To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel...To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.展开更多
One new 2-arylbenzofuran derivative, artocarstilbene B（1）, one new benzaldehyde derivative,（E）-3,5-dihydroxy-4-（3-methylbut-1-enyl）benzaldehyde（2）, as well as 18 known compounds（3–20） were obtained from the...One new 2-arylbenzofuran derivative, artocarstilbene B（1）, one new benzaldehyde derivative,（E）-3,5-dihydroxy-4-（3-methylbut-1-enyl）benzaldehyde（2）, as well as 18 known compounds（3–20） were obtained from the leaves of Artocarpus heterophyllus. Their structures were elucidated on the basis of extensive spectroscopic techniques including 2D NMR and HR-ESIMS. Many compounds exhibited moderate to weak inhibitory activity against the proliferation of the PC-3, NCI-H460, and A549 cancer cell lines.展开更多
文摘泛素连接酶E4B通过U-box基序可将经泛素活化酶(Ubiquitin-activating enzyme, E1)和泛素结合酶(Ubiquitin-conjugating enzyme, E2)传递的泛素(Ubiquitin, UB)标记至底物蛋白质。探究3个蛋白质:金属蛋白酶M20家族蛋白质2(Peptidase M20 domain-containing protein 2,PM20D2)、多腺苷酸结合蛋白质1(Polyadenylate-binding protein 1,PABPC1)、细胞色素C氧化酶Ⅰ翻译激活剂(Translational activator of cytochrome C oxidase Ⅰ,TACO1)是否可被E4B介导泛素化。从HEK293细胞中提取总RNA,反转录为cDNA,以其为模板调取底物基因并构建重组质粒,利用大肠杆菌表达系统表达并纯化泛素化过程所需的各个相关蛋白质,通过蛋白质体外泛素化实验,对3个蛋白质进行泛素化验证。结果表明3个蛋白质均可以在蛋白质水平被E4B泛素化,证明3个蛋白质都是E4B的底物,为进一步在细胞中研究其泛素化的机理奠定基础。
文摘To investigate the relationship between tendinopathy and higher production of prostaglandins E2 (PGE2) and leukotriene B4(LTB4) induced by cyclic stretching of human patellar tendon fibroblasts.Methods We used a novel in vitro model system to mimic in vivo conditions,where human patellar tendon fibroblasts (HPTFs) were uniaxially stretched with different magnitudes of stretching (4%,8% and 12%).Non-stretched fibroblasts were used as control.The productions of PGE2 and LTB4 as well as the expression of cycloxygenase (COX) and 5-lipoxygenase (5-LO) were then measured every four hours of cyclic stretching.In addition,we treated the cells with inhibitors of COX or 5-LO.Results It was found that cyclic stretching of fibroblasts at 8% and 12% of stretching increased PGE2 and LTB4 levels.Blocking the COX enzyme with indomethacin (25 mol/L) decreased PGE2 levels but increased LTB4 production and vice versa.Whereas decreasing LTB4 production with MK-886 (10 μmol/L) could increase PGE2 levels compared to cells tretched without inhibitors.Conclusion Cyclic stretching of HPTFs produces high levels of PGE2 and LTB4,where a balance exists:blocking PGE2 production increases the production of LTB4,and vice versa.Therefore,this study raises the possibility that the routine use of COX inhibitors in clinical treatment of tendinopathy may exacerbate the condition by causing neutrophil-mediated inflammatory and degenerative changes in the tendon due to increased levels of LTB4,which is a potent chemoattractant for neutrophils.17 refs,3 figs.
基金Financial supports from National Natural Science Foundation of China (No. 31500280)Shandong Provincial Natural Science Foundation, China (No. ZR2015PC006)
文摘One new 2-arylbenzofuran derivative, artocarstilbene B（1）, one new benzaldehyde derivative,（E）-3,5-dihydroxy-4-（3-methylbut-1-enyl）benzaldehyde（2）, as well as 18 known compounds（3–20） were obtained from the leaves of Artocarpus heterophyllus. Their structures were elucidated on the basis of extensive spectroscopic techniques including 2D NMR and HR-ESIMS. Many compounds exhibited moderate to weak inhibitory activity against the proliferation of the PC-3, NCI-H460, and A549 cancer cell lines.
