Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triph...Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.展开更多
本文综述了影像学定量评估方法在缺血性卒中侧支循环研究中的部分进展。侧支循环在急性缺血性脑卒中(AIS)和大动脉闭塞患者中是决定缺血性半暗区恢复率和脑梗死生长率的关键因素。侧支血流的调节机制通过挽救缺血半暗带区域的脑灌注来...本文综述了影像学定量评估方法在缺血性卒中侧支循环研究中的部分进展。侧支循环在急性缺血性脑卒中(AIS)和大动脉闭塞患者中是决定缺血性半暗区恢复率和脑梗死生长率的关键因素。侧支血流的调节机制通过挽救缺血半暗带区域的脑灌注来改善缺血性卒中的预后。文章详细介绍了脑卒中的病理生理机制、脑侧支循环的解剖和病理生理学、脑卒中相关影像检查方法、目前的治疗方法以及总结与展望。影像学技术如CT灌注成像(CTP)、CT血管成像(CTA)、磁共振灌注加权成像(PWI)、磁共振血管造影(MRA)以及动脉自旋标记成像(ASL)等在评估侧支循环和缺血半暗带方面发挥着重要作用。文章还探讨了静脉溶栓治疗(IVT)、动脉机械取栓(MT)和血管内治疗(EVT)等治疗方法,并展望了未来影像技术在侧支循环评估中的应用前景。This article reviews the partial progress of quantitative imaging evaluation methods in the study of collateral circulation in ischemic stroke. The collateral circulation is a key factor determining the recovery rate of ischemic penumbra and the growth rate of cerebral infarction in patients with acute ischemic stroke (AIS) and large artery occlusion. The regulatory mechanism of collateral blood flow improves the prognosis of ischemic stroke by rescuing cerebral perfusion in the ischemic penumbra area. The article provides a detailed introduction to the pathophysiological mechanisms of stroke, the anatomy and pathophysiology of cerebral collateral circulation, stroke related imaging examination methods, current treatment methods, and a summary and outlook. Imaging techniques such as CT perfusion imaging (CTP), CT angiography (CTA), magnetic resonance perfusion weighted imaging (PWI), magnetic resonance angiography (MRA), and arterial spin labeling imaging (ASL) play an important role in evaluating collateral circulation and ischemic penumbra. The article also explores treatment methods such as intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and endovascular treatment (EVT), and looks forward to the future application prospects of imaging technology in collateral circulation assessment.展开更多
基金supported by the Brazilian Government Research Foundation CAPES (Coordination for the Improvement of Higher Education Personnel,No.9028-11-0)the Sao Paulo State Research Foundation (Sao Paulo Government agency FAPESP,No.2011/12448-0)both granted to LECA and GDK,and by the research grant from Brazilian Government Agency CNPq (No.305064/2011-8) to LECA
文摘Inhibition of guanosine triphosphate（GTP） and cytidine triphosphate（CTP） biosynthetic pathways induces cells to assemble rod/ring（RR） structures,also named cytoophidia,which consist of the enzymes cytidine triphosphate synthase（CTPS） and inosine-50-monophosphate dehydrogenase 2（IMPDH2）.We aim to explore the interaction of CTPS and IMPDH2 in the generation of RR structures.He La and COS-7 cells were cultured in normal conditions or in the presence of 6-diazo-5-oxo-L-norleucine（DON）,ribavirin,or mycophenolic acid（MPA）.Over 90% of DON-treated cells presented RR structures.In He La cells,35% of the RR structures were positive for IMPDH2 alone,26% were CTPS alone,and 31% were IMPDH2/CTPS mixed,while in COS-7 cells,42% of RR were IMPDH2 alone,41% were CTPS alone,and 10% were IMPDH2/CTPS mixed.Ribavirin and MPA treatments induced only IMPDH2-based RR.Cells were also transfected with an N-terminal hemagglutinin（NHA）-tagged CTPS1 construct.Over 95% of NHA-CTPS1 transfected cells with DON treatment presented IMPDH2-based RR and almost 100% presented CTPS1-based RR;when treated with ribavirin,over 94% of transfected cells presented IMPDH2-based RR and 37% presented CTPS1-based RR,whereas 2% of untreated transfected cells presented IMPDH2-based RR and 28% presented CTPS1-based RR.These results may help in understanding the relationship between CTP and GTP biosynthetic pathways,especially concerning the formation of filamentous RR structures.
文摘本文综述了影像学定量评估方法在缺血性卒中侧支循环研究中的部分进展。侧支循环在急性缺血性脑卒中(AIS)和大动脉闭塞患者中是决定缺血性半暗区恢复率和脑梗死生长率的关键因素。侧支血流的调节机制通过挽救缺血半暗带区域的脑灌注来改善缺血性卒中的预后。文章详细介绍了脑卒中的病理生理机制、脑侧支循环的解剖和病理生理学、脑卒中相关影像检查方法、目前的治疗方法以及总结与展望。影像学技术如CT灌注成像(CTP)、CT血管成像(CTA)、磁共振灌注加权成像(PWI)、磁共振血管造影(MRA)以及动脉自旋标记成像(ASL)等在评估侧支循环和缺血半暗带方面发挥着重要作用。文章还探讨了静脉溶栓治疗(IVT)、动脉机械取栓(MT)和血管内治疗(EVT)等治疗方法,并展望了未来影像技术在侧支循环评估中的应用前景。This article reviews the partial progress of quantitative imaging evaluation methods in the study of collateral circulation in ischemic stroke. The collateral circulation is a key factor determining the recovery rate of ischemic penumbra and the growth rate of cerebral infarction in patients with acute ischemic stroke (AIS) and large artery occlusion. The regulatory mechanism of collateral blood flow improves the prognosis of ischemic stroke by rescuing cerebral perfusion in the ischemic penumbra area. The article provides a detailed introduction to the pathophysiological mechanisms of stroke, the anatomy and pathophysiology of cerebral collateral circulation, stroke related imaging examination methods, current treatment methods, and a summary and outlook. Imaging techniques such as CT perfusion imaging (CTP), CT angiography (CTA), magnetic resonance perfusion weighted imaging (PWI), magnetic resonance angiography (MRA), and arterial spin labeling imaging (ASL) play an important role in evaluating collateral circulation and ischemic penumbra. The article also explores treatment methods such as intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and endovascular treatment (EVT), and looks forward to the future application prospects of imaging technology in collateral circulation assessment.
