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Biomedical subjects

Zhi Chen

Publications and source records attributed to Zhi Chen.

At least 109 records · Page 6Linked to original sources
PubMed2003

Identification of novel IL-4/Stat6-regulated genes in T lymphocytes.

IL-4, primarily produced by T cells, mast cells, and basophiles, is a cytokine which has pleiotropic effects on the immune system. IL-4 induces T cells to differentiate to Th2 cells and activated B lymphocytes to proliferate and to synthesize IgE and IgG1. IL-4 is particularly important for the development and perpetuation of asthma and allergy. Stat6 is the protein activated by signal transduction through the IL-4R, and studies with knockout mice demonstrate that Stat6 is critical for a number of IL-4-mediated functions including Th2 development and production of IgE. In the present study, novel IL-4- and Stat6-regulated genes were discovered by using Stat6(-/-) mice and Affymetrix oligonucleotide arrays. Genes regulated by IL-4 were identified by comparing the gene expression profile of the wild-type T cells induced to polarize to the Th2 direction (CD3/CD28 activation + IL-4) to gene expression profile of the cells induced to proliferate (CD3/CD28 activation alone). Stat6-regulated genes were identified by comparing the cells isolated from the wild-type and Stat6(-/-) mice; in this experiment the cells were induced to differentiate to the Th2 direction (CD3/CD28 activation + IL-4). Our study demonstrates that a number a novel genes are regulated by IL-4 through Stat6-dependent and -independent pathways. Moreover, elucidation of kinetics of gene expression at early stages of cell differentiation reveals several genes regulated rapidly during the process, suggesting their importance for the differentiation process.

Animals↗
PubMed2003

Consequences of telomerase inhibition and combination treatments for the proliferation of cancer cells.

Telomerase is expressed in most types of tumor cells but not in most somatic cells, suggesting that telomerase inhibitors may be a powerful new approach to cancer chemotherapy. Here we explore this hypothesis by treating cultured human tumor cells with a 2'-O-methoxyethyl oligonucleotide that binds the telomerase RNA template and acts as a potent inhibitor. Treatment of DU145 (Rb(-), p53(-)) and LNCaP (Rb(+), p53(+)) cells causes telomeres to shorten and cell proliferation to stop. Decreased cell proliferation in culture is not observed immediately but occurs after several weeks and is accompanied by telomere shortening. Antiproliferative effects are more profound for cells growing in soft agar or in colony formation assays, with 90% reduction in the colony-forming ability of LNCaP cells after less than 2 weeks of exposure to the inhibitor. Decreased growth of DU145 and LNCaP tumors and large reductions in prostate-specific antigen levels are also observed in vivo in xenograft models. Short-term treatment of cells with telomerase inhibitors does not increase the effects of standard antiproliferative agents paclitaxel, doxorubicin, etoposide, cisplatin, or carboplatin. Long-term inhibition and telomere shortening sensitize DU145 cells, but not LNCaP cells, to cisplatin or carboplatin. These results demonstrate that methoxyethyl oligomers directed against the template region of telomerase are potent agents and that significant antiproliferative effects can be observed after 2-3 weeks of treatment. Reduced cell proliferation and tumor growth support the hypothesis that telomerase inhibition can make a useful contribution to chemotherapy and should encourage broad testing of telomerase inhibitors.

Animals↗
PubMed2003

Effect of polymer concentration on partitioning and molecular recognition in plasticized poly(vinyl chloride).

Mixtures of poly(vinyl chloride) (PVC) with plasticizers have been used in ion-selective electrodes for many years. The same material has proven useful in solid-phase microextraction (SPME), both with and without artificial receptors. We hypothesized that by changing the polymer concentration in plasticized PVC membranes containing artificial receptor from the standard 33 wt %, the selectivity of the extraction of barbiturates over similar molecules could be improved. Partition coefficients and receptor-substrate formation constants of a target species, phenobarbital, in membranes with various polymer concentrations were determined. Diffusion coefficients of the solute phenobarbital in receptor-free membranes were also determined. Kamlet-Taft solvatochromic properties beta and pi* were measured for the PVC/dioctyl sebacate materials. Cohesive energy densities were calculated for the same materials. Partition coefficients for phenobarbital (from aqueous solution to membrane) decrease as [PVC] increases, while the formation constants for the complex of the solute with its receptor increase. Diffusion coefficients decrease as the polymer concentration increases as well. The increase in polymer concentration brings about a decrease in hydrogen-bonding basicity and an increase in dipolarity and cohesive energy density. The values of the solvatochromic parameters determined at various compositions are highly correlated; thus, it is impossible to calculate how much each factor contributes to the changes associated with partition and complex formation. The solvatochromic "polarizability correction factor" has been determined to be 0 for PVC. In SPME experiments at 30%, 40%, and 50% (w/w) PVC, as polymer concentration increases, selectivity for barbiturate extraction over other cyclic imides becomes better in the presence of barbiturate receptor and worse without receptor.

Journal Article↗
PubMed2003

Telomerase inhibitors: a new option for chemotherapy.

Telomerase is expressed in most types of tumors but not in most somatic cells. This observation has led to two hypotheses: (i) telomerase activity is necessary for the proliferation of cancer cells and (ii) telomerase inhibitors are a powerful strategy for cancer chemotherapy. The properties and function of human telomerase are reviewed briefly. The effects of telomerase inhibitors on telomere length and tumor cell proliferation are then described. Much evidence, both pro and con, has accumulated about the value of telomerase as a target for therapy. Resolving the controversy will require a thorough understanding of telomere biology and clinical trials designed around potent inhibitors.

Antineoplastic Agents↗
PubMed2003

[Modulation and implications in pathogenesis of interferon gamma receptor 1 in patients with chronic hepatitis B].

OBJECTIVE: To study the possible differences in the interferon gamma receptor (IFN-gamma R1) response among a variety of clinical types in patients with chronic hepatitis B (CHB) and implications in pathogenesis. METHODS: The serum level of IFN-gamma and the expression level of IFN-gamma R1 in peripheral leucocytes, from 53 CHB patients, were examined by ELISA and flow cytometry respectively, which were compared with the baseline levels of 15 healthy controls and were performed correlation analysis with alanine aminotransferase (ALT), total bilirubin (TBil) in serum and morphological change in hepatic tissues. RESULTS: The results showed that the level of IFN-gamma R1 (28.89% 11.77%) expressed on the membranes of lymphocytes in CHB patients, which correlated with liver inflammation (r=0.621, P<0.01) and serum TBil level (r=0.575, P<0.01), was much higher than that (9.23% 1.30%) of the healthy controls (Z=3.988, P<0.05), and no obvious difference on the membranes of leucocytes. The serum levels of IFN-gamma in patients with cirrhosis and severe hepatitis were higher than those of healthy controls. And the two was no difference from each other, but the standard deviation in each group was relatively large. CONCLUSION: These findings suggest that the IFN-gamma signal transduction pathway is modulated through up-regulating the expression of IFN-gamma R1 on the membranes of lymphocytes, which takes part in the immuno-pathogenesis in CHB patients.

Adult↗
PubMed2003

[Expression of MAGE, GAGE, and BAGE genes in human hepatocellular carcinoma].

OBJECTIVE: To observe the expression of MAGE, GAGE and BAGE genes in human hepatocellular carcinoma (HCC) cell lines. METHODS: The expression levels of MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE mRNAs in HCC cell lines SMMC-7721, QQY-7701, BEL-7402 were studied by reverse transcription polymerase chain reaction and were compared with those in biopsied liver tissues. RESULTS: MAGE-1 and BAGE mRNAs were expressed in SMMC-7721 cells. MAGE-3 and BAGE mRNAs were expressed in QQY-7701 cells. MAGE-1 and GAGE1-2 mRNAs were expressed in BEL-7402 cells. None of these genes was expressed in biopsied liver tissues. CONCLUSIONS: MAGE-1, MAGE-3, GAGE1-8, GAGE1-2 and BAGE are expressed in hepatocellular carcinoma cell lines. These tumor-specific antigens can be used as molecular markers for early diagnosis and possible targets for immunotherapy of human HCC.

Antigens, Neoplasm↗
PubMed2003

[Expression of Shh, Ptc1, Ptc2 mRNA in the cap stage of mouse molar].

OBJECTIVE: To investigate the expression of Shh and its receptors Ptc1 and Ptc2 mRNA in the cap stage of mouse molar and discuss its role in early tooth morphogenesis. METHODS: The embryonic mouse heads of early tooth development (E10.5 - E15.5) were obtained and 5 micro m serial sections were made. Immunohistochemical staining of PCNA was carried out by SP method. The expression pattern of Shh, Ptc1, and Ptc2 mRNA was analysed by in situ hybridization. RESULTS: E14.5, outer dental epithelium, inner dental epithelium, stellate reticulum and underlying dental mesenchyme were PCNA positive. Most of the enamel knot cells were PCNA negative. A few of the enamel knot cells were PCNA positive. Shh, Ptc1, and Ptc2 mRNA were strongly expressed in outer dental epithelium, inner dental epithelium, stellate reticulum and the enamel knot. CONCLUSION: In the cap stage, Shh as a paracrine and autocrine signaling molecule might stimulate epithelium and mesenchyme proliferation.

Animals↗
PubMed2003

[The relaxation effects of tetrandrine on the corpus cavernosum tissue of rabbit in vitro].

OBJECTIVES: To study the relaxation effects of tetrandrine on the corpus cavernosum tissue of rabbit in vitro. METHODS: 1. The fluctuation of the dose-response relaxation curves for the contraction of KCl induced by tetrandrine was observed with isolated rabbit corpus cavernosum tissue. 2. Isolated strips of rabbit corpus cavernosum tissue were precontracted with 10 mumol/L phenylephrine(PE). Relaxation in response to cumulative doses of tetrandrine was determined in the absence and presence of nitric oxide synthase inhibitor (L-NNA) and soluble guanylate cyclase inhibitor (methylthioninium). RESULTS: 1. The dose-response curves of KCl were shifted to the right nonparallelly, and the maximal responses were depressed to (73.0 +/- 3.8)% and (41.5 +/- 3.4)%, respectively, in the presence of tetrandrine(10 mumol/L, 30 mumol/L). 2. On rabbit cavernosal muscle stripes precontracted with PE(10 mumol/L), increasing concentrations of tetrandrine (1 mumol/L, 10 mumol/L, 30 mumol/L and 100 mumol/L) showed dose dependent relaxation [(6.0 +/- 1.4)%, (21.3 +/- 2.2)%, (47.4 +/- 3.3)%, and (68.1 +/- 3.6)%, P < 0.01]. However, in the meantime, it was found that these relaxation effects were not affected by the presence of L-NNA and methylthioninium (P > 0.05). CONCLUSIONS: Tetrandrine was effective in relaxing rabbit corpus cavernosum tissue in vitro in a dose-dependent style. The mechanism might be related with its blocking effect on calcium channel, but not the NO-cGMP passage.

Alkaloids↗
PubMed2003

Expression of MAGE-A1 and MAGE-A3 genes in human salivary gland carcinomas.

OBJECTIVE: To determine at the mRNA level whether the MAGE-A1 and -A3 genes are expressed in cancer cell lines from salivary glands and relevant clinical carcinomas, and thus to distinguish cancerous tissues from normal tissues and benign tumors in salivary glands. METHODS: The expression of the MEGE-A1 and MEGE-A3 genes at the mRNA level was determined by reverse transcription and polymerase chain reaction (RT-PCR) in 2 cell lines of human adenoid cyst carcinomas (ACC-2 and ACC-M), in 18 malignant tumors and 9 benign salivary gland tumors, and in 10 samples of normal salivary gland tissues. RESULTS: Both MAGE-A1 and -A3 genes were expressed in ACC-2 and ACC-M cell lines. None of the 9 benign tumors or the 10 normal tissue samples of salivary glands expressed the genes. The MAGE-A1 and -A3 genes were expressed in 9 (50%) and 11 (61%) of 18 salivary gland carcinomas, respectively, and at least 1 of the 2 genes was expressed in 14 (78%) of them. Of the 18 salivary gland carcinomas, 6 low-differentiated carcinomas (33%) expressed both genes, whereas 4 high-differentiated carcinomas (22%) expressed neither gene. CONCLUSIONS: The MAGE-A1 and -A3 genes can be expressed in cancer cell lines of salivary glands and relevant clinical carcinomas in addition to other malignant tumors of various histological origins. The results suggest the possibility of immunotherapy against salivary gland carcinomas by using MAGE-gene-encoded products as target antigens for tumor-rejection.

Adult↗
PubMed2003

[Rapid detection of Streptococcus mutans and streptococcus sobrinus in human saliva by nested polymerase chain reaction].

OBJECTIVE: To establish a simple and rapid method to detect Streptococcus mutans and streptococcus sobrinus simultaneously in human saliva. METHODS: Chromosomal DNA from the bacteria was obtained by the extraction method with phenol-chloroform. A nested PCR method with two sets of primers specific for portions of the glucosyltransferase genes (gtfB of S. mutans and gtfI of S. sobrinus), was optimized to detect S. mutans and S. sobrinus from standard strains, clinical strains and directly in human saliva. RESULTS: The first process of nested PCR was capable of amplifying DNA fragments specific for these species from chromosomal DNA extracted from 10(5) CFU cells of standard and clinical strains, or from 1 ml clinical saliva samples containing 10(5) CFU cells of either species. a second process of nested PCR, using the first PCR product as a template with new internal primers to detect 10(3) CFU of either streptococcal species in 1ml saliva samples. CONCLUSION: Nested PCR could detect S. mutans and S. sobrinus rapidly and simply in human saliva. This finding would be important to studies of elucidation the role of these two streptococcal species in the etiology of dental caries.

Humans↗
PubMed2003

[Construction and expression in vitro of a targeted fusion anticaries DNA vaccine].

OBJECTIVE: To construct and detect the targeted anti-caries fusion DNA vaccine pGJA-P encoding the A-P fragment of pac, glu fragment of gtfB and extracellular region of the human CTLA4 and the Fc region of human Iggamma(1) gene for the targeting antigen to APC. METHODS: The extracellular region of the human CTLA4 and the Fc region of human Iggamma(1) genes were amplified by RT-PCR from human lymphocytes, and the genes were cloned into pUC(m-T) vector respectively. After sequencing, Fc region of human Iggamma(1) gene was cloned to the downstream of CTLA4 gene fragment as the recombinant plasmid pGJ. The fusion gene was then inserted into the plasmid pGLUA-P to get the recombinant plasmid pGJA-P. The CHO cells were transfected with liposome and the expression of fusion protein in cultured supernatants were detected using Western blotting. RESULTS: The plasmids pGJ and pGJA-P carried the CTLA4-Ig fusion gene and CTLA4-Ig fusion gene, A-P fragment of pac gene and glu fragment of gtfB gene respectively. The expressed protein could response to specific anti-PAc antibody. CONCLUSION: The targeted fusion anti-caries DNA vaccine pGJA-P is constructed successfully and expressed in eukaryotic cells correctly.

Animals↗
PubMed2003

Apolipoprotein E genotype in patients with Alzheimer's disease.

OBJECTIVE: To explore the frequency and significance of ApoE gene polymorphisms in patients with sporadic Alzheimer's disease (AD). METHODS: Single nucleotide polymorphisms of the ApoE gene were analyzed in 32 cases of AD and 26 controls, using PCR and gene sequencing. RESULTS: The single nucleotide polymorphism of ApoE gene 462C/G was significantly associated with AD (P < 0.05). CONCLUSIONS: The 462C/G polymorphism might be a specific genotype in Chinese patients with sporadic AD.

Aged↗
PubMed2003

[Effects of tetramethylpyrazine on cytosolic free calcium concentration in penis corpus cavernsum smooth muscle cells in rabbits].

OBJECTIVE: To study the effects of Chinese medicine tetramethylpyrazine (TMP) on intracellular free calcium ([Ca2+]i) in cultured penis corpus cavernosum smooth muscle cell (PCSMC) in rabbits. METHODS: By using laser scanning confocal microscope (LSCM), the [Ca2+]i fluorescence signal changes was investigated in cultured PCSMC loaded with Ca2+ indicator Fluo-3/AM and divided into potassium chloride(KCl) group and norepinephrine (NE) group. Compared with verapamil (Ver), the effects of TMP was observed in different concentrations on [Ca2+]i increase induced by high potassium and NE. RESULTS: TMP had no obvious effect on resting PCSMC [Ca2+]i. It was found that 1, 10, 100 mumol/L TMP significantly inhibited [Ca2+]i increase induced by high potassium-depolarization. The peak inhibition rates were (38.6 +/- 3.0)%, (44.1 +/- 2.4)% and (53.7 +/- 4.1)% respectively. TMP could also inhibit cytosolic calcium pool release induced by 1 mumol/L NE. The peak inhibition rates were (13.9 +/- 2.7)%, (21.2 +/- 1.9)% and (29.5 +/- 3.6)% respectively. CONCLUSIONS: TMP can inhibit rabbit PCSMC [Ca2+]i significantly by suppressing voltage-dependent calcium channel and cytosolic calcium pool release. The effect, similar to Ver, signifies the important mechanism of erectile dysfunction (ED) therapy.

Animals↗
PubMed2003

[Detection and analysis of the new kind of G743C and G743A point mutation of HBV P gene in hepatitis B virus infected patients resistant to lamivudine].

OBJECTIVE: To explore the point mutation in hepatitis B virus polymerase (HBV P) gene in HBV-infected patients resistant to lamivudine. METHODS: HBV P gene was amplified by PCR and the products was sequenced to analyze the YMDD mutation. Then the variants were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with the following restriction enzymes: Fok I, Ssp I, Alw441 and were separated by 8.0% polyacrylamide gel electrophoresis. RESULTS: Comparing with the sequences of standard HBV genome, there were 16 patients with G743C mutation and 1 patient with G743A mutation, and the codon ATG turned to ATC and ATA, YMDD motif changed into YIDD. But this kind of YIDD mutation was not proved by PCR-RFLP assay in the 17 patients. CONCLUSIONS: The G743C and G743A mutations in HBV P gene, resulting in YMDD motif changed into YIDD, are detected only by direct sequencing, not by PCR-RFLP. The new kind of G743C and G743A point mutations in HBV P gene is important for the detection of HBV P gene YMDD mutation.

Adult↗
PubMed2003

[High-resolution electron microscopy of carious dissolution of enamel nano-crystals].

OBJECTIVES: To investigate the carious dissolution mechanism of enamel apatite nano-crystals at lattice fringe level and the possible correlation between the carious dissolution and the appearance of central dark line (CDL) in enamel crystals. METHODS: The body of the lesion in incipient enamel caries was observed by high resolution transmission electron microscopy (HRTEM, JOEL-2010 operating at 200 kv), combined with selected-area argon-ion-beam thinning technique. RESULTS: In the body of the lesion, the preferential core dissolution was found in most of enamel nano-crystals, whereas the peripheral dissolution of individual crystal could be occasionally observed. The initial carious dissolution of individual enamel apatite crystal occurred as a number of small electron-lucent spots along the central dark line with blurry, bent or disconnected lattice fringes. These small electron-lucent spots fused with each other to form large electron-lucent areas. Finally the central perforation was frequently seen in the crystals. The CDL always appeared in the same place with central perforation in carious crystals, which could be seen to extend along the CDL. CONCLUSIONS: The initial carious dissolution is directly related to the lattice defects in the enamel nano-crystals. The preferential core dissolution can be partly ascribed to the CDL, which is presumed to be particularly susceptible area to caries.

Dental Caries↗
PubMed2003

[Expression of homeobox gene Msx-1, Msx-2 and Dlx-2 during murine mandibular first molar development].

OBJECTIVE: To observe the expression of homeobox gene Msx-1, Msx-2 and Dlx-2 during murine mandibular first molar development. METHODS: The murine heads or mandibles on embryonic days 11-18 (E11-18) and postnatal day 1-3 (P1-3) were removed, fixed and embedded, 5 micro m serial sections were cut in the coronal plane. Msx-1, Msx-2 and Dlx-2 RNA probes were synthesized by in vitro transcription and labeled with digoxigenin. Msx-1, Msx-2 and Dlx-2 mRNA expression was observed after in situ hybridization. RESULTS: During molar development Msx-1 transcripts appeared only in mesenchymal cells, not in epithelial cells. Msx-2 and Dlx-2 both expressed in the epithelial and mesenchymal cells. At the initiation stage of the molar development Msx-2 and Dlx-2 had similar expression. At the bud stage (E13-14) Msx-2 mRNA signaling was intensive in the enamel organ and slight in the dental mesenchyme; Dlx-2 signaling was stronger in the dental papilla. At cap stage (E15-16) Msx-2 showed prominent mRNA signaling in enamel knot and Dlx-2 was maximal in the dental papilla. At the late bell stage (P2-3) Msx-2 transcripts were observed in odontoblasts but not labeled in ameloblasts, and Dlx-2 transcripts appeared in ameloblasts but no labeling was seen in odontoblasts. CONCLUSIONS: Msx-1, Msx-2 and Dlx-2 are expressed in various patterns during murine mandibular first molar development, suggesting they possibly play a role in the interaction between the epithelium and mesenchyme during the molar development.

Animals↗
PubMed2002

Telomerase inhibition, telomere shortening, and decreased cell proliferation by cell permeable 2'-O-methoxyethyl oligonucleotides.

Telomerase is an attractive target for chemotherapy. Testing this hypothesis will require potent inhibitors with favorable pharmacokinetic properties. We report that 2'-methoxyethyl oligonucleotides complementary to the telomerase RNA component diffuse across cell membranes without the need for cationic carrier lipid, inhibit telomerase, and cause telomeres to shorten. The ability of antitelomerase oligomers to enter cells without the need to add lipid will simplify preclinical studies and may suggest advantages for clinical use.

Cell Division↗