PubMed Health⌕ Search

Biomedical subjects

Yang Lu

Publications and source records attributed to Yang Lu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Kadlongilactones A and B, two novel triterpene dilactones from Kadsura longipedunculata possessing a unique skeleton.

[structure: see text] Two novel triterpene dilactones with an unprecedented rearranged hexacyclic skeleton, kadlongilactones A (1) and B (2), have been isolated from the leaves and stems of Kadsura longipedunculata Finet et Gagnep (Schisandraceae). Their structures were established by comprehensive 1D and 2D NMR spectroscopic analysis, coupled with single-crystal X-ray crystallographic diffraction. Compounds 1 and 2 exerted significant inhibitory effects against human tumor K562 cells with IC(50) = 1.40 and 1.71 microg/mL, respectively.

Cell Line, Tumor↗
PubMed2005

Panaxynol induces neurite outgrowth in PC12D cells via cAMP- and MAP kinase-dependent mechanisms.

Panaxynol, a polyacetylene ((3R)-heptadeca-1,9-diene-4,6-diyn-3-ol; syn. falcarinol), was isolated from the lipophilic fractions of Panax notoginseng, a Chinese traditional medicinal plant. In the present study, we reported the neurotrophic effects of panaxynol on PC12D cells and mechanism involved in neurite outgrowth of the cells. Panaxynol could morphologically promote neurite outgrowth in PC12D cells, concentration-dependently reduce cell division and up-regulate molecular marker (MAP1B) expression in PC12D cells. Panaxynol induces the elevation of intracellular cAMP in PC12D cells. The neurite outgrowth in PC12D cells induced by panaxynol could be inhibited by the protein kinase A inhibitor RpcAMPS and by MAP kinase kinase 1/2 inhibitor U0126. These observations reveal that panaxynol could induce the differentiation of PC12D cells in a process similar to but distinct from that of NGF and the panaxynol's effects were via cAMP- and MAP kinase-dependent mechanisms.

Alkynes↗
PubMed2005

[Mice transduced with double-mutant dihydrofolate reductase-cytidine deaminase fusion gene attained protection from high dose chemotherapy].

OBJECTIVE: To explore the feasibility of transferring fusion gene of dihydrofolate reductase (DHFR) gene and cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose methotrexate (MTX) and cytosine arabinoside (Ara-C) in the bone marrow cells and to improve the tolerance of myelosuppression following combination chemotherapy. METHODS: Human double-mutant dihydrofolate reductase-cytidine deaminase fusion gene was transferred into two mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assays were performed in mouse bone marrow cells by retroviral infection and after treatment by drugs (Ara-C, MTX, and Ara-C + MTX). DNA was extracted from mouse bone marrow cells. The expression of drug resistant genes in mouse bone marrow cells after transferring by retroviral vector was checked by polymerase chain reaction (PCR). RESULTS: Bone marrow cells after coculture with the retroviral producer cells transduced with the genes (SFG-F/S-CD) showed the drug resistance colonies yield (Colony formation after exposure to Ara-C, MTX and Ara-C + MTX were 56%, 22% and 14%, respectively) and the increase in drug resistant to both MTX and Ara-C (P < 0.005). Expression of DHFR and CD gene in extracted DNA of transfected mice were demonstrated by PCR. CONCLUSIONS: Double drug resistant gene can not only integrate and co-express in mice bone marrow cells but also increase the drug resistance to MTX and Ara-C.

Animals↗
PubMed2005

Tagalsins I and J, two novel tetraterpenoids from the mangrove plant, Ceriops tagal.

[reaction: see text] Two novel bisdolabrane backbone tetraditerpenoids, tagalsins I (1) and J (2), were isolated from the mangrove plant, Ceriops tagal, and their structures were elucidated by means of extensive two-dimensional NMR (COSY, HMQC, HMBC, and NOESY), IR, and MS data analysis. The stereochemistry of 1 was further determined by single-crystal X-ray diffraction.

Crystallography, X-Ray↗
PubMed2005

The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression.

We have previously shown that the antiepidermal growth factor receptor monoclonal antibody cetuximab (C225; Erbitux), which was recently approved for the treatment of metastatic colorectal cancer, has antiangiogenic properties, inhibiting vascular endothelial growth factor (VEGF) secretion in culture and in animal models. Here, we have furthered the study by demonstrating that cetuximab reduces cellular levels of hypoxia-inducible factor-1 alpha (HIF-1alpha), a transcriptional regulator of VEGF expression, in A431 epidermoid carcinoma cells under both normoxic and hypoxic culture conditions. Expression of a constitutively active Ras in A431 cells rendered cellular resistance to the cetuximab-mediated reduction of the HIF-1alpha level. Cell lines with naturally occurring phosphatase and tensin homologue deleted on chromosome 10 mutations or deletions were also resistant to cetuximab-mediated reduction of the HIF-1alpha level. Pharmacologic inhibition of phosphatidylinositol 3-kinase with LY294002 reduced the HIF-1alpha level in both normoxic and hypoxic A431 cells, whereas inhibition of the mitogen-activated protein kinase kinase by PD98059 reduced the level of HIF-1alpha only in normoxic A431 cells. In addition, cetuximab reduced the cellular level of HIF-1alpha in the presence of a proteasome inhibitor, lactacystin, indicating that cetuximab acts mainly at the level of protein synthesis. The reduction of HIF-1alpha in response to cetuximab treatment was accompanied by transcriptional inhibition of VEGF expression, measured by a luciferase assay in A431 cells transfected with a vector containing the VEGF hypoxia response element. Taken together, our results indicate that the previously demonstrated inhibition of VEGF by cetuximab occurs at the level of transcription in response to a reduced level of HIF-1alpha and justify further testing of therapeutic strategies that combine cetuximab with approaches inhibiting the function of VEGF or the VEGF receptor.

Antibodies, Monoclonal↗
PubMed2005

Structure and anti-HIV activity of micrandilactones B and C, new nortriterpenoids possessing a unique skeleton from Schisandra micrantha.

Two new highly oxygenated nortriterpenoids with a unique norcycloartane skeleton, micrandilactones B and C, were isolated from Schisandra micrantha; micrandilactone C exhibited an EC50 value of 7.71 microg/mL (SI > 25.94) against HIV-1 replication with minimal cytotoxicity, and the potent anti-HIV-1 activity and unique structural features of make it a promising lead for therapeutic development of a new generation of anti-HIV drug.

Animals↗
PubMed2005

Lancifodilactone G: a unique nortriterpenoid isolated from Schisandra lancifolia and its anti-HIV activity.

[structure: see text]. Lancifodilactone G (1), a novel, highly oxygenated nortriterpenoid featuring a partial enol structure and a spirocyclic moiety, was isolated from the medicinal plant Schisandra lancifolia. Its structure and stereochemistry were determined from extensive one- and two-dimensional NMR and mass spectral data, coupled with single-crystal X-ray analysis. Compound 1 exerted minimal cytotoxicity against C8166 cells (CC50 > 200 microg/mL) and showed anti-HIV activity with EC50 = 95.47 +/- 14.19 microg/mL and a selectivity index in the range of 1.82-2.46.

Anti-HIV Agents↗
PubMed2005

Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells.

INTRODUCTION: We have shown previously that overexpression of constitutively active Akt or activation of Akt caused by constitutively active Ras or human epidermal growth factor receptor-2 (HER2) confers on breast cancer cells resistance to chemotherapy or radiotherapy. As an expanded study we here report differential responses in terms of phosphorylation and activation of Akt as a result of treatment with doxorubicin in a panel of breast cancer cell lines. METHODS: The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate. RESULTS: Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase. CONCLUSION: Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy.

Antibiotics, Antineoplastic↗
PubMed2005

Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles.

SARS-CoV is a newly identified coronavirus that causes severe acute respiratory syndrome (SARS). Currently, there is no effective method available for prophylaxis and treatment of SARS-CoV infections. In the present study, the influence of small interfering RNA (siRNA) on SARS-CoV nucleocapsid (N) protein expression was detected in cultured cells and mouse muscles. Four siRNA expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were prepared, and their inhibitory effects on expression of N and enhanced green fluorescence protein (EGFP) fusion protein were observed. A candidate siRNA was proved to down-regulate N and EGFP expression actively in a sequence-specific manner. The expression vector of this siRNA was constructed and confirmed to reduce N and EGFP expression efficiently in both cultured cells and adult mouse muscles. Our findings suggest that the siRNA should provide the basis for prophylaxis and therapy of SARS-CoV infection in human.

Animals↗
PubMed2005

Generation of mouse anti-human urate anion exchanger antibody by genetic immunization and its identification.

BACKGROUND: Human urate anion exchanger (hURAT1) as a major urate transporter expressed on renal tubular epithelial cells regulates blood urate level by reabsorbing uric acid. Antibody is an important tool to study hURAT1. This study aimed, by genetic immunization, to produce mouse anti-hURAT1 polyclonal antibody with high throughput and high specificity and to detect the location of hURAT1 in human kidney. METHODS: Human renal total RNA was isolated and the entire cDNA of hURAT1 was amplified by RT-PCR. The sequence of intracellular high antigenicity fragment (A280 to R349) was chosen by prediction software of protein antigenicity, and its cDNA was amplified from cDNA of hURAT1, and then cloned into pBQAP-TT vector to construct recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization. Mice were inoculated with this recombinant plasmid and two other adjuvant plasmids, pCMVi-GMCSF and pCMVi-Flt3L, which helped to enhance the antibody's generation. After four weeks, the mice were sacrificed to obtain the anti-hURAT1 antibody from serum. The antibody was identified by western blot analysis and immunohistochemistry. At the same time, rabbit anti-hURAT1 antibody was produced by protein immunization. The specificity and efficiency between the rabbit and mouse anti-hURAT1 antibody were compared by western blot analysis and immunohistochemistry. RESULTS: The entire cDNA of hURAT1 and cDNA of its intracellular high immunogenic fragment were amplified successfully. Recombinant plasmid pBQAP-TT-hURAT1-210 for genetic immunization was confirmed by restriction digestion and sequencing. Both the mouse anti-hURAT1 antibody and rabbit anti-hURAT1 antibody recognized 58 kD hURAT1 and 64 kD glycosylated hURAT1 protein bands in western blot. Immunohistochemically, hURAT1 was located at the brush border membrane of renal proximal tubular cells. In addition, the throughput and specificity of the mouse anti-hURAT1 antibody were higher than those of the rabbit anti-hURAT1 antibody. CONCLUSION: Genetic immunization can generate anti-hURAT1 polyclonal antibody of high throughput and specificity.

Animals↗
PubMed2005

Protection of human cerebral neurons from neurodegenerative insults by gene delivery of soluble tumor necrosis factor p75 receptor.

Apoptosis plays an important role in neuronal cell death in both chronic and acute human neurodegenerative diseases, including amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and human immunodeficiency virus (HIV) encephalopathy. We evaluated the ability of the extracellular binding domain of a dimeric tumor necrosis factor receptor (p75TNFR) to prevent neurotoxicity and death of human fetal cerebral neurons that were exposed in vitro to toxic agents known to be implicated in human neurological disorders, including tumor necrosis factor (TNFalpha) and the HIV proteins Tat and gp120. The extracellular domain of p75TNFR is capable of binding and neutralizing both soluble and transmembrane-anchored TNFalpha. We efficiently transduced human neurons using adenoviral vectors expressing p75TNFR (Ad.p75TNFR) or a control gene (lacZ). Treatment of control cultures with the toxic agents TNFalpha, TNFalpha plus actinomycin D, or Tat and gp120, induced neurotoxic alterations and apoptotic death of neurons. By contrast, transduction of neurons with Ad.p75TNFR prevented apoptosis and cell death due to these agents. We conclude that viral vector transfer of the p75TNFR gene efficiently protects human neurons from TNFalpha-, Tat- or gp120-induced apoptosis and cell death. These results suggest that p75TNFR transduction of neurons by viral vectors could be therapeutically useful in the treatment of many human neurodegenerative diseases.

Adenoviridae↗
PubMed2005

Lancifodilactone F: a novel nortriterpenoid possessing a unique skeleton from Schisandra lancifolia and its anti-HIV activity.

[structures: see text] Lancifodilactone F (1), possessing an unprecedented rearranged pentanortriterpenoid backbone derived from cycloartane, was isolated from the leaves and stems of Schisandra lancifolia (Rehd. et Wils) A. C. Smith. Its structure was established by comprehensive NMR and MS spectroscopic analysis, coupled with single-crystal X-ray experiment. Compound 1 exerted minimal cytotoxicity against C8166 cells (CC50 > 200 microg/mL) and showed anti-HIV activity with EC50 = 20.69 +/- 3.31 microg/mL and a selectivity index > 6.62.

Anti-HIV Agents↗
PubMed2005

Ginsenoside-Rd from Panax notoginseng enhances astrocyte differentiation from neural stem cells.

Neural stem cells cultured as neurospheres were used to assess the effects of P. notoginseng on the production of neurons and glia. The crude saponins (PNS) and ginsenoside-Rd promote the differentiation of neurospheres into astrocytes. Ginsenoside-Rd increases the production of astrocytes in a dose-dependent manner. On the other hand, both PNS and ginsenoside-Rd induce a weak but significant effect by decreasing the number of neurons. The other ginsenosides do not induce any differentiation on both neurons and astrocytes.

Animals↗
PubMed2005

Norlignans from Sequoia sempervirens.

Six new norlignans, named sequosempervirins B-G (1-6), together with three known norlignans, agatharesinol (7), agatharesinol acetonide (8), and sugiresinol (9), were isolated from the branches and leaves of Sequoia sempervirens. Their structures were determined mainly by high-resolution mass spectroscopy (HR-MS), and various 1D- and 2D-NMR methods, as well as, in the case of 1, by means of X-ray diffraction. Compound 8 showed anticancer activity towards the A549 non-small-cell lung-cancer cell line (IC50 = 27.1 microM). The acetone extract of S. sempervirens was found to be antifungal towards Candida glabrata (IC50 = 15.98 microg/ml), and both the acetone and MeOH extracts inhibited the proteolytic activity of cathepsin B (IC50 = 4.58 and 5.49 microg/ml, resp.).

Antifungal Agents↗
PubMed2005

NMR assignments and single-crystal X-ray diffraction analysis of deoxyloganic acid.

7-Deoxyloganic acid (1), citrusin C (2), 3,4-dihydroxyl benzoic acid (3) and (E)-caffeic acid (4) were isolated from the water-soluble fraction of ethanol extracts of Morina nepalensis var. alba Hand.-Mazz. and their structures were determined on the basis of spectroscopic evidence. The total assignments of 1H and 13C NMR spectra of 1 in solvents CD3OD, D2O and CDCl3 were reported, in addition to the single-crystal X-ray diffraction analysis of its tetraacetate 1a. All compounds were obtained from Morina genus for the first time.

Iridoids↗
PubMed2005

Activation of gelatinases by fibrin is PA/plasmin system-dependent in human glomerular endothelial cells.

Evidence suggests that fibrin deposit is related to severity of glomerulonephropathy. Fibrin is considered to play an active role beyond a haemostatic plug or temporary matrix in response to injury. We have reported that fibrin induced specific morphological changes and up-regulated intercellular adhesion molecule-1 expression of glomerular endothelial cells (GECs). Changes of gelatinases activity have been implicated playing a prominent role in glomerular diseases involving matrix turnover. This study examined whether overlying fibrin influences the expression of gelatinase A and B in cultured human GECs and mechanism underlying the activation. No gelatinase activity was detectable in supernatant of cultured GECs; however, physiological concentration of fibrin (0.5-2.0 mg/ml) induced a dramatic expression of activated MMP-2 and MMP-9 at both mRNA and protein level in a dose and time dependent manner. Increased mRNA level of membrane-type 1 matrix metalloproteinases (MT1-MMPs) was also found. Interestingly, we observed that fibrin also induced the expression of tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 by casein zymographic and reverse zymographic analysis. Fibrin plate assay revealed the net activity was PA predominant. Serine protease inhibitor aprotinin blocked the conversion of pro-gelatinase A and B to their active forms. The results demonstrate that overlying fibrin increased the secretion of gelatinase A and B from GECs. PA/plasmin proteolytic pathways contributed to the activation of gelatinases.

Base Sequence↗
PubMed2005

Terpenoids from the roots and rhizomes of Nardostachys chinensis.

A new diterpene, 10-isopropyl-2,2,6-trimethyl-2,3,4,5-tetrahydronaphtha[1,8-bc]oxocine-5,11-diol (1), and a new monoterpene, 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one, together with four known sesquiterpenes, delta1(10)-aristolene-9beta-ol, debilon, nardosinone, and kanshone A, were isolated from the roots of Nardostachys chinensis. The structures of the new compounds were established on the basis of their spectroscopic data, and the structure of 1 was confirmed by X-ray crystallographic analysis.

Diterpenes↗