Herpes simplex virus (HSV), the viral agent causing human genital herpes, recurs easily and poses significant harm to patients, while also being associated with atherosclerosis (AS). Currently, no effective therapy or...Herpes simplex virus (HSV), the viral agent causing human genital herpes, recurs easily and poses significant harm to patients, while also being associated with atherosclerosis (AS). Currently, no effective therapy or vaccine exists to combat HSV. Previous studies have demonstrated the presence of HSV and its DNA in AS-diseased tissue, yet the precise pathogenesis of HSV involvement remains unclear. To investigate the genetic mechanism of HSV-induced vascular endothelial injury and AS, a type of human umbilical vein endothelial cells (ECV-304 cells) cultured in vitro were infected with herpes simplex virus type 2 (HSV-2). The effect of HSV-2 on differential gene expression in ECV304 cells was investigated by gene microarray technology during the early stages of infection. The results revealed a total of 462 differentially expressed genes, with 318 genes exhibiting up-regulated expression and 144 genes showing down-regulated expression. Furthermore, bioinformatics analysis revealed that all 462 differentially expressed genes were implicated in 237 distinct biological processes. Notably, 79 of these biological processes demonstrated statistically significant differences (P < 0.05), encompassing critical functions such as protein synthesis, ribosome biogenesis and assembly, as well as DNA and mRNA metabolism. Our findings have unveiled the differentially expressed genes of HSV-2 in ECV304 cells during infection, offering crucial insights into the pathogenic mechanisms underlying HSV-2 invasion of endothelial cells and the pathobiology of AS.展开更多
The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene ...The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene therapy,cell localization,cell lineage tracking,synthetic biology,information storage,etc.However,developing idealized editors in various fields is still a goal for future development.This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system.It first explains the application of ideas for improvement such as“substitution”,“combination”,“adaptation”,and“adjustment”in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology.It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system.Finally,it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.展开更多
Mitogen-activated protein kinase(MAPK)signal pathways are important components in signal transduction connecting cell-surface receptors to critical regulatory targets within cells,mediating multiple intracellular sign...Mitogen-activated protein kinase(MAPK)signal pathways are important components in signal transduction connecting cell-surface receptors to critical regulatory targets within cells,mediating multiple intracellular signal cascades and phosphorylating their target proteins,such as transcriptional factors ELK-1,SRE and AP-1,and finally activating the expression of intracellular functional genes.Zinc finger genes are some of the largest gene families in humans,and Zinc finger proteins play an essential role in altering gene expression by acting as transcription factors.Zinc finger proteins are also involved in multiple cell processes,including proliferation,differentiation and development,by interacting with DNA.Here,we reported the transcriptional activities of the domains of zinc finger gene ZNF569 taking advantage of MAPK pathway.Overexpression of ZNF569 in COS-7 cells dramatically inhibited the transcriptional repressor activities of SRE and AP-1,which was also confirmed by subcellular localization analysis.Report assays indicated that the potent repression domains of ZNF569 were the KRAB and ZNF motifs.The results suggested that ZNF569 protein might act as a transcriptional repressor in MAPK signaling pathway to regulate cellular processes.展开更多
文摘Herpes simplex virus (HSV), the viral agent causing human genital herpes, recurs easily and poses significant harm to patients, while also being associated with atherosclerosis (AS). Currently, no effective therapy or vaccine exists to combat HSV. Previous studies have demonstrated the presence of HSV and its DNA in AS-diseased tissue, yet the precise pathogenesis of HSV involvement remains unclear. To investigate the genetic mechanism of HSV-induced vascular endothelial injury and AS, a type of human umbilical vein endothelial cells (ECV-304 cells) cultured in vitro were infected with herpes simplex virus type 2 (HSV-2). The effect of HSV-2 on differential gene expression in ECV304 cells was investigated by gene microarray technology during the early stages of infection. The results revealed a total of 462 differentially expressed genes, with 318 genes exhibiting up-regulated expression and 144 genes showing down-regulated expression. Furthermore, bioinformatics analysis revealed that all 462 differentially expressed genes were implicated in 237 distinct biological processes. Notably, 79 of these biological processes demonstrated statistically significant differences (P < 0.05), encompassing critical functions such as protein synthesis, ribosome biogenesis and assembly, as well as DNA and mRNA metabolism. Our findings have unveiled the differentially expressed genes of HSV-2 in ECV304 cells during infection, offering crucial insights into the pathogenic mechanisms underlying HSV-2 invasion of endothelial cells and the pathobiology of AS.
基金supported by the National Natural Science Foundation of China(81970324)partially supported by grants from the National Key R&D Program of China 2023YFC3403400。
文摘The innovation of CRISPR/Cas gene editing technology has developed rapidly in recent years.It is widely used in the fields of disease animal model construction,biological breeding,disease diagnosis and screening,gene therapy,cell localization,cell lineage tracking,synthetic biology,information storage,etc.However,developing idealized editors in various fields is still a goal for future development.This article focuses on the development and innovation of non-DSB editors BE and PE in the platform-based CRISPR system.It first explains the application of ideas for improvement such as“substitution”,“combination”,“adaptation”,and“adjustment”in BE and PE development and then catalogues the ingenious inversions and leaps of thought reflected in the innovations made to CRISPR technology.It will then elaborate on the efforts currently being made to develop small editors to solve the problem of AAV overload and summarize the current application status of editors for in vivo gene modification using AAV as a delivery system.Finally,it summarizes the inspiration brought by CRISPR/Cas innovation and assesses future prospects for development of an idealized editor.
基金This study was supported in part by the National Natural Science Foundation of China(No.30270722,30270644,30570934,3021010392)National Basic Research Program of China(No.2005CB522505)the Foundation of Hunan Province(No.04FJ2006).
文摘Mitogen-activated protein kinase(MAPK)signal pathways are important components in signal transduction connecting cell-surface receptors to critical regulatory targets within cells,mediating multiple intracellular signal cascades and phosphorylating their target proteins,such as transcriptional factors ELK-1,SRE and AP-1,and finally activating the expression of intracellular functional genes.Zinc finger genes are some of the largest gene families in humans,and Zinc finger proteins play an essential role in altering gene expression by acting as transcription factors.Zinc finger proteins are also involved in multiple cell processes,including proliferation,differentiation and development,by interacting with DNA.Here,we reported the transcriptional activities of the domains of zinc finger gene ZNF569 taking advantage of MAPK pathway.Overexpression of ZNF569 in COS-7 cells dramatically inhibited the transcriptional repressor activities of SRE and AP-1,which was also confirmed by subcellular localization analysis.Report assays indicated that the potent repression domains of ZNF569 were the KRAB and ZNF motifs.The results suggested that ZNF569 protein might act as a transcriptional repressor in MAPK signaling pathway to regulate cellular processes.
