Biomedical subjects

Wei Chen

Publications and source records attributed to Wei Chen.

At least 109 records · Page 6Linked to original sources

PubMed2006

Association of TNF-alpha polymorphism with susceptibility to and severity of non-small cell lung cancer.

BACKGROUND: Genetic polymorphisms in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene are involved in the regulation of expression levels and have been associated with various inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter region of the TNF-alpha gene (-308 G/A and -238 G/A) for their role in the susceptibility to and severity of non-small cell lung cancer (NSCLC), by means of an allelic association study. METHODS: Using a case-control study design, lung cancer patients (n = 202) and appropriate age- and sex-matched controls recruited from the health check-up unit (n = 205) were subjected to genotype analysis for these polymorphisms, using a high-throughput allelic discrimination method. RESULTS: Genotype was analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique with genomic DNA isolated from peripheral blood lymphocytes. Overall, the distribution of the genotype frequencies of TNF-alpha-308 A/G and -238 A/G were significantly different between the lung cancer patients and the healthy controls, and also different between patients with lung cancers of various stages (p < 0.0001). Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were seen for individuals with TNF-alpha-308 AA/GA genotypes against GG genotype (an OR of 3.75, 95% CI 2.38-5.92, p < 0.0001), and lower ORs were seen for individuals with TNF-alpha-238 AA/GA genotypes against GG genotype (an OR of 0.26, 95% CI 0.13-0.50, p < 0.0001). The patients carrying a homologous AA or heterologous GA genotype at TNF-308 (p = 0.017), or a homologous GG genotype at TNF-238 (p = 0.001), had a tendency to advanced disease. CONCLUSIONS: A significant association between the 308 G/A and 238 G/A polymorphisms in the promoter region of TNF-alpha and the susceptibility to lung cancer was demonstrated. Also, these two polymorphisms were associated with the severity of lung cancer. The -308 A allele has a promotive effect for lung cancer development and progression, whereas the -238 A allele has a protective function against lung cancers.

Adenocarcinoma↗

PubMed2006

Far-infrared characteristics of ZnS nanoparticles measured by terahertz time-domain spectroscopy.

The optical and dielectric properties of ZnS nanoparticles are studied by use of terahertz time-domain spectroscopy (THz-TDS) over the frequency range from 0.3 to 3.0 THz. The effective medium approach combined with the pseudo-harmonic model of the dielectric response, where nanoparticles are embedded in the host medium, provides a good fit on the experimental results. The extrapolation of the measured data indicates that the absorption is dominated by the transverse optical mode localized at 11.6+/-0.2 THz. Meanwhile, the low-frequency phonon resonance of ZnS nanoparticles is compared with the single-crystal ZnS. The THz-TDS clearly reveals the remarkable distinction in the low-frequency phonon resonances between ZnS nanoparticles and single-crystal ZnS. The results demonstrate that the acoustic phonons become confined in small-size nanoparticles.

Journal Article↗

PubMed2006

Characterization of solvated electrons in hydrogen cyanide clusters: (HCN)n- (n=3, 4).

Theoretical studies of the solvated electrons (HCN)n- (n=3, 4) reveal a variety of electron trapping possibilities in the (HCN)n (n=3, 4) clusters. Two isomers for (HCN)3- and four isomers for (HCN)4- are obtained at the MP2aug-cc-pVDZ+dBF (diffusive bond functions) level of theory. In view of vertical electron detachment energies (VDEs) at the CCSD(T) level, the excess electron always "prefers" locating in the center of the system, i.e., the isomer with higher coordination number shows larger VDE value. However, the most stable isomers of the solvated electron state (HCN)3- and (HCN)4- are found to be the linear Cinfinitynu and Dinfinityh structures, respectively, but not the fullyl symmetric structures which have the largest VDE values.

Journal Article↗

PubMed2006

Voltage dependence of the carrier-mediated ion transport.

With regards to the common features of carrier-mediated transport, voltage dependence was studied, using an asymmetric, six-state model. Our study shows that for an ion exchanger, transporting one kind of ion via exchange with another kind, the ion flux as a function of the membrane potential shows a sigmoidal curve with a shallow slope, saturation behavior, and possibly a negative slope. These features are mainly due to the transport of ions with charges of the same sign in the opposite direction. Membrane potential depolarization can facilitate only one transport and hinder another. As a result, the ion flux cannot increase dramatically and has an upper limitation because the exchanging rate depends on competition of the two inversely voltage-dependent transport processes. In contrast, for unidirectional ion transporters, the ion flux will monotonically increase as a function of the membrane potential. Both the maximum ion flux and the voltage sensitivity are much higher than those of the ion exchanger.

Carrier Proteins↗

PubMed2006

A novel selective progesterone receptor modulator asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells.

CONTEXT: Asoprisnil, a selective progesterone (P4) receptor (PR) modulator (SPRM) with mixed P4 agonist/antagonist activities, reduces uterine leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. The evidence from clinical studies suggests that asoprisnil may directly target the uterine leiomyomata. OBJECTIVE AND METHODS: The present study evaluated the effects of asoprisnil on cell proliferation, the expression of apoptosis-related proteins, and apoptosis in cultured human uterine leiomyoma cells and matched normal myometrial cells. PR-A and PR-B expression in the two types of cells was comparatively evaluated. Cell proliferation, proliferating cell nuclear antigen (PCNA)-positive rate, and TUNEL-positive rate were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, immunocytochemistry, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay, respectively. The expression of apoptosis-related proteins and PR was assessed by Western blot analysis. RESULTS: Compared with untreated cultures, asoprisnil decreased the number of viable cultured cells, the PCNA-positive rate, and PCNA protein expression in cultured leiomyoma cells. Asoprisnil increased the TUNEL-positive rate, cleaved caspase-3, and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase expression and decreased Bcl-2 protein expression in cultured leiomyoma cells. These effects were dose and time dependent. In cultured myometrial cells, however, asoprisnil did not affect cell proliferation and apoptosis. PR-B expression was elevated in cultured leiomyoma cells compared with cultured myometrial cells, whereas no differences in PR-A expression were noted between the two cell types. CONCLUSIONS: These results show that asoprisnil inhibits proliferation and induces apoptosis in cultured uterine leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells, suggesting a cell type-specific effect.

Apoptosis↗

PubMed2006

Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells.

BACKGROUND: Previously, it was demonstrated that phenoxodiol induces apoptosis in epithelial ovarian carcinoma (EOC) cells and that it is capable of sensitizing these cells to Fas-mediated apoptosis. The objectives of this study were to determine whether phenoxodiol can also act as chemosensitizer to chemotherapeutic agents and to characterize the molecular mechanism behind its sensitizing effect. METHODS: Ten EOC cell lines were used in this study. The effect of phenoxodiol on the inhibitory concentration 50% (IC50) of carboplatin, paclitaxel, and gemcitabine was determined by the CellTiter 96 Assay. The in vivo effect of combination treatments with phenoxodiol and the above-mentioned agents was determined in animal xenograft models. Apoptosis was measured using the Caspase-Glo Assay and the apoptotic cascade was characterized by Western blot analyses. RESULTS: The results showed that phenoxodiol is able to sensitize EOC cells to carboplatin, paclitaxel, and gemcitabine both in vitro and in vivo. In addition, it was demonstrated that phenoxodiol is capable of inducing apoptosis by: 1) the activation of the mitochondrial pathway through caspase-2 and Bid signaling, and 2) the proteasomal degradation of the anti-apoptotic protein XIAP. CONCLUSION: Understanding the components of the apoptotic pathway activated by phenoxodiol, which allows it to sensitize EOC cells to chemotherapeutic agents, will provide valuable information on the characteristic mode of action of a chemosensitizer. This will help in the identification of novel drugs and in the design of better strategies for combination therapy in patients with recurrent ovarian carcinoma.

Animals↗

PubMed2006

Nonlinear optical properties of alkalides Li+(calix[4]pyrrole)M- (M = Li, Na, and K): alkali anion atomic number dependence.

A new type of alkalide compound, Li+(calix[4]pyrrole)M- (M = Li, Na, and K), is presented in theory, which may be stable at room temperature. It has been shown by our calculations that the first hyperpolarizability (beta) is considerably large by means of the density functional theory method. The beta values are determined at the B3LYP/6-311++G level (for the alkali atoms the 6-311++G(3df) basis set is employed) as 8.9 x 103, 1.0 x 104, and 2.4 x 104 au for M = Li, Na, and K, respectively. These beta values are much larger than that of electride Li+(calix[4]pyrrole)e- (beta = 7.3 x 103 au) by a factor of 1.2 to 3.4. Comparing to the cryptand calix[4]pyrrole, the beta values of Li+(calix[4]pyrrole)M- are enhanced by 20-60 times. It is revealed, for the first time, that the beta value of alkalide compounds depends on the atomic number of the alkali anion, and it can be enhanced by choosing the akali anions with larger atomic numbers. The alkali anion in the alkalide compound decreases the transition energy and also increases the oscillator strength of the main transition, consequently the beta value is enhanced. This study proposes such a novel way to synthesize and design new NLO materials by using the alkali atom with a larger atomic number to create an anion in alkalide compounds.

Journal Article↗

PubMed2006

The 2beta2-2beta3 loop of anthrax protective antigen contains a dominant neutralizing epitope.

Anthrax toxin consists of three proteins, protective antigen (PA), lethal factor, and edema factor. PA is the major component in the current anthrax vaccine, but the antigenic epitopes on it are not well-defined. We generated a pool of toxin-neutralizing anti-PA monoclonal antibodies (MAbs) to analyze the neutralizing epitopes of PA. Nine toxin-neutralizing MAbs obtained were found bound to three different domains of PA respectively, among which three MAbs with the strongest toxin-neutralizing activity recognized the same epitope within domain 2. This epitope was fine mapped to the chymotrypsin-sensitive site, (312)SFFD(315), in the 2beta(2)-2beta(3) loop of PA, using phage-displayed random peptide libraries and mutation analysis. The result demonstrated for the first time that the 2beta(2)-2beta(3) loop, which is involved in the transition of PA oligomers from prepore to pore, contains a dominant neutralizing epitope. This work contributes to the immunological and functional analysis of PA and offers perspective for the development of a new epitope vaccine against anthrax.

Animals↗

PubMed2006

Effect of functional group (fluorine) of aromatic thiols on electron transfer at the molecule-metal interface.

Electron transfer at the molecule-metal interface of self-assembled monolayers of 1,1';4',1''-terphenyl-4''-thiol (BBB) and its partially fluorinated counterpart (BFF: p-thiophenyl-nonafluorobiphenyl) on Au(111) is investigated by core-hole clock spectroscopy. Ultrafast electron transfer at the BBB/Au(111) interface in the low-femtosecond regime (on the same time scale as the C 1s core-hole lifetime, approximately 6 fs) was observed. In contrast, for BFF/Au(111), the interface electron transfer was forbidden during the core-hole decay. This strongly suggests that fluorination of phenyl rings significantly enhances the localization of the excited electrons in the LUMO.

Journal Article↗

PubMed2006

Acanthamoeba keratitis: clinical characteristics and management.

OBJECTIVE: To review the clinical characteristics, treatment, and outcome of patients with Acanthamoeba keratitis (AK). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty consecutive patients with AK were referred to the Beijing Tongren Hospital, Capital University of Medical Science, China. METHODS: Retrospective analysis of medical records from 20 consecutive patients with AK between December 1, 1997 and March 30, 2003. Risk factors, laboratory investigations, clinical manifestations, treatments, and outcomes were analyzed. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the end of follow-up. RESULTS: Of the 20 patients presented in this series, 12 patients were students and 6 were farmers. Risk factors included contact lens wear (12/20) and trauma (6/20). Corneal ulceration, diffuse stromal infiltration, and ring infiltration were the main clinical manifestations. The diagnosis of all patients was based on the laboratory investigation. Smear and culture positive specimens were 19 of 20 and 12 of 20, respectively. Images of cysts were demonstrated with confocal microscopy in 4 patients. Treatment was combined instillation of chlorhexidine (0.02%), neomycin (0.5%), metronidazole (0.4%), and/or lesion cauterization with chlorhexidine (1%), and corneal lesion debridement. The mean duration of therapy was 70 days (range, 18-150 days). Nineteen lesions healed with scar formation. The BCVA was better or equal to 20/100 in 7 eyes. CONCLUSIONS: Early diagnosis of AK is the key challenge in clinical practice. The combined use of antiacanthamoeba agents, debridement, and cauterization may be a best choice of treatment for patients who are diagnosed early in the course of their disease.

Acanthamoeba Keratitis↗

PubMed2006

Cloning from tissue surrogates: antimicrobial peptide (esculentin) cDNAs from the defensive skin secretions of Chinese ranid frogs.

The defensive skin secretions of amphibians are a rich source of bioactive peptides. Here we describe a rapid technique for skin granular gland transcriptome cloning from a surrogate tissue-the secretion itself. cDNA libraries were constructed from lyophilized skin secretion from each of the Chinese frogs (Rana schmackeri, Rana versabilis, and Rana plancyi fukienensis) using magnetic oligo(dT) bead-captured polyadenylated mRNA as templates. Specific esculentin cDNAs were amplified by 3'-RACE using a degenerate primer designed for a consensus nucleotide sequence in the 5' untranslated region of previously characterized ranid frog peptide cDNAs. The cloned cDNAs were found to encode the antimicrobial peptides esculentins 1 and 2 from each of the species examined. The presence of predicted peptide structures in skin secretions was confirmed by MALDI-TOF mass spectrometry and automated Edman degradation. This experimental approach can thus rapidly expedite parallel transcriptome and peptidome analysis of amphibian granular gland secretions without harming or sacrificing donor animals.

Amino Acid Sequence↗

PubMed2006

Ultrafast electron transfer from oligo(p-phenylene-ethynylene)thiol to gold.

The electron transfer dynamics of oligo(p-phenylene-ethynylene) (OPE) SAM on Au(111) was studied by resonant photoemission spectroscopy. The ultrafast electron transfer from OPE molecules to Au substrate was clearly observed. The time scale for this charge transfer is much less than 6 fs, the core-hole lifetime for C 1s. This strongly suggests that there is an intense interfacial electronic coupling between OPE molecules and the Au substrate.

Journal Article↗

PubMed2006

Optimization of an effective extraction procedure for the analysis of microcystins in soils and lake sediments.

Microcystin analysis in sediments and soils is considered very difficult due to low recovery for extraction. This is the primary limiting factor for understanding the fate of toxins in the interface between water and sediment in both the aquatic ecosystem as well as in soils. In the present study, a wide range of extraction solvents were evaluated over a wide range of pH, extraction approaches and equilibration time to optimize an effective extraction procedure for the analysis of microcystins in soils and lake sediments. The number of extractions required and acids in extraction solutions were also studied. In this procedure, EDTA-sodium pyrophosphate solution was selected as an extraction solvent based on the adsorption mechanism study. The optimized procedure proved to be highly efficient and achieved over 90% recovery. Finally, the developed procedure was applied to field soil and sediment sample collected from Chinese lakes during bloom seasons and microcystins were determined in six of ten samples.

Bacterial Toxins↗

PubMed2006

[The detection of protein expression of clusterin and Ki-67 and the status of cell apoptosis in bladder transitional cell carcinoma].

OBJECTIVE: To investigate the expression of clusterin protein in bladder transitional cell carcinoma (BTCC) and it's association with tumor cell proliferation and apoptosis. METHODS: A tissue microarray (TMA) containing 87 informative cases of BTCCs was constructed firstly. The methods of immunohistochemistry and terminal deoxynucleotidyl transferase-mediated nick end-labeling were then used to examine the expression of clusterin and Ki-67 protein and the status of cell apoptosis in BTCC, respectively, and the correlations between different markers and the clusterin expression associated with patients' clinico-pathological features were evaluated. RESULTS: In TMA of 87 BTCCs, 37 (43%) cases were observed overexpression of clusterin. A significant association of clusterin expression with BTCC's pathological grade, as well as with tumors clinical stage was observed (P < 0.01), where the frequency of overexpression of clusterin in poor differentiated BTCCs (G(3), 71%) and tumors in more advanced stage (T(2-4), 62%) was significantly higher than that in well differentiated BTCCs (G(1-2), 29%) and tumors in early stage (T(a-1), 28%). In addition, a significant correlation between clusterin expression and tumors apoptotic index (AI) was evaluated (P < 0.01), in which 57% of BTCCs with overexpression of clusterin were observed a lower AI, while 72% of tumors with normal expression of this protein showed a higher AI, but no correlation between clusterin and Ki-67 expression. CONCLUSIONS: The overexpression of clusterin is associated positively with BTCC's malignant clinical phenotypes including tumor's differentiation and invasive depth, and it is correlated inversely with AI of tumor cells.

Apoptosis↗

PubMed2006

[Etiology, diagnosis and management of spontaneous per renal hemorrhage].

OBJECTIVE: To investigate the etiology, diagnosis, and management of spontaneous perirenal hemorrhage (SPH). METHODS: The clinical data of 35 patients, 10 males and 12 females, aged 35.9 (12-77), with the diagnosis of SPH, without history of trauma, anticoagulant use, dialysis, and renal transplantation, were analyzed. RESULTS: The underlying disease of SPH included angiomyolipoma (18 cases), renal cell carcinoma (7 cases), kidney cyst (2 cases), renal artery aneurysm (3 cases), rupture of renal artery aneurysm accompanied with pregnancy (2 cases), renal pheochromocytoma (3 cases 2 of which accompanied with pregnancy), congenital stricture of pelvic ureter junction (1 case), and liver cancer (1 case). The most common underlying diseases were nephrogenic (96%) with angiomyolipoma ranking first (54%) followed by renal cell carcinoma (21%). The underlying diseases were diagnosed correctly in 23 cases (69%). CT helped in diagnosis of 34 cases. Surgery was performed on most of the cases. CONCLUSION: The most common causes of SPH is renal neoplasms more than 50% of which are benign. Renal artery aneurysm and pheochromocytoma tend to rupture during pregnancy. CT is the first method of choice in diagnosis.

Adolescent↗

PubMed2006

Linkage analysis of rheumatoid arthritis in US and UK families reveals interactions between HLA-DRB1 and loci on chromosomes 6q and 16p.

OBJECTIVE: HLA is the most strongly associated locus in rheumatoid arthritis (RA), accounting for up to one-third of the genetic contribution. Conditioning on the effect of true disease loci such as HLA can lead to increased power to detect effects at other loci and, in addition, allows investigation of the underlying disease models, including interactions. The aim of this study was to detect susceptibility loci for RA by conditioning on HLA in a large sample of affected sibling pairs (ASPs) and to test for evidence of interaction between novel loci and HLA. METHODS: Genotype data from 3 whole-genome linkage scans for RA in a US population and a UK population were pooled, resulting in a combined data set of 886 ASPs. This pooling of data increased the power to detect loci showing low levels of heterogeneity. Nonparametric linkage analysis was performed to identify regions of interest. Joint 2-locus analysis was then performed for HLA and each of the loci that demonstrated evidence of linkage in the 886 ASPs. RESULTS: Evidence for linkage was most significant at HLA (P = 4 x 10(-16)), with 7 non-HLA loci showing some evidence for linkage (P = 0.05-0.003). Joint modeling of these loci with HLA provided evidence for linkage at a genome-wide significance level for loci on 6q (P = 2.7 x 10(-6)) and 16p (P = 2 x 10(-4)). CONCLUSION: These data provide the most convincing evidence to date that 6q and 16p harbor susceptibility genes. In addition, these loci may interact with HLA, facilitating the search for candidate genes within this region.

Adult↗

PubMed2006

Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice.

Rac, a small, GTP-binding protein in the Rho family, regulates several cellular functions, including the activation of NADPH oxidase, a major intracellular producer of reactive oxygen species (ROS). Hepatic stellate cells (HSCs) isolated from mice that are genetically deficient in NADPH oxidase produce less ROS, and their activation during chronic liver injury is abrogated, resulting in decreased liver fibrosis. Therefore, we hypothesized that HSC ROS production and activation would be enhanced, and fibrosis worsened, by increasing Rac expression in HSCs. To achieve this, we used transgenic mice that express constitutively active human Rac1 under the control of the alpha-smooth muscle actin (alpha-sma) promoter, because alpha-sma expression is induced spontaneously during HSC activation. Transgene expression was upregulated progressively during culture of primary Rac-transgenic HSCs, and this increased HSC ROS production as well as expression of activation markers and collagen. Similarly, Rac mice treated with carbon tetrachloride (CCl(4)) accumulated greater numbers of activated HSCs and had more liver damage, hepatocyte apoptosis, and liver fibrosis-as well as higher mortality-than CCl(4)-treated wild-type mice. In conclusion, sustained activation of Rac in HSCs perpetuates their activation and exacerbates toxin-induced liver injury and fibrosis, prompting speculation that Rac may be a therapeutic target in patients with cirrhosis.

Actins↗

PubMed2006

Royal crown-shaped electride Li3-N3-Be containing two superatoms: new knowledge on aromaticity.

The structure and aromaticity of a royal crown-shaped molecule Li(3)-N(3)-Be are studied at the CCSD(T)/aug-cc-pVDZ level. This molecule is a charge-separated system and can be denoted as Li(3) (2+)N(3) (3-)Be(+). It is found that the Li(3) (2+) ring exhibits aromaticity mainly because the Li(3) (2+) ring can share the pi-electron with the N(3) (-3) ring. The 4n+2 electron counter rule can be satisfied for the Li(3) (2+) subunit if the shared pi valence electron of N(3) (3-) subunit is also taken into account. This new knowledge on aromaticity of a ring from the interactions between subunits is revealed first time in this paper. Li(3)-N(3)-Be can be also regarded as a molecule containing two superatoms (Li(3) and N(3)), which may be named as a "superomolecule." Li(3)-N(3)-Be is a new metal-nonmetal-metal type sandwich complex. The N(3) (3-) trianion in the middle repulses the electron clouds of the two metal subunits (mainly to the Li(3) superatom) to generate an excess electron, and thus Li(3)-N(3)-Be is also an electride. This phenomenon of the repulsion results in: (a) the HOMO energy level increased, (b) the electron cloud in HOMO distended, (c) the area of the negative NICS value extended, and (d) the VIE value lowered. So the superomolecule Li(3)-N(3)-Be is not only a new metal-nonmetal-metal type sandwich complex but also a new type electride, which comes from the interaction between the alkali superatom (Li(3)) and the nonmetal superatom (N(3)).

Journal Article↗