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ABSTRACT: We have previously demonstrated that DNA demethylation of CD40L on the X chromosome is responsible for female susceptibility to systemic lupus erythematosus (SLE). It is unknown whether aberrant methylation of the CD40L gene also contributes to the higher incidence of rheumatoid arthritis (RA) in females. In this study, we used real-time RT-PCR and flow cytometry to compare CD40L expression levels, and bisulfite sequencing to assess the methylation status of the CD40L promoter region. The results show that CD40L is upregrulated in CD4(+) T cells of female patients with RA. In addition, the CD40L promoter region in CD4(+) T cells from female RA patients was found to be demethylated, which corresponded with increased CD40L mRNA expression. These findings suggest that DNA demethylation contributes to CD40L expression in RA CD4(+) T cells and may in part explain the female preponderance of this disease.
Clinical Immunology 07/2012; 145(1):13-8. · 4.05 Impact Factor
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ABSTRACT: In previous studies, we demonstrated that miR-193b expression is reduced in melanoma relative to benign nevi, and also that miR-193b represses cyclin D1 and Mcl-1 expression. We suggested that stathmin 1 (STMN1) might be a target of miR-193b. STMN1 normally regulates microtubule dynamics either by sequestering free tubulin heterodimers or by promoting microtubule catastrophe. Increased expression of STMN1 has been observed in a variety of human malignancies, but its association with melanoma is unknown. We now report that STMN1 is upregulated during the progression of melanoma relative to benign nevi, and that STMN1 is directly regulated by miR-193b. Using an experimental cell culture approach, overexpression of miR-193b using synthetic microRNAs repressed STMN1 expression, whereas inhibition of miR-193b with anti-miR oligos increased STMN1 expression in melanoma cells. The use of a luciferase reporter assay confirmed that miR-193b directly regulates STMN1 by targeting the 3'-untranslated region of STMN1 mRNA. We further demonstrated that STMN1 is overexpressed in malignant melanoma compared with nevi in two independent melanoma cohorts, and that its level is inversely correlated with miR-193b expression. However, STMN1 expression was not significantly associated with patient survival, Breslow depth, mitotic count or patient age. STMN1 knockdown by small-interfering RNA in melanoma cells drastically repressed cell proliferation and migration potential, whereas ectopic expression of STMN1 using lentivirus increased cell proliferation and migration rates. Subsequent gene expression analysis indicated that interconnected cytoskeletal networks are directly affected following STMN1 knockdown. In addition, we identified deregulated genes associated with proliferation and migration, and revealed that p21(Cip1/Waf1) and p27(Kip) could be downstream effectors of STMN1 signaling. Taken together, our study suggests that downregulation of miR-193b may contribute to increased STMN1 expression in melanoma, which consequently promotes migration and proliferation of tumor cells.Oncogene advance online publication, 4 June 2012; doi:10.1038/onc.2012.141.
Oncogene 06/2012; · 6.37 Impact Factor
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ABSTRACT: Angiotensin II (Ang II) induces oxidative stress and apoptosis in vascular endothelial cells. We hypothesized that propofol may attenuate Ang II-induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed to identify the underlying mechanisms.
Endothelial cells were pre-treated with propofol and then stimulated with Ang II. Apoptosis was examined by TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on Ang II-modulated NADPH oxidase expression and activity, nitric oxide synthase III (NOSIII) expression and phosphorylation and activity, lipid peroxidation, superoxide anion generation, nitric oxide production, caspase activity, and protein expression of cytochrome c, Bcl-2, and C-IAP-1 were measured.
Ang II induced apoptosis, which was attenuated by 50 µM propofol (P<0.05). Propofol ameliorated Ang II-induced NADPH oxidase expression and activation (P<0.01), lipid peroxidation (P<0.05), and superoxide anion generation (P<0.05), whereas restoring NOSIII phosphorylation and activity (P<0.01) were down-regulated by Ang II. Propofol attenuated Ang II-modulated cytochrome c release, and the expression of Bcl-2 and C-IAP-1. In addition, propofol inhibited Ang II-induced caspase-9 (P<0.01) and caspase-3 activity (P<0.01).
Propofol protected HCAECs from Ang II-induced apoptosis by interfering with the generation of oxidative stress and redox-sensitive apoptotic pathways.
BJA British Journal of Anaesthesia 07/2011; 107(4):525-32. · 4.24 Impact Factor
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ABSTRACT: The effects of pyruvate (Pyr), creatine pyruvate (Cr-Pyr) and creatine (Cr) on lipid and protein metabolism were compared in broiler chickens. A total of 400 1-day-old male birds (Aconred) were allocated to four groups, each of which included four replicates (25 birds per replicate). Treatments consisted of unsupplemented basal diet (Control), basal diet containing 2% Pyr, basal diet containing 3% Cr and basal diet containing 5% Cr-Pyr. Cr-Pyr and Pyr significantly decreased the hepatic triglyceride and serum total cholesterol concentration (P < 0.01). Cr-Pyr markedly increased the serum non-esterified fatty acid and high-density lipoprotein cholesterol concentrations (P < 0.05), whereas the expression of carnitine palmitoyl transferase I (P < 0.05) and peroxisome proliferators-activated receptor-α (P < 0.01) mRNA in the liver were both decidedly enhanced in the Cr-Pyr group. The relative leg muscle weight was higher in the Cr-Pyr group than in the control group, whereas the serum uric acid content and hepatic glutamic-oxaloacetic transaminase activity were lower in the Cr-Pyr and Cr groups (P < 0.05), respectively. Muscle insulin-like growth factor I (P < 0.05) expression was enhanced, and the myostatin (P < 0.01) mRNA level was reduced in both the Cr-Pyr and Cr groups. In addition, Cr-Pyr did not alter body weight or the feed conversion ratio. These results indicate that, compared with Pyr and Cr alone, Cr-Pyr has a bifunctional role in broiler chickens, in that it influences both lipid and protein metabolism.
animal 05/2011; 5(7):1082-9. · 1.74 Impact Factor
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Y Shi, J Chen,
Z Li,
Z Zhang,
H Yu,
K Sun,
X Wang,
X Song,
Y Wang,
Y Zhen,
T Yang,
K Lou,
Y Zhang,
G Zhang,
Y Hu,
J Ji,
R Hui
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ABSTRACT: In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G(1) arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C>T (rs2297882) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio=1.73 (95% confidence interval: 1.33-2.25), P=4.6 × 10(-5)). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.
Oncogene 04/2011; 30(39):4107-17. · 6.37 Impact Factor
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ABSTRACT: Three full-length complementary DNA (cDNA) clones were isolated encoding the skeletal myosin light chain 1 (MLC1; 1237 bp), myosin light chain 2 (MLC2; 1206 bp) and myosin light chain 3 (MLC3; 1079 bp) from the fast white muscle cDNA library of mandarin fish Siniperca chuatsi. The sequence analysis indicated that MLC1 and MLC3 were not produced from differentially spliced messenger RNAs (mRNA) as reported in birds and rodents but were encoded by different genes. The MLC2 encodes 170 amino acids, which include four EF-hand (helix-loop-helix) structures. The primary structures of the Ca(2+)-binding domain were well conserved among the MLC2s of seven other fish species. The ontogenetic expression analysis by real-time PCR showed that the three light-chain mRNAs were first detected in the gastrula stage, and their expression increased from the tail bud stage to the larval stage. All three MLC mRNAs showed longitudinal expression variation in the fast white muscle of S. chuatsi, especially MLC1 which was highly expressed at the posterior area. Taken together, the study provides a better understanding about the MLC gene structure and their expression pattern in muscle development of S. chuatsi.
Journal of Fish Biology 04/2011; 78(4):1225-38. · 1.68 Impact Factor
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ABSTRACT: Amylin, a secretory protein mainly produced by pancreatic beta cells, is elevated in the circulation of patients with diseases related to acute and chronic inflammation, including acute pancreatitis, pancreas graft rejection, obesity and insulin resistance. TNF-α is involved in these disorders. We investigated the effect of TNF-α on amylin levels and the underlying mechanisms, using murine pancreatic beta cell line MIN6 and pancreatic islets.
Amylin, proinsulin and prohormone convertase 1/3, 2 (Pc1/3, Pc2 [also known as Pcsk1/3 and Pcsk2, respectively]) mRNA levels, and amylin promoter and nuclear factor κB (NF-κB) activation were examined by real-time PCR and luciferase reporter assay, respectively. Amylin protein level and mitogen-activated protein kinase phosphorylation were detected by western blot. Activator protein 1 (AP1) activation was examined by electrophoretic mobility shift assay (EMSA).
TNF-α acutely induced amylin expression at the transcriptional level and increased proamylin and the intermediate form of amylin in MIN6 cells and islets. However, it had no effect on proinsulin, Pc1/3 and Pc2 expression. Studies with (1) MIN6 cells treated with inhibitors of MEK1/2, c-Jun-N-terminal kinase (JNK) or protein kinase Cζ (PKC(ζ)), (2) MIN6 cells expressing a c-Jun-dominant negative construct and (3) islets from Fos knockout mice demonstrated that TNF-α induced amylin expression through the PKC(ζ)-extracellular signal-regulated kinase (ERK)/JNK pathways. EMSA showed that (PKC(ζ)), JNK and ERK1/2 were involved in TNF-α-induced AP1 activation, suggesting that TNF-α induces murine amylin expression through the (PKC(ζ)) - ERK1/2 - AP and PKC(ζ) - JNK - AP1 pathways. Further studies showed that TNF-α also induced murine amylin expression through the phosphatidylinositol 3 kinase-NF-κB signalling pathway and enhanced human amylin promoter activation through NF-κB and AP1.
TNF-α acutely induces amylin gene expression in beta cells through multiple signalling pathways, possibly contributing to amylin elevation in acute inflammation-related pancreatic disorders.
Diabetologia 03/2011; 54(3):617-26. · 6.81 Impact Factor
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Y Zheng,
Y Liu,
Q Wu,
H Hong,
H Zhou, J Chen,
H Wang,
W Xian,
J Li,
Z Liu,
Z Pei,
L Chen
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ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) S1647T has been identified as a risk variant for Parkinson's disease (PD) in Han Chinese.
To replicate the association of LRRK2 S1647T with risk of PD, we conducted a case-control study of this variant involving 406 PD subjects and 412 controls from southern mainland China.
The results showed that the frequency of A allele was higher in patients with PD (OR=1.238, 95% CI: 1.015-1.510, P=0.035) compared to controls. In a multivariate logistic regression analysis with the disease group (patients with PD vs. controls) as the dependent variable and genotype as an independent factor adjusting for the effect of age and gender, the homozygous S1647T genotype (AA) was associated with an increased risk of PD (OR=1.815, 95% CI:1.270-2.594, P=0.001). The pooled analysis of present data and the data from the previous work demonstrated that the frequency of A allele was higher in patients with PD (OR=1.2, 95% CI: 1.09-1.32, P<0.0001).
LRRK2 S1647T increases the risk of Parkinson's disease in southern China.
European Journal of Neurology 03/2011; 18(3):538-40. · 3.69 Impact Factor
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ABSTRACT: We report a novel Al(2)O(3) nanoparticle-decorated tubular SiC nanostructure, which shows a remarkable enhanced field emission property with low turn-on and threshold field. The formation of Al(2)O(3) nanoparticle-decorated tubular SiC on Si substrates is achieved in one-step via simple heating evaporation process for the first time. The nanostructure consists of tubular SiC and the Al(2)O(3) nanoparticles, which homogeneously decorate on the surface of the tubular SiC with an average diameter of 7.8 nm and narrow diameter distribution. Moreover, compared with the same density and sized bare tubular SiC, the Al(2)O(3) nanoparticle-decorated tubular SiC nanostructure has an obvious reduction in turn-on (from 8.8 to 2.4 V μm(-1)) and threshold field (from 23.5 to 5.37 V μm(-1)). The very low turn-on and threshold field is also comparable to that of carbon nanotubes, which indicates the Al(2)O(3) nanoparticle-decorated tubular SiC is of huge potential application in future field emission display devices.
Physical Chemistry Chemical Physics 11/2010; 13(3):985-90. · 3.57 Impact Factor
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ABSTRACT: The concurrent detection of hepatitis B e antigen (HBeAg) and its corresponding antibody (anti-HBe) in patients with chronic hepatitis B virus (HBV) infection is well established but the clinical features remain poorly understood. Demographic information, clinical and laboratory data were collected from 1624 consecutive inpatient records of patients with chronic hepatitis B. Viral genotype, basic core promoter and precore mutations were determined by direct sequencing. In vitro HBeAg and anti-HBe binding experiments were conducted with three pairs of HBeAg-positive and anti-HBe-positive serum samples, which were mixed at variable ratios and incubated at 37°C for 3-24h. Of the 1624 chronic patients, 169 (10.4%) had concurrent HBeAg and anti-HBe positivity, and this was associated with intermediate age and HBV-DNA load, higher alanine aminotransferase level and more pronounced liver damage compared with HBeAg-positive or anti-HBe-positive patients alone. HBeAg and anti-HBe titres (median and interquartile range, S/CO) in the concurrent positive group were 4.2 (1.8-9.6) and 0.54 (0.27-0.72), which were closer to their respective cut-off values than those of HBeAg-positive or anti-HBe-positive groups alone. For the cases successfully sequenced, 110/134 (82.1%) harboured T1762/A1764 or/and A1896 mutants. The binding experiments showed that HBeAg and anti-HBe could be concurrently observed provided an optimal ratio (HBeAg to anti-HBe) was chosen. In antiviral treatment-naive patients, concurrence of HBeAg and anti-HBe was not uncommon, and such patients had profound liver disease. An optimal ratio between HBeAg and anti-HBe led to their concurrent detection when sera were tested by sensitive assays.
Journal of Viral Hepatitis 07/2010; 18(9):646-52. · 4.09 Impact Factor
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ABSTRACT: The chitinase-like protein YKL-40, which binds chitin but lacks chitinase activity, has been found to be either the cause or a biomarker for asthma. The aim of our study was to investigate whether serum YKL-40 levels are increased in Chinese patients with asthma and identify its correlation to acute exacerbation, total serum immunoglobulin (Ig)E, the percentage of peripheral blood eosinophils and lung function. We quantified serum YKL-40 levels, total IgE levels and peripheral blood eosinophil percentages in patients with asthma, as well as in controls from the communities surrounding our hospital. The lung function of asthma subjects was also measured. Our data showed that the serum YKL-40 levels were significantly elevated in patients with asthma compared with controls and, when the asthma subjects were stratified, serum YKL-40 levels in the exacerbation group were higher than those in the stable and control groups. In addition, serum YKL-40 levels correlated positively with total serum IgE levels and the percentage of peripheral blood eosinophils, but correlated inversely with lung functions. Thus, we conclude that YKL-40 is found in increased quantities in the serum of Chinese patients with asthma, and its level correlates with exacerbation attacks, indicating that high levels of serum YKL-40 may be a biological characteristic of the exacerbation of asthma.
European Respiratory Journal 04/2010; 35(4):757-60. · 5.89 Impact Factor
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I. J. Humanoid Robotics. 01/2010; 7:55-72.
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J. Chen,
T. Yang,
H. Yu,
K. Sun,
Y. Shi,
W. Song,
Y. Bai,
X. Wang,
K. Lou,
Y. Song,
Y. Zhang,
R. Hui
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ABSTRACT: Angiopoietin-1 is a vascular strengthening factor during vascular development and a protective factor for pathological vascular inflammation and leakage. Brain vascular leaking and inflammation are two important pathological processes of stroke; therefore, we hypothesized that variants of the microRNA-binding site in angiopoietin-1 would affect its expression and confer a risk of stroke. To test our hypothesis, a predicted microRNA-binding site was found in the 3'-UTR of angiopoietin-1 using bioinformatics; variant rs2507800 was identified to be located in the miR-211-binding site of angiopoietin-1. Secondly, the effects of the identified variant on angiopoietin-1 translation were assessed using a luciferase reporter assay and ELISA. We found that the A allele of rs2507800 suppressed angiopoietin-1 translation by facilitating miR-211 binding, but not the T allele. Subjects carrying the TT genotype had higher plasma angiopoietin-1 levels than those with the A allele. Finally, the association of the variant with stroke was tested in 438 stroke patients and 890 controls, and replicated in an independent population of 1791 stroke patients and 1843 controls. The TT genotype resulted in a significant reduction in overall stroke risk {OR, 0.51 [95% confidence interval (CI), 0.36-0.74], P = 0.0003}, ischemic stroke [OR, 0.56 (95% CI, 0.36-0.85), P = 0.007] and hemorrhagic stroke [OR, 0.46 (95% CI, 0.26-0.80), P = 0.007]. These results were confirmed in an independent study. Our results provide evidence that the TT genotype (rs2507800) in the 3'-UTR of angiopoietin-1 might reduce the risk of stroke by interfering with miR-211 binding.
Hum Mol Genet. 01/2010; 19(12):2524-33.
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ABSTRACT: GDF15 (growth-differentiation factor 15) is a novel antihypertrophic factor which is induced in the heart in response to pressure overload and plays an important regulatory role in the process of hypertrophy. In the present study, we have investigated the relationship between GDF15 gene variants and left ventricular hypertrophy in human essential hypertension. A community-based hypertensive population sample of 1527 individuals (506 men and 1021 women) was genotyped for three GDF15 genetic variants, including one tag variant -3148C>G (rs4808793) and two exonic variants +157A>T (rs1059369) and +2438C>G (rs1058587). The effects of those variants on gene expression were studied by use of luciferase reporter assays and the determination of plasma GDF15 levels. Only the tag variant -3148G was significantly associated with a lower risk of left ventricular hypertrophy [odds ratio=0.75 (95% confidence interval, 0.63-0.89); P=0.0009]. Multiple regression analyses confirmed that -3148G predicted the decrease in left ventricular end-diastolic diameter (beta=-0.10, P=0.0001), end-systolic diameter (beta=-0.09, P=0.0007), mass (beta=-0.11, P<0.0001) and indexed mass (beta=-0.12, P<0.0001). These effects were independent of conventional factors, including gender, age, body surface area, blood pressure, diabetes, cigarette smoking and alcohol consumption. The transcription activity of the -3148G-containing construct was increased 1.45-fold (P=0.015) at baseline and 1.73-fold (P=0.008) after stimulation with phenylephrine when compared with the -3148C construct. The -3148G allele was also associated with a significant increase in the plasma GDF15 level in hypertensive subjects (P=0.04). In conclusion, the results show that a promoter haplotype containing the -3148G variant increases GDF15 transcription activity and is associated with favourable left ventricular remodelling in human essential hypertension.
Clin Sci (Lond). 01/2010; 118(2):137-45.
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J. Xu,
W. Li,
X. Bao,
H. Ding, J. Chen,
W. Zhang,
K. Sun,
J. Wang,
X. Wang,
H. Wang,
H. Yu,
W. Song,
W. Ma,
L. Zhang,
C. Wang,
D. Wang,
R. Hui
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ABSTRACT: uPA (urokinase-plasminogen activator) and its receptor (uPAR) have been implicated in a broad spectrum of pathophysiological processes, including fibrinolysis, proteolysis, inflammation, atherogenesis and plaque destabilization, all of which are involved in the pathogenesis of MI (myocardial infarction). We hypothesized that putative functional genetic variation in the two genes encoding uPA and uPAR (PLAU and PLAUR respectively) might influence the susceptibility to MI. We genotyped rs4065 [3'-UTR (untranslated region) *141C>T) and rs2227564 (Pro141Leu) in the PLAU gene as well as rs344781 (-516T>C) in the PLAUR gene in 633 MI patients and 1237 gender- and age-matched control subjects. Our results showed that the T allele of rs4065 was significantly associated with an increased risk of MI, with an adjusted OR (odds ratio) of 1.38 [95% CI (confidence interval), 1.07-1.78; P=0.012) under the dominant model, 1.4 (95% CI, 1.12-1.75; P=0.003) under the additive model and 2.5 (95% CI, 1.15-5.41; P=0.02) under the recessive model. The findings were then replicated in another independent case-control study including 545 MI patients and 597 control subjects. In conclusion, our results suggest that rs4065 might be a previously unknown genetic risk factor for MI in the Chinese Han population.
Clin Sci (Lond). 01/2010; 119(8):353-9.
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ABSTRACT: Large scale single-crystalline tubular beta-SiC was prepared via a simple thermal evaporation method without any template and catalyst, and the nanostructure showed excellent field emission properties.
Chemical Communications 11/2009; · 6.17 Impact Factor
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ABSTRACT: SiC nanowires have been fabricated by a simple catalyst-free method using detonation soot powders and silicon wafers. We characterize their microstructures by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The results show that the nanowires consist of single-crystalline β phase SiC cores with diameters of 30−100 nm and lengths of 0.5−1.5 μm wrapped with a very thin amorphous oxide layer. The axial growth direction of each nanowire is preferentially along the κ direction, while the low density of planar defects are detected. Unique optical properties are found in the Raman spectroscopy that has a blue shift of about 8 cm−1 compared to the bulk β-SiC crystal. Furthermore, field-emission measurements show a relativly low threshold field of 6.2 Vμm−1, suggesting that it is a promising material for applications in flat panel display. Finally, a possible growth model based on a VS mechanism was proposed to explain the growth of the SiC nanowires.
09/2009;
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ABSTRACT: Cyclin A1 is essential for leukemia progression, and its expression is tightly regulated by acinus, a nuclear speckle protein. However, the molecular mechanism of how acinus mediates cyclin A1 expression remains elusive. Here we show that transcription corepressor CtBP2 directly binds acinus, which is regulated by nerve growth factor (NGF), inhibiting its stimulatory effect on cyclin A1, but not cyclin A2, expression in leukemia. NGF, a cognate ligand for the neurotrophic receptor TrkA, promotes the interaction between CtBP2 and acinus through triggering acinus phosphorylation by Akt. Overexpression of CtBP2 diminishes cyclin A1 transcription, whereas depletion of CtBP2 abolishes NGF's suppressive effect on cyclin A1 expression. Strikingly, gambogic amide, a newly identified TrkA agonist, potently represses cyclin A1 expression, thus blocking K562 cell proliferation. Moreover, gambogic amide ameliorates the leukemia progression in K562 cells inoculated nude mice. Hence, NGF downregulates cyclin A1 expression through escalating CtBP2/acinus complex formation, and gambogic amide might be useful for human leukemia treatment.
Oncogene 09/2009; 28(43):3825-36. · 6.37 Impact Factor
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ABSTRACT: Serum paraoxonase (PON1) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL. Paraoxonase 1 (PON1) was implicated in susceptibility to stroke in previous studies. We investigated the correlation between the paraoxonase Gln-Arg 192 polymorphism (PON1Q/R192) and stroke including cerebral hemorrhage and cerebral infarction.
The association between the paraoxonase Gln-Arg 192 polymorphism (PON1Q/R192) and stroke was investigated in 1019 subjects, which involved 305 cases with cerebral hemorrhage, 375 cases with cerebral infarction and 339 healthy controls.
The PON1Q/R192 genotype distribution in the cerebral hemorrhage group was QQ13.1%, QR48.2% and RR38.7% and in the cerebral infarction group was QQ13.6%, QR44.0% and RR42.4% respectively. There was no significant difference in PON1Q/R192 allele and genotype distribution between the patient group and the control group (P > 0.05). The PON1 polymorphism was not associated with cerebral hemorrhage or infarction.
Our study suggests that serum paraoxonase (PON1) is not associated with cerebral hemorrhage or infarction, although it is a lipolactonase which is associated with HDL-apolipoprotein A-I (HDL-apoA-I) and plays a role in the prevention of atherosclerosis.
Acta neurologica Belgica 09/2009; 109(3):205-9. · 0.54 Impact Factor
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ABSTRACT: Inflammatory bowel disease (IBD) is characterized by heavy production of proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Interactions of the autonomic nervous system with local immune cells play an important role in the development of IBD, and the balance of autonomic nerve function is broken in IBD patients with sympathetic overactivity. However, the function of catecholamines in the progress of colitis is unclear. In this study, we examined the role of catecholamines via alpha2-adrenoreceptor in acute murine colitis. The expression of tyrosine hydroxylase (TH) and dopamine b-hydroxylase (DBH), two rate-limiting enzymes in catecholamine synthesis, was detected by immunohistochemistry in murine colitis. Murine colitis was induced by dextran sodium sulphate or trinitrobenzene sulphonic acid (TNBS), and the mice were administered RX821002 or UK14304, alpha2-adrenoceptor antagonists or agonists. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, TNF-alpha and IL-1beta production and histology. Lamina propria mononuclear cells (LPMCs) from mice with TNBS colitis were cultured in the absence or presence of RX821002 or UK14304, and stimulated further by lipopolysaccharide. TH and DBH are induced in LPMCs of inflamed colon, the evidence of catecholamine synthesis during the process of colitis. RX821002 down-regulates the production of proinflammatory cytokines from LPMCs, while UK14304 leads to exacerbation of colitis. Together, our data show a critical role of catecholamines via alpha2-adrenoreceptors in the progress of acute colitis, and suggest that use of the alpha2-adrenoceptor antagonist represents a novel therapeutic approach for the management of colitis.
Clinical & Experimental Immunology 03/2009; 156(2):353-62. · 3.36 Impact Factor
