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Biomedical subjects

Y Dong

Publications and source records attributed to Y Dong.

At least 55 records · Page 3Linked to original sources

A pregnane steroid from Aglaia lawii and structure confirmation of cabraleadiol monoacetate by X-ray crystallography.

The pregnane steroid, (E)-aglawone, along with four known triterpenes, and a known sterol mixture were isolated from the bark of Aglaia lawii (Wight) Saldanha ex Ramamoorty (Meliaceae). The structural determination/identification was accomplished by a combination of 1D- and 2D-NMR spectroscopic techniques. The relative stereochemistry of the known triterpene, 20S,24S-epoxydammarane-3alpha,25-diol acetate, was also unequivocally determined for the first time by X-ray crystallography. The isolates were not active against various human cancer cell lines.

Crystallography, X-Ray↗

Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism-based quantitative structure-activity relationship (QSAR) study.

Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure-activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K(ow))-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K(ow)-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K(ow), energy of lowest unoccupied orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular connectivity dices (1chi(p)).

Animals↗

Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter.

The aim of this study was to examine whether the human alpha-fetoprotein (AFP) enhancer could be used to induce hepatocellular carcinoma (HCC)-selective expression of the herpes simplex virus thymidine kinase (HSV-tk) gene which is under the control of the phosphoglycerate kinase (pgk) promotor. The human AFP enhancer was linked with the non-tissue-specific, human housekeeping pgk promoter in a retroviral vector. AFP-producing HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter were much more susceptible to the prodrug, ganciclovir (GCV), than those infected with the same retroviruses without the AFP enhancer. Non-HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter exhibited profoundly increased resistance to GCV compared with those infected with the same retroviruses without the AFP enhancer. Northern blot analysis revealed that the AFP enhancer caused enhanced HSV-tk expression in AFP-producing HCC cells and suppressed HSV-tk expression in non-HCC cells. Our results indicate that the AFP enhancer could give HCC selectivity to the pgk promoter, and that this novel strategy may be useful for HCC-selective cancer gene therapy.

Blotting, Northern↗

Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with development of hepatocellular carcinomas.

Mammalian cell cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address the role of these cell cycle proteins in hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis were used as a human experimental system. The inbred LEC (Long-Evans with a cinnamon-like coat color) rats were used as an animal experimental HCC model. Immunohistochemical staining of serial paraffin sections was performed using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2 were concurrently overexpressed in hepatocellular carcinomas both in human and rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were shown to increase along with the development of hepatocellular carcinomas. Analysis of the correlation between expression of cyclin E and CDK2 and clinicopathological parameters revealed a significant correlation between expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated with poorly differentiated HCCs. The results suggest that overexpression of cyclin E and CDK2 plays an important role in the development of hepatocellular carcinoma.

Journal Article↗

Vaccenic acid feeding increases tissue levels of conjugated linoleic acid and suppresses development of premalignant lesions in rat mammary gland.

The objective of this report was to determine whether vaccenic acid (t11-18:1) is converted efficiently to conjugated linoleic acid (c9,t11-18:2, CLA) in rats via the delta 9-desaturase reaction and, if so, whether vaccenic acid could substitute for CLA as an anticancer agent. In Study 1, rats were fed 1%, 2%, or 3% vaccenic acid in their diet, and tissue levels of CLA and CLA metabolites were determined in liver and mammary gland. In general, concentrations of CLA and CLA metabolites increased proportionately with an increase in vaccenic acid intake, at least up to the 2% dose level. Beyond this dose, there was clearly a plateauing effect. Thus vaccenic acid concentration increased from an undetectable level in the control to 78.5 nmol/mg lipid in the liver of rats fed a 2% vaccenic acid diet. This was accompanied by an increase in CLA from 2.3 to 33.6 nmol/mg lipid. These changes were also mirrored in the mammary gland, where increases in vaccenic acid (from 27.5 to 163.2 nmol/mg lipid) and CLA (from 17.8 to 108.9 nmol/mg lipid) were similarly observed. Vaccenic acid at 2% produced a CLA concentration in the mammary gland that was historically associated with a positive response in tumor inhibition based on our past experience. This provided the basis for selecting 2% vaccenic acid in Study 2, which was designed to evaluate its efficacy in blocking the development of premalignant lesions in the rat mammary gland. In this experiment, formation of histologically identifiable pathology due to intraductal proliferation of terminal end bud cells of mammary epithelium was used as the end point of analysis at 6 wk after carcinogen administration. Treatment with vaccenic acid reduced the total number of these premalignant lesions by approximately 50%. We hypothesize that the anticancer response to vaccenic acid is likely to be mediated by its endogenous conversion to CLA via delta 9-desaturase.

8,11,14-Eicosatrienoic Acid↗

Plasma tranexamic acid concentrations during cardiopulmonary bypass.

UNLABELLED: Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.

Adult↗

A multi-resolution wireless force sensing system based upon a passive SAW device.

Referring to the technology of SAW wireless identification systems, a multi-resolution wireless force sensing system, including a passive time-delay SAW device and a specific interrogation unit, is introduced in this paper. Using an IDT, which connects with an antenna, as the force sensing element is a design to transduce the electromagnetic wave into surface acoustic wave and vice versa. Several reflectors are designed to get multi-resolution. Sample/hold devices are used instead of high-speed A/D converter to construct a low-cost interrogation system. Properties of the sensing system are theoretically predicted and experimentally verified.

Journal Article↗

Force-frequency coefficient of symmetrical incomplete circular quartz crystal resonator.

The changes in the resonance frequencies of the thickness-shear vibration of symmetrical incomplete circular AT-cut quartz crystal resonators (QXRs), which are used as sensing elements in digital force sensors or pressure transducers, by the application of diametrical forces are discussed by considering the piezoelectric effect and the anistropic characteristics of crystal plates. Two-dimensional motion equations for predicting the frequency changes are derived from three-dimensional piezoelectricity equations, and equations deduced by Janiaud for solving the stress distribution in crystal plates are used to calculate the force-frequency coefficients of incomplete circular resonators. The results show that the piezoelectric effect of crystal plates decreases the force-frequency coefficient of the azimuth angle 0 degrees by 7% as compared with no piezoelectricity assumption. The incomplete circular shape can be applied to a larger load than the circular disc because the flat regions of the incomplete shape provide a distributed load application without the problems of stress concentration of a point force inherent to a circular disc. The incomplete shape gives an increased force sensitivity when compared with the complete disc near azimuth angle 0 degrees. The theoretical curves agree well with Ratajski's experimental results.

Journal Article↗

Genomic interspecies microarray hybridization: rapid discovery of three thousand genes in the maize endophyte, Klebsiella pneumoniae 342, by microarray hybridization with Escherichia coli K-12 open reading frames.

In an effort to efficiently discover genes in the diazotrophic endophyte of maize, Klebsiella pneumoniae 342, DNA from strain 342 was hybridized to a microarray containing 96% (n = 4,098) of the annotated open reading frames from Escherichia coli K-12. Using a criterion of 55% identity or greater, 3,000 (70%) of the E. coli K-12 open reading frames were also found to be present in strain 342. Approximately 24% (n = 1,030) of the E. coli K-12 open reading frames are absent in strain 342. For 1.6% (n = 68) of the open reading frames, the signal was too low to make a determination regarding the presence or absence of the gene. Genes with high identity between the two organisms are those involved in energy metabolism, amino acid metabolism, fatty acid metabolism, cofactor synthesis, cell division, DNA replication, transcription, translation, transport, and regulatory proteins. Functions that were less highly conserved included carbon compound metabolism, membrane proteins, structural proteins, putative transport proteins, cell processes such as adaptation and protection, and central intermediary metabolism. Open reading frames of E. coli K-12 with little or no identity in strain 342 included putative regulatory proteins, putative chaperones, surface structure proteins, mobility proteins, putative enzymes, hypothetical proteins, and proteins of unknown function, as well as genes presumed to have been acquired by lateral transfer from sources such as phage, plasmids, or transposons. The results were in agreement with the physiological properties of the two strains. Whole genome comparisons by genomic interspecies microarray hybridization are shown to rapidly identify thousands of genes in a previously uncharacterized bacterial genome provided that the genome of a close relative has been fully sequenced. This approach will become increasingly more useful as more full genome sequences become available.

Escherichia coli↗

Control of rat mammary epithelium proliferation by conjugated linoleic acid.

Past research showed that mammary gland morphogenesis in the pubescent rat was retarded by the feeding of conjugated linoleic acid (CLA). A major objective of the present study was to examine the proliferative activity and the expression of cell cycle regulatory proteins in the developing mammary epithelium of rats fed a mixture of CLA isomers (primarily as free fatty acid c9, t11-CLA and t10,c12-CLA) or a highly enriched natural source of c9,t11-CLA (as triacylglycerol in butterfat). In both experiments, the diets, with or without CLA, were started at weaning and continued for four weeks. The two CLA preparations were equally effective in suppressing bromodeoxyuridine labeling and the expression of cyclin D1 and cyclin A (determined by immunohistochemistry) in the terminal end buds and alveolar clusters of the mammary epithelium while it undergoes extensive ductal branching during pubescence. There was a trend of an increase, although not statistically significant, in the proportion of cells expressing the p16 and p27 cdk inhibitors. A separate experiment was designed to evaluate the effect of c9,t11-CLA (as a free fatty acid of > 90% purity) treatment on the rate of proliferation of the mammary epithelium as the animal matured from weanling to adult. The bromodeoxyuridine labeling data indicated that the mammary epithelium appeared to lose its sensitivity to CLA control of proliferation as it completely filled the fat pad and became quiescent. These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status.

Animals↗

Cyclin-dependent kinase inhibitor p27 is related to cell proliferation and prognosis in laryngeal squamous cell carcinomas.

An immunohistochemical study of both p27 and proliferating cell nuclear antigen (PCNA) was performed on 102 cases of laryngeal squamous cell carcinomas (LSCCs), and large variations in p27 expression were found among the tumours. Reduced expression of p27 was revealed in 54 (52.9 per cent) cases and correlated with tumour size, lymph node metastasis, and clinical stage, but did not correlate with age, sex, tumour site, or tumour grade. A significant positive correlation was found between the percentage of loss of p27 expression and the PCNA index (r = 0.844, p < 0.0001). Reduced expression of p27 was significantly correlated with both reducing disease-free and overall survival by univariate analysis. By multivariate analysis, reduced expression of p27, tumour grade, tumour size, lymph node metastasis as well as clinical stage were independent prognostic factors for overall survival of LSCCs. These findings indicate that reduced expression of p27 may be correlated with the malignant biological behaviour of LSCCs.

Aged↗

The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions.

The tissue kallikreins are serine proteases encoded by highly conserved multi-gene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13-26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5' or 3' untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25-44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.

Amino Acid Sequence↗

Apoptosis inducing novel anti-leukemic agent, bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV) [VO(SO4)(Me2-Phen)2] depolarizes mitochondrial membranes.

Bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV) [VO(SO(4) )(Me(2)-Phen)(2)] induces apoptosis in human NALM-6 leukemia cells. In the present report, we demonstrate that VO(SO(4) )(Me(2)-Phen)(2)-induced apoptosis is mediated through the generation of reactive oxygen species (ROS), depletion of glutathione and depolarization of mitochondrial membrane potential (DeltaPsim). Using multilaser flow cytometry methods, we further mapped out the death sequence that occurs in VO(SO(4))(Me(2)-Phen)(2)-treated leukemic cells. Triple labeling method to measure ROS, DeltaPsim and glutathione coupled with multilaser excitation flow cytometry showed that induction of ROS took place before the loss of mitochondrial permeability transition and depletion of glutathione. Correlated two parameter plots of glutathione content versus DeltaPsim showed that loss of DeltaPsim and depletion of glutathione closely follows each other. Translocation of phosphatidylserine to the outer leaflet of the cell membrane was the final step in the process before the cells became apoptotic. These results demonstrate that the mitochondrial permeability transition takes place during VO(SO(4))(Me(2)-Phen)(2)-induced apoptosis and is mediated through induction of ROS and depletion of glutathione.

Antineoplastic Agents↗

Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(I.V.) as a novel antileukemic agent with matrix metalloproteinase inhibitory activity.

We have examined the in vitro anticancer activity of METVAN [bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO(4))(Me(2)-Phen)(2)] against acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid leukemia (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-77, U266BL, and HS-SULTAN) cell lines as well as primary leukemic cells from patients with ALL, AML, and chronic acute myeloid leukemia (CML). METVAN induced apoptosis in NALM-6, MOLT-3, and HL-60 cells in a concentration-dependent fashion with EC(50) values of 0.19 +/- 0.03 microM, 0.19 +/- 0.01 microM, and 1.1 +/- 0.2 microM, respectively. METVAN induced apoptosis at low micromolar concentrations in primary leukemic cells from patients with ALL, AML, and CML. METVAN inhibited the constitutive expression of matrix metalloproteinase (MMP)-9 protein and its gelatinolytic activity in HL-60 cells and MMP-2 as well as MMP-9 gelatinolytic activities in leukemic cells from ALL, AML, and CML patients. Furthermore, METVAN inhibited the leukemic cell adhesion to the extracellular matrix proteins laminin, type IV collagen, vitronectin, and fibronectin and the invasion through Matrigel matrix. Further preclinical development of METVAN may provide the basis for the development of more effective chemotherapy programs.

Antineoplastic Agents↗

[Expression of human brain derived neurotrophic factor gene in E. coli].

The primers specific for the full-length BDNF coding sequence was designed and synthesized. The BDNF coding sequence was directly amplified from human genomic DNA by using PCR and inserted into vector pGEM-3Zf(+). The recombinant DNA was transformed into the host cells JM109 to obtain the positive clone pGEMBF18. The restriction enzyme analysis and DNA sequence detection confirmed that the inserted fragment of clone pGEMBF18 is the full-length BDNF coding sequence. The hBDNF DNA fragment was recovered from the clone pGEMBF18 and ligated with prokaryotic expression vector pGEX-5T to construct the recombinant expression plasmid p5TBF34. The E. coli JM109 transformed with p5TBF34 was induced with IPTG. A new protein band with apparent molecular weight 43 kDa was detected in the lysate of the transformed cell by using SDS-PAGE. The result of western hybridization showed that this fusion protein reacted specifically to the antibodies to human BDNF. The amount of the soluble fusion protein was about 503.04 mg/L lysate, 7.53% of total bacterial soluble protein of transformed cells, estimated by absorbance scanning of SDS-PAGE and protein quantitation.

Brain-Derived Neurotrophic Factor↗

Community health services in China: the experience of Tianjin City.

China's excellent community health system was seriously damaged during the early years of economic reform after 1982, and its reconstitution has become a major policy goal of the government since 1996. This article provides a brief overview of experiences in implementing the policy of community health care in a large Chinese city, Tianjin. I outline the policy setting and describe Tianjin's experiences. Some initial benefits of the new system are summarised and the difficulties and barriers are noted. I conclude with some suggestions for further improvement.

China↗

[Organochlorine residues in eggs of night heron breeding in Yuantouzhu, Wuxi and their functions as bioindicator].

This study analyzed chlorinated pesticides in eggs of night heron breeding in Yuantouzhu, Tai lake. The HCH isomers, DDT, DDD, DDE, endrine and heptachlor epoxide were detected out in egg samples. The residue level and the percent of detection of beta-HCH and p,p'-DDE were significantly high. The mean value of p,p'-DDE was 0.906 microgram/g dry weight. Most of the chlorinated pesticides in samples from Wuxi were higher than those of Gongqing city, Jiangxi province. Oppositely, the hatching rate of night heron egg in Wuxi region was lower than that in Gongqing city. It may be related to the difference of DDE residual levels. Using organochlorine residue in eggs of water-fowls as an indicator for environmental quality assessment is feasible.

Animals↗

[The experimental study of the anti-enterovirus effects of drugs in vitro].

OBJECTIVE: To screen the safe and effective anti-enterovirus drugs for clinical application. METHODS: The cytotoxicity of Ribavirin, Shuanghuanglian and Garlic were evaluated through MTT colorimetry and cell morphology. The antiviral activity of Ribavirin, Shuanghuanglian and Garlic were studied in HEL and Vero cells infected with CBV3 and ECHO11 by observing cytopathic effect (CPE), MTT colorimetry and plaque-reduction assay. The antiviral activity of these three drugs were compared and that of Shuanghuanglian and Garlic were also compared before and after ECHO11 absorbing by plaque-reduction assay. RESULTS: (1) The cytotoxicity of these three drugs were expressed as TC50(50% toxic concentration). TC50 of Ribavirin was 2 mg/ml, of Shuanghuanglian 5 mg/ml, of Garlic 12.5 micrograms/ml. (2) Ribavirin could inhibit CBV3 and ECHO11 at the concentration ranged from 1 mg/ml to 1.5 mg/ml. Shuanghuanglian could inhibit CBV3 and ECHO11 at the concentration of 0.5 mg/ml and the viral inhibiting effect was concentration-dependent. Garlic could inhibit CBV3 and ECHO11 at the concentration ranged from 2.5 micrograms/ml to 7.5 micrograms/ml and 5 micrograms/ml was the most effective. (3) Plaque-reduction assay was used to test the anti-virus (CBV3 and ECHO11) activity of these three drugs: plaque reduction rate of 1.5 mg/ml Ribavirin was 43.2% and 37.2%, of 2.5 mg/ml Shuanghuanglian was 81.1% and 88.4% and of 5 micrograms/ml Garlic was 66.2% and 77.4% respectively. The plaque reduction rate of Ribavirin was lower than the other two drugs (P < 0.05), between these two showed no significant difference (P > 0.05). The anti-ECHO11 activity of Shanghuanglian before ECHO11 adsorbing was higher than after ECHO11 adsorbing (P < 0.05). There was no significant difference between the plaque reduction rates of Garlic before and after ECHO11 adsorbin. CONCLUSION: All of the three drugs have anti-virus activity in vitro while Shuanghuanglian and Garlic are more effective. Among these three drugs, the cytotoxicity of Shuanghuanglian is the most weak and the anti-virus activity is the strongest. The antiviral activity of Shuanghuanglian adding before virus adsorbing was higher, so it seems that Shuanghuanglian can prevent EV infection.

Animals↗