6,250 research outputs found
Clinical manifestations and molecular epidemiology of necrotizing pneumonia and empyema caused by Streptococcus pneumoniae in children in Taiwan.
No full textYc-1 Potentiates the Antiplatelet Effect of Hydrogen Peroxide Via Sensitization of Soluble Guanylate Cyclase
No full textthe present study, we showed that 3-(5'-hydroxymethyl-2'- furyl)-1-benzyl indazole (YC-1), a nitric oxide (NO)- independent activator of soluble guanylate cyclase, could potentiate H2O2-induced inhibition of platelet aggregation and increase of platelet cGMP levels. The synergistic effect of YC-1 and H2O2 on platelet aggregation and increases of cGMP were almost completely prevented by catalase and a selective soluble guanylate cyclase inhibitor (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or partially attenuated by the hydroxyl radical scavenger mannitol. In contrast, superoxide dismutase failed to influence H2O2/YC-1 -induced inhibition of aggregation. Furthermore, YC-1 could enhance the activation of soluble guanylate cyclase caused by FeSO4/H2O2 and, this effect was prevented markedly by mannitol. These results suggest that YC-1 may enhance the antiaggregatory effect of H2O2 via the sensitization of platelet soluble guanylate cyclase. In addition, this phenomenon is, at least in part, dependent on H2O2-derived hydroxyl radical. (C) 1999 Elsevier Science B.V. All rights reserved
Yc-1 Inhibits Proliferation of Human Vascular Endothelial Cells through a Cyclic Gmp-Independent Pathway
No full textThis study was designed to investigate the effect of YC-1, 3 -(5'- hydroxymethyl-2'-furyl)-1-benzylindazole, in human umbilical vein endothelial cells (HUVECs) proliferation and its underlying mechanism. YC- 1 at a range of concentrations( 5-50 muM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. YC- 1 was not cytotoxic at these concentrations. [H-3]thymidine incorporation and flow cytometry analyses revealed that YC-1 treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Western blot analysis demonstrated that YC-1 (5-50 muM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins (CKIs), p 21 and p27, but did not induce any significant changes of cyclins and CDKs. In the YC-1-treated HUVEC, the formation of CDK2-p21 complex, but not CDK2-p27 complex, was increased and the assayable CDK2 kinase activity was decreased. These changes were in a dose-dependent manner. In contrast, the formations of CDK4-p21 and CDK4-p27 complex were slightly increased and the assayable CDK4 kinase activity was slightly decreased (if there were any changes). Pretreatment with guanylyl cyclase inhibitors, 1H-(1,2,4)oxadiazolo[4,3- a]quinozalin-1-one (ODQ) and methylene blue, inhibited the YC-1-induced increase of cyclic GMP level, but did not change significantly the magnitude of the YC-1-induced inhibition of thymidine incorporation and cell number in HUVEC. These results indicate that YC-1-induced cell cycle arrest in HUVEC occurred when the cyclin-CDK system was inhibited just as p21 and p27 protein levels were augmented. This YC-1-induced antiproliferation effect in HUVEC is via acyclic GMP-independent pathway
Yc-1 Prevents Sodium Nitroprusside-Mediated Apoptosis in Vascular Smooth Muscle Cells
No full textObjective: Nitric oxide signaling pathways are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, the authors investigated whether YC-1, a soluble guanylyl cyclase (sGC) activator, regulates apoptosis in vascular smooth muscle cells (VSMC). Methods and results: Sodium nitroprusside (SNP ) (1 mM) induced cGMP (guanosine 3' :5'-cyclic monophosphate)-independent apoptosis in rat vascular smooth muscle cells using MTT assay and TUNEL- reaction techniques. Furthermore, sodium nitroprusside induced apoptosis via Bcl-2 down-regulation, cytochrome c release reaction, and caspase-3 activation by Western blotting analysis and enzymatic assay methods. YC-1 abolished these apoptotic signaling cascades and prevented apoptosis through a cGMP-involved pathway, and phosphatidylinositol (PI) 3-kinase behaved a downstream event in this pathway. Conclusions: These results suggest that YC-1 inhibits sodium nitroprusside-induced vascular smooth muscle cells apoptosis via a cGMP- and phosphatidylinositol 3-kinase- involved inhibition on Bcl-2 down-regulation/cytochrome c release/ caspase -3 activation cascades. The ability of YC-1 to prevent smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved
Yc-1 Inhibits Hif-1 Expression in Prostate Cancer Cells: Contribution of Akt/Nf-Kappa B Signaling to Hif-1 Alpha Accumulation during Hypoxia
No full textHypoxia-inducible factor 1 ( HIF-1), a transcription factor that is critical for tumor adaptation to microenvironmental stimuli, represents an attractive chemotherapeutic target. YC-1 is a novel antitumor agent that inhibits HIF-1 through previously unexplained mechanisms. In the present study, YC- 1 was found to prevent HIF-1 alpha and HIF-1 beta accumulation in response to hypoxia or mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1 alpha protein half -life nor mRNA level was affected by YC- 1. However, YC-1 was found to suppress the PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1 alpha expression at the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced activation of nuclear factor ( NF)-kappa B, a downstream target of Akt. Two modulators of the Akt/NF- kappa B pathway, caffeic acid phenethyl ester and evodiamine , were observed to decrease HIF-1 alpha expression. Additionally, overexpression of NF-kappa B partly reversed the ability of wortmannin to inhibit HIF-1 alpha-dependent transcriptional activity, suggesting that NF-kappa B contributes to Akt-mediated HIF-1 alpha accumulation during hypoxia. Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression
The yield per recruit analysis for lizard fish, Saurida undosquamis , in the southern Taiwan Strait.
No full textA Potential Role of Yc-1 on the Inhibition of Cytokine Release in Peripheral Blood Mononuclear Leukocytes and Endotoxemic Mouse Models
No full textTo evaluate the anti-sepsis potential of YC-1,we have examined the effect of YC-1 on the regulation of cytokine production in human leukocytes and endotoxemic mice. The data demonstrated thatYC-1 showed a preferential inhibition on proinflammatory cytokine production without inhibition of cell growth or induction of cytotoxicity in human leukocytes. On the other hand, in the septic mouse model, treatment with an intraperitoneal application of LPS caused a cumulative death within 27 hours.The post- treatment administration of YC-1 significantly increased the survival rate in endotoxemic mice. Furthermore, several mediators were detected and the data showed thatYC-1 profoundly blocked LPS-induced NO as well asTNF-α production, and prevented lung damage by histological examination. Samples from the animal model showed that LPS-induced NF- κ B/DNA binding activity and consequent up-regulation of iNOS expression in tissues were abolished by post-administration of YC-1.Furthermore,YC-1,by itself,did not modify cGMP content while significantly inhibit LPS-induced cGMP formation, suggesting thatYC-1-mediated effect was not through a cGMP- elevating pathway.Taken together, it is evident that the post-treatment administration of YC-1 after LPS application significantly inhibits NF- κ B activation, iNOS expression, NO over-production, and cytokine release reaction resulting in an improved survival rate in endotoxemic mice. It is suggested thatYC-1 may be a potential agent for the therapeutic treatment of sepsis
The association between glutathione S-transferase P1, M1 polymorphisms and asthma in Taiwanese schoolchildren.
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