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Biomedical subjects

L Zeng

Publications and source records attributed to L Zeng.

At least 199 records · Page 11Linked to original sources

New bioactive monotetrahydrofuran Annonaceous acetogenins, annomuricin C and muricatocin C, from the leaves of Annona muricata.

The leaves of Annona muricata have yielded two additional monotetrahydrofuran Annonaceous acetogenins, annomuricin C [1] and muricatocin C [2]. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are at the C-10/C-11 and C-10/C-12 positions in 1 and 2, respectively. The absolute configurations of 1 and 2, except for positions C-10 and C-11 or C-12, were determined by Mosher ester methodology. The C-10/C-11 and C-10/C-12 acetonides (1c, 2c) suggested relative stereochemistry and significantly enhanced the cytotoxicities against the A-549 human lung and the MCF-7 human beast solid tumor cell lines. One known monotetrahydrofuran acetogenin, gigantetronenin, not described previously from this plant, was also found.

4-Butyrolactone↗

Longicin and goniothalamicinone: novel bioactive monotetrahydrofuran acetogenins from Asimina longifolia.

Longicin [1] and (2,4-cis and trans)-goniothalamicinone [2], two new monotetrahydrofuran Annonaceous acetogenins, have been isolated from the leaves and twigs of Asimina longifolia (the long leaf paw paw) by the use of the brine shrimp lethality test for bioactivity-directed fractionation. The structures were elucidated based on spectroscopic and chemical methods. Compound 1 was converted to its ketolactone isomer, (2,4-cis and trans)-longicinone [3], to aid the stereochemical elucidation of 1. Compounds 1-3 showed selective and potent cytotoxicities to certain human tumor cell lines, with the potency of 1 against pancreatic carcinoma (PaCa-2) over one million times that of adriamycin. Nine known cytotoxic acetogenins, annonacin, xylomaticin, isoannonacin, gigantetrocins A and B, muricatetrocins A and B, gigantetrocin-A-one and goniothalamicin, were also isolated for the first time from this species.

4-Butyrolactone↗

Additional bioactive acetogenins, annomutacin and (2,4-trans and cis)-10R-annonacin-A-ones, from the leaves of Annona muricata.

In a continuation of our research on bioactive components from the leaves of Annona muricata, three novel monotetrahydrofuran Annonaceous acetogenins, namely, annomutacin [1], (2,4-trans)-10R-annonacin-A-one [2], and (2,4-cis)-10R- annonacin-A-one [3], have been identified. Their structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, and the absolute configurations were determined by Mosher ester methodology. A known bioactive amide, N-p-coumaroyl tyramine, was also found. Compound 1 and the mixture of compounds 2 and 3 showed selective cytotoxicities against the human A-549 lung tumor cell line.

4-Butyrolactone↗

Asimilobin and cis- and trans-murisolinones, novel bioactive Annonaceous acetogenins from the seeds of Asimina triloba.

Three new bioactive Annonaceous acetogenins, asimilobin [1], cis-murisolinone [2], and trans-murisolinone [3], have been isolated from an ethanolic extract of the seeds of Asimina triloba by directing the fractionation with brine shrimp lethality. The structure were elucidated based on spectroscopic and chemical methods, In addition, cis- and trans-bullatacinone, which are known compounds, were obtained. Asimilobin [1] has adjacent bis-THF rings, located at C-10 to C-17 and having only one flanking hydroxyl group at C-18. Compounds 1-3 showed cytotoxicity values comparable with adriamycin against six human solid tumor cell lines.

Animals↗

Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus.

Spontaneous mutations at the mouse Fused (Fu) locus cause dominant skeletal and neurological defects and recessive lethal embryonic defects including neuroectodermal abnormalities and axial duplications. Here, we describe a new allele at the Fu locus caused by a transgenic insertional mutation, H epsilon 46. Embryos homozygous for the H epsilon 46 insertion die at day 9-10 post coitum and display phenotypic defects similar to those associated with Fu alleles. The H epsilon 46 locus was cloned and shown to contain a 20-kb deletion at the site of transgene insertion with no other detectable rearrangements. Genomic probes from the H epsilon 46 locus were mapped to a genetic locus closely linked to Fu on chromosome 17 and were hybridized to a YAC contig covering the FuKi critical region. Compound heterozygotes between H epsilon 46 and FuKi were inviable and displayed abnormalities at the same stage of embryogenesis as do homozygotes for either of the two mutations, demonstrating that these two recessive lethal mutations belong to the same complementation group. A genomic probe from the wild-type H epsilon 46 locus detected a transcript that is disrupted by the transgenic insertion, representing a candidate for the wild-type allele of Fused.

Alleles↗

Stimulation of matrix metalloproteinase-dependent migration of T cells by eicosanoids.

Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), at nanomolar to micromolar concentrations, elicited migration of human blood T cells and cultured T lymphoblastoma cells of the Tsup-1 line through a layer of Matrigel basement membrane matrix. The density of Tsup-1 cell high-affinity receptors was low for PGE2 and high for LTB4, resulting in respectively predominant chemokinetic and chemotactic stimulation of migration. Migration-enhancing concentrations of PGE2 and LTB4 also increased Tsup-1 cell content and secretion of matrix metalloproteinases (MMPs) 2, 3, and 9, which were quantified by Western blots and zymography, and augmented Tsup-1 cell-surface expression of the MMPs, as shown by flow cytometry. That a specific MMP inhibitor suppressed migration of blood T cells and Tsup-1 cells through Matrigel, but did not affect PGE2- and LTB4-initiated T cell migration through micropore filters without Matrigel, suggests dual requirements for MMP expression and enhanced motility in T cell passage through basement membranes.

Cell Line↗

Molecular characterization of the 3' terminus of the simian hemorrhagic fever virus genome.

The 3' end of the simian hemorrhagic fever virus (SHFV) single-stranded RNA genome was cloned and sequenced. Adjacent to the 3' poly(A) tract, we identified a 76-nucleotide noncoding region preceded by two overlapping reading frames (ORFs). The ultimate 3' ORF of the viral genome encodes the capsid protein, and the penultimate ORF encodes the smallest SHFV envelope protein. These two ORFs overlap each other by 26 nucleotides. Northern (RNA) blot hybridization analyses of cytoplasmic RNA extracts from SHFV-infected MA-104 cells with gene-specific probes revealed the presence of full-length genomic RNA as well as six subgenomic SHFV-specific mRNA species. The subgenomic mRNAs are 3' coterminal. In its virion morphology and size, genome structure and length, and replication strategy, SHFV is most similar to lactate dehydrogenase-elevating virus, equine arteritis virus, and porcine reproductive and respiratory syndrome virus.

Amino Acid Sequence↗

Fibrin sealant matrix supports outgrowth of peripheral sensory axons.

It has been suggested that fibrin-based matrix has an important role during the early stage of nerve regeneration. A fibrin sealant matrix, which was made by combining diluted human fibrinogen and thrombin, was used as a substrate for in vitro elongation of neurites and in vivo regeneration of axons. In the in vitro experiment, dissociated embryonic chick sensory neurons were cultured on dishes coated with fibrin sealant matrix and compared with the solution of thrombin/calcium chloride, or with poly-D-lysine (PDLctr). After 16 hours, cultures were stained immunohistochemically with a monoclonal antineurofilament antibody. The neurons survived well, and an abundant network of neurites, qualitatively similar to that on PDLctr, developed on the fibrin sealant matrix. The percentage of neurons that had outsprout at 16 hours was the same both in the fibrin sealant matrix and PDLctr groups. By contrast, all the neurons plated on the dishes treated with the solution of thrombin/calcium chloride were dead after 16 hours. Immunohistochemical staining of fibrinogen also showed an even distribution of fibrin matrix over the culture dishes. For the in vivo experiments, 48 rat sciatic nerves were cut and reconnected with two epineurial stitches. Fibrin sealant matrix or phosphate buffer solution was applied to the transsected and repaired region. Pinch reflex test showed that the regeneration of the leading sensory fibre was significantly faster in the fibrin sealant matrix group than in the control group at 3 and 4 days. These results indicate that fibrin sealant matrix accelerates regeneration of axons in vivo during the early phase, and also supports elongation of neurites in vitro.

Animals↗

Diarrhoea in piglets and monkeys experimentally infected with Balantidium coli isolated from human faeces.

Ten piglets and four monkeys free from Balantidium were dosed with human faecal homogenate which contained 1.2 x 10(4)-4.8 x 10(4) B. coli cysts. The infection resulted in severe diarrhoea in piglets 1-6 and hydrocortisone-treated monkeys 1-2, moderate diarrhoea in piglets 7-10 and a subclinical infection in monkeys 3-4. In piglets 1-3 and monkeys 1-2, heavy infection of the intestinal mucosa extended from the terminal ileum to the rectum and the mucosa was severely damaged. In piglets 4-10, infection was heavy in the large intestine with moderate mucosal damage.

Animals↗

Independent down-regulation of EP2 and EP3 subtypes of the prostaglandin E2 receptors on U937 human monocytic cells.

Co-expression of EP2 and EP3 subtypes of prostaglandin E2 (PGE2) receptors (R) by U937 human monocytic cells permitted comparative studies of desensitization of each subtype. Specific binding of [3H]PGE2 to membranes of U937 cells showed a Kd of 2.9 +/- 0.3 nM (mean +/- SEM) and a Bmax of 40.5 +/- 1.0 fmol/mg protein, and was competitively inhibited by PGE2 > or = PGE1 > PGF2 alpha > PGD2 > PGI2. EP2 R and EP3 R mRNA were detected by reverse transcription-polymerase chain reaction and Northern blots. EP3 R expression was demonstrated by inhibition of [3H]PGE2 binding with the EP1/EP3 agonist sulprostone [50% inhibitory concentration (IC50 = 3.3 +/- 0.6 nM)] and the EP3/EP2 agonist M&B 28767 (IC50 = 2.1 +/- 0.3 nM), but not with the EP1 antagonist SC-19220. EP2 R protein was identified by Western blot analysis using specific rabbit IgG antibodies to an amino-terminal peptide of the EP2 R. EP2 R transduced PGE2 stimulation of significant increases in cellular [cAMP]i [50% effective concentration (EC50 = 20 +/- 2.5 nM)], and EP3 R mediated sulprostone inhibition of forskolin elevation of [cAMP]i (IC50 = 1.3 +/- 0.4 nM). Pretreatment of U937 cells with phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), for 1 hr reduced the total number, but not the affinity, of PGE2 R by down-regulating principally EP2 R. In contrast, a 24-hr exposure to PMA, which is known to down-regulate PKC, suppressed both the total number and affinity of PGE2 R on U937 cells with concurrent reductions in EP2 R and EP3 R. The down-regulation of EP2 R by PMA at 1 hr was blocked by staurosporine, an inhibitor of PKC, whereas the down-regulation of EP3 R by PMA at 24 hr was blocked by indomethacin. Pretreatment of U937 cells with PGE2 for 1 and 24 hr reduced both the binding affinity and the total number of PGE2 R, by co-ordinate suppression of the EP2 R and EP3 R. Desensitization of EP2 R and EP3 R for 1 hr with PGE2 suppressed subsequent PGE2-evoked chemokinetic responses to PGE2, whereas selective down-regulation of EP2 R alone by PMA for 1 hr had no effects on U937 cell migration. Thus expression of each subtype of PGE2 R is regulated independently and EP3 R, but not EP2 R, transduces PGE2 effects on migration of mononuclear phagocytes.

Base Sequence↗

The analysis of disparity evoked potentials by a new form of static random-dot stereograms.

PURPOSE: A new form of static random-dot stereograms free of monocular clues was designed as stimulus to elicit disparity evoked potentials. METHODS: Disparity evoked potentials were recorded in 40 stereo-normal subjects. The stimulator was a white-black static random-dot stereograms generated by a computer and had no monocular clues. Every subject was tested in disparity stimulus, zero disparity stimulus, monocular stimulus and wearing prism condition. RESULTS: A characteristic wide positive wave at about 250 ms was consistently recorded in disparity stimulus, which may be regarded as evidence of the presence of stereopsis. In contrast, recordings for zero disparity stimulus, monocular vision, stimulus and wearing prism condition all demonstrated a markedly difference from recording for disparity stimulus.

Adolescent↗

[Isolation and identification of extrem thermophilic bacteria from hot springs of Sichuan and Tibet].

Eleven strains of extrem thermophilic bacteria belonging to the Bacillus Stearothermophiles were isolated from the hot springs of Sichuan and Tibet. The cells were gram-positive, sporulating and motile. The optimum temperature for growth was between 65 degrees C to 70 degrees C; the maximum 94 degrees C, and minimum 40 degrees C. The colour of colony was yellow to bright orange. The G+C content of the DNA in strains has been found to be in the range 48.4-53.15 mol%.

China↗

Isoforms of the EP3 subtype of human prostaglandin E2 receptor transduce both intracellular calcium and cAMP signals.

The EP3 subtype of prostaglandin E2 receptor transduces diverse physiological responses in mammalian tissues through signaling pathways coupled to heterotrimeric G proteins. Distinct cDNA clones encoding five isoforms of the EP3 receptor were isolated from a human uterus cDNA library. The human EP3 receptor isoforms designated hEP3-I, I', II, III, and IV are derived from alternative RNA splicing and differ only in the distal sequences of their carboxyl-terminal cytoplasmic tails. The unique cytoplasmic tails consist of 31 amino acids for isoforms I and I', 29 for II, 6 for III, and 15 for IV. When stably expressed in CHO cell transfectants, all isoforms exhibited similar EP3-specific binding of [3H]-PGE2 and PGE2 analogs. The EP3-selective agonist M&B 28767 both decreased the intracellular cAMP concentration ([cAMP]i) and increased the intracellular concentration of calcium ([Ca2+]i) with quantitative differences among different isoforms, but none mediated an increase in [cAMP]i. Pertussis toxin treatment completely blocked the decrease in [cAMP]i, but not the increase in [Ca2+]i evoked by M&B 28767. PGE2-induced desensitization of [3H]PGE2 binding by isoforms III and IV was rapid and transient, whereas that by isoform II was slow and persistent. Reverse transcription-PCR amplification of EP3 receptor messages in human kidney and uterine tissue RNA detected expression of all isoforms with different abundancies. The dual signal transduction pathways and distinctive tissue distribution of isoforms of the EP3 receptor are consistent with its mediation of diverse functions of PGE2.

Alprostadil↗

Intrapleural production of interleukin 6 during mesothelioma and its modulation by gamma-interferon treatment.

In vivo production of monokines was analyzed in 17 human malignant pleural mesotheliomas. High concentrations of interleukin 6 (IL-6) were detected in pleural effusions, contrasting with low levels of IL-1 beta and tumor necrosis factor alpha. This production arose from malignant cells, as shown by immunochemical analysis of pleural cells and by production of IL-6 by mesothelial cell lines. Intrapleural administration of recombinant human gamma-interferon to six patients led to a marked decrease in intrapleural IL-6 concentrations in all cases. This treatment was associated with in situ activation of macrophages and cytotoxic T-lymphocytes, as indicated by increased intrapleural neopterin and soluble CD8 concentrations. In vitro gamma-interferon had no effect on the production of IL-6 by mesothelial cell lines but decreased the growth of 3 of 6 mesothelioma cell lines. These results indicate that systemic manifestations of malignant mesothelioma, including fever, cachexia, and thrombocytosis may be related to the production of IL-6 by malignant cells, and that local gamma-interferon infusion may reduce this production by stimulating antitumoral immunity and/or by directly decreasing the proliferation of malignant cells.

Biopterins↗

Specificity of DnaK-peptide binding.

The sequence specificity of DnaK substrate binding has been studied using a peptide display library. Based on the amino acid patterns that appeared in this selection, short peptides were synthesized for direct measurements of DnaK affinity. The results show that peptides enriched in internal hydrophobic residues are preferential DnaK substrates, and negatively charged peptides have poor affinity. The isolated C-terminal domain of DnaK binds peptides. Peptide dissociation studies indicate that bound peptides are released from the C-terminal fragment and from DnaK at identical rates. ATP stimulates peptide dissociation from DnaK but not from the C-terminal fragment.

Amino Acid Sequence↗

Immunocytochemical characterization of cell lines from human malignant mesothelioma: characterization of human mesothelioma cell lines by immunocytochemistry with a panel of monoclonal antibodies.

A panel of nine monoclonal antibodies was used to characterize human mesothelioma cell lines that we established from human malignant mesothelioma. The antigens detected were cytokeratin, vimentin, epithelial membrane antigen, carcinoembryonic antigen, Leu-M1 (CD15), desmin, factor VIII-related antigen (von Willebrand factor antigen), OV632, and ME1, a specific monoclonal antibody directed against human malignant mesothelioma. The technique used was the alkaline phosphatase anti-alkaline phosphatase method. All 30 cell lines, either epithelial, sarcomatous, or mixed, showed strong reactivity with cytokeratin and vimentin antibodies. None of the cell lines demonstrated any reactivity with carcinoembryonic antigen, Leu-M1, or factor VIII antibodies; moreover, all of 22 cell lines studied were positive for ME1 antibody and 10 of 12 cell lines studied were positive for OV632. Some interesting features were noted: only two of the 30 cell lines presented a weak positive staining with epithelial membrane antigen, and nine of 19 cell lines tested demonstrated a cytoplasmic staining pattern with desmin antibody. These results show that established human mesothelioma cell lines still possess the immunocytochemical characteristics that are basically consistent with the immunohistochemical features described in tumor tissues of malignant mesothelioma. These characteristics can be used to identify the mesothelioma cells grown from human malignant mesothelioma. Hence, the mesothelioma cell lines will provide a useful tool for the investigation of the cell biology of the tumor and the mechanisms of mesothelial cell transformation, as well as the in vitro evaluation of the effects of some drugs in order to develop new therapies for malignant mesothelioma.

Actins↗