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Find video protocols related to scientific articles indexed in Pubmed.
ABO blood group, Epstein-Barr virus infection and prognosis of patients with non-metastatic nasopharyngeal carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-18-2014
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A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear.
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A single amino acid substitution in CFTR converts ATP to an inhibitory ligand.
J. Gen. Physiol.
PUBLISHED: 09-15-2014
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Cystic fibrosis (CF), one of the most common lethal genetic diseases, is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel that, when phosphorylated, is gated by ATP. The third most common pathogenic mutation, a glycine-to-aspartate mutation at position 551 or G551D, shows a significantly decreased open probability (Po) caused by failure of the mutant channel to respond to ATP. Recently, a CFTR-targeted drug, VX-770 (Ivacaftor), which potentiates G551D-CFTR function in vitro by boosting its Po, has been approved by the FDA to treat CF patients carrying this mutation. Here, we show that, in the presence of VX-770, G551D-CFTR becomes responsive to ATP, albeit with an unusual time course. In marked contrast to wild-type channels, which are stimulated by ATP, sudden removal of ATP in excised inside-out patches elicits an initial increase in macroscopic G551D-CFTR current followed by a slow decrease. Furthermore, decreasing [ATP] from 2 mM to 20 µM resulted in a paradoxical increase in G551D-CFTR current. These results suggest that the two ATP-binding sites in the G551D mutant mediate opposite effects on channel gating. We introduced mutations that specifically alter ATP-binding affinity in either nucleotide-binding domain (NBD1 or NBD2) into the G551D background and determined that this disease-associated mutation converts site 2, formed by the head subdomain of NBD2 and the tail subdomain of NBD1, into an inhibitory site, whereas site 1 remains stimulatory. G551E, but not G551K or G551S, exhibits a similar phenotype, indicating that electrostatic repulsion between the negatively charged side chain of aspartate and the ?-phosphate of ATP accounts for the observed mutational effects. Understanding the molecular mechanism of this gating defect lays a foundation for rational drug design for the treatment of CF.
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Renal sympathetic denervation modulates ventricular electrophysiology and has a protective effect on ischaemia-induced ventricular arrhythmia.
Exp. Physiol.
PUBLISHED: 08-28-2014
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Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear. Thirty-three mongrel dogs were included in the present study. Renal sympathetic denervation was performed by radiofrequency ablation of the adventitial surface of the renal artery. In group 1 (n = 8), programmed stimulation was performed before and after RSD to determine the ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. The same parameters were measured in five other animals that underwent sham RSD to serve as controls. In group 2 (n = 10), acute myocardial ischaemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD, and the incidence of ventricular arrhythmia (VA) was calculated during 1 h of recording. In another 10 dogs (group 3), AMI was induced and VA was measured with sham RSD. In group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximal slope (Smax) of the restitution curve and suppressed APD alternans at each site. Renal sympathetic denervation also significantly decreased the spatial dispersion of ERP, APD and Smax. In the five control animals, no significant electrophysiological change was detected after sham RSD. The occurrence of spontaneous VA during 1 h of AMI in group 2 was significantly lower than that in group 3. These data suggest that RSD stabilizes ventricular electrophysiological properties in normal hearts and reduces the occurrence of VA in hearts experiencing AMI.
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Fan beam image reconstruction with generalized fourier slice theorem.
J Xray Sci Technol
PUBLISHED: 08-01-2014
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For parallel beam geometry the Fourier reconstruction works via the Fourier slice theorem (or central slice theorem, projection slice theorem). For fan beam situation, Fourier slice can be extended to a generalized Fourier slice theorem (GFST) for fan-beam image reconstruction. We have briefly introduced this method in a conference. This paper reintroduces the GFST method for fan beam geometry in details. The GFST method can be described as following: the Fourier plane is filled by adding up the contributions from all fanbeam projections individually; thereby the values in the Fourier plane are directly calculated for Cartesian coordinates such avoiding the interpolation from polar to Cartesian coordinates in the Fourier domain; inverse fast Fourier transform is applied to the image in Fourier plane and leads to a reconstructed image in spacial domain. The reconstructed image is compared between the result of the GFST method and the result from the filtered backprojection (FBP) method. The major differences of the GFST and the FBP methods are: (1) The interpolation process are at different data sets. The interpolation of the GFST method is at projection data. The interpolation of the FBP method is at filtered projection data. (2) The filtering process are done in different places. The filtering process of the GFST is at Fourier domain. The filtering process of the FBP method is the ramp filter which is done at projections. The resolution of ramp filter is variable with different location but the filter in the Fourier domain lead to resolution invariable with location. One advantage of the GFST method over the FBP method is in short scan situation, an exact solution can be obtained with the GFST method, but it can not be obtained with the FBP method. The calculation of both the GFST and the FBP methods are at O(N^3), where N is the number of pixel in one dimension.
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pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery.
Nanotechnology
PUBLISHED: 07-30-2014
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We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4?-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4?-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC??) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.
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A strategy for characterization of persistent heteroduplex DNA in higher plants.
Plant J.
PUBLISHED: 07-24-2014
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Heteroduplex DNA (hDNA) generated during homologous recombination (HR) is an important component that shapes genetic diversity in sexually reproducing organisms. However, studies of this process in higher plants are limited. This is because hDNAs are difficult to capture in higher plants as their reproductive developmental model only produces normal gametes and does not preserve the mitotic products of the post-meiotic segregation (PMS) process which is crucial for studying hDNAs. In this study, using the model system for tree and woody perennial plant biology (Populus), we propose a strategy for characterizing hDNAs in higher plants. We captured hDNAs by constructing triploid hybrids originating from a cross between unreduced 2n eggs (containing hDNA information as a result of inhibition chromosome segregation at the PMS stage) with normal male gametes. These triploid hybrids allowed us to detect the frequency and location of persistent hDNAs resulting from HR at the molecular level. We found that the frequency of persistent hDNAs, which ranged from 5.3 to 76.6%, was related to locations of the simple sequence repeat markers at the chromosomes, such as the locus-centromere distance, the surrounding DNA sequence and epigenetic information, and the richness of protein-coding transcripts at these loci. In summary, this study provides a method for characterizing persistent hDNAs in higher plants. When high-throughput sequencing techniques can be incorporated, genome-wide persistent hDNA assays for higher plants can be easily carried out using the strategy presented in this study.
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[Epidemic situation and prevention strategy of schistosomiasis in Ya' an City after Lushan Earthquake on April 20, 2013].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 07-24-2014
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This paper analyzes the recently epidemic status of schistosomiasis, the change of natural and social factors, and field survey and evaluation data of schistosomiasis in Ya'an City after Lushan Earthquake on April 20, 2013, and proposes that it is necessary to strengthen the conventional schistosomiasis control measures, the control of exogenous infection sources, the control of Oncomelania hupensis snails and health education for ensuring no major epidemics after the disaster. This paper also recommends the direction and suggestions for future schistosomiasis control in Ya' an City.
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A novel biosensor-based microarray assay for the visualized detection of CYP2C19 ?2, ?3, ?4 and ?5 polymorphisms.
Clin. Chem. Lab. Med.
PUBLISHED: 07-07-2014
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Abstract Background: A number of studies have indicated that the conversion of clopidogrel to its active metabolite is reduced in patients who carry the CYP2C19 *2, *3, *4 or *5 loss-of-function allele, resulting in decreased response of platelet to clopidogrel treatment and worse cardiovascular outcome. The aim of this study was to develop a novel biosensor-based microarray to visually detect CYP2C19 polymorphisms. Methods: The target DNA was amplified from regions flanking the respective alleles using 5'-biotinylated reverse primer, and plasmids were prepared for the respective alleles. High stringency reversed hybridization, horseradish peroxidase-labeled streptavidin reaction, and color development, with multiple washes in different steps, were carried out and the results were recorded with an optical camera. The gene chips were tested for specificity, detection limit, intra- and inter-batch variations using the constructed plasmids. Finally, 88 clinical samples were assayed with this microarray as well as direct sequencing. Results: The results could be seen with the naked eye. Concordance tests indicated that for alleles *2, *3, *4, and *5, the ? values between this assay and plasmids all reached 1.000. The detection limit was 5×102 cells/mL. Concordance test between direct sequencing and the microarray assay using 88 clinical samples gave rise to the ? value of 0.983, and p<0.01, indicating very high concordance. Conclusions: This novel biosensor-based microarray assay can amplify the signal in situ so that it can be detected by simple instruments or even the naked eyes. It is promising for clinical application in hospital laboratories.
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Microfluidic-based measurement of erythrocyte sedimentation rate for biophysical assessment of blood in an in vivo malaria-infected mouse.
Biomicrofluidics
PUBLISHED: 07-01-2014
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This study suggests a new erythrocyte sedimentation rate (ESR) measurement method for the biophysical assessment of blood by using a microfluidic device. For an effective ESR measurement, a disposable syringe filled with blood is turned upside down and aligned at 180° with respect to gravitational direction. When the blood sample is delivered into the microfluidic device from the top position of the syringe, the hematocrit of blood flowing in the microfluidic channel decreases because the red blood cell-depleted region is increased from the top region of the syringe. The variation of hematocrit is evaluated by consecutively capturing images and conducting digital image processing technique for 10?min. The dynamic variation of ESR is quantitatively evaluated using two representative parameters, namely, time constant (?) and ESR-area (AESR). To check the performance of the proposed method, blood samples with various ESR values are prepared by adding different concentrations of dextran solution. ? and AESR are quantitatively evaluated by using the proposed method and a conventional method, respectively. The proposed method can be used to measure ESR with superior reliability, compared with the conventional method. The proposed method can also be used to quantify ESR of blood collected from malaria-infected mouse under in vivo condition. To indirectly compare with the results obtained by the proposed method, the viscosity and velocity of the blood are measured using the microfluidic device. As a result, the biophysical properties, including ESR and viscosity of blood, are significantly influenced by the parasitemia level. These experimental demonstrations support the notion that the proposed method is capable of effectively monitoring the biophysical properties of blood.
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Carotid baroreceptor stimulation prevents arrhythmias induced by acute myocardial infarction through autonomic modulation.
J. Cardiovasc. Pharmacol.
PUBLISHED: 07-01-2014
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: Electrical carotid baroreceptor stimulation (CBS) has shown therapeutic potential for resistant hypertension and heart failure by resetting autonomic nervous system, but the impacts on arrhythmias remains unclear. This study evaluated the effects of CBS on ventricular electrophysiological properties in normal dog heart and arrhythmias after acute myocardial infarction (AMI). In the acute protocol, anesthetized open chest dogs were exposed to 1 hour left anterior descending coronary occlusion as AMI model. Dogs were received either sham treatment (Control group, n = 8) or CBS (CBS group, n = 8), started 1 hour before AMI. CBS resulted in pronounced prolongation of ventricular effective refractory period and reduction of the maximum action potential duration restitution slope (from 0.85 ± 0.15 in the baseline state to 0.67 ± 0.09 at the end of 1 hour, P < 0.05) before AMI. Number of premature ventricular contractions (277 ± 168 in the Control group vs. 103 ± 84 in the CBS group, P < 0.05) and episodes of ventricular tachycardia/ventricular fibrillation (7 ± 3 in the Control group vs. 3 ± 2 in the CBS group, P < 0.05) was decreased compared with the control group during AMI. CBS buffered low-frequency/high-frequency ratio raise during AMI. Ischemic size was not affected by CBS. CBS may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone.
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Nanoassemblies driven by cyclodextrin-based inclusion complexation.
Chem. Commun. (Camb.)
PUBLISHED: 06-28-2014
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Nanoscaled supramolecular systems have attracted significant attention because of their promising applications in many fields. This review focuses on recent advances in the construction of nanoassemblies driven by cyclodextrin (CD)-based inclusion complexation and their application in biomedical and biomimetic fields. As a result of the reversibility of the CD-based host-guest interactions, CD-based driving forces provide the opportunity to generate complex and sophisticated nanoassemblies with tunable properties.
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Time series analysis of demographic and temporal trends of tuberculosis in Singapore.
BMC Public Health
PUBLISHED: 06-25-2014
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Singapore is an intermediate tuberculosis (TB) incidence country, with a recent rise in TB incidence from 2008, after a fall in incidence since 1998. This study identified population characteristics that were associated with the recent increase in TB cases, and built a predictive model of TB risk in Singapore.
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Modulation of microenvironmental pH and utilization of alkalizers in crystalline solid dispersion for enhanced solubility and stability of clarithromicin.
Arch. Pharm. Res.
PUBLISHED: 06-19-2014
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Clarithromycin (CAM) is known to be poorly water-soluble and acid-labile drug. Various alkalizers such as MgO, Na2CO3, Na2HPO4 and NaHCO3 were utilized to modulate the microenvironmental pH (pHM) and to improve the low stability and solubility of CAM in a crystalline-solid dispersion system (CSD). Polyvinylpyrrolidone (PVP K-30) and hydroxypropylmethylcellulose (HPMC) 4000-based CSDs containing alkalizers were prepared by cosolvent precipitation followed by evaporation process. The dried-CSDs mixed with microcrystalline cellulose, 2 % croscarmellose sodium, and 1 % magnesium stearate was then directly compressed into tablet. A dissolution test was carried out in 900 mL of pH 5.0 buffer solutions at 37 °C with a 50 rpm paddle speed. pHM, surface morphology, and structural behaviors were investigated. The dissolution rates of CAM in CSD containing alkalizers were improved. The drug in CSD remained crystalline as observed by differential scanning calorimetry and powder X-ray diffraction. Scanning electron microscopy revealed nearly identical images regardless of the sorts and amounts of carriers. PVP-based CSD tablet without alkalizer showed greater drug release, while HPMC-based CSD tablet without alkalizer retarded drug release due to its greater swelling capability. However, when the alkalizers were added in CSD tablet, the drug release was sharply increased. NaHCO3 induced the most rapid drug release while MgO retarded drug dissolution. Alkalizers in CSD also could maintain the pHM of the tablet above pH 5 under acidic conditions. The use of pH modifiers in CSDs could provide a useful method to improve the dissolution rate and stability of CAM via modulation of pHM without changing drug crystallinity.
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Research on protein thermal condensation detection based on phase modulation SPR imaging.
Biotechnol. Appl. Biochem.
PUBLISHED: 05-22-2014
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A novel SPR imaging biomolecular interaction detection method based on time domain phase modulation is presented in this thesis. Experimental apparatus of SPR imaging biomolecular interaction detection based on TDPM is established?and in order to detect biomolecular interaction. During the experimental pretreatment process, prepared the 2×2 lysozyme array chip and detect lysozyme thermal condensation state by the experimental apparatus. Extract the changed phase information through the Stoilov algorithm. Further obtain the interactive SPR curves and calculate kinetic parameters. It can sensitively acquire real-time phase change caused by biomolecular interaction based on interference imaging, and resolve the related bioinformation, which is a potential tool for proteomics research. This article is protected by copyright. All rights reserved.
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Role of interventional radiology in trauma care: retrospective study from single trauma center experience.
Am J Emerg Med
PUBLISHED: 05-10-2014
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Although interventional management is now regarded as essential in trauma care, the effect on clinical result remains uncertain. We conducted this retrospective study to figure out the role of interventional management in trauma care.
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Changes in velocity profile according to blood viscosity in a microchannel.
Biomicrofluidics
PUBLISHED: 05-01-2014
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Red blood cells (RBCs) are important to dictate hemorheological properties of blood. The shear-thinning effect of blood is mainly attributed to the characteristics of the RBCs. Variations in hemorheological properties alter flow resistance and wall shear stress in blood vessels. Therefore, detailed understanding of the relationship between the hemorheological and hemodynamic properties is of great importance. In this study, blood viscosity and blood flow were simultaneously measured in the same microfluidic device by monitoring the flow-switching phenomenon. To investigate blood flows according to hemorheological variations, the flow rate of blood samples (RBCs suspended in autologous plasma, dextran-treated plasma, and in phosphate buffered saline solution) was precisely controlled with a syringe pump. Velocity profiles of blood flows were measured by using a micro-particle imagevelocimetry technique. The shape of velocity profiles was quantified by using a curve-fitting equation. It is found that the shape of the velocity profiles is highly correlated with blood viscosity. To demonstrate the relationship under ex vivo conditions, biophysical properties and velocity profiles were measured in an extracorporeal rat bypass loop. Experimental results show that increased blood viscosity seems to induce blunt velocity profile with high velocity component at the wall of the microchannel. Simultaneous measurement of blood viscosity and velocity profile would be useful for understanding the effects of hemorheological features on the hemodynamic characteristics in capillary blood vessels.
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Genotype-Phenotype Correlations in Severe Acne in a Han Chinese Population.
Dermatology (Basel)
PUBLISHED: 04-28-2014
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Background: Two novel susceptibility gene loci (1q24.2 and 11p11.2) for severe acne have been identified in a genome-wide association study of a Han Chinese population. Objective: The current study investigated the relationships of these gene loci with clinical phenotypes, including onset age, atrophic scarring, hypertrophic scarring and family history. Furthermore, we investigated the correlations between these four clinical phenotypes. Methods: We used the ?(2) test to compare the allele frequency among the different clinical phenotypes. We calculated Spearman's correlation coefficient to measure the relationship between the different clinical phenotypes. Results: We identified significant associations between the 11p11.2 locus and disease family history (p < 0.05). We also determined that hypertrophic scarring was moderately correlated with atrophic scarring (rs = 0.315). Conclusions: This study suggests that the susceptibility gene locus 11p11.2 may contribute to the complex phenotypes of severe acne, particularly in cases of hereditary severe acne, whereas there are also correlations between the different phenotypes. © 2014 S. Karger AG, Basel.
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Reticulation of low density shape memory polymer foam with an in vivo demonstration of vascular occlusion.
J Mech Behav Biomed Mater
PUBLISHED: 04-26-2014
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Predominantly closed-cell low density shape memory polymer (SMP) foam was recently reported to be an effective aneurysm filling device in a porcine model (Rodriguez et al., Journal of Biomedical Materials Research Part A 2013: (http://dx.doi.org/10.1002/jbm.a.34782)). Because healing involves blood clotting and cell migration throughout the foam volume, a more open-cell structure may further enhance the healing response. This research sought to develop a non-destructive reticulation process for this SMP foam to disrupt the membranes between pore cells. Non-destructive mechanical reticulation was achieved using a gravity-driven floating nitinol pin array coupled with vibratory agitation of the foam and supplemental chemical etching. Reticulation resulted in a reduced elastic modulus and increased permeability, but did not impede the shape memory behavior. Reticulated foams were capable of achieving rapid vascular occlusion in an in vivo porcine model.
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Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion.
J. Cardiovasc. Electrophysiol.
PUBLISHED: 04-24-2014
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Renal sympathetic nerve (RSN) activity plays a key role in systemic sympathetic hyperactivity. Previous studies have shown that cardiac sympathetic hyperactivity, especially the left stellate ganglion (LSG), contributes to the pathogenesis of ventricular arrhythmias (VAs) after acute myocardial infarction (AMI).
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No association between Y chromosomal haplogroups and severe acne in the Han Chinese population.
J. Hum. Genet.
PUBLISHED: 04-01-2014
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Severe acne presents sexual dimorphism in its incidence in Chinese population. It is more prevalent in males. To assess the possible Y chromosomal contribution to severe acne risk in Han Chinese males, we analyzed 2041 Y chromosomal SNPs (Y-SNPs) in 725 severe acne cases and 651 controls retrieved from our recent genome-wide association study data. After data filtering, we assigned 585 cases and 494 controls into 12 Y chromosomal haplogroups based on 307 high-confidence Y-SNPs. No statistically significant difference in the distribution of Y chromosomal haplogroup frequencies was observed between the case and control groups. Our results showed a lack of association between the incidence of severe acne and the different Y chromosomal haplogroup in the Han Chinese population.
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Evolutionary pattern of rDNA following polyploidy in Leymus (Triticeae: Poaceae).
Mol. Phylogenet. Evol.
PUBLISHED: 03-20-2014
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Ribosomal ITS polymorphism and its ancestral genome origin of polyploid Leymus were examined to infer the evolutionary outcome of rDNA gene following allopolyploid speciation and to elucidate the geographic pattern of ITS variation. The results demonstrated that different polyploids have experienced varying fates, including maintenance or homogenization of divergent arrays, occurrence of chimeric repeats and potential pseudogenes. Our data suggested that (1) the Ns, P/F, and St genomic types in Leymus were originated from Psathyrostachys, Agropyron/Eremopyrum, and Pseudoroegneria, respectively; (2) the occurrence of a higher proportion of Leymus species with predominant uniparental rDNA type might associate with the segmental allopolyploid origin, nucleolar dominance of alloploids, and rapid radiation of Leymus; (3) maintenance of multiple parental ITS types in allopolyploid might result from long generation times associated to vegetative multiplication, number and chromosomal location of ribosomal loci and/or recurrent hybridization; (4) the rDNA genealogical structure of Leymus species might associate with the geographic origins; and (5) ITS sequence clade shared by Leymus species from Central Asia, North America, and Nordic might be an outcome of ancestral ITS homogenization. Our results shed new light on understanding evolutionary outcomes of rDNA following allopolyploid speciation and geographic isolation.
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Multiple Hypointense Vessels on Susceptibility-Weighted Imaging in Acute Ischemic Stroke: Surrogate Marker of Oxygen Extraction Fraction in Penumbra?
Cerebrovasc. Dis.
PUBLISHED: 03-13-2014
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Background: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. Methods: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. Results: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). Conclusions: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere. © 2014 S. Karger AG, Basel.
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Effect of peroxisome proliferator-activated receptor ? on the cholesterol efflux of peritoneal macrophages in inflammation.
Mol Med Rep
PUBLISHED: 03-12-2014
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Atherosclerosis, a chronic inflammatory disorder characterized by lipid and cholesterol accumulation, is the principal contributing factor to the pathology of cardiovascular disease. Macrophages contribute to plaque development by internalizing native and modified lipoproteins that convert them into cholesterol-rich foam cells. With multiple factors, including hypercholesterolemia and inflammation, promoting atherosclerosis, it is of great significance to elucidate how the mechanism of cholesterol efflux from the macrophages changes and the role of peroxisome proliferator-activated receptor ? (PPAR?) in these situations. Following isolation and culture of peritoneal macrophages from C57BL/6 mice in the present study, the cells were divided into three groups: The control group, the ciglitazone group and the PPAR? antisense oligonucleotide group. The expression of PPAR? and nuclear factor of ? light polypeptide gene enhancer in B?cells inhibitor ? (I?B?) in each group was observed through the levels of protein and mRNA, and then the cholesterol efflux of each group was investigated. In addition, the same experiments were repeated following stimulation of each group with lipopolysaccharide (LPS). No significant difference in the expression levels of PPAR? between the control group and ciglitazone group was observed. The expression levels of PPAR? in the PPAR? antisense oligonucleotide group were evidently lower than those in the control group. Subsequent to stimulation with LPS, the expression levels of PPAR? in the three groups were higher than those of each group prior to stimulation. The cholesterol efflux of the PPAR? antisense oligonucleotide group was clearly suppressed following stimulation with LPS in comparison with that of the other groups. PPAR? contributes to anti-inflammation by protecting I?B? from being phosphorylated and degraded and promoting cholesterol efflux from peritoneal macrophages in inflammation.
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Effects of CO2 pneumoperitoneum on the expression of thymidine kinase 1 and Ki67 in colorectal carcinoma cells.
Surg Endosc
PUBLISHED: 03-10-2014
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To investigate thymidine kinase 1(TK-1) and Ki67 expression levels of human colorectal carcinoma cells line SW480 after exposure to a simulated laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different pressures and lengths of exposure time.
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Resistive memory for harsh electronics: immunity to surface effect and high corrosion resistance via surface modification.
Sci Rep
PUBLISHED: 02-27-2014
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The tolerance/resistance of the electronic devices to extremely harsh environments is of supreme interest. Surface effects and chemical corrosion adversely affect stability and operation uniformity of metal oxide resistive memories. To achieve the surrounding-independent behavior, the surface modification is introduced into the ZnO memristors via incorporating fluorine to replace the oxygen sites. F-Zn bonds is formed to prevent oxygen chemisorption and ZnO dissolution upon corrosive atmospheric exposure, which effectively improves switching characteristics against harmful surroundings. In addition, the fluorine doping stabilizes the cycling endurance and narrows the distribution of switching parameters. The outcomes provide valuable insights for future nonvolatile memory developments in harsh electronics.
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Effect of Th17 and Treg axis disorder on outcomes of pulmonary arterial hypertension in connective tissue diseases.
Mediators Inflamm.
PUBLISHED: 02-22-2014
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This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH) and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD), 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR ?t mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.
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Contradictory imaging and EEG results in resection surgery of bitemporal lobe epilepsy: A case report.
Exp Ther Med
PUBLISHED: 02-13-2014
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The present study describes the case of a 27-year-old, right-handed female with bilateral mesial temporal lobe epilepsy. Electroencephalogram (EEG) monitoring from implanted electrodes displayed two different and independent onsets on the two sides of the mesial temporal structures, which specifically included clinical generalized tonic clonic seizure (GTCS) discharges originating from the left mesial temporal lobe, as well as complex partial seizure (CPS) discharges arising from the right mesial region. However, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) showed a unilateral abnormality, as in right mesial temporal lobe sclerosis. A decision was made to resect one side of the mesial temporal lobe, in order to avoid memory function impairment, and, relying on the MRI results, the right side was selected. However, surgery did not leave the patient seizure-free. The CPSs gradually eased, while the GTCSs originating from the left side became severely aggravated. In describing this case, the drawbacks of current epileptic diagnostic methods and surgical strategies for bitemporal lobe epilepsy are discussed, and the requirement for more treatment options is emphasized.
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New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 02-09-2014
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For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with ?-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential.
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Genome sequence of mungbean and insights into evolution within Vigna species.
Nat Commun
PUBLISHED: 02-03-2014
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Mungbean (Vigna radiata) is a fast-growing, warm-season legume crop that is primarily cultivated in developing countries of Asia. Here we construct a draft genome sequence of mungbean to facilitate genome research into the subgenus Ceratotropis, which includes several important dietary legumes in Asia, and to enable a better understanding of the evolution of leguminous species. Based on the de novo assembly of additional wild mungbean species, the divergence of what was eventually domesticated and the sampled wild mungbean species appears to have predated domestication. Moreover, the de novo assembly of a tetraploid Vigna species (V. reflexo-pilosa var. glabra) provides genomic evidence of a recent allopolyploid event. The species tree is constructed using de novo RNA-seq assemblies of 22 accessions of 18 Vigna species and protein sets of Glycine max. The present assembly of V. radiata var. radiata will facilitate genome research and accelerate molecular breeding of the subgenus Ceratotropis.
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Association between SNPs in P53 binding regions and risk of esophageal squamous cell carcinoma.
Int. J. Biol. Markers
PUBLISHED: 01-27-2014
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The tumor protein 53 (TP53 or p53) plays an important role in tumor suppression by binding to the regulatory region of its target genes. Single nucleotide polymorphisms (SNP) located in the p53 binding regions are likely to affect the expression of p53 target genes and may contribute to susceptibility to common diseases. The role of the genetic variations in esophageal squamous cell carcinoma (ESCC) has been well explored. However, the role of p53 binding region variations in esophageal cancer is poorly understood.
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The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis.
Korean J Pediatr
PUBLISHED: 01-17-2014
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Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients.
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Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne.
Nat Commun
PUBLISHED: 01-09-2014
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Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P(combined)=4.41 × 10?? and rs1060573, P(combined)=1.28 × 10??) and 1q24.2 (SELL, rs7531806, P(combined)=1.20 × 10??) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.
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MiR-21 inhibits c-Ski signaling to promote the proliferation of rat vascular smooth muscle cells.
Cell. Signal.
PUBLISHED: 01-07-2014
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Previously, we reported that the decrease of endogenous c-Ski expression is implicated in the progression of vascular smooth muscle cell (VSMC) proliferation after arterial injury. However, the molecular mechanism of the down-regulation of c-Ski is not clear. In this study, a potential miR-21 recognition element was identified in the 3'-untranslated region (UTR) of rat c-Ski mRNA. A reporter assay revealed that miR-21 could recognize the miR-21 recognition element of c-Ski mRNA. In A10 rat aortic smooth muscle cells, overexpression of miR-21 significantly inhibited the expression of c-Ski protein and promoted cell proliferation, which could be blocked by inhibition of miR-21 or overexpression of c-Ski. Further investigation demonstrated that the effect of miR-21 on VSMC proliferation resulted from negative regulation of c-Ski to suppress p38-p21/p27 signaling, the downstream pathway of c-Ski in VSMCs. These results indicate that c-Ski is a target gene of miR-21. miR-21 specifically binds to the 3'-untranslated region of c-Ski and negatively regulates c-Ski expression to diminish the protective effects of c-Ski and stimulate VSMC proliferation in the progression of arterial injury.
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Low-Level Carotid Baroreceptor Stimulation Suppresses Ventricular Arrhythmias during Acute Ischemia.
PLoS ONE
PUBLISHED: 01-01-2014
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The autonomic imbalance during acute ischemia is involved in the occurrence of life-threatening arrhythmias.
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c-Ski inhibits autophagy of vascular smooth muscle cells induced by oxLDL and PDGF.
PLoS ONE
PUBLISHED: 01-01-2014
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Autophagy is increasingly being recognized as a critical determinant of vascular smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski inhibits VSMC proliferation stimulated by transforming growth factor ? (TGF-?), but it is not clear whether c-Ski has the similar protective role against other vascular injury factors and whether regulation of autophagy is involved in its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs were treated with 40 µg/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml platelet-derived growth factor (PDGF), both of which were autophagy inducers and closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy. This action of c-Ski resulted in inhibiting the cell proliferation, the decrease of contractile phenotype marker ?-SMA expression while the increase of synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF. Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL or PDGF on A10 cell growth and phenotype transition. And further investigation found that inhibition of AKT phosphorylation to downregulate proliferating cell nuclear antigen (PCNA) expression, was involved in the regulation of autophagy and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs. Collectively, c-Ski may play an important role in inhibiting autophagy to protect VSMCs against some harsh stress including oxLDL and PDGF.
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Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families.
PLoS ONE
PUBLISHED: 01-01-2014
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Syndactyly type 1 (SD1) is an autosomal dominant limb malformation characterized in its classical form by complete or partial webbing between the third and fourth fingers and/or the second and third toes. Its four subtypes (a, b, c, and d) are defined based on variable phenotypes, but the responsible gene is yet to be identified. SD1-a has been mapped to chromosome 3p21.31 and SD1-b to 2q34-q36. SD1-c and SD1-d are very rare and, to our knowledge, no gene loci have been identified.
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Bubble-free and pulse-free fluid delivery into microfluidic devices.
Biomicrofluidics
PUBLISHED: 01-01-2014
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The bubble-free and pulse-free fluid delivery is critical to reliable operation of microfluidic devices. In this study, we propose a new method for stable bubble-free and pulse-free fluid delivery in a microfluidic device. Gas bubbles are separated from liquid by using the density difference between liquid and gas in a closed cavity. The pulsatile flow caused by a peristaltic pump is stabilized via gas compressibility. To demonstrate the proposed method, a fluidic chamber which is composed of two needles for inlet and outlet, one needle for a pinch valve and a closed cavity is carefully designed. By manipulating the opening or closing of the pinch valve, fluids fill up the fluidic chamber or are delivered into a microfluidic device through the fluidic chamber in a bubble-free and pulse-free manner. The performance of the proposed method in bubble-free and pulse-free fluid delivery is quantitatively evaluated. The proposed method is then applied to monitor the temporal variations of fluidic flows of rat blood circulating within a complex fluidic network including a rat, a pinch valve, a reservoir, a peristaltic pump, and the microfluidic device. In addition, the deformability of red blood cells and platelet aggregation are quantitatively evaluated from the information on the temporal variations of blood flows in the microfluidic device. These experimental demonstrations confirm that the proposed method is a promising tool for stable, bubble-free, and pulse-free supply of fluids, including whole blood, into a microfluidic device. Furthermore, the proposed method will be used to quantify the biophysical properties of blood circulating within an extracorporeal bypass loop of animal models.
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A novel mutation in the TECTA gene in a Chinese family with autosomal dominant nonsyndromic hearing loss.
PLoS ONE
PUBLISHED: 01-01-2014
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TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The ?-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257-262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA.
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TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The -308 G/A polymorphism in the tumor necrosis factor (TNF) gene has been implicated in the risk of acne vulgaris, but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -308 G/A polymorphism and acne vulgaris risk.
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Effect of CO2 pneumoperitoneum on the expression of the chemokine receptors CXCR4 and CCR7 in colorectal carcinoma cells in vitro.
Chin. Med. J.
PUBLISHED: 12-18-2013
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The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery. The aim of this research was to investigate the effect of CO2 pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells.
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Vesicular gold assemblies based on host-guest inclusion and its controllable release of doxorubicin.
Nanotechnology
PUBLISHED: 11-14-2013
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We have developed a kind of gold nanoparticle (AuNP) in which polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) are attached on the surface of a gold nanocrystal through the host-guest inclusion between adamantane groups (ADA) and ?-cyclodextrin (?-CD). The resulting AuNPs become amphiphilic in water above body temperature and self-assemble into vesicles. It is found that these vesicles can load doxorubicin (Dox) effectively. With a decrease in temperature, the PNIPAM shifted from hydrophobic to hydrophilic, causing Au vesicles to disassemble into stable small AuNPs, triggering the release of Dox. These hybrid vesicles, combining polymer functionality with the intriguing properties of AuNPs, can first release free Dox and AuNP/Dox at a site of a tumor through the application of either simple ice packs or deeply penetrating cryoprobes, then the AuNP/Dox can be taken in by tumor cells and destroy them like miniature munitions. Furthermore, these vesicles showed other therapeutic possibilities due to the presence of gold. We believe that the development of such multi-functional vesicles will provide new and therapeutically useful means for medical applications.
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Graphene oxide doped conducting polymer nanocomposite film for electrode-tissue interface.
Biomaterials
PUBLISHED: 10-29-2013
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One of the most significant components for implantable bioelectronic devices is the interface between the microelectrodes and the tissue or cells for disease diagnosis or treatment. To make the devices work efficiently and safely in vivo, the electrode-tissue interface should not only be confined in micro scale, but also possesses excellent electrochemical characteristic, stability and biocompatibility. Considering the enhancement of many composite materials by combining graphene oxide (GO) for its multiple advantages, we dope graphene oxide into poly(3,4-ethylenedioxythiophene) (PEDOT) forming a composite film by electrochemical deposition for electrode site modification. As a consequence, not only the enlargement of efficient surface area, but also the development of impedance, charge storage capacity and charge injection limit contribute to the excellent electrochemical performance. Furthermore, the stability and biocompatibility are confirmed by numerously repeated usage test and cell proliferation and attachment examination, respectively. As electrode-tissue interface, this biomaterial opens a new gate for tissue engineering and implantable electrophysiological devices.
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Microfluidic biosensor for monitoring temporal variations of hemorheological and hemodynamic properties using an extracorporeal rat bypass loop.
Anal. Chem.
PUBLISHED: 10-14-2013
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In this study, we propose a novel microfluidic biosensor for monitoring hemorheological and hemodynamic properties using an extracorporeal rat bypass loop. To monitor temporal variations of biophysical properties including viscosity, flow rate, and pressure of rat blood, a complex fluidic network is established by connecting the abdominal aorta and jugular vein to an extracorporeal bypass loop including a flow stabilizer and a microfluidic biosensor. Three biophysical properties are simultaneously measured through label-free operation and sensorless detection based on two sequential flow controls in the microfluidic channel. A discrete fluidic-circuit model is employed to derive analytical formulas for the complex fluidic network. First, to evaluate the measurement accuracy of the proposed method, a peristaltic pump is used as substitute for a rat. The flow rate and viscosity of 20% glycerin (test fluid) circulating within the fluidic network are measured, and then the results are compared with those obtained using conventional methods. The normal differences between two measurement methods are less than 4%. Then, the proposed method is used to monitor temporal variations in biophysical properties of blood circulating within the complex fluidic network under normal and continuous hemodilution conditions. Rats require at least 30 min to adapt to different fluidic environments. The flow rate, pressure, and hematocrit of rat blood tend to decrease gradually because of continuous hemodilution effect. Furthermore, the reduced flow rate increases blood viscosity under hemodilution condition. These experiments demonstrate that the proposed method can effectively monitor temporal variations of biophysical properties of rat blood under ex vivo conditions.
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Serotonin Transporter (5-HTT) Gene Polymorphisms and Susceptibility to Epilepsy: A Meta-Analysis and Meta-Regression.
Genet Test Mol Biomarkers
PUBLISHED: 10-05-2013
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Aims: Serotonin transporter (5-HTT) plays a central role in the regulation of serotonin (5-hydroxytryptamine [5-HT]) synaptic function. Disturbances in 5-HT transmission are the most frequently reported neurobiological substrates of suicidal behavior. Emerging evidence has shown that the common polymorphisms in the 5-HTT gene may contribute to the risk of epilepsy, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the associations between 5-HTT gene polymorphisms and susceptibility to epilepsy. Methods: A literature search of PubMed, Embase, Web of Science, and China BioMedicine (CBM) databases was conducted on articles published before June 1st, 2013. Crude odds ratios with 95% confidence intervals were calculated. Results: Seven studies were assessed with a total 1303 epilepsy patients and 1288 healthy controls. The meta-analysis results indicated that there was no significant relationship between 5-HTT gene polymorphisms and an increased risk of epilepsy. Further subgroup analysis based on ethnicity also found no significant association between 5-HTT gene polymorphisms and epilepsy risk among both Caucasian and Asian populations. In addition, there was also no significant association between 5-HTT gene polymorphisms and the risk of psychiatric comorbidity in patients with epilepsy. Conclusion: In conclusion, the current meta-analysis indicates that 5-HTT gene polymorphisms might not be the primary determinants of epilepsy susceptibility. 5-HTT genes might be expected to interact with other genes in different signaling pathways to initiate and promote the epileptogenic process.
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Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing.
J Transl Med
PUBLISHED: 08-20-2013
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Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis.
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New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method.
Int J Pharm
PUBLISHED: 08-19-2013
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The content uniformity of low dose drugs in dosage forms is very important for quality assurance. The aim of this study was to prepare uniformly and homogeneously distributed dosage forms of very low-dose drugs using twin screw hot-melt extrusion (HME) and to investigate the distribution of drugs using instrumental analyses. For the feasibility of HME method, a very low amount of coumarin-6, a fluorescent dye, was used to visualize distribution images using confocal laser scanning microscope (CLSM). Limaprost, tamsulosin and glimepiride were then used as low-dose model drugs to study the applicability of HME for content uniformity and distribution behaviors. Hydrophilic thermosensitive polymers with low melting point, such as Poloxamer188 and polyethylene glycol (PEG) 6000, were chosen as carriers. The melt extrusion was carried out around 50°C, at which both carriers were easily dissolved but model drugs remained in solid form. The physicochemical properties of the hot-melt extrudates, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were measured. Content uniformity of the drugs was also checked by HPLC. CLSM imaging showed that model drugs were well distributed throughout the hot-melt extrudate, giving better content uniformity with low batch-to-batch variations compared with simple physical mixtures. DSC, PXRD and FT-IR data showed that there was no interaction or interference between model drugs and thermosensitive polymers. The current HME methods could be used to prepare uniformly distributed and reproducible solid dosage forms containing very low dose drugs for further pharmaceutical applications.
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Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with poor prognosis of patients with resected non-small cell lung cancer.
Oncol. Rep.
PUBLISHED: 08-15-2013
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Specific and sensitive enough molecular biomarkers are lacking to accurately predict the survival of non-small cell lung cancer (NSCLC) patients. ARHGEF5 and Src have been shown to play an important role in tumorigenesis. However, the involvement of ARHGEF5 and Src in NSCLC remains unknown. Therefore, we evaluated the expression of ARHGEF5 and Src in resected NSCLC tissues and the correlation of co-expression of ARHGEF5 and Src and the prognosis of patients with resected NSCLC. Positive expression of ARHGEF5 was detected in 133 cases of 193 patients (68.91%). A total of 193 NSCLC patients (male: 145; female: 48; average age: 61.84 years; age range: 31-84) were enrolled in this study, of which 99 cases were squamous cell carcinomas (SCCs) (51.30%) and 94 cases were adenocarcinomas (ADCs) (48.70%). The expression of ARHGEF5 was mainly located in the cytoplasm of tumor cells, but not in the corresponding adjacent lung tissues. The levels of ARHGEF5 were significantly associated with age, differentiation and tumor stage. ARHGEF5 protein expression was associated with Src protein expression in NSCLC (?(2) = 11.874, P<0.01) and in ADC (?(2) = 12.194, P<0.01), but not in SCC. Co-immunoprecipitation revealed that there was a physical interaction between Src and ARHGEF5 in lung cancer cells. The patients with ARHGEF5(+)/Src(+) had a shorter survival time compared with the other patients (29.37 months versus 39.90 months, P = 0.029). In conclusion, ARHGEF5/Src can be considered as a prognostic biomarker and a therapeutic target for patients with resected NSCLC.
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[Study of the association between SNP rs7903146(C/T) in TCF7L2 and metabolic syndrome in Chinese Korean and Han populations from Yanbian].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 08-09-2013
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To assess the association between a rs7903146(C/T) polymorphism of TCF7L2 gene and metabolic syndrome (MS), plasma lipoprotein, and plasma adiponectin (PA) in Chinese Korean and Han populations from Yanbian region.
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The polymorphism of CLOCK gene 3111T/C C>T is associated with susceptibility of Alzheimer disease in Chinese population.
J. Investig. Med.
PUBLISHED: 08-06-2013
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In the present study, it was examined whether polymorphism of circadian locomotor output cycle kaput (CLOCK) gene 3111T/C was associated with susceptibility of Alzheimer disease (AD).
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New ?-phospholactam as a carbapenem transition state analog: Synthesis of a broad-spectrum inhibitor of metallo-?-lactamases.
Bioorg. Med. Chem. Lett.
PUBLISHED: 07-19-2013
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In an effort to test whether a transition state analog is an inhibitor of the metallo-?-lactamases, a phospholactam analog of carbapenem has been synthesized and characterized. The phospholactam 1 proved to be a weak, time-dependent inhibitor of IMP-1 (70%), CcrA (70%), L1 (70%), NDM-1 (53%), and Bla2 (94%) at an inhibitor concentration of 100?M. The phospholactam 1 activated ImiS and BcII at the same concentration. Docking studies were used to explain binding and to offer suggestions for modifications to the phospholactam scaffold to improve binding affinities.
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ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma.
Mod. Pathol.
PUBLISHED: 07-11-2013
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Invasion and metastasis are the major cause of deaths in patients with esophageal cancer. In this study, we isolated cancer stem-like cells from an esophageal squamous cell carcinoma cell line EC109 based on aldehyde dehydrogenase 1A1 (ALDH1A1), and found that ALDH1A1(high) cells possessed the capacities of self-renewal, differentiation and tumor initiation, indications of stem cell properties. To support their stemness, ALDH1A1(high) cells exhibited increased potential of invasion and metastasis as compared with ALDH1A1(low) cells. ALDH1A1(high) esophageal squamous cell carcinoma cells expressed increased levels of mRNA for vimentin, matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9), but decreased the level of E-cadherin mRNA, suggesting that epithelial-mesenchymal transition and secretary MMPs may be attributed to the high invasive and metastatic capabilities of ALDH1A1(high) cells. Furthermore, we examined esophageal squamous cell carcinoma specimens from 165 patients and found that ALDH1A1(high) cells were associated with esophageal squamous dysplasia and the grades, differentiation and invasion depth, lymph node metastasis and UICC stage of esophageal squamous cell carcinoma, as well as poor prognosis of patients. Our results provide the strong evidence that ALDH1A1(high) cancer stem-like cells contribute to the invasion, metastasis and poor outcome of human esophageal squamous cell carcinoma.Modern Pathology advance online publication, 8 November 2013; doi:10.1038/modpathol.2013.189.
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Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1.
J. Virol.
PUBLISHED: 07-10-2013
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Retinoic acid-inducible gene I (RIG-I) is a key sensor for recognizing nucleic acids derived from RNA viruses and triggers beta interferon (IFN-?) production. Because of its important role in antiviral innate immunity, the activity of RIG-I must be tightly controlled. Here, we used yeast two-hybrid screening to identify a SEC14 family member, SEC14L1, as a RIG-I-associated negative regulator. Transfected SEC14L1 interacted with RIG-I, and endogenous SEC14L1 associated with RIG-I in a viral infection-inducible manner. Overexpression of SEC14L1 inhibited transcriptional activity of the IFN-? promoter induced by RIG-I but not TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3). Knockdown of endogenous SEC14L1 in both HEK293T cells and HT1080 cells potentiated RIG-I and Sendai virus-triggered IFN-? production as well as attenuated the replication of Newcastle disease virus. SEC14L1 interacted with the N-terminal domain of RIG-I (RIG-I caspase activation and recruitment domain [RIG-I-CARD]) and competed with VISA/MAVS/IPS-1/Cardif for RIG-I-CARD binding. Domain mapping further indicated that the PRELI-MSF1 and CRAL-TRIO domains but not the GOLD domain of SEC14L1 are required for interaction and inhibitory function. These findings suggest that SEC14L1 functions as a novel negative regulator of RIG-I-mediated antiviral signaling by preventing RIG-I interaction with the downstream effector.
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[A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a hamster model].
Yao Xue Xue Bao
PUBLISHED: 07-10-2013
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To obtain a better understanding of the progression of atherosclerosis and identify potential biomarkers, proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabonomics was used to study the metabolic changes in the plasma of hamster fed with a high-fat/cholesterol diet. Plasma samples were collected at different time points during the progression of atherosclerosis and individual proton NMR spectra were visually and statistically assessed using multivariate analyses. NMR results for all samples showed a time-dependent development from physiological to pathophysiological status during atherosclerosis. Analysis of the identified biomarkers of atherosclerosis suggests that lipid and amino acid metabolisms are significantly disturbed, together with inflammation, oxidative stress, following cholesterol overloading. The results enriched our understanding of the mechanism of atherosclerosis and demonstrated the effectiveness of the NMR-based metabonomics approach to study such a complex disease.
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Effects of ?-synuclein on the tumorigenicity and metastasis of colon cancer SW1116 cells in vitro and in vivo.
Oncol. Rep.
PUBLISHED: 07-02-2013
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Recent evidence suggests the involvement of ?-synuclein in tumorigenesis and tumor progression. The present study was designed to further clarify the effects of ?-synuclein on the biological features of colon cancer cells in vitro and in vivo. We constructed the eukaryotic expression vector and siRNA vector and selected stable transfectants to respectively upregulate and downregulate ?-synuclein expression in SW1116 cells. we found that silencing of ?-synuclein significantly attenuated SW1116 cell growth and colony formation in vitro (P<0.05), and overexpression of ?-synuclein moderately enhanced cell growth and colony formation, but not significantly when compared with the parental SW1116 cells and empty vector-transfected cells (P>0.05). Meanwhile, overexpression of ?-synuclein significantly facilitated SW1116 cell migration, invasion and adhesion to human liver sinusoidal endothelial cells (HLSECs) in vitro (P<0.05), and the effects were less attenuated by ?-synuclein knockdown (P>0.05). Furthermore, ?-synuclein promoted these malignant phenotypes in a ?-synuclein expression quantity-dependent manner not only in vitro but also in the in vivo expression. stable cells were injected subcutaneously into the right flank, and injected intrasplenically in nude mice. ?-synuclein knockdown suppressed the tumorigenicity of SW1116 cells in mice, which presented significantly smaller tumor masses on day 6 over a 30-day period, compared with empty vector cells (P<0.05). Meanwhile, overexpression of ?-synuclein led to a profound augmentation of liver metastasis in nude mice, not only in macroscopic appearance but also in the size and weight of livers (P<0.05). These results provide strong evidence that suggests ?-synuclein plays a positive role in the progression of colorectal cancer.
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Oncogenesis and the clinical significance of K-ras in pancreatic adenocarcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-28-2013
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The RAS family genes encode small GTP-binding cytoplasmic proteins. Activated KRAS engages multiple effector pathways, notably the RAF-mitogen-activated protein kinase, phosphoinositide-3-kinase (PI3K) and RalGDS pathways. In the clinical field, K-ras oncogene activation is frequently found in human cancers and thus may serve as a potential diagnostic marker for cancer cells in circulation. This mini-review aims to summarise information on Ras-induced oncogenesis and the clinical significance of K-ras.
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Molecular evolution and diversity of dimeric alpha-amylase inhibitor gene in Kengyilia species (Triticeae: Poaceae).
Gene
PUBLISHED: 06-23-2013
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Kengyilia Yen et J. L. Yang is a group of allohexaploid species with StYP genomic constitutions in the wheat tribe. To investigate the evolution and diversity of dimeric alpha-amylase inhibitor genes in the Kengyilia, forty-five homoeologous DAAI gene sequences were isolated from sampled Kengyilia species and analyzed together with those of its close relatives. These results suggested that (1) Kengyilia species from Central Asia and the Qinghai-Tibetan Plateau had different origins from those of the geographically differentiated P genome; (2) the St and P genomes of Kengyilia were donated by Pseudoroegneria and Agropyron, respectively, and the Y genome had an independent origin and showed an affinity with the St genome; (3) purifying selection dominated the DAAI gene members and the St-DAAI gene was evolving at faster rate than the P- and Y-DAAI genes in Kengyilia; and (4) natural selection was the main factor on the codon usage pattern of the DAAI gene in Kengyilia.
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Hybrid ZnO NR/graphene structures as advanced optoelectronic devices with high transmittance.
Nanoscale Res Lett
PUBLISHED: 06-09-2013
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A hybrid structure (HS) made of one-dimensional ZnO nanorods (NRs) and a two-dimensional synthesized graphene sheet was successfully constructed in this study. The uniform ZnO NRs were obtained by hydrothermal method and grown on a graphene surface that had been transferred to a polyethylene terephthalate substrate. The HS exhibited high transmittance (approximately 75%) over the visible wavelength range, even after cyclic bending with a small radius of curvature. Raman spectroscopy and Hall measurement were carried out to verify the chemical composition and electrical properties of the structure. Stable electrical conductance of the ZnO NR/graphene HS was achieved, and increase in carrier mobility decreased the resistance of the ZnO-with-graphene sheet in comparison with bare ZnO NRs.
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Targeted induction of apoptosis in glioblastoma multiforme cells by an MRP3-specific TRAIL fusion protein in vitro.
Tumour Biol.
PUBLISHED: 06-04-2013
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Single-chain Fv fragments (scFvs) consist of the variable heavy-chain (VH) and variable light-chain (VL) domains, which are the smallest immunoglobulin fragments containing the whole antigen-binding site. Human soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) proves to acquire a potent pro-apoptotic activity only after selective binding to a predefined tumor cell surface antigen and has no off-target effects towards normal cells. Glioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor and overexpresses human multidrug resistance protein 3 (MRP3). In this study, we designed a novel fusion protein, termed scFvM58-sTRAIL, in which the MRP3-specific scFv antibody M58 was genetically fused to the N-terminus of human soluble TRAIL (sTRAIL). The recombinant scFvM58-sTRAIL fusion protein, expressed in Escherichia coli, was purified by chromatography and tested for cytotoxicity. scFvM58-sTRAIL showed a significant apoptosis-inducing activity towards MRP3-positive GBM cells in vitro. The pro-apoptotic activity of scFvM58-sTRAIL towards GBM cells was strongly inhibited in the presence of the parental scFvM58 antibody, suggesting that cytotoxic activity is MRP3-restricted. In a control experiment with MRP3-negative Jurkat cells, scFvM58-sTRAIL did not induce apparent apoptosis. In addition, through target antigen-restricted binding, scFvM58-sTRAIL was capable of activating not only TRAIL-R1 but also TRAIL-R2. In conclusion, our results suggest that fusion protein scFvM58-sTRAIL with specificity for MRP3 is a highly selective therapeutic agent and may provide an alternative therapy for human GBM.
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Phylogenetic relationships and Y genome origin in Elymus L. sensu lato (Triticeae; Poaceae) based on single-copy nuclear Acc1 and Pgk1 gene sequences.
Mol. Phylogenet. Evol.
PUBLISHED: 06-03-2013
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To estimate the origin and genomic relationships of the polyploid species within Elymus L. sensu lato, two unlinked single-copy nuclear gene (Acc1 and Pgk1) sequences of eighteen tetraploids (StH and StY genomes) and fourteen hexaploids (StStH, StYP, StYH, and StYW genomes) were analyzed with those of 35 diploid taxa representing 18 basic genomes in Triticeae. Sequence and phylogenetic analysis suggested that: (1) the St, H, W, and P genomes were donated by Pseudoroegneria, Hordeum, Australopyrum, and Agropyron, respectively, while the Y genome is closely related to the Xp genome in Peridictyon sanctum; (2) different hexaploid Elymus s.l. species may derived their StY genome from different StY genome tetraploid species via independent origins; (3) due to incomplete lineage sorting and/or hybridization events, the genealogical conflict between the two gene trees suggest introgression involving some Elymus s.l. species, Pseudoroegneria, Agropyron and Aegilops/Triticum; (4) it is reasonable to recognize the StH genome species as Elymus sensu stricto, the StY genome species as Roegneria, the StYW genome species as Anthosachne, the StYH genome species as Campeiostachys, and the StYP genome species as Kengyilia. The occurrence of multiple origin and introgression could account for the rich diversity and ecological adaptation of Elymus s.l. species.
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Diagnostic and therapeutic strategy and the most efficient prognostic factors of breast malignant fibrous histiocytoma.
Sci Rep
PUBLISHED: 05-29-2013
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We analyzed the clinicopathological features of 9 breast malignant fibrous histiocytoma (MFH) patients. Immunohistochemistry was used to make both diagnosis and differential diagnosis, and to identify prognostic factors. All tumors lacked epithelial markers but expressed mesenchymal markers, suggesting a mesenchymal origin. Of the five cases expressing Ki-67, two of three patients with axillary lymph node involvement died between 6-8 months, and two died at 17 and 26 months after diagnosis. The two remaining cases, with low Ki-67 expression, had no recurrent or metastatic disease at 145 months after diagnosis. Previous studies have shown that surgery is the primary treatment of choice, but no clear benefit from adjuvant chemotherapy was observed. We demonstrate that axillary lymph node involvement and high expression of Ki-67 are associated with poorer prognosis. A literature review indicates surgery remains the first choice for MFH, but benefits from adjuvant chemotherapy remain unclear.
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Nitric oxide down-regulation of carotenoid synthesis and PSII activity in relation to very high light-induced singlet oxygen production and oxidative stress in Chlamydomonas reinhardtii.
Plant Cell Physiol.
PUBLISHED: 05-27-2013
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Nitric oxide (NO) was produced in Chlamydomonas reinhardtii cells 30 min after illumination at a very high light intensity of 3,000 µmol m?² s?¹ (VHL) followed by singlet oxygen (¹O?) production, lipid peroxidation, expression of oxidative stress-related genes, irreversible PSII inactivation and cell death. Treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), an NO scavenger, effectively reduced ¹O? levels and VHL damage, while treatment with diphenylamine (DPA), an ¹O? scavenger, only slightly reduced NO levels, though VHL damage was still effectively reduced. In the presence of cPTIO, the decline in minimum (Fo, Ft) and maximum (Fm, Fm) fluorescence after 60 min of VHL illumination can be slowed, and after recovery to 50 µmol m?² s?¹ conditions, PSII activity (Fv/Fm, Fv/Fm) and PSII donor-side and acceptor-side electron transfer were partially restored. This finding indicates that ¹O? production is induced by NO through inhibition of PSII electron transfer under VHL conditions. VHL illumination caused a decrease in carotenoid contents but a transient increase in the transcription of two enzymes involved in carotenoid synthesis, phytoene synthase (PSY) and phytoene desaturase (PDS), at 30 min followed by a decrease at 60 min. The VHL-induced decrease in PDS transcription can be inhibited in the presence of cPTIO. The results of the present study show that NO generated in C. reinhardtii cells under VHL conditions induces ¹O? accumulation due to a decrease in the ¹O?-scavenging capacity caused by NO-mediated inhibition of carotenoid synthesis and PSII electron transport, which, in turn, leads to oxidative damage and cell death.
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Phylogeny and molecular evolution of the Acc1 gene within the StH genome species in Triticeae (Poaceae).
Gene
PUBLISHED: 05-23-2013
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To estimate the phylogeny and molecular evolution of a single-copy gene encoding plastid acetyl-CoA carboxylase (Acc1) within the StH genome species, two Acc1 homoeologous sequences were isolated from nearly all the sampled StH genome species and were analyzed with those from 35 diploid taxa representing 19 basic genomes in Triticeae. Sequence diversity patterns and genealogical analysis suggested that (1) the StH genome species from the same areas or neighboring geographic regions are closely related to each other; (2) the Acc1 gene sequences of the StH genome species from North America and Eurasia are evolutionarily distinct; (3) Dasypyrum has contributed to the nuclear genome of Elymus repens and Elymus mutabilis; (4) the StH genome polyploids have higher levels of sequence diversity in the H genome homoeolog than the St genome homoeolog; and (5) the Acc1 sequence may evolve faster in the polyploid species than in the diploids. Our result provides some insight on evolutionary dynamics of duplicate Acc1 gene, the polyploidy speciation and phylogeny of the StH genome species.
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Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis.
Curr Drug Deliv
PUBLISHED: 05-21-2013
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Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets.
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Why ligand cross-reactivity is high within peptide recognition domain families? A case study on human c-Src SH3 domain.
J. Theor. Biol.
PUBLISHED: 05-15-2013
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Many important protein-protein interactions in eukaryotic signaling networks are mediated by peptide recognition domains (PRDs), which bind short linear sequence motifs in other proteins. However, high ligand cross-reactivity is observed within most PRD families, rendering a broad specificity for the family members. In the present study, we attempt to explore the molecular mechanism and physicochemical origin of PRD cross-reactivity. In the procedure, a structure-based method called atomic cross-nonbonded interaction analysis (ACNIA) is described to extract atomic-level nonbonded interaction information at domain-peptide interface and to correlate the information with peptide affinity based on a set of structure-solved, affinity-known protein-peptide complex samples compiled from numerous literatures and databases. The ACNIA-derived affinity predictor is tested rigorously with statistical validation approach, which is also demonstrated to be capable of perceiving slight structural change in the interface using three distinct panels of SH3-binding peptide data. Subsequently, with help of the affinity predictor we adopt the human c-Src SH3 domain, one of the most sophisticated PRDs, as a paradigm to investigate the ligand cross-reactivity within SH3 family. It is found that most of the family members have only few non-essential residue differences in their peptide-binding pockets, and thus exhibit a similar peptide recognition profile and high cross-reactivity. The cross-reactivity is even shared by different subclasses of SH3 domains. The findings suggest that inherent binding specificity is not the only factor to select appropriate binders for specific SH3 domains, and other aspects such as cellular context and the rest of the SH3-containing proteins may play important roles in reducing their ligand cross-reactivity.
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Inhibition of PTEN expression and activity by angiotensin II induces proliferation and migration of vascular smooth muscle cells.
J. Cell. Biochem.
PUBLISHED: 04-23-2013
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PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor and has been suggested recently to be involved in the regulation of cardiovascular diseases. The molecular mechanisms of this regulation are however poorly understood. This study shows that down regulation of PTEN expression and activity by angiotensin II (Ang II) increased proliferation and migration of vascular smooth muscle cells (VSMCs). The presence of Ang II induced rapid PTEN phosphorylation and oxidation in accordance with increased AKT and FAK phosphorylation. The Ang II-mediated VSMC proliferation and migration was inhibited when cellular PTEN expression was increased by AT1 inhibitor losartan, PPAR? agonist rosiglitazone, NF-?B inhibitor BAY 11-7082. Over expression of PTEN in VSMCs by adenovirus transduction also resulted in inhibition of cell proliferation and migration in response to Ang II. These results suggest that PTEN down-regulation is involved in proliferation and migration of VSMCs induced by Ang II. This provides insight into the molecular regulation of PTEN in vascular smooth muscle cells and suggests that targeting the action of PTEN may represent an effective therapeutic approach for the treatment of cardiovascular diseases.
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Genome-wide SNP discovery in mungbean by Illumina HiSeq.
Theor. Appl. Genet.
PUBLISHED: 04-20-2013
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Mungbean [Vigna radiata (L.) Wilczek], a self-pollinated diploid plant with 2n = 22 chromosomes, is an important legume crop with a high-quality amino acid profile. Sequence variation at the whole-genome level was examined by comparing two mungbean cultivars, Sunhwanokdu and Gyeonggijaerae 5, using Illumina HiSeq sequencing data. More than 40 billion bp from both mungbean cultivars were sequenced to a depth of 72×. After de novo assembly of Sunhwanokdu contigs by ABySS 1.3.2 (N50 = 9,958 bp), those longer than 10 kb were aligned with Gyeonggijaerae 5 reads using the Burrows-Wheeler Aligner. SAMTools was used for retrieving single nucleotide polymorphisms (SNPs) between Sunhwanokdu and Gyeonggijaerae 5, defining the lowest and highest depths as 5 and 100, respectively, and the sequence quality as 100. Of the 305,504 single-base changes identified, 40,503 SNPs were considered heterozygous in Gyeonggijaerae 5. Among the remaining 265,001 SNPs, 65.9 % (174,579 cases) were transitions and 34.1 % (90,422 cases) were transversions. For SNP validation, a total of 42 SNPs were chosen among Sunhwanokdu contigs longer than 10 kb and sharing at least 80 % sequence identity with common bean expressed sequence tags as determined with est2genome. Using seven mungbean cultivars from various origins in addition to Sunhwanokdu and Gyeonggijaerae 5, most of the SNPs identified by bioinformatics tools were confirmed by Sanger sequencing. These genome-wide SNP markers could enrich the current molecular resources and might be of value for the construction of a mungbean genetic map and the investigation of genetic diversity.
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Triple pathology in patients with temporal lobe epilepsy: A case report and review of the literature.
Exp Ther Med
PUBLISHED: 03-30-2013
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The coexistence of three intracranial lesions related to epileptic pathogenesis is known as triple pathology and has rarely been reported. In this study we report a case of temporal lobe epilepsy (TLE) with the coexistence of hippocampal sclerosis (HS), focal cortical dysplasia (FCD) and ganglioglioma in the temporal lobe. A 29-year-old male who had experienced recurrent seizures for four years was admitted to hospital. Cerebral magnetic resonance imaging (MRI) was conducted and T2-weighted and fluid-attenuated inversion recovery sequence (FLAIR) images revealed a reduced hippocampal volume with an increased FLAIR signal on the right side and a slightly enlarged temporal horn, which are typical imaging findings for HS and FCD. The patient underwent resectioning of the right anterior temporal lobe, hippocampus and amygdala, in addition to the lesion located in the medial temporal lobe. Immunohistochemical analysis of the medial temporal lobe lesion confirmed a ganglioglioma (WHO grade I) in the medial temporal lobe. During the first eight months following surgery, the patients seizures were controlled with zonisamide and phenytoin. Electroencephalogram (EEG) assessment post-surgery confirmed the absence of epileptic discharges. Based on a literature review and a detailed review of this case, we postulate two possible explanations for the pathogenesis of triple pathology: i) triple pathology is a combination of pathological progression and occasionality; and ii) triple pathology lesions have similar pathological origins.
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Double-blind, randomized, controlled clinical trial of the effects of diosmectite and basic fibroblast growth factor paste on the treatment of minor recurrent aphthous stomatitis.
Oral Surg Oral Med Oral Pathol Oral Radiol
PUBLISHED: 03-13-2013
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This study investigated the effectiveness and safety of topical application of diosmectite (DS) and basic fibroblast growth factor (bFGF) paste in the treatment of minor recurrent aphthous stomatitis.
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Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-25-2013
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Vx-770 (Ivacaftor), a Food and Drug Administration (FDA)-approved drug for clinical application to patients with cystic fibrosis (CF), shifts the paradigm from conventional symptomatic treatments to therapeutics directly tackling the root of the disease: functional defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by pathogenic mutations. The underlying mechanism for the action of Vx-770 remains elusive partly because this compound not only increases the activity of wild-type (WT) channels whose gating is primarily controlled by ATP binding/hydrolysis, but also improves the function of G551D-CFTR, a disease-associated mutation that abolishes CFTRs responsiveness to ATP. Here we provide a unified theory to account for this dual effect of Vx-770. We found that Vx-770 enhances spontaneous, ATP-independent activity of WT-CFTR to a similar magnitude as its effects on G551D channels, a result essentially explaining Vx-770s effect on G551D-CFTR. Furthermore, Vx-770 increases the open time of WT-CFTR in an [ATP]-dependent manner. This distinct kinetic effect is accountable with a newly proposed CFTR gating model depicting an [ATP]-dependent "reentry" mechanism that allows CFTR shuffling among different open states by undergoing multiple rounds of ATP hydrolysis. We further examined the effect of Vx-770 on R352C-CFTR, a unique mutant that allows direct observation of hydrolysis-triggered gating events. Our data corroborate that Vx-770 increases the open time of WT-CFTR by stabilizing a posthydrolytic open state and thereby fosters decoupling between the gating cycle and ATP hydrolysis cycle. The current study also suggests that this unique mechanism of drug action can be further exploited to develop strategies that enhance the function of CFTR.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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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.