INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Jiang Zhu,Ruinan Qu,Yawei Wang,Ruoyao Ni,Kai Tian,Chan Yang,Mei Li,Michael Kristensen,Xinghui Qiu
Populations of many insect species have evolved a variety of resistance mechanisms in response to insecticide selection. Current knowledge about mutations responsible for insecticide resistance is largely achieved from studies on target-site resistance, while much less is known about metabolic resistance. Although it is well known that P450 monooxygenases are one of the major players involved in insecticide metabolism and resistance, understanding mutation(s) responsible for CYP-mediated resistance has been a big challenge. In this study, we used the house fly to pursue a better understanding of P450 mediated insecticide resistance at the molecular level. Metabolism studies illustrated that CYP6G4 had a broad-spectrum metabolic activity in metabolizing insecticides. Population genotyping revealed that the CYP6G4v1 allele harboring a DNA insertion (MdIS1) had been selected in many house fly populations on different continents. Dual luciferase reporter assays identified that the MdIS1 contained a CncC/Maf binding site, and electrophoretic mobility shift assay confirmed that transcription factor CncC was involved in the MdIS1-mediated regulation. This study highlights the common involvement of the CncC pathway in adaptive evolution, and provides an interesting case supportive of parallel evolution in P450-mediated insecticide resistance in insects.
研究领域:
昆虫学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
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IF 11.556
Lun Zhang,Shuiqing Gui,Yinghua Xu,Jiali Zeng,Jian Wang,Qingru Chen,Liqian Su,Ziyan Wang,Rui Deng,Fujiang Chu,Wenbin Liu,Xiaobao Jin,Xuemei Lu
Ulcerative colitis (UC) is a modern refractory disease with steadily increasing incidence worldwide that urgently requires effective and safe therapies. Therapeutic peptides delivered using nanocarriers have shown promising developments for the treatment of UC. We developed a novel colon-accumulating oral drug delivery nanoplatform consisting of Musca domestica cecropin (MDC) and mesoporous carbon nanoparticles (MCNs) and investigated its effects and mechanism of action for the treatment of UC. Methods: An optimized one-step soft templating method was developed to synthesize MCNs, into which MDC was loaded to fabricate MDC@MCNs. MCNs and MDC@MCNs were characterized by BET, XRD, and TEM. MDC and MDC@MCNs resistance to trypsin degradation was measured through Oxford cup antibacterial experiments using Salmonella typhimurium as the indicator. Uptake of MDC and MDC@MCNs by NCM460 cells was observed by fluorescence microscopy. The biocompatibility of MDC, MCNs, and MDC@MCNs was evaluated in three cell lines (NCM460, L02, and NIH3T3) and C57BL/6 mice. Dextran sulphate sodium was used to establish models of NCM460 cell injury and UC in mice. MTT assay, flow cytometry, and mitochondrial membrane potential assay were applied to determine the effects of MDC@MCNs on NCM460 cells injury. Additionally, a variety of biological methods such as H&E staining, TEM, ELISA, qPCR, Western blotting, and 16s rDNA sequencing were performed to explore the effects and underlying mechanism of MDC@MCN on UC in vivo . Colonic adhesion of MCNs was compared in normal and UC mice. The oral biodistributions of MDC and MDC@MCNs in the gastrointestinal tract of mice were also determined. Results: MDC@MCNs were successfully developed and exhibited excellent ability to resist destruction by trypsin and were taken up by NCM460 cells more readily than MDC. In vitro studies showed that MDC@MCNs better inhibited DSS-induced NCM460 cells damage with lower toxicity to L02 and NIH3T3 cells compared with MDC. In vivo results indicated that MDC@MCNs have good biocompatibility and significantly improved colonic injury in UC mice by effectively inhibiting inflammation and oxidative stress, maintaining colonic tight junctions, and regulating intestinal flora. Moreover, MDC@MCNs were strongly retained in the intestines, which was attributed to intestinal adhesion and aggregation of MCNs, serving as one of the important reasons for its enhanced efficacy after oral administration compared with MDC. Conclusion: MDC@MCNs alleviated DSS-induced UC by ameliorating colonic epithelial cells damage, inhibiting inflammation and oxidative stress, enhancing colonic tight junctions, and regulating intestinal flora. This colon-accumulating oral drug delivery nanoplatform may provide a novel and precise therapeutic strategy for UC.
研究领域:
药学
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纳米技术
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胃肠病学
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免疫学
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生物医学工程
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DOI
PubMed
高影响因子
ENERGY & FUELS
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2017
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IF 3.091
Zi-zhe Cai,Sheng-qing Wu,Guo Sun,Yi Niu,Dong Zheng,Shi-yi Peng,Wen-zhe Yang,Yong Wang,Depo Yang
With the cost of traditional lipid feedstocks constituting 70% of the total cost of biolubricant production, it is urgent to find a new lipid source for the biodiesel and biolubricant industry. With the elevated acid value (61.8 mg of KOH/g) of housefly larval lipids, converting the free fatty acid (FFA) into a biolubricant could serve as a value-added approach to the larval diesel industry, other than pretreatment by acid-catalyzed esterification for biodiesel production. This study developed a method of producing high-purity fatty acid n-octyl esters (FAOEs) from housefly (Musca domestica L.) larvae. The housefly larva free fatty acids (HLFFAs) from the larva lipids were obtained by wipe-film short-path distillation. FAOEs were produced by esterifying n-octanol with HLFFAs (catalyzed by benzenesulfonic acid under the following conditions: catalyst loading, 2 wt %; molar ratio of n-octanol to FFA, 3:1; temperature, 100 °C; time, 2 h). Excess n-octanol was effectively removed by high-vacuum (80 Pa) distillation at 90 °C. The unreacted FFAs were neutralized using demethylated crude glycerin, which is a byproduct of biodiesel production. A practical method of producing high-purity fatty acid n-octyl esters (99.19 wt %) derived from housefly larva lipids was thus developed, and the product could serve as a replacement for certain low-viscosity mineral lubricants such as liquid paraffin, polyalphaolefin 6, and SN 500.
研究领域:
生物资源技术
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可再生能源
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绿色化学
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脂质工程
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工业生物技术
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DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2022
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IF 4.966
Jiang Zhu,Jing Feng,Kai Tian,Chong Li,Mei Li,Xinghui QIU
The house fly ( Musca domestica L.) (Diptera: Muscidae) is a global vector that can transmit >250 human and animal diseases. The control of house flies has heavily relied on the application of various chemical insecticides . The carbamate insecticide propoxur has been widely used for the control of house flies, and resistance to propoxur has been documented in many house fly populations worldwide. Previous studies have identified several propoxur resistance-conferring mutations in the target protein acetylcholinesterase ; however, the molecular basis for metabolic resistance to propoxur remains unknown. In this study, we investigated the involvement of CYP6G4, a cytochrome P450 overexpressed in many insecticide resistant populations of Musca domestica , in propoxur metabolism and resistance by using combined approaches of recombinant protein-based insecticide metabolism and the Drosophila GAL4/UAS transgenic system. The recombinant CYP6G4 and its redox partners (NADPH-dependent cytochrome P450 reductase and cytochrome b 5) were functionally expressed in Escherichia coli . Metabolism experiments showed that CYP6G4 was able to transform propoxur with a turnover rate of around 0.79 min −1 . Six metabolites were putatively identified, suggesting that CYP6G4 could metabolize propoxur via hydroxylation , O-depropylation and N -demethylation. Moreover, bioassay results showed that ectopic overexpression of CYP6G4 in fruit flies significantly increased their tolerance to propoxur. Our in vivo and in vitro data convincingly demonstrate that CYP6G4 contributes to propoxur metabolism and resistance.
研究领域:
昆虫学
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分子生物学
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毒理学
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杀虫剂抗性
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产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
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2022
·Vol. 77
·期 1
·96-108
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IF 3.192
Zhang Sichen,Qian Chunguo,Li Hailing,Zhao Zhimin,Xian Jianchun,Yang Depo
Neuroprotective antioxidants, especially peptide-based antioxidants, are effective against oxidative stress in neurodegenerative disorders. In this study, we measured the neuroprotective effects of the antioxidant peptide DFTPVCTTELGR (DR12) from housefly Musca domestica L. pupae. Treatment of PC12 and HT22 cells with DR12 significantly reduced glutamate-induced cytotoxicity. Peptide DR12 appeared to exert its neuroprotective effects by attenuating production of reactive oxygen species and malonaldehyde, upregulating the endogenous antioxidants superoxide dismutase and glutathione, and reversing the loss of mitochondrial membrane potential. In addition, DR12 treatment activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Structure–activity analysis indicated that the superior neuroprotective function of DR12 was related to its cysteine residue. In summary, DR12 may be an attractive therapeutic peptide or precursor to treat neurodegenerative diseases.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子