SENSORS AND ACTUATORS B-CHEMICAL
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2021
·
IF 7.46
Yingli Han,Yuehua Wang,Fangyu Zhou,Yuyang Jiang,Feng Liu
Human apurine/apyrimidine endonuclease (APE) is a multifunctional enzyme that affects the occurrence and development of cancer through DNA repair and redox regulation. It has been identified as a tumor marker for detection and prognosis and drug target due to its overexpression in a variety of cancers. However, the accurate detection of APE 1 activity is still a huge challenge. Traditional approaches exist some disadvantages, including low sensitivity, complex operation and professional equipment requirements. Therefore, it is necessary to develop a fast, sensitive and simple biosensor to detect APE 1 activity in vivo and in vitro. In this report, a new tetrahedral molecular beacon (TMB) probe is designed for the detection of APE 1 activity. This probe not only has the advantage that the tetrahedron can enter the cells without a transfection agent, but also has the advantages of simple operation and low cost. The extracellular detection limit of TMB is as low as 0.0026 U/mL, and this program has successfully achieved APE 1 intracellular imaging to distinguish cancer cells overexpressing APE 1 from normal cells. In addition, the probe which is an effective mean for screening APE 1 inhibitor can also monitor the response of APE 1 to different drugs. All in all, our probe can be successfully applied to detect APE 1 activity in vivo and vitro, and can achieve living cells drug screening. And this probe also provides a general method for the detection of other endogenous biological targets in living cells.
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FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Xinyue Peng,Luyi Tan,Jia Song,Yuefei Lai,Susu Yu,Feifei Xu,Qinzhi Wei,Zhini He,Wenli Cheng,Wenjuan Zhang,Xingfen Yang
Geniposide (GP) is the homology of medicine and food with bioactive effects of antioxidation and resistance to apoptosis in the liver. It's of great significance to explore the biosafety exposure limits and action mechanisms of GP. This study detected the global DNA methylation microenvironment and the regulation of specific genes in GP against cellular apoptosis induced by hydrogen peroxide (H 2 O 2 ) of human hepatocyte L-02 cells. The half inhibitory concentration (IC 50 ) of GP on normal L-02 cells was 57.7 mg/mL. GP exerted new epigenetic activity, increased DNMT1 , decreased TET1 and TET2 expression, and reversed the demethylation effect to some extent, thereby increasing the overall genomic DNA methylation level at the concentration of 900 μg/mL. GP pretreatment could also adjust the level of P53, Bcl-2 and AKT altered by H 2 O 2 , reducing their specific DNA methylation levels in the promoter regions of AKT and Bcl-2 to inhibit apoptosis. Taken together, GP regulates the global DNA methylation level and controls the expression changes of P53, Bcl-2 and AKT, jointly inhibiting the occurrence of apoptosis in human hepatocytes and providing the newly theoretical references for its safety evaluation.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2020
·
IF 5.573
Gui-Bin Liang,Jian-Hua Wei,Hong Jiang,Ri-Zhen Huang,Jing-Ting Qin,Hui-Ling Wang,Heng-Shan Wang,Ye Zhang
Four series of new 3-nitro naphthalimides derivatives , 4 ( 4a‒4f ), 5 ( 5a‒5i ), 6 ( 6a‒6e ) and 7 ( 7a‒7j ), were designed and synthesized as antitumor agents . Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3, A549 and MGC-803 cancer cell lines in comparison with 5-fluorouracil (5-FU), mitonafide and amonafide . Nude mouse xenotransplantation model assay results indicated that compounds 6b and 7b exhibited good in vivo antiproliferative activity in MGC-803 xenografts in comparison with amonafide and cisplatin , suggesting that compounds 6b and 7b could be good candidates for antitumor agents. Gel electrophoresis assay indicated that DNA and Topo I were the potential targets of compounds 6b and 7b , and comet assay confirmed that compounds 6b and 7b could induce DNA damage, while the further study showed that the 6b - and 7b -induced DNA damage was accompanied by the upregulation of p-ATM, P-Chk2, Cdc25A and p-H2AX. Cell cycle arrest studies demonstrated that compounds 6b and 7b arrested the cell cycle at the S phase, accompanied by the upregulation of the expression levels of the antioncogene p21 and the down-regulation of the expression levels of cyclin E. Apoptosis assays indicated that compounds 6b and 7b caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-3, caspase-9 and PARP and the downregulation of Bcl-2. These mechanistic studies suggested that compounds 6b and 7b exerted their antitumor activity by targeting to DNA, thereby inducing DNA damage and Topo I inhibition, and consequently causing S stage arrest and the induction of apoptosis.
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ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Zhongnan Huang,Wenjie Wang,Yingfei Wang,Han Wang,Yimin Pang,Quan Yuan,Jie Tan,Weihong Tan
Developing rapid, sensitive, and facile nucleic acid detection technologies is of paramount importance for preventing and controlling infectious diseases. Benefiting from the advantages such as rapid response, low cost, and simple operation, electrochemical impedance spectroscopy holds great promise for point-of-care nucleic acid detection. However, the sensitivity of electrochemical impedance spectroscopy for low molecular weight nucleic acids testing is still limited. This work presents a DNA nanolock-based porous electrode to improve the sensitivity of electrochemical impedance spectroscopy. Once the target nucleic acids are recognized by the DNA probes, the pore-attached DNA nanolock caused remarkable impedance amplification by blocking the nanopores. Taking SARS-CoV-2 nucleic acid as a model analyte, the detection limit of the porous electrode was as low as 0.03 fM for both SARS-CoV-2 RNA and DNA. The integration of a porous electrode with a wireless communicating unit generates a portable detection device that could be applied to direct SARS-CoV-2 nucleic acid testing in saliva samples. The portable device could effectively distinguish the COVID-19 positive and negative samples, showing a sensitivity of 100% and a specificity of 93%. Owing to its rapid, ultrasensitive, specific, and portable features, the as-designed DNA nanolock and porous electrode-based portable device holds great promise as a point-of-care platform for real-time screening of COVID-19 and other epidemics.
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JACS Au
·
2023
·
IF 8
Xiangyuan Ouyang,Nan Jia,Jing Luo,Le Li,Jiangshan Xue,Huaiyu Bu,Gang Xie,Ying Wan
Metal nanoclusters (NCs) have emerged as a promising class of fluorescent probes for cellular imaging due to their high resistance to photobleaching and low toxicity. Nevertheless, their widespread use in clinical diagnosis is limited by their unstable intracellular fluorescence. In this study, we develop an intracellularly biosynthesized fluorescent probe, DNA nanoribbon-gold NCs (DNR/AuNCs), for long-term cellular tracking. Our results show that DNR/AuNCs exhibit a 4-fold enhancement of intracellular fluorescence intensity compared to free AuNCs. We also investigated the mechanism underlying the fluorescence enhancement of AuNCs by DNRs. Our findings suggest that the higher synthesis efficiency and stability of AuNCs in the lysosome may contribute to their fluorescence enhancement, which enables long-term (up to 15 days) fluorescence imaging of cancer cells (enhancement of ∼60 times compared to free AuNCs). Furthermore, we observe similar results with other metal NCs, confirming the generality of the DNR-assisted biosynthesis approach for preparing highly bright and stable fluorescent metal NCs for cancer cell imaging.
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NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 9
·4195-4201
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IF 3.591
Hai-Bo Wang,An-Li Mao,Bei-Bei Tao,Hong-Ding Zhang,Yan-Ming Liu
Molecular logic computation has drawn extensive attention in the fields of bioanalysis, intelligent diagnostics of diseases and other nanotechnology areas. DNA-templated Au nanoclusters (DNA-AuNCs) possess some excellent features, including high luminescence, good photo-stability and easy preparation. Herein, taking these advantages of DNA-AuNCs, we have designed and constructed a universal platform of label-free and enzyme-free multiple molecular logic gates, including NOR, XNOR, IMPLY, OR, AND, and INHIBIT. The experimental results have demonstrated the feasibility of these logic gates operations using Hg2+, Cu2+, biothiols, melamine and pyrophosphate (PPi) as inputs. Thus, the universal platform can be utilized for the determination of biothiols, melamine and pyrophosphate (PPi) via logic outputs. The strategy exhibited low cost, easy operation and versatile design, and can offer a promising platform for the development of functional logic systems.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 15
·3847-3859
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IF 4.157
Xiao Jing,Liu Zhang,Li Chunxiang,Wang Jinglun,Huang Haowen,Yi Qingfeng,Deng Keqin,Li Xiaofang
Graphdiyne (GDY) adsorbed DNA probes have been used as a fluorescent sensing platform, but topics including DNA adsorption affinities, DNA probe displacement, and fluorescence quenching ability were rarely researched. Herein, the adsorption affinity of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) on a tremella-like GDY was tuned by modulating the surface chemistry of GDY. The fluorescence quenching ability of GDY with different oxidation degrees was compared. The nonspecific displacement of DNA probes on GDY was studied. Under the same concentrations, GDY with low oxidation degree exhibited stronger adsorption affinity and higher adsorption capacity to both ssDNA and dsDNA than highly oxidized GDY. DNA adsorbed on low-oxidized GDY was more resistant to displacement by other DNAs. Protein showed strong interaction with different GDY and could displace DNA probes on GDY. Based on these findings, an ideal GDY with proper oxidation degree, exhibiting high surface affinity for ssDNA and low affinity for dsDNA, was used as scavenger of redundant ssDNA fluorescent probe in an enzyme-assisted amplification system for sensitive ochratoxin (OTA) detection. This study has enhanced our fundamental understanding of DNA adsorption by GDY. It also provided a rational way to apply GDY for fluorescence sensing in a complicated system. Graphical abstract
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PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Xu Li,Yue Yuan,Yuting Wang,Fengming Zhang,Rui Zhao,Di Shao,Shuyun Bi
The investigation on the binding interaction mechanism of florfenicol with DNA in vitro was reported via multi-spectroscopy measurements and molecular docking approach in the present work. The static fluorescence quenching process accompanied with non-radiation energy transfer between florfenicol and DNA was confirmed by Stern-Volmer analysis, lifetime measurement and fluorescence resonance energy transfer study. Florfenicol was the A-T rich minor groove binding agent of DNA. Various experiments including site marker competitive experiments, viscosity measurements, helix melting studies, ionic strength measurements, thermal denaturation experiments, circular dichroism (CD) spectra measurements and UV–vis spectra characteristics were carried out to disclose the interaction mode. In addition, molecular docking stimulated appropriate binding orientation to further prove above experimental results. The binding constants were 6.92 × 10 3 , 6.21 × 10 3 and 5.61 × 10 3 M −1 at 291, 301 and 311 K respectively and the binding distance r 0 was 5.30 nm. Thermodynamic parameters, such as Δ H Ө =−7.90 kJ mol −1 and Δ S Ө = 46.39 J mol −1 K −1 , showed that electrostatic attraction was the key force in the binding.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2021
·Vol. 101
·期 11
·4490-4497
·
IF 3.639
Ming Li,Xia Hong,Xuchun Qiu,Chuqin Yang,Yuhao Mao,Yan Li,Zhenjiang Liu,Daolin Du
BACKGROUND The ultrasensitive monitoring strategy of zearalenone (ZEN) is essential and desirable for food safety and human health. In the present study, a coupling of gold nanoparticles-DNA barcode and direct competitive immunoassay-based real-time polymerase chain reaction signal amplification (RT-IPCR) for ZEN close to the sensitivity of PCR-like levels is described and evaluated. RESULTS The RT-IPCR benefited from the use of a DNA barcode and RT-PCR detection strategy, thus resulting in ultrasensitive and simple detection for ZEN. Under the optimal RT-IPCR, the linear range of detection was from 0.5 to 1000 pg mL −1 and the limit of detection was 0.5 pg mL −1 , which was 400-fold lower than the enzyme-linked immunosorbent assay. The detection procedure was simplified and the detection time was shortened. The specificity, accuracy and precision of the RT-IPCR confirmed a high performance. ZEN-positive contamination levels were from 0.056 to 152.12 ng g −1 by the RT-IPCR, which was demonstrated to be highly reliable by liquid chromatography-tandem mass spectrometry. CONCLUSION The proposed RT-IPCR could be used as an alternative for detecting ZEN with satisfactory ultrasensitivity, simplicity, low cost and high-throughput. The present study could provide a strategy for the ultrasensitive detection of the small molecule with a simple and practical approach, which has significant appeal and application prospects.
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BIOLOGICAL TRACE ELEMENT RESEARCH
·
2021
·Vol. 199
·期 10
·3728-3736
·
IF 3.738
Han Gaochao,Tan Zhuangsheng,Jing Haiming,Ning Junyu,Li Zinan,Gao Shan,Li Guojun
Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy. This study aimed to conduct an in vivo rodent alkaline comet assay, and as a companion test to the lanthanum nitrate carcinogenicity test. We conducted an oral gavage experiment for 180 days (26 weeks) to test for the persistence of DNA damage of long-term low-dose accumulation of lanthanum nitrate (12.5, 25, and 50 mg/kg body weight), in F1 hybrid C57-ras transgenic mice (CB6F1) by using alkaline comet assay in the blood and liver. The comet assay revealed that all the tested concentrations of lanthanum nitrate did not induce DNA damage in any of the tissues investigated, whereas DNA damage was induced in the positive control group. These results could indicate that lanthanum nitrate can accumulate in tissues and organs of the mice after exposure, and does not possess DNA damage in C57-ras transgenic mice after repeated treatments at oral doses up to 50 mg/kg·BW for 26 weeks; also, it did not cause pathological changes in the liver of the mice.
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Biosensors-Basel
·
2020
·Vol. 10
·期 12
·211
·
IF 3.24
Min-Xin Mao,Rong Zheng,Chi-Fang Peng,Xin-Lin Wei
In this work, a paper device consisted of a patterned paper chip, wicking pads, and a base was fabricated. On the paper chip, DNA–gold nanoparticles (DNA–AuNPs) were deposited and Hg2+ions could be adsorbed by the DNA–AuNPs. The formed DNA–AuNP/Hg2+nanozyme could catalyze the tetramethylbenzidine (TMB)–H2O2chromogenic reaction. Due to the wicking pads, a larger volume of Hg2+sample could be applied to the paper device for Hg2+detection and therefore the color response could be enhanced. The paper device achieved a cut-off value of 50 nM by the naked eye for Hg2+under optimized conditions. Moreover, quantitative measurements could be implemented by using a desktop scanner and extracting grayscale values. A linear range of 50–2000 nM Hg2+was obtained with a detection limit of 10 nM. In addition, the paper device could be applied in the detection of environmental water samples with high recoveries ranging from 85.7% to 105.6%. The paper-device-based colorimetric detection was low-cost, simple, and demonstrated high potential in real-sample applications.Keywords:paper device;signal enhancement;mercury ion;colorimetric detection
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ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Libo Zhu,Zhen Zhang,Quanjun Liu
With the development in DNA self-assembly technology, DNA origami nanostructures have been widely applied in biomedical research. Solid-state nanopores represent an emerging single-molecule sensing platform for studying nanostructures with arbitrary dimensions and physical characteristics, including DNA origami. Here, we employed relatively narrow silicon nitride nanopores to detect the deformation and translocation of DNA origami nanoplates with dimensions of approximately 60 × 54 nm. We performed translocation experiments using three nanopore diameters that are all smaller than the plat dimensions. Analysis of current blockade signals and the representative events reveals three types of translocation orientations for the nanoplates. Furthermore, by studying the electrical signal characteristics (current change and dwell time) for the different diameter pores, we obtained information about the translocation behaviors for the DNA nanoplates through different constrictions. Our investigation provides an approach to analyze the deformation and translocation of DNA origami structures.
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