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Biomedical subjects

Lu Wang

Publications and source records attributed to Lu Wang.

At least 55 records · Page 3Linked to original sources
PubMed2006

Effects of oxymatrine on proliferation and apoptosis in human hepatoma cells.

Oxymatrine, a natural quinolizidine alkaloid, has been known having cytotoxic and chemopreventive effects on various cancer cells. To investigate the possible mechanism of oxymatrine's role on cancer cells, in the present study, we examined further the effects of oxymatrine on the growth, proliferation, apoptosis and expression of bcl-2 and p53 gene in human hepatoma SMMC-7721 cells in vitro. Our results show that oxymatrine notably inhibits the growth and proliferation of SMMC-7721 cells and it present a dose-dependence and time-dependence manner within definite reacting dose and time. Oxymatrine block SMMC-7721 cells in G2/M and S phase; prevent cells entering into G0/G1 phase. It results in an obvious accumulation of G2/M and S phase cells while decrease of G0/G1 phase cells. Oxymatrine induce apoptosis of SMMC-7721 cells and apoptotic rate amount to about 60% after treatment with 1.0 mg/ml oxymatrine for 48 h. We also find that oxymatrine down-regulate expression of bcl-2 gene while up-regulate expression of p53 gene. These results demonstrate that oxymatrine inhibit the proliferation and induce apoptosis of human hepatoma SMMC-7721 cells, and suggest that this effect was mediated probably by a significant cell cycle blockage in G2/M and S phase, down-regulation of bcl-2 and up-regulation of p53.

Alkaloids↗
PubMed2006

Solvent-tuned azido-bridged Co2+ layers: square, honeycomb, and Kagomé.

Three azido-bridged Co2+ complexes with square, honeycomb, and Kagomé layered structures were synthesized and structurally characterized. Crystallization solvents are found to be critical in generating the observed topologies. These structurally related complexes are of significance in studying two-dimensional antiferromagnetism and geometric frustration.

Journal Article↗
PubMed2006

Purification of humanized monoclonal antibody by hydrophobic interaction membrane chromatography.

Humanized monoclonal antibodies (mAbs) hold significant promise as biopharmaceuticals. One of the main challenges faced in the purification of mAbs is their separation from bovine serum albumin, which is the main protein present in most mammalian cell culture media. This paper discusses the purification of humanized mAb hIgG1-CD4 from CHO cell culture media by hydrophobic interaction membrane chromatography using a stack of microporous synthetic membranes. The effects of solution conditions on mAb solubility and binding on the membrane were first studied. The separation of a simulated mixture of bovine albumin and the mAb was then carried out to examine the feasibility of mAb purification. Separation experiments carried out under optimized conditions demonstrated that this membrane-based technique could be used for mAb purification from cell culture media. High purity (97%) and recovery (in excess of 97%) were obtained.

Animals↗
PubMed2006

Coronary risk factors and myocardial perfusion in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: The purpose of this study was to determine the cross-sectional relation between myocardial perfusion and coronary heart disease (CHD) risk factors among adults with no clinical CHD. BACKGROUND: Clinical studies suggest that myocardial perfusion is often abnormal in individuals without CHD but with risk factors. Epidemiologic study in asymptomatic populations is lacking. METHODS: Two hundred twenty-two men and women, ages 45 to 84 years and free of a CHD diagnosis, in the University of Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (MESA) had myocardial blood flow (MBF) determined using cardiac magnetic resonance imaging at rest and during adenosine-induced hyperemia. Perfusion reserve (PR) was calculated as the ratio of hyperemic to rest MBF. RESULTS: Both resting and hyperemic MBF were lower in men than in women, even after considering age and menopause. Hyperemic MBF was also significantly lower in subjects who were older, and in those with higher blood pressure, higher fasting glucose, and lower low-density lipoprotein cholesterol. After adjusting for age, gender, and race, reduced PR was independently associated with hypertension, higher diastolic blood pressure, and higher total and low-density lipoprotein cholesterol, but was not associated with cigarette smoking, obesity, physical activity, or diabetes. Moreover, hyperemic MBF and PR were correlated strongly and inversely with estimated 10-year CHD risk based on Framingham equations (p for trends: <0.0001). CONCLUSIONS: Coronary vasoreactivity is reduced in asymptomatic individuals with a greater coronary risk factor burden. Our study results imply that changes in coronary vascular reactivity, in response to risk factors, may be detected in adults without symptomatic CHD.

Adenosine↗
PubMed2006

Antimony-based antileishmanial compounds prolong the cardiac action potential by an increase in cardiac calcium currents.

Antimonial agents are a mainstay for the treatment of leishmaniasis, a group of protozoal diseases that includes visceral leishmaniasis, or Kala Azar. Chemotherapy with trivalent potassium antimony tartrate (PAT) and, more importantly, pentavalent antimony-carbohydrate complexes, such as sodium stibogluconate (SSG), has been reported to prolong the QT interval and produce life-threatening arrhythmias. PAT is chemically related to As2O3, which alters cardiac excitability by inhibition of human ether a-go-go related gene (hERG) trafficking and an increase of cardiac calcium currents. In this study, we report that PAT does not block hERG currents on short-term exposure but reduces current density on long-term exposure (IC50, 11.8 microM) and inhibits hERG maturation on Western blots (IC50, 62 microM). Therapeutic concentrations of 0.3 microM PAT increase cardiac calcium currents from -4.8 +/- 0.7 to -7.3 +/- 0.5 pA/pF at 10 mV. In marked contrast, pentavalent SSG, the drug of choice for the treatment of leishmaniasis, did not affect hERG/IKr or any other cardiac potassium current at therapeutic concentrations. However, both cardiac sodium and calcium currents were significantly increased on long-term exposure to 30 microM SSG in isolated guinea pig ventricular myocytes. We propose that the increase in calcium currents from -3.2 +/- 0.3 to -5.1 +/- 0.3 pA/pF at 10 mV prolongs APD90 from 464 +/- 35 to 892 +/- 64 ms. Our data suggest that conversion of Sb(V) into active Sb(III) in patients produces a common mode of action for antimonial drugs, which define a novel compound class that increases cardiac risk not by a reduction of hERG/IKr currents but-for the first time-by an increase in cardiac calcium currents.

Action Potentials↗
PubMed2006

Abdominal drainage was unnecessary after hepatectomy using the conventional clamp crushing technique.

A prophylactic abdominal drainage catheter is routinely inserted by many surgeons in patients after hepatic resection. Between January 2002 and September 2004, 462 consecutive patients who had undergone hepatic resection using a clamp crushing method by the same surgical team were retrospectively divided into the drainage group (n = 357) and the nondrainage group (n = 105). There was no difference in hospital mortality between the two groups of patients (drainage group, 0.6% vs. nondrainage group, 0%; P = 1.0). However, there was a greater incidence of surgical complications in the drainage group (31.4% vs. 8.6%, P < 0.001), and greater incidence of wound complications and subphrenic complications in the drainage group compared to the nondrainage group (24.4% vs. 4.8%, P < 0.001). In addition, the mean (+/- SEM) postoperative hospital stay of the drainage group was 13 +/- 6.5 days, which was significantly longer than that of the nondrainage group (9.7 +/- 3.3 days, P = 0.001). On multivariate analysis, abdominal drainage and intraoperative bleeding were the independent risk factors that were significantly associated with the incidence of drainage-related complications. The results suggested that routine abdominal drainage is unnecessary after hepatic resection when the conventional clamp crushing method is used during parenchyma transection.

Abdomen↗
PubMed2006

An intrinsically shielded hydrogel for the adsorptive recovery of lysozyme.

The present paper addresses the selective recovery of lysozyme from egg white using CM-dextran (carboxymethyldextran)-based hydrogels containing Cibacron Blue as an affinity ligand and co-immobilized BSA intended to act as a shielding agent to reduce non-specific adsorption. Initial studies using pure lysozyme were conducted that indicated that the adsorption capacity increased with ligand density and that adsorption was well described by a Langmuir-type isotherm. The inclusion of BSA as a putative shielding agent did not decrease the adsorption capacity for lysozyme in single-adsorbate experiments. To assess the effectiveness of the shielding strategy, subsequent experiments were conducted with both defined lysozyme/ovalbumin mixtures and hen's-egg white. From these studies, the optimal operating conditions for lysozyme recovery have been determined. These include: optimal initial egg-white concentration [a 10% (v/v) solution of native egg white in the chosen buffer], affinity-ligand density (1.86 mM) and ligand-to-shielding-agent ratio (4:1). The purity of lysozyme obtained from egg white was improved from 69% with a non-shielded hydrogel to 94% with an intrinsically shielded hydrogel. Finally, the possibility of using a protein, rather than dextran-backbone-based, hydrogel was investigated. It was found that BSA could take the place of CM-dextran as the gel backbone in a simplified synthesis, producing a gel which also proved effective for lysozyme recovery with a 30% lysozyme in egg-white solution purified to approx. 92% in a single adsorption-desorption cycle.

Adsorption↗
PubMed2006

CD4+ T-cell modulation of visceral nociception in mice.

BACKGROUND & AIMS: Although inflammatory and immune cells are present in the gut in the absence of pathology, their presence does not result in sensitization of sensory nerves, implying the existence of a local antinociceptive influence. We hypothesized that a component of the immune system exerts an antinociceptive influence, thus enabling the gut to function in the absence of undue pain or discomfort. METHODS: Visceromotor responses to colorectal distention were measured in mice with severe combined immune deficiency (SCID) and their wild-type controls. RESULTS: SCID mice exhibited significantly lower pain thresholds. Transfer of CD4(+) T, but not B lymphocytes, normalized visceral pain in these mice. The restoration of normal visceral nociception following T-cell reconstitution in SCID mice was blocked by naloxone methiodide. Using an enzyme immunoassay and immunohistochemistry for beta-endorphin, we showed that in vitro stimulation of T lymphocytes induced the synthesis and release of beta-endorphin and that transfer of T cells into SCID mice increased the expression of beta-endorphin in the enteric nervous system. CONCLUSIONS: These findings indicate that the immune system is a critical determinant of visceral nociception and that T lymphocytes provide an important opioid-mediated antinociceptive influence in the gut.

Animals↗
PubMed2006

The consumption of lycopene and tomato-based food products is not associated with the risk of type 2 diabetes in women.

Lycopene is a major carotenoid with potent antioxidant properties that may provide protection against the development of type 2 diabetes mellitus (DM). In this study we examined the association between baseline dietary intakes of lycopene, lycopene-containing foods, and the subsequent development of type 2 DM in a large prospective cohort study. We analyzed a total of 35,783 women from the United States, aged > or =45 y and free from self-reported cardiovascular disease, cancer, and DM at baseline. Intakes of lycopene and total and individual tomato-based food products were assessed by a 131-item-validated semiquantitative food-frequency questionnaire. During a median follow-up of 10.2 y, 1544 cases of incident type 2 DM were documented. After adjusting for age, total energy intake, randomized treatment assignment, body mass index, and other known DM risk factors, the multivariate-adjusted relative risks and 95% CI of type 2 DM across increasing quintiles of dietary lycopene, were 1.00 (baseline), 1.10 (0.94-1.29), 1.10 (0.94-1.29), and 1.07 (0.91-1.26) (P linear trend = 0.56). Compared with women who consumed <1.5 servings/wk total tomato-based food products, women who consumed 1.5 to <4, 4 to <7, 7 to <10, and > or =10 servings/wk had multivariate relative risks (95% CI) of 1.03 (0.88-1.20), 1.02 (0.87-1.20), 1.09 (0.89-1.33), and 1.04 (0.80-1.36), respectively (P linear trend = 0.54). The associations for individual tomato-based food products were similar to the results for the combination of all tomato products. Our study found little evidence for an association between dietary intake of lycopene or lycopene-containing foods and the risk of type 2 DM.

Antioxidants↗
PubMed2006

Intensity modulated radiation therapy (IMRT) decreases acute skin toxicity for women receiving radiation for breast cancer.

OBJECTIVE: To determine the clinically observed incidence and severity of acute skin toxicity with breast intensity modulated radiation therapy (IMRT), and compare the results with a matched cohort of patients treated by conventional radiation therapy. Our hypothesis is that measures to decrease dose inhomogeneity within the breast and skin with IMRT will improve acute skin toxicity. MATERIALS AND METHODS: The study population consists of 73 women with early stage breast cancer treated with breast-conserving surgery and IMRT. The IMRT technique involves an iteration method for optimization to generate the IMRT plan, Monte Carlo dose calculation, and a step-and-shoot technique using multileaf collimation for beam delivery. Other aspects of the technique including the clinical definition of the clinical target volume by the physician, patient positioning, tangential beam orientation, dose and field sizes were unchanged compared conventional tangential radiation. These patients were matched one-to-one to a control group of 60 women treated with conventional photon radiation by using their bra size and chest wall separation. The study end point was acute skin toxicity. RESULTS: There were no observed differences in the acute toxicity based upon common terminology criteria for adverse events (CTC) for acute radiation dermatitis. There was no desquamation in 42% of IMRT patients, dry desquamation in 37% and moist desquamation in 21%. The degree of desquamation was greater for conventional patients compared with IMRT patients -52% grade 0, 10% grade 1, and 38% grade 2 (P = 0.001). Subgroup analysis showed desquamation was significantly lower with IMRT for small (P = 0.038) and large breast sizes (P = 0.037), but not medium sizes (P = 0.454). For large breast sizes, the incidence of moist desquamation grade 2 was 48% with IMRT compared with 79% in controls. Significant predictors of moist desquamation on stepwise logistic regression were use of IMRT (P = 0.0011) and breast size (P < 0.0001). CONCLUSIONS: IMRT is associated with a decrease in severity of acute desquamation compared with a matched control group treated with conventional radiation therapy. As with conventional radiation, breast size remains the most important prognostic factor for acute skin toxicity. The CTC grading system for acute radiation dermatitis is not sensitive when applied to modern breast cancer treatment because of its dependence of subjective rating of erythema and inability to gauge variations in desquamation. Further study of patient symptoms, quality of life, and cosmesis is needed to evaluate the benefit of IMRT for breast cancer.

Breast Neoplasms↗
PubMed2006

Cloning, expression and functional study of translation elongation factor 2 (EF-2) in zebrafish.

We have identified translation elongation factor 2 (EF-2) in zebrafish (GenBank Accession No. AAQ91234). Analysis of the DNA sequence of zebrafish EF-2 shows that the 2826 bp cDNA spans an open reading frame between nucleotide 55 to 2631 and encodes a protein of 858 amino acids. Zebrafish EF-2 protein shares 92%, 93%, 93% and 92% identity with the corresponding amino acid sequence in human, mouse, Chinese hamster and Gallus EF-2, respectively. Whole-mount in situ hybridization showed that zebrafish EF-2 was a developmentally regulated gene and might play important roles during the early development of zebrafish embryos. Therefore, we further studied the function of EF-2 during early embryogenesis. Using morpholino antisense oligo knockdown assays, anti-MO injected embryos were found to display abnormal development. The yolk balls were larger than normal and the melanophores spreading on their bodies became fewer. Furthermore, their tails were incurvate and their lenses were much smaller than those of the normal embryos. However the EF-2 overexpression data showed that extra EF-2 protein had no obvious effect on zebrafish embryonic development.

Amino Acid Sequence↗
PubMed2006

[Transcription factor activity profile of human hepatocellular carcinoma cell lines with different metastatic potentials].

OBJECTIVES: To examine the activities of transcription factors (TFs) in human hepatocellular carcinoma (HCC) cell lines with different metastatic potentials, so as to identify the TFs associated with HCC metastasis. METHODS: Transcription factor activity profile of Hep3B, MHCC97L and MHCC97H, three HCC cell lines with different metastatic potentials, were examined using protein/DNA array. Electrophoretic mobility shift assays (EMSA) and Western blot were used to confirm the results obtained by protein/DNA array. RESULTS: From a total of 345 screened TFs, 7 activity differential TFs were found, of which 5 showed increased activity, including p53, hypoxia inducible factor-1 alpha (HIF-1alpha), signal transducer and activator of transcription 3 (Stat3) and Sp1, and 2 showed decreased activity including Rb and Smad3. CONCLUSION: The abnormal functioning of transcription factors is closely associated with HCC metastasis. Our present findings could be of help in expanding our understanding of the mechanism of HCC metastasis and identify new predictive biomarkers and therapeutic targets.

Carcinoma, Hepatocellular↗
PubMed2006

[Role of alpha-adrenergic receptors in vascular hyperreactivity in rats with high level spinal injury].

OBJECTIVE: To explore the vascular reactivity of abdominal aorta to agonists of alpha-adrenergic receptors in rat with high level transection of the spinal cord, and to quantify the expression of alpha-AR mRNA subtypes, in order to investigate relationship between alpha-AR and hyperreactivity of abdominal aorta. METHODS: Four weeks after transection of the spinal cord at the level of 4th thoracic vertebra, the rats were sacrificed, and abdominal aorta rings were adopted to assay sensitivity to phenylephrine and clonidine with isolated organ perfusion system. Alpha(1A)-AR, alpha(1B)-AR, alpha(1D)-AR, alpha(2A)-AR, alpha(2B)-AR, alpha(2C)-AR mRNA expressions were quantified by real time polymerase chain reaction (PCR). RESULTS: Compared with abdominal aorta, of rat with sham operation, reactivity of aorta of rat after transection of spinal cord to clonidine was significantly higher (P<0.05 or P<0.01), but difference of vascular reactivity to phenylephrine between them was not significant (P>0.05). Expressions of alpha(1A)-AR mRNA, alpha(1D)-AR mRNA, alpha(2A)-AR mRNA, alpha(2B)-AR mRNA, alpha(2C)-AR mRNA were significantly higher (P<0.05 or P<0.01), while the expression of alpha(1B)-AR mRNA did not vary significantly. CONCLUSION: Vascular hyperreactivity to agonist of alpha(2)-AR may be the mechanism of hyperreactivity of abdominal aorta in rat after transection of spinal cord. Although alpha(1)-AR mRNA expression is higher in aorta of rat with spinal cord injury, vascular hyperreactivity is not the result of upregulation of alpha(1)-AR sensitivity.

Adrenergic alpha-Agonists↗
PubMed2006

[Reconstructing the JAK/STATs signal pathway restored the anti-proliferative response of MHCC97 on interferon alpha].

OBJECTIVE: To elucidate the roles of JAK/STATs signal pathway on anti-proliferative effects induced by IFN-alpha in MHCC97. METHODS: An IRF9 expression vector was transfected into MHCC97 with Dosper. The expression of IRF9, cycle regulating proteins and the forming of ISGF3 complex were detected using Western blot and EMSA, respectively. Cell proliferation and distribution were monitored using MTT and flow cytometry. RESULTS: High expression of IRF9 restored the anti-proliferative response of MHCC97 on IFN-alpha treatment and delayed the cell transition from S phase to G2 phase induced by IFN-alpha. CONCLUSION: The integrity and functions of JAK/STATs signal pathway played an important role in mediating the anti-proliferative effects of IFN-alpha in MHCC97.

Carcinoma, Hepatocellular↗
PubMed2006

[Relationship between polymorphisms of vitamin D receptor gene and familial aggregation of HBsAg carriers].

OBJECTIVE: To determine whether -Taq I T/C and -Fok I C/T polymorphisms of vitamin D receptor (VDR) gene are associated with the familial aggregation of hepatitis B virus (HBV) infection. METHODS: Based on a population-based case-control family design, 288 family members from 27 case families and 230 family members from 27 control families were recruited. VDR gene polymorphisms were analyzed. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of VDR-Taq I TT genotype in the case families was significantly higher than that in the control families (P < 0.05) , however, the frequency of VDR-Fok I CC genotype in the case families was significantly higher than that in the control families (P < 0.05). The frequency of family members carriying Taq I T-Fok I C haplotype in the case families was significantly higher than that in the control families (OR = 1.67, P < 0.05), however, the frequency of family members carrying Taq I C-Fok I T haplotype in the case families was significantly lower than that in the control families (OR = 0. 24, P < 0.05). The similar results were found in the familial biological kinship relatives with any HBV-infected makers. CONCLUSION: VDR-Taq I and -Fok I gene polymorphisms are likely to play a substantial role in HBsAg familial aggregation.

Case-Control Studies↗
PubMed2005

Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential.

PURPOSE: Little information is available on the heterogeneity of the vascular endothelium in hepatocellular carcinoma. The aim of this study was to identify the differentially expressed genes in tumor endothelial cells from highly metastatic hepatocellular carcinoma. EXPERIMENTAL DESIGN: Magnetic beads conjugated with anti-CD31 antibody were used to isolate vascular endothelial cells from hepatocellular carcinoma xenografts with different metastatic potentials in nude mice. Gene expression profiles for different endothelial cells were compared by use of cDNA microarray. The up-regulated gene was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry. RESULTS: cDNA microarray analysis revealed differential expression patterns in seven genes consistently presented in endothelial cells isolated from hepatocellular carcinoma with different metastatic potentials. Overexpression of platelet-derived growth factor receptor alpha was found only in the endothelium of highly metastatic hepatocellular carcinoma, which was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry. Oral administration of STI571 (imatinib mesylate or Glivec), a protein tyrosine kinase inhibitor of platelet-derived growth factor receptor, combined with s.c. injection of IFN-alpha not only effectively reduced tumor weight (by 81.8%) and microvessel density (by 70.2%) but also inhibited lung metastasis (by 100%). Furthermore, immunohistochemical analysis of platelet-derived growth factor receptor alpha in human hepatocellular carcinoma tissues revealed its correlation with postoperative recurrence, especially in patients without microvessel invasion. CONCLUSIONS: The gene expression of hepatocellular carcinoma vascular endothelium is different between tumors with different metastatic potential. Platelet-derived growth factor receptor alpha, which is overexpressed in endothelium of highly metastatic hepatocellular carcinoma, may serve as a biomarker for predicting metastasis and a therapeutic target for highly metastatic hepatocellular carcinoma.

Animals↗
PubMed2005

Modulation of gene expression in MHCC97 cells by interferon alpha.

AIM: To elucidate the molecular mechanisms of the inhibitory effects of IFN-alpha on tumor growth and metastasis in MHCC97 xenografts. METHODS: Three thousand international units per milliliter of IFN-alpha-treated and -untreated MHCC97 cells were enrolled for gene expression analysis using cDNA microarray. The mRNA levels of several differentially expressed genes in cDNA microarray were further identified by Northern blot and RT-PCR. RESULTS: A total of 190 differentially expressed genes including 151 IFN-alpha-repressed and 39-stimulated genes or expressed sequence tags from 8,464 known human genes were found to be regulated by IFN-alpha in MHCC97. With a few exceptions, mRNA levels of the selected genes in RT-PCR and Northern blot were in good agreement with those in cDNA microarray. CONCLUSION: IFN-alpha might exert its complicated anti-tumor effects on MHCC97 xenografts by regulating the expression of functional genes involved in cell metabolism, proliferation, morphogenesis, angiogenesis, and signaling.

Carcinoma, Hepatocellular↗