SENSORS AND ACTUATORS B-CHEMICAL
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2026
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IF 8.3
Xinyi Zhang,Chunyu Su,Yuan Ming,Bingying Jiang,Yun Xiang,Ruo Yuan
Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-DNA (BPDE-DNA) adduct is a critical biomarker for assessing DNA damage caused by carcinogen exposure and exhibits significant potential in lung cancer early warning. However, conventional BPDE-DNA detection methods are often constrained by limited sensitivity, complexity and high costs. This work presents the fabrication of a highly sensitive electrochemical BPDE-DNA biosensor based on a new polymerase activity inhibition strategy coupled with AuNPs/MoS 2 /Ti 3 C 2 and HRP-catalyzed signal amplifications. A three-strand DNA complex is designed to capture the target BPDE-DNA adduct by means of a toehold-mediated strand displacement reaction (TSDR) on AuNPs/MoS 2 /Ti 3 C 2 -modifed electrode. The bulky structure of the BPDE moiety subsequently introduces steric hindrance to inhibit extension of BPDE-DNA by Klenow fragment (KF) polymerase to displace the biotin-modified sequence in the three-strand complex. Streptavidin-horseradish peroxidase (STV-HRP) is then attached to electrode surface via high-affinity biotin-STV binding. The anchored HRP coupled with AuNPs/MoS 2 /Ti 3 C 2 catalyzes redox reaction of the 3,3’,5,5’-tetramethylbenzidine (TMB)/H 2 O 2 substrate solution, resulting in a substantially amplified electrochemical current for detecting BPDE-DNA in range of 0.5 pM to 10 nM with low detection limit of 0.34 pM. Our sensor methodology not only introduces a new steric hindrance strategy for BPDE-DNA detection but also offers a robust electrochemical platform for monitoring other low levels of DNA adducts.
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DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Meng-Die Li,Li-Hong Chen,Hui-Xian Xiang,Ya-Lin Jiang,Bian-Bian Lv,De-Xiang Xu,Hui Zhao,Lin Fu
Benzo[a]pyrene (BaP) and its metabolic end product benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE), are known toxic environmental pollutants. This study aimed to analyze whether sub-chronic BPDE exposure initiated pulmonary fibrosis and the potential mechanisms. In this work, male C57BL6/J mice were exposed to BPDE by dynamic inhalation exposure for 8 weeks. Our results indicated that sub-chronic BPDE exposure evoked pulmonary fibrosis and epithelial-mesenchymal transition (EMT) in mice. Both in vivo and in vitro , BPDE exposure promoted nuclear translocation of Snail. Further experiments indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) and p62 were upregulated in BPDE-exposed alveolar epithelial cells. Moreover, Nrf2 siRNA transfection evidently attenuated BPDE-induced p62 upregulation. Besides, p62 shRNA inhibited BPDE-incurred Snail nuclear translocation and EMT. Mechanically, BPDE facilitated physical interaction between p62 and Snail in the nucleus, then repressed Snail protein degradation by p62-dependent autophagy-lysosome pathway, and finally upregulated transcriptional activity of Snail. Additionally, aryl hydrocarbon receptor (AhR) was activated in BPDE-treated alveolar epithelial cells. Dual-luciferase assay indicated activating AhR could bind to Nrf2 gene promoter. Moreover, pretreatment with CH223191 or α-naphthoflavone (α-NF), AhR antagonists, inhibited BPDE-activated Nrf2-p62 signaling, and alleviated BPDE-induced EMT and pulmonary fibrosis in mice. Taken together, AhR-mediated Nrf2-p62 signaling contributes to BaP-induced EMT and pulmonary fibrosis.
研究领域:
毒理学
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肺科学
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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
SCIENCE OF THE TOTAL ENVIRONMENT
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2023
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IF 9.8
Hongmei Zou,Mingxuan Zhang,Jin Chen,Stanley Aniagu,Yan Jiang,Tao Chen
Benzo[ a ]pyrene (BaP) is a representative polycyclic aromatic hydrocarbon widely present in the environment. We previously reported that the aryl hydrocarbon receptor (AHR) mediates BaP-induced apoptosis and cardiac malformations in zebrafish embryos, but the underlying molecular mechanisms were unclear. Since BaP is a mutagenetic compound, we hypothesize that BaP induces apoptosis and heart defects via AHR-mediated DNA damage. In this study, zebrafish embryos were exposed to BaP at a concentration of 0.1 μM from 2 to 72 h post fertilization, either with or without inhibitors/agonists. AHR activity and levels of reactive oxygen species (ROS) were examined under a fluorescence microscope. mRNA expression levels were quantified by qPCR. DNA damage and apoptosis were detected by immunofluorescence. Our findings revealed that BaP exposure significantly increased BPDE-DNA adducts, mitochondrial damage, apoptosis and heart defects in zebrafish embryos. These effects were counteracted by inhibiting AHR/cyp1a1 using pharmaceutical inhibitors or genetic knockdown. Furthermore, we observed that spironolactone, an antagonist of nucleotide excision repair (NER), significantly enhanced BaP-induced BPDE-DNA adducts, mitochondrial damage, apoptosis and heart malformation rates. Conversely, SRT1720, a SIRT1 agonist, reduced the adverse effects of BaP. Supplementation with spironolactone also enhanced γ-H2AX signals in the heart of zebrafish embryos exposed to BaP. Additional experiments demonstrated that BaP suppressed the expression of SIRT1. We further established that AHR, when activated by BaP, directly inhibited SIRT1 transcription, leading to downregulation of XPC and XPA, which are essential NER genes involved in the recognition and verification steps of the NER process. Taken together, our results indicate that AHR mediates BaP-induced DNA damage in the heart of zebrafish embryos by inducing BPDE-DNA adduct formation via the AHR/Cyp1a1 signalling pathway, as well as suppressing NER via AHR-mediated inhibition of SIRT1.
研究领域:
毒理学
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发育生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
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2019
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IF 2.197
YiXun Li,Huan Li,Yong Duan,XueMei Cai,DingYun You,Feng Zhou,ChuanQi Yang,XiaoYu Tuo,ZiJie Liu
Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.
研究领域:
癌症研究
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纳米技术
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细胞生物学
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分子生物学
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环境健康
✓ 已验证
DOI
PubMed
高影响因子
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