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Yi Wang

Publications and source records attributed to Yi Wang.

At least 199 records · Page 11Linked to original sources
PubMed2004

Synthesis and biodistribution of (99m)Tc-carbonyltechnetium-labeled fatty acids.

In order to image myocardial metabolism, (99m)Tc(CO)(3)(+) complexes containing fatty acids were evaluated. At first, 11-(1-imidazolyl)-undecanoic acid (IUA) and 11-(2-(4-bromo-phenylazo)-1-imidazolyl)-undecanoic acid (BPIUA) were synthesized and the corresponding carbonyltechnetium-labeled complexes were prepared. However, unfortunately similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of (99m)Tc(CO)(3)-IUA and (99m)Tc(CO)(3)-BPIUA in mice demonstrated poor heart-to-blood ratios, thus these complexes cannot be used as heart-imaging reagents. In addition, Tween-80 can improve the biodistribution of the complexes for myocardial imaging.

Animals↗
PubMed2004

The effect of gemfibrozil on the pharmacokinetics of rosuvastatin.

BACKGROUND: Coadministration of statins and gemfibrozil is associated with an increased risk for myopathy, which may be due in part to a pharmacokinetic interaction. Therefore the effect of gemfibrozil on rosuvastatin pharmacokinetics was assessed in healthy volunteers. Rosuvastatin has been shown to be a substrate for the human hepatic uptake transporter organic anion transporter 2 (OATP2). Inhibition of this transporter could increase plasma concentrations of rosuvastatin. The effect of gemfibrozil on rosuvastatin uptake by cells expressing OATP2 was also examined. METHODS: In a randomized, double-blind, 2-period crossover trial, 20 healthy volunteers were given oral doses of gemfibrozil, 600 mg, or placebo twice daily for 7 days. On the fourth morning of each dosing period, a single oral dose of rosuvastatin, 80 mg, was coadministered. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and rosuvastatin-lactone were measured. In addition, the effect of gemfibrozil on the uptake of radiolabeled rosuvastatin by OATP2-transfected Xenopus oocytes was studied. RESULTS: Gemfibrozil increased the rosuvastatin area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration [AUC(0-t)] 1.88-fold (90% confidence interval, 1.60-2.21) and the maximum observed rosuvastatin plasma concentration (C(max)) 2.21-fold (90% confidence interval, 1.81-2.69) compared with placebo. N-desmethyl rosuvastatin AUC(0-t) and C(max) decreased by 48% and 39%, respectively. Pharmacokinetics of rosuvastatin-lactone was unchanged. The in vitro results indicate that the maximum gemfibrozil inhibition of rosuvastatin OATP2-mediated uptake was 50%; the inhibition constant for the inhibitory process was 4.0 +/- 1.3 micromol/L. CONCLUSIONS: Gemfibrozil increased rosuvastatin plasma concentrations approximately 2-fold, which is similar to the effect of gemfibrozil on pravastatin, simvastatin acid, and lovastatin acid plasma concentrations and substantially less than the effect observed for cerivastatin. Gemfibrozil inhibition of OATP2-mediated rosuvastatin hepatic uptake may contribute to the mechanism of the drug-drug interaction. Care is warranted when gemfibrozil is coadministered with rosuvastatin and other statins.

Administration, Oral↗
PubMed2004

An adaptive and iterative algorithm for refining multiple sequence alignment.

Multiple sequence alignment is a basic tool in computational genomics. The art of multiple sequence alignment is about placing gaps. This paper presents a heuristic algorithm that improves multiple protein sequences alignment iteratively. A consistency-based objective function is used to evaluate the candidate moves. During the iterative optimization, well-aligned regions can be detected and kept intact. Columns of gaps will be inserted to assist the algorithm to escape from local optimal alignments. The algorithm has been evaluated using the BAliBASE benchmark alignment database. Results show that the performance of the algorithm does not depend on initial or seed alignments much. Given a perfect consistency library, the algorithm is able to produce alignments that are close to the global optimum. We demonstrate that the algorithm is able to refine alignments produced by other software, including ClustalW, SAGA and T-COFFEE. The program is available upon request.

Algorithms↗
PubMed2004

Independent pathways of P-selectin and complement-mediated renal ischemia/reperfusion injury.

Evidence from in vitro studies indicates that complement activation regulates the expression of P-selectin on endothelial cells. This suggests that in disorders such as ischemia/reperfusion injury, in which both complement and P-selectin have been shown to play a role, complement activation is a primary event and the effects of P-selectin are secondary. To test this hypothesis in vivo, we examined a mouse kidney model of ischemia/reperfusion injury. Surprisingly, the time course and extent of expression of P-selectin was unaltered in C3-deficient mice compared with wild-type mice, in which there was rapid but transient up-regulation of P-selectin on capillary walls and slower accumulation of complement split product on the tubular epithelium. In addition, treatment with anti-P-selectin antibody to reduce the neutrophil-mediated reperfusion damage was equally effective in the absence of C3. These data imply that complement and P-selectin-mediated pathways of renal reperfusion injury are mutually independent, a conclusion that is possibly explained by the differences in the location and time kinetics of complement activation and P-selectin expression. We conclude that in vivo interaction between complement and P-selectin is limited because of time and spatial considerations. Consequently, complement and P-selectin pose distinct targets for therapy.

Animals↗
PubMed2004

Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells.

The multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), the MDR1 gene product, is one of the major obstacles in leukemia treatment. The present study was designed to explore a MDR1-targeted small interfering RNA (si-MDR1) approach for reversal of P-gp-mediated MDR in the MDR human leukemia cell line k562/A02. It was found that si-MDR1 significantly inhibited MDR1 expression at both mRNA and protein levels. Depletion of MDR1 by si-MDR1 correlated with the increased sensitivity of the cells to cytotoxic agents and with the enhanced intracellular retention of daunorubicin (DNR). One base-pair mutated control (si-MDR1-Mut) lost the effect of si-MDR1 on both the degradation of mdr1 mRNA and the reduction of P-gp expression. These findings indicate that siRNA specifically and efficiently interferes with the expression of mdr1 and could be used as a molecularly defined therapeutic approach for MDR in the treatment of leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.

DNA single-strand break repair (SSBR) is important for maintaining genome stability and homeostasis. The current SSBR model derived from an in vitro-reconstituted reaction suggests that the SSBR complex mediated by X-ray repair cross-complementing protein 1 (XRCC1) is assembled sequentially at the site of damage. In this study, we provide biochemical data to demonstrate that two preformed XRCC1 protein complexes exist in cycling HeLa cells. One complex contains known enzymes that are important for SSBR, including DNA ligase 3 (DNL3), polynucleotide kinase 3'-phosphatase, and polymerase beta; the other is a new complex that contains DNL3 and the ataxia with oculomotor apraxia type 1 (AOA) gene product aprataxin. We report the characterization of the new XRCC1 complex. XRCC1 is phosphorylated in vivo and in vitro by CK2, and CK2 phosphorylation of XRCC1 on S518, T519, and T523 largely determines aprataxin binding to XRCC1 though its FHA domain. An acute loss of aprataxin by small interfering RNA renders HeLa cells sensitive to methyl methanesulfonate treatment by a mechanism of shortened half-life of XRCC1. Thus, aprataxin plays a role to maintain the steady-state protein level of XRCC1. Collectively, these data provide insights into the SSBR molecular machinery in the cell and point to the involvement of aprataxin in SSBR, thus linking SSBR to the neurological disease AOA.

Amino Acids↗
PubMed2004

Myocardial viability: breath-hold 3D MR imaging of delayed hyperenhancement with variable sampling in time.

A method for visualizing myocardial infarction with a three-dimensional (3D) breath-hold gated acquisition was examined. By using variable sampling in time, whole heart coverage with a single volume acquisition was achieved in 24 heart beats. In a study of 35 patients, in whom 3D volume acquisition was compared with a two-dimensional (2D) acquisition, all regions of myocardial infarction were correctly identified at 3D examination. The mean imaging time for 12 section locations was 8.0 minutes +/- 3.0 with a 2D approach compared with 22 seconds +/- 4 with a 3D approach (P <.001). Advantages were also noted for infarct contrast-to-noise ratio: 60 +/- 37 for 3D versus 33 +/- 20 for 2D imaging (P <.001). No significant differences (P >.05) were noted at qualitative assessment of myocardial suppression, endocardial border visualization, respiratory and cardiac motion artifacts, or confidence of transmurality of the infarct.

Aged↗
PubMed2004

CD86 blockade in genetically modified porcine cells delays xenograft rejection by inhibiting T-cell and NK-cell activation.

Porcine xenografts transplanted into primates are rejected in spite of immunosuppression. Identification of the triggering mechanisms and the strategies to overcome them is crucial to achieve long-term graft survival. We hypothesized that porcine CD86 (pCD86) contributes to xenograft rejection by direct activation of host T cells and NK cells. Formerly, we designed the human chimeric molecule hCD152-hCD59 to block pCD86 in cis. To test the efficacy in vivo, we have utilized a pig-to-mouse xenotransplant model. First, we showed that hCD152-hCD59 expression prevents the binding of murine CD28Ig to pCD86 on porcine aortic endothelial cells (PAEC) and dramatically reduces IL-2 secretion by Con A-stimulated mouse splenocytes in coculture. Moreover, IFN-gamma secretion by IL-12-stimulated mouse NK cells was averted after coculture with hCD152-hCD59 PAEC. In vivo, control PAEC implanted under the kidney capsule were rapidly rejected (2-4 weeks) in BALB/c and BALB/c SCID mice. Rejection of hCD152-hCD59 PAEC was significantly delayed in both cases. Signs of immune modulation in the hCD152-hCD59-PAEC BALB/c recipients were identified such as early hyporesponsiveness and diminished antibody response. Thus, simply modifying the donor xenogeneic cell can diminish both T cell and NK cell immune responses. We specifically demonstrate that pCD86 contributes to rejection of porcine xenografts.

Animals↗
PubMed2004

[Proliferation regulation effect of cyclin G1 antisense oligodeoxy-nucleotides with liposomal transfection on HL-60 cell].

To investigate the effect of cyclin G1 antisense oligodeoxynucleotide (ASON) with liposomal transfection on mediating proliferation of HL-60 cell, the cyclin G1 ASON with liposomal transfection was used in vitro in co-culture with HL-60 cell, the protein and mRNA expression levels of cyclin G1 were measured by immunocytochemistry assay and RT-PCR. The cell apoptosis was detected by electron microscopy, in situ cell apoptosis detection kit (POD), DNA gel electrophoresis and flow cytometry (FCM). The results showed that in the cyclin G1 ASON group the protein and mRNA expression of cyclin G1 were significantly inhibited as compared with sense oligodeoxynucleotide (SON) group and blank group. When the ASON concentration increased, the proliferation ratio of HL-60 cell and CFU of HL-60 were also significantly inhibited. There was apoptosis of HL-60 cell. In conclusion, cyclin G1 ASON can specifically inhibit its protein and mRNA expression levels as well as the HL-60 cell proliferations and can accelerate the apoptosis of leukemia cells with concentration-dependent effect of ASON.

Apoptosis↗
PubMed2004

[Reversal of multi-drug resistance in K562/A02 cells by small interference RNA of mdr1 gene].

OBJECTIVE: To investigate the effect of small interference RNA (siRNA) on mdr1 and P-glyco-protein (P-gp) expression of multi-drug resistance (MDR) human leukemia cell line K562/A02. METHODS: Three si RNAs (si-mdr1-1, si-mdr1-2, si-mdr1-3) which were specifically targeted mdr1 gene were synthesized and transfected into K562/A02 cells. Expression of mdr1 mRNA was assayed by RT-PCR. P-gp expression and intracellular daunorubicin (DNR) concentration were determined by flow cytometry. 50% inhibition concentration (IC(50)) of doxorubicin (ADM) on K562/A02 was determined by MTT method. RESULTS: Treatment of K562/A02 cell with the 3 kinds of siRNAs resulted in a reversal of MDR of a different extent. The third siRNA was more effective in the suppression of mdr1 with a significant reduction of (58.0 +/- 1.54)% of the mdr1 mRNA expression. Positive expression rate of p170 decreased from (76.0 +/- 1.0)% to (19.6 +/- 1.9)%, and the relative efficiency of K562/A02 to ADM was 70.4%. The intracellular accumulation of DNR increased after siRNA treatment. CONCLUSION: The siRNA could effectively restore the sensitivity of K562/A02 cells to conventional chemotherapeutic agents.

Base Sequence↗
PubMed2004

[Exon polymorphism of human RHD gene].

OBJECTIVE: To study exon polymorphism of human RHD gene and investigate the genetic mechanism of RhD-negative individuals. METHODS: PCR using sequence-specific primers (PCR-SSP) was performed on 40 RhD-positive, 120 RhD-negative and 2 weak D blood samples. RESULTS: All 10 exons could be detected in the 40 RhD-positive and 2 weak D samples. Out of the 120 RhD-negative samples, 28 (23.33%) carried 10 exons, 19 (15.83%) lost most of the 10 exons (with mainly intermediate deletion), and 73 (60.83%) had deletion of all the 10 exons; 19 samples of Del phenotype identified from the 120 RhD-negative samples had all the 10 exons. CONCLUSION: Polymorphism of the exon structure of RHD gene is present in RhD-negative individuals, characterized chiefly by gross deletion, partial deletion and non-deletion.

Asian People↗
PubMed2004

[Effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere-telomerase system in K562 cell line].

The aim was to explore the modulating and inhibiting effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere length and telomerase activity in K562 cell line, and to study their anti-tumor mechanism and seek new method of therapy for acute leukemia. Human erythroleukemia cell line K562 was co-cultured with arsenic trioxide, ginseng saponin, beta-elemene separately, cells were collected after 24, 48 and 72 hours for further detecting. Telomere length and telomerase activity were detected by the methods of Southern-blot and PCR-ELISA respectively. The effects of these drugs on telomere length and telomerase activity were observed at different concentrations and length of time. The results showed that (1) telomerase activity of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene. The inhibiting effects depended on drug concentrations and length of time. When co-cultured at proper concentration and period of time, telomerase activity could be inhibited; (2) viability of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene, the inhibiting effect depends on drug concentrations and length of time; (3) after co-cultured with arsenic trioxide, ginseng saponin, and beta-elemene for 72 hours, telomere length of K562 cell line prolonged a little. It is concluded that (1) arsenic trioxide, ginseng saponin and beta-elemene can inhibit telomerase activity in K562 cell line, the suppression of telomerase activity may be one of the mechanisms of anti-tumor effect; (2) arsenic trioxide, ginseng saponin and beta-elemene can inhibit the growth of K562 cell line, the inhibiting effect depends on concentration and time; (3) when telomerase activity was suppressed, the telomere length prolonged a little, indicating that in K562 cell line may exist another mechanism to regulate telomere length, except telomerase activation.

Arsenic Trioxide↗
PubMed2004

[Therapeutic effect of "anti-hepatic-fibrosis 268" on hepatic fibrosis in rats].

OBJECTIVE: To investigate the effects of the proprietary Chinese Medicine "anti-hepatic-fibrosis 268" on hepatic fibrosis and the related mechanisms. METHODS: The model of CCl4-induced hepatic damage was established in SD rats. 54 male rats were divided into four groups, namely high dose and low dose "anti-hepatic-fibrosis 268" groups, colchicine control group, and model control group. Using Masson stain and light microscope, the authors examined the rats' hepatic tissues and counted the hepatic fiber components, then examined and counted TGF-beta1, alpha-SMA, FN, Type I, III collagen by means of immunohistochemical technique. The groups were compared and the internal relationships of the data were analyzed. RESULTS: The levels of FN, LN, Type I and III collagen, TGF-beta1, and alpha-SMA of the CCl4 damaged rats increased (P<0.01). After 3 weeks of high dose "anti-hepatic-fibrosis 268" treatment, the levels of TGF-beta1, alpha-SMA, FN, LN, Type I and III collagen decreased (P<0.01) and the degree hepatic fibrosis took a favorable turn significantly (P<0.05) as compared with the model control. In the rats of the low dose group, the levels of TGF-beta1, alpha-SMA, FN, Type III collagen significantly decreased (P<0.05), the levels of LN, Type I collagen were not different from the model control; The hepatic fibrosis improved to a certain extent (P<0.05). CONCLUSION: The mechanism of reversing hepatic fibrosis by "anti-hepatic-fibrosis 268" in this experiment is that the medicine regulates TGF-beta1 and further affects alpha-SMA, thus resulting in the decline of FN, Type I, III collagen levels in liver extracellular matrix.

Actins↗
PubMed2004

[Myocardial matrix metalloproteinases activities in mice with viral myocarditis and their relationship with cardiac function and myocardial collagen amount].

OBJECTIVE: To investigate the dynamic changes of myocardial matrix metalloproteinases (MMPs) activities in mice with viral myocarditis (VM) and their relationships with cardiac function and myocardial collagen amount and to explore the role of MMPs in the pathologic lesion of VM. METHODS: Sixty-five six-week-old male DBA/2 mice were obtained from the Chinese Academy of Medical Sciences. They were divided into two groups randomly. Mice in infected group (n=50) were inoculated intraperitoneally with 0.14 ml of coxsackievirus B3 (CVB3, Nancy strain). Control mice (n=15) were inoculated intraperitoneally with 0.14 ml of Eagle's solution. Eight infected mice were sacrificed on day 3, 7, 10, 21 and 30, respectively and fifteen control mice were killed on day 30 after inoculation. Total protein concentration was determined according to the method of Bradford, while MMPs activities were measured with SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate intraperitoneally (0.01-0.015 ml/g). Cardiac systolic function indexes, such as peak velocity of aorta (Vp) and flow velocity integral of aorta (Vi) were determined by echocardiography. Histological cross sections of hearts were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Myocardial collagen amount was measured by determination of hydroxyproline quantification. RESULTS: In virus-infected mice, both MMP-2 and MMP-9 activities were increased significantly compared with those in controls and reached the peak on day 10 (P < 0.01). On day 10, cardiac systolic function indexes (Vp and Vi) were all significantly lower than those at other stages after virus inoculation and in control group (P < 0.05). There was no obvious elevation in myocardial collagen amount in mice with VM at acute stage (P > 0.05). While the myocardial collagen amount in infected group at recovery stage (on day 21 and 30) increased significantly compared with controls. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores, respectively (r =0.801, 0.821 P < 0.01), while they negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi, respectively (r = -0.711, -0.755, P < 0.01). However, Vp and Vi negatively correlated with myocardial histopathological scores (r = -0.756, -0.584, P < 0.01). CONCLUSIONS: In mice with VM, the activities of myocardial MMP-2 and MMP-9 at acute stage increased significantly, then myocardial collagen amount elevated in recovery stage. These changes were associated with myocardial remodeling and cardiac dysfunction. Myocardial MMP activities are important markers of myocardial pathologic lesion. They are of value in the evaluation of the severity of myocardial damage and cardiac dysfunction in mice with VM.

Animals↗
PubMed2004

Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis.

BACKGROUND: Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM. METHODS: Sixty-five six-week-old male DBA/2 mice were divided into two groups. Mice in the infected group (n = 50) were inoculated intraperitoneally with 0.14 ml of Coxsackievirus B3 (CVB3, Nancy strain). Control mice (n = 15) were inoculated intraperitoneally with 0.14 ml of Eagle's medium. Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation. MMP activity was measured on an SDS-PAGE substrate gel embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0.01 ml/g - 0.015 ml/g). Cardiac systolic function indices, such as peak velocity of the aorta (Vp), flow velocity integral of the aorta (Vi), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography. Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of hydroxyproline quantification. RESULTS: In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 (P < 0.01). On day 10, cardiac systolic function indices (EF, FS, Vp, and Vi) were all significantly lower compared both to other stages following viral inoculation and to the control group (P < 0.05). In the acute stage, the amount of myocardial collagen in mice with VM was not significantly different from normal control mice (P > 0.05). However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores (r = 0.801, 0.821, P < 0.01) and negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi (r = -0.711, -0.755, P < 0.01). However, Vp negatively correlated with myocardial histopathological scores (r = -0.756, P < 0.01). CONCLUSIONS: In mice with VM, the activities of myocardial MMP-2 and MMP-9 increase significantly during the acute stage, and the total quantity of myocardial collagen increases by the time of recovery. These changes are associated with myocardial interstition remodeling and cardiac dysfunction. MMP activity is an important reference marker for myocardial pathological lesions and can be used to evaluate the severity of myocardial interstitial damage and cardiac dysfunction.

Animals↗
PubMed2004

Effects of ulinastatin on renal ischemia-reperfusion injury in rats.

AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats. METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12,500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope. RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significant effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin, reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

Animals↗