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Find video protocols related to scientific articles indexed in Pubmed.
CYP2J2 overexpression attenuates non-alcoholic fatty liver disease induced by high fat diet in mice.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 11-13-2014
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Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, anti-apoptotic, and anti-oxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 weeks of high fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared to controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress compared to wild-type control mice. These effects were associated with inhibition of NF-?B/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced in?ammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-?B/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related in?ammation and oxidative stress, and reveal a new molecular mechanism underlying EETs-mediated anti-in?ammatory and antioxidant effects which could aid in the design of new therapies for the prevention and treatment of NAFLD.
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Dipeptidyl Peptidase IV as a Potential Target for Selective Prodrug Activation and Chemotherapeutic Action in Cancers.
Mol. Pharm.
PUBLISHED: 11-04-2014
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The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI50 = 261 ?M) compared to that in SK-MEL-5 cells (GI50 = 807 ?M) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/?g protein) compared to SK-MEL-5 cells (0.68 pmol/min/?g protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.
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Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-03-2014
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Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5(+)) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5(+) or Lgr6(+) cells from taste tissue can generate continuously expanding 3D structures ("organoids"). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5(+) cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6(+) cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5(+) or Lgr6(+) cells, validating the use of this model for the study of taste cell generation.
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[Feasibility study for the dexmetomidine utend the drug induced sleep endoscopy].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-18-2014
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To explore the application of the Dexmedetomidine utend drug induced sleep endoscopy.
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Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin.
Oncotarget
PUBLISHED: 09-17-2014
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Adriamycin, a widely used anthracycline antibiotic in multiple chemotherapy regimens, has been challenged by the cardiotoxicity leading to fatal congestive heart failure in the worst condition. The present study demonstrated that Dihydromyricetin, a natural product extracted from ampelopsis grossedentat, exerted cardioprotective effect against the injury in Adriamycin-administrated ICR mice. Dihydromyricetin decreased ALT, LDH and CKMB levels in mice serum, causing a significant reduction in the toxic death triggered by Adriamycin. The protective effects were also indicated by the alleviation of abnormal electrocardiographic changes, the abrogation of proliferation arrest and apoptotic cell death in primary myocardial cells. Further study revealed that Dihydromyricetin-rescued loss of anti-apoptosis protein ARC provoked by Adriamycin was involved in the cardioprotection. Intriguingly, the anticancer activity of Adriamycin was not compromised upon the combination with Dihydromyricetin, as demonstrated by the enhanced anticancer effect achieved by Adriamycin plus Dihydromyricetin in human leukemia U937 cells and xenograft models, in a p53-dependent manner. These results collectively promised the potential value of Dihydromyricetin as a rational cardioprotective agent of Adriamycin, by protecting myocardial cells from apoptosis, while potentiating anticancer activities of Adriamycin, thus further increasing the therapeutic window of the latter one.
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Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.
Med Chem
PUBLISHED: 09-12-2014
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A series of novel non-peptide boronic acid derivatives were designed and synthesized via rational drug design principles. All target compounds were screened for the proteasome inhibitory activities in vitro. Selected compounds (6a and 7j) were evaluated for their cytotoxic activities in vitro. Among these tested compounds, two (6a, 7j) displayed better proteasome inhibitory activities than that of the lead compound PI-083, and compound 6a was the most potent one with IC?? value of 161.90±29.46 nM. However, both of the two compounds (6a, 7j) exhibited weak cytotoxic activities, the discrepancy may lie in the compensatory pathways of the ubiquitin-proteasome pathway that promote tumor cell survival.
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Large-Scale Fabrication of Pseudocapacitive Glass Windows that Combine Electrochromism and Energy Storage.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-18-2014
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Multifunctional glass windows that combine energy storage and electrochromism have been obtained by facile thermal evaporation and electrodeposition methods. For example, WO3 films that had been deposited on fluorine-doped tin oxide (FTO) glass exhibited a high specific capacitance of 639.8?F?g(-1) . Their color changed from transparent to deep blue with an abrupt decrease in optical transmittance from 91.3?% to 15.1?% at a wavelength of 633?nm when a voltage of -0.6?V (vs. Ag/AgCl) was applied, demonstrating its excellent energy-storage and electrochromism properties. As a second example, a polyaniline-based pseudocapacitive glass was also developed, and its color can change from green to blue. A large-scale pseudocapacitive WO3 -based glass window (15×15?cm(2) ) was fabricated as a prototype. Such smart pseudocapacitive glass windows show great potential in functioning as electrochromic windows and concurrently powering electronic devices, such as mobile phones or laptops.
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[A novel one-tube multiplex RT-PCR assay for simultaneous detection of six human coronaviruses].
Zhonghua Yu Fang Yi Xue Za Zhi
PUBLISHED: 07-03-2014
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To develop an one-tube multiplex RT-PCR assay for simultaneous detection of six human coronaviruses (HCoVs).
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Repair of Achilles tendon defect with autologous ASCs engineered tendon in a rabbit model.
Biomaterials
PUBLISHED: 06-24-2014
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Adipose derived stem cells (ASCs) are an important cell source for tissue regeneration and have been demonstrated the potential of tenogenic differentiation in vitro. This study explored the feasibility of using ASCs for engineered tendon repair in vivo in a rabbit Achilles tendon model. Total 30 rabbits were involved in this study. A composite tendon scaffold composed of an inner part of polyglycolic acid (PGA) unwoven fibers and an outer part of a net knitted with PGA/PLA (polylactic acid) fibers was used to provide mechanical strength. Autologous ASCs were harvested from nuchal subcutaneous adipose tissues and in vitro expanded. The expanded ASCs were harvested and resuspended in culture medium and evenly seeded onto the scaffold in the experimental group, whereas cell-free scaffolds served as the control group. The constructs of both groups were cultured inside a bioreactor under dynamic stretch for 5 weeks. In each of 30 rabbits, a 2 cm defect was created on right side of Achilles tendon followed by the transplantation of a 3 cm cell-seeded scaffold in the experimental group of 15 rabbits, or by the transplantation of a 3 cm cell-free scaffold in the control group of 15 rabbits. Animals were sacrificed at 12, 21 and 45 weeks post-surgery for gross view, histology, and mechanical analysis. The results showed that short term in vitro culture enabled ASCs to produce matrix on the PGA fibers and the constructs showed tensile strength around 50 MPa in both groups (p > 0.05). With the increase of implantation time, cell-seeded constructs gradually form neo-tendon and became more mature at 45 weeks with histological structure similar to that of native tendon and with the presence of bipolar pattern and D-periodic structure of formed collagen fibrils. Additionally, both collagen fibril diameters and tensile strength increased continuously with significant difference among different time points (p < 0.05). In contrast, cell-free constructs failed to form good quality tendon tissue with fibril structure observable only at 45 weeks. There were significant differences in both collagen fibril diameter and tensile strength between two groups at all examined time points (p < 0.05). The results of this study support that ASCs are likely to be a potential cell source for in vivo tendon engineering and regeneration.
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Model selection and diagnostics for joint modeling of survival and longitudinal data with crossing hazard rate functions.
Stat Med
PUBLISHED: 05-09-2014
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Comparison of two hazard rate functions is important for evaluating treatment effect in studies concerning times to some important events. In practice, it may happen that the two hazard rate functions cross each other at one or more unknown time points, representing temporal changes of the treatment effect. Also, besides survival data, there could be longitudinal data available regarding some time-dependent covariates. When jointly modeling the survival and longitudinal data in such cases, model selection and model diagnostics are especially important to provide reliable statistical analysis of the data, which are lacking in the literature. In this paper, we discuss several criteria for assessing model fit that have been used for model selection and apply them to the joint modeling of survival and longitudinal data for comparing two crossing hazard rate functions. We also propose hypothesis testing and graphical methods for model diagnostics of the proposed joint modeling approach. Our proposed methods are illustrated by a simulation study and by a real-data example concerning two early breast cancer treatments. Copyright © 2014 John Wiley & Sons, Ltd.
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Ranolazine attenuates hypoxia- and hydrogen peroxide-induced increases in sodium channel late openings in ventricular myocytes.
J. Cardiovasc. Pharmacol.
PUBLISHED: 04-08-2014
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Ranolazine attenuates cardiac arrhythmic activity associated with hypoxia and hydrogen peroxide (H2O2) by inhibition of late sodium current (late INa). The mechanism of ranolazine's action on Na channels was investigated using whole-cell and single-channel recording from guinea pig isolated ventricular myocytes. Hypoxia increased whole-cell late INa from -0.48 ± 0.02 to -3.99 ± 0.07 pA/pF. Ranolazine at 3 and 9 ?mol/L reduced the hypoxia-induced late INa by 16% ± 3% and 55% ± 3%, respectively. Hypoxia increased the mean open probability and open time of Na-channel late openings from 0.016 ± 0.001 to 0.064 ± 0.007 milliseconds and from 0.693 ± 0.043 to 1.081 ± 0.098 milliseconds, respectively. Ranolazine at 3 and 9 ?mol/L attenuated the hypoxia-induced increase of open probability by 19% ± 7% and 61% ± 1%, and increase of open time by 26% ± 19% and 74 ± 21%, respectively. H2O2 increased the mean open probability and open time of Na-channel late openings from 0.013 ± 0.002 to 0.107 ± 0.015 milliseconds and from 0.689 ± 0.075 to 1.487 ± 0.072 milliseconds, respectively. Ranolazine at 3 and 6 ?mol/L reduced the H2O2-induced increase of mean open probability by 60% ± 7% and 95% ± 2%, and the increase of mean open time by 31% ± 21% and 82% ± 8%. In conclusion, the inhibition by ranolazine of hypoxia- and H2O2-stimulated late INa is due to reduction of both the open probability and open time of Na-channel late openings.
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[Research on the patterns of upper airway obstructive levels by drug-induced sleep endoscopy].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 04-01-2014
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To identify the patterns of airway collapse in patients with obstructive sleep apnea hypopnea syndrome(OSAHS) by dexmedetomidine induced sleep endoscopy.
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Functional toll-like receptor 3 expressed by oral squamous cell carcinoma induced cell apoptosis and decreased migration.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 03-07-2014
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The aim of this study was to investigate the expression and function of toll-like receptor 3 (TLR3) in oral squamous cell carcinoma (OSCC).
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Significantly enhanced photocatalytic activities and charge separation mechanism of Pd-decorated ZnO-graphene oxide nanocomposites.
ACS Appl Mater Interfaces
PUBLISHED: 02-28-2014
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Electron-hole recombination is one of the major factors limiting the efficiency of ZnO-based photocatalysts. In this work, a 2-fold enhancement strategy was employed to suppress electron-hole recombination and boost photocatalytic efficiency. First, significantly enhanced photocatalytic activity of ZnO by introducing graphene oxide (GO) was systematically investigated. Hybrid photocatalysts with different weight ratios of ZnO to GO (from 0.95:0.05 to 0.70:0.30) were synthesized and characterized. The results indicated that when the proportion ratio of ZnO to GO reached 0.85:0.15, the as-synthesized ZnO-GO nanocomposite exhibited the maximum photocatalytic efficiency on methylene blue with an apparent rate constant ?app almost 10 times faster than that of pure ZnO under UV illumination. GO was suggested to enhance the photocatalytic activity of ZnO because of its great capability in dye adsorption and charge separation. Second, Pd nanoparticles were introduced to decorate ZnO-GO to produce generally better photocatalyst ZnO-GO-Pd nanocomposites. The junction between Pd and ZnO was believed to also effectively separate the photogenerated charges due to the metal-semiconductor diode effect. These two systems of ZnO-GO and ZnO-GO-Pd nanocomposites are expected to have a broad range of applications in environmental conservation.
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Genetic variations in the thrombin-activatable fibrinolysis inhibitor gene and risk of cardiovascular disease: a systematic review and meta-analysis.
Thromb. Res.
PUBLISHED: 02-26-2014
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An imbalance between coagulation and fibrinolytic system plays an important role in the pathogenesis of arterial thrombosis. It has been identified that elevated plasma thrombin-activatable fibrinolysis inhibitor (TAFI) concentration, an anti-fibrinolytic factor, is associated with an increased risk of cardiovascular disease (CVD). But the effect of genetic variations in TAFI gene on the risk of CVD is inconclusive.
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Reversible dimers of the atypical antipsychotic quetiapine inhibit p-glycoprotein-mediated efflux in vitro with increased binding affinity and in situ at the blood-brain barrier.
ACS Chem Neurosci
PUBLISHED: 02-07-2014
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The multidrug resistance transporter P-glycoprotein (P-gp) is highly expressed in the capillary endothelial cells of the blood-brain barrier (BBB) where it functions to limit the brain penetration of many drugs, including antipsychotic agents used to treat schizophrenia. Therefore, in an effort to inhibit the transporter, we designed dimers of the antipsychotic drug and P-gp substrate quetiapine (QT), linked by variable length tethers. In P-gp overexpressing cells and in human brain capillary endothelial hCMEC/D3 cells, the dimer with the shortest tether length (QT2C2) (1) was the most potent inhibitor showing >80-fold better inhibition of P-gp-mediated transport than monomeric QT. The dimers, which are linked via ester moieties, are designed to revert to the therapeutic monomer once inside the target cells. We demonstrated that the addition of two sterically blocking methyl groups to the linker (QT2C2Me2, 8) increased the half-life of the molecule in plasma 10-fold as compared to the dimer lacking methyl groups (QT2C2, 1), while retaining inhibitory potency for P-gp transport and sensitivity to cellular esterases. Experiments with purified P-gp demonstrated that QT2C2 (1) and QT2C2Me2 (8) interacted with both the H- and R-binding sites of the transporter with binding affinities 20- to 30-fold higher than that of monomeric QT. Using isolated rat brain capillaries, QT2C2Me2 (8) was a more potent inhibitor of P-gp transport than QT. Lastly, we showed that QT2C2Me2 (8) increased the accumulation of the P-gp substrate verapamil in rat brain in situ three times more than QT. Together, these results indicate that the QT dimer QT2C2Me2 (8) strongly inhibited P-gp transport activity in human brain capillary endothelial cells, in rat brain capillaries, and at the BBB in an animal model.
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Interleukin-10-1082A/G and -592C/A Polymorphisms with risk of Parkinson's disease: a meta-analysis.
Int. J. Neurosci.
PUBLISHED: 02-07-2014
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Several studies have been conducted in recent years to evaluate the risk of Parkinson's disease (PD) and polymorphisms of interleukin-10 (IL-10). However, the results were conflicting. Therefore, we performed this meta-analysis of published case-control studies to assess this association. Systematic searches of electronic databases PubMed Web of Science, BIOSIS Previews, Science Direct, Chinese Biomedical Database, WANFANG Database, and Chinese National Knowledge Infrastructure with hand searching of the references of identified articles were conducted. Data were extracted using a standardized form and pooled odd ratios with 95% confidence intervals were calculated to evaluate the strength of the association. A total of seven case-control studies involving 1912 PD cases and 1740 controls were included, concerning two polymorphisms (-1082A/G and -592C/A) of IL-10 gene. No significant associations were found in the overall analysis for both -1082A/G and -592C/A polymorphisms with PD risk. Similar lacking associations were observed in subgroup analysis based on ethnicity and age of onset. In conclusion, there is no enough evidence for association between IL-10 polymorphisms (-1082A/G and -592C/A) and risk of PD at present. Well-designed studies with larger sample size and multi-ethnicity studies are warranted in the future.
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A two-tube multiplex reverse transcription PCR assay for simultaneous detection of viral and bacterial pathogens of infectious diarrhea.
Biomed Res Int
PUBLISHED: 01-26-2014
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Diarrhea caused by viral and bacterial infections is a major health problem in developing countries. The purpose of this study is to develop a two-tube multiplex PCR assay using automatic electrophoresis for simultaneous detection of 13 diarrhea-causative viruses or bacteria, with an intended application in provincial Centers for Diseases Control and Prevention, China. The assay was designed to detect rotavirus A, norovirus genogroups GI and GII, human astrovirus, enteric adenoviruses, and human bocavirus (tube 1), and Salmonella, Vibrio parahaemolyticus, diarrheagenic Escherichia coli, Campylobacter jejuni, Shigella, Yersinia, and Vibrio cholera (tube 2). The analytical specificity was examined with positive controls for each pathogen. The analytical sensitivity was evaluated by performing the assay on serial tenfold dilutions of in vitro transcribed RNA, recombinant plasmids, or bacterial culture. A total of 122 stool samples were tested by this two-tube assay and the results were compared with those obtained from reference methods. The two-tube assay achieved a sensitivity of 20-200 copies for a single virus and 10(2)-10(3)?CFU/mL for bacteria. The clinical performance demonstrated that the two-tube assay had comparable sensitivity and specificity to those of reference methods. In conclusion, the two-tube assay is a rapid, cost-effective, sensitive, specific, and high throughput method for the simultaneous detection of enteric bacteria and virus.
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Dracorhodin perchlorate induces apoptosis in primary fibroblasts from human skin hypertrophic scars via participation of caspase-3.
Eur. J. Pharmacol.
PUBLISHED: 01-21-2014
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Hypertrophic scar (HS) is an abnormally proliferative disorder characterized by excessive proliferation of fibroblasts and redundant deposition of extracellular matrix. An unbalance between fibroblast proliferation and apoptosis has been assumed to play an important role in HS formation. To explore the regulative effects of dracorhodin perchlorate (Dp), one of the derivants of dracorhodin that is a major constituent in the traditional Chinese medicine, on primary fibroblasts from human skin hypertrophic scars, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis were respectively used to evaluate the inhibitory effect of Dp on the cells and to determine cell cycle distribution. Additionally, cellular apoptosis was separately detected with Hoechst 33258 staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression levels of caspase-3 mRNA and protein were respectively measured with reverse transcription-polymerase chain reaction and western blot analysis, and caspase-3 activity were determined using a colorimetric assay kit. The results showed that Dp significantly inhibited cell growth, and induced apoptosis in fibroblasts in a dose-and time-dependent manner, arresting cell cycle at G1 phase. Additionally, Dp slightly up-regulated caspase-3 mRNA expression in fibroblasts, but significantly down-regulated caspase-3 protein expression in a dose- and time-dependent manner, and concurrently elevated caspase-3 activity. Taken together, these data indicated that Dp could effectively inhibit cell proliferation, and induced cell cycle arrest and apoptosis in fibroblasts, at least partially via modulation of caspase-3 expression and its activity, which suggests that Dp is an effective and potential candidate to develop for HS treatment.
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Sex differences in the association between dietary restraint, insulin resistance and obesity.
Eat Behav
PUBLISHED: 01-14-2014
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Restrained food consumption may alter metabolic function and contribute to eventual weight gain; however, sex differences in these relationships have not been assessed. The objective of this study was to examine the relationship between restrained eating and insulin resistance and the influence of body mass index and sex on this relationship in a large community sample of both men and women. We hypothesized that restrained eating would be related to insulin resistance and this relationship would be influenced by sex and body mass index.
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Synthesis and evaluation of Strychnos alkaloids as MDR reversal agents for cancer cell eradication.
Bioorg. Med. Chem.
PUBLISHED: 01-11-2014
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Natural products represent the fourth generation of multidrug resistance (MDR) reversal agents that resensitize MDR cancer cells overexpressing P-glycoprotein (Pgp) to cytotoxic agents. We have developed an effective synthetic route to prepare various Strychnos alkaloids and their derivatives. Molecular modeling of these alkaloids docked to a homology model of Pgp was employed to optimize ligand-protein interactions and design analogues with increased affinity to Pgp. Moreover, the compounds were evaluated for their (1) binding affinity to Pgp by fluorescence quenching, and (2) MDR reversal activity using a panel of in vitro and cell-based assays and compared to verapamil, a known inhibitor of Pgp activity. Compound 7 revealed the highest affinity to Pgp of all Strychnos congeners (Kd=4.4?M), the strongest inhibition of Pgp ATPase activity, and the strongest MDR reversal effect in two Pgp-expressing cell lines. Altogether, our findings suggest the clinical potential of these synthesized compounds as viable Pgp modulators justifies further investigation.
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Low-cost high-performance solid-state asymmetric supercapacitors based on MnO2 nanowires and Fe2O3 nanotubes.
Nano Lett.
PUBLISHED: 01-07-2014
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A low-cost high-performance solid-state flexible asymmetric supercapacitor (ASC) with ?-MnO2 nanowires and amorphous Fe2O3 nanotubes grown on flexible carbon fabric is first designed and fabricated. The assembled novel flexible ASC device with an extended operating voltage window of 1.6 V exhibits excellent performance such as a high energy density of 0.55 mWh/cm(3) and good rate capability. The ASC devices can find numerous applications as effective power sources, such as powering color-switchable sun glasses and smart windows.
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New insights into FAK phosphorylation based on a FAT domain-defective mutation.
PLoS ONE
PUBLISHED: 01-01-2014
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Mounting evidence suggests that the FAK N-terminal (FERM) domain controls FAK phosphorylation and function; however, little is known regarding the role of the C terminal (FAT) domain in FAK regulation. We identified a patient-derived FAK mutant, in which a 27-amino acid segment was deleted from the C-terminal FAT domain (named FAK-Del33). When FAK-Del33 was overexpressed in specific tumor cell lines, Y397 phosphorylation increased compared with that observed in cells expressing FAK-WT. Here, we attempt to unveil the mechanism of this increased phosphorylation. Using cell biology experiments, we show that FAK-Del33 is incapable of co-localizing with paxillin, and has constitutively high Y397 phosphorylation. With a kinase-dead mutation, it showed phosphorylation of FAK-Del33 has enhanced through auto-phosphorylation. It was also demonstrated that phosphorylation of FAK-Del33 is not Src dependent or enhanced intermolecular interactions, and that the hyperphosphorylation can be lowered using increasing amounts of transfected FERM domain. This result suggests that Del33 mutation disrupting of FAT's structural integrity and paxillin binding capacity leads to incapable of targeting Focal adhesions, but has gained the capacity for auto-phosphorylation in cis.
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Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1?, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1? (HIF-1?), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.
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Robust stabilization control based on guardian maps theory for a longitudinal model of hypersonic vehicle.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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A typical model of hypersonic vehicle has the complicated dynamics such as the unstable states, the nonminimum phases, and the strong coupling input-output relations. As a result, designing a robust stabilization controller is essential to implement the anticipated tasks. This paper presents a robust stabilization controller based on the guardian maps theory for hypersonic vehicle. First, the guardian maps theories are provided to explain the constraint relations between the open subsets of complex plane and the eigenvalues of the state matrix of closed-loop control system. Then, a general control structure in relation to the guardian maps theories is proposed to achieve the respected design demands. Furthermore, the robust stabilization control law depending on the given general control structure is designed for the longitudinal model of hypersonic vehicle. Finally, a simulation example is provided to verify the effectiveness of the proposed methods.
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Relationship between interleukin-10 -1082A/G polymorphism and risk of ischemic stroke: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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To analyze the association between -1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.
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The bamboo-eating giant panda (Ailuropoda melanoleuca) has a sweet tooth: behavioral and molecular responses to compounds that taste sweet to humans.
PLoS ONE
PUBLISHED: 01-01-2014
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A growing body of behavioral and genetic information indicates that taste perception and food sources are highly coordinated across many animal species. For example, sweet taste perception is thought to serve to detect and motivate consumption of simple sugars in plants that provide calories. Supporting this is the observation that most plant-eating mammals examined exhibit functional sweet perception, whereas many obligate carnivores have independently lost function of their sweet taste receptors and exhibit no avidity for simple sugars that humans describe as tasting sweet. As part of a larger effort to compare taste structure/function among species, we examined both the behavioral and the molecular nature of sweet taste in a plant-eating animal that does not consume plants with abundant simple sugars, the giant panda (Ailuropoda melanoleuca). We evaluated two competing hypotheses: as plant-eating mammals, they should have a well-developed sweet taste system; however, as animals that do not normally consume plants with simple sugars, they may have lost sweet taste function, as has occurred in strict carnivores. In behavioral tests, giant pandas avidly consumed most natural sugars and some but not all artificial sweeteners. Cell-based assays revealed similar patterns of sweet receptor responses toward many of the sweeteners. Using mixed pairs of human and giant panda sweet taste receptor units (hT1R2+gpT1R3 and gpT1R2+hT1R3) we identified regions of the sweet receptor that may account for behavioral differences in giant pandas versus humans toward various sugars and artificial sweeteners. Thus, despite the fact that the giant panda's main food, bamboo, is very low in simple sugars, the species has a marked preference for several compounds that taste sweet to humans. We consider possible explanations for retained sweet perception in this species, including the potential extra-oral functions of sweet taste receptors that may be required for animals that consume plants.
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Spiroketal-Based Diphosphine Ligands in Pd-Catalyzed Asymmetric Allylic Amination of Morita-Baylis-Hillman Adducts: Exceptionally High Efficiency and New Mechanism.
J. Am. Chem. Soc.
PUBLISHED: 12-24-2013
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Exceptionally high activity (with a TON up to 4750) of the palladium complexes of SKP ligand was discovered in the catalysis of asymmetric allylic amination of MBH adducts with aromatic amines. A comprehensive mechanistic study indicates that the unique structural features of the SKP ligand, with a long P···P distance in its solid-state structure, were favorable for allowing two P atoms to play a bifunctional role in the catalysis. Herein, one of the P atom forms a C-P ?-bond with the terminal carbon atom of allyl moiety as a Lewis base, and an alternative P atom coordinates to Pd atom. The cooperative action of organo- and organometallic catalysis discovered in the present catalytic system is most likely responsible for its high activity, as well as excellent regio- and enantioselectivities. The mechanism disclosed in the present catalytic system is distinct from most of the currently recognized mechanisms for Pd-catalyzed allylic substitutions.
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Resveratrol-mediated reduction of collagen by inhibiting proliferation and producing apoptosis in human hypertrophic scar fibroblasts.
Biosci. Biotechnol. Biochem.
PUBLISHED: 12-07-2013
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Hypertrophic scar (HS) is a dermal fibroproliferative disorder characterized by excessive deposition of extracellular matrix. Here, to investigate the regulative effects of resveratrol, a natural antioxidant compound, on fibroblasts from human skin HS tissue, a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the inhibitory effect of resveratrol on cells. Cellcycle progression and apoptosis were measured by flow cytometry and Hoechst 33258 staining respectively. The hydroxyproline content and mRNA expression levels of type I and III procollagen were measured separately by ELISA and reverse transcription-polymerase chain reaction (RT-PCR). The results indicated that resveratrol significantly inhibited cell growth, arresting the cell cycle at the G1 phase and inducing apoptosis in the fibroblasts, decreasing hydroxyproline (or collagen) levels, and downregulating the expression levels of type I and III procollagen mRNA. Taken together, these data indicate that resveratrol-mediated reduction of collagen in fibroblasts is at least partially effected by causing inhibitory cell growth, cellcycle arrest, and apoptosis, and they suggest that resveratrol is a potential agent for HS treatment.
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Larger late sodium current density as well as greater sensitivities to ATX II and ranolazine in rabbit left atrial than left ventricular myocytes.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 12-06-2013
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An increase of cardiac late sodium current (INa.L) is arrhythmogenic in atrial and ventricular tissues, But the densities of INa.L and thus the potential relative contributions of this current to Na(+) influx and arrhythmogenesis in atria and ventricles are unclear. In this study, whole-cell and cell-attached patch clamp techniques were used to measure INa.L in rabbit left atrial and ventricular myocytes under identical conditions. The density of INa.L was 67% greater in atrial (0.50 ± 0.09 pA/pF, n = 20) than in left ventricular cells (0.30 ± 0.07 pA/pF, n = 27, P < 0.01) when elicited by step pulses from -120 to -20 mV at a rate of 0.2 Hz. Similar results were obtained using step pulses from -90 to -20 mV. Anemone toxin II (ATX II) increased INa.L with an EC50 value of 14 ± 2 nM and a Hill slope of 1.4 ± 0.1 (n = 9) in atrial myocytes and with an EC50 of 21 ± 5 nM and a Hill slope of 1.2 ± 0.1 (n = 12) in ventricular myocytes. Na(+) channel open probability (but not mean open time) was greater in atrial than in ventricular cells in the absence and presence of ATX II. The INa.L inhibitor ranolazine (3, 6, 9 ?M) reduced INa.L more in atrial than ventricular myocytes in the presence of 40 nM ATX II. In summary, rabbit left atrial myocytes have a greater density of INa.L and higher sensitivities to ATX II and ranolazine than rabbit left ventricular myocytes.
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A rapid and efficient method for primary culture of human adipose-derived stem cells.
Organogenesis
PUBLISHED: 11-22-2013
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Adipose tissue contains some populations, adipose-derived stem cells (ADSCs) which can differentiate into adipogenic, chondrogenic, osteogenic, myogenic, and endothelial cells. Furthermore, adipose tissue can be easily obtained in large quantities through a simple liposuction. ADSCs are thought to be an alternate source of autologous adult stem cells for cell-based therapy. However, it is time-consuming and inefficient to harvest ADSCs by using a traditional collagenase-digestion method. To meet the demand of large quantities of ADSCs in the basic and applied research of regenerative medicine, we developed a rapid and efficient method for isolation and culture of primary ADSCs. The results indicated that the ADSCs obtained with our method possessed strong abilities of proliferation and colony formation in vitro, and could keep low level of cell senescence with stable population doubling during long-term culture in vitro. Furthermore, these harvested ADSCs were capable to differentiate into osteogenic and adipogenic lineages in the specific induction medium. In addition, the results of flow cytometry analysis indicated that these ADSCs could positively express multiple CD markers, such as CD44, CD105, CD29, CD90, and CD13, and hardly expressed CD31, CD34, CD45, and CD106, which was homologous to the mesenchymal stem cells. Therefore, the ADSCs isolated with our method are consistent with previously reported characteristics of the ADSCs. This new method that we established in this study is an efficient tool to isolate and culture the stem cells from adipose tissue.
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Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction.
Ren Fail
PUBLISHED: 10-24-2013
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Abstract Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved. Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20?mg·kg(-1)·day(-1)). Histological changes were examined using periodic acid-Schiff and Massons trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-?, and TGF-? levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot. Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-?, and TGF-?, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage. Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.
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TiO2 nanowires for potential facile integration of solar cells and electrochromic devices.
Nanotechnology
PUBLISHED: 10-09-2013
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Self-powered systems usually consist of energy-acquisition components, energy-storage components and functional components. The development of nanoscience and nanotechnology has greatly improved the performance of all the components of self-powered systems. However, huge differences in the materials and configurations in the components cause large difficulties for integration and miniaturization of self-powered systems. Design and fabrication of different components in a self-powered system with the same or similar materials/configurations should be able to make the above goal easier. In this work, a proof-of-concept experiment involving an integrated self-powered color-changing system consisting of TiO2 nanowire based sandwich dye-sensitized solar cells (DSSCs) and electrochromic devices (ECDs) is designed and demonstrated. When sunlight illuminates the entire system, the DSSCs generate electrical power and turn the ECD to a darker color, dimming the light; by switching the connection polarity of the DSSCs, the lighter color can be regained, implying the potential application of this self-powered color-changing system for next generation sun glasses and smart windows.
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Autophagy blockade sensitizes the anticancer activity of CA-4 via JNK-Bcl-2 pathway.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-26-2013
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Combretastatin A-4 (CA-4) has already entered clinical trials of solid tumors over ten years. However, the limited anticancer activity and dose-dependent toxicity restrict its clinical application. Here, we offered convincing evidence that CA-4 induced autophagy in various cancer cells, which was demonstrated by acridine orange staining of intracellular acidic vesicles, the degradation of p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate fluorescence. Interestingly, CA-4-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitors (3-methyladenine and bafilomycin A1) or small interfering RNAs against the autophagic genes (Atg5 and Beclin 1). The enhanced anticancer activity of CA-4 and 3-MA was further confirmed in the SGC-7901 xenograft tumor model. These findings suggested that CA-4-elicited autophagic response played a protective role that impeded the eventual cell death while autophagy inhibition was expected to improve chemotherapeutic efficacy of CA-4. Meanwhile, CA-4 treatment led to phosphorylation/activation of JNK and JNK-dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor or JNK siRNA inhibited autophagy but promoted CA-4-induced apoptosis, indicating a key requirement of JNK-Bcl-2 pathway in the activation of autophagy by CA-4. We also identified that pretreatment of Bcl-2 inhibitor (ABT-737) could significantly enhance anticancer activity of CA-4 due to inhibition of autophagy. Taken together, our data suggested that the JNK-Bcl-2 pathway was considered as the critical regulator of CA-4-induced protective autophagy and a potential drug target for chemotherapeutic combination.
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Helical Self-Assembly of Optically Active Phthalocyanine Derivatives: Effect of Zn?O Coordination Bond on Morphology and Handedness of Nanostructures.
Chemphyschem
PUBLISHED: 06-27-2013
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Two optically active phthalocyanine derivatives with eight peripheral chiral (S)-4-(2-methylbutoxy)biphenyl moieties on the ?-position of the phthalocyanine ring are synthesized. The circular dichroism (CD) spectra show signals in the Q absorption region for both compounds 1 and 2 in chloroform solution, indicating the effective chiral-information transfer from the peripheral chiral (S)-4-(2-methylbutoxy)biphenyl side chains to the phthalocyanine chromophore at the molecular level. Their self-assembling properties are further investigated by using electronic absorption and Fourier transform infrared spectroscopy, transmission electronic microscopy, scanning electronic microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Experimental results reveal the effect of the metal-coordination bond on molecular packing models in these nanostructures, which in turn results in the self-assembled nanostructures with different morphologies, from nanosheets for 1 to helical nanofibers for 2. In addition, good semiconducting properties of the nanostructures fabricated from phthalocyanine derivatives 1 and 2 are revealed by current-voltage measurements.
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Perilla oil and exercise decrease expressions of tumor necrosis factor-alpha, plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia.
J Tradit Chin Med
PUBLISHED: 06-25-2013
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To verify the effects of perilla oil on the regulation of blood lipid levels in patients with hyperlipidemia.
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Electroacupuncture and lumbar transplant of GDNF-secreting fibroblasts synergistically attenuate hyperalgesia after sciatic nerve constriction.
Am. J. Chin. Med.
PUBLISHED: 05-29-2013
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Electroacupuncture (EA) has been shown to induce potent analgesic effects on neuropathic pain in both patients and rodents. Cell therapy to release antinociceptive agents near the pain processing centers of the spinal cord is a promising next step in the development of treatment modalities. This study investigated the effects of the combination of EA and cell therapy by glial cell line-derived neurotrophic factor (GDNF) on neuropathic pain in rats. The hyperalgesic state was induced by chronic constriction injury (CCI) of the sciatic nerve and fibroblasts genetically modified to secrete bioactive GDNF (FBs-GDNF) were used for cell therapy. Fifty-eight rats with neuropathic pain were randomly divided into five groups (CCI+PBS, n = 11; CCI+FBs-GDNF, n = 12; CCI+EA+PBS, n = 11; CCI+EA+FBs-pLNCX2, n = 12; CCI+EA+FBs-GDNF, n = 12). On the 7th day after CCI, the rats received intrathecal transplantation of FBs-GDNF or control fibroblasts (FBs-pLNCX2). In the meantime, EA was administered once every other day from the 7th day after CCI surgery for 21 days. The paw withdrawal latency (PWL) to radiant heat was measured every other day. The results showed that the ipsilateral PWL of the rats from all three EA treatment groups significantly increased starting on the 12th day compared with the PBS control group. Strikingly, the group which received EA treatment and FBs-GDNF transplantation (CCI+EA+FBs-GDNF) showed a significantly decreased thermal hyperalgesia after 2 weeks post CCI surgery compared with the groups which received EA treatment and FBs-pLNCX2 transplantation (CCI+EA+FBs-pLNCX2) or PBS (CCI+EA+PBS) as well as the FBs-GDNF transplantation group without EA treatment (CCI+FBs-GDNF). Our data suggest that EA and cell therapy can synergistically attenuate hyperalgesia in neuropathic pain rats.
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Axonal and glial responses to a mid-thoracic spinal cord hemisection in the Macaca fascicularis monkey.
J. Neurotrauma
PUBLISHED: 05-13-2013
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A comprehensive understanding of the pathology of spinal cord injury (SCI) in non-human primates may facilitate greatly the development of new strategies to promote recovery in humans with SCI. Relatively few studies, however, have been conducted to systemically examine pathological changes in the monkey, a non-human primate, after SCI. We report axonal, glial, and fibrotic responses in the spinal cord of monkey Macaca fascicularis after a thoracic (T) 8-9 lateral hemisection. We examined these changes at three regions--i.e., the lesion epicenter, the peri-lesion area, and the lateral white matter of the intact, contralateral hemicord at 7 (subacute) and 30 (early chronic) days post-injury. The lateral hemisection resulted in a marked axon and myelin loss, along with tissue loss, at the lesion epicenter at both time points. Unexpectedly, axonal loss and myelin degeneration, along with reactive gliosis and microglia/macrophages activation, were also observed in the contralateral spared hemicord, indicating a spread of the initial damage to the contralateral side. In addition, activated microglia/macrophages were found both within the injury epicenter and the peri-lesion area, indicating that they participate in injury-induced immune responses that may exacerbate the secondary damage. In contrast to rodents, substantial reactive astrocytic responses at the lesion border were not observed in the monkey. Conversely, a deposit of robust fibrotic scar was observed at the injury epicenter, which filled the space originally created by the hemisection. Thus, understanding the pathology of monkey SCI may provide clinically relevant information in designing repair strategies targeting specific problems associated with human SCIs.
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Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-? memory in human CD4(+) T lymphocytes.
Eur. J. Immunol.
PUBLISHED: 05-03-2013
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Cytokine memory for IFN-? production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-? capture assay, we found early IFN-?-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-?-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-? memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.
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The methylation of the PcMYB10 promoter is associated with green-skinned sport in Max Red Bartlett pear.
Plant Physiol.
PUBLISHED: 04-29-2013
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Varieties of the European pear (Pyrus communis) can produce trees with both red- and green-skinned fruits, such as the Max Red Bartlett (MRB) variety, although little is known about the mechanism behind this differential pigmentation. In this study, we investigated the pigmentation of MRB and its green-skinned sport (MRB-G). The results suggest that a reduction in anthocyanin concentration causes the MRB-G sport. Transcript levels of PcUFGT (for UDP-glucose:flavonoid 3-O-glucosyltransferase), the key structural gene in anthocyanin biosynthesis, paralleled the change of anthocyanin concentration in both MRB and MRB-G fruit. We cloned the PcMYB10 gene, a transcription factor associated with the promoter of PcUFGT. An investigation of the 2-kb region upstream of the ATG translation start site of PcMYB10 showed the regions -604 to -911 bp and -1,218 to -1,649 bp to be highly methylated. A comparison of the PcMYB10 promoter methylation level between the MRB and MRB-G forms indicated a correlation between hypermethylation and the green-skin phenotype. An Agrobacterium tumefaciens infiltration assay was conducted on young MRB fruits by using a plasmid constructed to silence endogenous PcMYB10 via DNA methylation. The infiltrated fruits showed blocked anthocyanin biosynthesis, higher methylation of the PcMYB10 promoter, and lower expression of PcMYB10 and PcUFGT. We suggest that the methylation level of PcMYB10 is associated with the formation of the green-skinned sport in the MRB pear. The potential mechanism behind the regulation of anthocyanin biosynthesis is discussed.
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A semisynthetic taxane Yg-3-46a effectively evades P-glycoprotein and ?-III tubulin mediated tumor drug resistance in vitro.
Cancer Lett.
PUBLISHED: 04-27-2013
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Tumor resistance, especially that mediated by P-glycoprotein (P-gp) and ?-III tubulin, is a major obstacle to the efficacy of most microtubule-targeting anticancer drugs in clinics. A novel semisynthetic taxane, 2-debenzoyl-2-(3-azidobenzyl)-10-propionyldocetaxel (Yg-3-46a) was shown to be highly cytotoxic to breast cancer cell lines MCF-7 and MCF/ADR which overexpressed P-gp via long term culture with doxorubicin, and cervical cancer cell lines Hela and Hela/?III which overexpressed ?III-tubulin via stable transfection with TUBB3 gene. siRNA transfection experiments also confirmed that Yg-3-46a can circumvent P-gp and ?-III tubulin mediated drug resistance. In addition, its cytotoxicity was lower than that of paclitaxel in the human mammary cell line HBL-100 and the human telomerase-immortalized retinal pigment epithelium cell line (hTERT-RPE1), suggesting a better safety margin for this compound in vivo. It exhibited more potent microtubule polymerization ability than paclitaxel in vitro, and also induced G2/M phase arrest in MCF-7/ADR cells. Moreover, it was found to induce apoptosis in MCF-7/ADR cells through the caspase-dependent death-receptor pathway by enhancing levels of Fas and FasL, and activating caspase-8 and 3. Yg-3-46a was found to be a poorer substrate of P-gp compared to paclitaxel, in both binding and ATPase experiments, which is likely responsible for its ability to circumvent P-gp mediated multidrug resistance (MDR). All of these results indicate that Yg-3-46a is a novel microtubule-stabilizing agent that has the potential to evade drug resistance mediated by P-gp and ?-III tubulin overexpression.
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Effect of Chinese herbs on immunoglobulin A nephropathy: a randomized controlled trial.
J Tradit Chin Med
PUBLISHED: 04-20-2013
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The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN).
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PITPs as targets for selectively interfering with phosphoinositide signaling in cells.
Nat. Chem. Biol.
PUBLISHED: 04-05-2013
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Sec14-like phosphatidylinositol transfer proteins (PITPs) integrate diverse territories of intracellular lipid metabolism with stimulated phosphatidylinositol-4-phosphate production and are discriminating portals for interrogating phosphoinositide signaling. Yet, neither Sec14-like PITPs nor PITPs in general have been exploited as targets for chemical inhibition for such purposes. Herein, we validate what is to our knowledge the first small-molecule inhibitors (SMIs) of the yeast PITP Sec14. These SMIs are nitrophenyl(4-(2-methoxyphenyl)piperazin-1-yl)methanones (NPPMs) and are effective inhibitors in vitro and in vivo. We further establish that Sec14 is the sole essential NPPM target in yeast and that NPPMs exhibit exquisite targeting specificities for Sec14 (relative to related Sec14-like PITPs), propose a mechanism for how NPPMs exert their inhibitory effects and demonstrate that NPPMs exhibit exquisite pathway selectivity in inhibiting phosphoinositide signaling in cells. These data deliver proof of concept that PITP-directed SMIs offer new and generally applicable avenues for intervening with phosphoinositide signaling pathways with selectivities superior to those afforded by contemporary lipid kinase-directed strategies.
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MDCT and MRI for the diagnosis of complex fractures of the tibial plateau: A case control study.
Exp Ther Med
PUBLISHED: 04-01-2013
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The aim of this study was to evaluate the clinical value of multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) in the diagnosis and treatment of complex fractures of the tibial plateau. A total of 71 patients with complex fractures of the tibial plateau (estimated Schatzker classifications III, V and VI) were included in this study. The X-ray, MDCT and MRI data obtained from the patients were analyzed. MDCT was the most sensitive method in the diagnosis of tibial articular surface collapse, cruciate ligament tibial avulsion fracture, degree of fracture comminution and degree of fracture displacement (P<0.01). MRI was the most sensitive method in the diagnosis of injuries of the cruciate and collateral ligaments, menisci and cartilage peeling of the articular surfaces (P<0.01). MDCT and MRI were demonstrated to be more sensitive than X-rays for the diagnosis of insidious damage around the knee.
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Bi-layer collagen/microporous electrospun nanofiber scaffold improves the osteochondral regeneration.
Acta Biomater
PUBLISHED: 03-20-2013
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An optimal scaffold is crucial for osteochondral regeneration. Collagen and electrospun nanofibers have been demonstrated to facilitate cartilage and bone regeneration, respectively. However, the effect of combining collagen and electrospun nanofibers on osteochondral regeneration has yet to be evaluated. Here, we report that the combination of collagen and electrospun poly-l-lactic acid nanofibers synergistically promotes osteochondral regeneration. We first fabricated bi-layer microporous scaffold with collagen and electrospun poly-l-lactic acid nanofibers (COL-nanofiber). Mesenchymal stem cells were cultured on the bi-layer scaffold and their adhesion, proliferation and differentiation were examined. Moreover, osteochondral defects were created in rabbits and implanted with COL-nanofiber scaffold. Cartilage and subchondral bone regeneration were evaluated at 6 and 12weeks after surgery. Compared with COL scaffold, cells on COL-nanofiber scaffold exhibited more robust osteogenic differentiation, indicated by higher expression levels of OCN and runx2 genes as well as the accumulation of calcium nodules. Furthermore, implantation of COL-nanofiber scaffold seeded with cells induced more rapid subchondral bone emergence, and better cartilage formation, which led to better functional repair of osteochondral defects as manifested by histological staining, biomechanical test and micro-computed tomography data. Our study underscores the potential of using the bi-layer microporous COL-nanofiber scaffold for the treatment of deep osteochondral defects.
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Protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. on carbon tetrachloride-induced hepatotoxicity in rats.
J. Membr. Biol.
PUBLISHED: 02-21-2013
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Hepatoprotective agents could prevent tissue damage and reduce morbidity and mortality rates; such agents may include folkloric or alternative treatments. The present study evaluated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on carbon tetrachloride (CCl?)-induced hepatotoxicity in rats. Sprague-Dawley male rats were orally treated with SGF daily and received CCl? intraperitoneally twice a week for 4 weeks. Our results showed that SGF at doses of 100, 300 and 500 mg/kg significantly reduced the elevated activities of serum aminotransferases (ALT and AST), alkaline phosphatase and lactate dehydrogenase and the level of hepatic thiobarbituric acid-reactive substances compared to the CCl?-treated group. Moreover, SGF treatment was also found to significantly increase the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glutathione compared with CCl?-induced intoxicated liver. Histopathologic examination revealed that CCl?-induced hepatic damage was markedly reversed by SGF. The results suggest that SGF has hepatoprotective and antioxidant properties in CCl?-induced liver injury in rats.
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The clinical outcomes of new hyaluronan nasal dressing: a prospective, randomized, controlled study.
Am J Rhinol Allergy
PUBLISHED: 02-15-2013
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Poor postoperative wound healing after endoscopic sinus surgery (ESS) remains a significant problem. This study evaluates the efficacy and safety of a new absorbable hyaluronan hydrogel.
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Hydrogenated ZnO core-shell nanocables for flexible supercapacitors and self-powered systems.
ACS Nano
PUBLISHED: 02-07-2013
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Although MnO2 is a promising material for supercapacitors (SCs) due to its excellent electrochemical performance and natural abundance, its wide application is limited by poor electrical conductivity. Inspired by our results that the electrochemical activity and electrical conductivity of ZnO nanowires were greatly improved after hydrogenation, we designed and fabricated hydrogenated single-crystal ZnO@amorphous ZnO-doped MnO2 core-shell nanocables (HZM) on carbon cloth as SC electrodes, showing excellent performance such as areal capacitance of 138.7 mF/cm(2) and specific capacitance of 1260.9 F/g. Highly flexible all-solid-state SCs were subsequently assembled with these novel HZM electrodes using polyvinyl alcohol/LiCl electrolyte. The working devices achieved very high total areal capacitance of 26 mF/cm(2) and retained 87.5% of the original capacitance even after 10?000 charge/discharge cycles. An integrated power pack incorporating series-wound SCs and dye-sensitized solar cells was demonstrated for stand-alone self-powered systems.
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Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue.
Stem Cells
PUBLISHED: 02-05-2013
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Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate (CV) and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knockin allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of CV and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue.
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Blockade of the human ether-a-go-go-related gene potassium channel by ketamine.
J. Pharm. Pharmacol.
PUBLISHED: 01-13-2013
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The inhibition of the cardiac rapid delayed rectifier potassium current (IKr ) and its cloned equivalent human ether-a-go-go-related gene (hERG) channel illustrate QT interval prolonging effects of a wide range of clinically used drugs. In this study, the direct interaction of the intravenous anaesthetic ketamine with wild-type (WT) and mutation hERG currents (IhERG ) was investigated.
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Association analysis of polymorphisms in ROCK2 with cardiovascular disease in a Chinese population.
PLoS ONE
PUBLISHED: 01-11-2013
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Rho-kinase (ROCK) has been shown to play an important role in cardiovascular disease such as coronary artery disease (CAD) and hypertension. Recently, common variants of ROCK2 have been reported to influence blood pressure, but the relationship between common ROCK2 variants and cardiovascular disease has not been extensively studied in the Chinese population.
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MEK/ERK dependent activation of STAT1 mediates dasatinib-induced differentiation of acute myeloid leukemia.
PLoS ONE
PUBLISHED: 01-01-2013
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Dasatinib (BMS-354825) is a FDA-approved multitargeted kinase inhibitor of BCR/ABL and Src kinases. It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib. Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1). We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm. Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes. Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation. We further found that dasatinib-induced activation of STAT1 was regulated by the MEK/ERK kinases. The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced. MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells. Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.
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Calmodulin kinase II and protein kinase C mediate the effect of increased intracellular calcium to augment late sodium current in rabbit ventricular myocytes.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 12-21-2011
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An increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) augments late sodium current (I(Na.L)) in cardiomyocytes. This study tests the hypothesis that both Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) mediate the effect of increased [Ca(2+)](i) to increase I(Na.L). Whole cell and open cell-attached patch clamp techniques were used to record I(Na.L) in rabbit ventricular myocytes dialyzed with solutions containing various concentrations of [Ca(2+)](i). Dialysis of cells with [Ca(2+)](i) from 0.1 to 0.3, 0.6, and 1.0 ?M increased I(Na.L) in a concentration-dependent manner from 0.221 ± 0.038 to 0.554 ± 0.045 pA/pF (n = 10, P < 0.01) and was associated with an increase in mean Na(+) channel open probability and prolongation of channel mean open-time (n = 7, P < 0.01). In the presence of 0.6 ?M [Ca(2+)](i), KN-93 (10 ?M) and bisindolylmaleimide (BIM, 2 ?M) decreased I(Na.L) by 45.2 and 54.8%, respectively. The effects of KN-93 and autocamtide-2-related inhibitory peptide II (2 ?M) were not different. A combination of KN-93 and BIM completely reversed the increase in I(Na.L) as well as the Ca(2+)-induced changes in Na(+) channel mean open probability and mean open-time induced by 0.6 ?M [Ca(2+)](i). Phorbol myristoyl acetate increased I(Na.L) in myocytes dialyzed with 0.1 ?M [Ca(2+)](i); the effect was abolished by Gö-6976. In summary, both CaMKII and PKC are involved in [Ca(2+)](i)-mediated augmentation of I(Na.L) in ventricular myocytes. Inhibition of CaMKII and/or PKC pathways may be a therapeutic target to reduce myocardial dysfunction and cardiac arrhythmias caused by calcium overload.
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Assembly and in vitro functional analysis of zinc finger nuclease specific to the 3 untranslated region of chicken ovalbumin gene.
Anim. Biotechnol.
PUBLISHED: 12-03-2011
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Synthetic zinc finger nucleases (ZFNs) are useful for the improvement of site directed integration of foreign gene into vertebrate chromosomes. To facilitate site-directed integration of foreign genes into the 3-untranslated region of the chicken ovalbumin gene, we have constructed ZFN expression vectors using Zinc Finger Consortium Vector Kits and tested the functionality of these ZFN constructs. Coding sequences for 6 zinc fingers were assembled following the modular assembly method. The zinc finger assembly was fused to two FokI catalytic domains. Various configurations of linker regions between domains were tested for their influence on enzymatic activity, using plasmid substrate containing the target sequence. Results indicated that ZFN with an elongated linker between two nuclease domains had a high catalytic activity.
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Characterization of clioquinol and analogues as novel inhibitors of methionine aminopeptidases from Mycobacterium tuberculosis.
Tuberculosis (Edinb)
PUBLISHED: 11-23-2011
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Mycobacterium tuberculosis, the causative agent of tuberculosis claims about five thousand lives daily world-wide, while one-third of the world is infected with dormant tuberculosis. The increased emergence of multi- and extensively drug-resistant strains of M. tuberculosis (Mtb) has heightened the need for novel antimycobacterial agents. Here, we report the discovery of 7-bromo-5-chloroquinolin-8-ol (CLBQ14)-a congener of clioquinol (CQ) as a potent and selective inhibitor of two methionine aminopeptidases (MetAP) from M. tuberculosis: MtMetAP1a and MtMetAP1c. MetAP is a metalloprotease that removes the N-terminal methionine during protein synthesis. N-terminal methionine excision (NME) is a universally conserved process required for the post-translational modification of a significant part of the proteome. The essential role of MetAP in microbes makes it a promising target for the development of new therapeutics. Using a target-based approach in a high-throughput screen, we identified CLBQ14 as a novel MtMetAP inhibitor with higher specificity for both MtMetAP1s relative to their human counterparts. We also found that CLBQ14 is potent against replicating and aged non-growing Mtb at low micro molar concentrations. Furthermore, we observed that the antimycobacterial activity of this pharmacophore correlates well with in vitro enzymatic inhibitory activity. Together, these results revealed a new mode of action of clioquinol and its congeners and validated the therapeutic potential of this pharmacophore for TB chemotherapy.
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Synovial and peripheral blood CD4+FoxP3+ T cells in spondyloarthritis.
J. Rheumatol.
PUBLISHED: 09-15-2011
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Regulatory T cells are characterized by expression of the transcription factor FoxP3 and are thought to be involved in the pathogenesis of autoimmune diseases. We determined the frequency and phenotypic characteristics of CD4+FoxP3+ T cells in the blood and synovial fluid (SF) of patients with inflammatory joint diseases.
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[Repair of soft tissue defects of lower extremity by using cross-bridge contralateral distally based posterior tibial artery perforator flaps or peroneal artery perforator flaps].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 08-09-2011
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To discuss the feasibility of repairing soft tissue defects of lower extremity with a distally based posterior tibial artery perforator cross-bridge flap or a distally based peroneal artery perforator cross-bridge flap.
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Effects of atorvastatin on bone metabolism and bone mineral density in Wistar rats.
Pharmazie
PUBLISHED: 08-05-2011
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To investigate the effects of atorvastatin on bone formation, bone resorption and bone mineral density in Wistar rats.
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Molecular mechanism of species-dependent sweet taste toward artificial sweeteners.
J. Neurosci.
PUBLISHED: 07-29-2011
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The heterodimer of Tas1R2 and Tas1R3 is a broadly acting sweet taste receptor, which mediates mammalian sweet taste toward natural and artificial sweeteners and sweet-tasting proteins. Perception of sweet taste is a species-selective physiological process. For instance, artificial sweeteners aspartame and neotame taste sweet to humans, apes, and Old World monkeys but not to New World monkeys and rodents. Although specific regions determining the activation of the receptors by these sweeteners have been identified, the molecular mechanism of species-dependent sweet taste remains elusive. Using human/squirrel monkey chimeras, mutagenesis, and molecular modeling, we reveal that the different responses of mammalian species toward the artificial sweeteners aspartame and neotame are determined by the steric effect of a combination of a few residues in the ligand binding pocket. Residues S40 and D142 in the human Tas1R2, which correspond to residues T40 and E142 in the squirrel monkey Tas1R2, were found to be the critical residues for the species-dependent difference in sweet taste. In addition, human Tas1R2 residue I67, which corresponds to S67 in squirrel monkey receptor, modulates the higher affinity of neotame than of aspartame. Our studies not only shed light on the molecular mechanism of species-dependent sweet taste toward artificial sweeteners, but also provide guidance for designing novel effective artificial sweet compounds.
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Effects of C7 substitutions in a high affinity microtubule-binding taxane on antitumor activity and drug transport.
Bioorg. Med. Chem. Lett.
PUBLISHED: 06-08-2011
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Some C-7 modified analogs of 3, a taxane with high affinity for binding to microtubules, were prepared through multistep transformations. Most of the analogs, bearing less lipophilic C-7 substituents than propionyl in 3, exhibited comparable binding affinities to microtubules but less cytotoxicity against drug-sensitive as well as multidrug-resistant tumor cells overexpressing P-glycoprotein. In addition, these C7 modifications increased P-glycoprotein-mediated drug transport in both directions in a Caco-2 cell assay.
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Simultaneous determination of urinary tryptophan, tryptophan-related metabolites and creatinine by high performance liquid chromatography with ultraviolet and fluorimetric detection.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 05-30-2011
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A high performance liquid chromatography method with ultraviolet and fluorimetric detection has been developed for the simultaneous determination of urinary creatinine (Cr), tryptophan (Trp) and three Trp-related metabolites including kynurenine (Kyn), kynurenic acid (Kyna) and 5-hydroxyindole-3-acetic acid (5-HIAA). Samples were pretreated by centrifugation after a freeze-thaw cycle to remove protein and other precipitates. Separation was achieved by an Agilent HC-C18 (2) analytical column and a gradient elution program with a constant flow rate 1mL/min at an ambient temperature. Total run time was 30 min. Cr, Kyn and Kyna were measured by a variable wavelength detector at wavelengths 258 nm, 365 nm and 344 nm respectively. Trp and 5-HIAA were measured by a fluorescence detector with an excitation wavelength of 295 nm and an emission wavelength of 340 nm. This allowed the determination of Kyn/Cr, Kyna/Cr, Trp/Cr and 5-HIAA/Cr concentration ratios in a single run on the same urine sample. Good linear responses were found with correlation coefficient (r)>0.999 for all analytes within the concentration range of physiological level. The limit of detection of the developed method was: Cr, 0.0002 g/L; Kyn, 0.1 ?mol/L; Kyna, 0.04 ?mol/L; Trp, 0.02 ?mol/L and 5-HIAA, 0.01 ?mol/L. Recoveries from spiked human urine were: Cr, 93.0-106.4%; Kyn, 97.9-106.9%; Kyna, 98.5-105.6%; Trp, 96.7-105.2% and 5-HIAA, 96.1-99.7%. CVs of repeatability and intermediate precision of all analytes were less than 5%. This method has been applied to the analysis of urine samples from normal subjects.
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A meta-analysis of CDH1 C-160A genetic polymorphism and gastric cancer risk.
DNA Cell Biol.
PUBLISHED: 05-25-2011
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We explored the role of the C-160A single-nucleotide polymorphism (SNP) of CDH1 in susceptibility to gastric cancer through a systematic review and meta-analysis. Fourteen studies were included, the original groups collapsed, and re-grouped in accordance with the most appropriate genetic model. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. No significant association of C-160A was found with the overall risk of developing gastric cancer, but the apparently opposite tendency was noted between Caucasians and Asians, and a statistically significant association was found among Asians. The seemingly opposite tendency of associations was also seen between noncardia and cardia types or between sporadic diffuse and intestinal types of gastric cancer, but no statistically significant findings were noted. Genotyping techniques, sample size, quality appraisal scores, or article publication time did not constitute the source of heterogeneity across studies; and no publication biases were found in our meta-analysis.
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[Association of IL-1beta gene -31T/C polymorphism with chronic rhinosinusitis].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 05-25-2011
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To investigate the relationship between polymorphism of IL-1beta gene 31T/C and chronic rhinosinusitis.
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NF-kappaB P50/P65 hetero-dimer mediates differential regulation of CD166/ALCAM expression via interaction with micoRNA-9 after serum deprivation, providing evidence for a novel negative auto-regulatory loop.
Nucleic Acids Res.
PUBLISHED: 05-13-2011
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CD166/ALCAM plays an important role in tumor aggression and progression as well as protecting cancer cells against apoptosis and autophagy. However, the mechanism by which pro-cell death signals control CD166 expression remains unclear. Here we show that following serum deprivation (SD), upregulation of CD166 protein is shorter than that of CD166 mRNA. Molecular analysis revealed both CD166 and miR-9-1 as two novel NF-?B target genes in hepatoma cells. In vivo activation and translocation of the NF-?B P50/P65 hetero-dimer into the nucleus following the phosphorylation and accompanied degradation of its inhibitor, I?B?, contributes to efficient transcription of both genes following SD. We show that following serum starvation, delayed up-regulation of miR-9 represses translation of CD166 protein through its target sites in the 3-UTR of CD166 mRNA. We also propose that miR-9 promotes cell migration largely due to inhibition of CD166. Collectively, the study elucidates a novel negative auto-regulatory loop in which NF-?B mediates differential regulation of CD166 after SD.
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Polymorphisms of human vascular endothelial growth factor gene are associated with acute cerebral infarction in the Chinese population.
Eur. Neurol.
PUBLISHED: 05-09-2011
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Vascular endothelial growth factor (VEGF) plays a key role in the development of cerebral infarction as a major mediator of angiogenesis. The aim of this study was to investigate whether the VEGF gene polymorphisms were associated with the risks of acute cerebral infarction.
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Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.
Arthritis Res. Ther.
PUBLISHED: 05-04-2011
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In this study, we analysed the number of IL-17(+) cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls.
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Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice.
Prostaglandins Other Lipid Mediat.
PUBLISHED: 04-20-2011
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Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. The anti-inflammatory, anti-apoptotic, pro-angiogenic, and anti-hypertensive properties of EETs in the cardiovascular system suggest a beneficial role for EETs in diabetic nephropathy. This study investigated the effects of endothelial specific overexpression of CYP2J2 epoxygenase on diabetic nephropathy in streptozotocin-induced diabetic mice. Endothelial CYP2J2 overexpression attenuated renal damage as measured by urinary microalbumin and glomerulosclerosis. These effects were associated with inhibition of TGF-?/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF-?1-induced renal tubular epithelial-mesenchymal transition in vitro. These findings highlight the beneficial roles of the CYP epoxygenase-EET system in the pathogenesis of diabetic nephropathy.
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Late sodium current contributes to the reverse rate-dependent effect of IKr inhibition on ventricular repolarization.
Circulation
PUBLISHED: 04-11-2011
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The reverse rate dependence (RRD) of actions of I(Kr)-blocking drugs to increase the action potential duration (APD) and beat-to-beat variability of repolarization (BVR) of APD is proarrhythmic. We determined whether inhibition of endogenous, physiological late Na(+) current (late I(Na)) attenuates the RRD and proarrhythmic effect of I(Kr) inhibition.
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[The expression and clinical pathological significance of PDCD in laryngocarcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 04-08-2011
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To investigate the expression and clinical pathological significance of PDCD4 in laryngocarcinoma tissue and its potential significance to clinic.
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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.