Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, es...Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.展开更多
Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiol...Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.展开更多
The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here,...The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 （PHF20） functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout （KO） for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly（ADP-ribose） polymerase 1 （PARP1） and directly binds to promoter regions of octamer-binding transcription factor 4 （OCT4） and sex determining region Y-box 2 （SOX2） to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit （H3K4me3）. Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.展开更多
文摘Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.
文摘Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.
基金This work was supported by grants from the National Natural Science Foundation of China （81572766 and 31771630）, the National Key Research and Development Program of China （2017YFA0103800）, Guangdong Innovative and Entrepreneurial Research Team Program （2016ZT06S029）, Guangdong Natural Science Foundation （2016A030313215 and 2016A030313238）, SYSU Young Teachers Training Program （16YKZD14） and grants （CA101795 and IU54CA210181） from U.S. National Cancer Institute, National Institutes of Health （NIH）, DOD （W81XWH-16- 1-0417）, and CPRIT （DP150099, RP170537, and RP150611）.
文摘The differentiation status of neuroblastoma （NB） strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 （PHF20） functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout （KO） for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly（ADP-ribose） polymerase 1 （PARP1） and directly binds to promoter regions of octamer-binding transcription factor 4 （OCT4） and sex determining region Y-box 2 （SOX2） to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit （H3K4me3）. Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.
