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Yang Zhang

Publications and source records attributed to Yang Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2003

Hydroxyl-substituted sulfonylureas as potent inhibitors of specific [3H]glyburide binding to rat brain synaptosomes.

We are seeking to discover potent CNS-active sulfonylureas with structural features that allow for the formation of several types of prodrugs. We report herein the syntheses of compounds comprising an initial series of hydroxyl-substituted analogues of the potent ATP-sensitive potassium channel blockers glyburide (glibenclamide) and gliquidone. Somewhat unexpectedly, several of the compounds were found to be comparably potent to glyburide as inhibitors of specific [(3)H]glyburide binding in rat brain preparations.

Animals↗
PubMed2003

Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway.

Inappropriate activation of downstream target genes by the oncoprotein beta-catenin is implicated in development of numerous human cancers. beta-catenin and its fruitfly counterpart Armadillo act as a coactivator in the canonical Wnt/Wingless pathway by binding to Tcf/Lef transcription factors. Here we report a conserved nuclear protein, named Chibby, which was identified in a screen for proteins that directly interact with the C-terminal region of beta-catenin. In mammalian cultured cells we demonstrate that Chibby inhibits beta-catenin-mediated transcriptional activation by competing with Lef-1 to bind to beta-catenin. Inhibition of Drosophila Chibby by RNA interference results in segment polarity defects that mimick a wingless gain-of-function phenotype, and overexpression of the wingless target genes engrailed and Ultrabithorax. In addition, epistasis experiments indicate that chibby acts downstream of wingless and upstream of armadillo.

Animals↗
PubMed2003

Mechanism of human S-adenosylmethionine decarboxylase proenzyme processing as revealed by the structure of the S68A mutant.

S-Adenosylmethionine decarboxylase (AdoMetDC) is a pyruvoyl-dependent enzyme that catalyzes the formation of the aminopropyl group donor in the biosynthesis of the polyamines spermidine and spermine. The enzyme is synthesized as a protein precursor and is activated by an autocatalytic serinolysis reaction that creates the pyruvoyl group. The autoprocessing reaction proceeds via an N --> O acyl rearrangement, generating first an oxyoxazolidine anion intermediate followed by an ester intermediate. A similar strategy is utilized in self-catalyzed protein splicing reactions and in autoproteolytic activation of protein precursors. Mutation of Ser68 to alanine in human AdoMetDC prevents processing by removing the serine side chain necessary for nucleophilic attack at the adjacent carbonyl carbon atom. We have determined the X-ray structure of the S68A mutant and have constructed models of the proenzyme and the oxyoxazolidine intermediate. Formation of the oxyoxazolidine intermediate is promoted by a hydrogen bond from Cys82 and stabilized by a hydrogen bond from Ser229. These observations are consistent with mutagenesis studies, which show that the C82S and C82A mutants process slowly and that the S229A mutant does not process at all. Donation of a proton by His243 to the nitrogen atom of the oxyoxazolidine ring converts the oxyoxazolidine anion to the ester intermediate. The absence of a base to activate the hydroxyl group of Ser68 suggests that strain may play a role in the cleavage reaction. Comparison of AdoMetDC with other self-processing proteins shows no common structural features. Comparison to histidine decarboxylase and aspartate decarboxylase shows that these pyruvoyl-dependent enzymes evolved different catalytic strategies for forming the same cofactor.

Adenosylmethionine Decarboxylase↗
PubMed2003

TOUCHSTONE: a unified approach to protein structure prediction.

We have applied the TOUCHSTONE structure prediction algorithm that spans the range from homology modeling to ab initio folding to all protein targets in CASP5. Using our threading algorithm PROSPECTOR that does not utilize input from metaservers, one threads against a representative set of PDB templates. If a template is significantly hit, Generalized Comparative Modeling designed to span the range from closely to distantly related proteins from the template is done. This involves freezing the aligned regions and relaxing the remaining structure to accommodate insertions or deletions with respect to the template. For all targets, consensus predicted side chain contacts from at least weakly threading templates are pooled and incorporated into ab initio folding. Often, TOUCHSTONE performs well in the CM to FR categories, with PROSPECTOR showing significant ability to identify analogous templates. When ab initio folding is done, frequently the best models are closer to the native state than the initial template. Among the particularly good predictions are T0130 in the CM/FR category, T0138 in the FR(H) category, T0135 in the FR(A) category, T0170 in the FR/NF category and T0181 in the NF category. Improvements in the approach are needed in the FR/NF and NF categories. Nevertheless, TOUCHSTONE was one of the best performing algorithms over all categories in CASP5.

Algorithms↗
PubMed2003

TOUCHSTONE II: a new approach to ab initio protein structure prediction.

We have developed a new combined approach for ab initio protein structure prediction. The protein conformation is described as a lattice chain connecting C(alpha) atoms, with attached C(beta) atoms and side-chain centers of mass. The model force field includes various short-range and long-range knowledge-based potentials derived from a statistical analysis of the regularities of protein structures. The combination of these energy terms is optimized through the maximization of correlation for 30 x 60,000 decoys between the root mean square deviation (RMSD) to native and energies, as well as the energy gap between native and the decoy ensemble. To accelerate the conformational search, a newly developed parallel hyperbolic sampling algorithm with a composite movement set is used in the Monte Carlo simulation processes. We exploit this strategy to successfully fold 41/100 small proteins (36 approximately 120 residues) with predicted structures having a RMSD from native below 6.5 A in the top five cluster centroids. To fold larger-size proteins as well as to improve the folding yield of small proteins, we incorporate into the basic force field side-chain contact predictions from our threading program PROSPECTOR where homologous proteins were excluded from the data base. With these threading-based restraints, the program can fold 83/125 test proteins (36 approximately 174 residues) with structures having a RMSD to native below 6.5 A in the top five cluster centroids. This shows the significant improvement of folding by using predicted tertiary restraints, especially when the accuracy of side-chain contact prediction is >20%. For native fold selection, we introduce quantities dependent on the cluster density and the combination of energy and free energy, which show a higher discriminative power to select the native structure than the previously used cluster energy or cluster size, and which can be used in native structure identification in blind simulations. These procedures are readily automated and are being implemented on a genomic scale.

Algorithms↗
PubMed2003

Three new cytotoxic acylspermidines from the soft coral, Sinularia sp.

Three new acylated spermidines and two known related compounds were isolated from the Okinawan soft coral, Sinularia sp. These compounds were N',N",N"-trimethylspermidines that are acylated by a methyl-branched unsaturated fatty acid. These acylspermidines showed potent cytotoxicity against human tumor cell lines at an IC(50) value of 17 ng/ml and the induction of apoptotic phenomena.

Acylation↗
PubMed2003

Meta analysis of risk factors for colorectal cancer.

AIM: To study the risk factors for colorectal cancer in China. METHODS: A meta-analysis of the risk factors of colorectal cancer was conducted for 14 case-control studies, and reviewed 14 reports within 13 years which included 5034 cases and 5205 controls. Dersimonian and Laird random effective models were used to process the results. RESULTS: Meta analysis of the 14 studies demonstrated that proper physical activities and dietary fibers were protective factors (pooled OR<0.8), while fecal mucohemorrhage, chronic diarrhea and polyposis were highly associated with colorectal cancer (all pooled OR>4). The stratified results showed that different OR values of some factors were due to geographic factors or different resources. CONCLUSION: Risks of colorectal cancer are significantly associated with the histories of intestinal diseases or relative symptoms, high lipid diet, emotional trauma and family history of cancers. The suitable physical activities and dietary fibers are protective factors.

Case-Control Studies↗
PubMed2003

[Studies on immune function of Rabdosia excisa].

OBJECTIVE: To study the immune function of Rabdosia excisa decoction. METHODS: Weighting immune organ of mice, and studying the effects on carbon clearance rate in mice, lymphocyte transformation in vitro, the formation of serum hemolysin in mice and delayed hypersensitivity. RESULTS: 10 or 20 g/kg Rabdosia excisa decoction (RED) had no effect on spleen weight and thymus gland weight by ig. By i.p. 0.5, 2 g/kg RED or ig 20 g/kg RED, Rabdosia excisa group could inhibit the carbon clearance rate and lymphocyte transformation, but the group had no obvious effect on the formation of serum hemolysin. 2, 1, 0.5 and 0.25 g/kg RED could significantly inhibit delayed hypersensitivity by i.p. CONCLUSION: RED could significantly inhibit reticuloendothelial system and cellular immunity, but had no obvious effect on humoral immunity.

Adjuvants, Immunologic↗
PubMed2003

[Respiratory control during sleep and the development of nocturnal hypoxia in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: It is assumed that the reduced ventilatory control during sleep may be related to the nocturnal hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and daytime CO(2) retention. METHODS: Oxygen desaturation index (ODI(4)), sleep time spent when SaO(2) was below 90% (SIT(90)), the lowest SaO(2) (LSaO(2)) and the mean SaO(2) (MSaO(2)) during sleep were measured in 24 OSAHS patients with daytime PaCO(2) > or = 45 mm Hg and 39 with PaCO(2) < 45 mm Hg. Hypoxic (DeltaP(0.1)/DeltaSaO(2)) and hypercapnic (DeltaP(0.1)/DeltaPaCO(2)) responsiveness were measured in 11 eucapnic and 4 hypercapnic patients during wakefulness, NREM and REM sleep stages. RESULTS: Compared with the eucapnic patients, all the hypercapnic patients had more severe hypoxia during sleep (P < 0.05). Although both groups had similar chemical responsiveness during wakefulness, the hypercapnic patients had lower DeltaP(0.1)/DeltaSaO(2) and DeltaP(0.1)/DeltaPaCO(2) during both REM and NREM sleep (P < 0.05). CONCLUSION: The depressed chemical responsiveness during sleep plays an important role in the development of nocturnal hypoxia in OSAHS patients with daytime CO(2) retention.

Carbon Dioxide↗
PubMed2003

[Phase II clinical study of intratumoral H101, an E1B deleted adenovirus, in combination with chemotherapy in patients with cancer].

BACKGROUND & OBJECTIVE: In recent years,great development have been made in cancer therapeutics with replication-competent viruses (oncolytic viruses), E1B deleted adenovirus is one of promising viruses. The current study was designed to evaluate the efficacy and toxicity of intratumoral H101, a E1B-deleted adenovirus, in combination with chemotherapy on patients with cancer. METHODS: A total of 50 patients with malignant tumors in multiple centers clinical trial were treated with H101, 0.5ml 5x10(11) viral particle per day for 5 consecutive days every three weeks. Routine chemotherapy was performed at the same time. And the efficacy and toxicity were recorded. RESULTS: Among 46 valuable cases, the overall response rate was 30.4%. The response rate was 28.0% (14/50) among ITT population, including 3 complete response (CR) and 11 partial response (PR). The overall response rate of control lesion was 13.0%, including 1 case of CR and 5 cases of PR. Thus, the response rate in injected lesion is clearly higher than that in control lesion (P< 0.001). Main side effects were injection site pain (26.9%) and fever (30.2%). Grade 1 hepatic dysfunction was found in 4 patients, grade 2 in 1 patients, grade 4 in 1 patients. Grade 4 hematological toxicities were found in 4 patients. CONCLUSION: The study showed that the combination of genetically modified adenovirus (H101) and chemotherapy possessed some effect for treating the patients with refractory malignant tumors, and the toxicities were lower, well tolerated.

Adenoviridae↗
PubMed2003

[Modification of the antiapoptotic ability of H18 hybridoma cells].

To construct eukaryotic expression vector containing murine bcl-XL and stably express it in H18 hybridoma cells in order to enhance hybridoma cells antiapoptotic ability. PCR was used to obtain 710bp murine bcl-XL cDNA from pGEM-T-bcl-XL. Then the recombinant expression vector pEF-bcl-XL was constructed by cloning bcl-XL cDNA into eukaryotic expression vector pEF by Pst I and Xho I double digestion. After transfection into H18 hybridoma cells through lipofectamine 2000, the stable expression cell line was screened by 800mg/L G418. The expression of bcl-XL gene was detected by Western blotting. Flow cytometer was used to test the modified hybridoma cells ability to resist apoptosis induced by 0.4mmol/L Sodium Butyrate. The eukaryotic expression vector pEF-bcl-XL was successfully constructed and stably expressed in H18 hybridoma cells. Our data showed that stably transfected H18 cells expressed high levels of Bcl-XL. Under the condition of 0.4mmol/L NaBu, the production of antibody was to be significantly increased by more than 3-fold in stably transfected H18, which resulted from suppressing the NaBu-induced apoptosis and allowing stably transfected H18 cells to grow at higher viability and extend culture longevity by > 3 days. The increased culture longevity by inhibition of NaBu-induced apoptosis by inducible expression of Bcl-XL combined with the enhanced secretion of antibody by NaBu contributed to the enhancement of final antibody concentration in the stably transfected H18 cells culture. The final antibody concentration of stably transfected H18 cells in the presence of NaBu was three-fold higher than that of H18 cells culture in the absence of NaBu. Together, our results showed that butyrate is of practical interest for production of antibody. NaBu-induced apoptosis of hybridoma cells could be inhibited by inducible expression of Bcl-XL. The expression of murine bcl-XL gene in hyridoma cells and the increasing antiapoptosis ability of hybridoma cells are of significance in further use of hybridoma cells in high density large scale cell culture.

Animals↗
PubMed2002

Local energy landscape flattening: parallel hyperbolic Monte Carlo sampling of protein folding.

Among the major difficulties in protein structure prediction is the roughness of the energy landscape that must be searched for the global energy minimum. To address this issue, we have developed a novel Monte Carlo algorithm called parallel hyperbolic sampling (PHS) that logarithmically flattens local high-energy barriers and, therefore, allows the simulation to tunnel more efficiently through energetically inaccessible regions to low-energy valleys. Here, we show the utility of this approach by applying it to the SICHO (SIde-CHain-Only) protein model. For the same CPU time, the parallel hyperbolic sampling method can identify much lower energy states and explore a larger region phase space than the commonly used replica sampling (RS) Monte Carlo method. By clustering the simulated structures obtained in the PHS implementation of the SICHO model, we can successfully predict, among a representative benchmark 65 proteins set, 50 cases in which one of the top 5 clusters have a root-mean-square deviation (RMSD) from the native structure below 6.5 A. Compared with our previous calculations that used RS as the conformational search procedure, the number of successful predictions increased by four and the CPU cost is reduced. By comparing the structure clusters produced by both PHS and RS, we find a strong correlation between the quality of predicted structures and the minimum relative RMSD (mrRMSD) of structures clusters identified by using different search engines. This mrRMSD correlation may be useful in blind prediction as an indicator of the likelihood of successful folds.

Models, Molecular↗
PubMed2002

Ab initio protein structure prediction on a genomic scale: application to the Mycoplasma genitalium genome.

An ab initio protein structure prediction procedure, TOUCHSTONE, was applied to all 85 small proteins of the Mycoplasma genitalium genome. TOUCHSTONE is based on a Monte Carlo refinement of a lattice model of proteins, which uses threading-based tertiary restraints. Such restraints are derived by extracting consensus contacts and local secondary structure from at least weakly scoring structures that, in some cases, can lack any global similarity to the sequence of interest. Selection of the native fold was done by using the convergence of the simulation from two different conformational search schemes and the lowest energy structure by a knowledge-based atomic-detailed potential. Among the 85 proteins, for 34 proteins with significant threading hits, the template structures were reasonably well reproduced. Of the remaining 51 proteins, 29 proteins converged to five or fewer clusters. In the test set, 84.8% of the proteins that converged to five or fewer clusters had a correct fold among the clusters. If this statistic is simply applied, 24 proteins (84.8% of the 29 proteins) may have correct folds. Thus, the topology of a total of 58 proteins probably has been correctly predicted. Based on these results, ab initio protein structure prediction is becoming a practical approach.

Algorithms↗
PubMed2002

Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells.

Soybean consumption may be beneficial to prevention of certain human cancers. Low incidence of colon cancer in Asian countries is associated with consumption of soybean products. A limited number of human and animal studies suggested that soybean consumption might prevent colon cancer; other studies did not support this conclusion. Therefore, it is important to understand the biological effects of soybeans on colon cells. In the present study, cultures of Caco-2, SW620, and HT-29 cells were treated with soybean extract, the soluble fraction of a soybean product. The crude extract contains proteins and many soluble components of soybeans. After incubation with soybean extract (1-6%, vol/vol) for 24 h, most Caco-2 cells were found to contain numerous vacuoles within the cytoplasm and to become very flat. Exposure to > 6% soybean extract resulted in cell death and giant vacuoles. Soybean extract (0.25-2%) induced small vacuoles within the cytoplasm of SW620 cells. SW620 cells detached from culture dishes at > 2% soybean extract. Exposure to 0.5-2% soybean extract produced vacuoles within HT-29 cells similar to those observed in SW620 cells. Soybean extract significantly reduced density of Caco-2, SW620, and HT-29 cells. Reducing protein content of soybean extract reduced but did not abolish its effects on colon cells. Purified genistein (12.5 micrograms/ml) was capable of producing morphological changes similar to those observed after treatment of colon cells with soybean extract. Assays using annexin V-propidium iodide demonstrated that treatment of Caco-2 and SW620 cells with soybean extract increased cell death. Membranes of vacuoles in soybean-treated Caco-2 and SW620 cells were labeled with Texas red-conjugated wheat germ agglutinin, a cytological marker for the Golgi apparatus. Exposure to soybean extract enhanced protein levels of Rab6, a small GTP-binding protein that is involved in regulation of membrane traffic of the Golgi apparatus. Data from this study suggest that exposure to soybean extract or isoflavones affects morphology and survival of colon cancer cells and that the response to soybean extract varies depending on the cell lines examined.

Caco-2 Cells↗
PubMed2002

[The clinical effects of percutaneous lumbar discectomy combined with sodium hyaluronate in the treatment of lumbar intervertebral disc herniation].

OBJECTIVE: To investigate the therapeutic effect of percutaneous lumbar discectomy (PLD) combined with sodium hyaluronate (SH) injection in the treatment of lumbar intervertebral disc herniation. METHODS: Forty-eight patients suffered from lumbar disc herniation were divided into two groups and treated by PLD combined with SH injection into epidural cavity (treatment group) or single PLD (control group) respectively. All patients were followed up for 24 months. The therapeutic effects in both groups were assessed and compared according to Macnab's criterion. RESULTS: The patients in the treatment group got much more significant improvement than those in the control group, with shorter therapeutic course and more safety. CONCLUSION: PLD combined with SH injection into epidural cavity is more effective and safety in the treatment of lumbar disc herniation than of pure PLD.

Adolescent↗
PubMed2002

[Effect of exogenous hyaluronan on wound healing].

OBJECTIVE: To investigate the mechanism of impeded wound healing by exogenous hyaluronan (HA). METHODS: Wound healing models were established on 18 adult rabbit ears, which were randomly divided into 3 groups, the 2% HA treated-group (group A), the 1% HA treated-group(group B), and the PBS control group (group C). The process of wound healing was observed morphologically and histologically. The expression of alpha-smooth muscle actin in fibroblast was measured by immunohistochemical method. RESULTS: 1. The mean values of wound healing time of groups A, B and C were (11.7 +/- 0.6), (11.3 +/- 0.6), and (10.8 +/- 1.0) days respectively. Wound contraction was greater in group C than in group A and group B. 2. Compared with PBS controls, the collagen fibril was slender and arrayed regularly in HA treated wound. 3. The expression of alpha-smooth muscle actin was greater in group C than in groups A and B. CONCLUSION: It is one of reasons of impeded wound healing that exogenous HA inhibits the expression of alpha-smooth muscle protein and wound contraction. There exists dose-dependent effect.

Actins↗
PubMed2002

Pharmacokinetics and partial thromboplastin time after intravenous recombinant hirudin variant-2 in rhesus monkeys.

AIM: To study the pharmacokinetics (PK) and changes of kaolin partial thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 % of the total dose) plus infusion (the remained 50 % of the dose) in rhesus monkeys. METHODS: A crossover design was applied to research the PK and KPTT profiles of rHV-2 after single (with total dose at 1, 3, and 6 mg/kg, respectively) and multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay (ELISA) method was utilized to determine the level of rHV-2 in plasma. RESULTS: The concentration profiles of rHV-2 during or after administration were dependent both on the loading dose and the infusion rate. Mean Cmax after bolus in three single dose groups were 2.90, 9.78, and 15.68 mg/L, respectively. Infusions at rate of 8.35, 25, and 50 g/kg/h in 1 h resulted in steady-state levels of 0.73-0.86, 1.94-2.04, and 5.41-5.59 mg/L, respectively. The plasma rHV-2 levels during or after administration among doses were significantly different at most of the time points. Area under concentration-time curve (AUC) increased linearly with dose but systemic clearances were similar among different groups. KPTT was significantly prolonged (compared with baseline) at all dose levels, and trended to increase with dose. CONCLUSION: Both the loading dose and the infusion rate are very important for controlling the rHV-2 level, and the data may be helpful for optimizing dosage-regimen in clinical trials.

Animals↗