Biomedical subjects

Ling He

Publications and source records attributed to Ling He.

28 records · Page 2Linked to original sources

PubMed2003

Design of antineoplastic agents based on the '2-phenylnaphthalene-type' structural pattern--synthesis and biological activity studies of 11H-indolo[3.2-c]quinoline derivatives.

Designed as a new group of planar molecule containing the proposed 2-phenylnaphthalene-type structure, a number of 11H-indolo[3.2-c]quinoline derivatives were synthesized and evaluated biologically. Several compounds were found to possess cytotoxic activity against the growth of human promyelocytic leukemia cells (HL-60), against the small cell lung cancer (SCLC), and showed good response in the National Cancer Institute preclinical antitumor drug discovery 60-cell line panel.

Antineoplastic Agents↗

PubMed2003

EST pipeline system: detailed and automated EST data processing and mining.

Expressed sequence tags (ESTs) are widely used in gene survey research these years. The EST Pipeline System, software developed by Hangzhou Genomics Institute (HGI), can automatically analyze different scalar EST sequences by suitable methods. All the analysis reports, including those of vector masking, sequence assembly, gene annotation, Gene Ontology classification, and some other analyses, can be browsed and searched as well as downloaded in the Excel format from the web interface, saving research efforts from routine data processing for biological rules embedded in the data.

Automation↗

PubMed2003

Isolation and structure elucidation of Sch 642305, a novel bacterial DNA primase inhibitor produced by Penicillium verrucosum.

A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.

Arizona↗

PubMed2003

Crystal structure of the 1:2:2 adduct of piperazine, o-phthalic acid and water.

The adduct of piperazine, o-phthalic acid and water (1:2:2), C20H26N2O10, crystallizes in the monoclinic space group P21/c with a = 6.129(1), b = 12.810(2), c = 13.137(2)A, beta = 95.87(1) degrees, V = 1026.0(3)A3, Z = 2. The piperazinium adopts a chair comformer, and is tied with the hydrogen orthophthalate via a hydrogen bond of the N-H...O type. Because of bifurcated hydrogen bonding of C(sp3)H-O [3.0801(17) and 3.1408(18)A] and the shortest hydrogen bond of C(sp3)H-O [2.9758(17)A], C(sp3)H-O hydrogen bonds play important roles in stablizing the title adduct.

Journal Article↗

PubMed2003

Isolation and characterization of two new antifungal antibiotics from a basidiomycete.

Two novel antibiotics, Sch 484129 (1) and Sch 484130 (2), were isolated from the fermentation broth of a fungal culture, which was identified as a Basidiomycete. The new antibiotics were obtained by ethyl acetate extraction followed by reversed phase HPLC purification. Structure elucidation of 1 and 2 was accomplished by spectroscopic data analyses. Derivatizations of the major component 1 were performed in order to provide definitive structural information. Both components were identified as glycolipids and displayed antifungal activity against Saccharomyces and Aspergillus strains.

Antifungal Agents↗

PubMed2002

Ethanol induction of class I alcohol dehydrogenase expression in the rat occurs through alterations in CCAAT/enhancer binding proteins beta and gamma.

Alcohol dehydrogenase (ADH) is the principal ethanol-metabolizing enzyme. Ethanol induces rat Class I ADH mRNA and activity by an as yet unknown mechanism. In the current study, adult male rats were fed an ethanol-containing diet by continuous intragastric infusion for 42 days. Hepatic Class I ADH mRNA, protein, and activity levels in the ethanol-infused rats increased 3.9-, 3.3-, and 1.7-fold, respectively (p <0.05). Cis-acting elements within the proximal promoter region of the ADH gene were studied by electrophoretic mobility shift assay (EMSA). Hepatic nuclear extract (HNE) binding to either the consensus or ADH-specific CCAAT/enhancer binding protein (C/EBP) sites was >2.4-fold greater in ethanol-fed rats (p <0.05) than controls. Antibody-specific EMSA assays demonstrated binding of the transcription factor C/EBPbeta to the C/EBP site. Western blot immunoblot analysis of HNEs demonstrated 3.5- and 2.3-fold increases in C/EBPbeta (LAP) and C/EBPdelta (p <0.05), respectively, in ethanol-fed rats compared with controls, whereas levels of the truncated C/EBPbeta (LIP) and C/EBPgamma were lower in ethanol-fed rats (p <0.05). HNE from ethanol-fed rats increased (3-fold) the in vitro transcription of rat Class I ADH (p <0.05), and mutation of the C/EBP element in the proximal promoter region blocked this effect. Antisera against LIP or C/EBPgamma enhanced transcription efficiency (p <0.05). These data provide the first evidence for the mechanism by which ethanol regulates rat hepatic Class I ADH gene expression in vivo. This mechanism involves the C/EBP site and the enhancer binding proteins beta and gamma.

Alcohol Dehydrogenase↗

PubMed2002

Interaction of multidrug resistance reversal agents with P-glycoprotein ATPase activity on blood-brain barrier.

AIM: To gain further insights into the mechanism of the ATP-dependent interaction of P-glycoprotein (P-gp) with various multidrug resistance (MDR) reversal agents. METHODS: Bovine brain capillary endothelial cells (BCEC) were isolated from cerebral gray matter using modifications of the mechanical homogenization technique. Plasma membranes were prepared from BCEC. The P- gp adenosine triphosphatase (ATPase) activity of the isolated BCEC membranes was estimated by measuring inorganic phosphate liberation. RESULTS: The basal P-gp ATPase activity was increased by verapamil (Ver), vincristine (VCR), doxorubicin (Dox), tetrandrine (Tet), dauricine (DRC), berbamine (BBM), and daurisoline (DRS), with respective half-maximal activity concentrations Km of about 17, 5.9, 41, 2.3, 11, 23, and 22 micromol/L. Berberine (BBR) produced a relatively slight activation. dl-Tetrahydropalmatine (dl-THP) and l-tetrahydropalmatine (l-THP ) does not alter the basal P-gp ATPase activity. Cyclosporin A (CsA) inhibited both the basal and the drug-stimulated ATPase activity of P-gp with high affinity. Kinetic analysis indicated a competitive inhibition of Ver- or VCR-stimulated ATPase activity and a noncompetitive inhibition of Dox- or Tet-activated ATPase activity by CsA. Moreover, Dox inhibited Tet-activated P-gp ATPase activity in a noncompetitive manner. CONCLUSION: Various MDR reversal agents could interact with P-gp and alter its ATPase activity in different manners. This is the result of the b road molecular recognition specificity of P-gp. CsA, Ver, and VCR could bin d P-gp either on overlapping sites or distant but interacting sites, while CsA, Dox, and Tet could independently bind P-gp on separated sites on blood-brain barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells.

AIM: To search for novel effective P-glycoprotein (P-gp) reversal agents in the blood-brain barrier (BBB). METHODS: Using rhodamine123 (Rh123) to examine the functional activity of P-gp in cultured bovine brain capillary endothelial cells (BCEC) and screen various principles on P-gp modulation in BBB. RESULTS: All of tested compounds (1-10 micromol/L) increased the intracellular accumulation of Rh123 in a concentration-dependent manner. The rank order of these agents in increasing Rh123 accumulation in BCEC was: cyclosporin A (CsA) > tetrandrine (Tet) > vincrinstine (VCR) approximate, equals flunarizine (Flu) > dl-tetrahydropalmatine (dl-THP) > dauricine (DRC) > azithromycin (Azi) > verapamil (Ver) approximate, equals berbamine (BBM) > daurisoline (DRS) > berberine (BBR) approximate, equals doxorubicin (Dox) > l-tetrahydropalmatine (l-THP) > tetramethylpyrazine (TMP). These agents at concentration of 10 micromol/L increased Rh123 accumulation by 346 %, 203 %, 136 %, 129 %, 115 %, 103 %, 92 %, 87 %, 81 %, 75 %, 67 %, 67 %, 63 %, and 54 %, respectively. The effects of CsA, Tet, Ver, Flu, Azi, and dl-THP on cellular accumulation of Rh123 in BCEC were reversible. When CsA, Tet, Ver, Flu, Azi, or dl-THP-pretreated BCEC were examined at 48, 36, 24, 36, 36, or 12 h, respectively, after removing the agent, the amount of cellular Rh123 accumulation in BCEC returned to control levels (no drug treatment). CONCLUSION: The functional activity of P-gp on the blood-brain barrier could be modulated by various MDR-reversing agents and some principles with low toxicity extracted from medicinal herbs, such as some isoquinoline alkaloids without permanent modifying effects on the intrinsic level of P-gp function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Influence of An Adenosine Receptor Antagonist on Neurotransmitters in Parkinsonian Mice.

The effects of the adenosine A(2a) receptor antagonist, Quinazoline, on the monoamine transmitters NA, DA, 5-HT and 5-HIAA was studied using fluorecent method, and the influence of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and Quinazoline (CP66713) on the GABA positive reaction cells in globus pallidus was determined by immunohistochemistry technique in MPTP treated Parkinsonian mice. The results showed that MPTP decreased the content of DA, 5-HIAA and increased 5-HT, GABA obviously(pp<0.01). Quinazoline functioned opposite the action of MPTP, increasing the content of DA, 5-HIAA and decreasing the 5-HT. Quinazoline also reduced the GABA-positive reaction cells in globus pallidus of control mice and maintained the level of GABA-positive reaction cells of globus pallidus in MPTP treated mice, making it similar with the level of control.

Journal Article↗

PubMed1999

Site-Directed Mutagenesis of the Sterol Methyl Transferase Active Site from Saccharomyces cerevisiae Results in Formation of Novel 24-Ethyl Sterols.

Delta(24(28))-Sterols are end products of a mono C-methylation pathway catalyzed by the native Delta(24(25))- to Delta(24(28))-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae. Using a Tyr(81) to Phe mutant SMT enzyme of S. cerevisiae, generated by site-directed mutagenesis of a highly conserved residue in the sterol binding site, we found that several Delta(24(25))- and Delta(24(28))-sterols, which are not substrates for the native protein, were catalyzed to mono- and bis-C24-alkylated side chains. The mutant protein behaved similarly to the native protein in chromatography and in binding zymosterol, the preferred substrate. Zymosterol was converted to fecosterol by the Y81F mutant protein with similar turnover efficiency as the native protein (K(m) = 12 &mgr;M and k(cat) = 0.01 s(-)(1)); trace 24-ethyl sterols were detected from these incubations. 4alpha-Methyl zymosterol, which is not a normal substrate for the wild-type SMT enzyme, was converted to 4alpha-methyl fecosterol in high yield. When fecosterol and 4alpha-methyl fecosterol were assayed individually at saturating concentrations only fecosterol served as an effective substrate for the second C-transfer step (K(m) = 38 &mgr;M and k(cat) = 0.002 s(-)(1)), suggesting that successive C-methylation of Delta(24(28))-substrates is limited by product release and that molecular recognition of sterol features involves hydrogen bond formation. Isomeric 24-ethyl sterol olefins generated from 24(28)-methylene cholesterol were characterized by chromatographic (GC and HPLC) and spectral methods (MS and (1)H NMR), viz., fucosterol, isofucosterol, and clerosterol. Changes in rate of C-methylation and product distributions resulting from deuterium substitution at C28 were used to establish the kinetic isotope effects (KIEs) for the various deprotonations leading to C24-methylene, C24-ethylidene, and C24-ethyl sterols. An isotope effect on C28 methyl deprotonation generated during the first C(1)-transfer was detected with zymosterol and desmosterol paired with AdoMet and [(2)H(3)-methyl]AdoMet. A similar experiment to test for a KIE generated during the second C(1)-transfer reaction with AdoMet paired with 24(28)-methylenecholesterol and [28-(2)H(2)]24(28)-methylene cholesterol indicated an inverse isotope effect associated with C27 deprotonation. Alteration in the proportion of the C24 alkylated olefinic products generated by the pure Y81F mutant resulted from the suppression of the formation of Delta(24(28))-ethylidene sterols (C28 deprotonation) by a primary deuterium isotope effect with a compensating stimulation of the formation of 24-ethyl sterols (C27 deprotonation). Kinetic study on the rate of product formation indicated a normal KIE of k(H)/k(D) = 2.62 for the first C(1)-transfer. Alternatively, an inverse KIE was established with k(H)/k(D) = 0.9 for the second C(1)-transfer resulting from conversion of the 24(28)-double bond (sp(2) hybridization) to a 24beta-ethyl group (sp(3) hybridization). From the structures and stereochemical assignments of the C-ethyl olefin products, the stereochemistry of the attack of AdoMet in the second C(1)-transfer was found to operate a Si-face (backside) attack at C24, analogous to the first C(1)-transfer reaction.

Journal Article↗