ACS Catalysis
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2021
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IF 13.084
Fei Qiu,Yijun Yan,Junlan Zeng,Jian-Ping Huang,Lingjiang Zeng,Wei Zhong,Xiaozhong Lan,Min Chen,Sheng-Xiong Huang,Zhihua Liao
Hyoscyamine, a member of the class of compounds known as tropane alkaloids (TAs), is clinically used as an anticholinergic drug. Previous research has predicted that hyoscyamine is produced via the reduction of hyoscyamine aldehyde. In this study, we identified a root-expressed gene from Atropa belladonna, named AbHDH, which encodes a hyoscyamine dehydrogenase involved in the formation of hyoscyamine. Enzymatic assays indicated that AbHDH was able to not only reduce hyoscyamine aldehyde to produce hyoscyamine but also oxidize hyoscyamine to form hyoscyamine aldehyde under different conditions. To elucidate its catalytic mechanism, the crystal structure of AbHDH at a 2.4-Å resolution was also determined. Overexpression of AbHDH significantly enhanced the biosynthesis of hyoscyamine and the production of anisodamine and scopolamine in root cultures of A. belladonna. However, suppression of AbHDH using RNAi technology did not reduce the production of hyoscyamine, anisodamine, or scopolamine, though it did increase the accumulation of hyoscyamine aldehyde. In summary, this study provided timely biochemical and metabolic insights into hyoscyamine dehydrogenase, pointing to an alternative, promising way to produce pharmaceutical TAs via metabolic engineering in planta.
研究领域:
生物化学
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代谢学
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植物生物学
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药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2017
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IF 7.786
Zhi-qiang Yuan,Wei-liang Chen,Ben-gang You,Yang Liu,Shu-di Yang,Ji-zhao Li,Wen-jing Zhu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
Malignant proliferation and metastasis in non-small cell lung carcinoma (NSCLC) are great challenges for effective clinical treatment through conventional chemotherapy. The combinational therapy strategy of RNA interfering (RNAi) technology and chemotherapeutic agents have been reported to be promising for effective cancer therapy. In this study, based on multifunctional nanoparticles (NPs), the simultaneous delivery of etoposide (ETP) and anti-Enhancer of Zeste Homologue 2 (EZH2) siRNA for the effective treatment of orthotopic lung tumor was achieved. The NPs exhibited pH/redox dual sensitivity verified by particle size changes, morphological changes, and in vitro release of drugs. Confocal microscopy analysis confirmed that the NPs exhibited endosomal escape property and on-demand intracellular drug release behavior, which can protect siRNA from degradation and facilitate the chemotherapeutic effect respectively. In vitro tumor cell motility study demonstrated that EZH2 siRNA loaded in NPs can decrease the migration and invasion capabilities of tumor cells by downregulating the expression of EZH2 mRNA and protein. In particular, an antiproliferation study revealed that the co-delivery of siRNA and ETP in the multifunctional NPs can induce a synergistic therapeutic effect on NSCLC. In vivo targeting evaluation showed that cRGDyC-PEG modification on NPs exhibited a low distribution in normal organs and an obvious accumulation in orthotopic lung tumor. Furthermore, targeted NPs co-delivering siRNA and ETP showed superior inhibition on tumor growth and metastasis and produced minimal systemic toxicity. These findings indicated that multifunctional NPs can be utilized as a co-delivery system, and that the combination of EZH2 siRNA and ETP can effectively treat NSCLC.
研究领域:
药学
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纳米技术
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肿瘤学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INSECT PHYSIOLOGY
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2025
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IF 2.3
Xu Wu,Wen-Mei Li,Qiang Xu,Xiao-Ping Yi,Da-He Zhang,Ming-Zhe He,Yu-Hong Ren
RNA interference (RNAi) has shown excellent potential for pest management worldwide. However, the application of RNAi against insects can be inefficient and unreliable. Finding a better delivery system is a crucial factor for enhancing RNAi efficacy. Here, we present a novel and effective approach of conjugating double-stranded RNA (dsRNA) with a cell-penetrating disulfide polymer (CPD) to improve dsRNA stability and RNAi efficiency. The fall armyworm (FAW), Spodoptera frugiperda , is a globally agricultural insect. Chitin synthase B ( CHSB ) and methoprene-tolerant ( Met ) genes, which are essential for the development and growth of FAW, were selected as target genes. The CPD was synthesized using a two-step method for dsRNA delivery. The synthesized CPD/dsRNA complex protected dsRNA from nuclease degradation. The biological application of CPD in Sf9 cells demonstrated low cytotoxicity and high cell viability. Moreover, the CPD-loaded dsRNA entered the cells within 6 h. Bioassays of FAW showed that the relative expression levels of the CHSB and Met genes were reduced. Specifically, at 72 h, the relative expression levels of the CHSB and Met genes were 48.14 % and 37.60 % of those in the control group, respectively. The weight and body length of the larvae decreased significantly, and the mortality rate of CPD/ds CHSB reached 30 %. This CPD was demonstrated for the first time to have excellent delivery performance in insects and is expected to become a new and effective tool for pest control, representing a significant advancement in pest management.
研究领域:
昆虫学
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分子生物学
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害虫治理
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生物技术
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RNA干扰技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）