Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell se...Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell senescence in increasing sensitivity to this chemotherapy agent.This study aims to identify genes related to cell senescence in children diagnosed with NB,evaluate their influence on cisplatin sensitivity,and investigate potential strategies to enhance the efficacy of chemotherapy.Methods:Gene expression profiles and clinical data were obtained for 498 NB patients from the GEO database(GSE49710).The study focused on identifying genes that were differentially expressed between stage IV and other stages,particularly those linked to cell senescence and cisplatin resistance.To analyze the prognostic significance of these differentially expressed genes,we employed LASSO regression and multivariate Cox proportional hazards models.Transcriptomic and proteomic analyses of 15 NB specimens revealed a significant correlation between Flap endonuclease-1(FEN1)expression levels and both cellular senescence and sensitivity to cisplatin.We quantified FEN1 expression and cisplatin IC50 values in four different NB cell lines.The influence of FEN1 knockdown and overexpression on NB cell proliferation,invasion,and migration was evaluated using cloning assays,transwell assays,and scratch assays.Furthermore,we utilized Western blotting to analyze senescenceassociated proteins p21 and proliferating cell nuclear antigen(PCNA),thereby evaluating the role of FEN1 in cellular senescence.The impact of FEN1 on cisplatin sensitivity was investigated via the CCK-8 cell counting assay.Additionally,we investigated how FEN1 inhibitors might impact NB cell proliferation and enhance the therapeutic efficacy of cisplatin treatment.Results:FEN1 was found to be highly expressed in stage IV NB and showed a strong association with cisplatin sensitivity,establishing it as a critical molecular marker linked to poor patient prognosis.Notably,elevated FEN1 expression correlated with reduced sensitivity to cisplatin,as evidenced by higher IC50 values.In the SH-SY5Y cell line,FEN1 knockdown led to significant reductions in cell proliferation,invasion,and migration,along with an increase inβ-galactosidase staining—indicative of senescence.This knockdown also resulted in elevated levels of the p21 protein and decreased expression of PCNA,concurrently lowering cisplatin IC50 values.Conversely,FEN1 overexpression in the SK-N-SH cell line resulted in enhanced cell proliferation,invasion,and migration.This overexpression was associated with reducedβ-galactosidase staining,decreased levels of p21,and increased expression of PCNA,ultimately resulting in higher cisplatin IC50 values.Importantly,FEN1 inhibitors alone significantly impeded NB cell proliferation,and their combination with cisplatin further amplified this inhibitory effect compared to cisplatin treatment alone.Conclusions:Bioinformatics and sequencing analyses indicate that the senescence-related gene FEN1 is significantly associated with cisplatin sensitivity and adverse prognosis in pediatric NB.FEN1 plays a pivotal role in regulating NB cell proliferation,invasion,and migration,thereby facilitating cancer progression.Furthermore,it influences cisplatin sensitivity through its effects on cellular senescence.FEN1 inhibitors demonstrate potential both as monotherapies and in conjunction with cisplatin,suggesting that targeting FEN1 may be represent a valuable strategy for improving outcomes in high-risk NB patients.展开更多
Activity 1.Think about the following questions and write down your answers before reading the text.1.Have you ever tried Liuzhou Luosifen?If so,what did you think of it?2.What makes Liuzhou Luosifen unique compared to...Activity 1.Think about the following questions and write down your answers before reading the text.1.Have you ever tried Liuzhou Luosifen?If so,what did you think of it?2.What makes Liuzhou Luosifen unique compared to other types of noodles?展开更多
采用热解法制备FeN/C催化剂,考察催化剂前驱体中氮含量对其氧还原活性的影响.使用X射线衍射、比表面积和孔径分布测试、透射电子显微镜以及热重分析等方法对催化剂的结构、形貌及催化剂前驱体的热性质等进行表征,使用线性扫描伏安法对...采用热解法制备FeN/C催化剂,考察催化剂前驱体中氮含量对其氧还原活性的影响.使用X射线衍射、比表面积和孔径分布测试、透射电子显微镜以及热重分析等方法对催化剂的结构、形貌及催化剂前驱体的热性质等进行表征,使用线性扫描伏安法对催化剂的氧还原活性进行测试.结果表明,以1,10-菲啰啉为氮源,FeCl3为铁源,Black Pearl 2000为载体,催化剂前驱体中1,10-菲啰啉含量为20wt%,Fe含量为1wt%时,热处理制备所得催化剂粒子分布均匀,比表面积为824.48 m2·g-1,平均孔隙为10.58 nm,表面的氮元素含量为0.31wt%;并具有最好的氧还原催化活性.催化剂前驱体中氮源含量在热解过程中导致催化剂的比表面积、孔径结构及表面氮元素含量的变化是影响催化剂活性的关键因素.展开更多
基金supported by grant from Affiliated Hospital of Nantong University(YJXYY202204)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX24_2063).
文摘Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell senescence in increasing sensitivity to this chemotherapy agent.This study aims to identify genes related to cell senescence in children diagnosed with NB,evaluate their influence on cisplatin sensitivity,and investigate potential strategies to enhance the efficacy of chemotherapy.Methods:Gene expression profiles and clinical data were obtained for 498 NB patients from the GEO database(GSE49710).The study focused on identifying genes that were differentially expressed between stage IV and other stages,particularly those linked to cell senescence and cisplatin resistance.To analyze the prognostic significance of these differentially expressed genes,we employed LASSO regression and multivariate Cox proportional hazards models.Transcriptomic and proteomic analyses of 15 NB specimens revealed a significant correlation between Flap endonuclease-1(FEN1)expression levels and both cellular senescence and sensitivity to cisplatin.We quantified FEN1 expression and cisplatin IC50 values in four different NB cell lines.The influence of FEN1 knockdown and overexpression on NB cell proliferation,invasion,and migration was evaluated using cloning assays,transwell assays,and scratch assays.Furthermore,we utilized Western blotting to analyze senescenceassociated proteins p21 and proliferating cell nuclear antigen(PCNA),thereby evaluating the role of FEN1 in cellular senescence.The impact of FEN1 on cisplatin sensitivity was investigated via the CCK-8 cell counting assay.Additionally,we investigated how FEN1 inhibitors might impact NB cell proliferation and enhance the therapeutic efficacy of cisplatin treatment.Results:FEN1 was found to be highly expressed in stage IV NB and showed a strong association with cisplatin sensitivity,establishing it as a critical molecular marker linked to poor patient prognosis.Notably,elevated FEN1 expression correlated with reduced sensitivity to cisplatin,as evidenced by higher IC50 values.In the SH-SY5Y cell line,FEN1 knockdown led to significant reductions in cell proliferation,invasion,and migration,along with an increase inβ-galactosidase staining—indicative of senescence.This knockdown also resulted in elevated levels of the p21 protein and decreased expression of PCNA,concurrently lowering cisplatin IC50 values.Conversely,FEN1 overexpression in the SK-N-SH cell line resulted in enhanced cell proliferation,invasion,and migration.This overexpression was associated with reducedβ-galactosidase staining,decreased levels of p21,and increased expression of PCNA,ultimately resulting in higher cisplatin IC50 values.Importantly,FEN1 inhibitors alone significantly impeded NB cell proliferation,and their combination with cisplatin further amplified this inhibitory effect compared to cisplatin treatment alone.Conclusions:Bioinformatics and sequencing analyses indicate that the senescence-related gene FEN1 is significantly associated with cisplatin sensitivity and adverse prognosis in pediatric NB.FEN1 plays a pivotal role in regulating NB cell proliferation,invasion,and migration,thereby facilitating cancer progression.Furthermore,it influences cisplatin sensitivity through its effects on cellular senescence.FEN1 inhibitors demonstrate potential both as monotherapies and in conjunction with cisplatin,suggesting that targeting FEN1 may be represent a valuable strategy for improving outcomes in high-risk NB patients.
文摘Activity 1.Think about the following questions and write down your answers before reading the text.1.Have you ever tried Liuzhou Luosifen?If so,what did you think of it?2.What makes Liuzhou Luosifen unique compared to other types of noodles?
文摘采用热解法制备FeN/C催化剂,考察催化剂前驱体中氮含量对其氧还原活性的影响.使用X射线衍射、比表面积和孔径分布测试、透射电子显微镜以及热重分析等方法对催化剂的结构、形貌及催化剂前驱体的热性质等进行表征,使用线性扫描伏安法对催化剂的氧还原活性进行测试.结果表明,以1,10-菲啰啉为氮源,FeCl3为铁源,Black Pearl 2000为载体,催化剂前驱体中1,10-菲啰啉含量为20wt%,Fe含量为1wt%时,热处理制备所得催化剂粒子分布均匀,比表面积为824.48 m2·g-1,平均孔隙为10.58 nm,表面的氮元素含量为0.31wt%;并具有最好的氧还原催化活性.催化剂前驱体中氮源含量在热解过程中导致催化剂的比表面积、孔径结构及表面氮元素含量的变化是影响催化剂活性的关键因素.
