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Find video protocols related to scientific articles indexed in Pubmed.
[Comparison study of five scoring systems for evaluating prognosis of patients undergoing transjugular intrahepatic portosystemic shunt procedures].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-10-2014
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To compare the model for end-stage liver disease (MELD), delta model for end-stage liver disease (deltaMELD), MELD and serum sodium (MELD-Na), MELD score to serum sodium ratio index (MESO), and integrated end-stage liver disease model (iMELD) scoring systems for their utility in evaluating medium-short term prognosis of cirrhotic patients who underwent the transjugular intrahepatic portosystemic shunt (TIPS) procedure.
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Ultra-bright alkylated graphene quantum dots.
Nanoscale
PUBLISHED: 09-06-2014
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Highly efficient and stable photoluminescence (PL) are urgently desired for graphene quantum dots (GQDs) to facilitate their prospective applications as optical materials. Here, we report the facile and straightforward synthesis of alkylated graphene quantum dots (AGQDs) via the solvothermal reaction of propagatively alkylated graphene sheets (PAGenes). In contrast to most GQDs reported so far, the synthesized AGQDs process pH-independent and ultra-bright PL with a relative quantum yield of up to 65%. Structural and chemical composition characterization demonstrated that the synthesized AGQDs are nearly oxygen-defect-free with alkyl groups decorated on edges and basal plane, which may contribute to their greatly improved pH tolerance and high quantum efficiency. The photocatalytic performance of AGQDs-P25 nanocomposites was evaluated by the degradation of Rhodamine B under visible light. The photocatalytic rate is ca. 5.9 times higher than that of pure P25, indicating that AGQDs could harness the visible spectrum of sunlight for energy conversion or environmental therapy.
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A novel molecule Me6TREN promotes angiogenesis via enhancing endothelial progenitor cell mobilization and recruitment.
Sci Rep
PUBLISHED: 08-28-2014
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Critical limb ischaemia is the most severe clinical manifestation of peripheral arterial disease. The circulating endothelial progenitor cells (EPCs) play important roles in angiogenesis and ischemic tissue repair. The increase of circulating EPC numbers by using mobilization agents is critical for obtaining a better therapeutic outcome in patients with ischemic disease. Here, we firstly report a novel small molecule, Me6TREN (Me6), can efficiently mobilize EPCs into the blood circulation. Single injection of Me6 induced a long-lasting increase in circulating Flk-1(+) Sca-1(+) EPC numbers. In a mouse hind limb ischemia (HLI) model, local intramuscular transplantation of these Me6-mobilized cells accelerated the blood flow restoration in the ischemic muscles. More importantly, systemic administration of Me6 notably increased the capillary density, arteriole density and regenerative muscle weight in the ischemic tissue of HLI. Mechanistically, we found Me6 reduced stromal cell-derived factor-1? level in bone marrow by up-regulation of matrix metallopeptidase-9 expression, which allowed the dissemination of EPCs into peripheral blood. These data indicate that Me6 may represent a potentially useful therapy for ischemic disease via enhancing autologous EPC recruitment and promote angiogenesis.
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Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.
PLoS ONE
PUBLISHED: 08-25-2014
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Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model.
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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
Chen Wu, Zhaoming Wang, Xin Song, Xiao-Shan Feng, Christian C Abnet, Jie He, Nan Hu, Xian-Bo Zuo, Wen Tan, Qimin Zhan, Zhibin Hu, Zhonghu He, Weihua Jia, Yifeng Zhou, Kai Yu, Xiao-Ou Shu, Jian-Min Yuan, Wei Zheng, Xue-Ke Zhao, She-Gan Gao, Zhi-Qing Yuan, Fu-You Zhou, Zong-Min Fan, Ji-Li Cui, Hong-Li Lin, Xue-Na Han, Bei Li, Xi Chen, Sanford M Dawsey, Linda Liao, Maxwell P Lee, Ti Ding, You-Lin Qiao, Zhihua Liu, Yu Liu, Dianke Yu, Jiang Chang, Lixuan Wei, Yu-Tang Gao, Woon-Puay Koh, Yong-Bing Xiang, Ze-Zhong Tang, Jin-Hu Fan, Jing-jing Han, Sheng-Li Zhou, Peng Zhang, Dong-Yun Zhang, Yuan Yuan, Ying Huang, Chunling Liu, Kan Zhai, Yan Qiao, Guangfu Jin, Chuanhai Guo, Jianhua Fu, Xiaoping Miao, Changdong Lu, Haijun Yang, Chaoyu Wang, William A Wheeler, Mitchell Gail, Meredith Yeager, Jeff Yuenger, Er-Tao Guo, Ai-li Li, Wei Zhang, Xue-Min Li, Liang-Dan Sun, Bao-Gen Ma, Yan Li, Sa Tang, Xiu-Qing Peng, Jing Liu, Amy Hutchinson, Kevin Jacobs, Carol Giffen, Laurie Burdette, Joseph F Fraumeni, Hongbing Shen, Yang Ke, Yixin Zeng, Tangchun Wu, Peter Kraft, Charles C Chung, Margaret A Tucker, Zhi-Chao Hou, Ya-Li Liu, Yan-Long Hu, Li Wang, Guo Yuan, Li-Sha Chen, Xiao Liu, Teng Ma, Hui Meng, Li Sun, Xin-Min Li, Xiu-Min Li, Jian-Wei Ku, Ying-Fa Zhou, Liu-Qin Yang, Zhou Wang, Yin Li, Qirenwang Qige, Wen-jun Yang, Guang-Yan Lei, Long-qi Chen, En-Min Li, Ling Yuan, Wen-Bin Yue, Ran Wang, Lu-Wen Wang, Xue-Ping Fan, Fang-Heng Zhu, Wei-Xing Zhao, Yi-min Mao, Mei Zhang, Guo-Lan Xing, Ji-Lin Li, Min Han, Jing-Li Ren, Bin Liu, Shu-Wei Ren, Qing-Peng Kong, Feng Li, Ilyar Sheyhidin, Wu Wei, Yan-Rui Zhang, Chang-Wei Feng, Jin Wang, Yu-Hua Yang, Hong-Zhang Hao, Qi-De Bao, Bao-Chi Liu, Ai-Qun Wu, Dong Xie, Wan-Cai Yang, Liang Wang, Xiao-Hang Zhao, Shu-Qing Chen, Jun-Yan Hong, Xue-Jun Zhang, Neal D Freedman, Alisa M Goldstein, Dongxin Lin, Philip R Taylor, Li-dong Wang, Stephen J Chanock.
Nat. Genet.
PUBLISHED: 08-17-2014
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We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target.
Expert Opin. Ther. Targets
PUBLISHED: 07-31-2014
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Fibroblast growth factor 21 (FGF21) is one of the FGF family members that is produced mainly by tissues with high metabolic activity such as liver, pancreas, muscle and adipose tissue. The major function of FGF21 is to improve insulin sensitivity, ameliorate hepatic steatosis and enhance energy expenditure. Recently, several studies have reported a correlation between FGF21 and liver disease with numerous cross-sectional studies demonstrating significant correlation. This review will focus on the role of FGF21 in the pathogenesis of liver disease and its potential role as a biomarker and a new target for therapeutic intervention.
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[Characterization and simulation of far-infrared spectroscopy for saturated monohydric alcohols].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 07-11-2014
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Fourier transform infrared-attenuated total reflection (FTIR-ATR) was employed to measure the far-infrared (FIR) spectra in wavenumbers of 30-300 cm(-1) for six kinds of saturated monohydric alcohols, namely: methanol, ethanol, propanol, isopropanol, butanol and isobutanol. Further analysis of the FIR spectra for these monohydric alcohols with similar chemical structures reveals that absorption peaks are observed obviously for these alcohols in the 30-150 cm(-1) band, whereas not obvious peaks are measured in the 150-300 cm(-1) band. Moreover, it was found that the monohydric alcohols with higher hydroxy concentration possess lower average FIR transmission. In addition, the average FIR transmissions of linear chain monohydric alcohols are higher than those of the branched chain ones. Furthermore, the density functional theory (DFT) B3LYP/6-311G(d,p) basis set was employed to simulate the structures optimization and to calculate the responding frequencies of the methanol monomer and polymer. Simulation result indicates that no absorption peaks are found in the 30-150 cm(-1) band for the methanol monomer molecule, whereas there are obvious absorption peaks for the methanol polymers in the same band. In addition, the simulated absorption peak positions for the methanol polymers are in agreement with those experimentally measured. Both results indicate that the absorption of the methanol in Terahertz (THz) is attributed to the collective vibrations of different kinds of polymer, and that the polymer for methanol is mainly trimmer. This paper not only provides a new way to investigate the responding frequencies of organic molecule in THz band, but also is helpful for the FTIR-ATR study of other organic molecules.
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Refinement of Ischemic Stroke Risk in Patients with Atrial Fibrillation and CHA2 DS2 -VASc Score of 1.
Pacing Clin Electrophysiol
PUBLISHED: 05-07-2014
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 Patients with atrial fibrillation (AF) with CHA2 DS2 -VASc score of 1 (where CHA2 DS2 -VASc is CHA2 DS2 -Vascular disease, Age 65-74 years, Sex category) are recommended to receive antithrombotic therapy. Nonetheless, it remains unclear whether individual components that constitute CHA2 DS2 -VASc score contribute equally to the ischemic stroke risk, particularly in patients with CHA2 DS2 -VASc score of 1. The objective was to describe and compare the risk of ischemic stroke of the six individual components constituting CHA2 DS2 -VASc among AF patients with CHA2 DS2 -VASc score of 1.
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Influence of central metalloligand geometry on electronic communication between metals: syntheses, crystal structures, MMCT properties of isomeric cyanido-bridged Fe2Ru complexes, and TDDFT calculations.
Chemistry
PUBLISHED: 04-25-2014
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To investigate how the central metalloligand geometry influences distant or vicinal metal-to-metal charge-transfer (MMCT) properties of polynuclear complexes, cis- and trans-isomeric heterotrimetallic complexes, and their one- and two-electron oxidation products, cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CN-Fe(II)(dppe)Cp][PF6]2 (cis/trans-1[PF6]2), cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CNFe(III)-(dppe)Cp][PF6]3 (cis/trans-1[PF6]3) and cis/trans-[Cp(dppe)Fe(III)NCRu(II)(phen)2CN-Fe(III)(dppe)Cp][PF6]4 (cis/trans-1[PF6]4) have been synthesized and characterized. Electrochemical measurements show the presence of electronic interactions between the two external Fe(II)?atoms of the cis- and trans-isomeric complexes cis/trans-1[PF6]2. The electronic properties of all these complexes were studied and compared by spectroscopic techniques and TDDFT//DFT calculations. As expected, both mixed valence complexes cis/trans-1[PF6]3 exhibited different strong absorption signals in the NIR region, which should mainly be attributed to a transition from an MO that is delocalized over the Ru(II)-CN-Fe(II) subunit to a Fe(III) d?orbital with some contributions from the co-ligands. Moreover, the NIR transition energy in trans-1[PF6]3 is lower than that in cis-1[PF6]3, which is related to the symmetry of their molecular orbitals on the basis of the molecular orbital analysis. Also, the electronic spectra of the two-electron oxidized complexes show that trans-1[PF6]4 possesses lower vicinal Ru(II) ? Fe(III) MMCT transition energy than cis-1[PF6]4. Moreover, the assignment of MMCT transition of the oxidized products and the differences of the electronic properties between the cis and trans complexes can be well rationalized using TDDFT//DFT calculations.
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Bufalin exerts inhibitory effects on IL-1?-mediated proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes.
Inflammation
PUBLISHED: 04-23-2014
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Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1?)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1?-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-?B), both of which are involved in IL-1?-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1?-induced proliferation of RAFLSs through MAPK and NF-?B signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.
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A new spiroplasma isolate from the field cricket (Gryllus bimaculatus) in Taiwan.
J. Invertebr. Pathol.
PUBLISHED: 04-09-2014
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We briefly described the morphology and transmission pathway of a Spiroplasma sp. isolated from the field cricket, Gryllus bimaculatus in Taiwan, followed by the phylogenetic analysis based on the 16S rRNA gene sequence. The cricket spiroplasma infected the hemolymph, gut, muscle tissues and tracheal cells; therefore we suggest that the pathogen invaded tissues and organs from the hemolymph through the tracheal system and the endoplasmic reticular system. Based on 16S rRNA gene sequences and the phylogeny, this spiroplasma was most closely related to Spiroplasma platyhelix (Identity=95%) isolated from the dragonfly Pachydiplax longipennis and belongs to the Ixodetis clade.
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[Study on the induction and differentiation of megakaryocyte progenitor cell derived from umbilical cord blood].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 03-27-2014
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To build a protocol of separation and induction of megakaryocytes derived from cord blood mononuclear cells.
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Analysis of heart rate variability in masked hypertension.
Cell Biochem. Biophys.
PUBLISHED: 03-19-2014
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To investigate heart rate variability (HRV) in patients with masked hypertension (MH), participants were classified based on clinic and 24-h ambulatory blood-pressure monitoring: essential hypertension (EH, n = 40; MH, n = 36) and normotension (NT, n = 48). The HRV parameters were observed using a 24-h Holter monitor. Compared with NT controls, the parameters of HRV (SDNN, SDANN, SDNN Index, RMSSD, HF) and parameters in EH and MH patients had significantly decreased. No statistically significant difference in the HRV parameters was found between the EH and MH groups. The changes in HRV parameters show cardiac autonomic nerve dysfunction in patients with MH.
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Taiwanese Green Propolis and Propolin G Protect the Liver from the Pathogenesis of Fibrosis via Eliminating TGF-?-Induced Smad2/3 Phosphorylation.
J. Agric. Food Chem.
PUBLISHED: 03-15-2014
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Pathogenesis of fibrosis is a common process leading to chronic liver diseases and liver cirrhosis. New compounds for disease treatment and adjuvant therapy have been important issues in recent years. In this study, we isolated propolin G from Taiwanese green propolis (TGP) and investigated its antifibrotic effects by utilizing active hepatic stellate cells (HSCs) fibrosis model. Our results showed that TGP and propolin G inhibited ?-SMA, collagen expression, and proliferation of HSC-T6 cells after TGF-? treatment. They also reduced the accumulation of extracellular matrix (ECM) components such as collagen I?1 (Col I?1) through down-regulating JNK signaling. Subsequently, mRNA and protein expression of Smad2/3 but no other Smad members was specifically down-regulated in the presence of propolin G. This effect also significantly induced apoptosis-associated expression of cleaved caspase-3 and caspase-7 proteins for fibrotic cell clearance. In in vivo experiments, we found that propolin G and TGP can reduce plasma alanine aminotransferase (ALT) activation and perhaps lead to the prevention of alcohol-induced liver cirrhosis. Furthermore, TGP can significantly decrease the malondialdehyde (MDA) level but has no influence on plasma or hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, suggesting TGP protects the liver from alcohol-induced injury through antioxidant-independent pathways. In conclusion, this study provides a new perspective of propolin G and TGP on liver protection, and its application has potential for health management by daily supplement or adjuvant therapy in related diseases.
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Effects of cattail biomass on sulfate removal and carbon sources competition in subsurface-flow constructed wetlands treating secondary effluent.
Water Res.
PUBLISHED: 03-11-2014
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Sulfate is frequently found in the influent of subsurface-flow constructed wetlands (SSF CWs) used as tertiary treatments. To reveal the effects of plants and litters on sulfate removal, as well as the competition for organic carbon among microorganisms in SSF CWs, five laboratory-scale SSF CW microcosms were set up and were operated as a batch system with HRT 5 d. The results showed that the presence of Typha latifolia had little effect on sulfate removal in CWs, with or without additional carbon sources. Cattail litter addition greatly improved sulfate removal in SSF CWs. This improvement was linked to the continuous input of labile organic carbon, which lowers the redox level and supplies a habitat for sulfate reducing bacteria (SRB). The presence of SRB in cattail litter indicated the possibility of sulfate removal around the carbon supplier, but the quantity of microbes in cattail litter was much lower than that in gravel. Stoichiometry calculations showed that the contribution of SRB to COD removal (21-26%) was less than that of methane-producing bacteria (MPB) (47-61%) during the initial stage but dominated COD removal (42-65%) during the terminal stage. The contributions of aerobic bacteria (AB) and denitrification bacteria (DB) to COD removal were always lower than that of SRB. It was also observed that the variations in COD: S ratio had a great influence on the relative abundance of genes between SRB and MPB and both of them could be used as good predictors of carbon competition between SRB and MPB in CWs.
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Genomic and molecular characterization of esophageal squamous cell carcinoma.
Nat. Genet.
PUBLISHED: 03-05-2014
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Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.
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MicroRNA-126 modulates the tumor microenvironment by targeting calmodulin-regulated spectrin-associated protein 1 (Camsap1).
Int. J. Oncol.
PUBLISHED: 02-14-2014
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Plasma miRNAs have been reported as biomarkers for various diseases. In this study, we investigated whether plasma concentrations of miR-126 may be useful as biomarkers for laryngeal squamous cell carcinoma (LSCC). We examined the function and mechanism of miR-126 in LSCC by using cell biology and molecular pathology techniques such as western blotting, quantitative PCR, IHC and IF. The expression of Camsap1 mRNA and protein is higher in cancer tissues compared to that in normal tissues. Both miR-126 and Camsap1 were related with the prognosis of LSCC patients. We found that miR-126 was able to inhibit LSCC partly by suppressing Camsap1 expression. In addition, Camsap1 expression induced microtubule formation and aggregation. This mechanism possibly explains why loss of miR-126 is frequently associated with tumor metastasis.
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Observation of an all-boron fullerene.
Nat Chem
PUBLISHED: 02-11-2014
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After the discovery of fullerene-C60, it took almost two decades for the possibility of boron-based fullerene structures to be considered. So far, there has been no experimental evidence for these nanostructures, in spite of the progress made in theoretical investigations of their structure and bonding. Here we report the observation, by photoelectron spectroscopy, of an all-boron fullerene-like cage cluster at B40(-) with an extremely low electron-binding energy. Theoretical calculations show that this arises from a cage structure with a large energy gap, but that a quasi-planar isomer of B40(-) with two adjacent hexagonal holes is slightly more stable than the fullerene structure. In contrast, for neutral B40 the fullerene-like cage is calculated to be the most stable structure. The surface of the all-boron fullerene, bonded uniformly via delocalized ? and ? bonds, is not perfectly smooth and exhibits unusual heptagonal faces, in contrast to C60 fullerene.
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Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment.
Cancer Prev Res (Phila)
PUBLISHED: 02-11-2014
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Pancreatic cancer, as the fourth leading cause of cancer-related deaths, carries a poor prognosis with a median survival of 6 months and a dismal 5-year survival rate of 3% to 5%. These statistics highlight an urgent need for novel chemopreventive and therapeutic strategies for this malignancy. Metformin and aspirin have been explored as two emerging cancer chemoprevention agents for different types of cancers, including pancreatic cancer. Here, we review the effects of both metformin and aspirin on pancreatic tumorigenesis and their potential actions in pancreatic cancer. Special attention is paid to their effects on the important signaling pathways of pancreatic cancer development as well as possible mechanisms for synergy between these two agents. For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways. For aspirin, the major mechanism is the anti-inflammatory action through the inhibition of COX-1/COX-2 and modulation of the NF?B or STAT3 pathway. In addition, aspirin may activate AMPK, and both agents may affect Notch, Wnt/?-catenin, and other signaling pathways. The combination of metformin and aspirin will provide additive and possibly synergistic effects for the prevention and treatment of pancreatic cancer.
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A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30.
Cell Res.
PUBLISHED: 02-11-2014
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Mitochondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3. The inhibition of USP30 by S3 leads to an increase of non-degradative ubiquitination of Mfn1/2, which enhances Mfn1 and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.
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The influence of multivalent cations on the flocculation of activated sludge with different sludge retention times.
Water Res.
PUBLISHED: 02-03-2014
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The mechanism governing the flocculation of activated sludge (AS) with different sludge retention times (SRTs) was studied in this paper. AS samples were cultivated in 8 lab-scale reactors with SRTs of 5 d, 7.5 d, 10 d, 12.5 d, 15 d, 20 d, 30 d, and 40 d. The bulk solution, loosely bound extracellular polymeric substances (LB-EPS), tightly bound EPS (TB-EPS), and pellet were extracted for all 8 AS samples. There was a clear trend that the effluent turbidity decreased as the SRT increased, and we deduced that this is because AS samples with longer SRTs have lower interaction energy barriers and lower LB-EPS content. Furthermore, the concentrations of multivalent cations (especially trivalent cations) in the pellets were found to be closely correlated to the AS flocculability, total interaction energy (Wtot), and LB-EPS content. The multivalent (especially trivalent) cations possess greater binding ability, and this ability to bind tightly to AS in large quantities is responsible for the superior flocculability of AS samples with longer SRTs. Hence, the concentrations of multivalent cations in the pellets are an important indicator of AS flocculability. We deduced that variations in the quantities of multivalent cations that tightly bind with the AS rather than remaining in the influent are the core reason behind observed fluctuations in the AS flocculability with different SRTs.
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Fibulin-3 suppresses Wnt/?-catenin signaling and lung cancer invasion.
Carcinogenesis
PUBLISHED: 01-30-2014
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The 5 year survival rate of lung cancer is <20%, with most patients dying from distant metastasis. However, the molecular mechanisms underlying lung cancer invasion and metastasis have not been fully characterized. In this study, we found that fibulin-3, a fibulin family extracellular matrix protein, functions as a suppressor of lung cancer invasion and metastasis. Fibulin-3 was downregulated in large fractions of lung tumors and cell lines, and inhibited lung cancer cell invasion and the expression of matrix metalloproteinase-7 (MMP-7), a promoter of lung cancer invasion. The expression levels of fibulin-3 and MMP-7 were inversely correlated in lung tumors. Fibulin-3 inhibited extracellular signal-regulated kinase (ERK) to activate glycogen synthase kinase 3? and suppress Wnt/?-catenin signaling, which induces MMP-7 expression in lung cancer cells. Furthermore, fibulin-3 expression impeded the growth and metastasis of lung tumors in mice. Collectively, these results suggest that downregulation of fibulin-3 contributes to lung cancer invasion and metastasis by activating Wnt/?-catenin signaling and MMP-7 expression.
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Effects of plant biomass on nitrogen transformation in subsurface-batch constructed wetlands: a stable isotope and mass balance assessment.
Water Res.
PUBLISHED: 01-25-2014
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Nitrate is commonly found in the influent of subsurface-batch constructed wetlands (SSB CWs) used for tertiary wastewater treatments. To understand the effects of plants and the litter on nitrate removal, as well as on nitrogen transformation in SSB CWs, six laboratory-scale SSB CW microcosms were set up in duplicate and were operated as batch systems with hydraulic residence time (HRT) of 5d. The presence of Typha latifolia enhanced nitrate removal in SSB CWs, and the N removed by plant uptake was mainly stored in aboveground biomass. Typha litter addition greatly improved nitrate removal in SSB CWs through continuous input of labile organic carbon, and calculated enrichment factors (?) were between -12.1‰--13.9‰ from the nitrogen stable isotope analysis, suggesting that denitrification plays a dominant role in the N removal. Most significantly, simultaneous sulfur-based autotrophic and heterotrophic denitrification was observed in CWs. Finally, mass balance showed that denitrification, sedimentation burial and plant uptake respectively contributed 54%-94%, 1%-46% and 7.5%-14.3% to the N removal in CWs.
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The role of Hath6, a newly identified shear-stress-responsive transcription factor, in endothelial cell differentiation and function.
J. Cell. Sci.
PUBLISHED: 01-24-2014
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The key regulators of endothelial differentiation that is induced by shear stress are mostly unclear. Human atonal homolog 6 (Hath6 or ATOH8) is an endothelial-selective and shear-stress-responsive transcription factor. In this study, we sought to elucidate the role of Hath6 in the endothelial specification of embryonic stem cells. In a stepwise human embryonic stem cell to endothelial cell (hESC-EC) induction system, Hath6 mRNA was upregulated synchronously with endothelial determination. Subsequently, gain-of-function and loss-of-function studies of Hath6 were performed using the hESC-EC induction model and endothelial cell lines. The overexpression of Hath6, which mimics shear stress treatment, resulted in an increased CD45(-)CD31(+)KDR(+) population, a higher tubular-structure-formation capacity and increased endothelial-specific gene expression. By contrast, the knockdown of Hath6 mRNA markedly decreased endothelial differentiation. Hath6 also facilitated the maturation of endothelial cells in terms of endothelial gene expression, tubular-structure formation and cell migration. We further demonstrated that the gene encoding eNOS is a direct target of Hath6 through a reporter system assay and western blot analysis, and that the inhibition of eNOS diminishes hESC-EC differentiation. These results suggest that eNOS plays a key role in linking Hath6 to the endothelial phenotype. Further in situ hybridization studies in zebrafish and mouse embryos indicated that homologs of Hath6 are involved in vasculogenesis and angiogenesis. This study provides the first confirmation of the positive impact of Hath6 on human embryonic endothelial differentiation and function. Moreover, we present a potential signaling pathway through which shear stress stimulates endothelial differentiation.
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CAPE promotes the expansion of human umbilical cord blood-derived hematopoietic stem and progenitor cells in vitro.
Sci China Life Sci
PUBLISHED: 01-22-2014
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Due to the low number of collectable stem cells from single umbilical cord blood (UCB) unit, their initial uses were limited to pediatric therapies. Clinical applications of UCB hematopoietic stem and progenitor cells (HSPCs) would become feasible if there were a culture method that can effectively expand HSPCs while maintaining their self-renewal capacity. In recent years, numerous attempts have been made to expand human UCB HSPCs in vitro. In this study, we report that caffeic acid phenethyl ester (CAPE), a small molecule from honeybee extract, can promote in vitro expansion of HSPCs. Treatment with CAPE increased the percentage of HSPCs in cultured mononuclear cells. Importantly, culture of CD34(+) HSPCs with CAPE resulted in a significant increase in total colony-forming units and high proliferative potential colony-forming units. Burst-forming unit-erythroid was the mostly affected colony type, which increased more than 3.7-fold in 1 ?g mL(-1) CAPE treatment group when compared to the controls. CAPE appears to induce HSPC expansion by upregulating the expression of SCF and HIF1-?. Our data suggest that CAPE may become a potent medium supplement for in vitro HSPC expansion.
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Removal processes of disinfection byproducts in subsurface-flow constructed wetlands treating secondary effluent.
Water Res.
PUBLISHED: 01-21-2014
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The removal efficiencies and the kinetics of disinfection byproducts (DBPs) were studied in six greenhouse laboratory-scale SSF CWs. Cattail (Typha latifolia) and its litter (collected from the aboveground samples of cattail in autumn) were used as a potential phytoremediation technology and as a primary substrate, respectively, for DBP removal. Results showed that most of the 11 DBPs (except chloroform and 1, 1-dichloropropanone) were efficiently removed (>90%) in six SSF CWs with hydraulic retention time of 5 d and there were no significant differences among the systems. Under the batch mode, the removal of DBPs in SSF CWs followed first-order kinetics with half-lives of 1.0-770.2 h. As a primary DBP in wastewater effluent, removal efficiencies for chloroform were higher in planted systems than in unplanted ones and plant uptake accounted for more than 23.8% of the removal. Plant litter greatly enhanced the removal of trihalomethanes (THMs) by supplying primary substrates and reducing conditions, and the formation of dichloromethane supported the anaerobic biodegradation of THMs via reductive dechlorination in SSF CWs. Trichloroacetonitrile was completely removed within 10 h in each system and hydrolysis was considered to be the dominant process as there was a rapid formation of the hydrolysis byproduct, trichloroacetamide.
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Effects of plant biomass on denitrifying genes in subsurface-flow constructed wetlands.
Bioresour. Technol.
PUBLISHED: 01-20-2014
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The effect of Typha latifolia and its litter on density and abundance of three denitrifying genes (nirS, nirK and nosZ) were investigated in six laboratory-scale SSF CW microcosms. Results showed that the copy numbers of nirS, nirK and nosZ in wetland microcosms were ranged between 10(8)-10(9), 10(6)-10(7) and 10(7)-10(8) copies g(-1), respectively. The presence of T. latifolia encouraged the growth of nirK containing bacteria. Addition of cattail litter could greatly stimulate the growth of bacteria containing nirS and nosZ gene. Path analysis illustrated that the presence of plants and litters had no significant direct impact on denitrifying genes, while it affected the denitrifying genes via alteration of dissolved oxygen and carbon sources.
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Peripheral glycerol injection: an alternative treatment of children with glossopharyngeal neuralgia.
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 01-15-2014
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Glossopharyngeal neuralgia is much less common in children and more difficult to relief its pain symptoms than the adults. We report an experience with peripheral glycerol injection for the control of pain in eight sick children with glossopharyngeal neuralgia. At the latest follow-up, 5 cases had a complete pain-free result after the treatment. There were two sick children who were recurred within three months, of which one child was respond to additional injections. It is concluded that the peripheral glycerol injection is safe and effective in the control of pain symptom among the children with glossopharyngeal neuralgia.
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Increased risk of colorectal malignant neoplasm in patients with nonalcoholic fatty liver disease: a large study.
Mol. Biol. Rep.
PUBLISHED: 01-13-2014
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Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk factor of colorectal benign adenomas and advanced neoplasms. The aim of this large cohort study was to further investigate the prevalence of colorectal malignant neoplasm (CRMN) in patients with NAFLD and determine whether association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males and 945 females) who underwent a routine colonoscopy according to international colorectal cancer screening guideline were recruited. Nature of colorectal lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary logistic regression analysis was applied to explore the related associations. Prevalence of CRMN was 29.3% (77/263) in patients with NAFLD, which was significantly higher than 18.0% (369/2,052) in the control group (P<0.05). In addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid colon than in control group (14.3 vs. 11.9%). The incidence of highly-differentiated colorectal adenocarcinoma in NAFLD group was significantly higher than control group (62.3 vs. 9.8%). Univariate analysis showed that NAFLD had strong association with CRMN (OR 2.043; 95% CI 1.512-2.761; P<0.05). After adjusting for metabolic and other confounding factors, NAFLD remained as an independent risk factor for CRMN (OR 1.868; 95% CI 1.360-2.567; P<0.05). NAFLD was an independent risk factor for CRMN. Sigmoid carcinoma and highly differentiated colorectal adenocarcinoma were more commonly found in NAFLD. (ClinicalTrials.gov number, NCT01657773, website: http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1 ).
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Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries.
Mol. Biol. Rep.
PUBLISHED: 01-12-2014
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In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan-Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5%. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0%, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95% confidence intervals: 1.285-5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3%, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0%, P = 0.404). Kaplan-Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.
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Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress.
Eur. J. Neurosci.
PUBLISHED: 01-10-2014
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Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors. Using a chronic unpredictable mild stress mouse depression model, we studied expression of TRIM32 in brain tissue samples and observed behavioral changes in Trim32 knockout mice. The results showed that TRIM32 protein but not its mRNA was significantly reduced in hippocampus in a time-dependent manner within 8 weeks of chronic stress. These stress-induced affective behaviors and reduction of TRIM32 protein expression were significantly reversed by antidepressant fluoxetine treatment. In addition, Trim32 knockout mice showed reduced anxiety and depressive behaviors and hyperactivities compared with Trim32 wild-type mice under normal and mild stress conditions. We conclude that TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress.
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Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model.
Int J Med Sci
PUBLISHED: 01-01-2014
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This study investigated the antifatigue effects of rutin, a flavonoid extracted from the ethyl acetate extract of S. involucrata. Mice were subjected to a weight-loaded forced swim test (WFST) on alternate days for 3 wk. Rutin was administered orally to the mice for 7 days in dosages of 15, 30, and 60 mg/kg body weight, and several biomarkers of physical fatigue were evaluated: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). On Day 7, the rutin-treated mice had a 3-fold longer exhaustive swimming time than the control mice, as well as significantly reduced blood LA concentrations. The 15, 30, and 60 mg/kg body weight rutin-supplemented groups displayed 11.2%, 22.5%, and 37.7% reduced malondialdehyde (MDA) concentrations, respectively, in brain and muscle tissues compared with the control exercised group. Our results indicated that the administration of rutin protected the mice against the depletion of SOD and GPx activities significantly. Following 7 days of rutin treatment, we sacrificed the mice and analyzed their soleus muscle and brain for peroxisome proliferator-activated receptor-? coactivator (PGC-1?) and sirtuin 1 (SIRT1) mRNA expression. We observed that rutin treatment increased PGC-1? and SIRT1 mRNA and protein expression. The changes in these markers of mitochondrial biogenesis were associated with increased maximal endurance capacity. The application of 2D gel electrophoresis to analyze the rutin-responsive protein profiles in the WFST mouse brain further revealed the upregulation of the CB1 cannabinoid receptor-interacting protein 1, myelin basic protein, Rho GDP dissociation inhibitor (GDI) alpha, and TPI, indicating that rutin might inhibit anxiety through the upregulation of the expression of anxiety-associated proteins. Western blot analysis of MAPK expression further confirmed the antianxiety effects of rutin. Our study results thus indicate that rutin treatment ameliorates the various impairments associated with physical fatigue.
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Variations in the MHC region confer risk to esophageal squamous cell carcinoma on the subjects from high-incidence area in northern china.
PLoS ONE
PUBLISHED: 01-01-2014
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The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.
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[Effect of AMLl-ETO Fusion Protein on the Expression of BCL-].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 12-28-2013
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This study was aimed to investigate the effect of AML1-ETO fusion protein on the anti-apoptotic gene BCL-2 in leukemic cells and to explore its role in leukemogenesis. The apoptotic levels of U937-WT, U937-Mock and U937-A/E1-4 cells were examined by flow cytometry. And cleaved caspase-3 protein expression was detected by Western blot. BCL-2 gene expression both in AML1-ETO-expressing cells or U937 nonexpressing cells and in leukemia cells of AML patients with or without t(8;21) was assessed by quantitative PCR. The chromatin immunoprecipitation (ChIP)-based PCR was used to investigate the direct interaction between the AML1-ETO and BCL-2 promoter in AML1-ETO positive leukemia cell line. The results indicated that in U937-A/E cells but not in U937-WT or U937-Mock cells, apoptotic cells statistically significantly increased, and AML1-ETO expression also significantly enhanced activation of caspase-3. AML1-ETO-expressing cell subclones displayed significantly low levels of BCL-2 mRNA in comparison with the non-transfected U937. In primary bone marrow cells of acute myeloid leukemia containing AML1-ETO, levels of BCL-2 mRNA were markedly lower as compared with other acute myeloid leukemias lacking this translocation. The enriched regions in transfected cells were located within BCL-2 promoter. It is concluded that BCL-2 is the direct target gene of AML1-ETO. AML1-ETO can down-regulate the expression of BCL-2.
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[Expression and diagnosis value of Fascin in non-small cell lung cancer patients].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-05-2013
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To evaluate the diagnostic significance of Fascin protein in non-small cell lung cancer (NSCLC) patients.
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The role of systemically delivered bone marrow-derived mesenchymal stem cells in the regeneration of periodontal tissues.
Int J Oral Maxillofac Implants
PUBLISHED: 11-27-2013
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Purpose: Recent studies have shown that periodontal ligament stem cells (PDLSCs) play a key role in periodontal regeneration. However, the origin of these cells remains unclear. Meanwhile, bone marrow is thought to be the most common source of adult stem cells in many tissues and organs. Thus, the present investigation sought to determine whether systemically delivered bone marrow-derived mesenchymal stem cells (BM-MSCs) could participate in periodontal regeneration and differentiate into periodontal-specific cells and to explore the origin of PDLSCs. Methods: Enhanced green fluorescent protein (EGFP)-labeled BMMSCs were delivered into lethally irradiated rats by intra-bone marrow (IBM) transplantation. Four weeks after transplantation, periodontal defects with and without infection of anaerobic cultured Porphyromonas gingivalis were established. The animals were killed 1, 2, 4, or 6 weeks after periodontal defect surgery. Histomorphologic analysis, direct observation with the fluorescence microscope, and immunohistochemical staining were performed to evaluate the localization and differentiation of BM-MSCs. Results: EGFP-positive BM-MSCs could be observed as early as 1 week after surgery, and the number of EGFP-positive cells reached a maximum at 2 weeks. Meanwhile, EGFP-positive cells were observed in the newly formed bone, PDL, and cementum 4 weeks after surgery. Immunohistochemical staining verified that EGFP-positive BM-MSCs could differentiate into osteoblasts. Conclusions: These findings provide direct evidence that BM-MSCs can participate in and modulate periodontal regeneration.
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The small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis.
Blood
PUBLISHED: 11-06-2013
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Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into the blood circulation has been widely used for hematopoietic transplantation. However, the current methods of cytokine- or small-molecule-stimulated HSPC mobilization are far from satisfactory. New mobilizing agents are needed to increase the number of stem cells in peripheral blood for effective reconstitution of hematopoiesis. Here, we report that the molecule Me6TREN (Me6) can induce rapid mobilization of hematopoietic progenitor cells, and that Me6 exhibits more significant effects than G-CSF or AMD3100. Me6 also mobilizes long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in primary and secondary transplant recipients. Mechanistically, Me6 inhibits both the SDF-1?-induced migration and VLA-4-mediated adhesion of mouse and human hematopoietic cells. Me6 appears to mobilize HSPCs by activating MMP-9 expression and disrupting the SDF-1?/CXCR4 axis. Therefore, Me6 may become a new, potent and efficacious mobilizing agent of HSPCs.
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[Differentiation potential of CD41? cells derived from the mouse aorta-gonad-mesonephros region, yolk sac and embryonic circulating blood].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 11-01-2013
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To compare the differentiation ability difference of hematopoietic, mesenchymal and endothelial potential between CD41? cells derived from the mouse aorta-gonadmesonephros (AGM) region, yolk sac (YS) and embryonic circulating blood (CB).
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Ribbon aromaticity in double-chain planar B(n)H2(2-) and Li2B(n)H2 nanoribbon clusters up to n = 22: lithiated boron dihydride analogues of polyenes.
Phys Chem Chem Phys
PUBLISHED: 10-04-2013
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We report an extensive density-functional theory and coupled-cluster CCSD(T) study on boron dihydride dianion clusters BnH2(2-) (n = 6-22) and their dilithiated Li2BnH2(0/-) salt complexes. Double-chain (DC) planar nanoribbon structures are confirmed as the global minima for the BnH2(2-) (n = 6-22) clusters. Charging proves to be an effective mechanism to stabilize and extend the DC planar nanostructures, capable of producing elongated boron nanoribbons with variable lengths between 4.3-17.0 Å. For the dilithiated salts, the DC planar nanoribbons are lowest in energy up to Li2B14H2 and represent true minima for all Li2BnH2(0/-) (n = 6-22) species. These boron nanostructures may be viewed as molecular zippers, in which two atomically-thin molecular wires are zipped together via delocalized bonds. Bonding analysis reveals the nature of ? plus ? double conjugation in the lithiated DC nanoribbon Li2BnH2(0/-) (n up to 22) model clusters, which exhibit a 4n pattern in adiabatic detachment energies, ionization potentials, and second-order differences in total energies. Band structure analysis of the infinite DC boron nanoribbon structure also reveals that both ? and ? electrons participate in electric conduction, much different from the monolayer boron ?-sheet in which only ? electrons act as carriers. A concept of "ribbon aromaticity" is proposed for this quasi-one-dimensional system, where regular ? versus ? alternation of the delocalized electron clouds along the nanoribbons results in enhanced stability for a series of "magic" nanoribbon clusters. The total number of delocalized ? and ? electrons for ribbon aromaticity collectively conforms to the (4n + 2) Hückel rule. Ribbon aromaticity appears to be a general concept in other nanoribbon systems as well.
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Effect of Paricalcitol on Left Ventricular Mass and Function in CKD--The OPERA Trial.
J. Am. Soc. Nephrol.
PUBLISHED: 09-19-2013
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Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 ?g) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 ?g one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.
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[Clinical observation of jianpi bushen formula to prevent collapse of osteonecrosis of femoral head].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-10-2013
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To observe the clinical effect of Jianpi Bushen formula to prevent the collapse of osteonecrosis of femoral head (ONFH) of type phlegm and blood stasis obstructing the collaterals. 50 cases (including 73 hips) of non-collapse ONFH (ARCO I, II, III a) were selected from the out-patient department of orthopedic in Guanganmen Hospital attached to China Academy of Chinese Medical Science. All the cases fit for diagnostic criteria were given Jianpi Bushen formula and followed up. Staging criteria was ARCO classification. Harris score evaluated the hip function. The mean follow-up time was 4.2 years (3-5.4 years). After a mean of 4.2 years (3-5.4 years) followed-up, 12 hips collapse occurred while 61 hips not (the non-collapse rate was 83.56%). Collapse did not occurred among the all 7 hips at stage ARCO I (the non-collapse rate was 100%). Among the 49 hips at stage ARCO II, 9 hips collapse occurred while 40 hips not (the non-collapse rate was 81.63%). Among the 17 hips at stage ARCO III a, 3 hips collapse occurred while 14 hips not (the non-collapse rate was 82.35%). Kaplan-Meier analysis showed the average survival time of non-collapse was 5 years (4. 8-5.2 years). The 3 year survival rate of non-collapse was 92.5%. The 4 year survival rate was 74% and the condition tended to be stability trend. The Harris score was 71.93 +/- 11.25 before treatment and 81.63 +/- 12.16 after treatment, significantly different. These results suggest that: Jianpi Bushen formula is an effective method for treating ONFH of type phlegm and blood stasis obstructing the collaterals. It can delay or prevent the collapse of femoral head and significantly improve the hip function.
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An engineered multidomain fungicidal peptide against plant fungal pathogens.
Sheng Li Xue Bao
PUBLISHED: 08-22-2013
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Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mammalian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alternatives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engineered a sexual mating pheromone of Candida albicans, ?-factor pheromone to colicin Ia. A peptide was constructed consisting of an ? mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity of pheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agricultural conditions.
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Liver X receptor ? inhibits osteosarcoma cell proliferation through up-regulation of FoxO1.
Cell. Physiol. Biochem.
PUBLISHED: 06-21-2013
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Osteosarcoma is the most common primary bone malignancy of adolescents and young adults.
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Prevalence of and associations with reduced exercise capacity in peritoneal dialysis patients.
Am. J. Kidney Dis.
PUBLISHED: 05-21-2013
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Exercise capacity is reduced in patients with end-stage renal disease on maintenance home peritoneal dialysis therapy, although the potential mechanisms and clinical implications remain unclear.
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Secondary prophylaxis of variceal bleeding for cirrhotic patients: a multiple-treatments meta-analysis.
Eur. J. Clin. Invest.
PUBLISHED: 05-03-2013
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OBJECTIVE: To evaluate comprehensively the effects of 12 prophylaxis interventions for secondary prophylaxis of variceal bleeding using multiple-treatments meta-analysis. METHODS: PubMed, EMBASE and the Cochrane Library were searched prior to November 2011. Randomized controlled trials (RCTs) comparing the interventions for secondary prophylaxis of variceal bleeding. The primary study outcomes were variceal rebleeding, mortality due to rebleeding and mortality due to all causes. RESULTS: We systematically reviewed 51 RCTs. Transjugular intrahepatic portosystemic shunt (TIPS), ?-blockers combined with endoscopic injection sclerotherapy (EIS) and endoscopic banding ligation (EBL) combined with EIS were superior to ?-blockers [odds ratios (OR) 0·13, 0·23 and 0·13, respectively] and EIS (0·19, 0·34 and 0·18, respectively) in reducing the rate of rebleeding. To reduce the mortality rate due to rebleeding, TIPS was more efficacious than ?-blockers (0·11), EBL (0·13), EIS (0·19), ?-blockers combined with isosorbide-5-mononitrate (5-ISMN) (0·16) and ?-blockers combined with EIS (0·14). In addition, ?-blockers combined with 5-ISMN were significantly more efficacious than ?-blockers (0·56) and EBL (0·64) to reduce the mortality rate due to all causes. EBL combined with argon plasma coagulation showed the best profile of reduction in rebleeding rate and mortality rate due to all causes. To reduce the mortality rate due to rebleeding, TIPS had the highest probability. EBL combined with EIS was the best choice according to the cumulative probabilities of being among the three most efficacious interventions for the three outcomes. CONCLUSIONS: Endoscopic banding ligation combined with EIS might be the first choice in the secondary prophylaxis of varices bleeding.
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Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.
Hepatology
PUBLISHED: 05-01-2013
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Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013).
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Treatment Of Glossopharyngeal Neuralgia With Peripheral Glycerol Injection:Our Experience In Twenty One Older Patients.
Clin Otolaryngol
PUBLISHED: 04-25-2013
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Idiopathic glossopharyngeal neuralgia is similar to trigeminal neuralgia, but much less common and medical therapy is generally less effective in controlling its pain symptoms.(1) Although surgical therapy could sufficiently eliminate their pain symptom, it can produce such complications as swallowing problem. Different from adults, an important aspect of those older patients with glossopharyngeal neuralgia may be in that they were ill with some aged-related diseases and put them in the high-risk medical status. So they could be not suitable for or refused to the invasive treatments. It is a challenging problem for clinicians to control pain symptom in this disease. This article is protected by copyright. All rights reserved.
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Surface hydrophilic modification of polyethersulfone membranes by surface-initiated ATRP with enhanced blood compatibility.
Colloids Surf B Biointerfaces
PUBLISHED: 04-15-2013
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Surface-initiated atom transfer radical polymerization (SI-ATRP) was used to tailor the functionality of polyethersulfone (PES) membranes. A two-step method including nitration reaction and amination reaction was used to synthesize aminated polyethersulfone (PES-NH2) for the preparation of PES/PES-NH2 membranes. Covalently tethered hydrophilic polymer brushes of poly(N-vinylpyrrolidone) (PVP) were prepared via SI-ATRP at low temperature in an aqueous solvent. Attenuated total reflection-Fourier transform infrared (ATR-FTIR), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), and water contact angle were used to characterize the modified membranes surfaces. The PVP-grafted PES membranes showed lower protein adsorption and suppressed platelet adhesion compared with the pristine PES membrane. Moreover, the activated partial thromboplastin time (APTT) for the PVP-grafted PES membranes was increased. These results indicated that the surface hydrophilic modification by grafting PVP brushes provided practical application for the PES membranes with good blood compatibility.
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A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis.
Free Radic. Biol. Med.
PUBLISHED: 03-28-2013
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We have previously shown that the natural diterpenoid derivative S3 induced Bim upregulation and apoptosis in a Bax/Bak-independent manner. However, the exact molecular target(s) of S3 and the mechanism controlling Bim upregulation are still not clear. Here, we identify that S3 targets the selenoproteins TrxR1 and TrxR2 at the selenocysteine residue of the reactive center of the enzymes and inhibits their antioxidant activities. Consequently, cellular ROS is elevated, leading to the activation of FOXO3a, which contributes to Bim upregulation in Bax/Bak-deficient cells. Moreover, S3 retards tumor growth in subcutaneous xenograft tumors by inhibiting TrxR activity in vivo. Our studies delineate the signaling pathway controlling Bim upregulation, which results in Bax/Bak-independent apoptosis and provide evidence that the compounds can act as anticancer agents based on mammalian TrxRs inhibition.
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Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance.
Autophagy
PUBLISHED: 03-21-2013
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Breast cancer tissue contains a small population of cells that have the ability to self-renew; these cells are known as cancer stem-like cells (CSCs). We have recently shown that autophagy is essential for the tumorigenicity of these CSCs. Salinomycin (Sal), a K (+) /H (+) ionophore, has recently been shown to be at least 100 times more effective than paclitaxel in reducing the proportion of breast CSCs. However, its mechanisms of action are still unclear. We show here that Sal blocked both autophagy flux and lysosomal proteolytic activity in both CSCs and non-CSCs derived from breast cancer cells. GFP-LC3 staining combined with fluorescent dextran uptake and LysoTracker-Red staining showed that autophagosome/lysosome fusion was not altered by Sal treatment. Acridine orange staining provided evidence that lysosomes display the characteristics of acidic compartments in Sal-treated cells. However, tandem mCherry-GFP-LC3 assay indicated that the degradation of mCherry-GFP-LC3 is blocked by Sal. Furthermore, the protein degradation activity of lysosomes was inhibited, as demonstrated by the rate of long-lived protein degradation, DQ-BSA assay and measurement of cathepsin activity. Our data indicated that Sal has a relatively greater suppressant effect on autophagic flux in the ALDH (+) population in HMLER cells than in the ALDH (-) population; moreover, this differential effect on autophagic flux correlated with an increase in apoptosis in the ALDH (+) population. ATG7 depletion accelerated the proapoptotic capacity of Sal in the ALDH (+) population. Our findings provide new insights into how the autophagy-lysosomal pathway contributes to the ability of Sal to target CSCs in vitro.
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Epigenetic regulation of the Wnt signaling inhibitor DACT2 in human hepatocellular carcinoma.
Epigenetics
PUBLISHED: 02-28-2013
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DACT2 (Dapper, Dishevelled-associated antagonist of ?-catenin homolog 2) is a member of the DACT family involved in the regulation of embryonic development. Human DACT2 is localized on 6q27, a region of frequent loss of heterozygosity in human cancers. However, the regulation of DACT2 expression and function in hepatocellular carcinoma (HCC) remains unclear. In this study, genetic and epigenetic changes of DACT2 were analyzed in HCC cell lines and primary cancer. We found no single-nucleotide polymorphism (SNP) associated with HCC. Promoter region methylation was correlated with loss or reduction of DACT2 expression, and restoration of DACT2 expression was induced by 5-aza-2-deoxycytidine (5-AZA) in HCC cell lines. Promoter region methylation was found in 54.84% of primary HCC. Reduction of DACT2 expression was associated with promoter hypermethylation, and expression of DACT2 was inversely related to ?-catenin expression in primary HCC. DACT2 suppressed cell proliferation, induced G 2-M arrest in cell lines and inhibited tumor growth in xenograft nude mice. The transcriptional activity of TCF-4 and the expression of Wnt signaling downstream genes were suppressed by DACT2 re-expression and reactivated by depletion of DACT2. In conclusion, DACT2 is frequently methylated in HCC and its expression is regulated by promoter hypermethylation. DACT2 suppresses HCC by inhibiting Wnt signaling in human HCC.
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Infusion of megakaryocytic progenitor products generated from cord blood hematopoietic stem/progenitor cells: results of the phase 1 study.
PLoS ONE
PUBLISHED: 02-04-2013
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Currently, a constant shortage in the supply of platelets has become an important medical and society challenge, especially in developing country, and the in vitro production of megakaryocytic progenitor cells (MPs) from cord blood could represent an effective platelet substitute. In the present study, our objective was to determine the safety and feasibility of ex vivo generated MPs in patients.
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Epigenetic silencing of Bcl-2, CEBPA and p14(ARF) by the AML1-ETO oncoprotein contributing to growth arrest and differentiation block in the U937 cell line.
Oncol. Rep.
PUBLISHED: 01-31-2013
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The AML1-ETO fusion transcription factor generated by the t(8;21) translocation is considered to deregulate the expression of genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors, resulting in acute myelogenous leukemia by recruiting co-repressor complexes to DNA. To investigate the role of AML1-ETO in leukemogenesis, we transfected the cloned AML1-ETO cDNA and expressed the AML1-ETO protein in U937 myelomonocytic leukemia cells. By focusing on the anti-apoptotic gene Bcl-2, the key regulator gene of granulocytic differentiation CCAAT/enhancer-binding protein ? (CEBPA) and the tumor suppressor gene p14(ARF), we found that both AML1-ETO-expressing cell lines and t(8;21) leukemia samples displayed low levels of these three genes. Chromatin immunoprecipitation assays demonstrated that Bcl-2, CEBPA and p14(ARF) were direct transcriptional targets of AML1-ETO. The universal binding of AML1-ETO to genomic DNA resulted in recruitment of methyl-CpG binding protein 2 (MeCP2), reduction of histone H3 or H4 acetylation and increased trimethylation of histone H3 lysine 9 as well as lysine 27 indicating that AML1-ETO induced heterochromatic silencing of Bcl-2, CEBPA and p14(ARF). These results suggested that the aberrant transcription factor AML1-ETO epigenetically silenced the function of the Bcl-2, CEBPA and p14(ARF) genes by inducing repressed chromatin configurations at their promoters through histone modifications.
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In vitro large scale production of human mature red blood cells from hematopoietic stem cells by coculturing with human fetal liver stromal cells.
Biomed Res Int
PUBLISHED: 01-30-2013
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In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs). HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 10(9)-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive ? -globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs) are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.
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Antitumor effects of Dasatinib on laryngeal squamous cell carcinoma in vivo and in vitro.
Eur Arch Otorhinolaryngol
PUBLISHED: 01-29-2013
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A novel drug named Dasatinib is a highly potent ATP-competitive orally active dual Src/Abl kinase inhibitor with anti-proliferative activity against solid tumors and CML (chronic myeloid leukaemia) cell lines. Dasatinib has been shown to have preclinical activity against human prostate, breast, pancreatic, lung, and head and neck cancer. To determine whether Dasatinib can inhibit the growth of laryngeal squamous cell carcinoma, in the present study, we investigated the antitumor effect of Dasatinib on Hep-2 cells. Hep-2 cells were treated with different concentrations of Dasatinib for different time. Cell proliferation, cell cycle distribution, and cell apoptosis were evaluated using MTT assay, flow cytometry, and fluorescent microscopy. It was found that Dasatinib exhibited significant efficacy in growth inhibition, cell cycle arrest at G0/G1 phase, and apoptosis induction in a dose- and time-dependent manner. Measuring the modulation of regulators in the cell cycle, apoptosis and signal transductions by western blot analysis showed that the effect of Dasatinib was due to suppression of the expression of Bax, Bcl-2, Caspase-3, and Caspase-8. Moreover, in vivo studies were performed in a nude mouse xenograft model, the new prescription (DDP + Dasatinib) was better than DDP alone in terms of therapeutic efficacy. In conclusion, the antitumor effect of Dasatinib on Hep-2 cells was due to the induction of cell cycle arrest as well as apoptosis. The possible mechanisms underlying the action might be attributed to the suppression of Src phosphorylation. This investigation suggests a potential clinical application of Dasatinib for the treatment of laryngeal cancer patients.
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Why to synthesize vaterite polymorph of calcium carbonate on the cellulose matrix via sonochemistry process?
Ultrason Sonochem
PUBLISHED: 01-20-2013
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Vaterite is an important biomedical material due to its features such as high specific surface area, high solubility, high dispersion, and small specific gravity. The purposes of this article were to explore the growth mechanism of vaterite on the cellulose matrix via sonochmistry process. In the work reported herein, the influences of experimental parameters on the polymorph of calcium carbonate were investigated in detail. The calcium carbonate crystals on the cellulose matrix were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Experimental results revealed that all the reactants, solvent, and synthesis method played an important role in the polymorph of calcium carbonate. The pure phase of vaterite polymorph was obtained using Na2CO3 as reactant in ethylene glycol on the cellulose matrix via sonochmistry process. Based on the experimental results, one can conclude that the synthesis of vaterite polymorph is a system process.
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Advances in cell lineage reprogramming.
Sci China Life Sci
PUBLISHED: 01-09-2013
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As a milestone breakthrough of stem cell and regenerative medicine in recent years, somatic cell reprogramming has opened up new applications of regenerative medicine by breaking through the ethical shackles of embryonic stem cells. However, induced pluripotent stem (iPS) cells are prepared with a complicated protocol that results in a low reprogramming rate. To obtain differentiated target cells, iPS cells and embryonic stem cells still need to be induced using step-by-step procedures. The safety of induced target cells from iPS cells is currently a further concerning matter. More broadly conceived is lineage reprogramming that has been investigated since 1987. Adult stem cell plasticity, which triggered interest in stem cell research at the end of the last century, can also be included in the scope of lineage reprogramming. With the promotion of iPS cell research, lineage reprogramming is now considered as one of the most promising fields in regenerative medicine, will hopefully lead to customized, personalized therapeutic options for patients in the future.
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Overexpression of miR -155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3.
PLoS ONE
PUBLISHED: 01-09-2013
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MicroRNA155 plays an important role in many solid malignancies. Expression and function of miR-155 in laryngeal carcinoma have not been fully understood. This study aims to investigate the expression and function of miR-155 in laryngeal squamous cell carcinoma (LSCC), the relationship between miR-155 and its downstream target suppressor of cytokine signaling 1 (SOCS1)-STAT3 pathway, and the related clinicopathological factors. Sixty-three samples of laryngeal squamous cell carcinoma and twenty-one samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and real-time PCR. Hep-2 cells were cultured and transfected with miR-155 mimic and ASO. Cell proliferation, migration and invasion assays were used to determine the role of miR-155 in regulation of LSCC growth, migration, and invasion, respectively. The expression levels of miR-155 in LSCC were significantly higher than those in the control mucosa tissues. Downregulation of SOCS1 expression and elevated expression of STAT3 were also observed in LSCC. The relevance of the three factors were statistically significant. Moreover, knockdown of miR-155 elevated SOCS1expression level, suppressed STAT3 expression, and inhibited hep-2 cells growth, migration and invasion. Whereas overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion. Furthermore, the miR-155 levels in T(3) T(4) stages, and poor/moderate cell differentiation were significantly higher than those in T(2) stage and higher degree of cell differentiation. The STAT3 protein in poor/moderate cell differentiation was significantly higher than those in higher degree of cell differentiation. We firstly demonstrated the aberrant expression and function of miR-155 and itsdownstream targets in LSCC. The current findings suggest that miR-155 play promotingrole during the development of LSCC, and miR-155 may be a useful marker for the prognosis and assessment of therapeutic effects.
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Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 12-08-2011
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Prior experimental studies show that thoracic spinal cord stimulation (SCS) improves left ventricular (LV) ejection fraction (LVEF). The mechanism of this improvement in the LV contractile function after SCS and its effects on the myocardial oxygen consumption remains unknown.
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Natural diterpenoid compound elevates expression of Bim protein, which interacts with antiapoptotic protein Bcl-2, converting it to proapoptotic Bax-like molecule.
J. Biol. Chem.
PUBLISHED: 11-07-2011
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Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak-independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knock-out murine embryonic fibroblasts and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane; this was accompanied by oligomerization of these proteins and deep embedding of Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane, thereby inducing apoptosis independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics.
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Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial.
J. Natl. Cancer Inst.
PUBLISHED: 11-04-2011
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Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown.
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Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis.
Hepatology
PUBLISHED: 11-03-2011
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The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result of frequent metastasis and tumor recurrence. Unfortunately, the underlying molecular mechanisms driving HCC metastasis are still not fully understood. It has been demonstrated that tumor stroma cells contribute to primary tumor growth and metastasis. Within the HCC environment, activated hepatic stellate cells (HSCs) can release a number of molecules and enhance cancer cell proliferation and invasiveness in a paracrine manner. Here, for the first time, we demonstrate that epimorphin (EPM; also called syntaxin-2), an extracellular protein, is strongly elevated in activated HSCs within tumor stroma. We show that knockdown of EPM expression in HSCs substantially abolishes their effects on cancer cell invasion and metastasis. Ectopic expression of EPM in HCC cancer cells enhances their invasiveness; we demonstrate that the cells expressing EPM have markedly increased metastasis potential. Furthermore, EPM-mediated invasion and metastasis of cancer cells is found to require up-regulation of matrix metalloproteinase-9 (MMP-9) through the activation of focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) axis.
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Comparative histopathology of mice infected with the 17XL and 17XNL strains of Plasmodium yoelii.
J. Parasitol.
PUBLISHED: 10-21-2011
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Plasmodium yoelii 17XL was used to investigate the mechanism of Plasmodium falciparum-caused cerebral malaria, although its histological effect on other mouse organs is still unclear. Here, histological examination was performed on mice infected with P. yoelii 17XL; the effect of P. yoelii 17XL infection on anemia and body weight loss, as well as its lesions in the brain, liver, kidney, lung, and spleen, also was investigated. Plasmodium yoelii 17XL-infected red blood cells were sequestered in the microcirculation of the brain and in the kidney. Compared with the nonlethal P. yoelii 17XNL strain, infection by P. yoelii 17XL caused substantial pulmonary edema, severe anemia, and significant body weight loss. Although P. yoelii 17XNL and 17XL produced a similar focal necrosis in the mouse liver, infection of P. yoelii 17XL induced coalescing of red and white pulp. Mortality caused by P. yoelii 17XL may be due to cerebral malaria, as well as respiratory distress syndrome and severe anemia. Plasmodium yoelii 17XL-infected rodent malaria seems to be a useful model for investigating severe malaria caused by P. falciparum.
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Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus.
Cardiovasc Diabetol
PUBLISHED: 09-24-2011
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Patients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.
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Role of epimorphin in bile duct formation of rat liver epithelial stem-like cells: involvement of small G protein RhoA and C/EBP?.
J. Cell. Physiol.
PUBLISHED: 09-22-2011
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Epimorphin/syntaxin 2 is a high conserved and very abundant protein involved in epithelial morphogenesis in various organs. We have shown recently that epimorphin (EPM), a protein exclusively expressed on the surface of hepatic stellate cells and myofibroblasts of the liver, induces bile duct formation of hepatic stem-like cells (WB-F344 cells) in a putative biophysical way. Therefore, the aim of this study was to present some of the molecular mechanisms by which EPM mediates bile duct formation. We established a biliary differentiation model by co-culture of EPM-overexpressed mesenchymal cells (PT67(EPM)) with WB-F344 cells. Here, we showed that EPM could promote WB-F344 cells differentiation into bile duct-like structures. Biliary differentiation markers were also elevated by EPM including Yp, Cx43, aquaporin-1, CK19, and gamma glutamyl transpeptidase (GGT). Moreover, the signaling pathway of EPM was analyzed by focal adhesion kinase (FAK), extracellular regulated kinase 1/2 (ERK1/2), and RhoA Western blot. Also, a dominant negative (DN) RhoA-WB-F344 cell line (WB(RhoA-DN)) was constructed. We found that the levels of phosphorylation (p) of FAK and ERK1/2 were up-regulated by EPM. Most importantly, we also showed that RhoA is necessary for EPM-induced activation of FAK and ERK1/2 and bile duct formation. In addition, a dual luciferase-reporter assay and CHIP assay was performed to reveal that EPM regulates GGT IV and GGT V expression differentially, possibly mediated by C/EBP?. Taken together, these data demonstrated that EPM regulates bile duct formation of WB-F344 cells through effects on RhoA and C/EBP?, implicating a dual aspect of this morphoregulator in bile duct epithelial morphogenesis.
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[Study on estimation of fall dormancy in alfalfa by near infrared reflectance spectroscopy and support vector machine model].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-19-2011
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The present study proposes a new approach to producing accurate estimates of fall dormancy (FD) in alfalfa in a rapid manner. Using near infrared spectroscopy, the approach produces results fast without causing damage to samples. Near infrared reflectance spectroscopy was applied to measuring the spectra of samples. Then principal component analysis (PCA) was conducted on the measurements. The top ten principal components were selected based on their cumulative contribution rates to build a support vector machine (SVM) model. Detailed analysis and discussions were conducted over their parameter and kernel classifications. The experiment found that when c = 0.339 2 and g = 32, the accuracy of the predictions of the test set can reach 98.182%. Therefore the approach can estimate the FD in alfalfa in a rapid and accurate manner. Moreover, it was compared with other approaches such as principal component regression, partial least squares regression, BP neural networks, and LVQ neural networks. The comparisons have shown that the PCA-SVM model can effectively address the small-sample-size problem and avoid local minimum.
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Genotyping cytomegalovirus UL97 mutations by high-resolution melting analysis with unlabeled probe.
Arch. Virol.
PUBLISHED: 08-18-2011
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Human cytomegalovirus (CMV) is an opportunistic pathogen, and infections with this virus can be treated with ganciclovir (GCV). Most GCV-resistant clinical CMV isolates contain a mutation in the UL97 gene. Genotypic assays for diagnostic screening of GCV-resistant CMV have been developed. High-resolution melting analysis (HRMA) with unlabeled probe is considered a perfect tool for this purpose. In this study, we have developed an HRMA-based genotypic test for the detection of UL97 mutations. Wild type and M460V/I mutants of UL97 were constructed. HRMA with unlabeled probe was used as a genotyping method for the detection of M460V/I mutations. The melting peaks obtained directly from PCR products did not enable us to distinguish the wild type from M460 mutants. The sensitivity and accuracy of HRMA were dramatically improved by using unlabeled probe. HRMA with unlabeled probe successfully distinguished M460V from M460I and served well for the detection of M460V/I mutations in clinical samples. HRMA with unlabeled probe proves to be a sensitive and cost-effective genotyping method for the detection of M460 mutations.
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[Insect odorant receptors and their olfactory signal transduction pathway].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 08-11-2011
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Protection against insect bites is one of the main strategies in prevention and control of the vector-borne diseases. However, due to the obvious shortcomings of traditional control methods, it is necessary to develop new control measures. Most insects rely on their olfactory systems for host and mate location. Interfering with insect olfactory systems is becoming a hot research area in the control of vector-borne diseases. As odorant receptors play a major role in perception of odorant molecules by insect olfactory system, this paper summarizes the recent progress on insect odorant receptors and their olfactory signal transduction.
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[Immunopathological mechanism of cerebral malaria].
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi
PUBLISHED: 08-10-2011
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Cerebral malaria is a severe complication of malaria. Early studies suggest that cerebral malaria is related to cytoadherence of parasitized red blood cells to the microvessel endothelium of brain. However, more and more evidence supported that the cause of cerebral malaria is uncontrolled inflammatory cytokines and infiltration of lymphocytes in brain microvessel. The article summarizes the research progress on immunological mechanism of cerebral malaria.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.