not induce abortion. In vitro, 16M?wzt was more susceptible to polymyxin B and complement-mediated killing than B. melitensis 16M was. Most importantly, although 16M?wzt had a rough phenotype, it was able to synthesize O-PS and did not induce detectable specific antibodies in sheep. These results suggested that 16M?wzt deserved to further systematic evaluation as a vaccine for target animal hosts due to its promising features.
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Oncogenic roles of Bmi1 and its therapeutic inhibition by histone deacetylase inhibitor in tongue cancer.
Lab. Invest.
PUBLISHED: 03-16-2014
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The polycomb complex protein Bmi1 (B lymphoma Mo-MLV insertion region 1 homolog) mediates epigenetic transcriptional silencing by modifying chromatin structure and is critical for stem cell homeostasis and tumorigenesis. Bmi1 is frequently overexpressed in human malignancies and therefore has key diagnostic and prognostic significance, and holds potential as a therapeutic target. Here we sought to characterize the expression patterns and oncogenic roles of Bmi1 in tongue squamous cell carcinoma and to determine the anticancer effects of histone deacetylase inhibitors (HDACis) via Bmi1 inhibition against tongue cancer. Our data revealed that Bmi1 was aberrantly overexpressed in a significant portion of tongue cancers. Elevated Bmi1 is associated with cervical node metastasis, Ki-67 abundance and reduced overall survival, and also serves as an independent prognostic factor for patient outcomes. Short-hairpin RNA-mediated Bmi1 knockdown inhibited cell proliferation and migration, induced cell apoptosis and senescence, reduced colony formation and CD44(+)CD133(+) sub-population as well as enhanced cisplatin chemosensitivity, presumably by modulation of p16, p14 and E-cadherin. Moreover, HDACi chemicals Trichostatin A (TSA) and sodium butyrate (NaB) potently inhibited Bmi1 and triggered similar phenotypic changes reminiscent of Bmi1 silencing, although TSA treatment seemed paradoxically to induce some epithelial-mesenchymal transition-like changes in tongue cancer cells. Importantly, NaB-induced antitumor effects were partially attenuated by enforced Bmi1 overexpression in vitro. Genetic Bmi1 silencing and pharmacological inhibition of Bmi1 by NaB treatment significantly impaired tumor growth in a tongue cancer xenograft model. Taken together, our results indicate that Bmi1 serves as a key driver and biomarker with multiple oncogenic functions underlying tongue tumorigenesis. Selected appropriate HDACi compounds like NaB may represent novel therapeutic agents against tongue cancer.Laboratory Investigation advance online publication, 6 October 2014; doi:10.1038/labinvest.2014.123.
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Bile acid signaling in lipid metabolism: Metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice.
Biochim. Biophys. Acta
PUBLISHED: 03-11-2014
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Bile acid synthesis is the major pathway for catabolism of cholesterol. Cholesterol 7?-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway in the liver and plays an important role in regulating lipid, glucose and energy metabolism. Transgenic mice overexpressing CYP7A1 (CYP7A1-tg mice) were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and diabetes. However the mechanism of resistance to HFD-induced obesity of CYP7A1-tg mice has not been determined. In this study, metabolomic and lipidomic profiles of CYP7A1-tg mice were analyzed to explore the metabolic alterations in CYP7A1-tg mice that govern the protection against obesity and insulin resistance by using ultra-performance liquid chromatography-coupled with electrospray ionization quadrupole time-of-flight mass spectrometry combined with multivariate analyses. Lipidomics analysis identified seven lipid markers including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides that were significantly decreased in serum of HFD-fed CYP7A1-tg mice. Metabolomics analysis identified 13 metabolites in bile acid synthesis including taurochenodeoxycholic acid, taurodeoxycholic acid, tauroursodeoxycholic acid, taurocholic acid, and tauro-?-muricholic acid (T-?-MCA) that differed between CYP7A1-tg and wild-type mice. Notably, T-?-MCA, an antagonist of the farnesoid X receptor (FXR) was significantly increased in intestine of CYP7A1-tg mice. This study suggests that reducing 12?-hydroxylated bile acids and increasing intestinal T-?-MCA may reduce high fat diet-induced increase of phospholipids, sphingomyelins and ceramides, and ameliorate diabetes and obesity. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.
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[Correlation analysis between miR-124 rs531564 polymorphisms and susceptibility to cervical cancer].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 03-05-2014
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To investigate the correlation between miR-124 rs531564 polymorphisms and the susceptibility to cervical cancer in Chinese Han women in Guangdong Province.
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A sparse ising model with covariates.
Biometrics
PUBLISHED: 03-01-2014
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There has been a lot of work fitting Ising models to multivariate binary data in order to understand the conditional dependency relationships between the variables. However, additional covariates are frequently recorded together with the binary data, and may influence the dependence relationships. Motivated by such a dataset on genomic instability collected from tumor samples of several types, we propose a sparse covariate dependent Ising model to study both the conditional dependency within the binary data and its relationship with the additional covariates. This results in subject-specific Ising models, where the subject's covariates influence the strength of association between the genes. As in all exploratory data analysis, interpretability of results is important, and we use ?1 penalties to induce sparsity in the fitted graphs and in the number of selected covariates. Two algorithms to fit the model are proposed and compared on a set of simulated data, and asymptotic results are established. The results on the tumor dataset and their biological significance are discussed in detail.
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Osteosarcoma metastasis: prospective role of ezrin.
Tumour Biol.
PUBLISHED: 02-25-2014
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Osteosarcoma is the most commonly diagnosed primary malignant bone tumor, with similar global incidence rate across childhood and adolescence. Patients with localized disease have a 5-year survival period of 80 %; however, the prognosis is poor in those with metastatic osteosarcoma. The origin of the primary tumor is most frequently the metaphyseal (actively growing) regions of the distal femur, proximal tibia, and proximal humerus, although the tumor can develop in any bone, and the most likely sites for metastasis are the lungs and bone. Ezrin is a member of the ezrin-radixin-moesin (ERM) family of proteins that functions as a cross-linker between the actin cytoskeleton and the plasma membrane, and ezrin also plays a positive role in maintaining cell shape and polarity and facilitates membrane-trafficking pathways, cell migration, cell signaling, growth regulation, and differentiation. There is strong evidence to suggest that ezrin is necessary for osteosarcoma metastasis. The objective of the current review is to summarize the know-how about metastatic progression in osteosarcoma, with a focus on ezrin. Despite the promise that preliminary studies on ezrin have shown, there is a great need to further analyze the role of ezrin in osteosarcoma metastasis and to determine its usefulness as a biomarker for the disease.
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Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes.
Life Sci.
PUBLISHED: 02-14-2014
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We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes.
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Tripterygium glycosides impairs the proliferation of granulosa cells and decreases the reproductive outcomes in female rats.
Birth Defects Res. B Dev. Reprod. Toxicol.
PUBLISHED: 02-11-2014
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This study was carried out to investigate the impact of tripterygium glycosides (TGs) on ovarian function of female rats in vitro and in vivo. In vitro studies showed that TG induced cells decrease at G1 phase and inhibited cell proliferation in rat granulosa cells. In vivo, female rats were intragastrically administered with TG at the dose of 60 mg/kg/day for consecutive 50 days. TG caused a prolonged estrous cycle, and a significant reduction in ovarian index, serum E2 level, and numbers of secondary and antral follicles (p < 0.05) in these rats. A significant reduction of viable embryos was demonstrated in TG-treated female rats after mating (p < 0.01). Further, we observed observed the reduced expression level of TGF-?1 after TG treatment in vitro and in vivo. Moreover, the expression of Smad2 and AKT was also decreased after TG treatment. These results suggest that TG can impair ovarian function through Smads-mediated TGF-?1 signal pathway.
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Histone deacetylase 8 suppresses osteogenic differentiation of bone marrow stromal cells by inhibiting histone H3K9 acetylation and RUNX2 activity.
Int. J. Biochem. Cell Biol.
PUBLISHED: 02-07-2014
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Bone marrow stromal cells (BMSCs) are multipotent progenitor cells with capacities to differentiate into the various cell types and hold great promise in regenerative medicine. The regulatory roles of histone deacetylases (HDACs) in osteoblast differentiation process have been increasingly recognized; however, little is known about the precise roles of HDAC8 in the osteogenic differentiation of BMSCs. Herein we aimed to investigate the roles of HDAC8 in the osteogenic differentiation of rat BMSCs by pharmacological and genetic manipulations in vitro. During osteogenic differentiation of BMSCs, pharmacological inhibition of HDAC8 by HDAC inhibitor valproic acid (VPA) promoted the level of histone H3 lysine 9 acetylation (H3K9Ac) and significantly enhanced the expression of osteogenesis-related genes Runx2, Osterix, osteocalcin (OCN), osteopontin (OPN) and alkaline phosphatase (ALP). Similarly, knockdown of HDAC8 using short interfering RNA triggered H3K9Ac and enhanced osteogenic differentiation of BMSCs, largely phenocopied the effects of VPA-mediated HDAC8 depletion. However, enforced expression of HDAC8 significantly reduced the level of H3K9Ac and inhibited osteogenic differentiation of BMSCs, which can be attenuated by VPA addition. Mechanistically, HDAC8 suppressed osteogenesis-related genes expression by removing the acetylation of histone H3K9, thus leading to transcriptional inhibition during osteogenic differentiation of BMSCs. Importantly, we found that HDAC8 physically associated with Runx2 to repress its transcriptional activity and this association decreased when BMSCs underwent osteogenic differentiation. Taken together, these results indicate that epigenetic regulation of Runx2 by HDAC8-mediated histone H3K9 acetylation is required for the proper osteogenic differentiation of BMSCs.
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Simple conditions for large morphological variations in thermoresponsive biopolymeric microstructures.
Chem. Commun. (Camb.)
PUBLISHED: 02-07-2014
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Thermoresponsive biopolymeric microstructures are prepared by exploiting the thermal phase transitions of emulsified elastin-like polypeptides (ELPs). ELP microbeads prepared below the transition temperature (Tt) have positively thermoresponsive pores. ELP microcapsules prepared above Tt have negatively thermoresponsive pores. Interestingly, the ELP microcapsules prepared at the temperature of the transition state displayed bidirectional thermoresponsive behavior.
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Role of IL-31 in regulation of Th2 cytokine levels in patients with nasal polyps.
Eur Arch Otorhinolaryngol
PUBLISHED: 01-23-2014
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Interleukin-31 (IL-31) is reported to be involved in Th2 cell-mediated diseases. However, the regulatory effect of IL-31 in the pathogenesis of nasal polyps (NPs) has not been understood. This study is aimed to determine whether IL-31 production is associated with Th2 cytokine levels and clinical severity in patients with NPs. Thirty patients with NPs and fifteen normal controls were included, and IL-31 production was determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The relationship between IL-31 expression and clinical severity was also evaluated. Besides, the effect of IL-31 on Th2 cytokine expression by polyp epithelial cells was investigated. We observed significantly enhanced IL-31 mRNA and protein level expression in NPs compared with normal control. IL-31+ cells were found to be positively correlated with clinical severity of NPs. Furthermore, we provided the direct evidence that IL-31 up-regulates Th2 cytokines expressed by polyp epithelial cells. Our results demonstrate that enhanced Th2 cytokine levels was correlated with IL-31 expression in NPs and provide a possible explanation for IL-31's regulatory role in the pathogenesis of NPs.
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A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression.
Mutat Res Fundam Mol Mech Mutagen
PUBLISHED: 01-07-2014
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miRNAs are small non-coding RNAs that play an important role in numerous physiological processes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs may change their property through altering miRNAs expression and/or maturation, resulting in diverse functional consequences. To date, the role of genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains poorly understood. Here we aimed to evaluate the influence of three common SNPs in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499 rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295 CAD patients and 283 controls. Genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a logistic regression analysis, we detected an association of rs2910164 in pre-miR-146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically significantly associated with the increased risk for CADs. As we used further genotype association models, we found a similar trend of the association in recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the genotypes of miR-146a rs2910164 were associated with its mature miRNA expression by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913 GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype carriers (P<0.05). We observed no association of the other two SNPs in miR-196a2 (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA.
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Detection of melamine in feed using liquid-liquid extraction treatment combined with surface-enhanced Raman scattering spectroscopy.
PLoS ONE
PUBLISHED: 01-01-2014
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A rapid, selective, and sensitive method to determine the melamine content in animal feeds was developed using surface-enhanced Raman scattering spectroscopy on aggregated 55 nm Au nanoparticles with liquid-liquid extraction sample preparation. Butyl alcohol was used as the initial extraction solvent, and liquid-liquid extraction was performed twice using HCl (pH 3-4) and 6:1 (v/v) n-butyl alcohol/ethyl acetate. The intensity of the matrix-based peak at 731 cm?¹ was set at 100 as a basis for the feeds, and the peak at 707 cm-1 was the characteristic peak of melamine used in the calculations. Sufficient linearity was obtained in the range 2-10 µg·g?¹ (R²?=?0.991). Limits of detection and quantification in the feeds were 0.5 and 2 µg·g?¹, respectively. The recovery rates were 82.5-90.2% with coefficients of variation below 4.02%. This new protocol could be easily developed for the routine monitoring of on-site feed quality and market surveillance.
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MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (?40%), BCL2 (?70%) and BCL6 (?50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.
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[Acceptability status of early antiretroviral therapy among HIV-positive men who have sex with men].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 12-20-2013
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To assess the acceptability and influence factors of early antiretroviral therapy (ART) among HIV-positive men who have sex with men (MSM) .
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The polycomb group protein EZH2 is a novel therapeutic target in tongue cancer.
Oncotarget
PUBLISHED: 12-19-2013
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EZH2, a core member of the Polycomb Repressor Complex 2 (PRC2), mediates transcriptional silencing by catalyzing the trimethylation of histone 3 lysine 27 (H3K27), which plays key roles in cancer initiation and progression. Here, we investigated the expression pattern and biological roles of EZH2 in tongue tumorigenesis by loss-of-function assays using small interference RNA and EZH2 inhibitor DZNep. Also we determined the therapeutic efficiency of DZNep against tongue cancer in vivo. We found that aberrantly overexpressed EZH2 was associated with pathological grade, cervical nodes metastasis and Ki-67 expression in tongue cancers. Elevated EZH2 correlated with shorter overall survival and showed significant and independent prognostic importance in patients with tongue cancer. Both genetic and pharmacological depletion of EZH2 inhibited cell proliferation, migration, invasion and colony formation and decreased CD44+ subpopulation probably in part through modulating p16, p21 and E-caherin. Moreover, DZNep enhanced the anticancer effects of 5-Fluorouracil. Furthermore, intratumoral EZH2 inhibition induced by DZNep intraperitoneal administration significantly attenuated tumor growth in a tongue cancer xenograft model. Taken together, our results indicate that EZH2 serves as a key driver with multiple oncogenic functions during tongue tumorigenesis and a new biomarker for tongue cancer diagnosis and prognostic prediction. These findings open up possibilities for therapeutic intervention against EZH2 in tongue cancer.
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Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in vitamin D receptor intestine-deficient mice.
J. Lipid Res.
PUBLISHED: 12-16-2013
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Vitamin D receptor (VDR) mediates vitamin D signaling involved in bone metabolism, cellular growth and differentiation, cardiovascular function and bile acid regulation. Mice with an intestine-specific disruption of VDR (Vdr?IEpC) have abnormal body size, colon structure and imbalance of bile acid metabolism. Lithocholic acid (LCA), a secondary bile acid that activates VDR, is among the most toxic of the bile acids that when overaccumulated in liver causes hepatotoxicity. Since CYP3A4 is a target gene of VDR involved bile acid metabolism, the role of CYP3A4 in VDR biology and bile acid metabolism was investigated. The CYP3A4 gene was inserted into Vdr?IEpC mice to produce the Vdr?IEpC/3A4 line. LCA was administered to control, transgenic-CYP3A4 (Tg-3A4), Vdr?IEpC and Vdr?IEpC/3A4 mice and hepatic toxicity, bile acid levels in liver, intestine, bile and urine were measured. VDR deficiency in intestine of the Vdr?IEpC mice exacerbates LCA-induced hepatotoxicity manifested by increased necrosis and inflammation, due in part to over-accumulation of hepatic bile acids including taurocholic acid and taurodeoxycholic. Intestinal expression of CYP3A4 in the Vdr?IEpC/3A4 mouse line reduces lithocholic acid-induced hepatotoxicity through elevation of LCA metabolism and detoxification, and suppression of bile acid transporter expression in small intestine. This study revealed that intestinal CYP3A4 protects against LCA hepatotoxicity.
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?-Smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma.
J. Oral Pathol. Med.
PUBLISHED: 11-14-2013
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?-Smooth muscle actin (?-SMA)-positive myofibroblasts play a pivotal role in progression and metastasis of solid carcinomas. Epithelial-mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor microenvironment are the important events in tumor metastasis. This study aimed to investigate the relationship between the expression of myofibroblasts marker, ?-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC).
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One-pot formation of fluorescent ?-lactams having an ?-phosphorus ylide moiety through three-component ?(?)-Michael reactions of phosphines with an enyne and N-tosyl aldimines.
Org. Biomol. Chem.
PUBLISHED: 11-11-2013
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We demonstrate a straightforward synthesis of ?-lactams possessing an ?-phosphorus ylide moiety from assembly of phosphines, N-tosyl aldimines and an enyne through an initial ?(?)-attack of phosphines to an enyne in up to 79% yield. The investigated multicomponent reaction tolerates a variety of triarylphosphines and electron-poor aldimines to give ?-lactams in one pot. One of the lactams, with the tri(p-tol)phosphine and 4-cyanophenyl moiety, exhibits fluorescence emission at 447 nm with a quantum yield of 0.11.
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A quantitative analysis of F-actin features and distribution in fluorescence microscopy images to distinguish cells with different modes of motility.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Actin is one of the most abundant proteins in eukaryote cells, playing a key role in cell dynamic morphological alterations and tumor metastatic spread. To investigate the relationship between the distribution patterns of actin and the aggressiveness of cancer cells, we developed an image analysis framework for quantifying cell F-actin distributions examined with fluorescence microscopy. The images are first segmented with multichannel information of both F-actin and nuclear staining. Using the watershed method and Voronoi tessellation, the cells can be well segmented based on both F-actin and nuclear information. Altogether, sixteen F-actin distribution features are calculated for each individual cell. A linear Support Vector Machine (SVM) is then applied in the feature space to separate cells with different modes of motility. Our results show that cells with different modes of motility can be distinguished by F-actin distributions. To our knowledge, this is the first study managing to distinguish cancer cells with different aggressiveness based on quantitative analysis of F-actin distribution patterns.
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Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.
Chemosphere
PUBLISHED: 10-04-2013
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Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure.
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[Vegetation biomass allocation and its spatial distribution after 20 years ecological restoration in a dry-hot valley in Yuanmou, Yunnan Province of Southwest China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 09-27-2013
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By using layering harvest method, a comparative study was conducted on the biomass allocation and its spatial distribution of 20-year-old Eucalyptus camaldulensis plantation, Leucaena leucocephala plantation, and E. camaldulensis-L. leucocephala plantation in Yuanmou dry-hot valley of Yunnan Province, Southwest China. The stand biomass in the mixed E. camaldulensis-L. leucocephala plantation (82.99 t x hm(-2)) was between that of monoculture E. camaldulensis plantation (60.64 t x hm(-2)) and L. leucocephala plantation (127.79 t x hm(-2)). The individual tree biomass of E. camaldulensis in the mixed plantation (44.32 kg) was 49.8% higher than that in monoculture plantation (29.58 kg). The branch and leaf biomass of L. leucocephala (25.4%) in monoculture plantation was larger than that of E. camaldulensis (8.9%) in monoculture plantation, and the aboveground biomass distribution ratio (78.0%) of L. leucocephala (25.4%) was also higher than that of E. camaldulensis (73.4%). The roots of L. leucocephala in both monoculture and mixed plantations were mainly distributed in 0-40 cm soil layer, while those of E. camaldulensis in monoculture and mixed plantations were mainly found in 0-80 cm and 0-60 cm, respectively. The proportion of biomass allocated to roots including medium roots, small roots, and fine roots of L. leucocephala in mixed plantation was higher than that in monoculture plantation, but it was contrary for E. camaldulensis. It was suggested that introducing L. leucocephala in E. camaldulensis plantation promoted the growth of E. camaldulensis, especially for its aboveground biomass, and increased the amount of lateral roots in 0-20 cm soil layer, which had significance in soil and water conservation in the study area.
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Ionic mechanisms underlying the effects of vasoactive intestinal polypeptide on canine atrial myocardium.
Circ Arrhythm Electrophysiol
PUBLISHED: 09-17-2013
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Vasoactive intestinal polypeptide (VIP) is released from intracardiac neurons during vagal stimulation, ischemia, and heart failure, which are associated with increased vulnerability to atrial fibrillation. VIP shortens atrial effective refractory periods in dogs. Endogenous VIP contributes to vagally mediated acceleration of atrial electric remodeling. VIP is also shown to prolong the duration of acetylcholine-induced atrial fibrillation. However, the ionic mechanisms underlying VIP effects are largely unknown.
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Vasodilation by in vivo activation of astrocyte endfeet via two-photon calcium uncaging as a strategy to prevent brain ischemia.
J Biomed Opt
PUBLISHED: 09-16-2013
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ABSTRACT. Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimers disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.
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A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women.
Gynecol. Oncol.
PUBLISHED: 09-04-2013
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MicroRNAs (miRNAs) play critical roles in cervical carcinogenesis. Common single nucleotide polymorphisms (SNPs) in pre/pri-miRNAs may change their property through altering miRNAs expression and/or maturation. Here we aimed to investigate the influence of three common SNPs in pre/pri-miRNAs (pri-miR-26a-1 rs7372209, pre-miR-27a rs895819 and pri-miR-100 rs1834306) on individual susceptibility to cervical cancer.
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The apoptosis-inducing effect of ginsenoside F4 from steamed notoginseng on human lymphocytoma JK cells.
Nat. Prod. Res.
PUBLISHED: 08-20-2013
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In this study, the inhibitory and apoptosis-inducing effect of ginsenoside F4 (GF4) from steamed notoginseng was investigated by using human lymphocytoma Jurkat (JK) cell. Cell Counting Kit-8 method was then used to assess the anti-proliferative effect of GF4, and Western blotting was run to detect the expression level of two apoptosis-related proteins including Bax and the Bcl-2. The results suggested that GF4 can effectively inhibit the proliferation of the cells, and Bax expression increased gradually, but Bcl-2 expression reduced with the increase of GF4 concentration. In conclusion, GF4 has inhibitory effect on human lymphocytoma JK cell by inducing its apoptosis. The mechanism of action could be related to the mitochondrial dysfunction and the increase of Bax expression and decrease of Bcl-2 expression by GF4.
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Identification of 2-piperidone as a biomarker of CYP2E1 activity through metabolomic phenotyping.
Toxicol. Sci.
PUBLISHED: 06-28-2013
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Cytochrome P450 2E1 (CYP2E1) is a key enzyme in the metabolic activation of many low molecular weight toxicants and also an important contributor to oxidative stress. A noninvasive method to monitor CYP2E1 activity in vivo would be of great value for studying the role of CYP2E1 in chemical-induced toxicities and stress-related diseases. In this study, a mass spectrometry-based metabolomic approach was used to identify a metabolite biomarker of CYP2E1 through comparing the urine metabolomes of wild-type (WT), Cyp2e1-null, and CYP2E1-humanized mice. Metabolomic analysis with multivariate models of urine metabolites revealed a clear separation of Cyp2e1-null mice from WT and CYP2E1-humanized mice in the multivariate models of urine metabolomes. Subsequently, 2-piperidone was identified as a urinary metabolite that inversely correlated to the CYP2E1 activity in the three mouse lines. Backcrossing of WT and Cyp2e1-null mice, together with targeted analysis of 2-piperidone in mouse serum, confirmed the genotype dependency of 2-piperidone. The accumulation of 2-piperidone in the Cyp2e1-null mice was mainly caused by the changes in the biosynthesis and degradation of 2-piperidone because compared with the WT mice, the conversion of cadaverine to 2-piperidone was higher, whereas the metabolism of 2-piperidone to 6-hydroxy-2-piperidone was lower in the Cyp2e1-null mice. Overall, untargeted metabolomic analysis identified a correlation between 2-piperidone concentrations in urine and the expression and activity of CYP2E1, thus providing a noninvasive metabolite biomarker that can be potentially used in to monitor CYP2E1 activity.
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Reconstruction of palatomaxillary defects following cancer ablation with temporalis muscle flap in medically compromised patients: a 15-year single institutional experience.
Clin Oral Investig
PUBLISHED: 06-16-2013
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Successful reconstruction of palatomaxillary defects following cancer ablation represents a formidable challenge for surgeons to achieve consistently favorable outcomes. The purpose of this article is to present our experience in oncologic palatomaxillary repair with temporalis muscle flap (TMF) for medically compromised patients who are not ideal candidates for microvascular reconstruction at a Chinese tertiary referral hospital over a 15-year period (1998-2012).
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[Analysis on CHENG Dan-ans exploration of quantification acupuncture and moxibustion stimulation].
Zhen Ci Yan Jiu
PUBLISHED: 05-09-2013
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As a physical therapy, there is a certain relationship between the stimulating quantity and the efficacy of acumoxibustion therapy. However, because of the thinking mode of traditional Chinese medicine in the ancient times, qualitative descriptions about acu-moxibustion stimulation in the classical literature are predominating. Mr. CHENG Dan-an, a famous master and educator of acupuncturology, conducted a series of exploration in both theory and clinical practice. In the present paper, the authors summarize Mr. Chengs viewpoints about the quantification of acupuncture intervention from 1) the number of the selected acupoints in a session of treatment, 2) gauges and materials of the filiform acupuncture needles, 3) stimulating strength of the needling, including the duration of acupuncture needle retaining, depth of needling and intensity of the needling manipulation, 4) frequency of the acupuncture intervention (interval between every two sessions of treatment). Regarding the moxibustion therapy, the stimulating quantity including the duration of the ignited moxa and the number of moxa cones applied at the acupoint area should be varied according to the patients physical constitutions, ages and the state of the illness or clinical conditions. Mr. Cheng also put forward his opinions about the quantification standards of moxibustion intervention.
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Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups.
Diagn Pathol
PUBLISHED: 05-05-2013
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The revised 2008 World Health Organization classification maintains a histological grading system (grades 1-3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosis of Chinese FL subgroups.
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Potential role of CYP2D6 in the central nervous system.
Xenobiotica
PUBLISHED: 04-25-2013
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1. Cytochrome P450 2D6 (CYP2D6) is a pivotal enzyme responsible for a major drug oxidation polymorphism in human populations. Distribution of CYP2D6 in brain and its role in serotonin metabolism suggest that CYP2D6 may have a function in the central nervous system. 2. To establish an efficient and accurate platform for the study of CYP2D6 in vivo, a human CYP2D6 (Tg-2D6) model was generated by transgenesis in wild-type (WT) C57BL/6 mice using a P1 phage artificial chromosome clone containing the complete human CYP2D locus, including the CYP2D6 gene and 5- and 3-flanking sequences. 3. Human CYP2D6 was expressed not only in the liver but also in the brain. The abundance of serotonin and 5-hydroxyindoleacetic acid in brain of Tg-2D6 is higher than in WT mice, either basal levels or after harmaline induction. Metabolomics of brain homogenate and cerebrospinal fluid revealed a significant up-regulation of L-carnitine, acetyl-L-carnitine, pantothenic acid, 2-deoxycytidine diphosphate (dCDP), anandamide, N-acetylglucosaminylamine and a down-regulation of stearoyl-L-carnitine in Tg-2D6 mice compared with WT mice. Anxiety tests indicate Tg-2D6 mice have a higher capability to adapt to anxiety. 4. Overall, these findings indicate that the Tg-2D6 mouse model may serve as a valuable in vivo tool to determine CYP2D6-involved neurophysiological metabolism and function.
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Irreversible electroporation and apoptosis in human liver cancer cells induced by nanosecond electric pulses.
Bioelectromagnetics
PUBLISHED: 04-18-2013
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The goal of this study was to assess the effect of nanosecond electric pulses on HepG2 human liver cancer cells. Electric pulses with a high strength of 10?kV/cm, duration of 500?ns and frequency of 1?Hz were applied to the cells. After delivery of electric pulses, apoptosis, intracellular calcium ion concentrations, transmembrane mitochondrial potentials, electropermeabilization and recovery from electropermeabilization in cells were investigated. The results showed that electric pulse treatment for 20?s and more could trigger apoptosis in cells. Real-time observation indicated an immediate increase in intracellular calcium ion concentration and a dramatic decrease in mitochondrial membrane potential in cells responding to electric pulses. In subsequent experiments, propidium iodide uptake in cells emerged after exposure to electric pulses, indicating electropermeabilization of the cell membrane. Furthermore, recovery from electropermeabilization was not observed even 4?h after the stimulation, demonstrating that irreversible electropermeabilization was induced by electric pulses. In conclusion, electric pulses with a high strength and nanosecond duration can damage cancer cells, accompanied by a series of intracellular changes, providing strong evidence for the application of electric pulses in cancer treatment.
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Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 04-02-2013
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CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17?-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1?, ?-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states.
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Phoxim-induced damages of Bombyx mori larval midgut and titanium dioxide nanoparticles protective role under phoxim-induced toxicity.
Environ. Toxicol.
PUBLISHED: 03-10-2013
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Phoxim (O,O-diethyl O-(alpha-cyanobenzylideneamino) phosphorothioate) is a powerful organophosphorus pesticide with high potential for Bombyx mori larvae of silkworm exposure. However, it is possible that during the phoxim metabolism, there is generation of reactive oxygen species (ROS) and phoxim may produce oxidative stress and neurotoxicity in an intoxicated silkworm. Titanium dioxide nanoparticles (TiO2 NPs) pretreatment has been demonstrated to increase antioxidant capacity and acetylcholinesterase (AChE) activity in organisms. This study was, therefore, undertaken to determine phoxim-induced oxidative stress and neurotoxicity to determine whether phoxim intoxication alters the antioxidant system and AChE activity in the B. mori larval midgut, and to determine whether TiO2 NPs pretreatment attenuates phoxim-induced toxicity. The findings suggested that phoxim exposure decreased survival of B. mori larvae, increased malondialdehyde (MDA), carbonyl and 8-OHdG levels, and ROS accumulation in the midgut. Furthermore, phoxim significantly decreased the activities of AChE, superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione-S-transferase (GST), and levels of ascorbic acid (AsA), reduced glutathione (GSH), and thiol in the midgut. TiO2 pretreatment, however, could increase AChE activity, and remove ROS via activating SOD, CAT, APX, GR, and GST, and accelerating AsA-GSH cycle, thus attenuated lipid, protein, and DNA peroxidation and improve B. mori larval survival under phoxim-induced toxicity. Moreover, this experimental system would help nanomaterials to be applied in the sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
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Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma: correlation with clinicopathological features and patients prognosis.
J. Oral Pathol. Med.
PUBLISHED: 02-28-2013
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BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of Hippo signaling pathway involved in stem cell differentiation and organ development. Recently, its deregulation has been linked to initiation and progression of various cancers. The purpose of this study was to investigate the expression of TAZ in tongue squamous cell carcinoma (TSCC) and its prognostic value in predicting patients outcomes. METHODS: TAZ expression and localization in a panel of TSCC cell lines and human immortalized oral epithelial cell (HIOEC) were determined by real-time RT-PCR, western blotting, and immunofluorescence. In 52 TSCC tumor specimens with detailed clinical and follow-up data, TAZ abundance was examined by immunohistochemistry and its associations with clinicopathological parameters, Ki-67 expression and patients survival were further assessed. RESULTS: TAZ mRNA and protein levels were significantly higher in TSCC cells and specimens than those in non-cancerous cells and normal tongue mucosa. Overexpression of TAZ in TSCC was significantly associated with tumor size (P = 0.033), pathological grade (P = 0.026), clinical stage (P = 0.013), Ki-67 expression (P = 0.0485), and reduced overall and disease-free survival (Kaplan-Meier analysis, log-rank test, P = 0.020, 0.019, respectively). Multivariate Cox regression analysis identified TAZ as an important independent predictor for survival of patients with TSCC [HR (hazard ratio), 4.351; 95% CI (95% confidence interval), 1.477-12.819; P = 0.008]. CONCLUSION: Our data indicate that aberrant TAZ overexpression is associated with key clinicopathological features and poor survival in TSCC. These results suggest that TAZ might play critical roles in tumorigenesis of TSCC and become a novel prognostic biomarker and potential therapeutic target for this malignancy.
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Insulin-like growth factor 1 (IGF-1) enhances the protein expression of CFTR.
PLoS ONE
PUBLISHED: 02-25-2013
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Low levels of insulin-like growth factor 1 (IGF-1) have been observed in the serum of cystic fibrosis (CF) patients. However, the effects of low serum IGF-1 on the cystic fibrosis transmembrane conductance regulator (CFTR), whose defective function is the primary cause of cystic fibrosis, have not been studied. Here, we show in human cells that IGF-1 increases the steady-state levels of mature wildtype CFTR in a CFTR-associated ligand (CAL)- and TC10-dependent manner; moreover, IGF-1 increases CFTR-mediated chloride transport. Using an acceptor photobleaching fluorescence resonance energy transfer (FRET) assay, we have confirmed the binding of CAL and CFTR in the Golgi. We also show that CAL overexpression inhibits forskolin-induced increases in the cell-surface expression of CFTR. We found that IGF-1 activates TC10, and active TC10 alters the functional association between CAL and CFTR. Furthermore, IGF-1 and active TC10 can reverse the CAL-mediated reduction in the cell-surface expression of CFTR. IGF-1 does not increase the expression of ?F508 CFTR, whose processing is arrested in the ER. This finding is consistent with our observation that IGF-1 alters the functional interaction of CAL and CFTR in the Golgi. However, when ?F508 CFTR is rescued with low temperature or the corrector VRT-325 and proceeds to the Golgi, IGF-1 can increase the expression of the rescued ?F508 CFTR. Our data support a model indicating that CAL-CFTR binding in the Golgi inhibits CFTR trafficking to the cell surface, leading CFTR to the degradation pathway instead. IGF-1-activated TC10 changes the interaction of CFTR and CAL, allowing CFTR to progress to the plasma membrane. These findings offer a potential strategy using a combinational treatment of IGF-1 and correctors to increase the post-Golgi expression of CFTR in cystic fibrosis patients bearing the ?F508 mutation.
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Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.
PLoS ONE
PUBLISHED: 02-19-2013
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Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl(3)) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl(3) led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl(3) exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure.
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Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice.
PLoS ONE
PUBLISHED: 02-13-2013
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Recent studies have demonstrated nanosized titanium dioxide (nano-TiO2)-induced fertility reduction and ovary injury in animals. To better understand how nano-TiO2 act in mice, female mice were exposed to 2.5, 5, and 10 mg/kg nano-TiO2 by intragastric administration for 90 consecutive days; the ovary injuries, fertility, hormone levels, and inflammation-related or follicular atresia-related cytokine expression were investigated. The results showed that nano-TiO2 was deposited in the ovary, resulting in significant reduction of body weight, relative weight of ovary and fertility, alterations of hematological and serum parameters and sex hormone levels, atretic follicle increases, inflammation, and necrosis. Furthermore, nano-TiO2 exposure resulted in marked increases of insulin-like growth factor-binding protein 2, epidermal growth factor, tumor necrosis factor-?, tissue plasminogen activator, interleukin-1?, interleukin -6, Fas, and FasL expression, and significant decreases of insulin-like growth factor-1, luteinizing hormone receptor, inhibin ?, and growth differentiation factor 9 expression in mouse ovary. These findings implied that fertility reduction and ovary injury of mice following exposure to nano-TiO2 may be associated with alteration of inflammation-related or follicular atresia-related cytokine expressions, and humans should take great caution when handling nano-TiO2.
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Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles.
J Biomed Mater Res A
PUBLISHED: 02-13-2013
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Titanium dioxide nanoparticles (TiO2 NPs) are widely used in toothpastes, sunscreens, and products for cosmetic purpose that the human use daily. Although the neurotoxicity induced by TiO2 NPs has been demonstrated, very little is known about the molecular mechanisms underlying the brain cognition and behavioral injury. In this study, mice were exposed to 2.5, 5, and 10 mg/kg body weight (BW) TiO2 NPs by nasal administration for 90 consecutive days, respectively, and their brains injuries and brain gene-expressed profile were investigated. Our findings showed that TiO2 NPs could be translocated and accumulated in brain, led to oxidative stress, overproliferation of all glial cells, tissue necrosis as well as hippocampal cell apoptosis. Furthermore, microarray data showed significant alterations in the expression of 249 known function genes, including 113 genes upregulation and 136 genes downregulation following exposure to 10 mg/kg BW TiO2 NPs, which were associated with oxidative stress, immune response, apoptosis, memory and learning, brain development, signal transduction, metabolic process, DNA repair, response to stimulus, and cellular process. Especially, significant increases in Col1a1, serine/threonine-protein kinase 1, Ctnnb1, cysteine-serine-rich nuclear protein-1, Ddit4, Cyp2e1, and Krev interaction trapped protein 1 (Krit1) expressions and great decreases in DA receptor D2, Neu1, Fc receptor-like molecules, and Dhcr7 expressions following long-term exposure to TiO2 NPs resulted in neurogenic disease states in mice. Therefore, these genes may be potential biomarkers of brain toxicity caused by TiO2 NPs exposure, and the application of TiO2 NPs should be carried out cautiously. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 470-478, 2014.
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?(?)-Michael addition of alkyl amines to dimethyl (E)-hex-2-en-4-ynedioate: synthesis of ?,?-dehydroamino acid derivatives.
Molecules
PUBLISHED: 02-07-2013
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The direct nucleophilic addition of alkyl amines to the ?(?)-carbon atom of dimethyl (E)-hex-2-en-4-ynedioate to generate ?,?-dehydroamino acid derivatives is reported. Herein, we have studied the reactivity of various primary and secondary alkyl amines in the ?-selective nucleophilic conjugate addition to conjugated dimethyl (E)-hex-2-en-4-ynedioate. The reaction with primary alkyl amines gives only the (2E,4E)-stereoisomer, while that with secondary alkyl amines gives the (2E,4E) and (2Z,4E)-stereoisomers of dimethyl (2-alkylamino)-muconic ester.
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Cardiac oxidative damage in mice following exposure to nanoparticulate titanium dioxide.
J Biomed Mater Res A
PUBLISHED: 01-30-2013
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Nanoparticulate titanium dioxide (nano-TiO2 ) is a widely used powerful nanoparticulate material with high stability, anticorrosion, and photocatalytic property. However, it is possible that during nano-TiO2 exposure, there may be negative effects on cardiovascular system in intoxicated mice. The present study was therefore undertaken to determine nano-TiO2 -induced oxidative stress and to determine whether nano-TiO2 intoxication alters the antioxidant system in the mouse heart exposed to 2.5, 5, and 10 mg/kg body weight nano-TiO2 for 90 consecutive days. The findings showed that long-term exposure to nano-TiO2 resulted in obvious titanium accumulation in heart, in turn led to sparse cardiac muscle fibers, inflammatory response, cell necrosis, and cardiac biochemical dysfunction. Nano-TiO2 exposure promoted remarkably reactive oxygen species production such as superoxide radicals, hydrogen peroxide, and increased malondialdehyde, carbonyl and 8-OHdG levels as degradation products of lipid, protein, and DNA peroxidation in heart. Furthermore, nano-TiO2 exposure attenuated the activities of antioxidative enzymes, such as superoxide dismutase, ascorbate peroxidase, glutathione reductase, glutathione-S-transferase, and levels of antioxidants including ascorbic acid, glutathione, and thiol in heart. Therefore, TiO2 NPs exposure may impair cardiovascular system in mice, and attention should be aroused on the application of nano-TiO2 and their potential long-term exposure effects especially on human beings.
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Strikingly dissimilar effect of Mn and Zn dopants imposed on local structural distortion of Ba0.5K0.5Fe2As2 superconductor.
J Synchrotron Radiat
PUBLISHED: 01-28-2013
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To clarify the contrasting impurity effects of Mn and Zn dopants on the critical temperature of optimally doped Ba0.5K0.5Fe2As2 superconductors, extended X-ray absorption fine-structure spectroscopy was implemented at the Fe and As K-edge. In Mn-doped compounds a gradual deviation of the symmetric FeAs4 tetrahedron and weakening of the Fe-As bond was observed. Conversely, in Zn-doped compounds the perfect FeAs4 tetrahedron is maintained and the Fe-As bond is rigid. The local structural details are consistent with the development of superconductivity in these two systems, suggesting a significant role played by the topology of the FeAs4 tetrahedron and rigidness of the Fe-As bond in Mn/Zn-doped Ba0.5K0.5Fe2As2 superconductors.
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Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy.
Nat. Med.
PUBLISHED: 01-24-2013
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Co-therapy with rifampicin (RIF) and isoniazid (INH) used to treat tuberculosis in humans frequently causes liver injury. Here, using a pregnane X receptor (PXR)-humanized mouse model, we found that co-treatment with RIF and INH causes accumulation of the endogenous hepatotoxin protoporphyrin IX in the liver through PXR-mediated alteration of the heme biosynthesis pathway. These results provide insight into the mechanism of liver injury induced by co-treatment with these compounds and may lead to their safer use in the clinic.
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Molecular mechanism of titanium dioxide nanoparticles-induced oxidative injury in the brain of mice.
Chemosphere
PUBLISHED: 01-04-2013
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Numerous studies have demonstrated that the brain is one of the target organs in acute or chronic titanium dioxide (TiO2) nanoparticles (NPs) toxicity, and oxidative stress plays an important role in this process. However, whether brain oxidative injury responds to TiO2 NPs by activating the P38-nuclear factor-E2-related factor-2 (Nrf-2) pathway is not fully understood. The present study aimed to examine activation of the P38-Nrf-2 signaling pathway associated with oxidative stress in the mouse brain induced by intranasal administration of TiO2 NPs for 90 consecutive days. Our findings indicate that TiO2 NPs caused overproliferation of spongiocytes and hemorrhage in the mouse brain. Furthermore, TiO2 NPs significantly activated p38, c-Jun N-terminal kinase, nuclear factor kappa B, Nrf-2 and heme oxygenase-1 expression in the brain, which in turn, led to increased production of reactive oxygen species, as well as lipid, protein and DNA peroxidation. These findings suggest that TiO2 NPs-induced oxidative damage in the mouse brain may occur via the p38-Nrf-2 signaling pathway. Therefore, application of TiO2 NPs in the environment should be performed with caution.
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Simultaneous identification and quantification of 20 ?-receptor agonists in feed using gas chromatography-tandem mass spectrometry.
PLoS ONE
PUBLISHED: 01-01-2013
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"Lean meat powder" is a class of toxic chemicals that have structures similar to that of ?-adrenergic receptor agonists. At least 16 chemicals from this class have been specifically banned by the 176(th) bulletin of the Chinese Department of Agriculture on breeding animals, and methods for monitoring the illicit use of ?-agonists in animal feed are required. Herein, a method to quantify 20 ?-agonists in feed, via analyte derivatization followed by gas chromatography-tandem mass spectrometry, has been developed. The optimized method has a good linear correlation (calibration coefficient > 0.99) between the quantitative ion peak area and the concentration of ?-agonists over a large working range (0.05-1 mg/kg). The limit of detection (LOD) was 0.01 mg/kg, the recoveries for three ?-agonists spikes (0.05, 0.1, and 1 µg/g) in feed ranged from 75.6 to 102.4%, repeatability ranged from 1.2 to 9.4% for all of the compounds, and intermediate precisions were lower than 13.8%. This precise, accurate method was applied to quantify 20 ?-agonists in actual feed samples and represents an excellent complement to existing quantification methods.
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PKscan: a program to identify H-type RNA pseudoknots in any RNA sequence with unlimited length.
Bioinformation
PUBLISHED: 01-01-2013
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A computer program written in C++ has been developed which can detect all potential H-type RNA pseudoknots within any given RNA sequence. There is no limit on the length of the input sequence. A validation run of the program using the full-length (8173 nt) genomic mRNA of simian retrovirus type-1 (SRV-1) identifies the established -1 frameshift stimulating pseudokont at the gagpro junction as the most stable pseudoknot within the genomic mRNA.
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Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2 through its association with adaptor proteins CAL and STX6.
PLoS ONE
PUBLISHED: 01-01-2013
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Golgi-localized cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand (CAL) and syntaxin 6 (STX6) regulate the abundance of mature, post-ER CFTR by forming a CAL/STX6/CFTR complex (CAL complex) that promotes CFTR degradation in lysosomes. However, the molecular mechanism underlying this degradation is unknown. Here we investigated the interaction of a Golgi-localized, membrane-associated RING-CH E3 ubiquitin ligase, MARCH2, with the CAL complex and the consequent binding, ubiquitination, and degradation of mature CFTR. We found that MARCH2 not only co-immunoprecipitated and co-localized with CAL and STX6, but its binding to CAL was also enhanced by STX6, suggesting a synergistic interaction. In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose-dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment. A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation. In addition, MARCH2 had no effect on a CFTR mutant lacking the PDZ motif, suggesting that binding to the PDZ domain of CAL is required for MARCH2-mediated degradation of CFTR. Indeed, silencing of endogenous CAL ablated the effect of MARCH2 on CFTR. Consistent with its Golgi localization, MARCH2 had no effect on ER-localized ?F508-CFTR. Finally, siRNA-mediated silencing of endogenous MARCH2 in the CF epithelial cell line CFBE-CFTR increased the abundance of mature CFTR. Taken together, these data suggest that the recruitment of the E3 ubiquitin ligase MARCH2 to the CAL complex and subsequent ubiquitination of CFTR are responsible for the CAL-mediated lysosomal degradation of mature CFTR.
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[Effects of electroacupuncture on expression of calmodulin in the hippocampus of rats with cerebral ischemia-reperfusion injury].
Zhongguo Zhen Jiu
PUBLISHED: 12-06-2011
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To investigate the protective effect of electroacupuncture (EA) on injured neurons and the signal transduction mechanism of calmodulin (CaM) in rats with cerebral ischemia-reperfusion injury (CIRI).
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(meso-5,5,7,12,12,14-Hexamethyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne)nickel(II) bis-[O,O-(1,2-phenyl-ene) dithio-phosphate].
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 11-25-2011
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In the crystal structure of the title compound, [Ni(C(16)H(36)N(4))](C(6)H(4)O(2)PS(2))(2), the Ni(II) cation is located on a center of inversion and is chelated by the folded tetra-amine macrocycle ligand in a slightly distorted NiN(4) square-planar geometry. Two symmetry-related O,O-(1,2-phenyl-ene)dithio-phosphate anions are located on either side of the Ni(II) cation, with Ni?S of 3.9558?(5)?Å, and link to the tetra-amine macrocycle ligand via N-H?S hydrogen bonding.
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High-Tc ferromagnetism in a Co-doped ZnO system dominated by the formation of a zinc-blende type Co-rich ZnCoO phase.
Chem. Commun. (Camb.)
PUBLISHED: 11-07-2011
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The modulation of the distribution of magnetic ions embedded in the host is crucial for the functionality of dilute magnetic semiconductors. Through an element-specific structural characterization, we observe the formation and enhancement of an unrevealed Co-doped ZnO phase and consequently magnetic properties from paramagnetism to ferromagnetism are controlled by surface-modification.
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Real-time vector quantization and clustering based on ordinary differential equations.
IEEE Trans Neural Netw
PUBLISHED: 10-31-2011
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This brief presents a dynamical system approach to vector quantization or clustering based on ordinary differential equations with the potential for real-time implementation. Two examples of different pattern clusters demonstrate that the model can successfully quantize different types of input patterns. Furthermore, we analyze and study the stability of our dynamical system. By discovering the equilibrium points for certain input patterns and analyzing their stability, we have shown the quantizing behavior of the system with respect to its vigilance parameter. The proposed system is applied to two real-world problems, providing comparable results to the best reported findings. This validates the effectiveness of our proposed approach.
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