Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB t...Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB transcription factor family includes several subunits （p50, p52, p65, c-Rel, and Rel B） that respond to myocardial ischemia. It has been proved that persistent myocyte NF-κB p65 activation in heart failure exacerbates cardiac remodeling. Mechods A recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent protein and anti-NF-κB p65 ribozyme （AAV9-R65-CMV-eGFP） was constructed. The cells were assessed by MTT assay, Annexin V–propidium iodide dual staining to study apoptosis. The expression of P65 and P50 were assessed by Western blot to investigate the under-lying molecular mechanisms. Results After stimulation with H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP decreased H2O2-induced P65 expression. Conclusions AAV9-R65-CMV-eGFP protects H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65 expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential to exert cardioprotective effects against oxidative stress, which might be of great importance to clinical efficacy for cardiovascular disease.展开更多
This study was conducted to elucidate the potential key candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension.Methods Expression profiles GSE2378 and GSE758 including 27 react...This study was conducted to elucidate the potential key candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension.Methods Expression profiles GSE2378 and GSE758 including 27 reactive optic nerve head astrocytes(ONHAs)by hypertensions and 26 normal controls,were integrated and deeply analyzed.Differentially expressed genes(DEGs)were sorted and candidate genes and pathways enrichment were analyzed.DEGs-associated protein-protein interaction network(PPI)was performed.Results A total of 119 consistently expressed genes were identified from 281 commonly changed DEGs,including 68 up-regulated genes and 51 down-regulated genes.PPI network complex filtered 75 DEGs(43 up-regulated and 32 down-regulated genes)of the 119 consistently altered DEGs and developed 117 edges,and 10 hub genes were identified.The most significant 3 modules were filtered from PPI,pathway enrichment analysis showed that module 1 was associated with extracellular exosome.Module 2 was mainly associated with antibody-dependent cellular cytotoxicity(ADCC)and module 3 was mainly associated with Hippo signaling pathway.Conclusion Taken above,using integrated bioinformatical analysis,we have identified DEGs candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension,which could improve our understanding of the cause and underlying molecular events,and these candidate genes and pathways could be therapeutic targets for glaucoma.展开更多
基金the National Natural Sci-ence Foundation of China，China Post-doctoral Science Foundation
文摘Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB transcription factor family includes several subunits （p50, p52, p65, c-Rel, and Rel B） that respond to myocardial ischemia. It has been proved that persistent myocyte NF-κB p65 activation in heart failure exacerbates cardiac remodeling. Mechods A recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent protein and anti-NF-κB p65 ribozyme （AAV9-R65-CMV-eGFP） was constructed. The cells were assessed by MTT assay, Annexin V–propidium iodide dual staining to study apoptosis. The expression of P65 and P50 were assessed by Western blot to investigate the under-lying molecular mechanisms. Results After stimulation with H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP decreased H2O2-induced P65 expression. Conclusions AAV9-R65-CMV-eGFP protects H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65 expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential to exert cardioprotective effects against oxidative stress, which might be of great importance to clinical efficacy for cardiovascular disease.
基金support from the China National Natural Science Foundation Funding Project(NO.81804150)Hunan University of Chinese Medicine,National Key Discipline of TCM Diagnostics Foundation Funding Project(No.2015ZYZD02)+5 种基金The Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese MedicineHunan Provincial Department of Education Innovation Platform Open Fund Project(16K065)Chinese Medicine Key Laboratory of Prevention and Treatment of Disease in Hunan Province(2017TP1018)Changsha Science and Technology Plan Project(KC1704005)Hunan Engineering Technology Research Center for the Prevention and Treatment of Otorhinolaryngologic Diseases and Protection of Visual Function with Chinese MedicineHunan Provincial Research Innovation Project for Graduate students(CX2017B426)
文摘This study was conducted to elucidate the potential key candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension.Methods Expression profiles GSE2378 and GSE758 including 27 reactive optic nerve head astrocytes(ONHAs)by hypertensions and 26 normal controls,were integrated and deeply analyzed.Differentially expressed genes(DEGs)were sorted and candidate genes and pathways enrichment were analyzed.DEGs-associated protein-protein interaction network(PPI)was performed.Results A total of 119 consistently expressed genes were identified from 281 commonly changed DEGs,including 68 up-regulated genes and 51 down-regulated genes.PPI network complex filtered 75 DEGs(43 up-regulated and 32 down-regulated genes)of the 119 consistently altered DEGs and developed 117 edges,and 10 hub genes were identified.The most significant 3 modules were filtered from PPI,pathway enrichment analysis showed that module 1 was associated with extracellular exosome.Module 2 was mainly associated with antibody-dependent cellular cytotoxicity(ADCC)and module 3 was mainly associated with Hippo signaling pathway.Conclusion Taken above,using integrated bioinformatical analysis,we have identified DEGs candidate genes and pathways in role of astrocyte involved in glaucoma with ocular hypertension,which could improve our understanding of the cause and underlying molecular events,and these candidate genes and pathways could be therapeutic targets for glaucoma.
