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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2021 · IF 9.028

DNA Cleavage by Chemically Exfoliated Molybdenum Disulfide Nanosheets

Yingcan Zhao,Jiayi Xu,Xingyu Jiang

Chemically exfoliated MoS2 (ce-MoS2) nanosheets have been widely used in biomedical and environmental fields. Some in vitro studies demonstrated that ce-MoS2 might induce toxicity. However, the understanding of the mechanism of potential toxicity is lacking. In this study, we found that ce-MoS2 could directly induce breakage of double-stranded DNA with or without an external energy input, making it different from other two-dimensional nanomaterials. In a dark environment, the DNA cleavage exhibited a pH-dependent trend due to reactive oxygen species generation under different pH values. Under photoirradiation, DNA cleavage could be enhanced. This study provides insights into the potential environmental risk and toxicity of ce-MoS2 in the aquatic environment.

研究领域: 生物医学 · 环境科学 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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RSC Advances · 2022 ·Vol. 12 ·期 29 ·18296-18300 · IF 4.036

Target-induced activation of DNAzyme for highly sensitive colorimetric detection of bleomycin via DNA scission

Xiaofei Liao,Mengyan Li,Li Zou

In this work, a label-free and sensitive colorimetric sensing strategy for the detection of bleomycin (BLM) was developed on the basis of BLM-mediated activation of G-quadruplex DNAzyme via DNA strand scission. A G-quadruplex based hairpin probe (G4HP) containing the scission site (5′-GT-3′) of BLM at the loop region and guanine (G)-rich sequences at its 5′-end was employed in this protocol. In the presence of BLM, it may cleave the 5′-GT-3′ site of the hairpin probe with Fe(II) as a cofactor, releasing the G-tetrads DNA fragment, which may further bind hemin to form a catalytic G-quadruplex-hemin DNAzyme. The resultant G-quadruplex DNAzyme has notable peroxidase-like activity, which effectively catalyzes the oxidation of 2,2′-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) (ABTS) by H2O2 to produce the blue-green-colored free-radical cation (ABTS·+). Therefore, the detection of BLM can be achieved by observing the color transition with the naked eye or measuring the absorbance at a wavelength of 420 nm using a UV-Vis spectrophotometer. Attributing to the specific BLM-induced DNA strand scission and the effective locking of G-tetrads in the stem of the G4HP, the colorimetric sensing strategy exhibits high sensitivity and selectivity for detection of BLM in human serum samples, which might hold great promise for BLM assay in biomedical and clinical research.

研究领域: 生物医学工程 · 分析化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYST · 2012 ·Vol. 137 ·期 19 ·4428-4434 · IF 4.23

Sensitive detection of H2O2 and H2O2-related reactant with Ru(bipy)2(7,8-dimethyl-dipyridophenazine)2+ and oligodeoxyribonucleotide

Cen Xiong,Zhiyou Xiao,Manjun Zhang,Liansheng Ling

A sensor for H2O2 and H2O2-related reactant was constructed with oligonucleotides and Ru(bipy)2dppx2+ (bipy = 2,2′-bipyridine, dppx = 7,8-dimethyl-dipyridophenazine), which was performed by converting the H2O2-induced DNA cleavage into the change of luminescence. The ‘DNA light switch’ Ru(bipy)2dppx2+ could emit strong luminescence in the presence of dsDNA. DNA cleavage occurred upon addition of H2O2 due to the Fenton reaction, which resulted in the decrease of the luminescence of Ru(bipy)2dppx2+. Therefore, the luminescence intensity depended on the concentration of H2O2 and H2O2-related reactants, and the detection limits for H2O2, uric acid and cholesterol were 0.20 μM, 0.46 μM and 1.25 μM, respectively. The recovery varied between 94.0% and 105.0% when the assay was applied to the determination of uric acid and cholesterol in biological samples, which demonstrated the good practicability of the assay.

研究领域: 分析化学 · 生物化学 · 传感器
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INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION · 2018 · IF 2.317

In vitro activities of inulin fermentation products to HCT-116 cells enhanced by the cooperation between exogenous strains and adult faecal microbiota

Dan-Ting Yin,Yu Fu,Xin-Huai Zhao

Inulin was fermented by adult faecal microbiota and 10 exogenous strains for 24 or 48 h. The contents of acetate, propionate, butyrate and lactate were quantified in the fermented products, and the growth-inhibitory and apoptosis-inducing effects on a human colon cell line (HCT-116 cells) were assessed. Most of these strains increased contents of acetate, propionate and butyrate, and promoted lactate conversion. Correlation analysis suggested that butyrate and lactate in the fermentation products were positively and negatively correlated with the measured inhibition ratios (p < .05). The results were mostly consistent with the verification trial results using standard acid solutions. The fermentation products could cause apoptosis via inducing DNA fragmentation and increasing total apoptotic populations in the treated cells. Moreover, the fermentation products with higher growth-inhibitory activities demonstrated the increased apoptosis-inducing properties. In conclusion, these strains could cooperate with adult faecal microbiota to confer inulin fermentation products with higher anti-colon cancer activity.

研究领域: 微生物学 · 癌症研究 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Arabian Journal of Chemistry · 2023 · IF 6

Structural characterization of chlorogenic acid-metal complexes derived from the aqueous extracts of medicinal plants and their DNA cleavage and antibacterial activities

Kangkang Zheng,Yafeng Liu,Liang Peng,Zhimin Li,Wenbin Xu

The discovery of organic components with pharmacological activities in medicinal plants is crucial for new drug development. We examined chlorogenic acid (CGA) using high-performance liquid chromatography to analyze the aqueous and methanolic extracts of medicinal plants dissolved in methanol or methanol containing 15% formic acid. We found that for the aqueous extract, the peak areas of various components dissolved in 15% formic acid methanol were significantly larger than those dissolved in methanol. For the differences in the methanolic extract, the peak areas of all chromatographic peaks were relatively small between the samples dissolved in the two solvents. Electrospray ionization time-of-flight mass spectrometry showed that CGA could react in hot water with the eight most common plant metal ions (Ca 2+ , Cu 2+ , Fe 3+ , Mg 2+ , Mn 2+ , Ni 2+ , Sr 2+ , and Zn 2+ ) to form complexes with different coordination forms. The bioactivity experiments showed that CGA-Cu complexes could cause DNA cleavage through oxidative damage. CGA-Ni, CGA-Mn, and CGA-Zn showed significantly stronger inhibition against Staphylococcus aureus than CGA and the corresponding metal ions. These results suggest that, during the decoction process of medicinal plants, CGA forms complexes with metal ions, which are likely to be one of the active ingredients in medicinal plants. Subsequently, further research is needed on the antibacterial mechanism of chlorogenic acid-metal complexes not mentioned in this article.

CAS / MDL: 64-18-6
研究领域: 药理学 · 分析化学 · 生物化学
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CHEMICO-BIOLOGICAL INTERACTIONS · 2024 · IF 4.7

Specific human CYP enzymes-dependent mutagenicity of tris(2-butoxyethyl) phosphate (an organophosphorus flame retardant) in human and hamster cell lines

Wenwen Luo,Keqi Hu,Yijing Chen,Lin Wang,Yungang Liu

Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4.

CAS / MDL: 78-51-3
研究领域: 毒理学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LUMINESCENCE · 2017 ·Vol. 32 ·期 6 ·988-998 · IF 1.509

Deciphering the intercalative binding modes of benzoyl peroxide with calf thymus DNA

Kaixin Xia,Guowen Zhang,Deming Gong

The binding of benzoyl peroxide (BPO), a flour brightener, with calf thymus DNA (ctDNA) was predicted by molecular simulation, and this were confirmed using multi-spectroscopic techniques and a chemometrics algorithm. The molecular docking result showed that BPO could insert into the base pairs of ctDNA, and the adenine bases were the preferential binding sites which were validated by the analysis of Fourier transform infrared spectra. The mode of binding of BPO with ctDNA was an intercalation as supported by the results from ctDNA melting and viscosity measurements, iodide quenching effects and competitive binding investigations. The circular dichroism and DNA cleavage assays indicated that BPO induced a conformational change from B-like DNA structure towards to A-like form, but did not lead to significant damage in the DNA. The complexation was driven mainly by hydrogen bonds and hydrophobic interactions. Moreover, the ultraviolet–visible (UV–vis) spectroscopic data matrix was resolved by a multivariate curve resolution–alternating least–squares algorithm. The equilibrium concentration profiles for the components (BPO, ctDNA and BPO–ctDNA complex) were extracted from the highly overlapping composite response to quantitatively monitor the BPO–ctDNA interaction. This study has provided insights into the mechanism of the interaction of BPO with ctDNA and potential hazards of the food additive.

CAS / MDL: 94-36-0
研究领域: 分子生物学 · 生物化学 · 药学
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · 2021 ·Vol. 47 ·期 6 ·1-10 · IF 4.101

Genotoxicity of chloroacetamide herbicides and their metabolites in vitro and in vivo

Xinyan Ma,Ying Zhang,Mingyang Guan,Weidong Zhang,Huifang Tian,Caixiao Jiang,Xiaoxin Tan,Weijun Kang

The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2‑ethyl‑6‑methyl-2-chloroacetanilide (CMEPA) and 6‑ethyl‑o‑toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co‑treatment with anti‑reactive oxygen species (ROS) reagent N‑acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co‑treatment with N‑acetylcysteine alleviated the pro‑apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N‑acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.

研究领域: 毒理学 · 分子生物学 · 发育生物学 · 环境科学
✓ 已验证 DOI PubMed 高影响因子
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY · 2018 ·Vol. 102 ·期 15 ·6659-6672 · IF 3.34

Nerol-induced apoptosis associated with the generation of ROS and Ca2+ overload in saprotrophic fungus Aspergillus flavus

Tian Jun,Gan Yeyun,Pan Chao,Zhang Man,Wang Xueyan,Tang Xudong,Peng Xue

The contamination of food with Aspergillus flavus and subsequent aflatoxins is one of the most serious safety problems in the world. In this study of nerol (NEL)’s antifungal mechanism of action, we observed morphological and physiological changes in Aspergillus flavus. We found that NEL resulted in elevated levels of reactive oxygen species (ROS) and calcium ions (Ca 2+ ). On ROS assays, compared with the controls, the proportion of fluorescent cells treated with concentrations of 0.25, 0.5, 1, and 2 μL/mL NEL increased to 8.4 ± 1.07%, 10.2 ± 1.72%, 13.4 ± 0.50%, and 26.2 ± 4.21%, respectively. Increased mitochondrial dysfunction and oxidative stress induced by the interactions between Ca 2+ and ROS subsequently activate the release of cytochrome c and caspase activity. Characteristic changes of apoptosis were also observed via various detection methods, including phosphatidylserine externalization, nuclear condensation, and DNA fragmentation. Meanwhile, we found that the expression of CaMKs increased significantly in NEL-treated cells. In conclusion, our findings indicate that NEL has great potential as an eco-friendly antifungal agent for food preservation.

CAS / MDL: 106-25-2
研究领域: 食品科学 · 微生物学 · 毒理学 · 药理学
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