Analytical Methods
·
2014
·Vol. 6
·期 16
·6536-6540
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IF 1.938
Jing Cao Si,Lu Lu,Zhong Feng Gao,Yu Zhang,Hong Qun Luo,Nian Bing Li
A sensitive and selective biosensor has been developed to detect the hydroxyl radical (˙OH), which was generated through the Fenton reaction. ˙OH could oxidatively damage DNA and cleave it into pieces. Based on this, taking [Ru(NH3)6]3+ as the electrochemical indicator, ˙OH was determined on a gold electrode with self-assembled DNA. The resulting electrochemical biosensor showed a wide linear range of detection from 125 pM to 625 nM with a detection limit of 80 pM and satisfactory selectivity.
研究领域:
生物化学
·
分析化学
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DOI
高影响因子
NUCLEIC ACIDS RESEARCH
·
2019
·Vol. 47
·期 22
·11514-11526
·
IF 11.147
Jie Jialong,Xia Ye,Huang Chun-Hua,Zhao Hongmei,Yang Chunfan,Liu Kunhui,Song Di,Zhu Ben-Zhan,Su Hongmei
Phosphorothioate (PS) modifications naturally appear in bacteria and archaea genome and are widely used as antisense strategy in gene therapy. But the chemical effects of PS introduction as a redox active site into DNA (S-DNA) is still poorly understood. Herein, we perform time-resolved spectroscopy to examine the underlying mechanisms and dynamics of the PS oxidation by potent radicals in free model, in dinucleotide, and in S-oligomer. The crucial sulphur-centered hemi-bonded intermediates -P–S∴S–P- were observed and found to play critical roles leading to the stable adducts of -P–S–S–P-, which are backbone DNA lesion products. Moreover, the oxidation of the PS moiety in dinucleotides d[GPSG], d[APSA], d[GPSA], d[APSG] and in S-oligomers was monitored in real-time, showing that PS oxidation can compete with adenine but not with guanine. Significantly, hole transfer process from A+• to PS and concomitant -P–S∴S–P- formation was observed, demonstrating the base-to-backbone hole transfer unique to S-DNA, which is different from the normally adopted backbone-to-base hole transfer in native DNA. These findings reveal the distinct backbone lesion pathway brought by the PS modification and also imply an alternative -P–S∴S–P-/-P–S–S–P- pathway accounting for the interesting protective role of PS as an oxidation sacrifice in bacterial genome.
研究领域:
生物化学
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分子生物学
·
基因治疗
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DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2025
·
IF 2.7
Lan Yang,Yewen Lin,Wenping Xu,Yang Zhang
Reactive oxygen species (ROS)-induced DNA oxidative damage is a significant manifestation of oxidative stress in the body and is closely associated with the onset and progression of various diseases. Although Pyripyropene A (PPPA) exhibits anti-tumor and anti-inflammatory activities, its antioxidant and protective effects against DNA oxidative injury remain unclear. In this study, using a hydrogen peroxide-induced oxidative injury model of L02 cells, it was found that PPPA could significantly reduce intracellular ROS and malondialdehyde (MDA) levels, enhance the activities of catalase (CAT) and reduced glutathione (GSH), and increase the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) clearance rate, confirming its antioxidant effect. Comet assay showed a reduction in DNA breakage, and down-regulation of phosphorylated histone (γ-H2AX) and 8-hydroxydeoxyguanosine (8-oxodG), indicating that it effectively alleviates DNA oxidative injury. Meanwhile, the upregulated expression of poly ADP-ribose polymerase (PARP) suggests that PPPA may promote repair by activating the DNA damage response (DDR). This study systematically clarify for the first time that PPPA exerts a protective effect by synergistically antioxidizing, reducing DNA injury, and potentially activating repair pathways, providing a theoretical basis for its application in neoplasm and oxidative stress-related diseases.
研究领域:
分子生物学
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药理学
·
氧化应激
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肿瘤学
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毒理学
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细胞生物学
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药物代谢
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DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2016
·
IF 4.173
Zhilei Liu,Yadong Hu,Haisha Liang,Zhongyuan Sun,Shan Feng,Haiteng Deng
PRDX3 is a mitochondrial peroxide reductase that regulates cellular redox state. It has been reported that PRDX3 is overexpressed in liver cancer, but how PRDX3 is involved in hepatocellular carcinoma (HCC) tumorigenesis and progression has not been well-characterized. In the present study, we established two stable cell lines by overexpressing or knocking down PRDX3 in HepG2 cells. We found that PRDX3 silencing decreased the growth rate of HepG2 cells and increased mtDNA oxidation. Quantitative proteomics identified 475 differentially expressed proteins between the PRDX3 knockdown and the control cells. These proteins were involved in antioxidant activity, angiogenesis, cell adhesion, cell growth, ATP synthesis, nucleic acid binding, redox, and chaperones. PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation. Taken together, our results indicate that PRDX3 promotes HCC growth and mediates cell migration and invasiveness and is a potential therapeutic target for HCC treatment.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Nanomaterials
·
2020
·Vol. 10
·期 10
·2044
·
IF 4.324
Weiwei Ye,Yu Zhang,Wei Hu,Liwen Wang,Yu Zhang,Ping Wang
A sensitive fluorescence resonance energy transfer (FRET) biosensor is proposed to detect 8-hydroxy-2′-deoxyguanosine (8-OHdG), which is a typical DNA oxidation damage product excreted in human urine. The FRET biosensor was based on carbon dots (CDs)-modified nanoporous alumina membrane with CDs as fluorescence donors. Gold nanoparticles were encapsulated in zeolitic imidazolate framework-8 to form Au@ZIF-8 nanoparticles as signal quenchers. CDs and Au@ZIF-8 nanoparticles were biofunctionalized by 8-OHdG antibody. The capture of 8-OHdG on the membrane substrates can bring Au@ZIF-8 nanoparticles closely to CDs. With 350 nm excitation, the fluorescence of CDs was quenched by Au@ZIF-8 nanoparticles and FRET effect occurred. The quenching efficiency was analyzed. The limit of detection (LOD) was 0.31 nM. Interference experiments of the FRET biosensor showed good specificity for 8-OHdG detection. The biosensor could detect urinary 8-OHdG sensitively and selectively with simple sample pretreatment processes. It shows applicability for detecting biomarkers of DNA damage in urine or other biological fluids.Keywords:nanoporous alumina membrane;fluorescence resonance energy transfer;Au@ZIF-8 nanoparticles;DNA oxidation damage;8-OHdG detection
研究领域:
生物传感技术
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医学诊断
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纳米生物学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 10
·e202300620
·
IF 2.9
Dang-Nan Zhou,Lu Han,Zhan Zhang,Yun-Long Wang,Xiao-Ping Zhang,Yun-Jie Wu,Gao-Lei Xi
Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors ( n ) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of ⋅OH-oxidation of the DNA system, compounds I ~ V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I ~ V could also inhibit Cu 2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS + ⋅), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien- p- tolylox radical (galvinoxyl⋅). The ability of compounds I ~ V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS + ⋅, galvinoxyl, and DPPH radicals, respectively. Graphical
研究领域:
化学
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药理学
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生物化学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Qi Lou,Lu Pan,Shengjin Xiang,Yueting Li,Jiahui Jin,Jingyang Tan,Baoshan Huang,Kaihui Nan,Sen Lin
Introduction Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
研究领域:
眼科
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药学
·
细胞生物学
·
炎症
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Xiaonan Cao,Mengxiao Fu,Qiyan Du,Zhongjie Chang
Nanomaterials have attracted much attention in the biomedical field. Black phosphorus quantum dots (BPQDs) have shown great potential in biomedical applications, but their potential risks to biosafety and environmental stability have not been fully evaluated. In the present study, zebrafish ( Danio rerio ) embryos were exposed to 0, 2.5, 5 and 10 mg/L BPQDs from 2 to 144 h post-fertilization (hpf) to explore developmental toxicity. The results showed that exposure to BPQDs for 96 h induced developmental malformations (tail deformation, yolk sac edema, pericardial edema, and spinal curvature) in zebrafish embryos. ROS and antioxidant enzyme activities (CAT, SOD, MDA and T-AOC) were substantially altered and the acetylcholinesterase (AChE) enzyme activity was significantly decreased in the BPQDs exposed groups. Locomotor behavior was inhibited after BPQDs exposure for 144 h in zebrafish larvae. A significant increase in 8-OHdG content indicates DNA oxidative damage in embryos. In addition, obvious apoptotic fluorescence signals were detected in the brain, spine, yolk sac and heart. At the molecular level, the mRNA transcript levels of key genes related to skeletal development (igf1, gh, MyoD and LOX), neurodevelopment (gfap, pomca, bdnf and Mbpa), cardiovascular development (Myh6, Nkx2.5, Myl7, Tbx2b, Tbx5 and Gata4) and apoptosis (p53, Bax, Bcl-2, apaf1, caspase-3 and caspase-9) were abnormal after BPQDs exposure. In conclusion, BPQDs induced morphological malformations, oxidative stress , locomotor behavior disorders, DNA oxidative damage and apoptosis in zebrafish embryos. This study provides a basis for further study on the toxic effects of BPQDs.
研究领域:
毒理学
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环境科学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Xiaorong Li,Yunhui Si,Jingxian Liang,Mengsha Li,Zhiwei Wang,Yinying Qin,Litao Sun
Mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as promising candidates for cell-free therapy in tissue regeneration. However, the native osteogenic and angiogenic capacities of MSC-Exos are often insufficient to repair critical-sized bone defects, and the underlying immune mechanisms remain elusive. Furthermore, achieving sustained delivery and stable activity of MSC-Exos at the defect site is essential for optimal therapeutic outcomes. Here, we extracted exosomes from osteogenically pre-differentiated human bone marrow mesenchymal stem cells (hBMSCs) by ultracentrifugation and encapsulated them in gelatin methacryloyl (GelMA) hydrogel to construct a composite scaffold. The resulting exosome-encapsulated hydrogel exhibited excellent mechanical properties and biocompatibility, facilitating sustained delivery of MSC-Exos. Osteogenic pre-differentiation significantly enhanced the osteogenic and angiogenic properties of MSC-Exos, promoting osteogenic differentiation of hBMSCs and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, MSC-Exos induced polarization of Raw264.7 cells from a pro-inflammatory phenotype to an anti-inflammatory phenotype under simulated inflammatory conditions, thereby creating an immune microenvironment conducive to osteogenesis. RNA sequencing and bioinformatics analysis revealed that MSC-Exos activate the p53 pathway through targeted delivery of internal microRNAs and regulate macrophage polarization by reducing DNA oxidative damage. Our study highlights the potential of osteogenic exosome-encapsulated composite hydrogels for the development of cell-free scaffolds in bone tissue engineering.
研究领域:
组织工程
·
再生医学
·
生物材料
·
干细胞生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2019
·
IF 4.561
Rui Wang,Xing Hu,Junhui Pan,Guowen Zhang,Deming Gong
Isoeugenol , a natural phenolic compound in plant essential oils, is known to have many biological and pharmacological properties . In the present work, the interaction of isoeugenol with calf thymus DNA (ctDNA) and its protective effect on DNA oxidative damage were investigated by multispectroscopic techniques, viscosity measurements, gel electrophoresis studies and molecular simulation. Analyses of ultraviolet-visible (UV–vis) absorption and fluorescence spectra indicated that isoeugenol could bind to ctDNA with a binding constant on the order of 10 3 L mol −1 , which was mainly driven by hydrogen bonding and van der Waals forces . The results from the viscosity measurements, competitive displacement studies and circular dichroism (CD) analysis indicated that the binding of isoeugenol to ctDNA was in the groove mode and that the A–T base pairs in the minor grooves of ctDNA were the main binding sites for isoeugenol, which was supported by molecular docking analyses. In addition, isoeugenol was found to show a protective effect against hydroxyl-induced DNA damage, which may be explained by its good antioxidant activity . These findings may improve the understanding of the mechanism of interaction between isoeugenol and ctDNA and provide a theoretical basis for the development of isoeugenol in the food and drug industry.
研究领域:
药理学
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生物化学
·
分子生物学
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产品关联
DOI
高影响因子
RENAL FAILURE
·
2024
·
IF 3
Tao Wei,Bohan Liu,Yi Chen,Chang Li
3-monochloropropane-1,2-diol esters (3-MCPDE) are a group of contaminants which are mainly formed during heat processing of edible oil and fat-based foods. The kidney is the primary target organ for the toxic effects of 3-MCPDE. 3-MCPD-di-palmitate exists in a variety of oils and fats, and is the most common and relatively high proportion of 3-MCPDE. In this study, we investigated the protective effect of ascorbic acid on 3-MCPD-di-palmitate-induced renal injury in rats. Thirty 8-week-old male Sprague-Dawley rats were randomly divided into 5 groups, namely control, 3-MCPD-di-palmitate (240 mg/kg·bw), 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (100 mg/kg·bw), 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (200 mg/kg·bw) and 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (500 mg/kg·bw). These treatments were administered via gavage for a duration of 4 weeks. The effects of ascorbic acid on 3-MCPDE-induced kidney injury in rats were investigated by evaluating the kidney index, renal function (BUN, CRE), renal histopathology, oxidative stress markers (ROS, GSH, MDA, and T-AOC), DNA oxidation marker (8-OHdG), and activities of Caspase 3 and 9. The results showed that the exposure to 3-MCPDE significantly increased the kidney index, BUN and CRE levels, ROS and MDA levels, 8-OHdG levels, and activities of Caspase 3 and 9, while decreasing GSH and T-AOC. The combined treatment with 3-MCPDE and ascorbic acid can effectively restore the aforementioned parameters. The present study concluded that ascorbic acid effectively attenuates the renal apoptosis and oxidative homeostasis induced by 3-MCPDE uptake thereby intervening in renal injury.
研究领域:
毒理学
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药理学
·
肾脏生理学
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氧化应激研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2020
·
IF 3.292
Zuntao Wu,Lin Bai,Runqi Tu,Lijie Zhang,Yue Ba,Huizhen Zhang,Xing Li,Xuemin Cheng,Wenjie Li,Hui Huang
Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.
研究领域:
神经毒理学
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神经科学
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分子生物学
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行为科学
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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）