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Find video protocols related to scientific articles indexed in Pubmed.
Further observations on serotype 2 Marek's disease virus-induced enhancement of spontaneous avian leukosis virus-like bursal lymphomas in ALVA6 transgenic chickens.
Avian Pathol.
PUBLISHED: 11-20-2014
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Breeders of 2009 generation of Avian Disease and Oncology Laboratory (ADOL) transgenic chicken line ALVA6, known to be resistant to infection with subgroups A and E avian leukosis virus (ALV), were vaccinated at hatch with a trivalent Marek's disease (MD) vaccine containing serotypes 1, 2, and 3 MD viruses (MDV) and were maintained under pathogen-free conditions from the day of hatch until 75 weeks of age. Spontaneous ALV-like bursal lymphomas also termed lymphoid leukosis (LL)-like lymphomas were detected in 7% of the ALVA6 breeders. There was no evidence of infection with exogenous and endogenous ALV as determined by virus isolation tests of plasma and tumor tissue homogenates. For the next three generations, serotype 2 MDV was eliminated from the trivalent MD vaccine used. Results show, for the first time, that removal of serotype 2 MDV from MD vaccines eliminated spontaneous LL-like lymphomas within 50-72 weeks of age for at least three consecutive generations. Two experiments were also conducted to determine the influence of in ovo vaccination with serotype 2 MD vaccines on enhancement of spontaneous LL-like lymphomas in ALVA6 chickens. Chickens from 2012 generation were each inoculated in ovo, or at hatch with 5000 plaque forming units of serotype 2 MDV. Results indicate that by 50 weeks of age, the incidence of spontaneous LL-like lymphomas in chicken inoculated in ovo with serotype 2 MDV was comparable to that in chickens inoculated with virus at hatch, suggesting that the augmentation effect of serotype 2 MDV is independent of age of vaccination.
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Glutathione S-transferase M1 and glutathione S-transferase T1 genotype in chronic pancreatitis: A meta-analysis.
J. Int. Med. Res.
PUBLISHED: 11-08-2014
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A meta-analysis to determine the association between chronic pancreatitis and glutathione-S transferase (GST) mu 1 (GSTM1) and theta 1 (GSTT1) deletions.
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The solution chemistry and reactivity of lacunary Keggin silicotungstates monitored in real-time by a combination of mass spectrometry and electrochemistry.
Dalton Trans
PUBLISHED: 11-08-2014
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The solution chemistry of a series of mono-, di- and trilacunary Keggin silicotungstates was investigated by electrospray ionization mass spectrometry (ESI-MS) and general electrospray features especially for lacunary POMs are summarized. The reactions of vanadium incorporation into the lacunary structures were successfully monitored in real-time by a combination of ESI-MS and differential pulse voltammetry (DPV). It was found that all the reactions took place instantaneously and that a subtle speciation change occurred at prolonged reaction times for the pair of reactants, monovacant silicotungstate and sodium metavanadate, suggesting a conversion of mono- to divanadium substituted derivatives. This was shown to result from a solution process, not an ESI-induced reaction, by DPV measurements. The relative stabilities of the V-substituted products were assessed in both solution and gas phases.
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A de novo transcriptomic analysis to reveal functional genes in Apolygus lucorum.
Insect Sci.
PUBLISHED: 10-27-2014
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The widespread planting of genetically engineered cotton producing the Cry1Ac toxin has led to significantly reduced pesticide applications since 1997. However, consequently, the number of green mirid bug (GMB), Apolygus lucorum (Meyer-Dür) has increased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera (Hübner), has become the major pest in transgenic Bt cotton field and influenced cotton yield. Disproportionately, only a few studies on GMB at a molecular level have been reported. Libraries from both third instar nymph and adult were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 unigenes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes (42.01%) matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes (DEGs) strategy between the two developmental stages: nymph and adult. The results demonstrated that thousands of genes were significantly differentially expressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding. This article is protected by copyright. All rights reserved.
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Leucogen Tablets at 60 mg Three Times per Day are Safe and Effective to Control Febrile Neutropenia.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
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To investigate whether it is safe to use leucogen tablets 60 mg three times per day (180 mg for a day) and whether this regimen could reduce the incidence of febrile neutropenia caused by chemotherapy.
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[The effects of lifestyle factors on the incidence of central obesity in Chinese adults aged 35-74 years].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 10-15-2014
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To understand the incidence of central obesity and its characteristics, and explore the effects of lifestyle factors on incidence of central obesity in Chinese adults aged 35-74 years.
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Th2 cytokine-primed airway smooth muscle cells induce mast cell chemotaxis via secretion of ATP.
J Asthma
PUBLISHED: 10-09-2014
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Abstract Objective: Mast cell infiltration into airway smooth muscle (ASM) bundle is an important feature of asthma. Extracellular adenosine triphosphate (eATP) contributes to the initiation of airway inflammation. eATP induces mast cells migration by acting through purinergic receptors. CD39 is an ectonucleotidase that degrades ATP to ADP and AMP. Whether eATP participates in the migration of mast cell towards ASM cells is still unknown.
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Proton energy optimization and reduction for intensity-modulated proton therapy.
Phys Med Biol
PUBLISHED: 10-08-2014
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Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To 'scan' the target volume, the proton beam is controlled by varying its energy to penetrate the patient's body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20?m?s(-1), changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.
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Ti7-containing, tetrahedral 36-tungsto-4-arsenate(iii) [Ti6(TiO6)(AsW9O33)4](20-).
Dalton Trans
PUBLISHED: 09-26-2014
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We have prepared the Ti7-containing, tetrahedral 36-tungsto-4-arsenate(iii) [Ti6(TiO6)(AsW9O33)4](20-) () by a simple, one pot procedure. Polyanion contains a novel Ti7-core, comprising a central TiO6 octahedron surrounded by six TiO5 square-pyramids, and capped by four {As(III)W9} trilacunary fragments. The title polyanion is solution-stable, as shown by (183)W NMR and mass spectrometry, and exhibits interesting biological properties.
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miR-134 Regulates Ischemia/Reperfusion Injury-Induced Neuronal Cell Death by Regulating CREB Signaling.
J. Mol. Neurosci.
PUBLISHED: 09-23-2014
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microRNA-134 (miR-134) has been reported to be a brain-specific miRNA and is differently expressed in brain tissues subjected to ischemic injury. However, the underlying mechanism of miR-134 in regulating cerebral ischemic injury remains poorly understood. The current study was designed to delineate the molecular basis of miR-134 in regulating cerebral ischemic injury. Using the oxygen-glucose deprivation (OGD) model of hippocampal neuron ischemia in vitro, we found that the overexpression of miR-134 mediated by recombinant adeno-associated virus (AAV) vector infection significantly promoted neuron death induced by OGD/reoxygenation, whereas the inhibition of miR-134 provided protective effects against OGD/reoxygenation-induced cell death. Moreover, cyclic AMP (cAMP) response element-binding protein (CREB) as a putative target of miR-134 was downregulated and upregulated by miR-134 overexpression or inhibition, respectively. The direct interaction between miR-134 and the 3'-untranslated region (UTR) of CREB mRNA was further confirmed by dual-luciferase reporter assay. Overexpression of miR-134 also inhibited the expression of the downstream gene of CREB, including brain-derived neurotrophic factor (BDNF) and the anti-apoptotic gene Bcl-2, whereas the inhibition of miR-134 upregulated the expression of BDNF and Bcl-2 in neurons after OGD/reoxygenation. Notably, the knockdown of CREB by CREB siRNA apparently abrogated the protective effect of anti-miR-134 on OGD/reoxygenation-induced cell death. Taken together, our study suggests that downregulation of miR-134 alleviates ischemic injury through enhancing CREB expression and downstream genes, providing a promising and potential therapeutic target for cerebral ischemic injury.
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Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.
Hum. Mol. Genet.
PUBLISHED: 09-23-2014
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Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
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MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression.
Tumour Biol.
PUBLISHED: 09-14-2014
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MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-492 plays an important role in cell tumorigenesis in multiple kinds of human cancer cells. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated miR-492's role in cell proliferation of breast cancer. MiR-492 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Overexpression of miR-492 promoted the proliferation and anchorage-independent growth of breast cancer cells. Bioinformatics analysis further revealed sex-determining region Y-box 7 (SOX7), a putative tumor suppressor, as a potential target of miR-492. Data from luciferase reporter assays showed that miR-492 directly binds to the 3'-untranslated region (3'-UTR) of SOX7 messenger RNA (mRNA) and repressed expression at both transcriptional and translational levels. Ectopic expression of miR-492 led to downregulation of SOX7 protein, which resulted in the upregulation of cyclin D1 and c-Myc. In functional assays, SOX7 silenced in miR-492-in-transfected ZR-75-30 cells has positive effect to promote cell proliferation, suggesting that direct SOX7 downregulation is required for miR-492-induced cell proliferation and cell cycle of breast cancer. In sum, these results suggest that miR-492 represents a potential onco-miR and participates in breast cancer carcinogenesis by suppressing SOX7 expression.
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COP9 signalosome subunit 6 binds and inhibits avian leukosis virus integrase.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-12-2014
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The retroviral integrase plays an essential role in the integration of reverse-transcribed retroviral cDNA into the host cell genome, and serves as an important target for anti-viral therapeutics. In this study, we identified the COP9 signalosome subunit 6 (CSN6) as a novel avian leukosis virus (ALV) integrase binding protein. Co-immunoprecipitation and GST pull-down assays showed that CSN6 bound to ALV integrase likely through direct interaction of CSN6 to the catalytic core of the integrase. We further demonstrated CSN6 inhibited integrase activity in vitro; knockdown of CSN6 in DF-1 promoted ALV production. These results indicated that CSN6 may be a negative regulator of ALV replication by binding to and inhibiting integrase. Our findings provided the insight into the integrase-based host defense system and may have implications in the development of integrase-based anti-viral strategies.
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Physical Activity Level and Incident Type 2 Diabetes among Chinese Adults.
Med Sci Sports Exerc
PUBLISHED: 08-10-2014
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To examine the association between physical activity level (PAL) and incident type 2 diabetes among middle-aged and older Chinese men and women in urban China.
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Overexpression of activated leukocute cell adhesion molecule in gastric cancer is associated with advanced stages and poor prognosis and miR-9 deregulation.
Mol Med Rep
PUBLISHED: 08-05-2014
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Activated leukocyte cell adhesion molecule (ALCAM) has been identified as a novel potential molecular marker of human tumors. The present study aimed to assess ALCAM as a prognostic marker for gastric cancer (GC), and to explore the mRNA deregulation underlying the abnormal expression of ALCAM. The mRNA and protein expression of ALCAM in GC and adjacent non?tumor tissues from 66 patients with GC were analyzed. The association between miR?9 and ALCAM mRNA expression was determined by quantitative polymerase chain reaction. Serum soluble ALCAM (sALCAM) was analyzed by ELISA in 72 patients with GC, 82 patients with gastric precancerous lesions and 73 controls. ALCAM and sALCAM levels were associated with certain clinicopathological variables, including overall survival. Compared with the non?tumor tissues, the expression of ALCAM mRNA in the GC tissues was significantly upregulated (P=0.013). The expression of miR?9 was reduced and inversely correlated with ALCAM mRNA levels in GC tissues and cell lines. The ALCAM mRNA level was reduced following ectopic overexpression of miR?9 in SGC?7901 human gastric cancer cells. The rates of membranous and cytoplasmic expression of ALCAM in GC tissues were 59.1 and 48.48%, respectively, and the serum sALCAM levels were significantly elevated in patients with GC. Elevated ALCAM mRNA, membranous ALCAM expression in GC tissues and high sALCAM levels are associated with advanced tumor stage, lymphatic invasion and shorter overall survival duration. The results of the current study indicated that membranous ALCAM expression and high serum sALCAM levels are independent prognostic markers of poor survival for patients with GC, and that the overexpression of ALCAM may be due to the downregulation of miR?9.
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A predictive model for evaluating responsiveness to pemetrexed treatment in patients with advanced colorectal cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-02-2014
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To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen.
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Clinical study on safety of cantharidin sodium and shenmai injection combined with chemotherapy in treating patients with breast cancer postoperatively.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-02-2014
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To assess side effects on Cantharidin sodium and Shenmai injection combined with chemotherapy in treating patients with breast cancer postoperatively.
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Noninvasive ventilation with complex critical care ventilator in the treatment of acute exacerbation of chronic obstructive pulmonary disease.
J. Int. Med. Res.
PUBLISHED: 07-31-2014
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To compare the clinical effect of noninvasive positive-pressure ventilation (NIPPV), delivered via critical care ventilator or miniventilator, in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
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Functional Analysis of SNPs in the Regulation of CARM1 Expression and Plasma Homocysteine Levels.
Circ Cardiovasc Genet
PUBLISHED: 07-28-2014
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-Hyperhomocysteinemia is a risk factor for cardiovascular disease. Coactivator- associated arginine methyltransferase 1 (CARM1) participates in the synthesis of homocysteine, but whether the genetic variations regulate CARM1 expression and homocysteine levels remains unknown.
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Differential expression and regulation of Ido2 in the mouse uterus during peri-implantation period.
In Vitro Cell. Dev. Biol. Anim.
PUBLISHED: 07-22-2014
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Ido2 is involved in tryptophan catabolism and immunity, but its physiological functions remain poorly understood. This study was undertaken to examine the expression and regulation of Ido2 gene in mouse uterus during the peri-implantation period. The results showed that Ido2 mRNA was highly expressed on day 4 of pregnancy and in the delayed implantation uterus. On days 5-8 of pregnancy, a low level of Ido2 expression was observed in the uteri. Simultaneously, Ido2 mRNA was also lowly expressed in the decidualized uterus. In the uterine stromal cells, 8-Br-cAMP could inhibit the expression of Ido2 mRNA. Moreover, Ido2 mRNA expression was gradually decreased after the stromal cells were treated with estrogen and progesterone and reached a nadir at 96 h. Further study found that overexpression of Ido2 could downregulate the expression of decidualization marker genes PRL, IGFBP1, and Dtprp under in vitro decidualization, while inhibition of Ido2 with devo-1-methyl-tryptophan (D-1-MT) could upregulate the expression of these marker genes. Under in vitro decidualization, overexpression of Ido2 could suppress the proliferation of uterine stromal cells and elevate the expression of Bax and MMP2 genes. On the contrary, Ido2 inhibitor D-1-MT could enhance the proliferation of stromal cells and expression of Bcl2 gene but decline the Bax/Bcl2 ratio. In the uterine stromal cells, estrogen and progesterone could induce the expression of Ido2 mRNA. These data indicate that Ido2 may be important for mouse embryo implantation and decidualization.
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[Incidence of obesity and its modifiable risk factors in Chinese adults aged 35-74 years: a prospective cohort study].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 07-11-2014
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To examine the incidence of obesity and its modifiable risk factors in Chinese adults aged 35-74 years.
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Alkaline Earth Guests in Polyoxopalladate Chemistry: From Nanocube to Nanostar via an Open-Shell Structure.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-10-2014
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The three novel, discrete palladium(II)-oxo clusters [CaPd12 O8 (PhAsO3 )8 ](6-) (CaPd12 ), [SrPd12 O6 (OH)3 (PhAsO3 )6 (OAc)3 ](4-) (SrPd12 ), and [BaPd15 O10 (PhAsO3 )10 ](8-) (BaPd15 ) encapsulating alkaline earth metal ions were prepared and fully characterized by a multitude of solution and solid-state physicochemical techniques. We have discovered a structure-directing template effect induced by the respective size of the alkaline earth guest ion, which determines the detailed condensation arrangement of the peripheral Pd(II) -oxo shell. The unprecedented SrPd12 with an open-shell type structure is of particular importance and reflects a successful strategy for deliberate design of new structural classes of polyoxo-noble-metalates. Furthermore, the unusual acetate-water ligand exchange phenomenon renders SrPd12 as a promising candidate for noble-metal-based catalysis.
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The targeting mechanism of DHA ligand and its conjugate with Gemcitabine for the enhanced tumor therapy.
Oncotarget
PUBLISHED: 07-09-2014
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Docosahexaenoic acid (DHA), an omega-3 C22 natural fatty acid serving as a precursor for metabolic and biochemical pathways, was reported as a targeting ligand of anticancer drugs. However, its tumor targeting ability and mechanism has not been claimed. Here we hypothesized that the uptake of DHA by tumor cells is related to the phosphatidylethanolamine (PE) contents in cell membranes. Thus, in this manuscript, the tumor-targeting ability of DHA was initially demonstrated in vitro and in vivo on different tumor cell lines by labeling DHA with fluorescence dyes. Subsequently, the tumor targeting ability was then correlated with the contents of PE in cell membranes to study the uptake mechanism. Further, DHA was conjugated with anticancer drug gemcitabine (DHA-GEM) for targeted tumor therapy. Our results demonstrated that DHA exhibited high tumor targeting ability and PE is the main mediator, which confirmed our hypothesis. The DHA-GEM displayed enhanced therapeutic efficacy than that of GEM itself, indicating that DHA is a promising ligand for tumor targeted therapy.
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Simulation of the recharging method of implantable biosensors based on a wearable incoherent light source.
Sensors (Basel)
PUBLISHED: 07-04-2014
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Recharging implantable electronics from the outside of the human body is very important for applications such as implantable biosensors and other implantable electronics. In this paper, a recharging method for implantable biosensors based on a wearable incoherent light source has been proposed and simulated. Firstly, we develop a model of the incoherent light source and a multi-layer model of skin tissue. Secondly, the recharging processes of the proposed method have been simulated and tested experimentally, whereby some important conclusions have been reached. Our results indicate that the proposed method will offer a convenient, safe and low-cost recharging method for implantable biosensors, which should promote the application of implantable electronics.
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DCE-MRI assessment of the effect of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme on tumor vasculature in patients with nasopharyngeal carcinomas.
BMC Cancer
PUBLISHED: 07-02-2014
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EBV-encoded latent membrane protein 1 (EBV-LMP1) is an important oncogenic protein for nasopharyngeal carcinoma (NPC) and has been shown to engage a plethora of signaling pathways. Correspondingly, an LMP1-targeted DNAzyme was found to inhibit the growth of NPC cells both in vivo and in vitro by suppressing cell proliferation and inducing apoptosis. However, it remains unknown whether an LMP1-targeted DNAzyme would affect the vasculature of NPC. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been applied in the clinical trials of anti-angiogenic drugs for more than ten years, and Ktrans has been recommended as a primary endpoint. Therefore, the objective of the current study was to use DCE-MRI to longitudinally study the effect of an EBV-LMP1-targeted DNAzyme on the vasculature of patients with NPC.
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Cotransplantation of human umbilical cord mesenchymal and haplo-hematopoietic stem cells in patients with severe aplastic anemia.
Cytotechnology
PUBLISHED: 06-22-2014
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To evaluate the efficacy and safety of cotransplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) and haploidentical hematopoietic stem cells (HSCs) and to determine the correlation factors affecting incidence of graft versus host disease (GVHD) in patients with severe aplastic anemia (SAA), twenty-four SAA patients received haploidentical HSCs and UC-MSCs co-transplantation. Grafts came from a combination of granulocyte colony stimulating factor (G-CSF)-primed bone marrow and G-CSF mobilized peripheral blood stem cell of haploidentical donors, and in vitro expanded third-party donor derived UC-MSCs were employed as the cell graft. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide and fludarabine with or without busulfan. GVHD was prevented by using cyclosporine A (CSA), ATG, anti-CD25 monoclonal antibody and mycophenolate mofetil. All 24 patients achieved hematopoietic reconstitution. Median time to absolute neutrophil count >2 × 10(9)/L and platelet count >20 × 10(9)/L were 11 and 13 days, respectively. An incidence of 25 % on grade I-II acute GVHD was found while an incidence of 25 % of grade III-IV acute GVHD was seen. Blood type (r = 0.152, P = 0.043) and patient/donor pair (r = 0.541, P = 0.022) were significantly correlated with incidence of cGVHD. Transplantation related mortality was observed in 20.8 % of the cases. Co-transplantation of haploidentical HSCs and hUC-MSCs on SAA was an effective and safe approach in reducing GVHD and transplantation related mortality. The adequate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.
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Targeting lysosomal membrane permeabilization to induce and image apoptosis in cancer cells by multifunctional Au-ZnO hybrid nanoparticles.
Chem. Commun. (Camb.)
PUBLISHED: 06-14-2014
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We have developed multifunctional Au-ZnO hybrid nanoparticles (NPs) for targeted induction lysosomal membrane permeabilization (LMP)-dependent apoptosis in cancer cells and real-time imaging.
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As a novel p53 direct target, bidirectional gene HspB2/?B-crystallin regulates the ROS level and Warburg effect.
Biochim. Biophys. Acta
PUBLISHED: 05-13-2014
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Many mammalian genes are composed of bidirectional gene pairs with the two genes separated by less than 1.0kb. The transcriptional regulation and function of these bidirectional genes remain largely unclear. Here, we report that bidirectional gene pair HspB2/?B-crystallin, both of which are members of the small heat shock protein gene family, is a novel direct target gene of p53. Two potential binding sites of p53 are present in the intergenic region of HspB2/?B-crystallin. p53 up-regulated the bidirectional promoter activities of HspB2/?B-crystallin. Actinomycin D (ActD), an activator of p53, induces the promoter and protein activities of HspB2/?B-crystallin. p53 binds to two p53 binding sites in the intergenic region of HspB2/?B-crystallin in vitro and in vivo. Moreover, the products of bidirectional gene pair HspB2/?B-crystallin regulate glucose metabolism, intracellular reactive oxygen species (ROS) level and the Warburg effect by affecting metabolic genes, including the synthesis of cytochrome c oxidase 2 (SCO2), hexokinase II (HK2), and TP53-induced glycolysis and apoptosis regulator (TIGAR). The ROS level and the Warburg effect are affected after the depletion of p53, HspB2 and ?B-crystallin respectively. Finally, we show that both HspB2 and ?B-crystallin are linked with human renal carcinogenesis. These findings provide novel insights into the role of p53 as a regulator of bidirectional gene pair HspB2/?B-crystallin-mediated ROS and the Warburg effect.
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PKM2: the thread linking energy metabolism reprogramming with epigenetics in cancer.
Int J Mol Sci
PUBLISHED: 04-23-2014
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Cancer metabolism reprogramming or alterations in epigenetics are linked to an incidence of cancer. It is apparent that epigenetic changes have been found in tumors, therefore, the complete epigenome and entire pathways relevant to cell metabolism are subject to epigenetic dysregulation. Here, we review the pyruvate kinase M2 (PKM2) isoform, a glycolytic enzyme involved in ATP generation and pyruvate production, which plays an essential role in tumor metabolism and growth, and also functions as a protein kinase that phosphorylates histones during genes transcription and chromatin remodeling. We also discuss the potential role of PKM2 in the dynamic integration between metabolic reprogramming and alterations in epigenetics during carcinogenesis and cancer progression.
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Immunoglobulin G binding protein (IGBP) from Rhipicephalus haemaphysaloides: identification, expression, and binding specificity.
Parasitol. Res.
PUBLISHED: 04-14-2014
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As the second most important human ectoparasite, ranked only after mosquitoes, the tick threatens the development of husbandry and even the health of humans worldwide. Immunoglobulin G binding proteins (IGBPs) are considered to be the major factors used by ticks to evade the host immune system and the damage caused by host antibodies. In this study, an IGBP-MB homologue was identified in the tick Rhipicephalus haemaphysaloides, which was predominantly detected in the salivary glands and hemolymph of male ticks. Recombinant IGBP (rIGBP/His) displayed significant binding activity to IgGs from rabbits and pigs, and bound to the F(ab)'2 but not the Fc fragment of rabbit IgG. Although the silencing of IGBP expression in ticks had no obvious effect on their blood-feeding and subsequent oviposition, antibodies raised to rIGBP/GST reduced the replete body weight (218.9?±?20 mg in the control group vs. 142.5?±?43.3 mg in the test group, P?
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Plasma membrane Ca2+-ATPase regulates Ca2+ signaling and the proliferation of airway smooth muscle cells.
Eur. J. Pharmacol.
PUBLISHED: 03-25-2014
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Plasma membrane Ca2+-ATPase (PMCA) plays an important role in regulating intracellular Ca2+ homeostasis by extruding excessive Ca2+ to extracellular spaces. PMCA has four isoforms and is widely expressed in different tissues and cells including airway smooth muscle cells (ASMCs). In the present study, we investigated the role of PMCA in the maintenance of Ca2+ homeostasis and regulation of ASMCs proliferation. By using Ca2+ fluorescence, we found that inhibition of PMCA with LaCl3 or carboxyeosin (CE) decreased the decay rate of Ca2+ transient induced by bradykinin (BK). No obvious decay was observed when SERCA was inhibited by thapsigargin (TpG). LaCl3 and CE also induced a spontaneous [Ca2+]i increase in the presence of TpG even in Ca2+-free bath solution. Both LaCl3 and CE inhibited UTP-induced Ca2+ oscillations in ASMCs. PCR assay found that PMCA1 and PMCA4 mRNA were expressed in rat ASMCs. The expression of PMCA4 was downregulated in proliferating ASMCs when compared to resting cells. Both the isoform-nonselective PMCA inhibitor caloxin 2a1 and PMCA4-selective inhibitor caloxin 1b1 decreased the decay rate of Ca2+ transient induced by TpG or BK. PMCA inhibitors except caloxin 2a1 promoted ASMCs proliferation. Annexin-V apoptosis assay detected that caloxin 2a1 increased ASMCs apoptosis, suggesting that inhibition of PMCA with different blockers results in different [Ca2+]i and thus different cellular response. Our results provide evidences to support the hypothesis that PMCA is involved in the regulation of Ca2+ homeostasis and ASMCs proliferation. These data suggest that PMCA may be a new target in the treatment of chronic asthma.
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Approach to the study of flavone di-C-glycosides by high performance liquid chromatography-tandem ion trap mass spectrometry and its application to characterization of flavonoid composition in Viola yedoensis.
J Mass Spectrom
PUBLISHED: 03-20-2014
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The mass spectrometric (MS) analysis of flavone di-C-glycosides has been a difficult task due to pure standards being unavailable commercially and to that the reported relative intensities of some diagnostic ions varied with MS instruments. In this study, five flavone di-C-glycoside standards from Viola yedoensis have been systematically studied by high performance liquid chromatography-electrospray ionization-tandem ion trap mass spectrometry (HPLC-ESI-IT-MS(n) ) in the negative ion mode to analyze their fragmentation patterns. A new MS(2) and MS(3) hierarchical fragmentation for the identification of the sugar nature (hexoses or pentoses) at C-6 and C-8 is presented based on previously established rules of fragmentation. Here, for the first time, we report that the MS(2) and MS(3) structure-diagnostic fragments about the glycosylation types and positions are highly dependent on the configuration of the sugars at C-6 and C-8. The base peak ((0,2) X1 (0,2) X2 (-) ion) in MS(3) spectra of di-C-glycosides could be used as a diagnostic ion for flavone aglycones. These newly proposed fragmentation behaviors have been successfully applied to the characterization of flavone di-C-glycosides found in V. yedoensis. A total of 35 flavonoid glycosides, including 1 flavone mono-C-hexoside, 2 flavone 6,8-di-C-hexosides, 11 flavone 6,8-di-C-pentosides, 13 flavone 6,8-C-hexosyl-C-pentosides, 5 acetylated flavone C-glycosides and 3 flavonol O-glycosides, were identified or tentatively identified on the base of their UV profiles, MS and MS(n) (n?=?5) data, or by comparing with reference substances. Among these, the acetylated flavone C-glycosides were reported from V. yedoensis for the first time. Copyright © 2014 John Wiley & Sons, Ltd.
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In vitro molecular evolution yields an NEIBM with a potential novel IgG binding property.
Sci Rep
PUBLISHED: 02-28-2014
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Staphylococcus aureus protein A (SpA) and protein G of groups C and G streptococci (SpG) are two well-defined bacterial immunoglobulin (Ig)-binding proteins (IBPs) with high affinity for specific sites on IgG from mammalian hosts. Both SpA and SpG contain several highly-homologous IgG-binding domains, each of which possesses similar binding characteristic of the whole corresponding proteins. Whether specific combinations of these domains could generate a molecule with novel IgG-binding properties remained unknown. We constructed a combinatorial phage library displaying randomly-rearranged A, B, C, D and E domains of SpA as well as the B2 (G2) and B3 (G3) domains of SpG. In vitro molecular evolution directed by human, rabbit, bovine, or goat polyclonal IgGs and four subclasses of mouse monoclonal IgGs generated one common combination, D-C-G3. A series of assays demonstrated that D-C-G3 exhibited a potential novel IgG binding property that was obviously different from those of both parent proteins. This study provides an example of successful protein engineering through in vitro molecular evolution and useful approaches for structure and function studies of IBPs.
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Evaluation and mitigation of the interplay effects of intensity modulated proton therapy for lung cancer in a clinical setting.
Pract Radiat Oncol
PUBLISHED: 02-19-2014
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The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects.
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Regulation of Mcl-1 by constitutive activation of NF-?B contributes to cell viability in human esophageal squamous cell carcinoma cells.
BMC Cancer
PUBLISHED: 02-11-2014
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Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments.
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On the interplay effects with proton scanning beams in stage III lung cancer.
Med Phys
PUBLISHED: 02-11-2014
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To assess the dosimetric impact of interplay between spot-scanning proton beam and respiratory motion in intensity-modulated proton therapy (IMPT) for stage III lung cancer.
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Glycolytic genes in cancer cells are more than glucose metabolic regulators.
J. Mol. Med.
PUBLISHED: 01-24-2014
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Nearly a hundred years of scientific research has revealed a notable preference of cancer cells to utilize aerobic glycolysis rather than mitochondrial oxidative phosphorylation for glucose-dependent ATP production, which is thought to be the root of tumor formation and growth. Glycolysis is a complex biochemical process that is mediated by multiple glycolytic genes. Besides regulating glucose metabolism, these genes are also suggested to possess various other functions related to cancer, including roles in cancer development and promotion, inhibition of apoptosis, cell cycle progression, and tumor metastasis. This article highlights the biological functions of glycolytic genes beyond their role in regulation of glycolysis and discusses their clinical implications, especially in regard to the use of glycolytic genes as biomarkers for early detection of cancer or as targets for novel anticancer treatments.
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Real-time fluorescence loop-mediated isothermal amplification for the diagnosis of hemorrhagic enteritis virus.
Virus Res.
PUBLISHED: 01-21-2014
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Suspected cases of hemorrhagic enteritis associated with hemorrhagic enteritis virus (HEV) are becoming more frequent among yellow chickens in the Guangdong Province of China. In this study, we have developed a one-step, ecumenical, real-time fluorescence loop-mediated isothermal amplification (RealAmp) assay for the rapid diagnosis of HEV. The RealAmp assay was performed at 63°C and reduced the assay time to 15min, using a simple and portable device, the ESE-Quant Tube Scanner. The detection limit of DNA was 1fg/?l, and the detection was specific only to HEV. We also used nested PCR to evaluate the application of the RealAmp assay. The coincidence rate of the two methods was 100%. Our data indicated that the RealAmp assay provides a sensitive, specific, and user-friendly diagnostic tool for the identification and quantification of HEV for field diagnosis and in laboratory research.
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Risk factors and surgical outcomes for spontaneous rupture of BCLC stages A and B hepatocellular carcinoma: a case-control study.
World J. Gastroenterol.
PUBLISHED: 01-05-2014
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To investigate the risk factors and surgical outcomes for spontaneous rupture of Barcelona Clinic Liver Cancer (BCLC) stages A and B hepatocellular carcinoma (HCC).
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Aptamer-based homogeneous protein detection using cucurbit[7]uril functionalized electrode.
Anal. Chim. Acta
PUBLISHED: 01-05-2014
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A new strategy for homogeneous protein detection is developed based on a cucurbit[7]uril (CB[7]) functionalized electrode. The analytical procedure consists of the binding of target protein to its aptamer in the test solution, followed by an exonuclease-catalyzed digestion of methylene blue (MB) tag labeled DNA oligonucleotides. Since CB[7] molecules immobilized on the electrode may efficiently capture the released MB-labeled nucleotides, the MB tags are concentrated to the electrode surface and subsequently yield highly sensitive electrochemical signal, which is related to the concentration of the target protein. The method combines the host-guest properties of CB[7] with the immobilization-free homogeneous assay, providing a powerful tool for protein detection. Taking the detection of osteopontin as an example, the proposed method can have a linear response to the target protein in a range from 50 to 500 ng mL(-1) with a detection limit of 10.7 ng mL(-1). It can also show high specificity and good reproducibility, and can be used directly for the assay of osteopontin in serum samples.
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A novel role of exogenous carbon monoxide on protecting cardiac function and improving survival against sepsis via mitochondrial energetic metabolism pathway.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Septic cardiac dysfunction is the main cause of death in septic patients. Here we investigate whether exogenous carbon monoxide can protect cardiac function and improve survival against sepsis by interfering with mitochondrial energetic metabolism. Male C57BL/6 mice were subjected to cecal ligation and puncture to induce sepsis. Exogenous carbon monoxide delivered from Tricarbonyldichlororuthenium (II) dimer (carbon monoxide releasing molecule II, 8 mg/kg) was used intravenously as intervention. We found that carbon monoxide significantly improved cardiac function (LVEF 80.26 ± 2.37% vs. 71.21 ± 1.37%, P < 0.001; LVFS 43.52 ± 1.92% vs. 34.93 ± 1.28%, P < 0.001) and increased survival rate of septic mice (63% vs. 25%, P < 0.01). This phenomenon might be owing to the beneficial effect of carbon monoxide on abolishing the elevation of cardiac enzyme activity, cytokines levels and apoptosis rate, then attenuating cardiac injury in septic mice. Meanwhile, carbon monoxide significantly reversed the loss of mitochondrial number, effectively inhibited cardiac mitochondrial damage in septic mice by modulating glucose uptake, adenosine triphosphate and lactate content. Furthermore upregulation of peroxisome proliferator-activated receptor-? coactivator-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A genes in cardiac tissue were revealed in septic mice treated with carbon monoxide. Taken together, the results indicate that exogenous carbon monoxide effectively modulated mitochondrial energetic metabolisms by interfering with expression of peroxisome proliferator-activated receptor-? coactivator-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A genes, consequently exerted an important improvement in sepsis-induced cardiac dysfunction.
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The MYC, TERT, and ZIC1 genes Are Common Targets of Viral Integration and Transcriptional Deregulation in Avian Leukosis Virus Subgroup J-Induced Myeloid Leukosis.
J. Virol.
PUBLISHED: 12-26-2013
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The integration of retroviruses into the host genome following nonrandom genome-wide patterns may lead to the deregulation of gene expression and oncogene activation near the integration sites. Slow-transforming retroviruses have been widely used to perform genetic screens for the identification of genes involved in cancer. To investigate the involvement of avian leukosis virus subgroup J (ALV-J) integration in myeloid leukosis (ML) in chickens, we utilized an ALV-J insertional identification platform based on hybrid-capture target enrichment and next-generation sequencing (NGS). Using high-definition mapping of the viral integration sites in the chicken genome, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. On the basis of previous statistical definitions, MYC, TERT, and ZIC1 genes were identified as common insertion sites (CIS) of provirus integration in tumor cells; these three genes have previously been shown to be involved in the malignant transformation of different human cell types. Compared to control samples, the expression levels of all three CIS genes were significantly up-regulated in chicken ML samples. Furthermore, they were frequently, but not in all field ML cases, deregulated at the mRNA level as a result of ALV-J infection. Our findings contribute to the understanding of the relationship between multi-pathotypes associated with ALV-J infection and the molecular background of tumorigenesis.
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Disruption of STAT3 by niclosamide reverses radioresistance of human lung cancer.
Mol. Cancer Ther.
PUBLISHED: 12-20-2013
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A major challenge affecting the outcomes of patients with lung cancer is the development of acquired radioresistance. However, the mechanisms underlying the development of resistance to therapy are not fully understood. Here we discovered that ionizing radiation (IR) induces phosphorylation of JAK2 and STAT3 in association with increased levels of Bcl2/Bcl-XL in various human lung cancer cells. To uncover new mechanism(s) of radioresistance of lung cancer, we established lung cancer cell model systems with acquired radioresistance. As compared to radiosensitive parental lung cancer cells (i.e. A549, H358 and H157), the JAK2/STAT3/Bcl2/Bcl-XL survival pathway is significantly more activated in acquired radioresistant lung cancer cells (i.e. A549-IRR, H358-IRR and H157-IRR). Higher levels of STAT3 were found to be accumulated in the nucleus of radioresistant lung cancer cells. Niclosamide, a potent STAT3 inhibitor, can reduce STAT3 nuclear localization in radioresistant lung cancer cells. Intriguingly, either inhibition of STAT3 activity by niclosamide or depletion of STAT3 by RNA interference reverses radioresistance in vitro. Niclosamide alone or in combination with radiation overcame radioresistance in lung cancer xenografts. These findings uncover a novel mechanism of radioresistance and provide a more effective approach to overcome radioresistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway, which may potentially improve lung cancer outcome, especially for those patients who have resistance to radiotherapy.
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A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits growth and promotes apoptosis of nasopharyngeal carcinoma cells.
Cell Oncol (Dordr)
PUBLISHED: 11-18-2013
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Stathmin, a microtubule associated protein (MAP), is an important molecular target for cancer therapy. Paclitaxel is one of the primary antitumor drugs targeting microtubules (MTs). We hypothesized that decreasing the expression level of Stathmin might improve the effectiveness of paclitaxel in the treatment of nasopharyngeal carcinoma (NPC).
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Differential expression and regulation of Tdo2 during mouse decidualization.
J. Endocrinol.
PUBLISHED: 11-06-2013
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Tryptophan 2,3-dioxygenase (Tdo2) is a rate-limiting enzyme which directs the conversion of tryptophan to kynurenine. The aim of this study was to examine the expression and regulation of Tdo2 in mouse uterus during decidualization. Tdo2 mRNA was mainly expressed in the decidua on days 6-8 of pregnancy. By real-time PCR, a high level of Tdo2 expression was observed in the uteri from days 6 to 8 of pregnancy, although Tdo2 expression was observed on days 1-8. Simultaneously, Tdo2 mRNA was also detected under in vivo and in vitro artificial decidualization. Estrogen, progesterone, and 8-bromoadenosine-cAMP could induce the expression of Tdo2 in the ovariectomized mouse uterus and uterine stromal cells. Tdo2 could regulate cell proliferation and stimulate the expression of decidual marker Dtprp in the uterine stromal cells and decidual cells. Overexpression of Tdo2 could upregulate the expression of Ahr, Cox2, and Vegf genes in uterine stromal cells, while Tdo2 inhibitor 680C91 could downregulate the expression of Cox2 and Vegf genes in uterine decidual cells. These data indicate that Tdo2 may play an important role during mouse decidualization and be regulated by estrogen, progesterone, and cAMP.
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[Stock assessment and management for Illex argentinus in Southwest Atlantic Ocean based on Bayesian Schaefer model].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 11-02-2013
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Abstract: Bayesian Schaefer model was applied to assess the stock of Illex argentinus in the Southwest Atlantic Ocean, with the risk of alternative management strategies for the squid analyzed. Under the scenarios of normal and uniform prior assumptions, the estimated model parameters and reference points were similar, and higher than the values under the scenario of logarithmic normal prior assumption. Under the three proposed scenarios, the fishing mortalities and the total catches in 2001-2010 were lower than the reference point F0.1 and the maximum sustainable yield (MSY), indicating that the I. argentinus was in an expected sustainable exploited level but not in over-fishing and over-fished. The results of decision analysis indicated that at the same harvest rate, the stock of the I. argentinus under the scenario of logarithmic normal prior assumption in 2025 would be the lowest, and the probability of collapse would be the highest. Under the three scenarios, the harvest rate in 2025 would be all 0.6 if the catch was the maximum. However, if the harvest rate was set to 0.6, the stock of the I. argentinus after 2025 would have definite risk, and thus, the harvest rate 0.4 and the catch 550000 t appeared to be the best management regulation or the baseline case.
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Genome-wide association study identifies 8 novel Loci associated with blood pressure responses to interventions in han chinese.
Circ Cardiovasc Genet
PUBLISHED: 10-28-2013
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Background- Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals BP responses to dietary intervention and cold pressor test. Methods and Results- We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 (P=7.29×10(-9)), CDCA7 (P=3.57×10(-8)), PIBF1 (P=1.78×10(-9)), ARL4C (P=1.86×10(-8)), IRAK1BP1 (P=1.44×10(-10)), SALL1 (P=7.01×10(-13)), TRPM8 (P=2.68×10(-8)), and FBXL13 (P=3.74×10(-9)). There was a strong dose-response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively (P=0.0003 for trend). Conclusions- Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.
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TRAF4 Is a Critical Molecule for Akt Activation in Lung Cancer.
Cancer Res.
PUBLISHED: 10-23-2013
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TRAF4 is an adapter protein overexpressed in certain cancers, but its contributions to tumorigenesis are unclear. In lung cancer cells and primary lung tumors, we found that TRAF4 is overexpressed. RNA interference-mediated attenuation of TRAF4 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that TRAF4, but not Skp2, was required for activation of the pivotal cell survival kinase Akt through ubiquitination. Furthermore, TRAF4 attenuation impaired glucose metabolism by inhibiting expression of Glut1 and HK2 mediated by the Akt pathway. Overall, our work suggests that TRAF4 offers a candidate molecular target for lung cancer prevention and therapy. Cancer Res; 73(23); 6938-50. ©2013 AACR.
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Regulation of microRNAs by epigenetics and their interplay involved in cancer.
J. Exp. Clin. Cancer Res.
PUBLISHED: 10-21-2013
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Similar to protein-coding genes, miRNAs are also susceptible to epigenetic modulation. Although numerous miRNAs have been shown to be affected by DNA methylation, the regulatory mechanism of histone modification on miRNA is not adequately understood. EZH2 and HDACs were recently identified as critical histone modifiers of deregulated miRNAs in cancer and can be recruited to a miRNA promoter by transcription factors such as MYC. Because miRNAs can modulate epigenetic architecture and can be regulated by epigenetic alteration, they could reasonably play an important role in mediating the crosstalk between epigenetic regulators. The complicated network between miRNAs and epigenetic machineries underlies the epigenetic--miRNA regulatory pathway, which is important in monitoring gene expression profiles. Regulation of miRNAs by inducing epigenetic changes reveals promising avenues for the design of innovative strategies in the fight against human cancer.
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Targeting EBV-LMP1 DNAzyme enhances radiosensitivity of nasopharyngeal carcinoma cells by inhibiting telomerase activity.
Cancer Biol. Ther.
PUBLISHED: 10-21-2013
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The latent membrane protein 1 (LMP1), which is encoded by the Epstein-Barr virus (EBV), has been suggested to be one of the major oncogenic factors in nasopharyngeal carcinoma (NPC). In previous studies, we experimentally demonstrated that downregulation of LMP1 expression by targeting EBV-LMP1 DNAzyme (Dz1) could increase the radiosensitivity of NPC. However, how Dz1 contributes to the radiosensitivity in NPC is still not clear. In the present study, we confirmed that Dz1 decreases LMP1 expression and downregulates the expression of the catalytic subunit of telomerase (hTERT), both at the protein and mRNA levels (P<0.01), and therefore, consequently inhibits telomerase activity (P<0.05) in LMP1-positive NPC cells. We also observed that LMP1 mediated Akt phosphorylation is involved in the regulation of hTERT expression and phosphorylation. After LMP1 and hTERT expression was silenced by Dz1- and hTERT-targeted siRNA, respectively, the radiosensitivity increased in CNE1-LMP1 cells (P<0.05). The inhibition was more significant after Dz1 treatment was combined with siRNA (P<0.01). We concluded that hTERT expression and phosphorylation could be regulated by LMP1 through the Akt pathway, and Dz1 enhances radiosensitivity of LMP1-positive NPC cells by inhibiting telomerase activity.
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Investigations of the fabrication and the surface-enhanced Raman scattering detection applications for tapered fiber probes prepared with the laser-induced chemical deposition method.
Appl Opt
PUBLISHED: 10-03-2013
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The process of depositing nanoparticles onto tapered fiber probes with the laser-induced chemical deposition method (LICDM) and the surface-enhanced Raman scattering (SERS) detection performance of the prepared probes are experimentally investigated in this paper. Our results show that the nanoparticle-deposited tapered fiber probes prepared with the LICDM method depend strongly on the value of the cone angle. For small-angle tapered probes the nanoparticle-deposited areas are only focused at the taper tips, because the taper surfaces are mainly covered by a relatively low-intensity evanescent field. By lengthening the reaction time or increasing the induced power or solution concentration, it is still possible to deposit nanoparticles on small-angle tapers with the light-scattering effect. With 4-aminothiophenol as the testing molecule, it was found that for given preparation conditions, the cone angles for the tapered probes with the highest SERS spectral intensities for different excitation laser powers are almost the same. However, such an optimal cone angle is determined by the combined effects of both the localized surface plasmon resonance strength and the transmission loss generated by the nanoparticles deposited.
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Phase II study on Javanica oil emulsion injection (Yadanzi®) combined with chemotherapy in treating patients with advanced lung adenocarcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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To investigate the efficacy and safety of Javanica oil emulsion injection (Yadanzi®) combined with pemetrexed and platinum (PP) for treating patients with advanced lung cancer.
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Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: Successful engraftment and mild GVHD.
Stem Cell Res
PUBLISHED: 09-26-2013
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Haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 21 young people with severe aplastic anemia (SAA) undergoing haplo-HSCT without T-cell-depleted. We observed that all patients had sustained hematopoietic engraftment without any adverse UC-MSC infusion-related events. Furthermore, we did not observe any increase in severe aGVHD. These data suggest that UC-MSCs, possibly thanks to their potent immunosuppressive effect on allo-reactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure and severe GVHD in haplo-HSCT.
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Electrochemical assay of the relationship between the inhibition of phosphatidylinositol 3-kinase pathway and estrogen receptor expression in breast cancer.
Anal Bioanal Chem
PUBLISHED: 07-24-2013
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Breast cancer has become one of the most threatening diseases to women throughout the world. Emerging evidence implies that estrogen receptor (ER) and phosphatidylinositol 3-kinase (PI3K) pathways play central roles in both breast cancer progression and response to therapy. In this work, we have probed into ER expression related to the PI3K pathway at the protein level with an electrochemical technique based on the detection of ER proteins in nuclear extracts with an Exonuclease III protection-based strategy. Experimental results show that an increased number of ER proteins can be detected upon PI3K inhibition, demonstrating the reversal effect of the PI3K inhibitor on ER expression. Moreover, treatment with different concentrations of the PI3K inhibitor NVP-BEZ235 can result in a dose-dependent alteration of ER protein levels, implying an intimate link between ER and PI3K pathways. This work may be a great help to understand the mysteries underlying PI3K-related endocrine resistance and to evaluate the effect of therapeutic interventions in the future.
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The role of necroptosis, an alternative form of cell death, in cancer therapy.
Expert Rev Anticancer Ther
PUBLISHED: 07-24-2013
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Programmed cell death plays an important role in animal development, tissue homeostasis and eliminating harmful or virally infected cells. Necroptosis, a novel form of programmed cell death, is caspase independent but RIPK and RIPK3 dependent. Moreover, it is suggested that necroptosis can be specifically inhibited by small molecular inhibitors such as necrostatin-1. Its signaling pathways have something in common with apoptosis, although the molecular mechanisms of necroptosis need to be further elucidated. Previous evidences suggest that necroptosis has significant effects in regulating various physiological processes and disease, such as ischemic brain injury, immune system disorders and cancer. In this review, the molecular mechanism of necroptosis is described and how it could be manipulated in the treatment of cancer is summarized.
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Therapeutic Evaluation of Epstein-Barr Virus-encoded Latent Membrane Protein-1 Targeted DNAzyme for Treating of Nasopharyngeal Carcinomas.
Mol. Ther.
PUBLISHED: 07-23-2013
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The ability of the 10-23 DNAzyme to specifically cleave RNA with high efficiency has fuelled expectation that this agent may have useful applications for targeted therapy. Here, we, for the first time, investigated the antitumor and radiosensitizing effects of a DNAzyme (DZ1) targeted to the Epstein-Barr virus (EBV)-LMP1 mRNA of nasopharyngeal carcinoma (NPC) in patients. Preclinical studies indicated that the DNAzyme was safe and well tolerated. A randomized and double-blind clinical study was conducted in 40 NPC patients who received DZ1 or saline intratumorally, in conjunction with radiation therapy. Tumor regression, patient survival, EBV DNA copy number and tumor microvascular permeability were assessed in a 3-month follow-up. The mean tumor regression rate at week 12 was significantly higher in DZ1 treated group than in the saline control group. Molecular imaging analysis showed that DZ1 impacted on tumor microvascular permeability as evidenced by a faster decline of the K(trans) in DZ1-treated patients. The percentage of the samples with undetectable level of EBV DNA copy in the DZ1 group was significantly higher than that in the control group. No adverse events that could be attributed to the DZ1 injection were observed in patients.Molecular Therapy (2013); doi:10.1038/mt.2013.257.
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EBV-LMP1-targeted DNAzyme induces DNA damage and causes cell cycle arrest in LMP1-positive nasopharyngeal carcinoma cells.
Int. J. Oncol.
PUBLISHED: 07-19-2013
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This study aimed to determine the molecular mechanisms underlying the effect of the LMP1-targeted DNAzyme 1 (DZ1) on cell cycle progression in nasopharyngeal carcinoma (NPC) cells. We showed that the active DZ1 inhibited the expression of latent membrane protein 1 (LMP1) and induced a G1 phase arrest. In addition, this cell cycle deregulation was shown to be accompanied by upregulation of the DNA damage marker ?-H2AX, downregulation of the DNA damage response factor p-p53-Ser15 and cell proliferation inhibition. To investigate what affected the cell cycle progression, we examined the expression of two checkpoint-related cyclins and cyclin-dependent kinases (CDKs). We found a decrease of cyclin D1 and cyclin E protein levels at 24 h from the DZ1 treatment. Moreover, we observed inhibition of CDK4 activity and decreased cyclin D1 expression in the complexes immunoprecipitated with CDK4 antibody. We also found a reduction in cdc2 phosphorylation at Thr161 which partially stands for the cdc2 kinase activity in DZ1-treated CNE1-LMP1 cells, although the downregulation of LMP1 expression had no effect on the cyclin B1 and cdc2 expression. Further, we analyzed changes in cdc2 kinase activity induced by DZ1 and found that the downregulation of the LMP1 expression resulted in a 5-fold reduction in cdc2 kinase activity in CNE1-LMP1. The data suggest that the downregulation of the LMP1 expression by DZ1 was able to induce DNA damage, which then further inhibited the cell proliferation and resulted in malfunction of cell cycle checkpoints that led to G1 phase arrest and the decrease in number of cells in G2/M phase.
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[Association between total antioxidant status and atherosclerosis in elderly patients with essential hypertension].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-15-2013
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To investigate the association between plasma total antioxidant status (TAS) and association with brachial-ankle pulsewave velocity (baPWV) in the elderly patients with essential hypertension(EH).
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Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity-modulated proton therapy treatment planning.
Phys Med Biol
PUBLISHED: 07-09-2013
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The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization (SIO) in intensity-modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the SIO routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable SIO (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming based model without MU constraints, i.e., a conventional SIO (CSIO) model, was also implemented to emulate commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post-processing procedure required by the TPS as well as the resultant deteriorating effect on ultimate dose distributions. This approach therefore allows IMPT plans to adopt all possible spot spacings optimally. Moreover, dosimetric benefits can be achieved using smaller spot spacings.
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Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy.
Ann. Hematol.
PUBLISHED: 06-13-2013
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Human leukocyte antigen haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 50 people with refractory/relapsed hematologic malignancy undergoing haplo-HSCT with myeloablative conditioning. We observed that all patients given MSCs showed sustained hematopoietic engraftment without any adverse UC-MSC infusion-related reaction. The median times to neutrophil >0.50 × 10(9)/L and platelet >20 × 10(9)/L engraftment were 12.0 and 15.0 days, respectively. We did not observe an increase in severe acute GVHD (aGVHD) and extensive chronic GVHD (cGVHD), too. Grade II-IV aGVHD was observed in 12 of 50 (24.0 %) patients. cGVHD was observed in 17 of 45 (37.7 %) patients and was extensive in 3 patients. Additionally, only five patients (10.0 %) experienced relapse at a median time to progression of 192 days. The probability that patients would attain progression-free survival at 2 years was 66.0 %. The results indicate that this new strategy is effective in improving donor engraftment and reducing severe GVHD, which will provide a feasible option for the therapy of high-risk hematologic malignancy.
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WITHDRAWN: miR-504 affects the radio-resistance in nasopharyngeal carcinoma by down-regulating the expression of nuclear respiratory factor 1.
Int. J. Biochem. Cell Biol.
PUBLISHED: 06-01-2013
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This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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Isolation, identification, and phylogenetic analysis of two avian leukosis virus subgroup J strains associated with hemangioma and myeloid leukosis.
Vet. Microbiol.
PUBLISHED: 05-31-2013
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Cases of myeloid leukosis and hemangioma associated with avian leukosis virus subgroup J (ALV-J) are becoming more frequent in China in commercial layer chickens and breeders of egg-type chickens. In this study, two strains of ALV-J (SCAU11-H and SCAU11-XG) associated with hemangioma and myelocytoma were isolated from commercial broiler breeder animals in 2011. Their full-length proviral sequences were analyzed, revealing several unique genetic differences between the two isolates, and suggesting that the two viruses were derived from two distinct lineages. Strain SCAU11-H showed high sequence homology to early Chinese isolates associated with hemangioma, while strain SCAU11-XG was genetically closer to the prototype strain, HPRS-103. The complete genomic nucleotide sequences of SCAU11-H and SCAU11-XG were 7471 bp and 7727 bp in length, respectively. They shared 94.8% identity with each other, and had 94.0-96.8% nucleotide identity to ALV-J reference isolates. Homology analysis of the env, pol, and gag genes of the two isolates and other references strains showed that the gag and pol genes of the two viruses were more conserved than the env gene. In addition, the two isolates had significant deletions and substitutions in their 3-UTR regions, compared to HPRS-103. These results suggest that the env gene and the 3-UTR regions in these ALV-J isolates have evolved rapidly, and might be involved in the oncogenic spectrum of ALV-J. The results of this study contribute to our further study of the relationship between ALV integration patterns and multi-pathotypes associated with ALV-J.
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Influencing factors of the quality of life in Chinese burn patients: Investigation with adapted Chinese version of the BSHS-B.
Burns
PUBLISHED: 05-02-2013
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The study aims to evaluate the quality of life (QOL) in burn patients in China and find out principal influencing factors, so as to provide evidence for interventions.
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Saturated Free Fatty Acid Sodium Palmitate-Induced Lipoapoptosis by Targeting Glycogen Synthase Kinase-3? Activation in Human Liver Cells.
Dig. Dis. Sci.
PUBLISHED: 04-14-2013
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Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD).
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Pemetrexed as a Component of First-, Second- and Third- line Chemotherapy in Treating Patients with Metastatic Lung Adenocarcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-09-2013
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Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 mg/m2 (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 mg/m2 and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 mg/m2 and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.
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MicroRNA and signal transduction pathways in tumor radiation response.
Cell. Signal.
PUBLISHED: 03-23-2013
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Tumor radiation response is an essential issue in radiotherapy and a core determining factor of tumor radioresistance or radiosensitivity. Multiple factors can influence tumor radiation response, and among them tumor genetic and epigenetic background, tumor microenvironment and tumor blood flow status may take a leading role. During the whole process of tumor radiation response, tumor radiosensitivity can be regulated in an orderly manner through some classical signal transduction pathways. Although these pathways have already owned multiple biological functions and involved in the process of carcinogenesis, their regulatory roles in tumor radiation response can not be ignored. MicroRNA (miRNA) is a class of non-coding RNA of about 22 nucleotides in length, which binds to the 3-untranslated region (3-UTR) of target gene and controls the expression of it at the post-transcriptional level. MiRNA participates in numerous physiology and pathology processes and acts as oncogene or tumor suppressor to affect cancer progression. Through interplaying with the key components in radiation related signal transduction pathways, miRNA could effectively activate the expression of DNA damage response genes and cell cycle related genes in the nucleus, and play a critical role in the modulation of radiation response and radiosensitivity in tumor cells. In this review, we mainly elucidate the regulatory mechanisms and functions of miRNA in these radiation related signal transduction pathways from three different aspects which include the upstream receptors, midstream transducer pathways, and downstream effector genes.
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Determination of 30 synthetic food additives in soft drinks by HPLC/electrospray ionization-tandem mass spectrometry.
J AOAC Int
PUBLISHED: 03-22-2013
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A method combining SPE with HPLC/electrospray ionization-MS/MS was developed for simultaneous determination of 30 synthetic food additives, including synthetic colorants, preservatives, and sweeteners in soft drinks. All targets were efficiently separated using the optimized chromatographic and MS conditions and parameters in a single run within 18 min. The LOD of the analytes ranged from 0.01 to 20 microg/kg, and the method was validated with recoveries in the 80.8 to 106.4% range. This multisynthetic additive method was found to be accurate and reliable and will be useful to ensure the safety of food products, such as the labeling and proper use of synthetic food additives in soft drinks.
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Spiroketals of Pestalotiopsis fici provide evidence for a biosynthetic hypothesis involving diversified Diels-Alder reaction cascades.
J. Org. Chem.
PUBLISHED: 03-22-2013
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Chloropestolides B-G (1-6), six new metabolites featuring the chlorinated spiro[benzo[d][1,3]dioxine-2,7-bicyclo[2.2.2]octane]-4,8-dione (1-3) and spiro[benzo[d][1,3]dioxine-2,1-naphthalene]-2,4-dione (4-6) skeletons, and their putative biosynthetic precursor dechloromaldoxin (7) were isolated from the scale-up fermentation cultures of the plant endophytic fungus Pestalotiopsis fici . The structures of 1-7 were determined mainly by NMR experiments. The absolute configurations of 1-3 were deduced by analogy to the previously isolated metabolites from the same fungus (9 and 13-18), whereas those of 4, 5, and 7 were assigned by electronic circular dichroism (ECD) calculations. Structurally, the spiroketal skeletons found in 1-3 and 4-6 could be derived from 2,6-dihydroxy-4-methylbenzoic acid with chlorinated bicyclo[2.2.2]oct-2-en-5-one and 4a,5,8,8a-tetrahydronaphthalen-2(1H)-one, respectively. Biogenetically, compounds 1-6 were derived from the same Diels-Alder precursors as the previously isolated 9 and 12-18. In addition, compounds 2 and 3 were proposed as the biosynthetic intermediates of 17 and 16, respectively. Compound 1 was cytotoxic to three human tumor cell lines.
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An Exonuclease III Protection-Based Electrochemical Method for Estrogen Receptor Assay.
Int J Mol Sci
PUBLISHED: 03-06-2013
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Estrogen receptor (ER), expressed in approximately 80% of primary breast cancer cells, has proven to be a valuable predictive factor of the disease. Herein, by making use of the specific binding of ER to its DNA response elements, we propose an Exonuclease III (Exo III) protection-based electrochemical method for detecting ER proteins. In this assay, the presence of ER can protect the duplex DNA molecules immobilized on an electrode surface from Exo III-catalyzed digestion, resulting in an increased electrochemical signal. Experimental results have revealed that the proposed method can allow the quantification of ER in the range of 0.5 to 100 nM with a satisfactory detection limit of 0.38 nM. Furthermore, since this approach can also be employed to detect ER directly in nuclear extracts, it may be of great use in biomedical applications in the future.
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