背景:心肌肥大、椎间盘退行性疾病等疾病的发生与其组织细胞所处力学环境密切相关,而自噬在这些疾病的发病过程起到重要作用。目的:综述力学因素对不同组织细胞自噬的影响及其涉及的分子机制,为自噬的研究及相关疾病的预防治疗提供参考...背景:心肌肥大、椎间盘退行性疾病等疾病的发生与其组织细胞所处力学环境密切相关,而自噬在这些疾病的发病过程起到重要作用。目的:综述力学因素对不同组织细胞自噬的影响及其涉及的分子机制,为自噬的研究及相关疾病的预防治疗提供参考作用。方法:检索2000至2016年Web of Science和Pub Med数据库中关于力学因素对细胞自噬影响的文献,英文检索词为"autophagy,mechanical",进行系统的归纳总结和分析,排除内容相关性差或重复文献,最终得到52篇文献。结果与结论:(1)力学因素对心肌细胞、内皮细胞、软骨细胞、骨骼肌细胞等多种细胞的自噬产生影响,细胞自噬是细胞应对刺激的一种自我保护性反应,在受到生理水平的力学刺激时,细胞上调自噬水平,维持细胞的稳态、功能以及存活;(2)力学因素可能通过PI3K-AKT-mTOR、氧自由基、AKT-FoxO等通路引起细胞自噬,具体机制有待进一步研究。展开更多
Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs ma...Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.展开更多
文摘背景:心肌肥大、椎间盘退行性疾病等疾病的发生与其组织细胞所处力学环境密切相关,而自噬在这些疾病的发病过程起到重要作用。目的:综述力学因素对不同组织细胞自噬的影响及其涉及的分子机制,为自噬的研究及相关疾病的预防治疗提供参考作用。方法:检索2000至2016年Web of Science和Pub Med数据库中关于力学因素对细胞自噬影响的文献,英文检索词为"autophagy,mechanical",进行系统的归纳总结和分析,排除内容相关性差或重复文献,最终得到52篇文献。结果与结论:(1)力学因素对心肌细胞、内皮细胞、软骨细胞、骨骼肌细胞等多种细胞的自噬产生影响,细胞自噬是细胞应对刺激的一种自我保护性反应,在受到生理水平的力学刺激时,细胞上调自噬水平,维持细胞的稳态、功能以及存活;(2)力学因素可能通过PI3K-AKT-mTOR、氧自由基、AKT-FoxO等通路引起细胞自噬,具体机制有待进一步研究。
基金supported by grants from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2019ZX09301159)the“Thousand Talent Program”for Science and Technology Innovation Leader in Henan(No.194200510002)+1 种基金the Bingtuan Science and Technology Project(No.2019AB034)the Natural Science Foundation of Henan Province of China(No.202300410381).
文摘Objective Charcot-Marie-Tooth disease(CMT)severely affects patient activity,and may cause disability.However,no clinical treatment is available to reverse the disease course.The combination of CRISPR/Cas9 and iPSCs may have therapeutic potential against nervous diseases,such as CMT.Methods In the present study,the skin fibroblasts of CMT type 2D(CMT2D)patients with the c.880G>A heterozygous nucleotide mutation in the GARS gene were reprogrammed into iPSCs using three plasmids(pCXLE-hSK,pCXLE-hUL and pCXLE-hOCT3/4-shp5-F).Then,CRISPR/Cas9 technology was used to repair the mutated gene sites at the iPSC level.Results An iPSC line derived from the GARS(G294R)family with fibular atrophy was successfully induced,and the mutated gene loci were repaired at the iPSC level using CRISPR/Cas9 technology.These findings lay the foundation for future research on drug screening and cell therapy.Conclusion iPSCs can differentiate into different cell types,and originate from autologous cells.Therefore,they are promising for the development of autologous cell therapies for degenerative diseases.The combination of CRISPR/Cas9 and iPSCs may open a new avenue for the treatment of nervous diseases,such as CMT.
