目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织...目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织及癌旁正常组织中LncRNA-MAFG-AS1的表达水平,并分析其与结直肠癌临床病理特征之间的关系,所有患者随访截止日期到2019年12月31日,应用Kaplan-Meier(K-M)法进行生存分析,采用Cox回归模型分析结直肠癌预后的危险因素。结果结直肠癌组织中LncRNA-MAFG-AS1相对表达量为2.398±0.214,高于癌旁正常组织的1.032±0.132,差异有统计学意义(P<0.05)。当患者TNM分期更高、中高分化及存在淋巴结转移和远期转移时,LncRNA-MAFG-AS1过表达(P<0.05)。K-M生存分析显示高表达患者无进展生存时间(progression-free survival,PFS)为(20.36±3.21)个月,低表达患者为(29.71±4.23)个月;高表达患者的总生存时间(overall survival,OS)为(38.69±6.24)个月,低高表达患者为(54.26±5.14)个月;两组患者的PFS和OS差异有统计学意义(P<0.05)。Cox多因素回归分析显示,TNM分期更高、中高分化及存在淋巴结转移、远期转移以及LncRNA-MAFG-AS1高表达是影响结直肠癌预后的独立危险因素。结论LncRNA-MAFG-AS1在结直肠癌组织中呈高表达,且与结直肠癌患者分化程度、TNM分期、淋巴结和远期转移有关,是影响结直肠癌患者预后的独立风险因素。展开更多
Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium stat...Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.展开更多
Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rat...Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rate-limiting,catalyzed by glutamate-cysteine ligase,generates g-glutamylcysteine from gluta-mate and cysteine;the second is catalyzed by GSH synthetase,generates GSH from g-glutamylcysteine and glycine.GSH defends against oxidative stress,participates in detoxification of xenobiotics,de-termines the redox status of the cell,and regulates vital processes such as growth and apoptosis.Hepatic GSH plays a central role in the interorgan GSH homeostasis because sinusoidal efflux of hepatic GSH determines plasma GSH level.In liver diseases GSH homeostasis is perturbed by multiple mechanisms.Hepatic GSH biosynthesis is impaired in cholestatic liver injury,endotoxemia,and fibrotic injury largely because the expression of the GSH synthetic enzymes falls.Lower hepatic GSH level further exacerbates and perpetuates ongoing liver injury.However,in hepatocellular carcinoma GSH synthetic enzymes are upregulated and this may play a role in chemoresistance.This review focuses on the current under-standing of hepatic GSH synthesis in health and disease.展开更多
文摘目的探讨LncRNA-MAFG-AS1在结直肠癌中的表达及临床意义。方法选取我院行手术切除的结直肠癌组织及对应的癌旁正常组织各80例,应用定量即时聚合酶链锁反应(quantitative real time polymerase chain reaction,qRT-PCR)检测结直肠癌组织及癌旁正常组织中LncRNA-MAFG-AS1的表达水平,并分析其与结直肠癌临床病理特征之间的关系,所有患者随访截止日期到2019年12月31日,应用Kaplan-Meier(K-M)法进行生存分析,采用Cox回归模型分析结直肠癌预后的危险因素。结果结直肠癌组织中LncRNA-MAFG-AS1相对表达量为2.398±0.214,高于癌旁正常组织的1.032±0.132,差异有统计学意义(P<0.05)。当患者TNM分期更高、中高分化及存在淋巴结转移和远期转移时,LncRNA-MAFG-AS1过表达(P<0.05)。K-M生存分析显示高表达患者无进展生存时间(progression-free survival,PFS)为(20.36±3.21)个月,低表达患者为(29.71±4.23)个月;高表达患者的总生存时间(overall survival,OS)为(38.69±6.24)个月,低高表达患者为(54.26±5.14)个月;两组患者的PFS和OS差异有统计学意义(P<0.05)。Cox多因素回归分析显示,TNM分期更高、中高分化及存在淋巴结转移、远期转移以及LncRNA-MAFG-AS1高表达是影响结直肠癌预后的独立危险因素。结论LncRNA-MAFG-AS1在结直肠癌组织中呈高表达,且与结直肠癌患者分化程度、TNM分期、淋巴结和远期转移有关,是影响结直肠癌患者预后的独立风险因素。
文摘Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.
文摘Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rate-limiting,catalyzed by glutamate-cysteine ligase,generates g-glutamylcysteine from gluta-mate and cysteine;the second is catalyzed by GSH synthetase,generates GSH from g-glutamylcysteine and glycine.GSH defends against oxidative stress,participates in detoxification of xenobiotics,de-termines the redox status of the cell,and regulates vital processes such as growth and apoptosis.Hepatic GSH plays a central role in the interorgan GSH homeostasis because sinusoidal efflux of hepatic GSH determines plasma GSH level.In liver diseases GSH homeostasis is perturbed by multiple mechanisms.Hepatic GSH biosynthesis is impaired in cholestatic liver injury,endotoxemia,and fibrotic injury largely because the expression of the GSH synthetic enzymes falls.Lower hepatic GSH level further exacerbates and perpetuates ongoing liver injury.However,in hepatocellular carcinoma GSH synthetic enzymes are upregulated and this may play a role in chemoresistance.This review focuses on the current under-standing of hepatic GSH synthesis in health and disease.
