AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition(EMT) in human retinal pigment epithelial cells(ARPE-19) in vitro.METHODS: In vitro c...AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition(EMT) in human retinal pigment epithelial cells(ARPE-19) in vitro.METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/m L bevacizumab for 12, 24, and 48 h.Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1(ZO-1), vimentin and Notch-1 intracellular domain(NICD) was examined by immunofluorescence.The m RNA levels of ZO-1, α-SMA, Notch-1, Notch-2,Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR). The protein levels of α-SMA,NICD, Hes-1 and Dll-4 expression were examined with Western blot.RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells.Meanwhile, the m RNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The m RNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48 h, and while Dll4 m RNA and protein expression did not change after bevacizumab treatment.CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.展开更多
Metrics To the editor:The diabetes epidemic has increasingly become a major public health concern worldwide.In 2014,there were 102.9 million diabetic adults in China,representing 24.4%of the world's diabetic popul...Metrics To the editor:The diabetes epidemic has increasingly become a major public health concern worldwide.In 2014,there were 102.9 million diabetic adults in China,representing 24.4%of the world's diabetic population,even though China only comprised 18.7%of the global population at the time.[1]Furthermore,the estimated overall prevalence of diabetes and prediabetes was 10.9%and 35.7%,respectively,indicating China as one of the countries with the highest prevalence of diabetes in the world.[2]Although factors,including sedentary lifestyles and energy-dense diets,drive the diabetes epidemic,genetic architecture may also contribute to the susceptibility of an individual's response to environmental challenges.Aldehyde dehydrogenase(ALDH)2 is a key enzyme that eliminates toxic aldehydes by catalyzing their oxidation to non-reactive acids.Emerging evidence has suggested that individuals with ALDH2 deficiency have an increased risk of cardiovascular and metabolic diseases,in addition to alcohol intolerance,nitroglycerin tolerance,and carcinoma.[3]Notably,a unique ALDH2 loss-of-function allele,ALDH2∗2,is found in approximately 50%of the East Asian and 8%of the global populations.It has been reported that this ALDH2 mutation is associated with a higher prevalence of diabetes in coronary artery disease(CAD)patients,accompanied with increased C-reactive protein(CRP)levels.[4]ALDH2 mutation is also related to various diabetes risk factors,but the direct correlation remains elusive.Herein,we have explored the potential pathogenicity and mechanisms of ALDH2 deficiency in the development of type 2 diabetes in both laboratory and clinical settings.展开更多
基金Supported by the National Natural Science Foundation of China(No.81170815)the Taishan Scholar Program(No.ts20081148)+1 种基金the Science and Technology Development Foundation of Shinan District of Qingdao City(No.2012-3-004-YY)Youth Foundation of Shandong Academy of Medical Sciences(No.2014-41)
文摘AIM: To investigate the effect of bevacizumab treatment on Notch signaling and the induction of epithelial-of-mesenchymal transition(EMT) in human retinal pigment epithelial cells(ARPE-19) in vitro.METHODS: In vitro cultivated ARPE-19 cells were treated with 0.25 mg/m L bevacizumab for 12, 24, and 48 h.Cell morphology changes were observed under an inverted microscope. The expression of zonula occludens-1(ZO-1), vimentin and Notch-1 intracellular domain(NICD) was examined by immunofluorescence.The m RNA levels of ZO-1, α-SMA, Notch-1, Notch-2,Notch-4, Dll4, Jagged-1, RBP-Jk and Hes-1 expression were evaluated with quantitative real-time polymerase chain reaction(q RT-PCR). The protein levels of α-SMA,NICD, Hes-1 and Dll-4 expression were examined with Western blot.RESULTS: Bevacizumab stimulation increased the expression of α-SMA and vimentin in ARPE-19 cells which changed into spindle-shaped fibroblast-like cells.Meanwhile, the m RNA expression of Hes-1 increased and the protein expression of Hes-1 and NICD also increased, which Notch signaling was activated. The m RNA expression of Notch-1, Jagged-1 and RBP-Jk increased at 48 h, and while Dll4 m RNA and protein expression did not change after bevacizumab treatment.CONCLUSION: Jagged-1/Notch-1 signaling may play a critical role in bevacizumab-induced EMT in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal bevacizumab-associated complication.
基金supported by grants from the National Natural Science Foundation of China(No.81700279)the National Science Fund for Distinguished Young Scholars(No.81725002).
文摘Metrics To the editor:The diabetes epidemic has increasingly become a major public health concern worldwide.In 2014,there were 102.9 million diabetic adults in China,representing 24.4%of the world's diabetic population,even though China only comprised 18.7%of the global population at the time.[1]Furthermore,the estimated overall prevalence of diabetes and prediabetes was 10.9%and 35.7%,respectively,indicating China as one of the countries with the highest prevalence of diabetes in the world.[2]Although factors,including sedentary lifestyles and energy-dense diets,drive the diabetes epidemic,genetic architecture may also contribute to the susceptibility of an individual's response to environmental challenges.Aldehyde dehydrogenase(ALDH)2 is a key enzyme that eliminates toxic aldehydes by catalyzing their oxidation to non-reactive acids.Emerging evidence has suggested that individuals with ALDH2 deficiency have an increased risk of cardiovascular and metabolic diseases,in addition to alcohol intolerance,nitroglycerin tolerance,and carcinoma.[3]Notably,a unique ALDH2 loss-of-function allele,ALDH2∗2,is found in approximately 50%of the East Asian and 8%of the global populations.It has been reported that this ALDH2 mutation is associated with a higher prevalence of diabetes in coronary artery disease(CAD)patients,accompanied with increased C-reactive protein(CRP)levels.[4]ALDH2 mutation is also related to various diabetes risk factors,but the direct correlation remains elusive.Herein,we have explored the potential pathogenicity and mechanisms of ALDH2 deficiency in the development of type 2 diabetes in both laboratory and clinical settings.
