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Biomedical subjects

Wei Cao

Publications and source records attributed to Wei Cao.

At least 19 recordsLinked to original sources
PubMed2006

The ortho hydroxy-amino group: another choice for synthesizing novel antioxidants.

Four ortho hydroxy-amino derivatives have been designed based on the structures of flavonoids to explore the effect of the ortho hydroxy-amino group on the antioxidant properties of molecules, and their bond dissociation enthalpies (BDE), ionization potentials (IP), the highest occupied molecular orbitals (HOMO), and spin densities have been calculated. The results reveal that the ortho hydroxy-amino group plays an important role in promoting the antioxidant properties of molecules because of its lowering effect on BDE, IP, and spin density. The derivatives with ortho hydroxy-amino group show stronger antioxidant activity than the derivatives with mono hydroxy or ortho dihydroxy group. Thus, the ortho hydroxy-amino group can be used as another potential functional group to synthesize novel antioxidants as guessed.

Amino Acids↗
PubMed2006

Determination of AKF-PD in whole blood of rat by HPLC-UV.

An HPLC-UV method was developed and validated for the determination of AKF-PD in whole blood of rat. Phenacetin was chosen as the internal standard, and the separation was achieved on a C18 column with methanol and 0.02 M phosphate buffer (pH 3.2) as mobile phase. The obtained calibration graphs were linear (r = 0.9999, n = 9) in the range of 0.203-52.0 microg ml(-1). The low limit of quantitation was 0.203 microg ml(-1). This method can be used to study the pharmacokinetics of AKF-PD in rat.

Animals↗
PubMed2006

Polymorphism of Xeroderma Pigmentosum group G and the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus.

We investigated the effects of XPG His1104Asp polymorphism (rs17655) on the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus (SCCOLE). This population-based case-control study involves 611 new cases of lung cancer, 601 new cases of oropharyngeal, laryngeal and esophageal cancers, and 1,040 cancer-free controls. The XPG polymorphism was assayed by PCR-RFLP method for 497 lung cancer cases, 443 cases of oropharyngeal, laryngeal and esophageal cancers and 912 controls. Binary and polytomous unconditional logistic regression models were fitted to assess the main effects and the effect modifications between the polymorphism and environmental exposures. With the adjustment for potential confounders, the XPG Asp1104Asp genotype was inversely associated with lung cancer (odds ratio [OR] = 0.62, 95% confidence limits [CL] = 0.38, 1.0) and SCCOLE (OR = 0.47, 95% CL = 0.27, 0.82), with the combined His1104His and His1104Asp genotypes as the referent. With subjects having genotype Asp1104Asp and no tobacco smoking exposure as the common referent, the ORs on lung cancer were 13 (95% CL = 4.4, 37) for heavy tobacco smoking (>20 pack-years), 1.9 (95% CL = 0.78, 4.5) for having at least one copy of 1104His, and 23 (95% CL = 9.5, 56) for the joint effect, respectively. Compared to non-smokers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy smokers (>20 pack-years) having at least one copy of 1104His was 8.0 (95% CL = 2.7, 24). Similarly, compared to non-drinkers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy drinkers (> or =3 drinks/day) with at least one copy of 1104His was 10 (95% CL = 2.7, 38). In conclusion, our study suggests that the XPG Asp1104Asp genotype may be associated with decreased susceptibility to lung cancer and SCCOLE.

Adenocarcinoma↗
PubMed2006

A combined treatment TNF-alpha/doxorubicin alleviates the resistance of MCF-7/Adr cells to cytotoxic treatment.

The efficiency of anticancer therapy is often restricted by the development of drug resistance. Here, we report that the doxorubicin (DOX)-resistant MCF-7/Adr cells were more resistant to DOX-treatment than MCF-7 cells. However, an alternative treatment of DOX/TNF-alpha enhanced the cytotoxic effect in multidrug resistant MCF-7/Adr cell line. Treatment of cells with TNF-alpha following doxorubicin (DOX) resulted in a decrease of the activated Rel A/p65 in nuclei. Histone deacetylase 1 (HDAC1) was found to interact with Rel A/p65 in the complex, suggesting that HDAC1 is involved in mediating nuclear export of Rel A/p65. The combined treatment of TNF-alpha/DOX also resulted in a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis-1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma x gene (Bcl-xL), leading to efficient induction of caspase-8 cleavage and cell death. In previous work, we demonstrated that TNF-alpha promotes DOX-induced cell death and anti-cancer effect through downregulation of p21 in p53-deficient tumor cells. Thus, we proposed that alternative administration of TNF-alpha and DOX may be a new and efficient therapeutic strategy for patients that develop resistance to cytotoxic treatment.

Antibiotics, Antineoplastic↗
PubMed2006

Human plasmacytoid predendritic cells activate NK cells through glucocorticoid-induced tumor necrosis factor receptor-ligand (GITRL).

Plasmacytoid dendritic cell precursors (pDCs) are professional type I interferon-producing cells, a critical cell type in regulating innate and adaptive immune responses. By microarray gene expression analysis, we found that pDCs activated by virus or CpG-ODN preferentially express the ligand for the glucocorticoid-induced tumor necrosis factor receptor (GITRL), which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis. Using the same approaches, we found GITR is expressed by activated natural killer (NK) cells and T cells. We show that pDCs activated by CpG-ODN promote NK cell cytotoxicity and interferon (IFN)-gamma production through type I IFNs and GITRL. Using a GITRL-transfected cell line, we further demonstrate that GITRL promotes NK cell cytotoxicity and IFN-gamma production in synergy with interleukin-2 (IL-2), IFN-alpha, and NKG2D triggering. We also demonstrated that pDCs localized in close contact to NK cells in T-cell areas of the tonsils, and a subpopulation of the pDCs expressed GITRL. This study reveals a novel function of GITR/GITRL in pDC-mediated coactivation of NK cells.

Base Sequence↗
PubMed2006

17beta-estradiol (betaE2) protects human retinal Müller cell against oxidative stress in vitro: evaluation of its effects on gene expression by cDNA microarray.

17beta-estradiol (betaE(2)) is an effective neuroprotectant against hydrogen peroxide (H(2)O(2))-induced retinal neuronal cell death and light-induced photoreceptor degeneration. Müller cells are the principal macroglia responsible for supporting retinal neuronal survival, information processing and removing metabolic waste. However, the role of betaE(2) on human Müller cells is unclear. In this study, the effects of betaE(2) on human Müller cell survival and gene expression were examined. Our data revealed that betaE(2) is able to increase human Müller cell viability after exposure to H(2)O(2) through inhibition of apoptosis. Microarray analysis revealed significant changes in the expression of 69 genes (total of 21,324 genes screened) in cultured human Müller cells 6 h after betaE(2) treatment. Four of the betaE(2)-responsive genes [thrombospondin 1 (TSP1), mitogen-activated protein kinase kinase kinase 3 (MAP3K3), large conductance calcium-activated potassium channel beta2 subunit (KCNMB2), and SRY (sex-determining region Y)-box 11 (SOX11)] were validated by both real-time qRT-PCR and semi-quantitative RT-PCR. Interestingly, exposure of human Müller cells to betaE(2) increased pigment epithelium-derived factor (PEDF) gene expression as measured by both RT-PCR and real time qRT-PCR. Our data demonstrate, for the first time, that betaE(2) protects cultured human Müller cells against H(2)O(2)-induced cell death through the inhibition of apoptosis. This protective effect may operate through regulation of genes, such as TSP1, MAP3K3, SOX11, TSP1, and PEDF, and may in turn exert an important role in protecting retinal neurons.

Antioxidants↗
PubMed2006

Neuroprotection of insulin against oxidative stress-induced apoptosis in cultured retinal neurons: involvement of phosphoinositide 3-kinase/Akt signal pathway.

In order to investigate the neuroprotection of insulin in retinal neurons, we used retinal neuronal culture as a model system to study the protective effects of insulin against H2O2-induced cytotoxicity and apoptotic death. Primary retinal neuronal cultures were grown from retinas of 0-2-day old Sprague-Dawley rats. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Apoptotic cell death was evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling assay, and by DNA laddering analysis. Phosphoinositide 3-kinase (PI3K) activity was measured using phosphoinositide 4,5-bisphophate and [gamma-32P]ATP as substrate. Western blot analysis with anti-phospho-Akt (pS473) antibody was performed to examine the level of phosphorylated Akt. We observed that treatment with 100 microM H2O2 for 24 h significantly decreased cell viability and induced apoptotic death of retinal neurons, and that pretreatment with 10 nM insulin significantly inhibited or attenuated H2O2-induced cytotoxicity and apoptosis. Pretreatment with LY294002, a specific PI3K inhibitor, abolished the cytoprotective effect of insulin. Insulin also strongly activated both PI3K and the downstream effector Akt. These results suggest that insulin protects retinal neurons from oxidative stress-induced apoptosis and that the PI3K/Akt signal pathway is involved in insulin-mediated retinal neuroprotection.

Animals↗
PubMed2005

Attosecond and zeptosecond x-ray pulses via nonlinear Thomson backscattering.

Nonlinear Thomson backscattering of an intense circularly polarized laser by a counterpropagating energetic electron is investigated. The results show that in the scattering of a non-tightly-focused laser pulse with an intensity around 10(19) W/cm2 and a pulse duration of full width at half maximum by a counterpropagating electron with an initial energy of 10 MeV, a crescent-shaped pulse with a pulse duration of 469 s and the photon energy ranging from 230 eV to 2.5 keV is generated in the backward direction. It is shown that the radiated pulse shape and monochromaticity can be modified by changing the laser beam waist, while in the case of a tightly focused laser field, a single peak pulse with a shorter duration and better monochromaticity can be obtained. With increase of the electron initial energy, the peak power of the radiated pulse increases and the pulse duration decreases. An isolated powerful zeptosecond pulse with a peak power of about and photon energy up to several MeV can be obtained with a electron.

Journal Article↗
PubMed2005

Tobacco smoking, GSTP1 polymorphism, and bladder carcinoma.

BACKGROUND: Although cigarette smoking is considered a major risk factor for bladder carcinoma, little is known about the interaction between metabolic genes such as glutathione-S-transferase P1 and tobacco smoking in this process. GSTP1 may play a role in detoxification of tobacco-related carcinogens. METHODS: In this case-control study of 145 cases with bladder carcinoma (male:female = 7.5:1) and 170 noncancer controls (male:female = 3.7:1), the relation between genetic polymorphisms of GSTP1 and susceptibility to bladder carcinoma was investigated and the gene-environment interaction between tobacco smoking and GSTP1 polymorphism was evaluated. Epidemiological data were collected for all cases and controls by a standard questionnaire. Polymorphisms of GSTP1 were measured by polymerase chain reaction-restriction fragment length polymorphism. The logistic regression model in SAS was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Cigarette smoking was confirmed as a risk factor of bladder carcinoma with an OR of 3.1 (95% CI: 1.7-5.9) after controlling for potential confounding factors. The OR for pack-years of smoking as a continuous variable was 2.4 (95% CI: 2.0-2.8). The ORs were 7.6 (95% CI: 1.18-49.51) for isoleucine/valine (Ile/Val) and 6.5 (95% CI: 1.01-41.56) for Ile/Ile when the homozygous Val/Val was considered as comparison group after adjusting for age, gender, race, and education. The adjusted OR for interaction between smoking and the GSTP1 (any Ile genotype) was 11.42 (95% CI: 0.53-248.15). CONCLUSIONS: The results indicate that the Ile 105 allele is associated with an increased risk of bladder carcinoma and suggest that individuals who smoke and possess the Ile allele might be at increased risk for bladder carcinoma.

Alcohol Drinking↗
PubMed2005

HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor.

We previously described envelope glycoproteins of an HIV-1 isolate adapted in vitro for growth in microglia that acquired a highly fusogenic phenotype and lower CD4 dependence, as well as resistance to inhibition by anti-CD4 antibodies. Here, we investigated whether similar phenotypic changes are present in vivo. Envelope clones from the brain and spleen of an HIV-1-infected individual with neurological disease were amplified, cloned, and sequenced. Phylogenetic analysis demonstrated clustering of sequences according to the tissue of origin, as expected. Functional clones were then used in cell-to-cell fusion assays to test for CD4 and co-receptor utilization and for sensitivity to various antibodies and inhibitors. Both brain- and spleen-derived envelope clones mediated fusion in cells expressing both CD4 and CCR5 and brain envelopes also used CCR3 as co-receptor. We found that the brain envelopes had a lower CD4 dependence, since they efficiently mediated fusion in the presence of low levels of CD4 on the target cell membrane, and they were significantly more resistant to blocking by anti-CD4 antibodies than the spleen-derived envelopes. In contrast, we observed no difference in sensitivity to the CCR5 antagonist TAK-779. However, brain-derived envelopes were significantly more resistant than those from spleen to the fusion inhibitor T-1249 and concurrently showed slightly greater fusogenicity. Our results suggest an increased affinity for CD4 of brain-derived envelopes that may have originated from in vivo adaptation to replication in microglial cells. Interestingly, we note the presence of envelopes more resistant to a fusion inhibitor in the brain of an untreated, HIV-1-infected individual.

AIDS Dementia Complex↗
PubMed2005

Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells.

Recent studies suggest plasmacytoid predendritic cells (pDCs) and myeloid dendritic cells (mDCs) have the functional plasticity to produce similar amounts of type 1 interferons (IFNs) and interleukin-12 (IL-12), challenging the concept and existence of DC subsets with distinct function. In this study, we demonstrate that previous studies showed human pDCs produce large amounts of IL-12 because of contaminating mDCs. Using highly purified human DC subsets, we found that although pDCs make 300 times more IFN-alpha than mDCs and mDCs make 13 times more IL-12 p70 than pDCs in response to all the toll-like receptor ligands and CD40 ligands, pDCs rapidly make large amounts of IFN-alpha within the first 12 hours of activation and become refractory to further stimulation. pDCs preferentially expressed the transcriptional factors critical for type 1 IFN, but not for IL-12 transcription, and they dedicated 60% of new transcriptional activity to make 19 type 1 IFN subtypes. This study provides formal proof that the plasticity of DC subsets is limited and that different DC subsets evolve to perform distinct functions in linking innate and adaptive immunity.

CD40 Ligand↗
PubMed2005

TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand.

We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4(+) T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-alpha (TNF-alpha), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP-induced OX40L on DCs was required for triggering naive CD4(+) T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-alpha, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12-induced Th1 cell inflammation by promoting TNF-alpha, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10-producing regulatory Th cell responses into TNF-alpha-producing inflammatory Th cell responses.

Adult↗
PubMed2005

Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population.

The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] = 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI = 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI = 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested.

Adult↗
PubMed2005

Optimization of culture on the overproduction of TRAIL in high-cell-density culture by recombinant Escherichia coli.

Different nutrient-feeding cultures were carried out in producing recombinant protein of truncated tumor necrosis factor related apoptosis-inducing ligand (TRAIL) (114-281 amino acids of TRAIL) in Escherichia coli strain C600/pBV-TRAIL. The effects of preinduction specific growth rate, postinduction carbon source (glucose and glycerol), and feeding strategies were investigated. The higher preinduction specific growth rate (mu = 0.22 h(-1)) contributed to the increase in the TRAIL production, at which TRAIL was accumulated in bacterial cells as 7.2% of total cellular protein, corresponding to 1.99 g l(-1) in contrast with 5.1% (1.29 g l(-1)) at preinduction specific growth rate (mu = 0.1 h(-1)) during high-cell-density culture. Glycerol was superior to glucose as the postinduction carbon source for TRAIL production. Under similar culture conditions, the final concentration of TRAIL was produced 1.59-fold more when glycerol was used as postinduction carbon source than when glucose was used. At the same time, the results showed that it is efficient to adopt the pH-stat feeding strategy at postinduction for the overproduction of TRAIL. The TRAIL production was increased up to 4.51 g l(-1), approximately 16.1% of total cellular protein. The mechanisms behind the preinduction specific growth rate effect on the expression level may be ascribed to the leakage secretion of acetate.

Acetates↗
PubMed2005

Bright cyclic light accelerates photoreceptor cell degeneration in tubby mice.

Photoreceptor cell death is an irreversible, pathologic event in many blinding retinal diseases including retinitis pigmentosa, age-related macular disease, and retinal detachment. Light exposure can exacerbate a variety of human retinal diseases by increasing the rate of photoreceptor cell death. In the present study, we characterize the kinetics of photoreceptor cell death in Tubby (homozygous tub/tub, which have inherited, progressive retinal degeneration) mice born and raised in a bright cyclic light environment. Our data show that raising tub/tub mice in a bright cyclic light environment induces rapid loss of photoreceptors. This effect can be slowed, but not prevented, by raising animals in constant darkness, which suggests the involvement of phototransduction in the accelerated death of photoreceptors in this animal. We further demonstrated that the activities of cytosolic cytochrome c and caspases-3 and -9 were significantly increased in the retinas of tub/tub mice. Raising animals in darkness significantly reduced the increased activities of caspases-3 and -9, as well as cytosolic cytochrome c. We also observed that rhodopsin, a phototransduction protein, is not restricted to the rod outer segment, but is distributed throughout the rod cell, including the inner segments, cell bodies, and synapses. In addition, the light-dependent translocation and compartmentalization of arrestin and transducin are affected by the tubby mutation. Our results support the interpretation that problems in protein trafficking in the photoreceptors of the tub/tub mouse may contribute to retinal degeneration.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Simultaneous determination of 6beta-hydroxycortisol and cortisol in human urine and plasma by liquid chromatography with ultraviolet absorbance detection for phenotyping the CYP3A activity.

This study describes an high-performance liquid chromatographic (HPLC)-UV method for the simultaneous determination of 6beta-hydroxycortisol (6beta-OHF) and cortisol (F) in human urine and plasma. The within-day relative standard deviation of the three concentrations for both analytes was less than 6.2%. Accuracy determined at three concentrations ranged between 95 and 107%. The extraction recoveries were 64.1+/-4.3 and 88.1+/-2.4% at three concentrations for 6beta-OHF and F in urine, respectively. The extraction recoveries were 88.7+/-1.4% at three concentrations for F in plasma. This is the first HPLC method that can simultaneously determine 6beta-OHF and F in human urine and plasma and is suitable for routine assessment of the CYP3A activity expressed as 6beta-hydroxylation clearance.

Adult↗
PubMed2005

The recognition pattern of gammadelta T cells.

The main function of immune system is to recognize and respond to foreign antigens. During the course of evolution, the body has successfully developed four kinds of mechanisms to recognize antigens, including pattern recognition mediated by macrophages, missing-self and induced-self recognition for NK cells, antigen specific recognition for alphabeta T cells and B cells and "broad-spectrum specific" recognition for gammadelta T cells. The three formers have made great progress these years. However, details of antigen recognition by gammadelta T cells are still mysterious. Gammadelta T cells, a class of T cells only existing in primates, differ from alphabeta T cells in TCR diversity, the structure of TCR-CD3 complex, the tissue distribution, the antigens that they recognize and the way involved in recognition. Here, we shed light on the recognition mechanism of gammadelta T cells against several known antigens and discuss the possible response pattern along the research historical process. We put forward a recognition hypothesis for gammadelta TCR that is conformational recognition based on germline encoded recognition. The key germline encoded amino acids dominate the "putative binding box" and are responsible for recognition. Meanwhile, after gammadelta T cells are activated, several other molecules such as CD69, CD16, 2B4, NKG2D also participate in inducing cytotoxicity of activated gammadelta T cells. Obviously, the illustration of recognition mechanism for gammadelta T cells will help to comprehensively understand the whole immune system and design the higher effective multi-epitope vaccines for tumor and infection immunity.

Animals↗