1.Progress on roles and mechanisms of CCAAT/enhancer binding protein β in endometrium decidualization
Fangfang DI ; Jiansheng LIU ; Shang LI ; Yanzhi DU
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(6):865-869
CCAAT/enhancer binding protein β (C/EBPβ) is a critical member of C/EBP family.C/EBPβ,based on the leucine zipper located in C terminal of the protein,can regulate transcriptional activities of downstream target genes involved in diverse cellular processes,such as proliferation and differentiation.Recently published studies have identified that C/EBPβ is essential in the decidualization of endometrial stromal cells.This review summarizes the roles and mechanisms of C/EBPβ during the courses of decidualization,which is aimed at providing novel insights for dysfunctional decidualization.
2. Inhibition and mechanism of Xihuang pill on mice bearing hepatoma H
Yanzhi LIU ; Shouying DU ; Yan WANG ; Kaili LIU ; Wenhua ZHOU ; Yingli WANG ; Yan WANG ; Kaili LIU ; Yingli WANG ; Yanzhi LIU ; Ping ZHU
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(7):754-761
AIM: To study the inhibitory effect of Xihuang Pill on H
3.Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor.
Yinghui WEI ; Meiling ZHANG ; Jing HU ; Yingsi ZHOU ; Mingxing XUE ; Jianhang YIN ; Yuanhua LIU ; Hu FENG ; Ling ZHOU ; Zhifang LI ; Dongshuang WANG ; Zhiguo ZHANG ; Yin ZHOU ; Hongbin LIU ; Ning YAO ; Erwei ZUO ; Jiazhi HU ; Yanzhi DU ; Wen LI ; Chunlong XU ; Hui YANG
Protein & Cell 2023;14(6):416-432
Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans
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Apolipoprotein E4/genetics*
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Cytosine
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Mutation
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Blastocyst
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Heterozygote
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Gene Editing
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CRISPR-Cas Systems