1."Ethical Consideration about the Technology of ""Three-parent Test Tube Baby"""
Meijie HE ; Aojie CAI ; Qi SI ; Xiaohan CHENG ; Xiangdong KONG
Chinese Medical Ethics 2017;30(3):319-322
Three-parent test tube baby technology is important to solve the mitochondrial genetic disease.Once available,it raises greatly ethical controversy such as breaking traditional family values,hitting the religious belief,existing unknown risks,correctly handling the failed embryo,as well as the influence on the social status of the babies.Regarding these controversy,we can discuss it from several aspects.Because the development of ethics is behind the progress of science and technology,we should affirm the value of three-parent test tube baby technology and balance the development of science and technology with respecting the religious beliefs.Strict supervision system and standard application system reflect our respect for life.Incomprehension to the unknown things should become the motivation of our inquiry.We should face up to our fear of three-parent test tube baby technology,and thus to strengthen research and deepen understanding.Based on the above argument,this paper puts forward the ethical principles that should be followed in the development of three-parent test tube baby technology,namely respect,benefit,no harm and justice.
2.Development of Gene Therapy and Its Ethical Reflection
Qi SI ; Aojie CAI ; Xiaohan CHENG ; Meijie HE ; Xiangdong KONG
Chinese Medical Ethics 2017;30(12):1496-1499
Since CRISPR/Cas9 has been discovered,it opens a new era for gene therapy with its low cast,high efficiency,short cycle,easy operation and other characteristics.In 2015,Huang Junjiu had used the technique to nodify human embryonic cell for the first time,leading to widespread attention at home and abroad.For nearly 50 years,ethical discussion of gene therapy has never stopped.Through reviewing the development of gene therapy,this paper analyzed several key issues of ethical controversy in gene therapy,such as safety,effectiveness,justice,right,interest orientation and so on,and put forward that gene therapy and ethics are not two opposite sides and cannot be treated separately,the development of gene therapy should follow certain ethical norms and technical norms and it should use the bioethical principles to direct gene therapy.
3.Current status of GSDME research in malignant tumors
Yuan ZHANG ; Qinmei FENG ; Meijie MA ; Zhiyu BAI ; Qi LI
Journal of International Oncology 2023;50(5):285-289
Pyroptosis is a type of programmed cell death distincted from apoptosis and necrosis, which is accompanied by the lysis of cell membranes and the release of cell contents. Pyroptosis occurs as mediated by Gasdermin protein family and is dependent on the activity of caspase. GSDME is one of the most important members of the Gasdermin protein superfamily. GSDME-mediated pyroptosis relies on the activity of caspase-3. In recent years, with further research on pyroptosis, the mechanism of GSDME-induced pyroptosis is becoming clear. Numerous studies have shown that GSDME-mediated pyroptosis plays an important role in the occurrence and development of tumors, as well as chemotherapy resistance. However, GSDME-mediated pyroptosis has no specificity and can induce pyroptosis of normal cells in the body while inducing tumor cell pyroptosis, thus causing different degrees of damage to various organs of the body. Further study on the mechanism of GSDME-induced pyroptosis, the role of GSDME in malignant tumors and the adverse reactions of chemotherapy can provide new ideas for tumor monitoring, treatment and prognosis judgment.
4.METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity.
Xiaoyang DOU ; Lulu HUANG ; Yu XIAO ; Chang LIU ; Yini LI ; Xinning ZHANG ; Lishan YU ; Ran ZHAO ; Lei YANG ; Chuan CHEN ; Xianbin YU ; Boyang GAO ; Meijie QI ; Yawei GAO ; Bin SHEN ; Shuying SUN ; Chuan HE ; Jun LIU
Protein & Cell 2023;14(9):683-697
METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals
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Mice
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Methylation
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Chromatin
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Histones/metabolism*
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RNA, Messenger/genetics*
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Methyltransferases/metabolism*
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RNA/metabolism*