目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma...目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)以及癌旁组织中的表达差异,进一步研究这些表达与AEG患者的临床病理特点之间的联系。方法:从TCGA(The Cancer Genome Atlas)数据库中检索了XRCC1和EIF4EBP1在胃癌患者中的表达水平和临床数据,并从中筛选出AEG患者的相关数据。研究其在胃癌和AEG中的表达水平和相关性,以及AEG的表达水平与总生存期之间的联系。对我院128例2014年1月至2019年12月的AEG组织和癌旁组织石蜡包埋切片进行免疫组化(immunohistochemistry,IHC)染色,检测XRCC1和EIF4EBP1蛋白的表达水平,同时收集患者的相关临床资料。研究这两种蛋白质的表达水平和它们之间的相关性,以及它们的表达水平与临床病理特征之间的联系。结果:在TCGA数据库里,XRCC1和EIF4EBP1在412个胃癌组织样本中的表达水平明显超过了36个正常组织样本(P<0.001)。并且在这412个胃癌组织样本中,XRCC1和EIF4EBP1的表达之间呈正相关关系(r=0.349,P<0.001)。在其中的AEG患者中,XRCC1和EIF4EBP1在99例AEG组织样本中的表达水平明显超过了14例正常食管胃结合部组织样本(XRCC1:P=0.015,EIF4EBP1:P=0.046),但在这99例AEG组织中,XRCC1和EIF4EBP1的表达之间没有显著相关性(P=0.066)。在临床样本中,128例AEG组织样本中XRCC1和EIF4EBP1的高表达率分别为53.1%(68/128)和82%(105/128),超过了癌旁组织样本的高表达率33.6%(43/128)和54.7%(70/128),且在128例AEG组织样本中,XRCC1和EIF4EBP1的表达呈现出正相关性(r=0.245,P=0.005)。在AEG组织中,XRCC1和EIF4EBP1的表达与患者的大体类型、是否神经侵犯、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期以及总生存期之间,没有显示出具有统计学意义的相关性。在对AEG患者的总生存状况进行多因素分析时,脉管癌栓的形成(P=0.002)和临床分期(P=0.003)与患者的总生存率有着显著的关联。结论:在AEG组织中,XRCC1和EIF4EBP1的表达水平相对于癌旁组织更高,并且这两者表达之间存在正相关关系。在不同的XRCC1和EIF4EBP1表达水平的AEG患者中,无论是大体类型、是否侵犯神经、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期还是总生存期,都没有显著的差异。脉管癌栓及临床分期是决定AEG患者生存预后的关键因素。展开更多
Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combinat...Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.展开更多
文摘目的:探索X-射线修复交叉互补基因1(X-ray repair cross-complementing gene 1,XRCC1)和真核生物翻译起始因子4E结合蛋白1(eukaryotic translation initiation factor 4E binding protein 1,EIF4EBP1)在食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)以及癌旁组织中的表达差异,进一步研究这些表达与AEG患者的临床病理特点之间的联系。方法:从TCGA(The Cancer Genome Atlas)数据库中检索了XRCC1和EIF4EBP1在胃癌患者中的表达水平和临床数据,并从中筛选出AEG患者的相关数据。研究其在胃癌和AEG中的表达水平和相关性,以及AEG的表达水平与总生存期之间的联系。对我院128例2014年1月至2019年12月的AEG组织和癌旁组织石蜡包埋切片进行免疫组化(immunohistochemistry,IHC)染色,检测XRCC1和EIF4EBP1蛋白的表达水平,同时收集患者的相关临床资料。研究这两种蛋白质的表达水平和它们之间的相关性,以及它们的表达水平与临床病理特征之间的联系。结果:在TCGA数据库里,XRCC1和EIF4EBP1在412个胃癌组织样本中的表达水平明显超过了36个正常组织样本(P<0.001)。并且在这412个胃癌组织样本中,XRCC1和EIF4EBP1的表达之间呈正相关关系(r=0.349,P<0.001)。在其中的AEG患者中,XRCC1和EIF4EBP1在99例AEG组织样本中的表达水平明显超过了14例正常食管胃结合部组织样本(XRCC1:P=0.015,EIF4EBP1:P=0.046),但在这99例AEG组织中,XRCC1和EIF4EBP1的表达之间没有显著相关性(P=0.066)。在临床样本中,128例AEG组织样本中XRCC1和EIF4EBP1的高表达率分别为53.1%(68/128)和82%(105/128),超过了癌旁组织样本的高表达率33.6%(43/128)和54.7%(70/128),且在128例AEG组织样本中,XRCC1和EIF4EBP1的表达呈现出正相关性(r=0.245,P=0.005)。在AEG组织中,XRCC1和EIF4EBP1的表达与患者的大体类型、是否神经侵犯、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期以及总生存期之间,没有显示出具有统计学意义的相关性。在对AEG患者的总生存状况进行多因素分析时,脉管癌栓的形成(P=0.002)和临床分期(P=0.003)与患者的总生存率有着显著的关联。结论:在AEG组织中,XRCC1和EIF4EBP1的表达水平相对于癌旁组织更高,并且这两者表达之间存在正相关关系。在不同的XRCC1和EIF4EBP1表达水平的AEG患者中,无论是大体类型、是否侵犯神经、有无脉管癌栓、分化程度、T分期、N分期、HER-2的表达、临床分期还是总生存期,都没有显著的差异。脉管癌栓及临床分期是决定AEG患者生存预后的关键因素。
基金funded by the National Natural Science Foundation of China(82103818)the Suzhou Applied Basic Research(Medical and Health)Science and Technology Innovation Project(SYW2024179)+1 种基金Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases,Soochow University(KJS2437)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Alzheimer’s disease(AD)has become an important public health issue worldwide.p-Coumaric acid(CA)and lactoferrin(Lf)possessed antioxidant,anti-inflammatory,and anti-AD activities.Herein,we hypothesized that a combination treatment of CA and Lf would synergistically improve AD symptoms and studied its mechanisms.Twelve-week-old amyloid precursor protein(APP)/presenilin 1(PS1)mice were treated with CA,Lf,or both CA and Lf for 8 weeks.Results showed that individual and combined treatments could ameliorate cognitive deficits to varying degrees,with stronger effects for combined intervention than for CA or Lf alone.Specifically,combined treatment was most effective in improving nesting ability and reducing amyloidββ_(1-42)(Aβ_(1-42))deposition in mice.Moreover,combined treatment was more effective in suppressing APP,β-site APP cleavage enzyme 1,and inflammation;it inhibited the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)signaling pathway in the hippocampus and colon and upregulated the expression of tight junction protein zonula occludens-1 in the colon;it also decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the relative abundance of Prevotellaceae,Lachnospira,and Eubacterium at the genus level.Overall,the combination of CA and Lf may ameliorate cognitive deficits in APP/PS1 mice by improving inflammation and inhibiting the C/EBPβ/AEP signaling pathway via modulating gut microbiome.
