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Find video protocols related to scientific articles indexed in Pubmed.
DoGSD: the dog and wolf genome SNP database.
Nucleic Acids Res.
PUBLISHED: 11-19-2014
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The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ?19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.
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RIP1-dependent Bid cleavage mediates TNF?-induced but Caspase-3-independent cell death in L929 fibroblastoma cells.
Apoptosis
PUBLISHED: 11-16-2014
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L929 fibroblastoma cells (L929-A) and L929 fibrosarcoma cells (L929-N) are different cell lines that are commonly used to study the cytotoxicity of tumor necrosis factor alpha (TNF?). TNF? has been reported to induce necrosis in both of these cell lines. However, comparing the TNF?-induced cell death in these two cell lines, we found that, unlike the L929-N cells that show typical RIP3-dependent necrosis, TNF?-induced cell death in L929-A cells is pan-caspase inhibitor Z-VAD-FMK (Z-VAD)-sensitive, which does not depend on RIP3. We also confirmed that the cell death signal in the L929-A cells was initiated through cytosol-preassembled ripoptosome and that the knockdown of either Caspase-8 or RIP1 protein blocked cell death. Compared with the L929-N cells, the L929-A cell line had lower levels of constitutive and inducible TNF? autocrine production, and the pan-caspase inhibitors Z-VAD or Q-VD did not kill the L929-A cells as they affect the L929-N cells. Moreover, the L929-A cells expressed less RIP3 protein than the L929-N cells; therefore, TNF? failed to induce RIP3-dependent necroptosis. In addition, the ripoptosome-mediated cell death signal was transduced to the mitochondria through Caspase-8-mediated and RIP1 kinase activity-dependent Bid cleavage. The RIP1 kinase inhibitor Necrostatin-1 (Nec-1) or Caspase-8 knockdown completely blocked Bid cleavage, and the knockdown of Bid or Bax/Bak prevented TNF?-induced cell death in the L929-A cells. Although the activation of Bax/Bak decreased the mitochondrial membrane potential, the levels of mitochondrial intermembrane space proteins, including cytochrome-c (cyt-C) and Smac, declined, and western blotting and immunofluorescence staining analysis did not determine whether these proteins were redistributed to the cytosol. In addition, the mitochondrial outer membrane protein Tom20 was also reduced, indicating that the reduced mitochondria proteins may be induced by the reduced mitochondria numbers. No efficient cyt-C release was observed; therefore, the limited activation and cleavage of downstream caspases, including Caspase-9, Caspase-7, Caspase-6 and Caspase-3, was insufficient to kill the cells. The Caspase-9, Caspase-6 and Caspase-3/7 inhibitors or Caspase-9 and -3 knockdown also failed to block cell death, and the overexpression of Bcl-2 also did not abrogate cell death. Moreover, the dead cells showed necrotic-like but not apoptotic characteristics under transmission electronmicroscopy, and these features were significantly different from mitochondrial apoptosis, indicating that the effector caspases were not the executioners of cell death. These new discoveries show that TNF?-induced cell death in L929-A cells is different than typical RIP3-dependent necrosis and Caspase-8/Caspase-3-mediated apoptosis. These results highlight that caution is necessary when using different L929 cells as a model to investigate TNF?-induced cell death.
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Variations in the Natural (15)N Abundance of Brassica chinensis Grown in Uncultivated Soil Affected by Different Nitrogen Fertilizers.
J. Agric. Food Chem.
PUBLISHED: 11-06-2014
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To further investigate the method of using ?(15)N as a marker for organic vegetable discrimination, the effects of different fertilizers on the ?(15)N in different growing stages of Brassica chinensis (B. chinensis) grown in uncultivated soil were investigated with a pot experiment. B. chinensis was planted with uncultivated soil and different fertilizer treatments and then harvested three times in three seasons consecutively. For the spring experiments in the years of 2011 and 2012, the ?(15)N value of B. chinensis, which increased due to organic manure application and decreased due to chemical fertilizer application, was significantly different (p < 0.05) with manure treatment and chemical treatment. The ?(15)N value of vegetables varied among three growing stages and ranged from +8.6‰ to +11.5‰ for the control, from +8.6‰ to +12.8‰ for the compost chicken manure treatment, from +2.8‰ to +7.7‰ for the chemical fertilizer urea treatment, and from +7.7‰ to +10.9‰ for the compost-chemical fertilizer treatment. However, the ?(15)N values observed in the autumn experiment of 2011 without any fertilizer application increased ranging from +13.4‰ to +15.4‰, + 11.2‰ to +17.7‰, +10.7‰ to +17.1‰, and +10.6‰ to +19.1‰, respectively, for the same treatments mentioned above. This result was not significantly different between manure treatment and chemical treatment. The ?(15)N values of soil obtained in the spring of 2011 during three growing stages were slightly affected by fertilizers and varied in the range of +1.6‰ to +2.5‰ for CK, +4.7‰ to +6.5‰ for compost treatment, +2.1‰ to +2.4‰ for chemical treatment, and +2.7‰ to +4.6‰ for chemical-compost treatment, respectively. High ?(15)N values of B. chinensis were observed in these experiments, which would be useful to supplement a ?(15)N database for discriminating organic vegetables. Although there was a significant difference between manure treatment and chemical treatment, it was still difficult to discriminate whether a labeled organic vegetable was really grown without chemical fertilizer just with a fixed high ?(15)N value, especially for the vegetables planted simultaneously with chemical and compost fertilizer.
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Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases.
Br. J. Pharmacol.
PUBLISHED: 10-21-2014
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Cardiovascular disease remains a major cause of disability and death worldwide. Autonomic imbalance, characterized by suppressed vagal (parasympathetic) activity and increased sympathetic activity, correlates with various pathological conditions including heart failure, arrhythmia, ischemia/reperfusion injury and hypertension. Conventionally, pharmacologic interventions have primarily targeted suppressing sympathetic over-activation such as ?-blockers treatment, while vagal modulation has always been neglected. Emerging evidence has documented the improvement of cardiac and vascular function mediated by vagal nerve. Many investigators have tried to explore the effective ways to enhance vagal tone and normalize autonomic nervous system. In the review, we attempt to give an overview of these therapeutic strategies including direct vagal activation (electrical vagal stimulation, acetylcholine administration and acetylcholine receptor activation), pharmacologic modulation (adenosine, cholinesterase inhibitors, statins) and exercise training, and provide valuable information for combination therapy, contributing to establishment of a comprehensive system on vagal modulation from the aspects of clinical application and lifestyle improvement. In addition, the mechanisms contributing to the benefits of enhancing vagal tone are diverse and have not yet been fully defined. We endeavor to outline the recent findings which advance our knowledge regarding the manifold favorable effects exerted by vagal activation: anti-inflammatory pathways, modulation of nitric oxide (NO) synthase and NO signaling, regulation of redox state, improvement of mitochondrial biogenesis and function and potential calcium regulation. This clear sketch may help to develop novel therapeutic strategies targeting enhancing vagal activity for the treatment of cardiovascular diseases.
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FPGA-based multi-channel fluorescence lifetime analysis of Fourier multiplexed frequency-sweeping lifetime imaging.
Opt Express
PUBLISHED: 10-17-2014
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We report a fast non-iterative lifetime data analysis method for the Fourier multiplexed frequency-sweeping confocal FLIM (Fm-FLIM) system [Opt. Express 22, 10221 (2014)]. The new method, named R-method, allows fast multi-channel lifetime image analysis in the system's FPGA data processing board. Experimental tests proved that the performance of the R-method is equivalent to that of single-exponential iterative fitting, and its sensitivity is well suited for time-lapse FLIM-FRET imaging of live cells, for example cyclic adenosine monophosphate (cAMP) level imaging with GFP-Epac-mCherry sensors. With the R-method and its FPGA implementation, multi-channel lifetime images can now be generated in real time on the multi-channel frequency-sweeping FLIM system, and live readout of FRET sensors can be performed during time-lapse imaging.
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[Comprehensive chemical pattern recognition of atractylodis rhizoma].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-04-2014
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A method of comprehensive chemical pattern recognition of Atractylodis Rhizoma was established by GC-MS fingerprint, principal component analysis, cluster analysis and discriminant analysis. A DB-wax column (0.25 mm x 60 m, 0.25 microm) with El ion source and 70 V electron multiplier were used for GC-MS analysis. Using principal component analysis, cluster analysis, and discriminant analysis, 15 common peaks of sample fingerprints for chemical pattern recognition research were analysed. The same results were obtained from the fingerprint, principal component analysis and cluster analysis, which could use to distinguish genuine Atractylodes lancea, ungenuine A. lancea and A. chinensis. Thus, this method could be used for the quality control and comprehensive evaluation of Atractylodis Rhizoma.
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[Risk factors of benign anastomostic strictures after esophagectomy with cervical reconstruction].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 10-03-2014
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To identify the risk factors of benign cervical anastomotic strictures after esophagectomy.
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Self-Grown Ni(OH)2 Layer on Bimodal Nanoporous AuNi Alloys for Enhanced Electrocatalytic Activity and Stability.
ACS Appl Mater Interfaces
PUBLISHED: 09-25-2014
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Au nanostructures as catalysts toward electrooxidation of small molecules generally suffer from ultralow surface adsorption capability and stability. Here, we report Ni(OH)2 layer decorated nanoporous (NP) AuNi alloys with a three-dimensional and bimodal porous architecture, which are facilely fabricated by a combination of chemical dealloying and in situ surface segregation, for the enhanced electrocatalytic performance in biosensors. As a result of the self-grown Ni(OH)2 on the AuNi alloys with a coherent interface, which not only enhances adsorption energy of Au and electron transfer of AuNi/Ni(OH)2 but also prohibits the surface diffusion of Au atoms, the NP composites are enlisted to exhibit significant enhancement in both electrocatalytic activity and stability toward glucose electrooxidation. The highly reliable glucose biosensing with exceptional reproducibility and selectivity as well as quick response makes it a promising candidate as electrode materials for the application in nonenzymatic glucose biosensors.
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[Chemical constituents from Euphorbia lunulata].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-24-2014
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The chemical constituents from Euphorbia lunulata was investigated in this paper. Fourteen compounds were isolated and purified by column chromatographies on silica gel and preparative HPLC. Their structures were identified by physiochemical properties and NMR data analysis as lupeol (1), euphol (2), cassipourol(3) , 24-methylenecycloartan-3beta-ol (4), 24-hydroperoxycycloart-25-en-3beta-ol (5), 25-hydroperoxycycloart-23-en-3beta-ol (6), betulin (7), uvaol (8), (23E) -25-methoxycycloart-23-en-3beta-ol (9), (23E) -cycloart-23,25-dien-3beta-ol (10), 24-methylenecycloartan-3beta, 28-diol (11), salicinolide (12), 2alpha, 3beta, 5alpha, 9alpha, 15beta-pentaacetoxy-11,12-epoxy-7beta, 8alpha-diisobutyryloxyjatropha-6 (17) -en-14-one (13) and 3beta, 5alpha, 15beta-triacetoxy-7beta-isobutyryloxy-9alpha-nicotinoyloxyjatropha-6 (17), 11(E)-dien-14-one (14). Among them, compounds 1-11 were isolated from E. lunulata for the first time.
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Multi-Fault Detection of Rolling Element Bearings under Harsh Working Condition Using IMF-Based Adaptive Envelope Order Analysis.
Sensors (Basel)
PUBLISHED: 09-19-2014
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When operating under harsh condition (e.g., time-varying speed and load, large shocks), the vibration signals of rolling element bearings are always manifested as low signal noise ratio, non-stationary statistical parameters, which cause difficulties for current diagnostic methods. As such, an IMF-based adaptive envelope order analysis (IMF-AEOA) is proposed for bearing fault detection under such conditions. This approach is established through combining the ensemble empirical mode decomposition (EEMD), envelope order tracking and fault sensitive analysis. In this scheme, EEMD provides an effective way to adaptively decompose the raw vibration signal into IMFs with different frequency bands. The envelope order tracking is further employed to transform the envelope of each IMF to angular domain to eliminate the spectral smearing induced by speed variation, which makes the bearing characteristic frequencies more clear and discernible in the envelope order spectrum. Finally, a fault sensitive matrix is established to select the optimal IMF containing the richest diagnostic information for final decision making. The effectiveness of IMF-AEOA is validated by simulated signal and experimental data from locomotive bearings. The result shows that IMF-AEOA could accurately identify both single and multiple faults of bearing even under time-varying rotating speed and large extraneous shocks.
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Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models.
Oncotarget
PUBLISHED: 09-17-2014
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The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.
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Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice.
Oncotarget
PUBLISHED: 09-13-2014
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Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.
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Producing more grain with lower environmental costs.
Nature
PUBLISHED: 09-03-2014
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Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs. Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.
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TLR4 signaling: A potential therapeutic target in ischemic coronary artery disease.
Int. Immunopharmacol.
PUBLISHED: 08-23-2014
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Atherosclerosis has been widely considered as a chronic inflammation process, which triggers a wide range of cardiovascular diseases such as ischemic coronary artery disease (CAD). Toll-like receptor 4 (TLR4), a primary receptor of the innate immune system, plays a pivotal role in the initiation and progression of atherosclerosis. Here we summarize recent progress on understanding the activation and function of TLR4 signaling in the initiation and development of CAD, with the focus on the role of TLR4 as a link between CAD and other inflammatory diseases. Furthermore, we list a variety of drugs which exert anti-atherosclerosis effects via targeting TLR4 signaling. Finally, we discuss the promise of TLR4 signaling as a therapeutic target for CAD.
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Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway.
Int. J. Oncol.
PUBLISHED: 08-21-2014
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Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.
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Optimal Cutoff Scores for Dementia and Mild Cognitive Impairment of the Montreal Cognitive Assessment among Elderly and Oldest-Old Chinese Population.
J. Alzheimers Dis.
PUBLISHED: 08-21-2014
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Background: All versions of the Montreal Cognitive Assessment (MoCA) lack population-based data of 80-plus individuals. The norms and cut-off scores for mild cognitive impairment (MCI) and dementia of the MoCA are different among five Chinese versions. Objective: To provide the cut-off scores in detecting MCI and dementia of the Peking Medical Union College Hospital version of the MoCA (MoCA-P). Methods: In a cross-sectional survey, Chinese veterans aged ?60 years completed the MoCA-P and the Mini-Mental State Examination (MMSE). Results: Among 7,445 elderly veterans, 5,085 (68.30%) were aged ?80 years old, 2,621 (35.20%) had 6 years of education or less, 6,847 (91.97%) were male, and 2,311 (31.04%) and 984 (13.22%) veterans were diagnosed as having MCI and dementia, respectively. Adding two points and one point to the MoCA scores for the primary and middle school groups, respectively, can fully adjust for the notable impact of education but cannot compensate for the effect of age. In the three age groups (60-79, 80-89, and ?90 years old), the optimal MoCA-P cut-off scores for detecting MCI were ?25, ?24, and ?23, respectively, and for detecting dementia were ?24, ?21, and ?19, respectively, which demonstrated relatively high sensitivities and specificities. The areas under the curves for the MoCA-P for detecting MCI and dementia (0.937 and 0.908, respectively) were greater than those for the MMSE (0.848 and 0.892, respectively). Conclusion: Compared with the MMSE, the MoCA-P is significantly better for detecting MCI in the elderly, particularly in the oldest old population, and it also displays more effectiveness in detecting dementia.
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Clinical applications of the indirect immunofluorescence assay for detection of anti-cell membrane-associated DNA antibodies in Juvenile Systemic Lupus Erythematosus.
Pediatr. Res.
PUBLISHED: 08-15-2014
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BackgroundJuvenile-onset systemic lupus erythematosus (JSLE) has a higher mortality risk compared to adult-onset SLE. We compared the diagnostic value of anti-cmDNA antibodies with that of anti-nucleosome antibodies (AnuA), anti-Sm antibodies and anti-dsDNA antibodies and human B lymphocyte Raji cells with that of human promyelocytic leukemia HL60 cells as substrates in an indirect immunofluorescence assay to detect anti-cmDNA antibodies in JSLE patients.MethodsWe recruited 92 JSLE patients and 71 patients with other rheumatic diseases. Anti-cmDNA antibodies and ANA were detected in patient sera using indirect immunofluorescence assays. Anti-dsDNA antibodies were detected by combining ELISA and indirect immunofluorescence. Anti-Sm antibodies were detected by double immunodiffusion assay and immunoblotting, while anti-nucleosome antibodies (AnuA) were detected by ELISA.ResultsJSLE group had a significantly higher percentage of patients positive for anti-cmDNA compared to patients with other rheumatoid diseases. Using one antibody for diagnosis, anti-cm DNA antibodies has highest accuracy as 84.0%, using 2 antibodies, the combination of anti-cm DNA and anti-dsDNA antibodies has 90.8 % accuracy. Raji cells used as substrate demonstrated a stronger intensity of fluorescent patterns compared to HL60 cells.ConclusionThe high sensitivity, specificity and accuracy of detection of anti-cmDNA antibodies make it a valuable diagnostic tool for JSLE.Pediatric Research (2014); doi:10.1038/pr.2014.182.
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Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections.
Immunol. Invest.
PUBLISHED: 08-02-2014
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Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?
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Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma.
Neuro-oncology
PUBLISHED: 07-24-2014
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3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed.
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In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-Duramycin.
Nucl. Med. Biol.
PUBLISHED: 07-21-2014
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(99m)Tc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury.
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Ethynylflavones, Highly Potent, and Selective Inhibitors of Cytochrome P450 1A1.
Chem. Res. Toxicol.
PUBLISHED: 07-18-2014
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The flavone backbone is a well-known pharmacophore present in a number of substrates and inhibitors of various P450 enzymes. In order to find highly potent and novel P450 family I enzyme inhibitors, an acetylene group was incorporated into six different positions of flavone. The introduction of an acetylene group at certain locations of the flavone backbone lead to time-dependent inhibitors of P450 1A1. 3'-Ethynylflavone, 4'-ethynylflavone, 6-ethynylflavone, and 7-ethynylflavone (KI values of 0.035-0.056 ?M) show strong time-dependent inhibition of P450 1A1, while 5-ethynylflavone (KI value of 0.51 ?M) is a moderate time-dependent inhibitor of this enzyme. Meanwhile, 4'-ethynylflavone and 6-ethynylflavone are highly selective inhibitors toward this enzyme. Especially, 6-ethynylflavone possesses a Ki value of 0.035 ?M for P450 1A1 177- and 15-fold lower than those for P450s 1A2 and 1B1, respectively. The docking postures observed in the computational simulations show that the orientation of the acetylene group determines its capability to react with P450s 1A1 and 1A2. Meanwhile, conformational analysis indicates that the shape of an inhibitor determines its inhibitory selectivity toward these enzymes.
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Back analysis of geomechanical parameters in underground engineering using artificial bee colony.
ScientificWorldJournal
PUBLISHED: 07-17-2014
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Accurate geomechanical parameters are critical in tunneling excavation, design, and supporting. In this paper, a displacements back analysis based on artificial bee colony (ABC) algorithm is proposed to identify geomechanical parameters from monitored displacements. ABC was used as global optimal algorithm to search the unknown geomechanical parameters for the problem with analytical solution. To the problem without analytical solution, optimal back analysis is time-consuming, and least square support vector machine (LSSVM) was used to build the relationship between unknown geomechanical parameters and displacement and improve the efficiency of back analysis. The proposed method was applied to a tunnel with analytical solution and a tunnel without analytical solution. The results show the proposed method is feasible.
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Phase I trial of hepatic arterial infusion (HAI) of floxuridine with modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable liver metastases from colorectal cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 07-16-2014
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To determine the maximum tolerated dose (MTD) and preliminary efficacy of concurrent hepatic arterial infusion (HAI) of floxuridine (FUDR) and systemic modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable hepatic metastases from colorectal cancer.
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A modular designed copolymer with anti-thrombotic activity and imaging capability.
Chem. Commun. (Camb.)
PUBLISHED: 07-12-2014
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Through a modular ROMP (ring-opening metathesis polymerization) strategy, a random copolymer with anti-thrombotic activity and imaging capability has been constructed from RGD, rhodamine B and PEG modified norbornene monomers. As we expected, these tri-component polynorbornenes exhibit significant enhancement in anti-thrombotic efficacy and bioavailability in vivo.
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Scrotal sparganosis mimicking scrotal teratoma in an infant: a case report and literature review.
Korean J. Parasitol.
PUBLISHED: 07-05-2014
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Sparganosis is an infection with a parasitic tapeworm larva that occurs by eating infected foods or drinking contaminated water. The larvae can migrate to a tissue or muscle in the chest, abdominal wall, extremities, eyes, brain, urinary tract, pleura, pericardium, spinal canal, or scrotum. Herein, we report a 5-month old infant with scrotal sparganosis who was initially suspected to have a scrotal inflammatory mass with a history of applying raw frog meat into the umbilicus. Preoperative ultrasound examinations and computed tomography (CT) scanning misdiagnosed the mass as a scrotal teratoma. The scrotal mass was surgically removed, and the histopathology proved it to be scrotal sparganosis. This case displays the youngest patient ever reported with scrotal sparganosis, and the first description of CT characteristics of scrotal sparganosis. A detailed medical history is necessary for patients with scrotal masses suspected of sparganosis. In addition, ultrasound and CT examinations are helpful to rule out other causes of a scrotal mass.
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Polarization-insensitive resonances with high quality-factors in meta-molecule metamaterials.
Opt Express
PUBLISHED: 07-01-2014
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Achieving narrow resonance is an area of interest within the field of metamaterials. However, only a few studies have investigated the polarization-insensitive resonances. A general principle for improving quality Q-factor of a sharp resonance is still unclear. In this work, we proposed a kind of planar meta-molecule metamaterials, which can exhibit polarization-insensitive resonance with high Q-factor. The proposed structures have a unit cell consisting of four arrayed ring resonant elements with two different sizes. Moreover, the investigation on surface current and two referential simulated structures confirm a principle for improving Q-factor.
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Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo.
Oncol. Rep.
PUBLISHED: 06-29-2014
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In breast cancer, metastasis is the main reason for patient mortality. In the present study, we used breast cancer MDA-MB-231 cells and a mouse xenograft model to demonstrate the effect of emodin on the migration, invasion and metastasis of human breast cancer MDA-MB-231 cells and the related mechanisms. In vitro, wound healing and Transwell assays showed that emodin dose-dependently inhibited the migration and invasion of MDA-MB-231 cells. Enzyme-linked immunosorbent assay (ELISA) showed that emodin decreased the secretion of MMP-2 and MMP-9. Western blot analysis showed that emodin downregulated the expression levels of MMP-2, MMP-9, uPA and uPAR as well as p38 inhibitor SB203580 and ERK inhibitor PD980559, even though TIMP-1 and TIMP-2 were not obviously changed in the MDA-MB-231 cells. Furthermore, emodin inhibited the activity of p38 and ERK1/2 in the MDA-MB-231 cells. In vivo, emodin inhibited lung metastasis in mice bearing the breast cancer MDA-MB-231 xenografts with no obvious changes in body weight, liver and kidney functions. These results indicated that emodin inhibited the lung metastasis of human breast cancer in a mouse xenograft model, and inhibited the invasion of MDA-MB-231 cells associated with the downregulation of MMP-2, MMP-9, uPA and uPAR expression as well as decreased activity of p38 and ERK.
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Eicosapentaenoic acid promotes thermogenic and fatty acid storage capacity in mouse subcutaneous adipocytes.
Biochem. Biophys. Res. Commun.
PUBLISHED: 06-27-2014
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In this study, we determined if eicosapentaenoic acid (EPA) promotes beneficial metabolic activities of subcutaneous adipocytes. Stromal-vascular (SV) cells were isolated from inguinal adipose tissue of C57BL/6 mice and induced to differentiate into adipocytes. EPA effect on thermogenic and mitochondrial gene expression and oxidative metabolism were assessed in inguinal adipocytes. When added to SV cell cultures during 8 day differentiation, EPA significantly increased the expression of thermogenic genes UCP1-3, CIDEA and VEGF?. Moreover, EPA increased mitochondrial DNA content and the expression of genes involved in mitochondrial biogenesis including PGC1?, Nrf1 and COXiv. However, this effect was not perceived when EPA was added to mature inguinal adipocytes for 24h, suggesting that EPA exerts its browning effect via recruiting brite adipocytes. Consistently, long-term EPA treatment also upregulated AMPK? phosphorylation and CPT1 expression and increased glucose uptake and GLUT4 mRNA expression, suggesting improved mitochondrial oxidation. Additionally, EPA-treated adipocytes had enlarged lipid droplets and increased expression of triglyceride synthesis genes GPAT1 and GPAT3, while significantly decreased glycerol release and down-regulation of HSL and ATGL gene expression. We conclude that EPA enhances energy dissipation capacity by recruiting brite adipocytes to stimulate oxidative metabolism and reduces fatty acid release by facilitating fatty acid storage in subcutaneous adipocytes.
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Methods for the development of tumor-targeting bacteria.
Expert Opin Drug Discov
PUBLISHED: 06-21-2014
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For at least two centuries, there have been reports that cancer patients infected with various bacteria had what appeared to be spontaneous remission. In the late nineteenth and early twentieth centuries, W.B. Coley, of what is now the Memorial Sloan-Kettering Cancer Center, pioneered bacterial therapy of cancer in the clinic with considerable success. After Coley died in 1936, bacterial therapy of cancer started to go out of favor. In the current twenty-first century, there is great resurgent interest in developing bacterial therapy for treating cancer using either obligate or facultative anaerobic bacteria. There is also controversy about which bacteria are optimum for cancer treatment and whether bacteria should be used as tumor-targeting vectors, immune stimulators, or for direct tumor killing.
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Ultra-fast liquid chromatography with tandem mass spectrometry determination of ochratoxin A in traditional Chinese medicines based on vortex-assisted solid-liquid microextraction and aptamer-affinity column clean-up.
J Sep Sci
PUBLISHED: 06-13-2014
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A rapid, selective, and sensitive ultra-fast liquid chromatography with tandem mass spectrometry method was developed for the determination of ochratoxin A in traditional Chinese medicines based on vortex-assisted solid-liquid microextraction and aptamer-affinity column clean-up. Through optimizing the sample pretreatment procedures and chromatographic conditions, good linearity (r(2) ? 0.9993), low limit of detection (0.5-0.8 ?g/kg), and satisfactory recovery (83.54-94.44%) expressed the good reliability and applicability of the established method in various traditional Chinese medicines. Moreover, the aptamer-affinity column, prepared in-house, showed an excellent feasibility owing to its specific identification of ochratoxin A in various kinds of selected traditional Chinese medicines. The maximum adsorption amount and applicability value were 188.96 ± 10.56 ng and 72.3%, respectively. The matrix effects were effectively eliminated, especially for m/z 404.2?358.0 of ochratoxin A. The application of the developed method for screening the natural contamination levels of ochratoxin A in 25 random traditional Chinese medicines on the market in China indicated that only eight samples were contaminated with low levels below the legal limit (5.0 ?g/kg) set by the European Union. This study provided a preferred choice for the rapid and accurate monitoring of ochratoxin A in complex matrices.
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DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype.
J. Autoimmun.
PUBLISHED: 06-12-2014
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Systemic lupus erythematosus (SLE) is an autoimmune disease well known for its clinical heterogeneity, and its etiology secondary to a cross-talk involving genetic predisposition and environmental stimuli. Although genome-wide analysis has contributed greatly to our understanding of the genetic basis of SLE, there is increasing evidence for a role of epigenetics. Indeed, recent data have demonstrated that in patients with SLE, there are striking alterations of DNA methylation, histone modifications, and deregulated microRNA expression, the sum of which contribute to over-expression of select autoimmune-related genes and loss of tolerance. To address this issue at the level of clinical phenotype, we performed DNA methylation, mRNA and microRNA expression screening using high-throughput sequencing of purified CD4+ T cells from patients with SLE, compared to age and sex matched controls. In particular, we studied 42 patients with SLE and divided this group into three clinical phenotypes: a) the presence of skin lesions without signs of systemic pathology; b) skin lesions but also chronic renal pathology; and c) skin lesions, chronic renal pathology and polyarticular disease. Interestingly, and as expected, sequencing data revealed changes in DNA methylation in SLE compared to controls. However, and more importantly, although there were common methylation changes found in all groups of SLE compared to controls, there was specific DNA methylation changes that correlated with clinical phenotype. These included changes in the novel key target genes NLRP2, CD300LB and S1PR3, as well as changes in the critical pathways, including the adherens junction and leukocyte transendothelial migration. We also noted that a significant proportion of genes undergoing DNA methylation changes were inversely correlated with gene expression and that miRNA screening revealed the existence of subsets with changes in expression. Integrated analysis of this data highlights specific sets of miRNAs controlled by DNA methylation, and genes that are altered by methylation and targeted by miRNAs. In conclusion, our findings suggest select epigenetic mechanisms that contribute to clinical phenotypes and further shed light on a new venue for basic SLE research.
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WNT16B from ovarian fibroblasts induces differentiation of regulatory T cells through ?-catenin signal in dendritic cells.
Int J Mol Sci
PUBLISHED: 05-16-2014
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Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play growth-related roles in previous studies. In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation. We also demonstrated that fibroblast-derived WNT16B could result in accumulation of ?-catenin in dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth factor beta (TGF-?), which contributed to the differentiation of regulatory T cells in a co-culture environment. These results shed light on the roles of WNT16B in immune regulation, especially in regard to cancer treatment.
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HNRNPAB induces epithelial-mesenchymal transition and promotes metastasis of hepatocellular carcinoma by transcriptionally activating SNAIL.
Cancer Res.
PUBLISHED: 03-17-2014
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Expression of heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) has been reported to be dysregulated in tumors, but its specific contributions to tumor formation and progression are not fully understood. Here, we demonstrate that HNRNPAB is overexpressed in highly metastatic cells and tumor tissues from patients with hepatocellular carcinoma (HCC) with recurrence. We found that HNRNPAB overexpression promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. RNA interference-mediated silencing of the EMT factor SNAIL attenuated HNRNPAB-enhanced cell invasion in vitro and lung metastasis in vivo. Mechanistically, HNRNPAB acted to transactivate SNAIL1 transcription, which in turn inhibited transcription of the pivotal SNAIL target gene E-cadherin. Overexpression of HNRNPAB in HCC samples correlated with higher SNAIL levels, shorter overall survival, and higher tumor recurrence. HNRNPAB overexpression, alone or in combination with SNAIL, was found to be a significant independent risk factor for recurrence and survival after curative resection. In conclusion, our findings define HNRNPAB as an activator of EMT and metastasis in HCC that predicts poor clinical outcomes.
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Synthesis of potassium-modified graphitic carbon nitride with high photocatalytic activity for hydrogen evolution.
ChemSusChem
PUBLISHED: 03-14-2014
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Potassium-modified graphitic carbon nitride (K-g-C3N4) nanosheets are synthesized by a facile KCl-template method that holds the advantage of easy removal of residual template. A combination of XRD, X-ray photoelectron spectroscopy, and inductively coupled plasma analyses are utilized to characterize the obtained resultant K-g-C3N4 architectures, which are composed of nanosheets of variable thickness (<10?nm). Photocatalytic hydrogen evolution experiments under visible light irradiation showed that K-g-C3N4 nanosheets have high photocatalytic activities (up to about thirteen times higher than that of pure g-C3 N4 ) as well as good stability (no reduction in activity within 16?h); both features emanate from their unique structural characteristics. These results illustrate the viability of this methodology for the facile synthesis of efficient heterogeneous photocatalysts for potential commercial applications.
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Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways.
J. Pathol.
PUBLISHED: 02-17-2014
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Calpain small subunit 1 (Capn4) has been identified as a major gene that promotes metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which Capn4 promotes progression of HCC is not understood. In this study, we found that Capn4 expression was increased in highly metastatic HCC cell lines and in tumour tissue from HCC patients compared to healthy patient tissue. Over-expression of Capn4 in HCC cells enhanced tumour cell growth in vitro and increased invasiveness, tumourigenicity and lung metastasis in vivo. Protein microarray analyses showed that expression of multiple proteins was regulated by Capn4. Interestingly, Capn4 was found to physically associate with FAK and promoted hyperactivity of the FAK-Src signalling pathway via increased phosphorylation of specific tyrosine residues of FAK, Src and p130Cas. Knock-down of Capn4 expression suppressed the malignant behaviour of HCC cells and inhibited the FAK-Src signalling pathway. Furthermore, Capn4-mediated invasion and metastasis of HCC cells required up-regulation of matrix metalloproteinase-2 (MMP2) through activation of this signalling pathway. Our clinical data revealed that Capn4 expression correlated well with the levels of phospho-FAK, and over-expression of both Capn4 and phospho-FAK correlates with the poorest survival outcomes in HCC. In conclusion, our data showed that Capn4 can contribute to HCC growth and metastasis via activation of the FAK-Src signalling pathway and MMP2. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Synthesis and electrospinning carboxymethyl cellulose lithium (CMC-Li) modified 9,10-anthraquinone (AQ) high-rate lithium-ion battery.
Carbohydr Polym
PUBLISHED: 02-11-2014
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New cellulose derivative CMC-Li was synthesized, and nanometer CMC-Li fiber was applied to lithium-ion battery and coated with AQ by electrospinning. Under the protection of inert gas, modified AQ/carbon nanofibers (CNF)/Li nanometer composite material was obtained by carbonization in 280 °C as lithium battery anode materials for the first time. The morphologies and structures performance of materials were characterized by using IR, (1)H NMR, SEM, CV and EIS, respectively. Specific capacity was increased from 197 to 226.4 mAhg(-1) after modification for the first discharge at the rate of 2C. Irreversible reduction reaction peaks of modified material appeared between 1.5 and 1.7 V and the lowest oxidation reduction peak of the difference were 0.42 V, the polarization was weaker. Performance of cell with CMC-Li with the high degree of substitution (DS) was superior to that with low DS. Cellulose materials were applied to lithium battery to improve battery performance by electrospinning.
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Elevated pretreatment serum globulin albumin ratio predicts poor prognosis for advanced non-small cell lung cancer patients.
J Thorac Dis
PUBLISHED: 01-19-2014
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The aim of the present study was to explore the association between the pretreatment globulin albumin ratio (GAR) and the survival of advanced non-small cell lung cancer (NSCLC) patients.
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Catalytic conversion of biomass pyrolysis-derived compounds with chemical liquid deposition (CLD) modified ZSM-5.
Bioresour. Technol.
PUBLISHED: 01-14-2014
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Chemical liquid deposition (CLD) with KH550, TEOS and methyl silicone oil as the modifiers was used to modify ZSM-5 and deposit its external acid sites. The characteristics of modified catalysts were tested by catalytic conversion of biomass pyrolysis-derived compounds. The effects of different modifying conditions (deposited amount, temperature, and time) on the product yields and selectivities were investigated. The results show KH550 modified ZSM-5 (deposited amount of 4%, temperature of 20°C and time of 6h) produced the maximum yields of aromatics (24.5%) and olefins (16.5%), which are much higher than that obtained with original ZSM-5 catalyst (18.8% aromatics and 9.8% olefins). The coke yield decreased from 44.1% with original ZSM-5 to 26.7% with KH550 modified ZSM-5. The selectivities of low-molecule-weight hydrocarbons (ethylene and benzene) decreased, while that of higher molecule-weight hydrocarbons (propylene, butylene, toluene, and naphthalene) increased comparing with original ZSM-5.
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Celastrol Stimulates Hypoxia-Inducible Factor-1 Activity in Tumor Cells by Initiating the ROS/Akt/p70S6K Signaling Pathway and Enhancing Hypoxia-Inducible Factor-1? Protein Synthesis.
PLoS ONE
PUBLISHED: 01-01-2014
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Celastrol, a tripterine derived from the traditional Chinese medicine plant Tripterygium wilfordii Hook F. ("Thunder of God Vine"), has been reported to have multiple effects, such as anti-inflammation, suppression of tumor angiogenesis, inhibition of tumor growth, induction of apoptosis and protection of cells against human neurodegenerative diseases. However, the mechanisms that underlie these functions are not well defined. In this study, we reported for the first time that Celastrol could induce HIF-1? protein accumulation in multiple cancer cell lines in an oxygen-independent manner and that the enhanced HIF-1? protein entered the nucleus and promoted the transcription of the HIF-1 target genes VEGF and Glut-1. Celastrol did not influence HIF-1? transcription. Instead, Celastrol induced the accumulation of the HIF-1? protein by inducing ROS and activating Akt/p70S6K signaling to promote HIF-1? translation. In addition, we found that the activation of Akt by Celastrol was transient. With increased exposure time, inhibition of Hsp90 chaperone function by Celastrol led to the subsequent depletion of the Akt protein and thus to the suppression of Akt activity. Moreover, in HepG2 cells, the accumulation of HIF-1? increased the expression of BNIP3, which induced autophagy. However, HIF-1? and BNIP3 did not influence the cytotoxicity of Celastrol because the main mechanism by which Celastrol kills cancer cells is through stimulating ROS-mediated JNK activation and inducing apoptosis. Furthermore, our data showed that the dose required for Celastrol to induce HIF-1? protein accumulation and enhance HIF-1? transcriptional activation was below its cytotoxic threshold. A cytotoxic dose of Celastrol for cancer cells did not display cytotoxicity in LO2 normal human liver cells, which indicated that the novel functions of Celastrol in regulating HIF-1 signaling and inducing autophagy might be used in new applications, such as in anti-inflammation and protection of cells against human neurodegenerative diseases. Future studies regarding these applications are required.
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Comparison of Efficacy and Toxicity of Traditional Chinese Medicine (TCM) Herbal Mixture LQ and Conventional Chemotherapy on Lung Cancer Metastasis and Survival in Mouse Models.
PLoS ONE
PUBLISHED: 01-01-2014
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Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM) compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX) and cyclophosphamide (CTX). LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer.
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Cystic lymphangioma of adrenal gland: a clinicopathological study of 3 cases and review of literature.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Cystic lymphangioma of the adrenal gland is a rare and benign lesion, most often found incidentally during abdominal imaging studies, abdominal surgery or at autopsy. We aimed to retrospectively review all adrenal lymphangioma cases at our hospital, further document their lymphatic origin by immunohistochemical staining and discuss the differential diagnosis with other cystic adrenal gland lesions. A total of 3 adrenal lymphangioma cases were identified. All three patients were men and adults at time of diagnosis aged 41 years, 43 years, and 66 years, respectively. All were incidentally identified during investigating for unrelated reasons, two of which were discovered by routine radiologic check-up while the last one was found during imaging detection of ureteral cancer. The average size of an adrenal lymphangioma lesion was 3.2 cm (range, 2.5-4.6 cm). Histologically, all three cases showed a typical multicystic architecture with dilated spaces lined by flattened, bland, simple lining. The cystic spaces occasionally contained proteinaceous material but lacked red blood cell content. On immunohistochemical stains, D2-40 cytoplasmic staining was positive in all three lesions, whereas AE1/AE3 was negative, thus, confirming their lymphatic nature.
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Long intergenic non-coding RNAs (LincRNAs) identified by RNA-seq in breast cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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In an attempt to find the correlation of aberrant expression of long intergenic noncoding RNAs (lincRNAs) with cancer, twenty-five samples of breast cancer tissue and respective adjacent normal tissue were studied for the expression of lincRNAs by RNA-seq. Among the 538 lincRNAs studied, 124 lincRNAs were exclusively expressed in cancer adjacent tissues and 62 lincRNAs were exclusively expressed in the cancer tissues. Furthermore, the expression of 134 lincRNAs was higher while 272 lower in breast cancer tissue compared with adjacent tissue. The expression of four selected lincRNAs (BC2, BC4, BC5, and BC8) was validated by semi-quantitative and real-time PCR. It was revealed that expression of lincRNA-BC5 was positively correlated with patients' age, pathological stage, and progesterone receptor concentration, while lincRNA-BC8 was negatively correlated with progesterone receptor expression. Higher expression of lincRNA-BC4 was seen in advanced breast cancer grade. LincRNA-BC2 showed no specific changes in the pathological features studied. Interactions between selected lincRNAs and breast cancer associated proteins were highly suggested by RPIseq based on the specific secondary structure. The results demonstrated that this group of lincRNAs was aberrantly expressed in breast cancer. They might play important roles in the function of oncogenes or tumor suppressors affecting the development and progression of breast cancer.
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Membrane phospholipid redistribution in cancer micro-particles and implications in the recruitment of cationic protein factors.
J Extracell Vesicles
PUBLISHED: 01-01-2014
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Cancer cell-derived micro-particles (MPs) play important regulatory roles on cellular and system levels. These activities are attributed in part to protein factors carried by MPs. However, recruitment strategies for sequestering certain protein factors in MPs are poorly understood. In the current study, using exogenous and endogenously expressed phospholipid-binding probes, we investigated the distribution of membrane phospholipids in MPs as a potential mechanism for electrostatically enriching cationic protein factors in MPs. We detected a significant level of externalised phosphatidylethanolamine (PE) at the outer surface of MPs. This was accompanied, in the inner leaflet of the MP membrane, by a greater density of negatively charged phospholipids, particularly phosphatidylserine (PS). The local enrichment of PS in the inner surface of MPs was correlated with an elevated presence of small GTPases in a polybasic region (PBR)-dependent fashion. By employing a series of RhoA derivatives, including constitutively active and RhoA derivatives lacking a PBR, we could demonstrate that the congregation of RhoA in MPs was dependent on the presence of the PBR. A chimer with the fusion of PBR sequence alone to GFP significantly enhanced GFP localisation in MPs, indicative of a positive contribution of electrostatic interactions in RhoA recruitment to MPs. Using in silico thermodynamic simulations, we characterised the electrostatic interactions between PBR and anionic lipid membrane surface. In summary, the redistribution of membrane phospholipids in MPs has an impact on the local ionic density, and is likely a contributing factor in the electrostatic recruitment of membrane-associated proteins to MPs in a PBR-dependent fashion.
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Identification and differential expression of microRNAs in ovaries of laying and Broody geese (Anser cygnoides) by Solexa sequencing.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent functional studies have demonstrated that the microRNAs (miRNAs) play critical roles in ovarian gonadal development, steroidogenesis, apoptosis, and ovulation in mammals. However, little is known about the involvement of miRNAs in the ovarian function of fowl. The goose (Anas cygnoides) is a commercially important food that is cultivated widely in China but the goose industry has been hampered by high broodiness and poor egg laying performance, which are influenced by ovarian function.
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Giant circular polarization conversion in layer-by-layer nonchiral metamaterial.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 12-11-2013
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We studied numerically the transmission properties of a kind of layer-by-layer nonchiral metamaterial. Simulation results show that under certain off-normal incidence, giant circular polarization conversion occurs for both the right and left circularly polarized waves with a roughly 1 GHz operation band. Meanwhile, the copolarization transmissions are almost suppressed to zero, leading to the high purity circular polarization transformation. This phenomenon of giant circular polarization conversion is assumed to suffer from the strong magnetic response, which is illustrated by the surface current distributions of the structure. Compared with chiral structures, this nonchiral structure is easier to design and fabricate and is expected to be used as a promising circular polarization transformer.
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Transmission resonances in a metal film with arrays of asymmetry cross-shaped apertures.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 12-11-2013
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We studied numerically the transmission properties of the periodic array of asymmetric cross-shaped apertures in an Ag film. The relative positions of the two orthogonally oriented rectangular apertures are varied, rather than their length or width. Each transmission peak of the original symmetric cross-shaped apertures will split into two peaks in the case of the asymmetric cross-shaped apertures when the electric field is perpendicular to the long axis of the unchanged rectangular aperture. The wavelength of the shift peak has a linear relation with the asymmetry. This resonance response mainly results from the excitation of the trapped mode provided by the structural symmetry breaking. A distribution of the magnetic field and a simple Lagrange model are used to interpret these phenomena. In addition, the intensity of the transmission peaks can be tuned by changing the incident polarization angle.
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[Evaluation of the prognostic significance of refinement and stratification of distant metastasis status in 1016 cases of nasopharyngeal carcinoma].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-10-2013
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To investigate the prognostic factors for nasopharyngeal carcinoma (NPC) with different metastatic status, and to improve the NPC management by multi-level refinement and stratification of M1 stage distant metastases.
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Bisphosphonamidate Clodronate Prodrug Exhibits Selective Cytototxic Activity Against Melanoma Cell Lines.
Mol. Cancer Ther.
PUBLISHED: 12-05-2013
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Bisphosphonates are used clinically to treat disorders of calcium metabolism and malignant bone disease and are known to inhibit cancer cell growth, adhesion, and invasion. However, clinical use of these agents for the treatment of extraskeletal disease is limited due to low cell permeability. We recently described a bisphosphonamidate prodrug strategy for efficient intracellular release of bisphosphonates, including clodronate (CLO), in NSCLC cells. To evaluate anticancer activity of this prodrug class across many cancer cell types, the bisphosphonamidate clodronate prodrug (CLO prodrug) was screened against the NCI-60 cell line panel, and was found to exhibit selectivity toward melanoma cell lines. Here, we confirm efficient cellular uptake and intracellular activation of this prodrug class in melanoma cells. We further demonstrate inhibition of melanoma cell proliferation, induction of apoptosis, and an anti-tumor effect of CLO prodrug in a xenograft model. These data suggest a novel therapeutic application for the CLO prodrug and potential to selectively target melanoma cells.
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Percutaneous CT-Guided Radiofrequency Ablation as Supplemental Therapy After Systemic Chemotherapy for Selected Advanced Non-Small Cell Lung Cancers.
AJR Am J Roentgenol
PUBLISHED: 11-23-2013
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OBJECTIVE. The purpose of this study is to evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) as a supplemental therapy after systemic chemotherapy for selected patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS. We retrospectively reviewed the medical records of 220 patients with advanced NSCLC who were treated with platinum-doublet chemotherapy between January 2000 and January 2012. Among them, 49 patients underwent RFA as a supplemental therapy for tumors in partial response or stable diseases after first-line chemotherapy. The progression-free survival (PFS) was evaluated by Kaplan-Meier method. RESULTS. There were nine women and 40 men (median age, 60 years; range, 24-82 years), including 28 patients with stage IIIb cancer and 21 with stage IV cancer. All 49 patients (partial response, 23 patients; stable disease, 26 patients) underwent 67 RFA sessions for 61 targeted tumors after systemic chemotherapy. There were no procedure-related deaths. Pneumothorax requiring chest tubes developed in eight sessions (11.9%). Thirty-one patients (63.3%) had complete response, 12 patients (24.5%) had partial response, six patients (12.2%) had stable disease, and no patients had progressive disease. The median follow-up period was 19 months (range, 6-34), and the median PFS was 16 weeks (95% CI, 14.5-17.5). CONCLUSION. Percutaneous CT-guided RFA can be performed as a feasible minimally invasive supplemental therapy with satisfactory PFS after systemic chemotherapy for patients with advanced NSCLC.
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Epigallocatechin-3-Gallate Inhibits Homocysteine-Induced Apoptosis of Endothelial Cells by Demethylation of the DDAH2 Gene.
Planta Med.
PUBLISHED: 11-15-2013
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Our previous study showed that hypermethylation of dimethylarginine dimethylaminohydrolase 2 contributes to homocysteine-induced apoptosis of human umbilical vein endothelial cells. Epigallocatechin-3-gallate is a green tea-derived phenol which has been proved beneficial on atherosclerosis. It was demonstrated that epigallocatechin-3-gallate inhibits DNA methyltransferase activity and reactivates methylation-silenced genes in cancer cells. The aim of this study was to address whether epigallocatechin-3-gallate could induce DNA demethylation of the dimethylarginine dimethylaminohydrolase 2 gene, contributing to prevent endothelial cells from apoptosis induced by homocysteine. Human umbilical vein endothelial cells (ATCC, CRL-2480) were treated with homocysteine (1?mM) for 48 hours with or without epigallocatechin-3-gallate (20?µM) or 5-Aza (DNA methyltransferase inhibitor, 5?µM). Apoptosis rate of human umbilical vein endothelial cells was assayed by flow cytometry with an annexin V-FITC apoptosis detection kit. The mRNA and protein expression level of dimethylarginine dimethylaminohydrolase 2 and DNA methyltransferase 1 were detected by real-time PCR and Western blot, respectively. DNA methylation level of dimethylarginine dimethylaminohydrolase 2 was assayed by methylation specific PCR. The binding level of DNA methyltransferase 1 in the promoter of dimethylarginine dimethylaminohydrolase 2 was determined by chromatin immunoprecipitation-quantitative real-time PCR. It was shown that the apoptosis rate was decreased significantly in human umbilical vein endothelial cells treated with homocysteine compared with the control. Furthermore, the mRNA and protein level of dimethylarginine dimethylaminohydrolase 2 were downregulated, the dimethylarginine dimethylaminohydrolase 2 gene promoter was hypermethylated, and the DNA methyltransferase 1 mRNA and protein level were increased in human umbilical vein endothelial cells treated with homocysteine. Chromatin immunoprecipitation-quantitative real-time PCR revealed that homocysteine-induced binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter was increased. Pretreatment with epigallocatechin-3-gallate or 5-Aza inhibited such effects of homocysteine. In conclusion, epigallocatechin-3-gallate exerted protective effects on homocysteine-induced apoptosis in human umbilical vein endothelial cells by inhibiting promoter hypermethylation of the dimethylarginine dimethylaminohydrolase 2 gene and inducing dimethylarginine dimethylaminohydrolase 2 expression. These effects may be due to the decreased DNA methyltransferase 1 expression and binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter induced by epigallocatechin-3-gallate. This research suggests that modulating the epigenetic processes might be a novel plausible way for treatment of atherosclerosis.
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[Diagnosis and surgical treatment of parathyroid neoplasms].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-31-2013
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To explore the clinical features, diagnosis and surgical treatment of parathyroid neoplasms.
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Disruption of N-linked glycosylation promotes proteasomal degradation of the human ATP-binding cassette transporter ABCA3.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 10-18-2013
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The lipid transport protein, ABCA3, expressed in alveolar type 2 (AT2) cells, is critical for surfactant homeostasis. The first luminal loop of ABCA3 contains three putative N-linked glycosylation sites at residues 53, 124, and 140. A common cotranslational modification, N-linked glycosylation, is critical for the proper expression of glycoproteins by enhancing folding, trafficking, and stability through augmentation of the endoplasmic reticulum (ER) folding cycle. To understand its role in ABCA3 biosynthesis, we utilized EGFP-tagged fusion constructs with either wild-type or mutant ABCA3 cDNAs that contained glutamine for asparagine substitutions at the putative glycosylation motifs. In A549 cells, inhibition of glycosylation by tunicamycin increased the electrophoretic mobility (Mr) and reduced the expression level of wild-type ABCA3 in a dose-dependent manner. Fluorescence imaging of transiently transfected A549 or primary human AT2 cells showed that although single motif mutants exhibited a vesicular distribution pattern similar to wild-type ABCA3, mutation of N124 and N140 residues resulted in a shift toward an ER-predominant distribution. By immunoblotting, the N53 mutation exhibited no effect on either the Mr or ABCA3 expression level. In contrast, substitutions at N124 or N140, as well a N124/N140 double mutation, resulted in increased electrophoretic mobility indicative of a glycosylation deficiency accompanied by reduced overall expression levels. Diminished steady-state levels of glycan-deficient ABCA3 isoforms were rescued by treatment with the proteasome inhibitor MG132. These results suggest that cotranslational N-linked glycosylation at N124 and N140 is critical for ABCA3 stability, and its disruption results in protein destabilization and proteasomal degradation.
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[Assessment comparison between area sampling and personal sampling noise measurement in new thermal power plant].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 10-02-2013
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To compare the results of noise hazard evaluations based on area sampling and personal sampling in a new thermal power plant and to analyze the similarities and differences between the two measurement methods.
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Fluoride promotes osteoblastic differentiation through canonical Wnt/?-catenin signaling pathway.
Toxicol. Lett.
PUBLISHED: 09-22-2013
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Although fluoride is known to stimulate bone formation, the underlying mechanisms are not fully understood. Recent studies have implicated the Wnt/?-catenin pathway as a major signaling cascade in bone biology. Our earlier studies highlighted a probable role of canonical Wnt pathway in bone formation of chronic fluoride-exposed rats, but the mechanism remains unclear. The current study determined the involvement of Wnt/?-catenin signaling in fluoride-induced osteoblastic differentiation. Using primary rat osteoblasts, we demonstrated that fluoride significantly promoted osteoblasts proliferation and alkaline phosphate (ALP) expression as well as the mRNA expression levels of bone differentiation markers, including type I collagen (COL1A1), ALP and osteonectin. We further found fluoride induced phosphorylations at serine 473 of Akt and serine 9 of glycogen synthase kinase-3? (GSK3?), which resulted in GSK-3? inhibition and subsequently the nuclear accumulation of the ?-catenin, as shown by Western blot and immunofluorescence analysis. Moreover, fluoride also induced the expression of Wnt-targeted gene runt-related transcription factor 2 (Runx2). Importantly, the positive effect of fluoride on ALP activity and mRNA expressions of COL1A1, ALP, osteonection and Runx2 was abolished by DKK-1, a blocker of the Wnt/?-catenin receptor. Taken together, these findings suggest that fluoride promotes osteoblastic differentiation through Akt- and GSK-3?-dependent activation of Wnt/?-catenin signaling pathway in primary rat osteoblasts. Our findings provide novel insights into the mechanisms of action of fluoride in osteoblastogenesis.
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A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion.
Mamm. Genome
PUBLISHED: 09-16-2013
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Fertilization is the process that leads to the formation of a diploid zygote from two haploid gametes. This is achieved through a complex series of cell-to-cell interactions between a sperm and an egg. The final event of fertilization is the fusion of the gametes membranes, which allows the delivery of the sperm genetic material into the egg cytoplasm. In vivo studies in the laboratory mouse have led to the discovery of membrane proteins that are essential for the fusion process in both the sperm and egg. Specifically, the sperm protein Izumo1 was shown to be necessary for normal fertility. Izumo1-deficient spermatozoa fail to fuse with the egg plasma membrane. Izumo1 is a member of the Immunoglobulin Superfamily of proteins, which are known to be involved in cell adhesion. Here, we describe BART97b, a new mouse line with a recessive mutation that displays a fertilization block associated with a failure of sperm fusion. BART97b mutants carry a deletion that inactivates Spaca6, a previously uncharacterized gene expressed in testis. Similar to Izumo1, Spaca6 encodes an immunoglobulin-like protein. We propose that the Spaca6 gene product may, together with Izumo1, mediate sperm fusion by binding an as yet unidentified egg membrane receptor.
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Developmental Hypothyroxinemia and Hypothyroidism Reduce Proliferation of Cerebellar Granule Neuron Precursors in Rat Offspring by Downregulation of the Sonic Hedgehog Signaling Pathway.
Mol. Neurobiol.
PUBLISHED: 09-12-2013
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Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during development result in dysfunction of the central nervous system, affecting psychomotor and motor function, although the underlying mechanisms causing these alterations are still unclear. Therefore, our aim is to study the effects of developmental hypothyroxinemia, caused by mild ID, and developmental hypothyroidism, caused by severe ID or methimazole (MMZ), on the proliferation of cerebellar granule neuron precursors (CGNPs), an excellent experimental model of cerebellar development and function. The sonic hedgehog (Shh) signaling pathway is essential for CGNP proliferation, and as such, its activation is also investigated here. A maternal hypothyroxinemia model was established in Wistar rats by administrating a mild ID diet, and two maternal hypothyroidism models were developed either by administrating a severe ID diet or MMZ water. Our results showed that hypothyroxinemia and hypothyroidism reduced proliferation of CGNPs on postnatal day (PN) 7, PN14, and PN21. Accordingly, the mean intensity of proliferating cell nuclear antigen and Ki67 nuclear antigen immunofluorescence was reduced in the mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of the Shh signaling pathway on PN7, PN14, and PN21. Our study supports the hypothesis that developmental hypothyroxinemia induced by mild ID, and hypothyroidism induced by severe ID or MMZ, reduce the proliferation of CGNPs, which may be ascribed to the downregulation of the Shh signaling pathway.
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[Progress of study on interaction between platelets and endothelial cells].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 09-04-2013
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Endothelial lesion is the most well known example for the interaction between platelets and endothelial cells, but the recent researches indicate that platelets and endothelial cells also participate in inflammation, tumor metastasis and lymphovascular development. Under these situations, the activated platelets express adhesive molecules and degranulate, and regulate the permeability, adhesion, survival, proliferation and metastasis of endothelial cells. All the achievements push the research on the interaction between platelets and endothelial cells to a new era, which would be more significant. In this review, the latest advances and prospect of the interaction between platelets and endothelial cells in inflammation, tumor and lymphovascular development are summarized.
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Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4(+) T cells of psoriasis vulgaris.
Clin. Immunol.
PUBLISHED: 08-21-2013
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Psoriasis vulgaris (PV) is a chronic inflammatory and T cell-mediated autoimmune skin disease. An immune dysfunction that is manifested by abnormally activated T cells and defective regulatory T (Treg) cells may play an important role in the pathogenesis of PV. However, the precise mechanism of the immune dysfunction in PV patients still remains unclear. In this study, we found that miR-210 expression is increased significantly in CD4(+) T cells from patients with PV and confirmed that FOXP3 is a target gene of miR-210. We also found that overexpression of miR-210 inhibits FOXP3 expression and impairs the immunosuppressive functions of Treg cells in CD4(+) T cells from healthy controls. In contrast, inhibition of miR-210 increases FOXP3 expression and reverses the immune dysfunction in CD4(+) T cells from patients with PV. Our data demonstrates that increased miR-210 induces immune dysfunction via by FOXP3 in CD4(+) T cells from patients with PV.
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Detection of adulteration in fresh and frozen beefburger products by beef offal using mid-infrared ATR spectroscopy and multivariate data analysis.
Meat Sci.
PUBLISHED: 07-09-2013
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A series of authentic and offal-adulterated beefburger samples was produced. Authentic product (36 samples) comprised either only lean meat and fat (higher quality beefburgers) or lean meat, fat, rusk and water (lower quality product). Beef offal adulterants comprised heart, liver, kidney and lung. Adulterated formulations (46 samples) were produced using a D-optimal experimental design. Fresh and frozen-then-thawed samples were modelled, separately and in combination, by a classification (partial least squares discriminant analysis) and class-modelling (soft independent modelling of class analogy) approach. With the former, 100% correct classification accuracies were obtained separately for fresh and frozen-then-thawed material. Separate class-models for fresh and frozen-then-thawed samples exhibited high sensitivities (0.94 to 1.0) but lower specificities (0.33-0.80 for fresh samples and 0.41-0.87 for frozen-then-thawed samples). When fresh and frozen-then-thawed samples were modelled together, sensitivity remained 1.0 but specificity ranged from 0.29 to 0.91. Results indicate a role for this technique in monitoring beefburger compliance to label.
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Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice.
Toxicol. Appl. Pharmacol.
PUBLISHED: 07-03-2013
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Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4+ T cells, decreased IL-6 and IL-1? expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1? and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice.
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[Research advance in von Willebrand factor].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-03-2013
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von Willebrand factor (vWF) is a multimeric glycoprotein exclusively synthesized in endothelial cells and megakaryocytes. It plays important roles in the primary and secondary haemostasis. Deficiency or dysfunction of vWF may cause von Willebrand disease (vWD), and overexpression of vWF may cause thrombosis. Making an intensive study on vWF will help us to understand the pathophysiology, diagnosis and treatment of vWF-related diseases, such as vWD, TTP, venous thrombosis, stroke, and so on. In this article, the regulation of vWF activity and its relation with diseases mentioned above are reviewed.
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[Evaluation of a new method and instrument for detection platelet aggregation function and its clinical application].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-03-2013
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This study was purposed to evaluate a new method and instrument for detecting platelet aggregation function, establish the reference intervals for PL-11 platelet analyzer, and evaluate its clinical application. The evaluation was based on the guidelines of Clinical and Laboratory Standards Institute (CLSI or NCCLS) and Clinical Laboratory Improvement Amendment 88. Intravenous blood samples anticoagulanted with sodium citrate were detected by PL-11 platelet analyzer. The reference intervals were defined after statistic analysis. The clinical diagnostic significance of the PL-11 platelet analyzer was evaluated by testing the change rate of platelet maximum aggregation rate (MAR) of acute cerebral infarction (ACI) patients in the department of Neurology who took clopidogrel 7 d before and after. The result showed that all the parameters meet the standard of CLIA88. The platelet MAR of 247 healthy volunteers which was induced by PLR-06, PLR-07, PLR-09 and PLR-10, was detected by the PL-11 platelet analyzer, respectively. The MAR is 58.8 ± 10.1 (%), 61.2 ± 11.8 (%), 51 ± 10.2 (%), 53.1 ± 9.2 (%), respectively. The MAR of ACI patients is significantly lower than that after taking clopidogrel. It is concluded that the PL-11 platelet analyzer is an ideal platelet function detector for early warning and diagnosis of thromboembolic disease, which is worthy to be extended and applied.
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MiR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression.
Carcinogenesis
PUBLISHED: 05-13-2013
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Endothelial cells (ECs) are critical for angiogenesis, and microRNAs play important roles in this process. We investigated the regulatory role of microRNAs in ECs of hepatocellular carcinoma (HCC) by examining the microRNA expression profile of human umbilical vein endothelial cells (HUVECs) in the absence or presence of human HCC cells, and identified miR-146a as the most highly upregulated microRNA. Furthermore, we revealed that miR-146a promoted the expression of platelet-derived growth factor receptor ? (PDGFRA) in HUVECs, and this process was mediated by BRCA1. Overexpression of PDGFRA in the ECs of HCC tissues was associated with microvascular invasion and predicted a poorer prognosis. These results suggest that miR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a and PDGFRA may emerge as potential anti-angiogenic targets on ECs for HCC therapy.
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Computer-assisted system with multiple feature fused support vector machine for sperm morphology diagnosis.
Biomed Res Int
PUBLISHED: 04-15-2013
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Sperm morphology is an important technique in identifying the health of sperms. In this paper we present a new system and novel approaches to classify different kinds of sperm images in order to assess their health. Our approach mainly relies on a one-dimensional feature which is extracted from the sperms contour with gray level information. Our approach can handle rotation and scaling of the image. Moreover, it is fused with SVM classification to improve its accuracy. In our evaluation, our method has better performance than the existing approaches to sperm classification.
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The genomics of selection in dogs and the parallel evolution between dogs and humans.
Nat Commun
PUBLISHED: 03-27-2013
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The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.
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First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study.
Transl Res
PUBLISHED: 02-17-2013
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Surgical resections remain the primary curative interventions for hepatocellular carcinoma (HCC). However, lack of real-time intraoperative image guidance confines surgeons to subjective visual assessment of the surgical bed, leading to poor visualization of small positive nodules and the extension of diffuse HCC. To address this problem, we developed a wearable fluorescence imaging and display system (fluorescence goggle) for intraoperative imaging of HCCs in human patients. In this pilot study, both intravenous (IV) and transarterial hepatic (TAH) delivery of indocyanine green (ICG) were explored to facilitate fluorescence goggle-mediated HCC imaging. The results show that all primary tumors in patients (n = 4) who received TAH delivery of ICG were identified successfully by the fluorescence goggle. In addition, 6 satellite tumors were also detected by the goggle, 5 of which were neither identifiable via preoperative magnetic resonance imaging (MRI) and computed tomography (CT) nor by visual inspection and palpation. In the group (n = 5) that received ICG intravenously, only 2 of 6 tumors visible by preoperative MRI or CT were identified with the fluorescence goggle, demonstrating the limitation of this delivery route for a non-tumor-selective imaging agent. Comparative analysis shows that the HCC-to-liver florescence contrast detected by the goggle was significantly greater in patients that received TAH than IV delivery of ICG (P = 0.013). This pilot study demonstrates the feasibility of using the fluorescence goggle to identify multifocal lesions and small tumor deposits using TAH ICG delivery in HCC patients.
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A bis-Benzylidine Piperidone Targeting Proteasome Ubiquitin Receptor RPN13/ADRM1 as a Therapy for Cancer.
Cancer Cell
PUBLISHED: 02-01-2013
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The bis-benzylidine piperidone RA190 covalently binds to cysteine 88 of ubiquitin receptor RPN13 in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma (MM) lines, even those resistant to bortezomib, were sensitive to RA190 via endoplasmic reticulum stress-related apoptosis. RA190 stabilized targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After oral or intraperitoneal dosing of mice, RA190 distributed to plasma and major organs except the brain and inhibited proteasome function in skin and muscle. RA190 administration profoundly reduced growth of MM and ovarian cancer xenografts, and oral RA190 treatment retarded HPV16(+) syngeneic mouse tumor growth, without affecting spontaneous HPV-specific CD8(+) T cell responses, suggesting its therapeutic potential.
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Anti-human VWF monoclonal antibody SZ-123 prevents arterial thrombus formation by inhibiting VWF-collagen and VWF-platelet interactions in Rhesus monkeys.
Biochem. Pharmacol.
PUBLISHED: 01-04-2013
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The interactions between collagen, von Willebrand factor (VWF), and glycoprotein Ib (GPIb) are crucial for hemostasis and thrombosis. This axis represents a promising target for the development of new antithrombotic agents. In this study, we investigate the in vivo antithrombotic efficacy of an anti-VWF monoclonal antibody SZ-123 and its potential underlying mechanisms. Cyclic flow reductions (CFRs), an indicator of arterial thrombosis, were measured in the femoral artery of anesthetized Rhesus monkeys before and after intravenous administration of SZ-123. Ex vivo VWF binding to collagen, platelet agglutination, platelet count, and template bleeding time were used as measurements of antithrombotic activity. In addition, plasma VWF and SZ-123 levels, and VWF occupancy were measured by ELISA. Administration of 0.1, 0.3, and 0.6 mg/kg SZ-123 resulted in 45.3%, 78.2%, and 100% reductions in CFRs, respectively. When 0.3 and 0.6 mg/kg SZ-123 were administered, 100% of VWF was occupied by the antibody. Moreover, 100% ex vivo inhibition of VWF-collagen binding and 60-95% inhibition of platelet agglutination were observed from 15 min to 1 h. None of the doses resulted in significant prolongation of bleeding time. In vitro experiments revealed that SZ-123 not only blocks the collagen-VWF A3 interaction but also indirectly inhibits VWF A1 binding to GPIb? induced by ristocetin. Thus, we demonstrate that SZ-123 prevents in vivo arterial thrombus formation under high shear conditions by inhibiting VWF A3-collagen and VWF A1-platelet interactions and does not significantly prolong bleeding time.
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Factors Associated with Severe Deliberate Self-Harm among Chinese Internal Migrants.
PLoS ONE
PUBLISHED: 01-01-2013
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Studies on mental health status of Chinese internal migrants are sparse albeit desperately needed. Deliberate self-harm (DSH) is intimately related to mental disorders, especially depression based on literatures. The major aim of this study is to explore associated factors of severe DSH among Chinese internal migrants.
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What is Visualize?

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.

Video X seems to be unrelated to Abstract Y...

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.