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Biomedical subjects

Tao Peng

Publications and source records attributed to Tao Peng.

49 records · Page 3Linked to original sources

Oxidative DNA damage in peripheral leukocytes and its association with expression and polymorphisms of hOGG1: a study of adolescents in a high risk region for hepatocellular carcinoma in China.

AIM: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China. METHODS: Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay. RESULTS: There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P<0.001). HCC children (n=21) in Fusui county had a higher level of hOGG1 (P<0.01) and a lower level of 8-oxoG (P<0.05) than the controls (n=63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P<0.05) than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele. CONCLUSION: This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.

Adolescent↗

[Regression of vascular remodeling in renovascular hypertensive rats by tetrandrine and enalapril].

AIM: To observe the regression effect of tetrandrine (Tet) and enalapril (Ena) on vascular morphological changes in renovascular hypertensive (RH) rats. METHODS: Renovascular hypertension was induced by two kidney one clip (2K1C) operation. The morphometric measurements were performed in the aorta, caudal artery, renal arterioles, coronary arterioles and mesenteric arterioles. RESULTS: The wet weight of aorta, caudal artery and femoral artery of RH rats (18 weeks after 2K1C operation) were greater than those of sham-operated rats. The media thickness, lumen diameter, cross section of media, media over lumen ratio and the wet weight of abdomen aorta, caudal artery, coronary arterioles, renal arterioles and mesenteric arterioles were significantly increased, which were more significant in arterioles with the diameter smaller than 70 microns. There were no significant change in the number of the smooth muscle cells (VSMC) in most vessel wall, except in renal arterioles, where the number of smooth muscle cells were significantly increased. After Tet (50 mg.kg-1.d-1, p.o.) or Ena (6 mg.kg-1.d-1, p.o.) treated for 9 weeks from week 9 after 2K1C operation, almost all the changes in the media thickness, the media to lumen ratio, the cross section of media and the wet weight were ameliorated. CONCLUSION: In RH rats, mainly a hypertrophic and rearrangement remodeling in the wall of arteries and arterioles was observed with a proliferation of VSMC in renal arterioles. Tet and Ena were shown to regress vascular remodeling by markedly attenuating these changes in renovascular hypertensive rats.

Alkaloids↗

[Apoptosis gene expression profiling of placental trophoblast cells in patients with pregnancy induced hypertension].

OBJECTIVE: To explore the function of placental trophoblast cell apoptosis on the pathogenetic mechanism of pregnancy induced hypertension (PIH). METHODS: Apoptosis of trophoblast cells in 20 cases of PIH (PIH group) and in 10 cases of normal pregnancy (control group) were directly observed using the terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) method. Apoptosis gene expression patterns were screened with gene chip provided by Poxing Company, Shanghai. Standards for differently expressed genes were: (1) An absolute value of the natural logarithm of cy5 (PIH group)/cy3 (control group) greater than 0.69 with a difference of signal of cy5 2 times over that of cy3. (2) The signal value either cy3 or cy5 must be greater than 800. RESULTS: (1) TUNEL test showed that the number of trophoblast cells apoptosis per ten thousand micro m(2) was 1.584 in the PIH group and 0.032 in the control group with significant difference between the two groups (P < 0.01). (2) Ten differently expressed apoptosis genes were obtained through gene chip test (occupy 5% of total apoptosis gene in the gene chip). There was a significant decrease of apoptosis gene expression in all of PIH patient placental tissues (i.e a ratio of cy5/cy3 less than 1). Among them, there were genes that possess significant anti-apoptosis functions (including SFRP(2), IAP(2), DHCY24 and ATPIA1). CONCLUSIONS: Remarkable apoptosis was found in placental trophoblast cells of PIH patients. Significant decrease in genes with anti-apoptosis functions can result in the apoptosis of placental trophoblast cells and thus contributes to the pathogenesis of PIH.

Adult↗

[A new membrane-permeable peptide from human].

OBJECTIVE: To study the translocation ability of a new protein domain (Circadian locomotor output cycles kaput protein's DNA-binding peptide, hCLOCK's DNA_BIND) from human through the membrane. METHOD: hCLOCK's DNA_BIND, which was chemically synthesized and labeled with FITC at N-terminal, was incubated with the vascular endothelial cell (ECV-304) and primary culture neuroglial cells in the culture medium, the distribution of it was observed on a fluorescence microscope. RESULT: hCLOCK's DNA_BIND has the ability to translocate through the cell membrane and accumulate in the nucleus. The quantification of cellular uptake of it increases with the increase of incubation time and concentration. However, the peptide was internalized at 4 degrees C as efficiently as that at 37 degrees C. CONCLUSION: It is promising to provide a new safe carrier for the intracellular treatment.

Cell Membrane↗

[Effects of qianggu electuary on ovariectomized osteoporotic rats].

OBJECTIVE: To observe the effects of qianggu electuary (QGE), a Chinese herbal preparation, on ovariectomy-induced osteoporotic rats. METHOD: Female Wistar rats were ovariectomized and administered QGE, calcium gluconate (CG) and longmu zhuanggu granules (LMZG) for 12 weeks. Bone mineral density (BMD), indexes of biomechanics and serum E2, Ca were detected in grouped rats including QGE, CG, LMZG and control groups. RESULT: QGE could significantly increase the BMD and maximum load, maximum stress YP-load of femora in the osteoporotic rats. The values of E2 in ovariectomized osteoporotic rats decreased, compared with those of control normal rats (P > 0.05), while in the QGE treated rats, the values of E2 increased. CONCLUSION: QGE can increase the BMD and improve indexes of bone biomechanics in ovariectomized osteopotic rats, possibly due to its estrogen-like effect.

Animals↗

Structural requirements within the lipoyl domain for the Ca2+-dependent binding and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic subunit.

The inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2) 60-mer forms a Ca(2+)-dependent complex with the pyruvate dehydrogenase phosphatase 1 (PDP1) or its catalytic subunit, PDP1c, in facilitating large enhancements of the activities of PDP1 (10-fold) or PDP1c (6-fold). L2 binding to PDP1 or PDP1c requires the lipoyl-lysine prosthetic group and specificity residues that distinguish L2 from the other lipoyl domains (L1 in E2 and L3 in the E3-binding component). The L2-surface structure contributing to binding was mapped by comparing the capacities of well folded mutant or lipoyl analog-substituted L2 domains to interfere with E2 activation by competitively binding to PDP1 or PDP1c. Our results reveal the critical importance of a regional set of residues near the lipoyl group and of the octanoyl but not the dithiolane ring structure of the lipoyl group. At the other end of the lipoyl domain, substitution of Glu(182) by alanine or glutamine removed L2 binding to PDP1 or PDP1c, and these substitutions for the neighboring Glu(179) also greatly hindered complex formation (E179A > E179Q). Among 11 substitutions in L2 at sites of major surface residue differences between the L1 and L2 domains, only the conversion of Val-Gln(181) located between the critical Glu(179) and Glu(182) to the aligned Ser-Leu sequence of the L1 domain greatly reduced L2 binding. Certain modified L2 altered E2 activation of PDP1 differently than PDP1c, supporting significant impact of the regulatory PDP1r subunit on PDP1 binding to L2. Our results indicate hydrophobic binding via the extended aliphatic structure of the lipoyl group and required adjacent L2 structure anchor PDP1 by acting in concert with an acidic cluster at the other end of the domain.

Amino Acid Sequence↗

Novel technologies for studying virus-host interaction and discovering new drug targets for HCV and HIV.

A new paradigm for antiviral therapy focuses on targeting cellular genes that are critical for viral replication and pathogenesis. Several new technologies have contributed to the identification of such genes for human immunodeficiency virus and hepatitis C virus. These include proteomic approaches that identify cellular proteins that physically interact with viral proteins, genomic approaches that identify and functionally validate essential cellular co-factor genes, and novel cell biology systems that facilitate studies of virus-host interactions.

Gene Expression Regulation, Viral↗

Protection of mice against Coccidioides immitis intranasal infection by vaccination with recombinant antigen 2/PRA.

Subcutaneous vaccination with recombinant antigen 2/PRA (rAg2/PRA) protected BALB/c mice against intranasal infection with Coccidioides immitis. Subcutaneously vaccinated C57BL/6 mice and intranasally vaccinated BALB/c mice were protected against larger numbers of infecting spores. Weight loss correlated with lethality, but histologic appearance did not. These studies support rAg2/PRA vaccination to prevent coccidioidomycosis.

Administration, Intranasal↗

Localization within a proline-rich antigen (Ag2/PRA) of protective antigenicity against infection with Coccidioides immitis in mice.

Subunits of a proline-rich coccidioidal antigen (Ag2/PRA) of Coccidioides immitis were analyzed by comparison as vaccines in mice. The optimal dose of plasmid vaccine encoding full-length Ag2/PRA was determined to be between 10 and 100 microg. Mice vaccinated with plasmids encoding amino acids (aa) 1 to 106 were as protective as full-length Ag2/PRA (aa 1 to 194). The subunit from aa 27 to 106 was significantly but less protective. Plasmids encoding aa 90 to 151 or aa 90 to 194 were not protective. Analogous results were obtained with recombinant vaccines of the same amino acid sequences. In addition, mixtures of aa 90 to 194 with either aa 1 to 106 or aa 27 to 106 did not enhance protection compared to the active single-recombinant subunits alone. Humoral response of total immunoglobulin G (IgG) and subclasses IgG1 and IgG2a were detectable in subunit vaccinations but at significantly (100-fold) lower concentrations than after vaccination with plasmids encoding full-length Ag2/PRA. Since virtually all protection by vaccination with full-length Ag2/PRA can be accounted for in the first half of the protein (aa 1 to 106), this subunit could make a multicomponent vaccine more feasible by reducing the quantity of protein per dose and the possibility of an untoward reactions to a foreign protein.

Amino Acid Sequence↗

The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation.

RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.

Amino Acids↗

Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene.

Dexamethasone treatment increases urea excretion and decreases urea permeability and urea transporter UT-A1 protein abundance in the inner medullary collecting duct (IMCD) of adrenalectomized rats. We examined the effect of dexamethasone treatment for 3 days on the abundance of several UT-A mRNA transcripts in rat renal medulla. By Northern blot analysis, a significant decrease in mRNA expression was observed in the inner medulla of dexamethasone-treated rats compared with controls for UT-A1 (71%), UT-A3 (75%), and UT-A3b (75%), but not for UT-A2. We then tested the effect of 100 nM dexamethasone on the activity of promoter I in the UT-A gene, using LLC-PK(1)-GR101 cells that express the glucocorticoid receptor. Dexamethasone significantly decreased the activity of rat UT-A promoter I (72%) but did not affect UT-A promoter II. Deletion analysis and site-directed mutagenesis demonstrated that sequences between -423 and -244 are important for this inhibition and that a 10-bp sequence at -363, which binds a nuclear protein in a gel shift assay, is necessary for basal promoter activity. The specific factors involved in repression of UT-A promoter I activity by glucocorticoids remain to be determined.

Animals↗

Differential expression of individual UT-A urea transporter isoforms in rat kidney.

The rat renal urea transporter UT-A includes four mRNA isoforms: UT-A1, UT-A2, UT-A3, and UT-A4. This study detected by rapid amplification of cDNA ends (RACE), primer extension, and ribonuclease protection assay (RPA) a single transcription start site for UT-A1, UT-A3, and UT-A4, distinct from the one for UT-A2 and identified by 3'-RACE new transcripts of UT-A1, UT-A2, and UT-A3, characterized by alternative 3' untranslated sequences (UTR). Expression of an alternative 3'UTR resulted in UT-A1 and UT-A2 transcripts that are approximately 400 bp shorter than the original cDNA. These mRNA isoforms (UT-A1b and UT-A2b) were present in low abundance in the inner medulla. Expression of an alternative 3'UTR for UT-A3 resulted in a 3.5 kb transcript (UT-A3b), which is 1.5 kb longer than the original UT-A3 cDNA. UT-A3b mRNA was easily detected by Northern hybridization in the inner medulla. This study examined whether different states of hydration induce homogeneous changes in mRNA expression of individual UT-A isoforms in the kidney. Analysis of UT-A1, UT-A1b, UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA expression in rat kidney revealed that water deprivation markedly increases the relative abundance of UT-A2, UT-A2b, UT-A3, and UT-A3b mRNA in renal inner medulla, whereas UT-A1 and UT-A1b remain almost unchanged. The conclusion is that differential expression of individual UT-A mRNA isoforms occurs in the kidney and probably involves multiple regulatory mechanisms.

3' Untranslated Regions↗

3D-QSAR and receptor modeling of tyrosine kinase inhibitors with flexible atom receptor model (FLARM).

A set of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors was investigated with the aim of developing 3D-QSAR models using the Flexible Atom Receptor Model (FLARM) method. Some 3D-QSAR models were built with high correlation coefficients, and the FLARM method predicted the biological activities of compounds in test set well. The FLARM method also gave the pseudoreceptor model, which indicates the possible interactions between the receptor and the ligand. The possible interactions include two hydrogen bonds, one hydrophobic interaction, and one sulfur-aromatic interaction, which are in accord with those in the pharmacophore model given by the scientists at Novartis. This shows that the FLARM method can bridge 3D-QSAR and receptor modeling in computer-aided drug design. Pharmacophore can be obtained according to these results, and 3D searching can then be done with databases to find the lead compound of EGFR tyrosine kinase inhibitors.

Binding Sites↗