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    Home > The research team of Professor Wang Shilong from Tongji University reveals the molecular mechanism of nano layered double hydroxides as functional carriers to reduce the embryotoxicity induced by chemotherapy drugs

    The research team of Professor Wang Shilong from Tongji University reveals the molecular mechanism of nano layered double hydroxides as functional carriers to reduce the embryotoxicity induced by chemotherapy drugs

    • Last Update: 2019-12-15
    • Source: Internet
    • Author: User
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    Recently, Professor Wang Shilong's research group of Tongji University published a research paper entitled "layered double hydroxide ultimate economy of chemotherapeutical drug through bmp-smad signaling pathway" (DOI: 10.1016 / j.biomaterials 2019.119602) online in the journal biomaterials In this study, mouse embryonic stem cells (mESCs) and ICR pregnant mice were used as models to study the role of ldh-vp16 in embryonic development The results showed that nano loading could inhibit the apoptosis, self-renewal and differentiation of ESCs cells induced by drugs, recover the cell function and stem cell characteristics of ESCs, and explain the protective effect of nano materials as carriers on drug-induced embryotoxicity for the first time The process of embryo development is easily affected by various factors, and the toxicity of chemotherapy drugs to the fetus during pregnancy is often irreversible Therefore, the clinical application of drugs needs to carry out embryo safety evaluation Because of its infinite proliferation and multi-directional differentiation potential, MSECS is widely used in the study of embryo toxicity of drugs In this study, MSECS was used as an evaluation model of embryonic development in vitro It was found that the nano layered double hydroxide (LDH) could significantly reduce the cytotoxicity of MSECS induced by etoposide (VP16), including the effects on cell survival rate, clone formation ability, apoptosis, cell cycle and mitochondrial membrane potential, and restore MSECS to a large extent To maintain the stem cell characteristics of ESCs The embryotoxicity of VP16 and LDH-VP16 was evaluated by establishing ICR early pregnant rats model It was found that the injection of VP16 into pregnant rats resulted in delayed development of embryo, lack of expression of placental structure and marker gene, and abnormal spontaneous behavior of postnatal offspring However, the toxicity of the drug to embryos could be effectively reduced by carrying LDH Using transcriptome sequencing and weighted gene co expression network analysis (WGCNA) to verify the mechanism, we found that the bmp-smad signaling pathway related to development plays a key role in the in vitro and in vivo embryo protection of ldh-vp16 By adding BMP4 factor and signaling pathway inhibitor, we can achieve the cell level positive and negative functional verification Professor Wang Shilong and Professor Zhu Rongrong of the school of life science and technology of Tongji University and the research center of transformation medicine of Oriental Hospital, and Professor Qian Yechang of Baoshan Hospital of traditional Chinese and Western medicine in Shanghai are the co authors of this paper Wang Zhaojie is the first author of this paper This project is supported by NSFC, national key R & D projects and basic research fund of Central University.
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