Biomedical subjects

Wei Cao

Publications and source records attributed to Wei Cao.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Inhibition of 1,3,8-trihydroxy-5-methoxyxanthone on cytochrome P450s].

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION: TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.

Cytochrome P-450 Enzyme System↗

PubMed2006

[Clinical value of radionuclide imaging in differentiate the origin of cervical mass].

OBJECTIVE: To study the clinical value of thyroid imaging in differentiate the origin cervical mass. METHOD: Sixty-nine patients with cervical mass were subjected to 99mTc-pertechnetate imaging. 99Tc-MIBI hot spot imaging and perfusion imaging were performed in some of patients with cold or cool nodules. The findings of thyroid imaging were compared with follow up and histopathologic results. RESULT: Thirty-three of 69 patients were found with thyroid nodules, 36 patients mass were outside thyroid. Twelve of 33 thyroid nodules were found to be subacute thyroiditis. Two cases regarded as thyroglossal duct cyst were found to be ectopic thyroid glands. Twenty-seven of 36 masses out side thyroid were thyroglossal duct cysts. CONCLUSION: 99m Tc-pertechnetate imaging, 99mTc-MIBI hot spot imaging and perfusion imaging are useful to differentiate the origin of cervical mass, and differentiate ectopic thyroid from thyroglossal duct cyst.

Adolescent↗

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↗

PubMed2005

Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus.

Hassall's corpuscles-first described in the human thymus over 150 years ago-are groups of epithelial cells within the thymic medulla. The physical nature of these structures differs between mammalian species. Although Hassall's corpuscles have been proposed to act in both the removal of apoptotic thymocytes and the maturation of developing thymocytes within the thymus, the function of Hassall's corpuscles has remained an enigma. Here we report that human Hassall's corpuscles express thymic stromal lymphopoietin (TSLP). Human TSLP activates thymic CD11c-positive dendritic cells to express high levels of CD80 and CD86. These TSLP-conditioned dendritic cells are then able to induce the proliferation and differentiation of CD4(+)CD8(-)CD25(-) thymic T cells into CD4(+)CD25(+)FOXP3(+) (forkhead box P3) regulatory T cells. This induction depends on peptide-major histocompatibility complex class II interactions, and the presence of CD80 and CD86, as well as interleukin 2. Immunohistochemistry studies reveal that CD25(+)CTLA4(+) (cytotoxic T-lymphocyte-associated protein 4) regulatory T cells associate in the thymic medulla with activated or mature dendritic cells and TSLP-expressing Hassall's corpuscles. These findings suggest that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus.

Adult↗

PubMed2005

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers.

Although radiation is considered a risk factor for thyroid cancer, the potential relationship between radiation therapy and the risk of second primary cancer among patients with first primary thyroid cancer has not been evaluated. We identified 26,639 patients with first primary thyroid cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2000. Information on radiation therapy as well as second primary cancers was recorded in SEER. The proportional hazards model was utilized to estimate adjusted risk ratios (RRs) and their 95% confidence intervals (CIs) to assess the potential association between radiation therapy for thyroid cancer and the risk of second primary cancers. With 270,674.33 person-years of follow-up, 1,896 (7.1%) of the 26,639 patients with first primary thyroid cancer developed second primary cancers. Among the second primaries, 35 occurred in the thyroid. No obvious association was observed between radiation therapy and the overall risk of second primary cancer after ten years of follow-up (RR=1.07, 95% CI=0.88-1.30). However, an increased risk was seen for several cancers, including upper digestive system cancers (RR=1.66, 95% CI=1.07-2.57) and myeloid malignancies (RR=3.26, 95% CI=1.39-7.67). Radiation therapy was associated with reduced second cancer risks for thyroid cancer (RR=0.18, 95% CI=0.04-0.76). Beam radiation might be important to the digestive system, radioactive implants might be associated with the male genital system, radioisotopes might have an effect on myeloid malignancies, and combined beam radiation with radioactive implants or radioisotopes might be related to the increased risk of respiratory system cancers. This study suggests that radiation therapy for patients with first primary thyroid cancer might be associated with an increased risk of developing a second primary cancer in the upper digestive system and second primary myeloid malignancies. Radiation therapy for adult patients with thyroid cancer might be associated with a reduced risk of second primary thyroid cancer.

Aged↗

PubMed2005

Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma.

Glaucoma is a common cause of blindness affecting at least 66 million people worldwide. Pigmentary glaucoma is one of the most common forms of secondary glaucoma, and its pathogenesis remains unclear. Interleukin-18 (IL-18) is an important regulator of innate and acquired immune responses and plays an important role in inflammatory/autoimmunity diseases. Using the DBA/2J mouse as an animal model of human pigmentary glaucoma, we demonstrated for the first time that the expression of the IL-18 protein and gene in the iris/ciliary body and level of IL-18 protein in the aqueous humor of DBA/2J mice are dramatically increased with age. This increase precedes the onset of clinical evidence of pigmentary glaucoma, implying a pathogenic role of inflammation/immunity in this disease. We also observed that activated NF-kappaB and phosphorylated MAPK are increased in the iris/ciliary body of DBA/2J mice, suggesting that both signaling pathways may be involved in IL-18 mediated pathogenesis of pigmentary glaucoma in the eyes of DBA/2J mice. In addition, matrix metalloproteinase-2 (MMP-2) expression in the iris/ciliary body and the activity of MMP-2 in the aqueous humor are increased whereas tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression in the iris/ciliary body is decreased, indicating that the degradation process is involved in this mouse model of pigmentary glaucoma. Furthermore, the expressions of apoptosis-related genes, caspase-8, Fas, FADD, FAP, and FAF, and the activity of caspase-3 are increased in the iris/ciliary body of DBA/2J mice. Elucidation of biochemical and molecular mechanisms of IL-18 participation in the pathogenesis of pigmentary glaucoma should provide approaches for developing improved and targeted treatments to ameliorate this blinding disease. The possibility that altered IL-18 expression in the eye of DBA/2J mice initiates and/or amplifies the pathogenesis of pigmentary glaucoma requires further investigation.

Aging↗

PubMed2005

TNF-alpha promotes Doxorubicin-induced cell apoptosis and anti-cancer effect through downregulation of p21 in p53-deficient tumor cells.

p53 is a key regulator in cell apoptosis, and cancer cells deficient in p53 expression fail to respond to chemotherapy. Here we show that effective Doxorubicin (DOX)-induced apoptosis is p53-dependent. However, an alternative treatment of DOX/TNF-alpha/DOX restored sensitivity of p53-deficient cells to DOX-induced apoptosis. Treatment of cells with TNF-alpha resulted in a decrease of p21 (waf1/cip1/sdi1) expression following second dose of DOX. In previous work, we demonstrated that p21 suppressed DOX-induced apoptosis via its (cyclin-dependent kinase) CDK-binding and CDK-inhibitory activity. Thus, we propose that TNF-alpha enhances the anti-cancer effect of DOX through suppressing the anti-apoptotic activity of p21, and that a combined treatment TNF-alpha/Dox is an effective chemotherapeutic strategy for p53-deficient cancers.

Antineoplastic Agents↗

PubMed2005

Identification of mouse retinal genes differentially regulated by dim and bright cyclic light rearing.

Bright cyclic light rearing protects BALB/c mice from light-induced photoreceptor apoptosis compared to dim cyclic light rearing. We used a microarray approach to search for putative neuroprotection genes that were up- or down-regulated under these environmental conditions. Retinal protection by bright cyclic rearing was determined by quantitative histology and DNA fragmentation analysis. Total RNA was isolated from 5-week-old mice raised in bright (400 lux) or dim (5 lux) cyclic light and prepared for analysis on microarrays produced using a 70-mer oligonucleotide library that represented 16,463 mouse genes. Genes of interest were identified using statistically robust bioinformatics analysis methods that were developed in-house. Changes in some genes were confirmed with quantitative real time PCR. We found that 952 genes were up- or down-regulated by bright cyclic light rearing compared to dim cyclic light rearing. One hundred and eighty-four of them, having >/=2-fold differences, were grouped into 13 categories, and selected for further consideration. Eleven up-regulated and two down-regulated genes were confirmed by semi-quantitative PCR. Five neuroprotection-associated genes were up-regulated by bright cyclic light rearing as confirmed by real-time PCR. The human orthologue chromosomal location of 22 differentially expressed genes map to known retinal degeneration loci. Using PathwayAssist software, we modeled the pathway networks of up- and down-regulated genes that are functionally related to the retina. We identified retinal genes that are differentially regulated by environmental light history. Those that directly affect cell processes such as survival, apoptosis, and transcription are likely play a pivotal role in the regulation of retinal neuroprotection against light-induced photoreceptor apoptosis.

Adaptation, Ocular↗

PubMed2005

Production and purification of a novel antibiotic peptide, adenoregulin, from a recombinant Escherichia coli.

Adenoregulin is a member of dermaseptin family which are vertebrate antibiotic peptides having lethal effects against a broad spectrum of bacteria, fungi and protozoa. The 99 bp adenoregulin gene was cloned in the expression vector pET32a and transformed into Escherichia coli BL21(DE3). In fed-batch cultivation of BL21(DE3)/pET32a-adr, an exponential feeding strategy was applied to gain 60 g dry cells l-1. The recombinant fusion protein Trx-ADR was expressed in a soluble form. The fusion protein was isolated by Ni2+-chelating chromatography, cleaved with CNBr and purified to homogeneity through reverse phase-HPLC and size exclusion-HPLC. The purified recombinant adenoregulin had antibacterial activity against Escherichia coli K12D31 with apparent Mr of 3.4 kDa, identical to the anticipated value.

Amphibian Proteins↗