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Articles by J. Lu
Total Records ( 11 ) for J. Lu
  R. Zang , J. Bai , H. Xu , L. Zhang , J. Yang , L. Yang , J. Lu and J. Wu
  Real-time quantitative PCR (qPCR) is the most accurate method of quantifying gene expression, provided that suitable endogenous controls are used to normalize the data. To date, no reference genes have been validated for development in Lanzhou fat-tailed sheep (Ovis aries). We have determined the expression profiles of 7 housekeeping genes as candidate reference genes (Actb, Ywhaz, Sdha, Gapdh, Tubb2, Pgk1 and 18S rRNA) in 7 developmental stages (1, 3, 5, 7, 9, 11 and 13 months of age) and 6 tissues (omental fat, liver, tail fat, thigh muscle, subcutaneous fat (backfat above 12th and 13th rib) and perirenal fat) in Lanzhou fat-tailed sheep. The software packages geNorm, NormFinder and BestKeeper were used to evaluate the stability of potential reference genes; each produced comparable results. Initial results showed several of the candidate genes exhibited stable expression throughout development while Actb was identified as the least stable gene. Further analysis with geNorm, NormFinder and BestKeeper identified Gapdh, Tubb2, Sdha and Ywhaz as acceptably stable in gene expression. Comparison of diacylglycerol O-acyltransferase 1 (Dgat1) expression data normalized with geometric averages obtained from combinations of either Gapdh, Sdha, Ywhaz or Tubb2, Sdha, Ywhaz showed no significant differences, indicating that these two combinations are similar. The data provided in this paper may also be useful in guiding researchers performing gene expression in other species of sheep.
  Y Zhang , J Zhang , L Wang , E Quealy , B. D Gary , R. C Reynolds , G. A Piazza and J. Lu

Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX)-inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX-independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N-dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G1 arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis. Cancer Prev Res; 3(7); 885–95. ©2010 AACR.

  J Zhang , L Wang , L. B Anderson , B Witthuhn , Y Xu and J. Lu

Because the Selenium (Se) and Vitamin E Cancer Prevention Trial (SELECT) failed to show the efficacy of selenomethionine for prostate cancer prevention, there is a critical need to identify safe and efficacious Se forms for future trials. We have recently shown significant preventive benefit of methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) in the transgenic adenocarcinoma mouse prostate (TRAMP) model by oral administration. The present work applied iTRAQ proteomic approach to profile protein changes of the TRAMP prostate and to characterize their modulation by MSeA and MSeC to identify their potential molecular targets. Dorsolateral prostates from wild-type mice at 18 weeks of age and TRAMP mice treated with water (control), MSeA, or MSeC (3 mg Se/kg) from 8 to 18 weeks of age were pooled (9-10 mice per group) and subjected to protein extraction, followed by protein denaturation, reduction, and alkylation. After tryptic digestion, the peptides were labeled with iTRAQ reagents, mixed together, and analyzed by two-dimensional liquid chromatography/tandem mass spectrometry. Of 342 proteins identified with >95% confidence, the expression of 75 proteins was significantly different between TRAMP and wild-type mice. MSeA mainly affected proteins related to prostate functional differentiation, androgen receptor signaling, protein (mis)folding, and endoplasmic reticulum–stress responses, whereas MSeC affected proteins involved in phase II detoxification or cytoprotection, and in stromal cells. Although MSeA and MSeC are presumed precursors of methylselenol and were equally effective against the TRAMP model, their distinct affected protein profiles suggest biological differences in their molecular targets outweigh similarities. Cancer Prev Res; 3(8); 994–1006. ©2010 AACR.

  B Liu , D Chen , L Yang , Y Li , X Ling , L Liu , W Ji , Y Wei , J Wang , Q Wei , L Wang and J. Lu

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case–control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (–1304T>G and –1044A>T) with the Taqman assay, and we found that compared with the most common –1304TT genotype, carriers of –1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61–0.90 for TG, and OR = 0.62; 95% CI = 0.41–0.94 for GG] in an allele dose–response manner (adjusted Ptrend = 0.0005). Further stratification analysis showed that the protective role of the –1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the –1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted Pinteraction = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the –1304TT genotype. However, no significant association was observed between the –1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional –1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.

  C. Hu , W. Jia , R. Zhang , C. Wang , J. Lu , H. Wu , Q. Fang , X. Ma and K. Xiang


Aims  Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population.

Methods  We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured.

Results  Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively).

Conclusion  Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

  J. Lu , C. Hu , W. Hu , R. Zhang , C. Wang , W. Qin , W. Yu and K. Xiang
  Aims  Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes.

Methods  Three single nucleotide polymorphisms (SNPs) (rs10494366, rs12143842 and rs12029454) were genotyped in 1240 Type 2 diabetic patients (631 men and 609 women) and 1196 normal controls (433 men and 763 women). Individuals with overt diseases other than diabetes were excluded. Heart-rate corrected QT interval (QTc) was determined by standard 12-lead ECG and Bazett formula. Sex-pooled analysis and sex-specific analysis for genotype-phenotype association were both conducted.

Results  In the diabetic group, the rs12143842 T allele was associated with a 3.87-ms (= 0.014, empirical = 0.039) increase in QTc duration for each additional allele copy, while rs10494366 and rs12029454 exhibited no significant association with QTc. We found no evidence of association for the three SNPs in subjects with normal glucose regulation. No significant SNP-gender and -diabetes affection interaction was observed.

Conclusions  The genetic variant rs12143842 in NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Future studies in different populations are needed to validate this finding and to evaluate the impact of NOS1AP variants on cardiovascular events and sudden cardiac death in diabetic patients.

  W. Yu , F. Zhang , W. Hu , R. Zhang , C. Wang , J. Lu , F. Jiang , S. Tang , D. Peng , M. Chen , Y. Bao , K. Xiang , C. Hu and W. Jia


There is a close link between electrocardiographic ventricular repolarization QT parameters and Type 2 diabetes. The aim of the present study was to assess the effects of QT-related and diabetes-related variants in KCNQ1 on QT interval in a Chinese population.


We recruited 2415 patients with Type 2 diabetes and 1163 subjects with normal glucose regulation in the present study. QT interval was obtained and the heart rate-corrected QT interval (QTc) was calculated using Bazett's formula. Four single nucleotide polymorphisms in KCNQ1 were selected (rs12296050, rs12576239, rs2237892 and rs2237895) and genotyped.


 In participants with normal glucose regulation, the minor allele T of rs12296050 was associated with a 3.46-ms QTc prolongation under an additive model (P = 0.0109, empirical P = 0.0498). In patients with Type 2 diabetes, we did not find any association for the single nucleotide polymorphisms.


Our findings indicate that KCNQ1 is associated with QT interval in a Chinese population with normal glucose regulation.

  T. Cao , J.T. Weil , P. Maharjan , J. Lu and C.N. Coon
  Background and Objective: The requirement of sulfur amino acids for laying hens have been determined but the method in which methionine is regulated has not been studied. The aim of this research was to study the hepatic methionine-metabolizing enzymes and metabolites in laying hens. Materials and Methods: Five hundred forty Dekalb-XL laying hens were housed and fed a control diet until sampling. On day of sampling, six hens were sacrificed at each time period to allow for determination of hepatic enzymatic activities and metabolite concentrations during light and dark periods. Data was analyzed using the general linear models (GLM) procedure with statistical analysis software (SAS). Results: The enzymes and metabolites showed cyclical changes related to light and dark periods. During the light period of the day, layers showed elevated activities of methionine s-adenosyltransferase (EC; MAT), cystathionine ß-synthase (EC; CS) and cystathionase (EC; C-ase) and depressed activities of betaine-homocysteine methyltransferase (EC; BHMT) and N5methyltetrahydrofolate-homocysteine methyltransferase (EC; MFMT), as compared to the dark period of the day. The hens also had a decreased methionine to cysteine ratio (Met/Cys ratio), an increased methylation ratio (s-adenosylmethionine to s-adenosylhomocysteine ratio; SAM/SAH ratio) and an increased cystathionine (CYST) concentration in the liver during the light period. Conclusion: The changes of the enzymatic activities and metabolite concentrations suggest that the methionine metabolism of laying hens during the light period was in favor of methionine degradation through cysteine synthesis. Alternatively, the metabolism of hens during the dark period was in favor of methionine conservation by limiting the conversion of methionine to cysteine. Thus, feeding hens a higher cysteine diet several hours before lights are turned off may prove beneficial to counteract the limited cysteine synthesis from dietary methionine during the dark period of the day.
  T. Cao , J.T. Weil , P. Maharjan , J. Lu and C.N. Coon
  Background and Objective: Two experiments were conducted to determine the total sulfur amino acid requirements in laying hens. The objective of Experiment 1 was to determine the digestible methionine and cystine requirements for laying hens. An additional experiment (Experiment 2) was conducted to determine the cystine requirement for laying hens and determine the utilization efficiencies of supplemental methionine and cystine to meet the cystine requirement. Materials and Methods: In Experiment 1, one hundred and seventy-six laying hens were randomly assigned into 11 dietary treatments for a six-week period. One group of hens received a corn-soybean meal control diet containing 2,899 kcal ME kg1 and 19.5% CP, while the remaining ten groups of hens received 10 test diets containing 2,850 kcal ME kg1 and 15% CP. Five diets were deficient in cystine (0.148% digestible cystine), containing digestible methionine levels of 0.143, 0.240, 0.337, 0.434 and 0.531% and another five diets were excessive in cystine (0.450% digestible cystine), containing digestible methionine levels of 0.143, 0.231, 0.317, 0.407 and 0.495%. An additional experiment (Experiment 2) was conducted by assigning one hundred sixty laying hens to one of two series of diets, which were formulated to contain 0.319% digestible methionine and 0.148% digestible cystine, same as that in Experiment 1, with exception of the methionine level. Four levels of equimolar amounts of methionine or cysteine (½ cystine) were added to the basal diet. The added levels were 0.05, 0.10, 0.15 and 0.20% for methionine and 0.04, 0.08, 0.12 and 0.16% for cystine since the molecular weight of cysteine (½ cystine) is 80% of that of methionine. Data generated from each experiment was analyzed using the general linear models (GLM) and analysis of variance procedures with the help of statistical analysis software (SAS). A second-order polynomial regression analysis was conducted in order to determine the methionine requirements for laying hens. Results: The results showed that the requirement of digestible methionine and digestible cysteine for laying hens were 354 and 184 mg hen1 day1 for egg mass (EM), 349 and 193 mg hen1 day1 for feed conversion, 437 and 325 mg hen1 day1 for body weight change (BWC) and 367 and 189 mg hen1 day1 for EM+BWC, respectively. Deficient or excessive dietary methionine produced an increase of methionine degradation due to the increased body weight loss or the excessive dietary methionine, correspondingly. Optimum dietary methionine levels resulted in increased liver SAM/SAH concentration ratios (s-adenosylmethionine/s-adenosylhomocysteine) and decreased homocysteine (Hcy) levels. Conclusion: The results demonstrated that the utilization efficiencies of methionine and cysteine (½ cystine) were 100% on an equimolar basis for egg mass and 90% on an equimolar basis to prevent loss of body weight. When methionine was used to meet the cystine requirement, an utilization efficiency of 80% was adequate on a weight and concentration basis for egg mass and 72% for body weight maintenance. The practice of feeding ingredients with a substantial digestible cystine level for supporting body weight may be beneficial for laying hens.
  Y Hao , L Li , W Li , X Zhou and J. Lu

Bacterial virulence could be altered by the antimicrobial agents of the host. Our aim was to identify the damage and survival of Streptococcus sanguinis induced by lysozymes in vitro and to analyse the potential of oral microorganisms to shirk host defences, which cause infective endocarditis. S. sanguinis ATCC 10556 received lysozyme at concentrations of 12.5, 25, 50 and 100 µg/ml. Cells were examined by electron microscopy. The survival was assessed by colony counting and construction of a growth curve. Challenged by lysozymes, cells mainly exhibited cell wall damage, which seemed to increase with increasing lysozyme concentration and longer incubation period in the presence of ions. Cells with little as well as apparent lesion were observed under the same treatment set, and anomalous stick and huge rotund bodies were occasionally observed. After the removal of the lysozyme, some damaged cells could be reverted to its original form with brain heart infusion (BHI), and their growth curve was similar to the control cells. After further incubation in BHI containing lysozyme, S. sanguinis cell damage stopped progressing, and their growth curve was also similar to the control cells. The results suggested that the S. sanguinis lesions caused by the lysozyme in the oral cavity may be nonhomogeneous and that some damaged cells could self-repair and survive. It also indicated that S. sanguinis with damaged cell walls may survive and be transmitted in the bloodstream.

  J. Lu , Z. Dong , L. Chen and J. Yu
  We have theoretically and experimentally investigated polarization insensitive of all optical wavelength conversion for polarization multiplexing signal based on four-wave mixing (FWM) in nonlinear optical fiber. Optical polarization multiplexing technique can be used to double the transmission bit rate by adding data on each of two orthogonal optical states. At the receiver side, the two orthogonal signals can be obtained by direct detection. The eye diagrams of the original signals have been probed and compared with the converted one in this experiment. The characteristics of the converted signal have been fully studied and a little crosstalk which leads a better corresponding eye diagram has been obtained after polarization demultiplexing.
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