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您的检索式：作者名="Saifei Lei"
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| 1 | Activation of PXR causes drug interactions with Paxlovid in transgenic mice显示文摘Paxlovid is a nirmatrelvir(NMV)and ritonavir(RTV)co-packaged medication used for the treatment of coronavirus disease 2019(COVID-19).The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster.Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid.By using recombinant human cytochrome P450s(CYPs),we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism.The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice,which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV.Pregnane X receptor(PXR)is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression.We next explored the impact of drug-and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5.We found that PXR activation increased CYP3A4/5 expression,accelerated NMV metabolism,and reduced the systemic exposure of NMV.In summary,our work demonstrated that PXR activation can cause drug interactions with Paxlovid,suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid. | Saifei Lei Alice Guo Jie Lu Qian Qi Aaron S.Devanathan Junjie Zhu Xiaochao Ma | 2023 | Acta Pharmaceutica Sinica B2023，13，11： | 0 |
| 2 | Highly efficient photocatalytic reduction of nitrogen into ammonia by single Ru atom catalyst supported by BeO monolayer显示文摘Ammonia(NH_(3))is one of the most important building blocks of the chemical industry and a promising sustainable energy carrier.Conventional production of NH_(3)via the Haber-Bosch process requires high temperature and high pressure,which is energy demanding and suffers safety issues.Photocatalytic nitrogen reduction reaction(NRR)is a green and sustainable route for NH_(3) production,and has been expected to be an alternative for NH_(3)production under mild conditions.However,solar-driven N_(2)activated has appeared as the bottleneck for photocatalytic NRR.In this work,we propose that single Ru atom supported by BeO monolayer is a promising photocatalytic single atom catalyst(SAC)for efficient N_(2)activation with visible illumination.The high efficiency originates from the enhanced absorption in the visible range,as well as the back-donation mechanism when N_(2)were adsorbed on the SAC.Our results show that N_(2)can be efficiently activated by the Ru/BeO SAC and be reduced to NH_(3) with extremely low limiting potential of-0.41 V.The NRR process also exhibits dominate selectivity respect to hydrogen evolution. | Saifei Yuan Beixi Xu Shujuan Li Wenbiao Zhu Shulai Lei Wenyue Guo Hao Ren | 2022 | Chinese Chemical Letters2022，33，1： | 0 |
| 3 | Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice)显示文摘Background and aims:The herbal supplement Gancao,also known as licorice,belongs to the genus Glycyrrhiza and has been used worldwide for its hepatoprotective effect.Recent studies have raised concerns about potential herb-drug interactions associated with Gancao via pregnane X receptor(PXR)-mediated induction of hepatic cytochrome P4503A4(CYP3A4).The current work aimed to determine the phytochemicals in Gancao that activate PXR and induce CYP3A4.Methods:DPX2 cells were used for cell-based PXR reporter assays.The phytochemicals in Gancao extract were identified using a metabolomics approach.The effects of PXR activators identified from in vitro studies were further investigated in PXR-and CYP3A4-humanized mouse models.Results:Gancao was verified to be a PXR-activating herb.Two major phytochemicals in Gancao,gly-cyrrhizin(GZ)and glycyrrhetinic acid(GA),did not activate PXR in the cell-based reporter assays.However,glabridin was shown to activate PXR in a dose-dependent manner.In vivo studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator.Although GA did not active PXR in vitro,it induced CYP3A4 expression in a PXR-dependent manner in the PXR-and CYP3A4-humanized mice. | Anqi Cheng Saifei Lei Junjie Zhu Jie Lu Mary F.Paine Wen Xie Xiaochao Ma | 2022 | Liver Research2022，6，4： | 0 |
| 4 | Clinical perspectives of isoniazid-induced liver injury显示文摘Isoniazid(INH)is a synthetic anti-mycobacterial agent used to treat active or latent tuberculosis(TB).INH has been in clinical use for nearly 70 years and remains broadly utilized at the front line of anti-TB treatment.However,the potential for liver damage and even fulminant liver failure during INH-based TB treatment presents a major challenge for TB control programs worldwide.In this review,we discuss the hepatotoxic effects of INH and provide an overview of the mechanisms and their applications in prediction and prevention of INH hepatotoxicity in clinical practice. | Saifei Lei Ruizhi Gu Xiaochao Ma | 2021 | Liver Research2021，5，2： | 0 |
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