Biomedical subjects

Y C Shen

Publications and source records attributed to Y C Shen.

At least 37 records · Page 2Linked to original sources

PubMed1999

Synthesis of the Bycroft-Gowland structure of micrococcin P1.

[formula: see text] We describe the chemical synthesis of the accepted structure of micrococcin P1, a member of the thiostrepton group of antibiotics, and we show that this architecture does not correspond to that of the natural product. Methods developed during the present study should greatly facilitate ongoing efforts centering on the determination of the actual structure of microccin P1, in addition to being applicable to the synthesis of more complex thiostrepton congeners.

Anti-Bacterial Agents↗

PubMed1999

Taxane diterpenoids from the seeds of Chinese yew Taxus chinensis.

The taxoid chinentaxunine has been isolated from the seeds of Chinese yew Taxus chinensis, and its structure determined on the basis of spectral and chemical methods. In addition, the known taxol C, paclitaxel, 10-deacetyl taxol A, 10-deacetyl-7-epitaxol, 10-deacetyl-10-oxo-7-epi-taxol, taxinine M, taxchinin A, 10-deacetyl taxinine B and taxuspine X were also isolated and identified from this source.

Alkaloids↗

PubMed1999

Bioactive sesquiterpenes from a Taiwanese marine sponge Parahigginsia sp.

Five new sesquiterpenes, parahigginols A-D (1-4) and parahigginic acid (5), have been isolated from a Taiwanese marine sponge Parahigginsia sp. The structural assignments of the new compounds were based on their spectral data, including 1D and 2D NMR. Biological studies revealed that compounds 2-5 exhibited cytotoxicity against murine P-388 and human KB16, A549, and HT-29 tumor cells.

Animals↗

PubMed1999

Structures and cytotoxicity relationship of isoaaptamine and aaptamine derivatives.

A series of 9-O-acylisoaaptamine (3-14) and 4-N-acyl-dihydroaaptamine (16-19) derivatives have been prepared and evaluated for antitumor activity against murine P-388 and human tumor cells including KB16, A549, and HT-29 cell lines. All of compounds showed significant cytotoxicity against P-388 cells. Among them, compounds 9-11 showed potent activity as isoaaptamine (1). There was an apparent lack of linear relationship between cytotoxicity and carbon number of the side chain. The structure and activity relationship for these particular compounds are discussed.

Animals↗

PubMed1999

Tetrandrine ameliorates ischaemia-reperfusion injury of rat myocardium through inhibition of neutrophil priming and activation.

1. We have previously shown that tetrandrine (TTD), a bisbenzyltetrahydroiosquinoline isolated from the Chinese herb Stephania tetrandra, inhibits neutrophil adhesion, Mac-1 expression, and reactive oxygen species (ROS) production. To examine whether inhibition of neutrophil function may confer upon TTD the ability to prevent myocardial ischaemia-reperfusion (MI/R) injury, experiments were performed on rats subjected to coronary ligation followed by reperfusion for induction of MI/R injury. 2. Intravenous administration of TTD (0.1 and 1.0 mg kg-1) 15 min prior to coronary ligation completely prevented MI/R-associated mortality. TTD pretreatment also significantly reduced MI/R-induced ventricular tachyarrhythmia, myocardial infarct size, and neutrophil infiltration. 3. However, TTD pretreatment did not influence mean arterial blood pressure, heart rate, or product of pressure-rate, indicating that TTD extenuated MI/R through mechanisms independent of modulating haemodynamics or myocardial oxygen demand. 4. Peripheral blood neutrophils were isolated for ex vivo examination of shape change and Mac-1 upregulation of neutrophils, two sensitive indicators of proinflammatory priming, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion and ROS production, parameters commonly used for the assessment of neutrophil activation. 5. Neutrophils from MI/R animals showed significant shape change and Mac-1 upregulation, both of which were prevented by TTD-pretreatments. On the other hand, fMLP-induced adhesion and ROS production of neutrophils were markedly enhanced by MI/R but diminished in TTD-pretreated animals. 6. These data suggest that the protective effect of TTD against MI/R injury can be accounted for by inhibition of neutrophil priming and activation, thereby abolishing subsequent infiltration and ROS production that cause MI/R injury.

Alkaloids↗

PubMed1999

Taxumairol M: a new bicyclic taxoid from seeds of Taxus mairei.

In addition to taxol A (1), 10-deacetyltaxol A (2), 10-deacetyl-7-epi-taxol A (3), 10-deacetylbaccatin III (5), taxuspine Z, taxezopidine G, 5 alpha-cinnamoyloxy-9 alpha,10 beta,13 alpha-triacetoxytaxa-4(20)11-diene, taxinine J, and taxinine M, a new bicyclic taxoid named taxumairol M (4), has been isolated from the seeds of Taxus mairei. The structure of 4 was determined on the basis of spectral analysis.

Molecular Structure↗

PubMed1999

Impediment to calcium influx and reactive oxygen production accounts for the inhibition of neutrophil Mac-1 Up-regulation and adhesion by tetrandrine.

We studied the mechanisms by which the plant alkaloid tetrandrine (TTD) inhibits Mac-1-dependent neutrophil adhesion to fibrinogen. TTD (0.1-10 microM) significantly inhibited Mac-1 up-regulation and neutrophil adhesion, as induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol-myristate-acetate (PMA). Treatment of neutrophils with fMLP or PMA caused a rapid influx of Ca++ and accumulation of reactive oxygen species (ROS), both of which have been shown to enhance neutrophil adhesion via Mac-1 up-regulation. Because TTD antagonizes Ca++ influx and abrogates ROS, we examined the relationship between Ca++ influx, ROS formation, and Mac-1 expression in TTD-inhibited neutrophil adhesion. TTD alone caused a slight but statistically significant increase in [Ca++]i with no effect on adhesion. In contrast, TTD as well as two Ca++ channel antagonists, verapamil and nifedipine, markedly diminished fMLP- and PMA-induced Ca++ influx, Mac-1 up-regulation, and adhesion. TTD also inhibited increases in [Ca++]i and adhesion induced by the ionophore A23187 but failed to inhibit those induced by thapsigargin, an agent mobilizing Ca++ from intracellular stores. Thus, TTD impeded Ca++ influx from outward to avert neutrophil adhesion. Similarly, TTD and two ROS scavengers, superoxide dismutase and catalase, abolished ROS production, Mac-1 up-regulation, and neutrophil adhesion. Ca++ and ROS, therefore, represent two essential signals for Mac-1 up-regulation upon fMLP or PMA stimulation. Our data suggest that the antiadherent effect of TTD is mediated, in part, by the inhibition of Ca++ influx and ROS formation, resulting in suppressed up-regulation of Mac-1 and, in turn, neutrophil adhesion to fibrinogen.

Adult↗

PubMed1998

A new taxane diterpenoid from Taxus mairei.

A new 11(15-->1)-abeotaxane diterpene, taxumairol K (1), has been isolated from the ethanolic extract of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y. Hu. The structure of 1 was determined as 9alpha-(benzoyloxy)-2alpha,4alpha- diacetoxy-5beta ,20-epoxy-1beta, 7beta,10beta,13alpha-tetrahydroxy-11(15-->1)-abeota xane on the basis of spectral analysis. Taxumairol K (1) exhibited mild cytotoxicity against HeLa tumor cells.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: relationship with its antioxidant effect.

Magnolol, a phenolic compound isolated from a Chinese herbal drug, Magnolia officinalis, has been shown to protect rat heart from ischemia/reperfusion injury. Neutrophil adhesion plays a crucial process during this inflammatory response. To evaluate whether magnolol prevents ischemia/reperfusion injury by inhibiting neutrophil adhesion, we determined whether magnolol can inhibit adhesion of phorbol-12-myristate-13-acetate (PMA)-activated human neutrophils to a fibrinogen-coated surface in a dose-dependent manner. Using flow cytometric analysis, we observed that magnolol pretreatment (10 min at 37 degrees C) diminished PMA (100 ng/ml)-induced Mac-1 upregulation. PMA also induced rapid intracellular accumulation of superoxide (O2-.) and hydrogen peroxide (H2O2) in neutrophils; magnolol pretreatment attenuated the accumulation of these two substances. Inhibition of reactive oxygen species by superoxide dismutase and/or catalase, which decompose O2-. and H2O2, respectively, also abolished Mac-1 upregulation and neutrophil adhesion. We conclude that magnolol inhibits neutrophil adhesion and that this can account for its anti-ischemia/reperfusion injury effect. We propose that the inhibitory effect of magnolol on neutrophil adhesion to the extracellular matrix is mediated, at least in part, by inhibition of the accumulation of reactive oxygen species, which in turn suppresses the upregulation of Mac-1 that is essential for neutrophil adhesion.

Adult↗

PubMed1998

Chromosomal abnormalities of a new nasopharyngeal carcinoma cell line (NPC-BM1) derived from a bone marrow metastatic lesion.

An epithelial cell line, NPC-BM1, was established from a bone marrow biopsy of a female Taiwanese patient with nasopharyngeal carcinoma (NPC). Histopathology of the bone marrow biopsy and xenografts grown in severe combined immunodeficiency mice showed that the tumor was a nonkeratinizing, poorly differentiated carcinoma. NPC-BM1 cells grown as monolayers had a doubling time of 28.5 hours. Chromosome analysis showed that NPC-BM1 had the following features: 1) hypotetraploidy with a modal chromosome number of 87 (84-90); 2) numerically and structurally normal chromosomes 18; 3) numerical abnormalities without apparent structural alterations on chromosomes 14, 16, 17, 19, and 20; 4) ten structural abnormalities, t(1;9)(p11;q11), t(3;?;4)(p13;?;q13), add(4p),del(6p), i(8) [corrected] (q10),der(?)t(?;12),(?;p12),[corrected] add(21)(p11), del(X)(q24), add(X)(q22), and marker 1 (M1), in all metaphases examined, which were found to be present in two to five cell lines from primary NPC tumors reported previously; and 5) four other abnormalities, t(2;?;2)(p11.2;?;q21),t(11;22)(q11;q11),i(22)(q10), and marker 2 (M2), unique to this metastatic cell line. To the best of our knowledge, NPC-BM1 is the first NPC cell line derived from a distant metastatic site. Further evaluation of this cell line and additional metastatic NPC cell lines as well as primary NPC cell lines with respect to relations between the timing, karyotypic anomalies, and immunobiological characteristics in NPC progression and metastasis is warranted.

Adult↗

PubMed1997

New sesquiterpene hydroquinones from a Taiwanese marine sponge Polyfibrospongia australis.

Two new sesquiterpene hydroquinones, polyfibrospongols A (1) and B (2), were isolated from the Taiwanese marine sponge Polyfibrospongia australis Lendenfeld (Spongiidae) in addition to the known metabolites, dictyoceratin A (3), ilimaquinone (4), and 5-epi-ilimaquinone (9). The structures of these compounds have been determined mainly on the basis of spectral and chemical methods. Biological testing revealed that compounds 1 and 2 exhibited significant cytotoxicity against human KB-16, A-549, and murine P-388 tumor cell lines.

Animals↗

PubMed1997

Taxane diterpenes from Taxus mairei.

In addition to 7-O-deacetyl-1 beta-hydroxybaccatin I and 9-O-deacetyl-1 beta-hydroxybaccatin I, a new taxane taxumairol F has been isolated from the ethanolic extracts of the roots of Taxus mairei. Their structures were determined on the basis of spectral evidence and chemical correlation with 1-beta-hydroxybaccatin I.

Diterpenes↗

PubMed1997

Culture medium induced morphological changes of melanoma cells associated with change in sensitivity to lysis by lymphokine-activated killer cells.

Three sublines (Clones 1, 2 and 7) of the human melanoma CaCL 73-36 cell line with different cellular morphology, growth patterns, melanin content and surface antigenic profile were maintained in RPMI-1640 medium plus 10% fetal bovine serum (abbreviated as RPMI). Each subline was divided into two groups: one grown in RPMI and the other in Dulbecco's modified Eagle's medium plus 10% fetal bovine serum (abbreviated as DMEM) for 96 h. Phenotypically, Clone 2 expressed Class I and II MHC and ICAM-1 on the surface and in the cytoplasm, while Clones 1 and 7 failed to express these antigens in both the cytoplasm and on the cell surface. Melanotic Clones 1 and 7 cells became even more pigmented, had slower growth rates, and exhibited lower saturation densities when incubated in DMEM than when they were incubated in RPMI. On the other hand, Clone 2 cells maintained in RPMI were grossly amelanotic, contained defective-like melanosomes detected ultrastructurally, and had distinct clusters of microvilli polarly located in most of the cells. Such specialized ultrastructures were not affected by medium conditions. Analysis of sensitivity of the clonal sublines to cytolysis by allogeneic effector cells revealed that in spite of low levels of natural killer (NK) cytotoxicity noted, DMEM produced a 2- to 14-fold increase in sensitivity to NK cells, irrespective of which medium was used. Different levels of lymphokine-activated killer (LAK) cytolytic activity were clearly observed in sublines maintained in RPMI, with Clone 2 being the most sensitive and both Clones 1 and 7 being less sensitive. Cells grown in DMEM exhibited significantly higher levels of sensitivity to LAK cytolysis than cells grown in RPMI as revealed by their differences in lytic units (p < 0.05). This was likely due to the high levels of surface ICAM-1 expression in cells incubated in DMEM vs little expression of this adhesion molecule by cells grown in RPMI. Taken together, these results demonstrate the presence of heterogeneous subpopulations within the CaCL 73-36 melanoma cell line regarding their pigmentary status, antigenic profile, growth pattern and responsiveness to NK/LAK cytolysis. The results also call attention to the importance of utilizing a same medium in short- and long-term cultures of melanomas for biological studies and response evaluations of therapeutic agents such as LAK cells, when multiple cell targets from different patients or multi-metastatic cell lines from individual patients are to be compared. Finally, these melanoma sublines may be valuable for further elucidation of the relationship between MHC expression, and increased sensitivity to LAK cytolysis, and the role of the components of DMEM in the mechanism for the observed induction of cell differentiation and enhanced LAK cytolysis.

Animals↗

PubMed1997

Polymorphism of ADH and ALDH genes among four ethnic groups in China and effects upon the risk for alcoholism.

The alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) that metabolize ethanol are polymorphic. Different alleles encode subunits of the enzymes that differ in their rate of metabolizing ethanol. These polymorphisms are distributed differently among populations and have been shown to influence the risk for alcoholism in some Asian populations. We have examined the allele frequencies at the ADH2, ADH3, and ALDH2 loci in four populations from China (Han, Mongolian, Korean, and Elunchun) and in alcoholics within each population. The four populations differ in allele frequencies, with the Elunchun having a much lower frequency of ADH2*2 alleles, and the Mongolian and Elunchun having a much lower frequency of ALDH2*2 alleles. Within each population, alleles at one or more of these three loci are protective against alcoholism, although the populations differ in which loci play significant roles. The protective allele at each locus (ALDH2*2, ADH2*2, and ADH3*1) encodes a subunit that either metabolizes ethanol to acetaldehyde more rapidly or slows the conversion of acetaldehyde to acetate. Taken as a whole, data demonstrate that genetic differences in the enzymes that metabolize alcohol can substantially affect the risk for alcoholism.

Adolescent↗

PubMed1997

[Therapeutic effect of shuxuening combining neuroleptics for the treatment of chronic schizophrenia--a double blind study].

OBJECTIVE: To assess the therapeutic effect of Shuxuening (SXN), the extractum of Ginkgo biloba761 (EGb761) in treating chronic schizophrenia. METHODS: A double-blind, placebo-controlled multi-center research on the treatment of chronic schizophrenics with SXN was used. Five hundred and forty-five patients were randomly divided into either SXN group or the control group. Patients in the former group received SXN 120 mg three times daily. Patients in both groups received their maintenance neuroleptics throughout the 16-week research treatment. RESULTS: The patients' rating scores of brief psychiatric rating scale (BPRS) and Scale for the Assessment of Negative Symptoms reduced much greater in SXN group than those in the control group from the sixth week of treatment (P < 0.01). The effect of SXN for BPRS factors of retardation and thought disturbance was better than that of the control. SXN presented a better therapeutic effect for chronic schizophrenics than the control when rated with traditional global rating method as well, in which 44.98% marked improvement was obtained in SXN group compared to 20.98% in the control group. CONCLUSION: SXN combining neuroleptics, was an effective medicine for chronic schizophrenics. Moreover, it appeared few side-effects within the recommended dose range.

Adult↗

PubMed1996

New taxane diterpenoids from the roots of Taxus mairei.

Two new taxoids, taxumairols A (1) and B (2), have been isolated from extracts of the roots of Formosan Taxus mairei (Lemee & Levl.) S. Y. Hu. The structures of 1 and 2 were identified as 5 alpha, 7 beta, 9 alpha, 10 beta, 13 alpha-pentaacetoxy-20-(benzoyloxy)- 2 alpha, 4 alpha-dihydroxytax-11-ene and 2 alpha, 5 alpha, 10 beta,-13 alpha-tetraacetoxy-1 beta, 7 beta, 9 alpha-trihydroxy-4 beta,20-epoxytax-11-ene, primarily on the basis of 1D- and 2D-NMR techniques including DEPT, COSY, and HMBC experiments, as well as chemical correlation with known compounds. Taxumairol A (1) exhibited significant cytotoxicities against murine P-388 and human KB-16, A-549, and HT-29 tumor cell lines.

Animals↗

PubMed1996

Selective contact during TCR recognition.

Recent structural analysis of the peptide-MHC complex reveals that an antigenic peptide binds to MHC in only one conformation and that side chains anchoring in the binding pocket would not contact TCR. The identification of all the MHC-anchoring residues on an antigenic peptide is a prerequisite to understand how a given peptide interacts with the TCR. In a combination of binding analysis and model simulation, model peptide lambda repressor cl 16-26 was shown to bind to I-Ek through four anchor residues (Leu18, IIe21, Glu23 and Lys26), a pattern found in many I-Ek-binding peptides. TCR reactivity analysis clearly indicates a great variation in the interaction with cl 16-26 by T cells generated from different strains of I-Ek-bearing mice. Most of the T cell generated from A/J mice reacted with the central regions of cl 16-26, while there is a great diversity on the recognition of cl 16-26 by T cells from C3H and B10.BR mice. Despite the diverse interactions with antigenic peptide by these T cells, most TCR-E-k contacts are limited to the central region of the I-Ek beta-chain. T cells recognizing only the N-terminal part of cl 16-26 were found to contact I-Ek at nearly the same residues as T cells interacting with the C-terminal of cl 16-26. TCR-I-Ek recognition was apparently independent of TCR-cl 16-26 contact. The discordant TCR-peptide and TCR-MHC interaction may represent a unique feature of TCR recognition.

Amino Acid Sequence↗

PubMed1995

New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum.

Three new steroids, zhankuic acids A [1], B [2], and C [3], were isolated from the fruiting bodies of Antrodia cinnamomea by bioassay-guided fractionation. The structures of these compounds were elucidated by chemical reactions and detailed analysis of their 1H- and 13C-nmr spectra. Biological studies revealed that 1 exhibited cytotoxic activity against P-388 murine leukemia cells and 2 showed weak anticholinergic and antiserotonergic activities.

Animals↗