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Articles by M Wang
Total Records ( 17 ) for M Wang
  M Wang , J. J Wang , J Li , K Park , X Qian , J. x Ma and S. X. Zhang

We previously reported that circulating levels of pigment epithelium-derived factor (PEDF), a newly identified adipokine, are increased in patients with type 2 diabetes, correlating with body mass index. However, the role of PEDF in adipogenesis remains elusive. In the present study, we have investigated the effects and mechanisms of PEDF on adipocyte differentiation in 3T3-L1 preadipocytes. Differentiation of 3T3-L1 preadipocytes was induced in the presence or absence of human recombinant PEDF protein. The effects of PEDF on adipogenic gene expression, mitotic clonal expansion (MCE), and MAPK activation were investigated. Physiological concentrations of human PEDF protein inhibited adipocyte differentiation, evidenced by decreased lipid accumulation, downregulation of adipocyte markers, and inhibition of master adipogenic transcription factors such as C/EBP- and PPAR. The antiadipogenic effects of PEDF were observed only when PEDF was added to the cells on day 0, but not on day 3 during differentiation, suggesting that PEDF targets some early adipogenic events. Similarly, overexpression of PEDF by adenovirus attenuated adipocyte differentiation. Further studies revealed that PEDF, or U-0126, a specific MAPK/ERK inhibitor, sequentially inhibited the early activation of ERK and MCE. Moreover, PEDF attenuated expression and the phosphorylation of C/EBP-β at Thr188, an essential step for transcriptional activation of C/EBP-β. In addition, PEDF expression was decreased significantly in the first 24 h during adipocyte differentiation, suggesting that downregulation of PEDF may be essential for the initiation of MCE and adipogenesis. We conclude that PEDF inhibits adipogenesis in 3T3-L1 preadipocytes partially because of inhibition of the MAPK/ERK signaling pathway and MCE.

  M Wang , D. C Hood , J. S Cho , Q Ghadiali , G. V De Moraes , X Zhang , R Ritch and J. M. Liebmann

Objective  To explore the feasibility of obtaining a local measurement of the thickness of the retinal ganglion cell layer in patients with glaucoma using frequency-domain optical coherence tomography (fdOCT) and a computer-aided manual segmentation procedure.

Methods  The fdOCT scans were obtained from the horizontal midline for 1 eye of 26 patients with glaucoma and 20 control subjects. The thickness of various layers was measured with a manual segmentation procedure aided by a computer program. The patients were divided into low- and high-sensitivity groups based on their foveal sensitivity on standard automated perimetry.

Results  The RGC plus inner plexiform and the retinal nerve fiber layers of the low-sensitivity group were significantly thinner than those of the high-sensitivity group. While these layers were thinner in the patients than the controls, the thicknesses of inner nuclear layer and receptor layer were similar in all 3 groups. Further, the thinning of the retinal ganglion cell plus inner plexiform layer in 1 glaucoma-affected eye showed qualitative correspondence to the loss in 10-2 visual field sensitivity.

Conclusions  Local measures of RGC layer thickness can be obtained from fdOCT scans using a manual segmentation procedure, and these measures show qualitative agreement with visual field sensitivity.

  L Wang , C Yu , H Chen , W Qin , Y He , F Fan , Y Zhang , M Wang , K Li , Y Zang , T. S Woodward and C. Zhu

Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting-state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity.

  M Wang , R. E Long , M. A Comunale , O Junaidi , J Marrero , A. M Di Bisceglie , T. M Block and A. S. Mehta

Changes in glycosylation, most notably fucosylation, have been associated with the development of hepatocellular carcinoma (HCC). In this report, the levels of fucosylated kininogen (Fc-Kin) and fucosylated -1-antitrypsin were analyzed individually and in combination with the currently used marker, -fetoprotein, and a previously identified biomarker, Golgi protein 73 (GP73), for the ability to distinguish between a diagnosis of cirrhosis and HCC. This analysis was done on serum from 113 patients with cirrhosis and 164 serum samples from patients with cirrhosis plus HCC. The levels of Fc-Kin and fucosylated -1-antitrypsin were significantly higher in patients with HCC compared with those with cirrhosis (P < 0.0001). Greatest performance was achieved through the combination of Fc-Kin, -fetoprotein, and GP73, giving an optimal sensitivity of 95%, a specificity of 70%, and an area under the receiver operating characteristic of 0.94. In conclusion, the altered glycosylation of serum glycoproteins can act as potential biomarkers of primary HCC when used independently or in combination with other markers of HCC. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1914–21)

  M Wang , W Zhang , L Yuan , G Fu , Q Wei and Z. Zhang

A recent genome-wide association study identified two common variants that confer susceptibility to bladder cancer. We hypothesized that these variants are associated with risk of bladder cancer in Chinese populations. We genotyped rs9642880 G>T on 8q24 and rs710521 A>G on 3q28 in a two-stage case–control study of bladder cancer to evaluate the association and further examined the expression of MYC. We found that the rs9642880 G>T, but not the rs710521 A>G polymorphism, was associated with an increased risk of bladder cancer. Compared with the rs9642880 GG genotype, the GT/TT genotypes were associated with an odds ratio of 1.65 (95% confidence interval = 1.25–2.17), and this risk was more pronounced in young men and for low-risk tumors. Additional experiments revealed that the rs9642880 GT/TT genotypes were associated with enhanced levels of both MYC mRNA and protein in bladder tissues. Our findings suggested that the rs9642880 G>T polymorphism on 8q24 was independently associated with the risk of bladder cancer in Chinese populations.

  S Wang , J Tang , M Wang , L Yuan and Z. Zhang

Recently, two genome-wide association studies identified a significant association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and risk of diffuse-type of gastric cancer in Asians and bladder cancer in Caucasians, respectively. PSCA has been reported highly expressed in bladder cancer and been considered as a useful marker for diagnosis and progression of bladder cancer. To determine whether rs2294008 polymorphism is associated with risk of bladder cancer in Chinese populations, we conducted a hospital-based case–control study of 581 cases and 580 controls. Sixteen normal bladder tissues adjacent to tumors were used to evaluate the functionality of this polymorphism. We genotyped the rs2294008 polymorphism and assessed its association with risk of bladder cancer and messenger RNA (mRNA) expression in normal bladder tissues. A significant increased risk of bladder cancer was found for rs2294008 CT/TT genotypes (adjusted odds ratio, 1.38; 95% confidence interval, 1.09–1.75) compared with the CC genotype. Furthermore, analysis of PSCA mRNA expression identified a clear correlation of rs2294008 with expression levels of PSCA mRNA. These results indicated that the rs2294008 polymorphism of PSCA gene may play a role in bladder cancer carcinogenesis and it could be served as a biomarker for genetic susceptibility to bladder cancer in Chinese populations.

  Z Fu , M Wang , M Gucek , J Zhang , J Wu , L Jiang , R. E Monticone , B Khazan , R Telljohann , J Mattison , S Sheng , R. N Cole , G Spinetti , G Pintus , L Liu , F. D Kolodgie , R Virmani , H Spurgeon , D. K Ingram , A. D Everett , E. G Lakatta and J. E. Van Eyk

Advancing age induces aortic wall thickening that results from the concerted effects of numerous signaling proteins, many of which have yet to be identified. To search for novel proteins associated with aortic wall thickening, we have performed a comprehensive quantitative proteomic study to analyze aortic proteins from young (8 months) and old (30 months) rats and identified 50 proteins that significantly change in abundance with aging. One novel protein, the milk fat globule protein epidermal growth factor 8 (MFG-E8), increases 2.3-fold in abundance in old aorta. Transcription and translation analysis demonstrated that aortic MFG-E8 mRNA and protein levels increase with aging in several mammalian species including humans. Dual immunolabeling shows that MFG-E8 colocalizes with both angiotensin II and monocyte chemoattractant protein (MCP)-1 within vascular smooth muscle cells (VSMCs) of the thickened aged aortic wall. Exposure of early passage VSMCs from young aorta to angiotensin II markedly increases MFG-E8 and enhances invasive capacity to levels observed in VSMCs from old rats. Treatment of VSMCs with MFG-E8 increases MCP-1 expression and VSMCs invasion that are inhibited by the MCP-1 receptor blocker vCCI. Silencing MFG-E8 RNA substantially reduces MFG-E8 expression and VSMCs invasion capacity. The data indicate that arterial MFG-E8 significantly increases with aging and is a pivotal relay element within the angiotensin II/MCP-1/VSMC invasion signaling cascade. Thus, targeting of MFG-E8 within this signaling axis pathway is a potential novel therapy for the prevention and treatment of the age-associated vascular diseases such as atherosclerosis.

  K Matthews , P. E Noker , B Tian , S. D Grimes , R Fulton , K Schweikart , R Harris , R Aurigemma , M Wang , M. N Barnes , G. P Siegal , A Hemminki , K Zinn , D. T Curiel and R. D. Alvarez

Purpose: The purpose of this study was to evaluate the biodistribution and toxicity of Ad5.SSTR/TK.RGD, an infectivity-enhanced adenovirus expressing a therapeutic suicide gene and somatostatin receptor type 2 (for noninvasive assessment of gene transfer with nuclear imaging) in advance of a planned phase I clinical trial for recurrent ovarian carcinoma.

Experimental Design: Cohorts of Syrian hamsters were treated i.p. for 3 consecutive days with Ad5.SSTR/TK.RGD or control buffer with or without the prodrug ganciclovir (GCV) and euthanized on day 4, 19, or 56. Tissue and serum samples were evaluated for the presence of virus using qPCR analysis and were assessed for vector-related tissue or laboratory effects.

Results: Levels of Ad5.SSTR/TK.RGD in blood and tissues outside of the abdominal cavity were low, indicating minimal systemic absorption. GCV did not affect Ad5.SSTR/TK.RGD biodistribution. The mean Ad5.SSTR/TK.RGD viral level was 100-fold lower on day 19 than day 4, suggesting vector elimination over time. Animals in the Ad5.SSTR/TK.RGD ± GCV cohort had clinical laboratory parameters and microscopic lesions in the abdominal organs indicative of an inflammatory response. Toxicity in this dose cohort seemed to be reversible over time.

Conclusions: These studies provide justification for planned dosing of Ad5.SSTR/TK.RGD for a planned phase I clinical trial and insights regarding anticipated toxicity.

  A. Y. M Wang , C. W. K Lam , M Wang , I. H. S Chan , S. F Lui and J. E. Sanderson

Background and objectives: Residual renal function (RRF) predicts survival and shows an important inverse relation with cardiac hypertrophy in peritoneal dialysis (PD) patients. We hypothesized that valvular calcification and the calcification milieu may be part of the process linking loss of RRF and cardiac hypertrophy.

Design, setting, participants, & measurements: A cross-sectional study was conducted by performing two-dimensional echocardiography on 230 PD patients to assess valvular calcification and left ventricular (LV) mass and collecting 24-h urine for estimation of RRF.

Results: Patients having valvular calcification had lower RRF than those without. Patients with no RRF showed higher calcium-phosphorus product (Ca x P) and C-reactive protein (CRP). Using multiple logistic regression analysis, every 1-ml/min per 1.73 m2 increase in residual GFR was associated with a 28% reduction in the risk for valvular calcification. The association was lost after additional adjustment for Ca x P and CRP. Using multiple linear regression analysis, loss of RRF showed significant association with increased LV mass index, but this association was lost after additional adjustment for CRP, Ca x P, and valvular calcification. Patients with all three calcification risk factors, namely inflammation, high CaxP, and no RRF, showed the highest prevalence of valvular calcification and had the most severe cardiac hypertrophy.

Conclusions: The association among loss of RRF, valvular calcification, and cardiac hypertrophy was closely linked to increased inflammation and high Ca x P in PD patients. These data suggest that valvular calcification and the calcification milieu are part of the processes linking loss of RRF and worsening cardiac hypertrophy in PD.

  K. S Shultz , M Wang , E. M Crimmins and G. G. Fisher

There have been many tests of Karasek’s demand—control model of work stress. However, no studies have examined how the model may differentially apply to older versus younger workers. Due to age changes in cognitive processing, the psychological demands of jobs may interact differently with controls for younger versus older workers. Therefore, the study uses data from the Eurobarometer to examine how the demand—control model of work stress may function differently for older versus younger workers. The results indicate that different controls may in fact buffer different types of job demands for younger versus older workers. The findings reveal that only the interaction between problem solving and time to complete tasks was significant for younger workers. For older workers, however, the interactions between time deadlines and having sufficient time to complete tasks, autonomy, and the interaction between problem solving and schedule flexibility are significant predictors of self-reported stress.

  K Wang , D Tang , M Wang , J Lu , H Yu , J Liu , B Qian , Z Gong , X Wang , J Chen , M Gu and Z. Cheng
  Kejian Wang, Ding Tang, Mo Wang, Jufei Lu, Hengxiu Yu, Jiafan Liu, Baoxiang Qian, Zhiyun Gong, Xin Wang, Jianmin Chen, Minghong Gu, and Zhukuan Cheng

MER3, a ZMM protein, is required for the formation of crossovers in Saccharomyces cerevisiae and Arabidopsis. Here, MER3, the first identified ZMM gene in a monocot, is characterized by map-based cloning in rice (Oryza sativa). The null mutation of MER3 results in complete sterility without any vegetative defects. Cytological analyses show that chiasma frequency is reduced dramatically in mer3 mutants and the remaining chiasmata distribute randomly among different pollen mother cells, implying possible coexistence of two kinds of crossover in rice. Immunocytological analyses reveal that MER3 only exists as foci in prophase I meiocytes. In addition, MER3 does not colocalize with PAIR2 at the beginning of prophase I, but locates on one end of PAIR2 fragments at later stages, whereas MER3 foci merely locate on one end of REC8 fragments when signals start to be seen in early prophase I. The normal loading of PAIR2 and REC8 in mer3...

  J. W Johnston , K Gunaseelan , P Pidakala , M Wang and R. J. Schaffer

In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. Early ripening events such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 µl l–1). By contrast, later ripening events such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 µl l–1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity.

  C. M Lu , J Kwan , A Baumgartner , J. F Weier , M Wang , T Escudero , S Munne , H. F Zitzelsberger and H. U. G. Weier

Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival, as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multiclone and multicolor mapping experiments do not generate additional information. Our pooling protocol, described here with examples from thyroid cancer research and PGD, accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as 3 to 4 days. (J Histochem Cytochem 57:587–597, 2009)

  G. S Song , H. L Zhai , Y. G Peng , L Zhang , G Wei , X. Y Chen , Y. G Xiao , L Wang , Y. J Chen , B Wu , B Chen , Y Zhang , H Chen , X. J Feng , W. K Gong , Y Liu , Z. J Yin , F Wang , G. Z Liu , H. L Xu , X. L Wei , X. L Zhao , P. B. F Ouwerkerk , T Hankemeier , T Reijmers , R. v. d Heijden , C. M Lu , M Wang , J. v. d Greef and Z. Zhu

Heterosis is a biological phenomenon whereby the offspring from two parents show improved and superior performance than either inbred parental lines. Hybrid rice is one of the most successful apotheoses in crops utilizing heterosis. Transcriptional profiling of F1 super-hybrid rice Liangyou-2186 and its parents by serial analysis of gene expression (SAGE) revealed 1183 differentially expressed genes (DGs), among which DGs were found significantly enriched in pathways such as photosynthesis and carbon-fixation, and most of the key genes involved in the carbon-fixation pathway exhibited up-regulated expression in F1 hybrid rice. Moreover, increased catabolic activity of corresponding enzymes and photosynthetic efficiency were also detected, which combined to indicate that carbon fixation is enhanced in F1 hybrid, and might probably be associated with the yield vigor and heterosis in super-hybrid rice. By correlating DGs with yield-related quantitative trait loci (QTL), a potential relationship between differential gene expression and phenotypic changes was also found. In addition, a regulatory network involving circadian-rhythms and light signaling pathways was also found, as previously reported in Arabidopsis, which suggest that such a network might also be related with heterosis in hybrid rice. Altogether, the present study provides another view for understanding the molecular mechanism underlying heterosis in rice.

  D Gu , M Wang , Z Zhang and J. Chen

Published data regarding the association between the apurinic/apyrimidinic endonuclease 1 (APE1) T1349G (Asp148Glu) polymorphism and cancer risk show inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 27 published studies that included 12 432 cancer cases and 17 349 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of the associations. The overall results suggested that the variant genotypes were associated with a moderately increased risk of all cancer types (OR = 1.09, 95% CI = 1.01–1.18 for TG versus TT; OR = 1.08, 95% CI = 1.00–1.18 for GG/TG versus TT). In the stratified analyses, the risk remained for studies of colorectal cancer, European populations and population-based studies. Although some modest bias could not be eliminated, this meta-analysis supported that the APE1 T1349G polymorphism is a low-penetrance risk factor for cancer development.

  H Chu , M Wang , D Gu , D Wu , Z Zhang , J Tang and Z. Zhang

Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species and plays an important role in the aetiology of cancer. The MPO –463G>A polymorphism influences MPO transcription and has been implicated in cancer risk. However, results from published studies on the association between the MPO –463G>A polymorphism and risk of cancer are conflicting. To derive a more precise estimation of association between the MPO –463G>A polymorphism and risk of cancer, we performed a meta-analysis based on 43 case–control studies, including a total of 14 171 cancer cases and 17 319 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the –463A allele had a 0.93-fold lower cancer risk in a dominant model (OR = 0.93, 95% CI = 0.87–1.00). In the stratified analyses, we observed a similar association in European populations (heterozygote comparison: OR = 0.90, 95% CI = 0.82–0.99) and hospital-based studies (dominant model: OR = 0.88, 95% CI = 0.79–0.99). When stratified by cancer type, however, no significant association was found. The results suggested that the MPO –463A allele does not contribute to the development of cancer. Additional well-designed large studies are required to validate these findings in different populations.

  A. Y. M Wang , C. W. K Lam , M Wang , I. H. S Chan , S. F Lui , Y Zhang and J. E. Sanderson

Background. N-terminal-pro-brain natriuretic peptide, cardiac troponin T (cTnT) and high sensitivity C-reactive protein (hs-CRP) have been shown to predict mortality and cardiovascular outcomes in end-stage renal disease patients. However, it is not known which biomarkers have the strongest diagnostic potential for left ventricular (LV) abnormalities in chronic peritoneal dialysis (PD) patients, nor whether residual renal function may confound the diagnostic potential of these biomarkers.

Methods. Two hundred and thirty chronic PD patients underwent two-dimensional echocardiography to determine LV hypertrophy and ejection fraction and had simultaneous measurement of serum NT-pro-BNP, cTnT and hs-CRP.

Results. A significant gain in predictive power was observed when NT-pro-BNP or cTnT but not hs-CRP was included in the multivariable logistic regression models for severe LV hypertrophy (defined as LV mass index ≥ upper tertile, 247.8 g/m2) and systolic dysfunction (defined as ejection fraction ≤45%). Using ROC curve analysis, NT-pro-BNP had the highest diagnostic value for severe LV hypertrophy and systolic dysfunction compared to cTnT and hs-CRP, irrespective of residual renal function. An analysis based on the best cut-off threshold showed that NT-pro-BNP and cTnT had a negative predictive value of 87.1% and 92.6% for severe LV hypertrophy and 95.4% and 93.2% for systolic dysfunction, respectively. Furthermore, the best cut-off threshold of NT-pro-BNP and cTnT for excluding severe LV hypertrophy and systolic dysfunction was nearly 3-fold higher in anuric patients than in patients with residual renal function.

Conclusions. Serum NT-pro-BNP appeared most useful in excluding systolic dysfunction in chronic PD patients followed by cTnT. hs-CRP was not useful in this regard. Residual renal function confounded the interpretation of these biomarkers and reduced their predictive power. A nearly 30% higher cut-off threshold of NT-pro-BNP and cTnT had to be applied in anuric PD patients.

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