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Find video protocols related to scientific articles indexed in Pubmed.
Identification of a juxtamembrane mechano-sensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex.
Blood
PUBLISHED: 11-01-2014
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How glycoprotein (GP)Ib-IX complex on the platelet surface senses the blood flow through its binding to the plasma protein von Willebrand factor (VWF) and transmits a signal into the platelet remains unclear. Here we show that optical tweezer-controlled pulling of A1 domain of VWF (VWF-A1) on GPIb-IX captured by its cytoplasmic domain induced unfolding of a hitherto unidentified structural domain prior to the dissociation of VWF-A1 from GPIb-IX. Additional studies using recombinant proteins and mutant complexes confirmed its existence in GPIb-IX and enabled localization of this quasi-stable mechano-sensitive domain of ~60 residues between the macroglycopeptide region and the transmembrane helix of GPIb? subunit. These results suggest that VWF-mediated pulling under fluid shear induces unfolding of the mechano-sensitive domain in GPIb-IX, which may possibly contribute to platelet mechanosensing and/or shear resistance of VWF-platelet interaction. The identification of the mechano-sensitive domain in GPIb-IX has significant implications for the pathogenesis and treatment of related blood diseases.
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Microbiota in the throat and risk factors of laryngeal carcinoma.
Appl. Environ. Microbiol.
PUBLISHED: 09-21-2014
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The compositions and abundance of the microbiota in the ecological niche of human throat and their possible relationship between the microbiota and laryngeal cancer are poorly understood. To obtain insight into this, we enrolled 27 laryngeal carcinoma patients and 28 subjects with vocal cord polyps as controls. For each subject, we simultaneously collected swab samples from the upper throat near epiglottis (site I) and tissue samples from the vestibulum laryngis to the subglottic region (site II). The microbiota of the throat were fully characterized by pyrosequencing of barcoded 16S rRNA genes. We found 14 phyla, 20 classes, 38 orders, 85 families, and 218 genera in the throat of enrolled subjects. The main phyla were Firmicutes (54.7%), Fusobacteria (14.8%), Bacteroidetes (12.7%), and Proteobacteria (10.6%). Streptococcus (37.3%), Fusobacterium (11.3%), and Prevotella (10.6%) were identified as the three most predominant genera in the throat. The relative abundances of 23 bacterial genera in the site I were significantly different compared with the site II (p < 0.05). The relative proportions of 12 genera largely varied between laryngeal cancer patients and control subjects (p < 0.05). Collectively, this study outlined the spatial structure of microbial communities in the human throat. The spatial structure of bacterial communities significantly varied in two anatomical sites of the throat. The bacterial profiles in the throat were strongly different between laryngeal cancer patients and control subjects, and several of these microorganisms may be related to laryngeal carcinoma.
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A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis.
Blood
PUBLISHED: 09-10-2014
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Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib resistance in Bim(hi) cells, adaptive bortezomib-resistant cells displayed marked Bim downregulation. HDACI upregulated Bim and, when combined with ABT-737, which released Bim from Bcl-2/Bcl-xL, potently killed bortezomib-resistant cells. These events were correlated with Bim-associated autophagy attenuation, whereas Bim knockdown sharply increased autophagy in Bim(hi) cells. In Bim(low) cells, autophagy disruption by chloroquine (CQ) was required for HDACI/ABT-737 to induce Bim expression and lethality. CQ also further enhanced HDACI/ABT-737 lethality in bortezomib-resistant cells. Finally, HDACI failed to diminish autophagy or potentiate ABT-737-induced apoptosis in bim(-/-) mouse embryonic fibroblasts. Thus, Bim deficiency represents a novel mechanism of adaptive bortezomib resistance in MM cells, and Bim-targeting strategies combining HDACIs (which upregulate Bim) and BH3 mimetics (which unleash Bim from antiapoptotic proteins) overcomes such resistance, in part by disabling cytoprotective autophagy.
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Restriction of IL-22-producing T cell responses and differential regulation of regulatory T cell compartments by zinc finger transcription factor Ikaros.
J. Immunol.
PUBLISHED: 09-05-2014
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Proper immune responses are needed to control pathogen infection at mucosal surfaces. IL-22-producing CD4(+) T cells play an important role in controlling bacterial infection in the gut; however, transcriptional regulation of these cells remains elusive. In this study, we show that mice with targeted deletion of the fourth DNA-binding zinc finger of the transcription factor Ikaros had increased IL-22-producing, but not IL-17-producing, CD4(+) T cells in the gut. Adoptive transfer of CD4(+) T cells from these Ikaros-mutant mice conferred enhanced mucosal immunity against Citrobacter rodentium infection. Despite an intact in vivo thymic-derived regulatory T cell (Treg) compartment in these Ikaros-mutant mice, TGF-?, a cytokine well known for induction of Tregs, failed to induce Foxp3 expression in Ikaros-mutant CD4(+) T cells in vitro and, instead, promoted IL-22. Aberrant upregulation of IL-21 in CD4(+) T cells expressing mutant Ikaros was responsible, at least in part, for the enhanced IL-22 expression in a Stat3-dependent manner. Genetic analysis using compound mutations further demonstrated that the aryl hydrocarbon receptor, but not ROR?t, was required for aberrant IL-22 expression by Ikaros-mutant CD4(+) T cells, whereas forced expression of Foxp3 was sufficient to inhibit this aberrant cytokine production. Together, our data identified new functions for Ikaros in maintaining mucosal immune homeostasis by restricting IL-22 production by CD4(+) T cells.
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Cisplatin and paclitaxel target significant long noncoding RNAs in laryngeal squamous cell carcinoma.
Med. Oncol.
PUBLISHED: 09-01-2014
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The objectives of this study were to identify specific long noncoding RNAs (lncRNAs) in laryngeal squamous cell carcinoma (LSCC) and to clarify the function of cisplatin and paclitaxel on the confirmed laryngeal cancer lncRNAs. Fifty-four pairs of laryngeal tumor and adjacent normal tissue were collected. Candidate lncRNAs were searched in authorized databases. The significant lncRNAs were identified and confirmed through high-output real-time PCR. Chemotherapy assay evaluated the influences of cisplatin and paclitaxel on the significant lncRNAs. Thirty-seven cancer-related candidate lncRNAs were selected. Three up-expressed and two down-expressed significant lncRNAs were identified and confirmed. The expressions of lncRNA CDKN2B-AS1, HOTAIR and MALAT1 were dramatically reduced with the increasing concentration of cisplatin and paclitaxel and also lengthening of the treatment duration. Cisplatin and paclitaxel have target function on significant lncRNAs in LSCC, which presents novel molecular targets to cure LSCC patients and also leads an orientation for developing new drugs.
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p62/sequestosome 1 regulates aggresome formation of pathogenic ataxin-3 with expanded polyglutamine.
Int J Mol Sci
PUBLISHED: 08-25-2014
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The cellular protein quality control system in association with aggresome formation contributes to protecting cells against aggregation-prone protein-induced toxicity. p62/Sequestosome 1 (p62) is a multifunctional protein which plays an important role in protein degradation and aggregation. Although poly-ubiquitination is usually required for p62-mediated protein degradation and aggresome formation, several p62 substrates are processed to form aggregate in an ubiquitination-independent manner. In this study we demonstrate that p62 directly interacts with pathogenic Machado Joseph Disease (MJD)-associated protein ataxin-3 with polyglutamine (polyQ) expansion. Moreover, p62 could regulate the aggresome formation of pathogenic ataxin-3 and protect cells against pathogenic ataxin-3-induced cell death.
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Commensal bacteria protect against food allergen sensitization.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-25-2014
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Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.
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Efficient red electroluminescent devices with sterically hindered phosphorescent platinum(II) Schiff base complexes and iridium complex codopant.
Chem Asian J
PUBLISHED: 08-21-2014
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Sterically hindered platinum(II) Schiff base complexes were prepared. Complex 4, which displays red emission with a quantum yield of 0.29 in a thin film and a self-quenching rate constant of 1×10(-7) dm(3) mol(-1) ?s(-1), was used to fabricate organic light-emitting diodes with single or double emissive layers (EMLs). An iridium(III) complex with a wide band gap was codoped into the electron-dominant EML to act as a deep electron trapper, and red-light-emitting devices with the highest current, power, and external quantum efficiencies of 20.43?cd?A(-1) 18.33?Lm?W(-1), and 11.7%, respectively, were fabricated. A high current efficiency and EQE of up to 14.69?cd?A(-1) and 8.3%, respectively, were achieved at a high brightness of 1000?cd?m(-2). The significant delay of efficiency roll-off is attributed to the bulky 3D structure of the norbornene moiety at the periphery of the Schiff base ligand of 4 and to the new device design strategy. The fabricated device had a projected lifetime (LT50) of 18,000?h.
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[Silenced NgR gene expression by RNA interference to promote rats facial nerve regeneration in vitro].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 08-19-2014
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To suppress NgR gene expression in neural stem cells and observe differentiation of neural stem cells in vitro after interfered which provide nutritional support for the facial nerve repair in vivo.
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Gastroesophageal reflux and carcinoma of larynx or pharynx: a meta-analysis.
Acta Otolaryngol.
PUBLISHED: 08-18-2014
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The meta-analysis supported the proposition that the prevalence of gastroesophageal reflux disease (GERD) was associated with laryngeal cancer, particularly in the hospital-based control group and diagnosed by esophagogastroduodenoscopy (EGD) or esophageal pH monitoring. However, no significant association was found between GERD and pharyngeal carcinoma.
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MicroRNA-93 regulates cyclin G2 expression and plays an oncogenic role in laryngeal squamous cell carcinoma.
Int. J. Oncol.
PUBLISHED: 08-13-2014
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microRNA93 (miR-93) is expressed in the miR?106b-25 cluster, located in intron 13 of the MCM7 gene. Our previous study found that miR-93 was significantly upregulated in laryngeal squamous cell carcinoma (LSCC), and cyclin G2 (CCNG2) was a potential target of miR-93 in LSCC. However, the possible functions and molecular mechanisms of miR-93 in LSCC remain unknown. In the present study, we show that the level of CCNG2 protein expression was significantly lower in LSCC cancer tissue than normal tissues. The level of CCNG2 was correlated with clinical stages, lymph node metastasis and histological grade. We further show that the expression level of miR-93 was inversely correlated with CCNG2 expression in clinical specimens. Furthermore, gain-of-function assays revealed that miR-93 promoted cell proliferation, decreased apoptosis rates, induced cell cycle arrest and promoted cell migration and invasion, whereas silencing of miR-93 attenuated these carcinogenic processes. In addition, overexpression of miR-93 in Hep-2 cells could reduce the mRNA and protein levels of CCNG2, whereas silencing of miR-93 in Hep-2 cells significantly increased CCNG2 expression. A luciferase assay verified that miR-93 could bind to the 3' untranslated region of CCNG2. Importantly, ectopic expression of CCNG2 in miR-93 cells rescued the effect of miR-93 on LSCC proliferation. Knockdown of CCNG2 promoted cell proliferation resembling that of miR-93 overexpression. These findings demonstrated that miR-93 promotes tumor growth by directly suppressing CCNG2. Taken together, these results suggested that this newly identified miR-93-CCNG2 axis may be involved in LSCC proliferation and progression. Our findings provide novel potential targets for LSCC therapy and prognosis.
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Expression and purification of non-tagged recombinant mouse SPP1 in E. coli and its biological significance.
Bioengineered
PUBLISHED: 08-12-2014
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Secreted phosphoprotein 1 (SPP1) is a multifunctional protein expressed by cells from a large variety of tissues. It is involved in many physiological and pathological processes, including bone metabolism, inflammation progress, tumor metastasis, injury repair, hyperoxia-induced injury, and so on. Native SPP1 from multiple species have been isolated from the milk and urine, and recombinant SPP1 with different tags have been expressed and purified from bacteria. In our study, DNA fragments corresponding to mouse SPP1 without signal peptide were built into the pET28a(+) vector, and non-tagged recombinant mouse SPP1(rmSPP1) was expressed in Escherichia coli BL21(DE3). rmSPP1 was purified using a novel tri-step procedure, and the product features high purity and low endotoxin level. rmSPP1 can effectively increase hepatocellular carcinoma cell(HCC) proliferation in vitro, demonstrating its biological activity.
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Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-11-2014
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Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15mg/kg, once daily, by oral gavage) over 7weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation.
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Bcl-2 Decreases the Affinity of SQSTM1/p62 to Poly-Ubiquitin Chains and Suppresses the Aggregation of Misfolded Protein in Neurodegenerative Disease.
Mol. Neurobiol.
PUBLISHED: 08-04-2014
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Poly-ubiquitinated protein aggregate formation is the most striking hallmark of various neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. Mutations of many ubiquitin-associated proteins involved in the regulation of protein aggregation, such as SQSTM1/p62 (p62), parkin, and VCP, are closely linked to neurodegeneration. B-cell lymphoma 2 (Bcl-2) is a key regulator in autophagy, apoptosis, and mitochondria quality control in many cell types including neurons, and it plays important roles in the pathogenesis of neurodegenerative diseases mentioned above. Our previous work showed that Bcl-2 can directly bind to p62, and here we report that Bcl-2 directly interacts with the N-terminus of p62, but not the C-terminus (UBA domain). Interestingly and importantly, Bcl-2 affects the affinity of p62 to poly-ubiquitin chains and suppresses the aggregation of poly-ubiquitinated proteins such as mutant huntingtin associated with Huntington's disease. Our study reveals a role of Bcl-2 that involves in the regulation of misfolded proteins.
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MicroRNA-183 is involved in cell proliferation, survival and poor prognosis in pancreatic ductal adenocarcinoma by regulating Bmi-1.
Oncol. Rep.
PUBLISHED: 08-01-2014
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As a highly aggressive malignant disease, the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Yet, the mechanisms underlying the progression of PDAC remain unclear. MicroRNAs (miRNAs) may be involved in various human cancers as cancer suppressors or oncogenes. MicroRNA-183 (miR-183) was recently reported to be dysregulated in various types of cancer and to play an important role in the processes of cancer. However, the effects and potential mechanisms of action of miR-183 in PDAC have not been explored. In the present study, low expression of miR-183 was observed in PDAC tissues and cell lines. Low expression of miR-183 in PDAC was significantly associated with tumor grade, metastasis and TNM stage. Kaplan-Meier survival analysis demonstrated that patients harboring low expression of miR-183 had a significantly reduced overall survival than patients with a high level of miR-183 expression. The present study revealed that B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) expression was inversely correlated with miR-183. Our findings also demonstrated that a low level of miR-183 expression effectively suppressed the growth of PDAC cells via regulation of Bmi-1. Following Bmi-1 silencing or upregulation of miR-183, the expression levels of cyclin D1, cyclin-dependent kinase (CDK)2 and CDK4 were decreased. It is reasonable to conclude that alteration of miR-183 expression may regulate the function of PDAC cells by the downregulation of Bmi-1 expression.
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A novel wnt regulatory axis in endometrioid endometrial cancer.
Cancer Res.
PUBLISHED: 08-01-2014
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The Protocadherin 10 (PCDH10) is inactivated often by promoter hypermethylation in various human tumors, but its possible functional role as a tumor suppressor gene is not established. In this study, we identify PCDH10 as a novel Wnt pathway regulatory element in endometrioid endometrial carcinoma (EEC). PCDH10 was downregulated in EEC tumor cells by aberrant methylation of its promoter. Restoring PCDH10 levels suppressed cell growth and triggered apoptosis in EEC cells and tumor xenografts. Gene expression profiling revealed as part of the transcriptomic changes induced by PCDH10 a reduction in levels of MALAT1, a long noncoding RNA, that mediated tumor suppression functions of PCDH10 in EEC cells. We found that MALAT1 transcription was regulated by Wnt/?-catenin signaling via TCF promoter binding and PCDH10 decreased MALAT1 by modulating this pathway. Clinically, MALAT1 expression was associated with multiple parameters in patients with EEC. Taken together, our findings establish a novel PCDH10-Wnt/?-catenin-MALAT1 regulatory axis that contributes to EEC development. Cancer Res; 74(18); 5103-17. ©2014 AACR.
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Prognostic significance of ?-H2AX in laryngeal squamous cell carcinoma after surgery.
Chin. Med. J.
PUBLISHED: 07-22-2014
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The clinical significance of ?-H2AX in laryngeal squamous cell carcinoma (LSCC) has not yet been established. This study was performed to assess the expression of nuclear ?-H2AX in benign and malignant laryngeal lesions and to assess its clinicopathological significance.
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[Influence factors on the cryosurvival rate of post-thaw spermatozoa from sperm donors].
Zhonghua Nan Ke Xue
PUBLISHED: 07-18-2014
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To investigate the influence of seasons, blood types and semen parameters on the cryosurvival rate of frozen-thawed spermatozoa from sperm donors.
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Image tracking for the high similarity drug tablets based on light intensity reflective energy and artificial neural network.
Comput Math Methods Med
PUBLISHED: 07-17-2014
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It is obvious that tablet image tracking exerts a notable influence on the efficiency and reliability of high-speed drug mass production, and, simultaneously, it also emerges as a big difficult problem and targeted focus during production monitoring in recent years, due to the high similarity shape and random position distribution of those objectives to be searched for. For the purpose of tracking tablets accurately in random distribution, through using surface fitting approach and transitional vector determination, the calibrated surface of light intensity reflective energy can be established, describing the shape topology and topography details of objective tablet. On this basis, the mathematical properties of these established surfaces have been proposed, and thereafter artificial neural network (ANN) has been employed for classifying those moving targeted tablets by recognizing their different surface properties; therefore, the instantaneous coordinate positions of those drug tablets on one image frame can then be determined. By repeating identical pattern recognition on the next image frame, the real-time movements of objective tablet templates were successfully tracked in sequence. This paper provides reliable references and new research ideas for the real-time objective tracking in the case of drug production practices.
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Targeting SQSTM1/p62 induces cargo loading failure and converts autophagy to apoptosis via NBK/Bik.
Mol. Cell. Biol.
PUBLISHED: 07-07-2014
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In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cyclin T1 transcriptionally downregulated SQSTM1/p62 but did not affect autophagic flux. These interventions, or short hairpin RNA (shRNA) directly targeting SQSTM1/p62, resulted in cargo loading failure and inefficient autophagy, phenomena recently described for Huntington's disease neurons. These events led to the accumulation of the BH3-only protein NBK/Bik on endoplasmic reticulum (ER) membranes, most likely by blocking loading and autophagic degradation of NBK/Bik, culminating in apoptosis. Whereas NBK/Bik upregulation was further enhanced by disruption of distal autophagic events (e.g., autophagosome maturation) by chloroquine (CQ) or Lamp2 shRNA, it was substantially diminished by inhibition of autophagy initiation (e.g., genetically by shRNA targeting Ulk1, beclin-1, or Atg5 or pharmacologically by 3-methyladenine [3-MA] or spautin-1), arguing that NBK/Bik accumulation stems from inefficient autophagy. Finally, NBK/Bik knockdown markedly attenuated apoptosis in vitro and in vivo. Together, these findings identify novel cross talk between autophagy and apoptosis, wherein targeting SQSTM1/p62 converts cytoprotective autophagy to an inefficient form due to cargo loading failure, leading to NBK/Bik accumulation, which triggers apoptosis.
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Malignant Minor Salivary Gland Carcinomas of the Larynx.
ORL J. Otorhinolaryngol. Relat. Spec.
PUBLISHED: 05-27-2014
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Aims: To explore the clinical characteristics and treatment of malignant minor salivary gland carcinomas of the larynx. Methods: Clinical patient information regarding presentation, pathology, treatment and outcome was obtained through a review of patient charts. Results: Malignant minor salivary carcinomas in the larynx were confirmed pathologically in 15 patients (11 males, 4 females) between 2003 and 2010 in our hospital; 6 patients had mucoepidermoid carcinoma (MEC; 40%), 6 had adenoid cystic carcinoma (ACC; 40%) and 3 had adenocarcinoma (20%). The most common tumour location was the subglottis (60%), followed by the supraglottis (33%). In total, 13 patients underwent surgery, of which 10 (77%) had positive/insufficient resection margins. The mean follow-up time was 42.3 months, with a range of 8-129 months. The 3- and 5-year overall survival rates were 46.7 and 20%, respectively. Conclusion: Malignant minor salivary gland carcinoma of the larynx is a rare disease that showed male predominance in our study. The carcinomas were most often localised in the subglottic region, and the most common histological types were ACC and MEC. Wide-margin surgery with postoperative radiotherapy is advocated. The overall prognosis is poor compared to squamous cell carcinomas of the same location and tumour stage. © 2014 S. Karger AG, Basel.
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Dickkopf-1 is a novel prognostic biomarker for laryngeal squamous cell carcinoma.
Acta Otolaryngol.
PUBLISHED: 05-19-2014
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Dickkopf-1 (DKK1) is a novel prognostic biomarker for laryngeal squamous cell carcinoma (LSCC). DKK1 may be a promising strategy for the future treatment of LSCC metastasis and recurrence.
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Role of stromal cell-derived factor-1 in patients with non-ST elevation acute coronary syndrome.
Int Heart J
PUBLISHED: 05-07-2014
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The predictive value of stromal cell-derived factor-1 (SDF-1) has not been established in patients with non-ST elevation acute coronary syndrome (non-STEACS). A total of 678 consecutive patients with non-STEACS and moderate to high TIMI (Thrombolysis In Myocardial Infarction) risk scores were recruited. All patients underwent an early invasive strategy and then were followed-up for 18 months for clinical events. Left ventricular remodeling was assessed by echocardiography. Plasma concentrations of SDF-1 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were analyzed. SDF-1 level was an independent predictor of left ventricular remodeling (OR = 2.95, 95% CI = 2.02-4.30, P < 0.001). Cox regression analysis demonstrated that both SDF-1 and NT-proBNP levels were significant independent predictors of death, myocardial infarction, or heart failure (HR = 2.45, 95% CI = 1.71-3.50, P < 0.001; HR = 3.71, 95% CI = 2.41-5.70, P < 0.001, respectively). The area under the ROC curves for SDF-1 (0.776) and NT-proBNP (0.817) were similar. The logistic model with both markers yielded a larger area under the ROC curve (0.862) than that of SDF-1 (P < 0.001) or NT-proBNP (P = 0.0001) alone. In patients stratified by NT-proBNP (above 615.4 pmol/L), SDF-1 (above 2175.1 pg/mL) was associated with poorer outcome (P < 0.001). Findings were similar for death and heart failure as individual endpoints. In non-STEACS, higher SDF-1 levels were a significant predictor of death, myocardial infarction, or heart failure independently of baseline clinical characteristics and NT-proBNP, and the combination of SDF-1 and NTproBNP significantly improved risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers in non-ST elevation acute coronary syndrome.
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Notch1 overexpression associates with poor prognosis in human laryngeal squamous cell carcinoma.
Ann. Otol. Rhinol. Laryngol.
PUBLISHED: 05-01-2014
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This study aimed to investigate the expression of Notch1 in human laryngeal squamous cell carcinoma (LSCC) tissues and its relationship to clinicopathologic characteristics as well as their prognostic value in LSCC.
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Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.
PLoS Pathog.
PUBLISHED: 05-01-2014
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Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.
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Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice.
Food Funct
PUBLISHED: 05-01-2014
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Oxidative stress has been implicated in various pathological processes, including skin tumourigenesis. Cutaneum carcinoma is commonly responsible for considerable morbidity and mortality, and treatments have not progressed substantially in recent years. Alternative strategies, such as chemoprevention, are being considered. In this study, we investigated the chemomodulatory potential of lycopene against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and skin carcinogenesis in female ICR mice. Pretreatment with lycopene at various doses significantly delayed tumour formation and growth. These treatments markedly reduced the tumour incidence and tumour volume. Moreover, lycopene inhibited the formation of reactive oxygen species and malondialdehyde, prevented the loss of glutathione, and affected the activities of a battery of oxidant enzymes in the skin of mice. Furthermore, mice that were administered lycopene exhibited higher levels of translocation of nuclear-factor-erythroid-2-related factor 2 into the nucleus compared with the vehicle-treated and model mice. Collectively, these results indicated that lycopene exerts a protective effect against DMBA/TPA-induced cutaneum carcinoma through antioxidant defence.
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Toward an understanding of the gene-specific and global logic of inducible gene transcription.
Cold Spring Harb. Symp. Quant. Biol.
PUBLISHED: 04-19-2014
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Virtually all living organisms have evolved mechanisms to adapt to their environment by sensing environmental stresses and inducing the transcription of appropriate sets of response genes in a coordinated fashion. In the vertebrate immune system, the highly selective response to an environmental stimulus, often an invading microorganism, plays an especially important role in regulating the activities of, and interactions among, the many cell types involved in innate and adaptive immunity. It is now widely appreciated that the selective response to a stimulus requires the concerted action of signal transduction pathways, transcription factors, and chromatin structure. Many proteins and pathways that help to regulate a response have been characterized. However, our understanding of the gene-specific and global logic through which a highly selective response is elicited has only recently begun to emerge.
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A combo-pore approach for the programmable extraction of peptides/proteins.
Nanoscale
PUBLISHED: 04-04-2014
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A novel combo-pore approach has been designed for the programmable purification, minimisation of sample complexity, enrichment and sensitive detection of peptides in biosamples. This approach has a superior performance to conventional protocols and commercial products.
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Risk Factors of Stroke in Western and Asian Countries: A Systematic Review and Meta-analysis of Prospective Cohort Studies.
BMC Public Health
PUBLISHED: 04-03-2014
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There has been an increasing trend in the incidence of stroke worldwide in recent years, and the number of studies focusing on the risk factors for stroke has also increased every year. To comprehensively evaluate the risk factors of stroke identified in prospective Western and Asian cohort studies.
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EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization and in vitro evaluation.
Drug Deliv
PUBLISHED: 03-28-2014
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Abstract The objective of this study was to evaluate the potential of using polymeric micelles modified with a peptide (termed GE11) ligand of epidermal growth factor receptor as the targeted carriers to achieve increased accumulation in laryngeal cancer and enhanced intracellular delivery for the encapsulated anticancer drugs. Poly (ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles containing paclitaxel were prepared via film-hydration method followed by investigation of in vitro release of paclitaxel in phosphate-buffered saline. The average size of GE11-PEG-DSPE/paclitaxel micelle and mPEG-DSPE/paclitaxel were 35?±?2.8?nm [the polydispersity index (PDI)?=?0.207] and 28?±?2.1?nm (PDI?=?0.154), respectively. Micelles with or without GE11-modified had similar physicochemical properties. Transmission electron microscopy showed that the micelles were homogeneous and spherical in shape. Encapsulation efficiency and drug loading of the micelle were 74.11?±?3.89% and 3.58?±?2.82%, respectively. The in vitro targeting characteristic of GE11-modified micelles was investigated by observing the level of cellular uptake of fluorescent coumarin-6-loaded micelles on EGFR over-expressed human laryngeal cancer cell line Hep-2 and EGFR low-expressed human leukemic cell line U-937. Hep-2 cell proliferation was significantly inhibited by GE11-PEG-DSPE/paclitaxel micelle compared to mPEG-DSPE/paclitaxel micelle and Taxol in vitro. Our results suggested that GE11-PEG-DSPE micelle could be a promising strategy for enhancing paclitaxel's chemotherapeutic effects on EGFR over-expressed cancer cells.
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CC chemokine ligand 18 correlates with malignant progression of prostate cancer.
Biomed Res Int
PUBLISHED: 03-14-2014
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CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa.
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GSK3? promotes the differentiation of oligodendrocyte precursor cells via ?-catenin-mediated transcriptional regulation.
Mol. Neurobiol.
PUBLISHED: 03-11-2014
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Oligodendrocytes are generated by the differentiation and maturation of oligodendrocyte precursor cells (OPCs). The failure of OPC differentiation is a major cause of demyelinating diseases; thus, identifying the molecular mechanisms that affect OPC differentiation is critical for understanding the myelination process and repairing after demyelination. Although prevailing evidence shows that OPC differentiation is a highly coordinated process controlled by multiple extrinsic and intrinsic factors, such as growth factors, axon signals, and transcription factors, the intracellular signaling in OPC differentiation is still unclear. Here, we showed that glycogen synthase kinase 3? (GSK3?) is an essential positive modulator of OPC differentiation. Both pharmacologic inhibition and knockdown of GSK3? remarkably suppressed OPC differentiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays and Ki67 staining showed that the effect of GSK3? on OPC differentiation was not via cell death. Conversely, activated GSK3? was sufficient to promote OPC differentiation. Our results also demonstrated that the transcription of myelin genes was regulated by GSK3? inhibition, accompanying accumulated nuclear ?-catenin, and reduced the expression of transcriptional factors that are relevant to the expression of myelin genes. Taken together, our study identified GSK3? as a profound positive regulator of OPC differentiation, suggesting that GSK3? may contribute to the inefficient regeneration of oligodendrocytes and myelin repair after demyelination.
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Quantitative analysis and pharmacokinetics study of tigecycline in human serum using a validated sensitive liquid chromatography with tandem mass spectrometry method.
J Sep Sci
PUBLISHED: 02-12-2014
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Tigecycline, a novel intravenously administered glycylcycline antibiotic, currently plays a key role in the management of complicated multiorganism infections. However, current liquid chromatography with tandem mass spectrometry methods briefly describe parameters and the only reported internal standard was sometimes difficult to obtain. In our study, an updated liquid chromatography with tandem mass spectrometry method for the quantitative analysis of tigecycline in human serum was developed. Sample preparation involved precipitation with 20% trichloroacetic acid. Chromatographic separation of tigecycline and tetracycline (internal standard) was achieved on a Hypersil GOLD C18 column using gradient elution. The selected reaction monitoring transitions were performed at m/z 586.1?513.2 for tigecycline and m/z 445.1?410.2 for tetracycline. The assay was linear over the concentration range of 5-2000 ng/mL. The intra- and interday precisions at three concentration levels (10, 100, and 1600 ng/mL) were <15% and their accuracies were within the range of 95.1-106.1%. The mean recovery ranged from 94.3 to 105.6% and the matrix effect from 92.1 to 97.6%. Tigecycline was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in critically ill patients. The data demonstrated that our method allows quantification of tigecycline in serum in a quick and reliable manner for widespread application.
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Developmental and activity-dependent expression of LanCL1 confers antioxidant activity required for neuronal survival.
Dev. Cell
PUBLISHED: 02-10-2014
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Production of reactive oxygen species (ROS) increases with neuronal activity that accompanies synaptic development and function. Transcription-related factors and metabolic enzymes that are expressed in all tissues have been described to counteract neuronal ROS to prevent oxidative damage. Here, we describe the antioxidant gene LanCL1 that is prominently enriched in brain neurons. Its expression is developmentally regulated and induced by neuronal activity, neurotrophic factors implicated in neuronal plasticity and survival, and oxidative stress. Genetic deletion of LanCL1 causes enhanced accumulation of ROS in brain, as well as development-related lipid, protein, and DNA damage; mitochondrial dysfunction; and apoptotic neurodegeneration. LanCL1 transgene protects neurons from ROS. LanCL1 protein purified from eukaryotic cells catalyzes the formation of thioether products similar to glutathione S-transferase. These studies reveal a neuron-specific glutathione defense mechanism that is essential for neuronal function and survival.
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An improved integration method in serial femtosecond crystallography.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 01-28-2014
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Recent experiments in serial femtosecond crystallography (SFX) have demonstrated the feasibility of obtaining structural information from nanoscale crystals using X-ray free-electron lasers (XFELs). However, millions of crystals are required to determine one reliable structure. Here, an improved integration algorithm for SFX data processing is reported. By evaluating the dimensions of each crystal and correcting for the geometric factors of single patterns, the effective diffraction intensities, as opposed to the directly measured single-shot pattern diffraction intensities, can be merged to acquire more accurate integrated intensities which can be used for structure determination. This improvement enhances the quality of electron-density maps and decreases the number of diffraction patterns that are needed to solve the crystal structure in SFX experiments.
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Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial.
Head Neck
PUBLISHED: 01-28-2014
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The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin-based chemotherapy plus cetuximab as first-line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).
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Comparison of starch granule development and physicochemical properties of starches in wheat pericarp and endosperm.
J. Sci. Food Agric.
PUBLISHED: 01-17-2014
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The objectives of this study were: (i) to characterize structural development of starch granule in pericarp and endosperm during wheat caryopsis growth; (ii) to compare physicochemical properties of starches in pericarp and endosperm; (iii) to further discover the relationships between pericarp starches and endosperm starches. Wheat pericarp and endosperm at different development stages were observed by light microscopy and scanning electron microscopy, respectively. Structural properties of starches were determined using X-ray power diffraction and (13) C solid nuclear magnetic resonance.
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Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 01-02-2014
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The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists. Here, we investigated the metabolic actions of the CB1 inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo(-/-)) mice and their wild-type littermate controls (Adipo(+/+)). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo(+/+) and Adipo(-/-) mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased ?-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1 blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin.
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Enhancement of osseointegration of polyethylene terephthalate artificial ligament by coating of silk fibroin and depositing of hydroxyapatite.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Application of artificial ligament in anterior cruciate ligament reconstruction is one of the research focuses of sports medicine but the biological tendon-bone healing still remains a problem. The preliminary study of hydroxyapatite (HAP) coating on the polyethylene terephthalate (PET) surface could effectively induce the osteoblast differentiation, but the tendon-bone healing was still not stable. As a green synthesis process, the biomimetic mineralization can simulate the natural bone growth in vitro and in vivo.
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MicroRNA-135a inhibits cell proliferation by targeting Bmi1 in pancreatic ductal adenocarcinoma.
Int. J. Biol. Sci.
PUBLISHED: 01-01-2014
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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal solid tumor due to the lack of reliable early detection markers and effective therapies. MicroRNAs (miRNAs), noncoding RNAs that regulate gene expression, are involved in tumorigenesis and have a remarkable potential for the diagnosis and treatment of malignancy. In this study, we investigated aberrantly expressed miRNAs involved in PDAC by comparing miRNA expression profiles in PDAC cell lines with a normal pancreas cell line and found that miR-135a was significantly down-regulated in the PDAC cell lines. The microarray results were validated by qRT-PCR in PDAC tissues, paired adjacent normal pancreatic tissues, PDAC cell lines, and a normal pancreas cell line. We then defined the tumor-suppressing significance and function of miR-135a by constructing a lentiviral vector to express miR-135a. The overexpression of miR-135a in PDAC cells decreased cell proliferation and clonogenicity and also induced G1 arrest and apoptosis. We predicted Bmi1 may be a target of miR-135a using bioinformatics tools and found that Bmi1 expression was markedly up-regulated in PDAC. Its expression was inversely correlated with miR-135a expression in PDAC. Furthermore, a luciferase activity assay revealed that miR-135a could directly target the 3'-untranslated region (3'-UTR) of Bmi1. Taken together, these results demonstrate that miR-135a targets Bmi1 in PDAC and functions as a tumor suppressor. miR-135a may offer a new perspective for the development of effective miRNA-based therapy for PDAC.
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miR-365 promotes cutaneous squamous cell carcinoma (CSCC) through targeting nuclear factor I/B (NFIB).
PLoS ONE
PUBLISHED: 01-01-2014
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Aberrant expression of microRNAs plays vital roles in tumor development and progression. As transcription factors (TFs) are the critical components of signaling cascades, specific targeting effects of microRNAs to specific TFs may determine the role of microRNAs in different cancers. In this study, we identified Nuclear Factor I/B (NFIB) as one of the targets of miR-365 which was previously verified as an onco-miR in cutaneous squamous cell carcinoma (CSCC). Down-regulation of NFIB was a general feature in both CSCC cell lines and tumors from patients which show drastically up-regulated miR-365 expression levels. The siRNA-based knockdown of NFIB mimic the carcinogenic transformation of normal cells by ectopically expression of miR-365 which indicates depletion of NFIB is necessary for miR-365 to exert its pro-carcinogenic function. NFIB may represent a functional barrier targeted by miR-365 to the development of CSCC. Further studies also discovered a conserved feedback regulatory circuitry formed by NFIB and miR-365 in CSCC development which may be potentially utilized as therapeutic target to improve the clinical CSCC treatment.
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Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.
PLoS ONE
PUBLISHED: 01-01-2014
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The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.
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Calcium/Calmodulin-Dependent Protein Kinase Is Negatively and Positively Regulated by Calcium, Providing a Mechanism for Decoding Calcium Responses during Symbiosis Signaling.
Plant Cell
PUBLISHED: 12-24-2013
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The establishment of symbiotic associations in plants requires calcium oscillations that must be decoded to invoke downstream developmental programs. In animal systems, comparable calcium oscillations are decoded by calmodulin (CaM)-dependent protein kinases, but symbiotic signaling involves a calcium/CaM-dependent protein kinase (CCaMK) that is unique to plants. CCaMK differs from the animal CaM kinases by its dual ability to bind free calcium, via calcium binding EF-hand domains on the protein, or to bind calcium complexed with CaM, via a CaM binding domain. In this study, we dissect this dual regulation of CCaMK by calcium. We find that calcium binding to the EF-hand domains promotes autophosphorylation, which negatively regulates CCaMK by stabilizing the inactive state of the protein. By contrast, calcium-dependent CaM binding overrides the effects of autophosphorylation and activates the protein. The differential calcium binding affinities of the EF-hand domains compared with those of CaM suggest that CCaMK is maintained in the inactive state at basal calcium concentrations and is activated via CaM binding during calcium oscillations. This work provides a model for decoding calcium oscillations that uses differential calcium binding affinities to create a robust molecular switch that is responsive to calcium concentrations associated with both the basal state and with oscillations.
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Research of thermal sensor allocation and placement based on dual clustering for microprocessors.
Springerplus
PUBLISHED: 12-01-2013
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Dynamic thermal management techniques employ a set of on-chip thermal sensors to measure runtime thermal behavior of microprocessors so as to prevent the on-set of high temperatures. Therefore, effective analysis of thermal behavior and determination of the best allocation and placement of thermal sensors directly impact the effectiveness of the dynamic thermal management mechanisms. In this paper, we propose systematic and effective techniques for determining the fewest number of thermal sensors and the optimal locations based on dual clustering to provide a high fidelity thermal monitoring. Initially, we utilize the dual clustering algorithm to devise method that can reduce the number of sensors to a great extent while satisfying an expected accuracy. Then we identify an optimal physical location for each sensor such that the sensors attraction towards steep thermal gradient is maximized. Experimental results indicate the superiority of our techniques and confirm that our proposed methods are capable of creating a sensor distribution for a given microprocessor architecture using the number of thermal sensors of 2, 8, 15, 24, 35, depending on different expected hot spot temperature error accuracy of 5%, 4%, 3%, 2%, 1%, respectively.
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[Pro-apoptotic effects of luteolin on hepatoma HepG2 cells].
Zhejiang Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-30-2013
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To investigate the effect of luteolin on cell growth and apoptosis of HepG2 cells in vitro.
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Systematic review and meta-analysis of traditional Chinese medicine in the treatment of migraines.
Am. J. Chin. Med.
PUBLISHED: 10-15-2013
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Migraine is a chronic disorder characterized by recurrent moderate to severe headaches often in association with a number of autonomic nervous system symptoms. It is a common disease and incidence has increased yearly. Chinese medical treatments are popularly used in Asian countries, although they vary in effectiveness. In this study, we applied a systematic review method and combined meta-regression with meta-subgroup analysis to explore heterogeneity of clinical therapeutic efficacy upon meta-analysis of randomized controlled Chinese medical treatments for migraine. We also aimed to provide a more effective Chinese prescription and to advance the knowledge in evaluating validity of preventing or alleviating migraine symptoms with Chinese medical treatments. Twenty randomized migraine control trails, including 2246 patients, were collected from online databases: PubMed, MEDLINE, EMBASE, CENTRAL of Cochrane Library, CBM, integrated version of CMCI/CMCC, TCM online, CDFD, and CMFD from January 2000 to December 2011. The results showed that the major factors influencing therapeutic efficacy were either the specific medicine form of or its prescription type (p < 0.05). The use of TCM decoctions, especially those that condition the viscera, treat from the perspective of "wind", and target the Shaoyang gateway, could be the best migraine treatment in clinical TCM practice (RR > 1.30).
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Hypoxia induced multidrug resistance of laryngeal cancer cells via hypoxia-inducible factor-1?.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-1? (HIF- 1?).
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[Relationship between heroin spongiform leucoencephalopathy and respiratory chain complex I deficiency].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 09-27-2013
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To investigate the relationship between heroin spongiform leucoencephalopathy and respiratory chain complex I deficiency.
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Structural development of aleurone and its function in common wheat.
Mol. Biol. Rep.
PUBLISHED: 09-14-2013
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The wheat aleurone is formed from surface endosperm cells, and its developmental status reflects its biogenesis, structural characteristics, and physiological functions. In this report, wheat caryopses at different development stages were embedded in Spurrs low-viscosity embedding medium for observation of the development of aleurone cells (ACs) by light microscopy, scanning electron microscopy, and fluorescence microscopy, respectively. According to their structures and physiological characterization, the ACs development process was divided into five stages: endosperm cellulization, spherosome formation, aleurone grain formation, filling material proliferation, and maturation. Furthermore, ACs in different parts of the caryopsis formed differently. ACs near the vascular bundle developed earlier and formed transfer cells, but other ACs formed slowly and did not form transfer cells. ACs on the caryopsis backside were a regular square shape; however, ACs in the caryopsis abdomen were mainly irregular. There were also differences in development between wheat varieties. ACs were rectangular in hard wheat but square in soft wheat. ACs were larger and showed a greater degree of filling in hard compared to soft wheat. The storage materials in ACs were different compared to inner endosperm cells (IECs). The concentrations of minerals such as sodium, magnesium, silicon, phosphorus and potassium were higher in ACs than in IECs. ACs contained many aleurone grains and spherosomes, which store lipids and mineral nutrients, respectively. The cell nucleus did not disappear and the cells were still alive during aleurone maturation. However, IECs were dead and mainly contained amyloplast and protein bodies, which store starch and protein, respectively. Overall, the above results characterized major structural features of aleurone and revealed that the wheat aleurone has mainly four functions.
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Cheap and scalable synthesis of ?-Fe2O3 multi-shelled hollow spheres as high-performance anode materials for lithium ion batteries.
Chem. Commun. (Camb.)
PUBLISHED: 08-20-2013
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Delicate ?-Fe2O3 multi-shelled hollow spheres have been prepared by a simple and scalable spray drying method followed by annealing in air. The resulting material shows high specific capacity, good cycling stability, and excellent rate performance in lithium ion battery applications.
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[Research about the effect of exercise on the vascular endothelial cells AMPK activated in atherosclerotic rat].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 08-15-2013
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To study the molecular mechanism of exercise to improve cardiovascular health, and exploring the effect of different intensity exercise on AMP activated protein kinase (AMPK) protein expression and phosphorylation of vascular endothelial cells in rat.
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Efficient red organic electroluminescent devices by doping platinum(II) Schiff base emitter into two host materials with stepwise energy levels.
Opt Lett
PUBLISHED: 08-14-2013
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In this work, organic electroluminescent (EL) devices with double light-emitting layers (EMLs) having stepwise energy levels were designed to improve the EL performance of a red-light-emitting platinum(II) Schiff base complex. A series of devices with single or double EML(s) were fabricated and characterized. Compared with single-EML devices, double-EML devices showed improved EL efficiency and brightness, attributed to better balance in carriers. In addition, the stepwise distribution in energy levels of host materials is instrumental in broadening the recombination zone, thus delaying the roll-off of EL efficiency. The highest EL current efficiency and power efficiency of 17.36 cd/A and 14.73 lm/W, respectively, were achieved with the optimized double-EML devices. At high brightness of 1000 cd/m², EL efficiency as high as 8.89 cd/A was retained.
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Clinical trials of traditional Chinese medicine in the treatment of diabetic nephropathy-A systematic review based on a subgroup analysis.
J Ethnopharmacol
PUBLISHED: 07-26-2013
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The purpose of this study is to systematically evaluate the efficacy of traditional Chinese medicine (TCM) decoctions with different ingredients in the treatment of diabetic nephropathy (DN).
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Upregulation of glutamate transporter GLT-1 by mTOR-Akt-NF-?B cascade in astrocytic oxygen-glucose deprivation.
Glia
PUBLISHED: 07-24-2013
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Excessive extracellular glutamate leads to neuronal death in central nervous system. Excitatory glutamate transporter subtype 2 (GLT-1) carries bulk of glutamate reuptake in cerebral ischemia. Although GLT-1 expression fluctuates during the period of ischemia, little is known about its regulatory mechanism. Here we show an up-regulation of GLT-1 via mammalian target of rapamycin (mTOR)-Akt-nuclear factor-?B (NF-?B) signaling cascade in oxygen glucose deprivation (OGD). We found that brief rapamycin treatment significantly increased GLT-1 expression in cultured astrocytes. Rapamycin increased phosphorylation of raptor at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1 expression. This conclusion was further confirmed by raptor and rictor disruption experiments. Akt was activated by mTORC1 inhibition and required for GLT-1 expression because triciribine, a specific inhibitor of Akt, blocked the increase of GLT-1 expression. mTOR-Akt cascade then activated NF-?B and increased ?B-motif-binding phosphoprotein (KBBP) expression and GLT-1 transcription. We next demonstrated that mTOR-Akt-NF-?B cascade was activated in OGD and subsequently caused the upregulation of GLT-1. Supporting evidence included: (1) inhibition of Akt or NF-?B occluded OGD-induced GLT-1 upregulation; (2) Raptor knock-down plus OGD did not add to the increase of GLT-1 expression; (3) Intact mTORC2 was required for GLT-1 enhancement. In summary, our data first showed that mTOR-Akt-NF-?B cascade played critical roles to up-regulate GLT-1 in OGD. This signaling cascade may work to promote glutamate uptake in brain ischemia and neurodegenerative diseases.
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Oxidative stress and phthalate-induced down-regulation of steroidogenesis in MA-10 Leydig cells.
Reprod. Toxicol.
PUBLISHED: 07-15-2013
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Previous studies have shown that phthalate exposure can suppress steroidogenesis. However, the affected components of the steroidogenic pathway, and the mechanisms involved, remain uncertain. We show that incubating MA-10 Leydig cells with mono-(2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone (LH)-stimulated cAMP and progesterone productions. cAMP did not decrease in response to MEHP when the cells were incubated with cholera toxin or forskolin. Incubation of MEHP-treated cells with dibutyryl-cAMP, 22-hydroxycholesterol or pregnenolone inhibited the reductions in progesterone. Increased levels of reactive oxygen species (ROS) occurred in response to MEHP. In cells in which intracellular glutathione was depleted by buthionine sulfoximine pretreatment, the increases in ROS and decreases in progesterone in response to MEHP treatment were exacerbated. These results indicate that MEHP inhibits MA-10 Leydig cell steroidogenesis by targeting LH-stimulated cAMP production and cholesterol transport, and that a likely mechanism by which MEHP acts is through increased oxidative stress.
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MicroRNA-34a Targets Bcl-2 and Sensitizes Human Hepatocellular Carcinoma Cells to Sorafenib Treatment.
Technol. Cancer Res. Treat.
PUBLISHED: 07-11-2013
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MiR-34a, a direct target of p53, has been shown to target several molecules associated with the cell cycle and cell survival pathways, and its dysregulation is implicated in cancer drug resistance or sensitivity in several human cancers. However, the correlation between miR-34a expression and chemoresistance has not been explored in HCC. In this study, we confirmed that miR-34a was significantly down-regulated in HCC tissues and HCC cell lines by qRT-PCR. HCC tissues with lower miR-34a expression displayed higher expression of Bcl-2 protein than those with high expression of miR-34a; therefore, an inverse correlation is evident between the miR-34a level and Bcl-2 expression. Moreover, patients with lower miR-34a expression had significantly poorer overall survival. Bioinformatics and luciferase reporter assays revealed that miR-34a binds the 3-UTR of the Bcl-2 mRNA and represses its translation. Western blotting analysis and qRT-PCR confirmed that Bcl-2 is inhibited by miR-34a overexpression. Functional analyses indicated that the restoration of miR-34a reduced cell viability, promoted cell apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell lines by inhibiting Bcl-2 expression. This study is the first to demonstrate that miR-34a induces sensitivity to the anti-tumor effect of sorafenib in human HCC cells, suggesting a potential role of miR-34a in the treatment of HCC.
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Gender differences in prevalence and correlates of antisocial personality disorder among heroin dependent users in compulsory isolation treatment in China.
Addict Behav
PUBLISHED: 07-10-2013
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Little is known about gender difference in correlates of antisocial personality disorder (ASPD) among drug users.
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High levels of EphA3 expression are associated with high invasive capacity and poor overall survival in hepatocellular carcinoma.
Oncol. Rep.
PUBLISHED: 07-09-2013
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Although EphA3 expression has been associated with progression or prognosis in several types of tumors, the role of EphA3 in hepatocellular carcinoma (HCC) remains unknown. This study sought to investigate the clinicopathological and prognostic relevance of EphA3 expression in HCC as well as the underlying mechanisms responsible. EphA3 protein was mainly localized within the cytoplasm and at the cell membrane. High EphA3 expression was correlated with tumor size, tumor grade, metastasis, venous invasion and AJCC TNM stage (P<0.05), and patients with high levels of EphA3 expression were at a significantly increased risk for shortened survival time (P<0.05). In vitro, the downregulation of EphA3 expression decreased the invasive capacity of HCC cells via the regulation of VEGF. EphA3 may represent a novel candidate marker for patient prognosis as well a molecular target for HCC therapy.
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Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis.
EMBO J.
PUBLISHED: 07-09-2013
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Skeletal muscle differentiation is orchestrated by a network of transcription factors, epigenetic regulators, and non-coding RNAs. The transcription factor Yin Yang 1 (YY1) silences multiple target genes in myoblasts (MBs) by recruiting Ezh2 (Enhancer of Zeste Homologue2). To elucidate genome-wide YY1 binding in MBs, we performed chromatin immunoprecipitation (ChIP)-seq and found 1820 specific binding sites in MBs with a large portion residing in intergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to its known repressor function. No significant co-occupancy was found between YY1 and Ezh2, suggesting an additional Ezh2-independent function for YY1 in MBs. Further analysis of intergenic binding sites showed that YY1 potentially regulates dozens of large intergenic non-coding RNAs (lincRNAs), whose function in myogenesis is underexplored. We characterized a novel muscle-associated lincRNA (Yam-1) that is positively regulated by YY1. Yam-1 is downregulated upon differentiation and acts as an inhibitor of myogenesis. We demonstrated that Yam-1 functions through in cis regulation of miR-715, which in turn targets Wnt7b. Our findings not only provide the first genome-wide picture of YY1 association in muscle cells, but also uncover the functional role of lincRNA Yam-1.
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Delayed repair of facial nerve trauma: an experimental study in guinea pigs.
Acta Otolaryngol.
PUBLISHED: 06-18-2013
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The curative effect in the group where facial-facial anastomosis (FFA) was delayed for 7 days was similar to that in the immediate FFA group and had a better repair within 60 days.
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Establishment and characterization of a novel HPV-negative laryngeal squamous cell carcinoma cell line, FD-LSC-1, with missense and nonsense mutations of TP53 in the DNA-binding domain.
Cancer Lett.
PUBLISHED: 06-12-2013
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Laryngeal squamous cell carcinoma (LSCC) is a common malignancy in China; however, publically available LSCC cell lines are few and not established from Chinese populations. Hence, novel and well-characterized LSCC cell lines of Chinese origin are urgently needed to provide researchers with a comprehensive database for LSCC research. From 40 cases of LSCC, we established a novel cell line that was maintained for more than 100 passages in vitro and was found to have typical epithelial morphology and ultrastructure. In-depth characterization analysis revealed polyploidy in DNA content; a doubling time of some 24h; high tumorigenicity in immunodeficient mice; higher invasive potential and more sensitive to radiation and cisplatin compared with HeLa cell line; upregulated Ki67, Notch1, EGFR, and CK5 protein levels; negative infection of human papillomavirus (HPV) and mycoplasma; expression of head and neck squamous cell carcinoma (HNSCC) biomarkers; mutations of TP53 in exons 5 and 8; a near-triploid karyotype with complex structural aberrations; and dozens of dysregulated genes and miRNAs. Cell authentication testing by the American Type Culture Collection (ATCC) confirmed the human origin of this cell line. Our findings indicate that a novel and well-differentiated LSCC cell line recapitulating the primary tumors malignant characteristics is established and well characterized. It does not match any cell lines within the ATCC database and helps to elucidate the molecular pathogenesis of LSCC.
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Low-cost and large-scale synthesis of functional porous materials for phosphate removal with high performance.
Nanoscale
PUBLISHED: 06-03-2013
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A facile spray drying technique has been developed for large-scale and template-free production of nanoporous silica with controlled morphology, large pore size, and high pore volume, using commercially available fumed silica, Aerosil 200, as a sole precursor. This approach can be applied to the preparation of functional nanoporous materials, in this study, lanthanum oxide functionalised silica microspheres by introducing lanthanum nitrate in situ during the spray drying process and followed by a post-calcination process. The resultant lanthanum functionalised Aerosil microspheres manifest high phosphate adsorption capacity (up to 2.317 mmol g(-1)), fast kinetics, and excellent adsorption performance at a low phosphate concentration (1 mg L(-1)). In virtue of the easy and scalable synthesis method, low cost and high performances of the product, the materials we reported here are promising for water treatment. Our approach may be general and extended to the synthesis of other functional nanoporous materials with versatile applications.
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Characterizing dose-responses of catalase to nitrofurazone exposure in model ciliated protozoan Euplotes vannus for ecotoxicity assessment: Enzyme activity and mRNA expression.
Ecotoxicol. Environ. Saf.
PUBLISHED: 05-27-2013
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In environmental studies, some biological responses, known as biomarkers, have been used as a powerful bioassay tool for more than four decades. Disparity between enzyme activity and mRNA abundance leads to correlation equivocality, which makes the application of biomarkers for environmental risk assessment more complicated. This study investigates this disparity in the case of catalase when used as a biomarker for detecting ecotoxicity induced by antibiotics in aquatic ecosystems. In particular, dose-responses for catalase activity and mRNA expression abundance were investigated in Euplotes vannus which were exposed to graded doses of nitrofurazone for several discrete durations, and dose-response models were developed to characterize the dose-response dynamics. Significant differences were found in both catalase activity and mRNA expression abundance among the E. vannus treated with nitrofurazone. Catalase activity showed a hormetic-like effect in terms of dose-response, characterized by a biphasic relationship which was more clearly evident after a longer exposure period, while mRNA expression abundance increased linearly with the exposure duration. Additionally, the correlation between catalase activity and mRNA expression abundance reversed along with the duration of exposure to nitrofurazone. Taken together, our results demonstrate that catalase mRNA expression offers a more straightforward dose-response model than enzyme activity. Our findings suggest that both catalase enzyme activity and mRNA expression abundance can be used jointly as bioassay tools for detecting ecotoxicity induced by nitrofurazone in aquatic ecosystems.
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Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)?2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway.
Int. J. Oncol.
PUBLISHED: 04-21-2013
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and it carries a poor prognosis due to a high rate of recurrence or metastasis after surgery. Bmi-1 plays a significant role in the growth and metastasis of many solid tumours. However, the exact mechanisms underlying Bmi-1-mediated cell invasion and metastasis, especially in HCC, are not yet known. In the present study, we sought to evaluate the expression of Bmi-1 in HCC samples and its relationship with clinicopathological characteristics and prognostic value, we also investigated related mechanisms underlying Bmi-1-mediated cell invasion in HCC. Our results showed that Bmi-1 is upregulated in HCC tissues compared to matched non-cancer liver tissues; and its expression is positively associated with tumour size, metastasis, venous invasion and AJCC TNM stage, respectively; multivariate analysis showed that high expression of Bmi-1 was an independent prognostic factor for overall survival. In addition, the shRNA-mediated inhibition of Bmi-1 reduced the invasiveness of two HCC cell lines in vitro by upregulating phosphatase and the tensin homolog deleted on chromosome 10 (PTEN) expression, inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and downregulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 and vascular endothelial growth factor (VEGF). These data demonstrate that Bmi-1 plays a vital role in HCC invasion and that Bmi-1 is a potential therapeutic target for HCC.
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A comparison of glypican-3 with alpha-fetoprotein as a serum marker for hepatocellular carcinoma: a meta-analysis.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-09-2013
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Glypican-3(GPC3) has been reported as one of the most promising serum markers for hepatocellular carcinoma (HCC), while several studies have conflicting results for the diagnostic accuracy between GPC3 and alpha-fetoprotein (AFP).
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Percutaneous cryoablation for stage IV lung cancer: a retrospective analysis.
Cryobiology
PUBLISHED: 03-18-2013
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The aim of this study was to investigate the therapeutic effect of cryoablation treatment and palliative treatment in stage IV lung cancer. Fifty-four patients were enrolled into the study. Thirty-one patients received cryoablation treatment (including intra- and extrapulmonary tumors), and 23 patients had palliative treatment (no cryoablation). Both the safety of the procedure and overall survival (OS) for stage IV lung cancer were assessed during a 6.5 year follow-up period. The OS of patients in both groups and the effects of treatment timing and frequency were compared. The OS in the cryoablation group was significantly longer than in the palliative group (median OS: 14 months vs. 7 months, P = 0.0009). The OS of those who received delayed cryoablation treatment was longer than that observed for those who received timely treatment (median OS: 18.5 months vs. 10 months, P = 0.0485), but this was not observed in those who received palliative treatment (median OS: 7 months vs. 7.5 months, P = 0.9814). Multiple treatments played an important role in improving the OS of patients who received cryoablation treatment (median OS: 18 months vs. 14 months, P = 0.0376). There was a significant difference between cryoablation and palliative treatment, in terms of OS. In addition, multiple cryoablation treatments may have an advantage over single treatments.
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High CCR6/CCR7 expression and Foxp3+ Treg cell number are positively related to the progression of laryngeal squamous cell carcinoma.
Oncol. Rep.
PUBLISHED: 03-12-2013
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Chemokine receptors CCR6 and CCR7 have been reported to play important roles in T cell migration and organ-specific metastasis of various tumors. In the present study, we evaluated the expression and clinical significance of CCR6, CCR7, their ligands and CD4+CD25+Foxp3+ regulatory T cells in laryngeal squamous cell carcinoma (LSCC) and metastatic lymph nodes (LNs). The expression of CCR6, CCR7 and their ligands mRNA (CCL20, CCL19/CCL21) as well as the CCR6 and CCR7 proteins were detected by real-time RT-PCR and immunohistochemistry (IHC), respectively. Flow cytometry was used to investigate the percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs). Furthermore, a number of cytokines, including interleukin (IL)-2, IL-4, IL-10, IL-12p70, interferon (IFN)-? and transforming growth factor (TGF)-?1 were detected by ELISA. The results showed that CCR6 and CCR7 were expressed in tumors in situ, metastatic LNs and CD4+CD25+Foxp3+ Tregs. It was hypothesized that the expression profile of CCR6, CCR7 and the proliferation of CD4+CD25+Foxp3+ Tregs affected the process of LN metastasis in LSCC patients. Therefore, the increased percentage of the Foxp3+ Tregs and the upregulation of Foxp3 expression on CCR6+ Tregs in LSCC patients may have accounted for the downregulation of antitumor immunity in these patients, which could be valuable for assessment of prognosis in LSCC treatment.
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The influence of nitrogen on the development and accumulation of protein bodies in the developing endosperm of wheat caryopses.
Mol. Biol. Rep.
PUBLISHED: 03-11-2013
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The aim of the present work was to reveal the histological changes of protein bodies (PBs) in the developing wheat endosperm under nitrogen (N) treatment. For this purpose, the development and accumulation of PBs in the dorsal and ventral regions of wheat endosperm affected by N application at booting stage were investigated using light microscopy and Image-Pro Plus 6.0 software. The endosperm without N treatment contained many smaller PBs that were scattered in endosperm cells in an unordered pattern, whereas the endosperm with N treatment contained many larger PBs or aggregations that were concentrated in a certain region of endosperm cells. The amount and relative areas of PBs in wheat varieties cvs. Xumai 30 and Yangmai 13 were significantly increased by N application. However, the cultivars differed with the degree of response to N being cv. Xumai 30 > cv. Yangmai 13. These differences also varied with position in the endosperm in the order ventral > dorsal region. The initiation of PBs occurred 3 days earlier in N-treated endosperm than the control.
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MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma.
Int. J. Oncol.
PUBLISHED: 03-01-2013
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Due to invasion and intrahepatic metastasis, the prognosis for patients with hepatocellular carcinoma (HCC) is poor. However, the mechanisms underlying these processes of HCC remain unclear. Cancer stem cells may be involved in early systemic dissemination and metastasis formation and side population (SP) cells isolated from diverse cancer cells possess stem cell-like properties. However, the mechanisms involved in migration and invasion of cancer stem cells are not well understood. In this study, we identified and isolated populations of SP cells from HCC cell lines using flow cyto-metry. SP cells showed higher levels of migration and invasion capability. Higher expression of miR-21 was observed in SP cells. Silencing of miR-21 led to a reduction in the migration and invasion of these cells and overexpression of miR-21 can increase in cell migration and invasion. Overexpression of miR-21 did not cause degradation of PTEN or RECK or PDCD4 mRNA but drastically inhibited its protein expression. Consistent with these results, silencing miR-21 increased the levels of PTEN, RECK and PDCD4 protein, respectively. The role of silencing miR-21 was partially attenuated by silencing of PTEN or RECK or PDCD4 mRNA. The results of this study revealed the aberrant expression of miR-21 in SP cells and showed that miR-21 regulates the expression of multiple target proteins that are associated with tumor dissemination. MiR-21 is a pro-metastatic miRNA in SP cells and raises the possibility that therapy of HCC may be improved by pharmaceutical strategies directed towards miR-21.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.