1,677 research outputs found
Accumulation of organochlorine pesticides in marine fishes from coast of Taoyuan in Taiwan.
Sublethal effects of paraquat and malathion on the freshwater shrimp, Macrobrachium nipponense.
Measurement of the current and spectral analysis on the continental shelf in the East China Sea
YC-1 Antagonizes Wnt/β-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma
Novel drugs targeting Wnt signaling are gradually being developed for hepatocellular carcinoma (HCC) treatment. In this study, we used a Wnt-responsive Super-TOPflash (STF) luciferase reporter assay to screen a new compound targeting Wnt signaling. 3-(5′-Hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) was identified as a small molecule inhibitor of the Wnt/β-catenin pathway. Our coimmunoprecipitation (co-IP) data showed that YC-1 did not affect the β-catenin/TCF interaction. Then, by mass spectrometry, we identified the ErbB3 receptor-binding protein 1 (EBP1) interaction with the β-catenin/TCF complex upon YC-1 treatment. EBP1 encodes two splice isoforms, p42 and p48. We further demonstrated that YC-1 enhances p42 isoform binding to the β-catenin/TCF complex and reduces the transcriptional activity of the complex. The suppression of colony formation by YC-1 was significantly reversed after knockdown of both isoforms (p48 and p42); however, the inhibition of colony formation was maintained when only EBP1 p48 was silenced. Taken together, these results suggest that YC-1 treatment results in a reduction in Wnt-regulated transcription through EBP1 p42 and leads to the inhibition of tumor cell proliferation. These data imply that YC-1 is a drug that antagonizes Wnt/β-catenin signaling in HCC
Involvement of YC-1 in extracellular signal-regulated kinase action in rat cremasteric muscle
AbstractObjectivesThe nitric oxide (NO)–soluble guanylate cyclase (sGC) signalling pathway is attributed to the prevention of ischaemia–reperfusion (I/R)-induced leucocyte–endothelium adhesive interactions. YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole), a NO-independent sGC activator, has been shown to exert cardiovascular benefits, but its action on leucocyte–endothelium interactions remains unknown. In this study, the direct effect and the underlying mechanism of the anti-adhesive action of YC-1 have been examined in cremasteric microcirculation.MethodsRat cremaster muscle was subjected to 4 h pudic-epigastric artery ischaemia followed by 2 h reperfusion and intravital microscopy was used to observe leucocyte–endothelium interaction and to quantify functional capillaries in rat cremaster muscle flaps.Key findingsThe values for leucocyte rolling, adhering and transmigrating were 5.5-, 6.9- and 8.8-fold greater, respectively, in I/R than in sham-control animals. YC-1 treatment rescued functional capillary density and reduced leucocyte rolling, adhering and transmigrating in I/R injured cremaster muscles to levels observed in sham-controls. Interestingly, these effects were completely blocked by the MEK (extracellular signal-regulated kinase (ERK) kinase) inhibitor (PD98059) but not by sGC or protein kinase C inhibitors. Cotreatment of PD98059 with YC-1 caused a 3.3-, 7.5- and 8.3-fold increase in the values for leucocyte rolling, adhering and transmigrating, respectively, in postcapillary venules of I/R-injured cremaster muscle.ConclusionsThis study has indicated that the anti-adhesive and functional capillary density rescue properties of YC-1 were mediated predominantly by the activation of ERK but not sGC, although YC-1 was identified to be a sGC activator. A better understanding of the action of YC-1 on the microvasculature may help shed light on its therapeutic potential for cardiovascular disease.</jats:sec
Intrapleural minocycline following simple aspiration for initial treatment of primary spontaneous pneumothorax.
Up-regulation of tumor interleukin-8 expression by infliltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer.
Quantitative assessment of efficacy of Dysport (Botulinum toxin type A) in the treatment of idiopathic blepharospasm and hemifacial spasm
Salvage for unsuccessful aspiration of primary pneumothorax: thoracoscopic surgery or chest tube drainage?
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