Lin Wang

Huazhong University of Science and Technology, Wuhan, Hubei, China

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Publications (49)35.97 Total impact

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    ABSTRACT: Background Deceleration capacity (DC) is a newly found predictor of mortality after myocardial infarction. Age-, gender-, and circadian rhythm–related differences in DC may limit its predictive value, which should be considered in clinical settings.MethodsDC, average heart rate, and HRV parameters, including 24 hours, awaking state (15:00–20:00) and sleeping mode (00:00–05:00) strips from 24 hours Holter recordings in 636 subjects without heart diseases were examined. Heart rate variability was analyzed in time domains (standard deviation of all normal-to-normal intervals [SDNN], normal-to-normal RR intervals in all 5-minute segments [SDANN], and root mean square successive difference [RMSSD]).ResultsThe DC, SDNN, SDANN, RMSSD, and heart rate decreased with age. Deceleration capacity was significantly lower in patients greater than 50 years of age. The largest decrease of SDNN, SDANN, and RMSSD occurred in patients 30–39 years of age. The values of SDNN, SDANN, and DC of women were lower than that of men in the young and middle-aged groups, but age-related decrease of DC in men was greater than that in women. Heart rate of women was significantly higher than that of men in younger subjects, especially in a sleeping mode. There were higher values of DC and RMSSD during sleeping than that during a waking state.Conclusions The age, gender, and circadian rhythm may be useful when evaluating cardiac autonomic function and need to be considered when evaluating DC and HRV in clinical and scientific researches.
    Annals of Noninvasive Electrocardiology 08/2014; · 1.08 Impact Factor
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    ABSTRACT: The major structure elements of the AMP-activated protein kinase (AMPK) are α, β, and γ sunbunits. Mutations in γ2 subunit (PRKAG2) have been associated with a cardiac syndrome including inherited ventricular preexcitation, conduction disorder and hypertrophy mimicking hypertrophic cardiomyopathy. The aim of the present study was to identify PRKAG2 syndrome among patients presenting with left ventricular hypertrophy (LVH). Nineteen unrelated subjects with unexplained LVH were clinically and genetically evaluated. Among 4 patients with bradycardia, manifestations of preexcitation were only found in a 19 year old male who also developed congestive heart failure 3 years later. Electrophysiological study of this case identified the coexistence of an AV accessory pathway and AV conduction defect. Histological analysis of his ventricular tissue isolated by biopsy confirmed excessive glycogen accumulation, prominent myofibrillar disarray and interstitial fibrosis. Direct sequencing of his DNA revealed a heterozygous mutation in PRKAG2 consisting of an A-to-G transition at nucleotide 1453 (c.1453A>G), predicting a substitution of a glutamic acid for lysine at highly-conserved residue 485 (p.Lys485Glu, K485E), which was absent in his unaffected family members and in 215 healthy controls. To assess the role of K485 in the structure and function of the protein, computational modeling calculations and conservation analyses were performed. Electrostatic calculations indicate that K485 forms a salt bridge with the conserved D248 residue in the AMPK β subunit, which is critical for proper regulation of the enzyme, and the K485E mutant disrupts the connection. Our study identifies a novel de novo PRKAG2 mutation in a young, in which progression of the disease warrants close medical attention. It also underlines the importance of molecular screening of PRKAG2 gene in patients with unexplained LVH, ventricular preexcitation, conduction defect, and/or early onset of heart failure.
    PLoS ONE 01/2013; 8(5):e64603. · 3.53 Impact Factor
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    ABSTRACT: The human oncogene B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a member of the mammalian Polycomb group family. The overexpression of BMI-1 is associated with human malignancies. In this study, the effects of knockdown of BMI-1 by shRNA-mediated RNA interference on cell cycle and possible downstream targets in human cervical adenocarcinoma HeLa cells were investigated. As a result, when the shRNA plasmid was stably introduced into the cell line, the mRNA and protein of BMI-1 were specifically down-regulated, and the cells increased in the phase of G1 and cells in S phase significantly decreased by flow cytometric analysis; the knockdown of BMI-1 expression could lead to significant up-regulation of p16INK4a, HOXA9 and HOXC13 mRNA expression, but hTERT and HOXB4 mRNA expression did not change significantly. In conclusion, RNAi-mediated knockdown of BMI-1 expression can induce cell-cycle arrest and up-regulate p16INK4a, HOXA9 and HOXC13 in HeLa cells. Our results suggest that targeting BMI-1 might be a therapeutic potential for the treatment of cancer.
    Medical Oncology 12/2011; 28(4):1201-9. · 2.14 Impact Factor
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    ABSTRACT: Asthma is a common polygenic disease, caused by complex interactions between multiple genes and environmental factors. Study of the gene-gene interactions would contribute to a new insight into the pathogenesis and therapeutics of asthma. To evaluate the single and combined associations of eight single-nucleotide polymorphisms loci in five candidate genes with the development of asthma in Chinese children. We examined eight single-nucleotide polymorphisms (SNPs) in five key asthma susceptibility genes and performed single SNP association study, haplotype analysis, and gene-gene interactions analysis in 479 Chinese children, including 252 asthmatic subjects and 227 healthy controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Haplotype analysis was detected by SHEsis software. Gene-gene interactions were tested using the multifactor dimensionality reduction (MDR) method. There were significant differences of interleukin (IL)-13 R130Q and IL-13 C1923T in genotype and allele frequency distributions between the asthmatic group and control group. Furthermore, the A allele of IL-13 R130Q and the T allele of IL-13 C1923T were significantly associated with increased risk of asthma (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.20-2.09, p = .0010; OR = 1.57, 95% CI 1.19-2.08, p = .0014, respectively). By haplotype analysis, the C-G and T-A haplotypes consisting of IL-13 C1923T and IL-13 R130Q and the G-A and A-A haplotypes consisting of IL-4Ralpha I75V and IL-4Ralpha Q576R were significantly associated with asthma (p < .05). Using MDR, the authors detected significant gene-gene interactions with a best six-locus model among IL-4 -C33T, IL-13 R130Q, IL-4Ralpha I75V, IL-4Ralpha Q576R, STAT6 C2892T, and CD14 -C159T on the risk of asthma (OR = 4.43, 95% CI 1.30-15.04, p < .001, by 1000-fold permutation test). These data suggest that genetic variants in the IL-13 gene may play an important role in the development of pediatric asthma in Middle China. In addition, the significant gene-gene interactions among IL-4 -C33T, IL-13 R130Q, IL-4Ralpha I75V, IL-4Ralpha Q576R, STAT6 C2892T, and CD14 -C159T may increase an individual's susceptibility to asthma and contribute to the pathogenesis of asthma.
    Journal of Asthma 04/2010; 47(3):238-44. · 1.85 Impact Factor
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    ABSTRACT: There are limited prospective data on clopidogrel resistance and clinical outcome of patients with selective coronary drug-eluting stent (DES) implantation. To investigate whether clopidogrel resistance is associated with long-term thrombotic events in patients with selective coronary DES implantation. A total of 154 patients who underwent selective percutaneous coronary intervention (PCI) with DES were enrolled in this study. Platelet aggregation was measured using light transmittance aggregometry (LTA) before clopidogrel administration (baseline) and 24 hours after loading with clopidogrel 300 mg. Clopidogrel resistance was defined as ≤10% absolute difference between baseline aggregation and post-administration aggregation. All patients who received the same anti-platelet treatment were followed up for 1 year after discharge for the incidence of a composite endpoint consisting of cardiovascular death, myocardial infarction (MI) and revascularization, and secondly for the incidence of stent thrombosis. The incidence of clopidogrel resistance is 20.28% in our study population. Patients who are complicated by diabetes mellitus, smoke, or have a higher body mass index (BMI) tend to have clopidogrel resistance. Patients in the clopidogrel-resistant group have significantly higher incidences of composite endpoints (21.88% vs 4.92%; p = 0.006) and stent thrombosis (12.5% vs 1.64%; p = 0.017) than patients in the clopidogrel-response group during 1-year follow-up. Diabetes, smoking, and high BMI are associated with clopidogrel resistance, and clopidogrel resistance indicates an increased risk of long-term thrombotic events in patients implanted with DES.
    Drugs in R&D. 01/2010; 10(4):219-24.
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    ABSTRACT: The accurate assessment of a proto-oncogene, human epidermal growth factor receptor-2 gene (HER-2), is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry (IHC) is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization (FISH) has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases (34.6%) by FISH and the HER-2 protein over-expression (score 3+) in 15 cases (28.8%) by IHC. Immunohistochemically, 28.6% of the cases scored as 2+ and 93.3% of the cases scored as 3+ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer (P<0.005). No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.
    Journal of Huazhong University of Science and Technology 06/2009; 29(3):354-8. · 0.58 Impact Factor
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    ABSTRACT: To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 (TIM4) promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymorphisms (SNPs) in the promoter region of TIM4 were detected, including two new SNPs (at positions-1609,-153) and two reported SNPs (rs6874202, rs6882076). The frequency distribution of rs6882076 was different among different races (P<0.05). In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.
    Journal of Huazhong University of Science and Technology 08/2008; 28(4):447-50. · 0.58 Impact Factor
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    ABSTRACT: To observe the inhibitory effect of cyclin-dependent kinase inhibitor p21 on regulation of survivin transcription in human liver cancer HepG cells, and explore the related mechanisms. Doxorubicin (DOX) was used to treat HepG cells. Eukaryotic vector pEGFP-C2-p21 was transfected into HepG cells by lipofectamine and positive clones were screened out by G418. The mRNA expression of p21, p53 and survivin were detected by real-time fluorescent quantitative polymerase chain reaction (RQ-PCR). Flow cytometry was used to determine the cell cycle phases, and reverse transcription polymerase chain reaction (RT-PCR) was used to measure the levels of E2F-1 or p300. After treatment with DOX, the expression of p53 and p21 was increased, whereas that of survivin was reduced during 24 hours of the treatment. After transfection the p21 level was 2100.1-fold or 980.9-fold enhanced in comparison with that in HepG2 cells or HepG2-pEGFP cells. Survivin level was markedly down-regulated to 0.5% or 0.6% relative to that in the other two groups, nevertheless, significant p53 changes were not observed. Overexpression of p21 resulted in G1/G0 phase arrest (F = 31.59, P < 0.01), meanwhile, E2F-1 mRNA or p300 mRNA were less expressed compared with that in the other controls (F(E2F-1) = 125.28, P < 0.05; Fp300 = 46.01, P < 0.01). p21 could be a potential mediator of survivin suppression at transcription level in HepG2 cells, which might be through the block at G1/G0 phase and down-regulation of transcription factors E2F-1 and p300.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 08/2008; 30(8):583-7.
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    ABSTRACT: The effect of cyclin-dependent kinase inhibitors Cip1/Waf1 (p21) on regulatory expression of survivin transcription in human hepatocellular carcinoma cell HepG2 was observed and the related mechanisms explored. Doxorubicin (DOX) was used to treat HepG2. Eukaryotic vector pEGFP-C2-p21 was transfected into HepG2 by lipofectamine and positive clones were screened out by G418. The mRNA expression of p21 and survivin was detected by real-time fluorescent quantitative polymerase chain reaction (RQ-PCR). Flow cytometry was used to examine the cell cycle, and reverse transcription polymerase chain reaction (RT-PCR) was used to measure the levels of E2F-1 and p300. The results showed that: (1) After treatment with DOX, the expression of p21 was increased, whereas that of survivin was reduced during 24 h of treatment; (2) After transfection of pEGFP-C2-p21 into HepG2, p21 level was significantly enhanced to 2100.11-folds or 980.89-folds in comparison to HepG2 or HepG2-C2 group, and survivin level was markedly down-regulated to 0.54% or 0.59% relative to the control groups; (3) Overexpressed p21 resulted in G1/G0 phase arrest (F=31.59, P<0.01), meanwhile E2F-1 mRNA and p300 mRNA were reduced as compared with those of controls (F(E2F-1)=125.28, P<0.05; F(p300)=46.01, P<0.01). It was suggested that p21 could be a potential mediator of survivin suppression at transcription level in HepG2 cell, which might be through the block at G1/G0 phase and down-regulation of transcription factors E2F-1 and p300.
    Journal of Huazhong University of Science and Technology 06/2008; 28(3):308-13. · 0.58 Impact Factor
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    ABSTRACT: In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-mer peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFTF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A antigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.
    Journal of Huazhong University of Science and Technology 05/2008; 28(2):222-6. · 0.58 Impact Factor
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    ABSTRACT: Chemotherapy protocols using adriamycin (ADM) is a standard treatment for hepatoblastoma, but the treatment results became unsatisfied because of drug resistance. Recently, ADM combined gene therapy is a developing alternative treatment for hepatoblastoma. This study was to investigate the effect of ADM combined human p21CIP1 transfection on the proliferation of hepatoblastoma cell line HepG2. HepG2 cells were divided into empty control group (no treatment), ADM group (treated with 0.5 microg/mL ADM), blank control group (transfected with blank plasmid pcDNA3), p21 group (transfected with plasmid pcDNA3-p21), and combination group (ADM treatment plus p21 transfection). The proliferation of HepG2 cells was observed by MTT assay. The mRNA levels of p21 and survivin were detected by real-time polymerase chain reaction (PCR). After transfection, the mRNA level of p21 in p21 group was increased by 155 folds of that in empty control group (P<0.05). p21 inhibited the proliferation of HepG2 cells at Day 3 and Day 4 after transfection (P<0.01). The proliferation inhibition rate was significantly higher in combination group than in ADM group and p21 group (43.92% vs. 32.97% and 35.77% at Day 3, P<0.01; 59.86% vs. 39.35% and 40.96% at Day 4, P<0.01; 51.81% vs. 33.91% and 10.68% at Day 5, P<0.01). This effect was enhanced along with the increasing time of co-treatment from Day 1 to Day 4 (r=0.91, P<0.05), and it was obvious at Day 4 (Q =1.07). The mRNA level of survivin was significantly lower in combination group than in p21 group and ADM group (P<0.01). p21 gene transfection plus ADM can inhibit the proliferation of HepG2 cells and down-regulate the level of survivin mRNA, thus may be a potential therapeutic strategy against human hepatoblastoma.
    Ai zheng = Aizheng = Chinese journal of cancer 05/2008; 27(5):476-81.
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    ABSTRACT: To investigate the single nucleotide polymorphisms (SNPs) of -1516G/T in the promoter region and 4259G/T in the exon-3 region of the T cells immunoglobulin mucin-3 (TIM-3) and their linkage disequilibrium, and therefore to detect their haplotype relationship with allergic asthma of the Han population from Hubei province of China. The two polymorphisms were detected with allelic specific polymerase chain reaction (ASPCR). In the 175 asthmatic subjects and in the 202 healthy controls collected from June, 2004 to October 2007 in the Han population from Hubei province. The genotype and allele frequencies, the D' value between the two SNPs sites, the haplotype and their frequencies were calculated and analyzed, respectively. The genotype frequencies of GG, GT and TT in -1516G/T polymorphism of TIM-3 gene were 82.7% (167/202), 17.3% (35/202), 0 (0/202) respectively in the 202 controls, and 82.9% (145/175), 17.1% (30/175), 0 (0/175) respectively in the 175 asthmatic subjects. The genotype frequencies of GG, GT and TT in 4259G/T polymorphism of TIM-3 gene were 0.5% (1/202), 2.5% (5/202), 97.0% (196/202) respectively in the 202 controls and 0.6% (1/175), 5.7% (10/175), 93.7% (164/175) respectively in the 175 asthmatic subjects. The control group: D' = 1.0, the asthma group D' = 0. 9. The 3 haplotypes were G-G, G-T, T-T in the Han population from Hubei province of China, and their haplotype frequencies were distributed similarly in asthma 3.4% (12/350), 88.0% (308/ 350), 8.6% (30/350) and in the controls 1.7% (7/404), 89.6% (362/404), 8.7% (35/404). None of these differences were statistically significant (chi2 = 2.15, 0.47, 0.003 respectively, all P > 0.05). There are strong linkage disequilibrium between the two SNPs sites in TIM-3 gene in Han population from Hubei province, but the haplotypes G-G, G-T and T-T are not associated with asthma susceptibility of this population. We cannot exclude the possibility that the haplotypes of TIM-3 may be associated with asthma susceptibility in other ethnic populations or the susceptibility to other atopic diseases and autoimmunity diseases.
    Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 04/2008; 31(3):196-200.
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    ABSTRACT: To investigate the frequencies of -1516,-574 and 4259 single nucleotide polymorphisms (SNPs) of T cells immunoglobulin mucin -3(TIM-3) gene in Hubei population and address the question whether they are in linkage disequilibrium(LD) . Genotypes and allele frequencies of TIM-3 gene were examined by allele-specific polymerase chain reaction (AS-PCR) methods in 147 healthy Hubei Han individuals. Hardy-Weinberg equilibrium and Two-point LD analyses and haplotype frequencies were evaluated with Arlequin v3.1 software. The allele frequencies of the 3 SNPs were in agreement with Hardy-Weinberg equilibrium. Minor allelic frequencies of TIM-3 -1516G/T,-574T/G and 4259G/T were 8.5%,1.0% and 2.0%,respectively. The dominant haplotypes comprising the three loci were G-G-G(2.0%),G-G-T(88.4%), T-G-T(8.5%) and G-T-T(1.0%). LD analyses revealed that all of the coefficient of linkage disequilibrium (D') were 1. The -1516,-574 and 4259 loci of TIM-3 gene are in complete linkage disequilibrium. Our study has provided population genetic data on TIM-3 gene in Chinese Hubei Han population and a basis for searching immune-mediated disease-related TIM-3 haplotype.
    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 03/2008; 25(1):101-4.
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    ABSTRACT: To observe the effects of aspirin on nuclear factor kappaB (NF-kappaB)-DNA binding activity and on the expression of cyclooxygenase-2 (COX-2) in atherosclerotic plaque so as to explore its antiatherosclerotic mechanism. Thirty-six New Zealand male rabbits were randomly divided into 3 equal groups: high-cholesterol (HC) group, fed with food high in cholesterol and perfused into the empty stomach daily with distilled water for 12 weeks, high-cholesterol and aspirin (HC + A) group, fed with food high in cholesterol and perfused into the empty stomach daily with aspirin solution, and normal control (NC) group, fed with normal food and perfused into the empty stomach daily with distilled water, before the experiment, and 4, 8, and 12 weeks after the beginning of experiment peripheral blood samples were collected. The serum lipids were detected with enzymatic assays; and enzyme-linked immunosorbent assay was used to detect the level of high sensitive C-reactive protein (hs-CRP). By the end of experiment the rabbits were killed to take out the specimens of aorta to observe the neointima thickness and plaque area of aorta. Electrophoretic mobility shift assay was used to detect the NF-kappaB-DNA binding activity, and immunohistochemistry and morphometry were performed to observe the expression of COX-2 protein, the neointima thickness and plaque area of aorta respectively in all three groups. The levels of serum lipids, hs-CRP, NF-kappaB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta in the HC and HC + A groups were all significantly higher than those in the NC group (P < 0.05 -0.01). There was no significant differences in the serum lipids between the HC and HC + A groups (all P > 0.05), however, the levels of hs-CRP, NF-kappaB-DNA binding activity, expression of COX-2 protein, and neointima thickness and plaque area of aorta of the HC + A group were (5.14 +/- 0.32) microg/ml, (14.6 +/- 2.7) microg/ml, (0.342 +/- 0.02)A, (165 +/- 24) microm, and (24.3 +/- 7.6)% respectively, all significantly lower than those of the HC group [(9.39 +/- 0.79) microg/ml, (32.4 +/- 4.7) microg/ml, (0.572 +/- 0.061) A, (337 +/- 64) microm, and (49.5 +/- 21.3)%, all P < 0.05). By reducing the expression of COX-2.
    Zhonghua yi xue za zhi 12/2007; 87(46):3298-301.
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    ABSTRACT: This study was purposed to construct and identify the mammalian expression vector of pEGFP-BMI-1 and to detect whether it could express in human cervix cancer cell line HeLa. The cDNA fragment of BMI-1 obtained by RT-PCR was inserted into pEGFP-N1. The recombinant plasmid was confirmed by restriction enzyme digestion, PCR and DNA sequencing. pEGFP-BMI-1 was transfected into HeLa cells with lipofectamine 2000. The expression of pEGFP-BMI-1 was determined by EGFP fluorescence and Western blot analysis. SYBR Green I real-time RT-PCR was used to quantitate P16INK4a mRNA. The results showed that the correct construction of the recombinant plasmid pEGFP-BMI-1 has been shown by restriction enzyme digestion, PCR and DNA sequencing. pEGFP-BMI-1 could express BMI-1-EGFP fusion protein in HeLa cells. Real-time RT-PCR showed that P16INK4a mRNA expression was reduced to 9.2%. It is concluded that the vector of pEGFP-BMI-1 has been successfully constructed and it can be expressed in HeLa cells. This work has laid foundations for further study on biological functions and potential application of BMI-1.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 11/2007; 15(5):1056-60.
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    ABSTRACT: In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43), isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia, while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercellular communication by enhancing phosphorylation of Cx43.
    Journal of Huazhong University of Science and Technology 07/2007; 27(3):241-4. · 0.58 Impact Factor
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    ABSTRACT: A plasmid carrying DNA to be transcribed into a small interfering RNA against transketolase-like-1 mRNA was constructed and transfected into a human colon cancer cell line. The mRNA expression of transketolase gene family in the human colon cell line was determined by real-time polymerase chain reaction. The effect of anti-transketolase-like-1 small interfering RNA on cell proliferation and cell cycle in the human colon cancer cell line cells was detected by flow cytometry and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide. The transketolase-like-1 gene was significantly downregulated in human colon cancer cell line cells transfected with small interfering RNA transketolase-like-1 constructs compared with the cells transfected with control vector and the cells without transfection. In addition, the anti-transketolase-like-1 small interfering RNA construct significantly decreased the level of transketolase in the transfected human colon cancer cell line cells, arrested them in G0/G1 phase and substantially inhibited cell proliferation. No significant difference was found in the other two genes (transketolase and transketolase-like-2 genes) between the transfected human colon cancer cell line cells and the controls (P>0.05). Our data demonstrated that the transketolase-like-1 gene plays an important role in total transketolase activity and in the cell proliferation of human colon cancer. Transketolase-like-1 may serve as a target for novel anticancer therapies.
    Anti-Cancer Drugs 04/2007; 18(4):427-33. · 2.23 Impact Factor
  • Jie Shi, Lin Wang, Li-Hua Hu
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    ABSTRACT: Beta-catenin plays a central role in Wnt signaling pathway. The aberrant localization of beta-catenin in nucleus causes the transcription of down-stream target genes, which is the pathogenesy of some solid tumours. As the expression of adheren junction on hemopoietic cells is very low, there are a few studies on beta-catenin expression in leukaemia. This study was aimed to investigate beta-catenin localization and beta-catenin mRNA expression levels in 4 leukemia cell lines so as to explore a new oncogenic mechanism and to find out a new therapeutic target. The beta-catenin localization in leukemia cell lines was detected by immunocytochemistry, the beta-catenin mRNA expression level was assayed by real-time quantitative RT-PCR. The results showed that there was aberrant localization of beta-catenin in Jurkat and Thp-1, and beta-catenin mRNA expression level was not increased in these two cell lines, however, the mRNA expression levels of Jurkat and Thp-1 were lower than those of Daudi and K562. The beta-catenin mRNA expression level was not correlated with beta-catenin aberrant localization in these 4 cell lines. It is concluded that the aberrant localization of beta-catenin may play a role in the development of some leukemia, and the mechanism resulting in beta-catenin aberrant localization not take place at transcription level.
    Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2007; 14(6):1096-100.
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    ABSTRACT: Malignant ventricular arrhythmias can arise in a subset of congestive heart failure (CHF) patients after they undergo cardiac resynchronization therapy (CRT), thus counteracting the haemodynamic benefits typically associated with biventricular pacing. This study seeks to assess whether alteration of the ventricular transmural repolarization and conduction due to reversal of the depolarization sequence during epicardial or biventricular pacing facilitate the development of ventricular arrhythmias. ECGs and monophasic action potential (MAP) were recorded during programmed stimulation from right ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or both (biventricular, Bi-V) in 15 individuals without structural heart diseases. In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo, LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT, and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and compared. In subjects with or without structural heart disease, compared with RV-Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV-Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal-heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition to prolonged myocardial repolarization time and delayed endocardial activation. During follow-up, sudden death and arrhythmia storm occurred in two CHF patients after CRT. Epicardial and biventricular pacing prolong the time and increase the dispersion of myocardial repolarization and delay the transmural conduction. All of these should be considered as potential arrhythmogenic factors in CHF patients who receive CRT.
    Europace 12/2006; 8(11):1002-10. · 2.77 Impact Factor
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    ABSTRACT: To evaluate the effects of antiarrhythmic peptide (AAP10) on ventricular arrhythmias in rabbits with healed myocardial infarction (OMI). Thirty rabbits were randomly divided into three groups (n = 10 each): Sham group, left thoracotomy was performed without coronary ligation; OMI group and OMI + AAP10 group, the circumflex coronaries were ligated. Three months post operation, the electrophysiological and antiarrhythmic effects of AAP10 were assessed in the arterially perfused rabbit left ventricular wedge preparation. Sham and OMI group were perfused with Tyrode's solution and OMI + AAP10 group was perfused with Tyrode's solution + AAP10 (80 nmol/L). Transmembrane action potentials were recorded simultaneously from endocardium and epicardium together with a transmural ECG by use of 2 separate intracellular floating microelectrodes. The stimulus-response-interval (SRI) of the epicardium and the incidence of ventricular tachycardia (VT) were observed. Whole heart and left ventricular weights, the left ventricular thickness at infarct border zone were measured. Whole heart and left ventricular weights as well as the left ventricular thickness at the infarct border zone significantly increased post infarction. VT was induced in 8 out of 10 rabbits in OMI group and in 2 out of 10 rabbits in OMI + AAP10 group (P < 0.05). SRI was also significantly shortened in OMI + AAP10 group compared to OMI group [SRI-1: (20.59 +/- 0.79) ms vs. (28.71 +/- 0.55) ms; SRI-2: (30.42 +/- 0.74) ms vs. (38.67 +/- 0.49) ms, all P < 0.01]. However, the action potential morphology and duration were similar between OMI and OMI + AAP10 groups. The antiarrhythmic peptide (AAP10) can increase gap junctional intercellular conductance without affecting the action potential morphology and duration and decrease the incidence of inducible ventricular tachycardia.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 09/2006; 34(9):825-8.