Biomedical subjects

Jing-Jy Cheng

Publications and source records attributed to Jing-Jy Cheng.

11 recordsLinked to original sources

PubMed2006

Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12 cells from serum deprivation-induced apoptosis through the activation of adenosine A(2A) receptors.

Antrodia cinnamomea (formerly named Antrodia camphorata) is a rare medicinal fungus. We previously reported that it exhibits antioxidative, vasorelaxative, anti-inflammatory, and anti-angiogenic effects. When serum deprivation-induced apoptosis in neuronal-like PC12 cells was used as a stress model, the extract of A. cinnamomea displayed effectiveness in preventing serum-deprived apoptosis. Since our previous data show that the extract of A. cinnamomea contains adenosine (ADO), we attempt to investigate if the active component is ADO and to identify its targeting site in this study. After pre-incubation with ADO deaminase, neither ADO nor the extract of A. cinnamomea exerted any protection, demonstrating that the active component of A. cinnamomea is ADO. Furthermore, an ADO A(2A) receptor (A(2A)-R) antagonist was used and was able to block the protective effects of ADO and the extract of A. cinnamomea, demonstrating that the ADO targeting site in this model is A(2A)-R. Taken together, the protective effect of A. cinnamomea is owed to its active component, ADO, which acts through activation of A(2A)-R to prevent serum deprivation-induced PC12 cell apoptosis.

Adenosine↗

PubMed2006

Herbal remedy magnolol suppresses IL-6-induced STAT3 activation and gene expression in endothelial cells.

Magnolol (Mag), an active constituent isolated from the Chinese herb Hou p'u (Magnolia officinalis) has long been used to suppress inflammatory processes. Chronic inflammation is well known to be involved in vascular injuries such as atherosclerosis in which interleukin (IL)-6 may participate. Signal transducer and activator of transcription protein 3 (STAT3), a transcription factor involved in inflammation and the cell cycle, is activated by IL-6. In this study, we evaluated whether Mag can serve as an anti-inflammatory agent during endothelial injuries. The effects of Mag on IL-6-induced STAT3 activation and downstream target gene induction in endothelial cells (ECs) were examined. Pretreatment of ECs with Mag dose dependently inhibited IL-6-induced Tyr705 and Ser727 phosphorylation in STAT3 without affecting the phosphorylation of JAK1, JAK2, and ERK1/2. Mag pretreatment of these ECs dose dependently suppressed IL-6-induced promoter activity of intracellular cell adhesion molecule (ICAM)-1 that contains functional IL-6 response elements (IREs). An electrophoretic mobility shift assay (EMSA) revealed that Mag treatment significantly reduced STAT3 binding to the IRE region. Consistently, Mag treatment markedly inhibited ICAM-1 expression on the endothelial surface. As a result, reduced monocyte adhesion to IL-6-activated ECs was observed. Furthermore, Mag suppressed IL-6-induced promoter activity of cyclin D1 and monocyte chemotactic protein (MCP)-1 for which STAT3 activation plays a role. In conclusion, our results indicate that Mag inhibits IL-6-induced STAT3 activation and subsequently results in the suppression of downstream target gene expression in ECs. These results provide a therapeutic basis for the development of Mag as an anti-inflammatory agent for vascular disorders including atherosclerosis.

Animals↗

PubMed2005

Antiangiogenic activities of polysaccharides isolated from medicinal fungi.

Extracted polysaccharides from medicinal fungi, including Antrodia cinnamomea, Antrodia malicola, Antrodia xantha, Antrodiella liebmannii, Agaricus murrill, and Rigidoporus ulmarius, were investigated for their effects on vascular endothelial growth factor (VEGF)-induced tube formation in endothelial cells (ECs). Chemical analysis revealed that myo-inositol, sorbitol, fucose, galactosamine, glucosamine, galactose, glucose, and mannose were the neutral sugars in these polysaccharides. These fungal polysaccharides showed no toxicity to ECs. For the inhibition of endothelial tube formation, extracted polysaccharides from A. xantha and R. ulmarius were shown to produce greater inhibition compared to those from other fungi. Fucose, glucose and mannose were the predominant monosaccharides from these two fungi. These results suggest that monosaccharides may play a role in the inhibitory effect of these fungi on endothelial tube formation. In contrast to the inhibition on tube formation from polysaccharides of A. cinnamomea and A. malicola, polysaccharides from A. xantha and R. ulmarius, with molecular weight between 2693-2876 and 304-325 kDa, were critical for this inhibitory activity. Our results show that polysaccharides isolated from A. xantha and R. ulmarius provide greater antiangiogenesis than those from commercialized A. murrill (Brazilian mushroom) and A. cinnamomea. These studies provide a basis for the potential development of these polysaccharides for antiangiogenesis usage.

Angiogenesis Inhibitors↗

PubMed2005

Study for anti-angiogenic activities of polysaccharides isolated from Antrodia cinnamomea in endothelial cells.

The main purposes of this study were to investigate the regulation of polysaccharides isolated from A. cinnamomea on vascular endothelial growth factor (VEGF)-induced cyclin D1 expression and down stream signaling pathway that may correlate with their anti-angiogenc effects in endothelial cells (ECs). Crude and fractionated polysaccharides (Fra-1 to Fra-4) of A. cinnamomea showed slightly toxicity to ECs as compared with their inhibition concentration on angiogenic-related gene expression. The crude extract and fractionated fractions, except for Fra-2, of A. cinnamomea polysaccharides significantly decreased VEGFR2 phosphorylation on tyrosine 1054/1059, cyclin D1 promotor activity, and protein expression induced by VEGF. Crude extract of A. cinnamomea polysaccharides inhibited the binding of VEGF to KDR/flk-1 in a dose-dependent manner. These results indicated that inhibition of VEGF interaction with VEGF receptor 2 is the mechanism serves A. cinnamomea as a protective mechanism composing the anti-angiogenesis function. Furthermore, A. cinnamomea polysaccharides also blocked VEGF-induced migration and capillary-like tube formation of ECs on Matrigel. Taken together, these results indicate that A. cinnamomea polysaccharides inhibit cyclin D1 expression through inhibition of VEGF receptor signaling, leading to the suppression of angiogenesis.

Angiogenesis Inhibitors↗

PubMed2005

Antrodia camphorata prevents rat pheochromocytoma cells from serum deprivation-induced apoptosis.

Antrodia camphorata (A. camphorata) is a rare medicinal fungus with antioxidative, vasorelaxtative, anti-inflammatory and anti-hepatitive effects. However, the neuroprotective effect has not been studied. By using serum deprivation-induced apoptosis in neuronal-like PC12 cells as a cell stress model, we found that A. camphorata is effective in preventing serum-deprived apoptosis. Inhibitors of both a serine/threonine kinase and a specific protein kinase A (PKA) inhibited the protective effect of A. camphorata, indicating that A. camphorata prevents serum-deprived PC12 cell apoptosis through a PKA-dependent mechanism. A transcription inhibitor, actinomycin D, and a protein synthesis inhibitor, cyclohexamide, both attenuated the protective effect of A. camphorata, indicating a requirement for gene expression for protection by A. camphorata. On the other hand, A. camphorata also increased phosphorylated CREB, a transcription factor, which is H-89-inhibitable in this study, suggesting the possibility that A. camphorata prevents serum deprivation-induced PC12 cell apoptosis through a PKA/CREB-dependent pathway.

Animals↗

PubMed2005

Characterization and functional study of Antrodia camphorata lipopolysaccharide.

Lipopolysaccharide (LPS) is a highly proinflammatory molecule isolated from bacteria. This study demonstrated the existence of LPS in a medicinal fungus, Antrodia camphorata. Because no LPS had been identified in any fungus organism, the purification of LPS from A. camphorata was attempted. LPSs from six strains of A. camphorata (35396, 35398, 35716, B71, B85, and B86) were isolated. Chemical and functional properties were investigated on the fungus LPS. Compositional analysis revealed that sorbitol, fucose, galactose, and glucose were the neutral sugars in LPS of A. camphorata. Galactosamine, glucosamine, galactose, and glucose were the predominant monosaccharide species in E. coli O129 LPS molecules, whereas galactosamine and glucosamine were absent in A. camphorata LPS. Because these properties are different from those of bacterial LPS, the functions between fungus and bacterial LPS are also discussed. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, may be one of the primary targets of LPS action during sepsis. Assays for biological activity were performed on endothelial cells with anti-inflammatory effects associated with sepsis. A. camphorata LPS apparently showed a lesser extent of cytotoxicity than bacterial LPS. In contrary to the proinflammatory property of bacterial LPS, LPS from A. camphorata differentially reversed bacterial LPS-induced intercellular adhersion molecule-1 and monocyte adhesion; both were indicators during inflammatory process. In conclusion, basic chemical properties categorized A. camphorata extracts into lipopolysaccharide. However, the detailed functional structures and bioactivities of A. camphorata LPS were totally different from those of bacterial LPS. The investigation of the existence and anti-inflammatory effect of fungus LPS is at present a truly novel and important finding. These results show that LPS isolated from A. camphorata offers a novel therapeutic target for anti-inflammation against E. coli infection.

Animals↗

PubMed2005

Deterministic vs. probabilistic analyses to identify sensitive parameters in dose assessment using RESRAD.

The dose assessments for sites containing residual radioactivity usually involve the use of computer models that employ input parameters describing the physical conditions of the contaminated and surrounding media and the living and consumption patterns of the receptors in analyzing potential doses to the receptors. The precision of the dose results depends on the precision of the input parameter values. The identification of sensitive parameters that have great influence on the dose results would help set priorities in research and information gathering for parameter values so that a more precise dose assessment can be conducted. Two methods of identifying site-specific sensitive parameters, deterministic and probabilistic, were compared by applying them to the RESRAD computer code for analyzing radiation exposure for a residential farmer scenario. The deterministic method has difficulty in evaluating the effect of simultaneous changes in a large number of input parameters on the model output results. The probabilistic method easily identified the most sensitive parameters, but the sensitivity measure of other parameters was obscured. The choice of sensitivity analysis method would depend on the availability of site-specific data. Generally speaking, the deterministic method would identify the same set of sensitive parameters as the probabilistic method when 1) the baseline values used in the deterministic method were selected near the mean or median value of each parameter and 2) the selected range of parameter values used in the deterministic method was wide enough to cover the 5th to 95th percentile values from the distribution of that parameter.

Agriculture↗

PubMed2004

Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family.

Gastrodia elata (G. elata) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, and epilepsy. In this study, differential methanol (MeOH) extracts of G. elata were found to prevent serum-deprived rat pheochromocytoma (PC12) cell apoptosis by the MTT assay and Hoechst staining. A serine/threonine kinase inhibitor attenuated this protection. G. elata resulted in phosphorylation and dephosphorylation of ERK1/2 and JNK1/2-p38 MAPKs (members of the serine/threonine kinase family), respectively, as revealed by Western blot analysis. An upstream ERK inhibitor attenuated G. elata-induced ERK phosphorylation but not protective effect. Although JNK and p38 inhibitors attenuated their related enzyme activities during serum deprivation, only JNK inhibitor prevented serum-deprived apoptosis. Thus, G. elata prevents serum-deprived apoptosis through activation of the serine/threonine kinase-dependent pathway and suppression of JNK activity.

Analysis of Variance↗

PubMed2004

Resrad-recycle: a computer model for analyzing radiation exposures resulting from recycling radioactively contaminated scrap metals or reusing radioactively surface-contaminated materials and equipment.

RESRAD-RECYCLE is a computer code designed by Argonne National Laboratory (ANL) to be used in making decisions about the disposition of radioactively contaminated materials and scrap metals. It implements a pathway analysis methodology to evaluate potential radiation exposures resulting from the recycling of contaminated scrap metals and the reuse of surface-contaminated materials and equipment. For modeling purposes, it divides the entire metal recycling process into six steps: (1) scrap delivery, (2) scrap melting, (3) ingot delivery, (4) product fabrication, (5) product distribution, and (6) use of finished product. RESRAD-RECYCLE considers the reuse of surface-contaminated materials in their original forms. It contains representative exposure scenarios for each recycling step and the reuse process; users can also specify scenarios if desired. The model calculates individual and collective population doses for workers involved in the recycling process and for the public using the finished products. The results are then used to derive clearance levels for the contaminated materials on the basis of input dose restrictions. The model accounts for radiological decay and ingrowth, dilution and partitioning during melting, and distribution of refined metal in the various finished products, as well as the varying densities and geometries of the radiation sources during the recycling process. A complete material balance in terms of mass and radioactivity during the recycling process can also be implemented. In an international validation study, the radiation doses calculated by RESRAD-RECYCLE were shown to agree fairly well with actual measurement data.

Body Burden↗

PubMed2003

Activation of PKC-epsilon and ERK1/2 participates in shear-induced endothelial MCP-1 expression that is repressed by nitric oxide.

Vascular endothelial cells (ECs) continuously experience hemodynamic shear stress generated from blood flow. Previous studies have demonstrated that shear stress modulates monocyte chemotactic protein-1 (MCP-1) expression in ECs. This study explored the roles of protein kinase C (PKC), extracellular signal-regulated protein kinase (ERK1/2), and nitric oxide (NO) in sheared-induced MCP-1 expression in ECs. The activation of PKC-alpha and PKC-epsilon isoforms was observed in ECs exposed to shear stress. The use of an inhibitor (calphostin C) to PKC-alpha and PKC-epsilon decreased ERK1/2 activation and MCP-1 induction by shear, whereas an inhibitor (Go6976) to PKC-alpha did not affect ERK1/2 activation or MCP-1 induction. Inhibition of ERK1/2 activation by PD98059 blocked MCP-1 induction. Transfection of ECs with an antisense to PKC-epsilon abolished the shear inducibility of MCP-1 promoter. These results demonstrate that PKC-epsilon and ERK1/2 participate in shear-induced MCP-1 expression. We also examined the regulatory role of NO in MCP-1 expression. An NO donor (NOC18) suppressed shear-induced activation of PKC-epsilon and ERK1/2, and also repressed MCP-1 induction. Consistently, overexpression of endothelial nitric oxide synthase (eNOS) to enhance the endogenous generation of NO in ECs decreased the activation of PKC-epsilon and ERK1/2, and also inhibited MCP-1 expression. Taken together, these findings suggest that PKC-epsilon and ERK1/2 are critical in the signaling pathway(s) leading to the MCP-1 expression induced by shear stress. Additionally, this study indicates that NO, by repressing PKC-epsilon activity and ERK pathway activation, attenuates shear-induced MCP-1 expression.

Animals↗

PubMed2002

Cyclic strain activates redox-sensitive proline-rich tyrosine kinase 2 (PYK2) in endothelial cells.

Proline-rich tyrosine kinase 2 (PYK2), structurally related to focal adhesion kinase, has been shown to play a role in signaling cascades. Endothelial cells (ECs) under hemodynamic forces increase reactive oxygen species (ROS) that modulate signaling pathways and gene expression. In the present study, we found that bovine ECs subjected to cyclic strain rapidly induced phosphorylation of PYK2 and Src kinase. This strain-induced PYK2 and Src phosphorylation was inhibited by pretreating ECs with an antioxidant N-acetylcysteine. Similarly, ECs exposed to H(2)O(2) increased both PYK2 and Src phosphorylation. An increased association of Src to PYK2 was observed in ECs after cyclic strain or H(2)O(2) exposure. ECs treated with an inhibitor to Src (PPI) greatly reduced Src and PYK2 phosphorylation, indicating that Src mediated PYK2 activation. Whereas the protein kinase C (PKC) inhibitor (calphostin C) pretreatment was shown to inhibit strain-induced NADPH oxidase activity, ECs treated with either calphostin C or the inhibitor to NADPH oxidase (DPI) reduced strain-induced ROS levels and then greatly inhibited the Src and PYK2 activation. In contrast to the activation of PYK2 and Src with calcium ionophore (ionomycin), ECs treated with a Ca(2+) chelator inhibited both phosphorylation, indicating that PYK2 and Src activation requires Ca(2+). ECs transfected with antisense to PKCalpha, but not antisense to PKCepsilon(,) reduced cyclic strain-induced PYK2 activation. These data suggest that cyclic strain-induced PYK2 activity is mediated via Ca(2+)-dependent PKCalpha that increases NADPH oxidase activity to produce ROS crucial for Src and PYK2 activation. ECs under cyclic strain thus activate redox-sensitive PYK2 via Src and PKC, and this PYK2 activation may play a key role in the signaling responses in ECs under hemodynamic influence.

Animals↗