Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cereb...Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.展开更多
目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织...目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。展开更多
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm...The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].展开更多
Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated t...Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82260245(to YX),81660207(to YX),81960253(to YL),82160268(to YL),U1812403(to ZG)Science and Technology Projects of Guizhou Province,Nos.[2019]1440(to YX),[2020]1Z067(to WH)+1 种基金Cultivation Foundation of Guizhou Medical University,No.[20NSP069](to YX)Excellent Young Talents Plan of Guizhou Medical University,No.(2022)101(to WH)。
文摘Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.
文摘目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。
基金funded by the National Natural Science Foundation of China(Grant Nos.:82004081 and 52073145)the National Natural Science Foundation of Nanjing University of Chinese Medicine,China(Grant No.:NZY82004081).
文摘The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].
基金supported by grants from the Scientist Training Program of BAAFS (Grant No.JKZX202406)the Innovation and Capacity-Building Project of BAAFS (Grant No.KJCX20230221)+2 种基金Collaborative innovation program of the Beijing Vegetable Research Center (Grant No.XTCX202302)the National Natural Science Foundation of China (Grant No.32072567)the China Agriculture Research System of MOF and MARA (Grant No.CARS-A03)。
文摘Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.
