Biomedical subjects

Li Yang

Publications and source records attributed to Li Yang.

At least 181 records · Page 10Linked to original sources

PubMed2004

Association of differentially expressed genes with activation of mouse hepatic stellate cells by high-density cDNA microarray.

AIM: To characterize the gene expression profiles associated with activation of mouse hepatic stellate cell (HSC) and provide novel insights into the pathogenesis of hepatic fibrosis. METHODS: Mice HSCs were isolated from BALB/c mice by in situ perfusion of collagenase and pronase and single-step density Nycodenz gradient. Total RNA and mRNA of quiescent HSC and culture-activated HSC were extracted, quantified and reversely transcribed into cDNA. cDNAs from activated HSC were labeled with Cy5 and cDNAs from the quiescent HSC were labeled with Cy3, which were mixed with equal quantity, then hybridized with cDNA chips containing 4000 genes. Chips were washed, scanned and analyzed. Increased expression of 4 genes and decreased expression of one gene in activated HSC were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A total of 835 differentially expressed genes were identified by cDNA chip between activated and quiescent HSC, and 465 genes were highly expressed in activated HSC. The differentially expressed genes included those involved in protein synthesis, cell-cycle regulation, apoptosis, and DNA damage response. CONCLUSION: Many genes implicated in intrahepatic inflammation, fibrosis and proliferation were up-regulated in activated HSC. cDNA microarray is an effective technique in screening for differentially expressed genes between two different situations of the HSC. Further analysis of the obtained genes will help understand the molecular mechanism of activation of HSC and hepatic fibrosis.

Animals↗

PubMed2004

Inhibition of free radical initiated peroxidation of human erythrocyte ghosts by flavonols and their glycosides.

The in vitro peroxidation of human erythrocyte ghosts was used as a model to study the free radical-induced damage of biological membranes and the protective effect of flavonols and their glycosides, i.e., quercetin (Q), quercetin galactopyranoside (QG), quercetin rhamnopyranoside (QR), rutin (R), morin (MO), kaempferol (K) and kaempferol glucoside (KG). The peroxidation was initiated by a water-soluble free radical initiator 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AMPAD) at physiological temperature, and monitored by oxygen uptake. Kinetic analysis of the peroxidation process demonstrates that these flavonols and their glycosides are effective antioxidants against AMPAD-initiated oxidative damage of human erythrocyte ghosts, and that the flavonols bearing ortho-dihydroxyl groups possess significantly higher antioxidant activity than those bearing no such functionalities and the glycosides are less active than their parent aglycones.

Amidines↗

PubMed2004

Synergy between signal transducer and activator of transcription 3 and retinoic acid receptor-alpha in regulation of the surfactant protein B gene in the lung.

During respiratory cycles, airborne particles and pathogens are inhaled into the lung, which can cause cytokine production by respiratory macrophages and inflammatory responses. Secreted cytokines affect surfactant protein expression and homeostasis in the lung. In coculturing experiments in vitro, bronchoalveolar macrophages stimulated human surfactant protein B (hSP-B) gene transcription in primary alveolar type II epithelial cells in lipopolysaccharide-independent and -dependent ways. Neutralization by IL-6 antibody abolished lipopolysaccharide-dependent macrophage stimulation of hSP-B gene transcription. IL-6 treatment enhanced signal transducer and activator of transcription (Stat)3 phosphorylation at Y705 in alveolar type II epithelial cells and Clara cells in vivo. Biochemical analysis of functional domain swapping between Stat1 and Stat3 identified that the SH2 domain and the DNA binding domain are critical for Stat3 stimulation of hSP-B gene transcription. Glutathione-S-transferase pull-down study determined functional domains required for protein-protein interaction between Stat3 and retinoic acid receptor-alpha. Cotransfection of Stat3 and retinoic acid receptor-alpha into respiratory epithelial cells resulted in synergistic DNA binding and transcriptional activation on the hSP-B gene. To assess Stat3 physiological function, overexpression of a dominant negative Stat3 in respiratory epithelial cells in a doxycycline-controlled double transgenic mouse line caused pulmonary emphysema and increase of animal death during hyperoxia. Therefore, the IL-6/Stat3 signaling axis plays an important role in surfactant protein homeostasis and respiratory inflammation in the lung.

Animals↗

PubMed2004

Calcineurin-mediated BAD Ser155 dephosphorylation in ammonia-induced apoptosis of cultured rat hippocampal neurons.

We previously reported that ammonia induced apoptosis in cultured rat hippocampal neurons with moderate increases in the intracellular calcium concentration and decreases in phospho-BAD levels. Since this suggested the involvement of calcineurin in the apoptosis, the effects of calcineurin inhibitors, 1 microM cyclosporin A and 1 microM FK506, on the ammonia-induced neuronal apoptosis were tested. Both of the inhibitors abolished the neuronal apoptosis assessed by double staining with Hoechst 33258 and anti-neurofilament antibody, and the ammonia-induced decrease in phospho-BAD Ser(155) level. Thus, calcineurin appeared to be involved in the dephosphorylation of BAD at the sites including Ser(155) in ammonia-induced apoptosis.

Ammonia↗

PubMed2004

catena-Poly[[silver(I)-micro-ethane-1,2-diamine-kappa(2)N:N'] 3-fluorobenzoate monohydrate].

The title compound, [[Ag(C2H8N2)](C7H4FO2) x H2O]n, has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Ag atom is bicoordinated in a linear configuration by two N atoms from two symmetry-related ethylenediamine ligands, giving linear polymeric chains with [-Ag-N-C-C-N-]n backbones running parallel to the b axis. In the crystal packing, these linear chains are interconnected by N-H...O and O-H...O hydrogen bonds, and by weak Ag...OW interactions, forming layers parallel to the ab plane.

Journal Article↗

PubMed2004

Correlation of tumor-positive ratio and number of perigastric lymph nodes with prognosis of patients with surgically-removed gastric carcinoma.

AIM: To evaluate the tumor-positive ratio and number of perigastric lymph nodes as prognostic factors of gastric carcinoma in surgically-treated patients. METHODS: The postoperative survival of 169 patients with gastric cancer who were performed D2 curative gastrectomy was analyzed with regard to its lymph node metastasis ratio and number. Meanwhile correlation of tumor-positive ratio and number of perigastric lymph nodes with pathological parameters of these patients was studied. RESULTS: The overall 5-year survival rate of all the patients studied was 29.6%. The 5-year cumulative survival rate in patients with 1%-20% and more than 20% of tumor-positive lymph nodes was 70.6% and 12.0% respectively, and 46.6% and 17.4% in those with 1-5 and more than 5 of tumor-positive lymph nodes respectively, which were significantly decreased with the increment of involved lymph nodes assessed by either numbers or ratio (P<0.05). Multiple stepwise regression analysis showed that both the positive ratio and number of tumor-involved lymph nodes were sensitive prognostic factors in these surgically-treated patients, which were also significantly correlated with tumor size and depth of submucosal invasion (P<0.05). CONCLUSION: Tumor-positive ratio and number of perigastric lymph nodes are associated with cancer progression and five-year survival rate, and may serve as valuable prognostic factors of gastric cancer in surgically-treated patients.

Adult↗

PubMed2004

Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen.

Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibody-producing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4(+) T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.

Adoptive Transfer↗

PubMed2004

Synthesis of several chemokines but few cytokines by primed uncommitted precursor CD4 T cells suggests that these cells recruit other immune cells without exerting direct effector functions.

Antigen-stimulated naive CD4 T cells may differentiate into effector T cells such as Th1 and Th2 cells, or may remain as proliferating but uncommitted, primed, precursor cells (Thpp cells) that can subsequently differentiate into Th1 or Th2 cells in appropriate cytokine environments. To examine potential Thpp effector functions, we compared the genes expressed by mouse Thpp, naive, Th1 and Th2 cells, using Affymetrix GeneChip and RNase Protection assays. Similar to naive CD4 T cells, Thpp cells expressed IL-2 but not the cytokines characteristic of differentiated Th1 or Th2 cells, such as IFN-gamma, IL-4, or IL-5. However, Thpp, Th1 and Th2 cells, but not naive cells, expressed several CC chemokines including CCL1/TCA3, CCL5/RANTES, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, and CCL9/MIP-1 gamma. Secretion of the corresponding proteins was confirmed by ELISA and Elispot. Consistent with this chemokine expression, supernatants of activated Thpp, Th1 and Th2 cells but not naive CD4T cells induced pertussis toxin-sensitive chemotaxis of B and T cells. Supernatants of Thpp cells did not bias differentiation of naive CD4 T cells towards either Th1 or Th2 cells. The secretion of several chemokines, but few cytokines, by primed uncommitted Thpp cells suggests that their activation during an immune response may recruit effector cells without directly polarizing effector functions.

Animals↗

PubMed2004

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high levels of MMP9. Deletion of MMP9 in these cells completely abolishes their tumor-promoting ability. Gr+CD11b+ cells were also found to directly incorporate into tumor endothelium. Consistent with this observation, Gr+CD11b+ cells acquire endothelial cell (EC) properties in tumor microenvironment and proangiogenic culture conditions. Our data provide evidence that Gr+CD11b+ cells of immune origin induced by tumors directly contribute to tumor growth and vascularization by producing MMP9 and differentiating into ECs.

Animals↗

PubMed2004

Inhibition of human low density lipoprotein oxidation by flavonols and their glycosides.

Antioxidative effects of the flavonols and their glycosides, i.e., quercetin (Q), quercetin galactopyranoside (QG), quercetin rhamnolpyranoside (QR), rutin (R), morin (MO), myrecetin (MY), kaempferol (K) and kaempferol glucoside (KG), against free radical initiated peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2-amidino propane hydrochloride) (AAPH), or by cupric ion (Cu2+). The reaction kinetics were monitored either by the uptake of oxygen and the depletion of alpha-tocopherol (TOH) presented in the native LDL, or by the formation of thiobarbituric acid reactive substances (TBARS). Kinetic analysis of the antioxidation process demonstrates that these flavonols and their glycosides are effective antioxidants against AAPH- and Cu(2+)-initiated LDL peroxidation, the flavonols bearing ortho-dihydroxyl groups possess significantly higher antioxidant activity than those bearing no such functionalities, and the glycosides are less active than their parent aglycones.

Flavonols↗

PubMed2004

Strictinin as an efficient antioxidant in lipid peroxidation.

The antioxidant effect of strictinin (SOH), which was extracted from green tea leaves, against the peroxidation of linoleic acid in sodium dodecyl sulfate (SDS) and cetyl trimethylammonium (CTAB) micelles, against the peroxidation of low-density lipoprotein (LDL) and against oxidative hemolysis of human red blood cells (RBCs), has been studied. The peroxidation of linoleic acid and LDL, and oxidative hemolysis of RBCs were initiated thermally by a water-soluble azo initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), and the reaction kinetics in micelles and LDL were monitored by uptake of oxygen. The synergistic antioxidant effect of SOH with alpha-tocopherol (Vitamin E) was also studied by following the decay kinetics of alpha-tocopherol. Kinetic analysis of the antioxidation process demonstrates that SOH, used either alone or in combination with alpha-tocopherol, is an effective antioxidant against lipid peroxidation, but its effects significantly depend on the reaction medium.

Antioxidants↗

PubMed2004

Diarylheptanoids from the rhizomes of Zingiber officinale.

Seven new diarylheptanoids, i.e., (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxy-phenyl)heptan-3-one and 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane were isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe), along with 25 known compounds, i.e., 8 diarylheptanoids, 14 gingerol analogs, a diterpene and 2 steroids. Their structures were elucidated by spectroscopic and chemical methods.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Tumor-host immune interactions and dendritic cell dysfunction.

Several lines of evidence from recent years support the existence of cancer immunosurveillance, especially studies of natural killer (NK) cells and the IFN-gamma pathway. However, immune suppression is clearly observed in cancer patients and tumor-bearing animals as well. The fact is that although cancers often elicit a vigorous immune response during the early part of their growth, the immune response is soon down-regulated, permitting progressive tumor growth. Apparently, the intrinsic plasticity of tumors allows the immune system to sculpt the immunogenic phenotypes of tumors to escape efficient immune destruction. But most evidently, several mechanisms have now been found to contribute to the failure of immune control of tumor growth. Tumor cells have a very low level of MHC class II, costimulatory molecules, and weak antigens. They also produce immune suppressive factors (VEGF, IL-10, PGE(2)) that exert systemic effects on immune cell function. In particular, disabled dendritic cell differentiation, maturation, migration, and function are fundamental to this defect, as they are the most potent antigen-presenting cells (APCs) of the immune system, interacting with T and B lymphocyte as well as NK cells to induce and modulate immune responses. In addition, tumors also alter host hematopoiesis and produce large numbers of immature dendritic cells, and evidence shows that these cells are directly immune suppressive. Harnessing the immune system for effective cancer therapy has remained a great challenge. DC-based vaccines, or DC-based vaccines in combination with treatments designed to improve the host immune environment, may offer hope for more effective cancer immunotherapy. Tumor-host interactions are an important determinant of tumor behavior and response to therapy. How tumors interact with their hosts is thus a very broad and complex topic. In this chapter, we will focus on tumor-host immune interactions and the roles of dendritic cell dysfunction in tumor avoidance of host immune responses. We will survey recent findings regarding tumor immune surveillance, antitumor host immune responses, and how the immune system also functions to promote or select tumor variants with reduced immunogenicity. We will then discuss immune suppression caused by tumors, which is clearly observed in tumor-bearing animals and cancer patients. Finally, we will discuss altered dendritic cell function and differentiation in some detail, as it is likely to be one of the most fundamental mechanisms by which tumors escape immune responses.

Animals↗

PubMed2004

Epigenetic modification regulates both expression of tumor-associated genes and cell cycle progressing in human colon cancer cell lines: Colo-320 and SW1116.

The aim of this study is to assess the effects of DNA methylation and histone acetylation, alone or in combination, on the expression of several tumor-associated genes and cell cycle progression in two established human colon cancer cell lines: Colo-320 and SW1116. Treatments with 5-aza-2-deoxycytidine (5-aza-dC) and trichostatin A, alone or in combination, were applied respectively. The methylation status of the CDKN2A promoter was determined by methylation-specific PCR, and the acetylated status of the histones associated with the p21WAF1 and CDKN2A genes was examined by chromatin immunoprecipitation. The expression of the CDKN2A, p21WAF1, p53, p73, APC, c-myc, c-Ki-ras and survivin genes was detected by real-time RT-PCR and RT-PCR. The cell cycle profile was established by flow cytometry. We found that along with the demethylation of the CDKN2A gene promoter in both cell lines induced by 5-aza-dC alone or in combination with TSA, the expression of both CDKN2A and APC genes increased. The treatment of TSA or sodium butyrate up-regulated the transcription of p21WAF1 significantly by inducing the acetylation of histones H4 and H3, but failed to alter the acetylation level of CDKN2A-associated histones. No changes in transcription of p53, p73, c-myc, c-Ki-ras and survivin genes were observed. In addition, TSA or sodium butyrate was shown to arrest cells at the G1 phase. However, 5-aza-dC was not able to affect the cell cycle progression. In conclusion, regulation by epigenetic modification of the transcription of tumor-associated genes and the cell cycle progression in both human colon cancer cell lines Colo-320 and SW1116 is gene-specific.

Acetylation↗

PubMed2004

Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone.

In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.

Arteriosclerosis↗

PubMed2004

Eremophilane sesquiterpene lactones from Ligularia virgaurea ssp. oligocephala.

From an extract of the whole plant of Ligularia virgaurea ssp. oligocephala, three new eremophilane sesquiterpene lactones, 10alpha-hydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (1), 6alpha,10alpha-dihydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (2), 6beta,10beta-dihydroxyeremophila-7(11),8(9)-dien-12,8-olide (3), as well as four known sesquiterpene lactones with the same carbon skeleton, named toluccanolides A-C (4, 5, 7) and 6beta-hydroxy-8alpha-methoxyeremophila-1(10),7(11)-dien-12,8beta-olide (6) were isolated. Their structures were elucidated by spectroscopic methods including intensive 2D NMR techniques (gCOSY, gHMQC, gHMBC and 1H-1H NOESY for 2) and HR-ESI-MS.

Asteraceae↗

PubMed2004

Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by cellulose tryptophan adsorbent.

Whole blood immunoadsorption (WBIA) system, using an adsorbent to remove pathogenic antibodies of myasthenia gravis (MG), was studied. Cellulose-tryptophan adsorbent was synthesized and its adsorption capacity of binding with acetylcholine receptor in the plasma of MG patient was evaluated. Experimental autoimmune myasthenia gravis (EAMG) rabbits were induced by Ta183-200 peptide. The rabbits underwent extracorporeal whole blood adsorption for 2 h. Results showed no significant damages on blood cells and no changes in the concentration of electrolytes. Total protein decreased by 12.0% (P < 0.05), and globulin protein decreased 23.9 +/- 5.6% (P < 0.05). The mean overall removal of antibodies against Ta183-200 was 41.12%. The percentage of decrement of compound muscle action potential in 3, 5, 10Hz of EAMG rabbits all dropped down after the treatment. In conclusion, the adsorbent is biocompatible, was safe for whole blood immunoadsorption, and can remove antibodies in an MG patient effectively. Whole blood immunoadsorption improved clinical manifestation and neuromuscular function of the EAMG rabbits.

Animals↗

PubMed2004

A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG as a main start codon for translation initiation of human ACAT1 mRNA.

Human ACAT 1 cDNA K1 was first cloned and functionally expressed in 1993. There are two adjacent in-frame AUG codons, AUG(1397-1399) and AUG(1415-1417), at 5'-terminus of the open reading frame (ORF, nt 1397-3049) of human ACAT1 mRNA corresponding to cDNA K1. In current work, these two adjacent inframe AUGs at 5'-terminus of the predicted ORF (5'-ORF-AUGs) as start codons for translation initiation of human ACAT1 mRNA were characterized in detail. Codon mutations indicated that both of these two adjacent 5'-ORF-AUGs can be selected as start codons but the first 5'-ORF-AUG(1397-1399) is a main start codon consistent with that of the predicted ORF of human ACAT1 mRNA. Further deletion and mutation analyses demonstrated that a stable upstream stem-loop structure enhanced the selection of the first 5'-ORF-AUG(1397 -1399) as a main start codon, in addition to upstream nucleotide A in the -3 position, which is a key site of Kozak sequence. In addition, result of ACAT1 enzymatic activity assay showed no obvious difference between these two ACAT1 proteins respectively initiated from the two adjacent 5'-ORF-AUGs. This work showed that a stable upstream stem-loop structure could modulate the start codon selection during translation initiation of mRNAs that contain adjacent multi-5'-ORF-AUGs.

5' Untranslated Regions↗