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Biomedical subjects

Dan Wang

Publications and source records attributed to Dan Wang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Cantilever dynamics and quality factor control in AC mode AFM height measurements.

We show that inconsistent-imaging dynamics, in which the cantilever oscillates in the attractive regime on substrate background but in the repulsive regime on sample, leads to artifacts in apparent height in AC mode Atomic force microscopy. Active Q control can be used to effectively tune the imaging dynamics. Increased effective Q promotes the attractive regime, improves imaging sensitivity, and results in less invasive imaging of soft biological molecules.

DNA↗
PubMed2006

Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide.

AIMS: Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. METHODS: Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. RESULTS: The C(max) and AUC(0,infinity) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t(1/2) of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in t(max) values among the three genotypic groups was not statistically significant. CONCLUSIONS: Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.

Adult↗
PubMed2006

Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation.

AIB1, a member of the steroid receptor coactivator (SRC) family that participates in gene transcriptional activation by nuclear receptors and other transcription factors, is required for animal growth and reproductive development and implicated in breast carcinogenesis. The mechanisms underlying the AIB1 pleiotropic functions are not fully understood and neither is the regulation of its activity. Here, we showed that AIB1 was a sumoylated protein and the sumoylation attenuated the transactivation activity of AIB1, which is in contrast to the sumoylation of its paralogs, GRIP1 and SRC-1. The transactivation activity of AIB1 is enhanced by its phosphorylation by several kinases, including mitogen-activated protein kinase. We demonstrated in this report that estrogen treatment led to an increased phosphorylation and decreased sumoylation of AIB1 and that the sumoylation coordinated with phosphorylation in regulating the transcriptional activity of AIB1, providing a mechanism for post-translational modifications in regulating the transcriptional output of AIB1.

Acetyltransferases↗
PubMed2006

A biomimetic "polysoap" for single-walled carbon nanotube dispersion.

As-synthesized single-walled carbon nanotubes (SWNTs) are bundled mixtures of different species. The current challenge in the field of carbon nanotube research lies in the processing and separation of SWNTs, which first require efficient dispersion of individual SWNTs in solvents. We report DNA-mimicking polysoap surfactants that disperse SWNTs in aqueous solutions more effectively than DNA. The polysoaps are synthesized by functionalizing the side chain of poly(styrene-alt-maleic acid) with aminopyrene. The synthetic nature of the polysoap opens a new approach to further optimization of not only SWNT dispersion efficiency but also multi-functional SWNT dispersing surfactant.

Biomimetic Materials↗
PubMed2006

Sensitive bioassay for the simultaneous determination of pseudoephedrine and cetirizine in human plasma by liquid-chromatography-ion trap spectrometry.

A liquid chromatography-ion trap mass spectrometry coupled with electrospray ionization (HPLC-ESI-ion trap mass spectrometry) method for simultaneous determination of cetirizine and pseudoephedrine in human plasma is presented. Chromatographic separation was performed on a Hypurity C18 column (Thermo Hypersil-Keystone 2.1 mm x 150 mm, 5 microm, USA), The mobile phase was composed of 65% methanol and 35% water (contained 0.1% formic acid, 10 mM ammonium formate), which was run with a flow-rate of 0.2 ml/min at 40 degrees C. Quantitation was achieved by monitoring the product ions at m/z 166-->m/z 148 (pseudoephedrine), m/z 389.9-->m/z 201.1 (cetirizine), m/z 264-->m/z 246 (tramadol, IS). The calibration curve of pseudoephedrine and cetirizine was established with standard solutions. The limit of detection for pseudoephedrine and cetirizine each was 5 ng/ml. This simplified analytical method is sensitive, specific and accurate enough for simultaneous determination of pseudoephedrine and cetirizine in human plasma and is successfully applied to the pharmacokinetic study of pseudoephedrine and cetirizine.

Adult↗
PubMed2006

PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice.

Deposition of plaques containing amyloid beta (Abeta) peptides is a neuropathological hallmark of Alzheimer's disease (AD). Here we demonstrate that neuronal overexpression of the epsilon isozyme of PKC decreases Abeta levels, plaque burden, and plaque-associated neuritic dystrophy and reactive astrocytosis in transgenic mice expressing familial AD-mutant forms of the human amyloid precursor protein (APP). Compared with APP singly transgenic mice, APP/PKCepsilon doubly transgenic mice had decreased Abeta levels but showed no evidence for altered cleavage of APP. Instead, PKCepsilon overexpression selectively increased the activity of endothelin-converting enzyme, which degrades Abeta. The activities of other Abeta-degrading enzymes, insulin degrading enzyme and neprilysin, were unchanged. These results indicate that increased neuronal PKCepsilon activity can promote Abeta clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity.

Amyloid↗
PubMed2006

Selective interaction of large or charge-transfer aromatic molecules with metallic single-wall carbon nanotubes: critical role of the molecular size and orientation.

Using first principles calculations, we report for the first time that large nearly neutral aromatic molecules, such as naphthalene and anthracene, and small charge-transfer aromatic molecules, such as TCNQ and DDQ, interact more strongly with metallic single-wall carbon nanotubes (SWNTs) versus their semiconducting counterparts as the molecular orientation of DDQ is taken into account. Hence two new mechanisms for separating metallic and semiconducting SWNTs via noncovalent pi-pi stacking or charge-transfer interaction are suggested.

Journal Article↗
PubMed2006

Evolution of the electronic properties of metallic single-walled carbon nanotubes with the degree of CCl2 covalent functionalization.

The changes in energetic, structural, and electronic properties of the metallic (5,5) single-walled carbon nanotube (SWNT) with the degree of sidewall covalent functionalization of CCl(2) are investigated extensively by using density functional theory calculations. The saturation concentration of CCl(2) covalent functionalization is predicted to be 33.3%. The cycloadducts always adopt an open structure. A band gap opens as the functionalization concentration reaches 11% and then basically increases with increasing functionalization concentration. These results are in agreement with available experiments and can be applied to accurately predict the band gap of metallic SWNTs produced by the HiPco method at a given CCl(2) functionalization concentration.

Journal Article↗
PubMed2006

Insights into sperm cell motility signaling through sNHE and the CatSpers.

Successful natural reproduction normally requires vigorously motile spermatozoa. Using a signal peptide trapping strategy, we identified two new genes, a putative sperm Na+/H+ exchanger (sNHE) and the putative cation channel CatSper2, with unique and essential roles in sperm motility. Disruption of the sNHE or CatSper2 genes in mice caused male infertility due to immotile spermatozoa or failed motility hyperactivation, respectively, without other apparent abnormalities. The immotility phenotype of the sNHE null spermatozoa appears to result from an intimate association of sNHE and the atypical adenylyl cyclase (sAC), while a failure of calcium entry requiring an apparent CatSper1 and -2 heteromeric ion channel correlates with a hyperactivation defect in these null animals. The specific expression of sNHE and the CatSpers in spermatozoa and their required function in cell motility make them excellent potential targets for the development of novel male contraceptives.

Adenylyl Cyclases↗
PubMed2006

A comparison of wavefront aberrations in eyes wearing different types of soft contact lenses.

PURPOSE: The purpose of this study is to investigate the optical quality of eyes wearing different types of soft contact lenses (sCLs) using wavefront aberrometry. METHOD: A psychophysical aberrometer (WFA1000B; BriteEye, SuZhou, China) was used to measure wavefront aberrations for 56 eyes of 28 subjects under four conditions: 1) without contact lenses (non-CL), 2) with lathe-cut contact lenses (lathe-cut CL; Shuliang, Weicon Optics, Shanghai, China), 3) with cast-molded contact lenses (cast-molded CL; Vistavue, J&J Vision Care, U.S.), and 4) with spun-cast contact lenses (spun-cast CL; Lanfenzhiji, Justcome Optics, Beijing, China). The three types of sCLs were made from different materials and lens design. The root mean square (RMS) values of the wavefront aberrations and individual Zernike aberrations were calculated and compared among the CL-wearing conditions. RESULTS: Astigmatism was not significantly changed by any of the three soft contact lenses when compared with the non-CL condition. However, a significant difference in the RMS values of higher-order aberrations was observed between the lens types (F=8.29, p<0.0001). Induced higher-order aberrations were found for both the cast-molded CL and the spun-cast CL conditions. There were significant differences in the aberrations in each of the higher orders between the CL conditions (F=3.77, p=0.011 for third order; F=5.31, p=0.002 for fourth order; F=13.86, p<0.0001 for fifth and higher orders). More higher-order Zernike aberrations such as coma and spherical aberration were induced by cast-molded CLs and/or the spun-cast CLs. CONCLUSION: Wavefront aberrations in the eyes with soft contact lenses vary from one individual lens type to another. Although the variation in wavefront aberrations could be attributed to the differences in the methods of manufacture, influences from other factors such as the lens material and lens design could not be excluded and deserve further investigation.

Adult↗
PubMed2006

Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation.

1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. 2. The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients. 3. One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3 and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were determined and compared among the different genotype groups. 4. The frequency of the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1 genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal-Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non-expressors than expressors in the first week after renal transplantation. In addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7 (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3 variant genotype require a low dose of cyclosporine to reach target levels compared with those with the CYP3A5*1 allele.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of beta1-adrenoceptor in Chinese Han and Dai populations.

AIM: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of beta(1)-adrenoceptor may result in significant changes in the function of this receptor. The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles. METHODS: A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study. Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco0109I and BcgI. Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h). RESULTS: The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in the Dai population. CONCLUSION: The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the beta(1)-adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations. However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population.

Adolescent↗
PubMed2006

[Expression of deltaNp63 in salivary gland tumours].

OBJECTIVE: To detect the expression of deltaNp63 in human salivary gland tumor and analyze its role in the malignant salivary gland tumors. METHODS: Collecting the samples from 68 cases of pathologically proven salivary gland tumours and investigating the microscopic sections with HE stain and immunohistochemical-SP stain. RESULTS: It was found that the expression of deltaNp63 is gradually increased in the malignant tumours, the myoepithelial cells and the basal cells of the salivary gland tumors are positive, and the expression of deltaNp63 is correlated directly with benign and malignant tumor. CONCLUSION: deltaNp63 plays an important role in salivary gland tumours. deltaNp63 possesses some special activity that is characteristic of oncogene. p63 is a sensitive and highly specific marker of myoepithelial cells in salivary gland tumours and an additional marker for defining myoepithelial histogenesis. p63 is of definite clinical value in falicitating diagnosis and differential diagnosis.

Adenoma, Pleomorphic↗
PubMed2006

[Researching the character and stenosis of coronary calcified plaques by using 16-slice spiral CT].

OBJECTIVE: To explore the characters of coronary calcified plaques by using 16-slice spiral CT and determine their stenosis degree according to the results of catheter coronary angiography. METHODS: Twenty patients who had received 16-slice spiral CT coronary angiography and conventional coronary angiography (CAG) were found to be with calcified plaques. The characters of these plaques, including the diameter of calcified plaques and lumen diameter of the exact artery segment, were retrospectively analyzed. The stenosis degree of the corresponding segment was judged in accordance with the results of CAG. RESULTS: Totally 84 calcified plaques were observed in 16-slice spiral CT images in these 20 patients. Among them there were 16 small nodules (diameter: < 0.15 cm), 56 purely calcified plaques (diameter: > or = 0. 15 cm), and 12 complex plaques with calcify component. There was no obvious stenosis in artery segments with little calcified nodules. The stenosis degree of most segments with purely calcified plaques (75%) was less than 50%. The stenosis degree had no significant correlation with the size of plaques (P > 0.05). However, the stenosis degree of complex plaques had much closer relationship with the characters of mixed plaques. CONCLUSIONS: Most coronary segments with calcified plaques have slight stenosis. Their stenosis degree is not related with the size of plaques. The stenosis degree of complex plaques has a closer relationship with the characters of mixed plaques.

Adult↗
PubMed2006

[Studies on the association between beta 2-glycoprotein I and hepatotropism of hepatitis B virus].

OBJECTIVE: To further study the binding character of hepatitis B surface antigen (HBsAg) and beta 2-glycoprotein I (beta2GP I) and to explore whether beta2GP I plays an important role in the hepatotropism of hepatitis B virus. METHODS: Using Western blot technique, we observed the binding character of the HBsAg with reduced and non-reduced beta2GP I. RESULTS: rHBsAgs with reduced and non-reduced beta2GP I showed identical binding activity. CONCLUSIONS: The binding activity of HBsAg is dependent on tandem residues, but not on conformational structures of beta2GP I. There is a specific binding between HBV and beta2GP I, which may play an important role in HBV infection and is one of the reasons of hepatotropism of HBV.

Hepatitis B↗
PubMed2006

[Reversal of multidrug resistance of human hepatocellular carcinoma cells by wild-type p53 gene and related mechanisms].

BACKGROUND & OBJECTIVE: The mechanism of cell apoptosis plays an important role in tumor multidrug resistance (MDR). Wild-type p53 (wt-p53) gene is an activator of cell apoptosis, and is closely related to tumor MDR. This study was to explore the effect of p53 gene on the reversal of MDR of human hepatocellular carcinoma (HCC) and related mechanisms. METHODS: The eukaryotic expression plasmid pCR 3.1-p53 was constructed and transfected into human HCC cell line Bel-7402. Proliferation and chemosensitivity of Bel-7402 cells to vincristine (VCR) were measured by MTT assay. The morphology of transfected Bel-7402 cells was observed. The expression of P-glycoprotein (P-gp) was detected by immunochemistry. The expression of multidrug resistance gene 1 (mdr1), multidrug resistance related protein (MRP), glutathione S-transferase pi (GST pi), and topoisomerase II alpha (Topo II alpha) were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The growth of wt-p53-transfected Bel-7402 cells was obviously slower than that of untransfected cells. After transfection with wt-p53, the chemosensivity of Bel-7402 cells to VCR was enhanced at the concentration of 0.01, 0.1, 1.0, 10, and 25 microg/ml. The optimal concentration was 1.0 microg/ml. After wt-p53 transfection and VCR treatment, the number of Bel-7402 cells was decreased; the cells were swollen severely with irregular projections; pyknosis, karyorrhexis and karyolysis were observed. After wt-p53 transfection, the expression of mdr1 and P-gp in Bel-7402 cells was down-regulated remarkably, and the expression of Topo II alpha was up-regulated. CONCLUSION: Wild-type p53 gene raises chemosensitivity of Bel-7402 cells to VCR, which may be partly related to the down-regulation of mdr1 and up-regulation of Topo II alpha.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2005

Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis.

Tamoxifen, a selective oestrogen receptor modulator, has been used in the treatment of all stages of hormone-responsive breast cancer. However, tamoxifen shows partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial cancer. The molecular explanation for these observations is not known. Here we show that tamoxifen and oestrogen have distinct but overlapping target gene profiles. Among the overlapping target genes, we identify a paired-box gene, PAX2, that is crucially involved in cell proliferation and carcinogenesis in the endometrium. Our experiments show that PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, and that this activation is associated with cancer-linked hypomethylation of the PAX2 promoter.

Animals↗