BIOSENSORS & BIOELECTRONICS
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2012
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IF 5.602
Jing Wang,Wei-Wei Zhao,Hong Zhou,Jing-Juan Xu,Hong-Yuan Chen
In this work, we firstly enunciated the presence of synergy effect between the electron and energy transfer in an electrochemiluminescence (ECL) system involving the CdS NCs and Au NPs, based on which an amplified ECL biosensor was constructed for sensitive detection of DNA–protein interactions. Specifically, Au NPs modified on electrode, following by assembled probe DNA . Then the modified GCE was hybridized with SiO 2 @CdS/DNA conjugates. With DNA duplex as a rigid spacer, Au NPs could not only accelerate the electron transfer but also produce the surface plasma resonance upon excited ECL of CdS NCs. However, the enhanced ECL could be greatly suppressed by the binding of target protein. The prepared biosensor possesses excellent analytical performance with the linear range of target protein from 0.015 to 150 nM.
研究领域:
分析化学
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生物化学
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纳米技术
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生物传感器
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DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2021
·Vol. 109
·期 12
·2506-2515
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IF 4.396
Jing Wei Jin,Min Zhi Rong,Ming Qiu Zhang,Wing-Leung Wong
β-1,3-D-glucan has been reported to have a series of bioactivities including antitumor, antimicrobial, anti-inflammatory and antioxidative effects; however, its insolubility in neutral aqueous solution significantly restricts the potential application in biological and medicine fields. Herein, a water-soluble aminated β-1,3-D-glucan (AG) was synthesized and the anti-inflammatory effect, cytotoxicity and plasmid DNA (pDNA) binding capacity of AG, serum stability, the particle sizes and zeta potentials of AG/pDNA nanocomposites, and the transfection efficiency and mechanism of action were studied. AG shows no obvious cytotoxicity within the range of working concentration (1–64 μg/ml) and it exerts potent anti-inflammatory effect independent on Dectin-1 and TLR2. AG/pDNA nanocomposites prepared by electrostatic interaction possess an appropriate particle size ranged from 192.8 to 118.4 nm and zeta potentials ranged from 20.880 to 27.16 mV with the N/P ratios from 5 to 100. AG/pDNA nanocomposites at the N/P ratios of 10 and 20 were able to show superior transfection efficiencies in RAW 264.7 cells as a result of their suitable particle size, zeta potential, anti-inflammatory effect, and the specific interaction with pattern recognition receptors (Dectin-1 and TLR2). These results indicate that AG is a potential candidate for DNA delivery system due to its potent anti-inflammatory effect and high transfection efficiency.
研究领域:
药学
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生物技术
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2018
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IF 4.816
Yong-Yu Qi,Qian Gan,Ya-Xian Liu,Ya-Hong Xiong,Zong-Wan Mao,Xue-Yi Le
In the search for more effective anticancer drugs with less toxic side effects, dipeptides were introduced into the Cu(II) complex of 5-methyl-2-(2′-pyridyl)benzimidazole (HPBM). Analytical and spectroscopic techniques were employed to thoroughly characterize complexes [Cu(Gly-gly)(HPBM)(H 2 O)]ClO 4 ·0.5H 2 O ( 1 ) and [Cu(Gly- L -leu)(HPBM)(H 2 O)]ClO 4 ( 2 ) (where Gly-gly = Glycyl-glycine anion, Gly- L -leu = Glycyl- l -leucine anion). The solution stability studies performed by ultraviolet–visible (UV–Vis) spectroscopy confirmed the stability of the complexes in the buffer solutions. The DNA binding affinity was evaluated using multi-spectroscopy, viscosity measurement and molecular docking methods and further quantified by K b and K app values, revealing an intercalative mode. Moreover, gel electrophoresis analysis revealed that the complexes could damage CT DNA through a hydroxyl radical pathway in the presence of ascorbic acid . All the complexes displayed favorable antimicrobial and cytotoxic activities toward the tested microorganisms ( Bacillus subtilis , Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa ) and cancer cells (A549, HeLa and PC-3). Most importantly, the possible anticancer mechanism of the complexes was explored by determining the cells morphological changes, intracellular reactive oxygen species (ROS) levels, location in mitochondria, mitochondrial membrane potentials and the expression of Bcl-2 family proteins. The results showed that the complexes could induce apoptosis in HeLa cells through an ROS-mediated mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins.
研究领域:
化学
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药理学
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分子生物学
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癌症研究
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微生物学
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PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-27
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IF 11.4
Shan Junqi,Li Xinyu,Sun Runqi,Yao Yao,Sun Yan,Kuang Qin,Dai Xianling,Sun Yanlai
Background The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients. Methods Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc. Results To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis. Conclusions We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.
研究领域:
癌症生物学
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分子生物学
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脂质代谢
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肿瘤学
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DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 1
·171
·
IF 2.861
Xiangcong Wang,Maocai Yan,Qibao Wang,Huannan Wang,Zhengyang Wang,Jiayi Zhao,Jing Li,Zhen Zhang
Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis,1H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu2(C9H6O2N)4(H2O)2]·2H2O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constantKSVvalue was 3.99 × 104M−1. The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na+in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.Keywords:DNA-binding;antioxidant;anticancer;indole-2-carboxylicacid;copper(II) complexes
研究领域:
化学
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生物化学
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药理学
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癌症研究
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DOI
PubMed
高影响因子
Applied Materials Today
·
2020
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IF 8.352
Fangman Chen,Fan Zhang,Dan Shao,Weibin Zhang,Liqin Zheng,Wei Wang,Wendi Yang,Zheng Wang,Jianxin Chen,Wen-fei Dong,Fangnan Xiao,Yunkun Wu
Ruthenium-based agents are promising in cancer chemotherapy but lack specific targeting and controlled release properties. Herein, a new class of bioreducible mer-[Ru(III)Cl 3 (dmso)(L)] prodrugs with highly DNA binding affinity were designed and synthesized for nucleus-targeted chemotherapy and selective activation in response to the tumor microenvironment. In this regard, ruthenium(III) prodrugs were reduced into highly active ruthenium(II) drugs in response to high intracellular glutathione levels, resulting in tumor apoptosis through synergistic intercalation that blocked DNA replication and coordination that cleaved nuclear DNA. In light of this, a multifunctional nanodrug (Ru-MSN-PLip) was constructed by integrating RuDPNI prodrug-loaded mesoporous silica nanoparticles (Ru-MSN) with a fusion protein-incorporated liposome (PLip) to achieve multiple targeting and eGFP-based fluorescence imaging of nonsmall cell lung cancer. Due to fusion protein-based cancer cell recognition and Ru(III) prodrug-mediated nuclear DNA targeting, Ru-MSN-PLip achieved sequential delivery and greater antitumor activity. In addition, Ru-MSN-PLip exhibited long-term blood circulation and selective accumulation in tumors, leading to significantly limited tumor growth in vivo without notable toxicity. Our findings indicated the potential applications of these types of bioreducible and traceable nanoprodrugs for efficient and safe nonsmall cell lung cancer therapy.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 32
·6406-6411
·
IF 6.331
Jie Yu,Xidong He,Zigui Wang,Sha Liu,Dengyuan Hao,Xiaoyuan Li,Yubin Huang
Platinum nanoparticles (Pt-NPs) have been developed for enhanced toxicity against tumor cells. However, the therapeutic effect of Pt-NPs was severely limited by the lack of cellular uptake of Pt-NPs and an oxidative environment. The combination of starvation therapy with Pt-NP based chemotherapy in a well-designed nano-system is expected to eliminate tumors. Therefore, GOx and Pt-NPs were coated with PLGA to obtain a functional nano-system (GOx–Pt-NS), which increased the cellular uptake of Pt-NPs. The accumulation of GOx–Pt-NS in tumors increased significantly via the enhanced permeability and retention (EPR) effect of nanoparticles. In addition, protection of the GOx–Pt-NS overcame several drawbacks of GOx such as poor stability, short in vivo half-life, immunogenicity, and systemic toxicity. Glucose oxidase (GOx) elevated the gluconic acid ROS levels in tumor cells, resulting in an acidic and oxidative environment. The acidic and oxidative environment enhanced the conversion of Pt2+via Pt NPs as well as DNA-binding ability. Finally, combining GOx based starvation therapy with Pt-NP based chemotherapy was expected to eliminate tumors more efficiently through a synergistic strategy.
研究领域:
肿瘤学
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Endocrinology
·
2022
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IF 6.055
Jiayu Lin,Yuting Xiang,Jiana Huang,Haitao Zeng,Yanyan Zeng,Jiawen Liu,Taibao Wu,Qiqi Liang,Xiaoyan Liang,Jingjie Li,Chuanchuan Zhou
In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase ( OGA ) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. NAT10 might regulate OGA stability and expression by suppressing its degradation. To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA , we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein-coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. Rsph6a , Gm7788 , Gm41780 , Trpc7 , Gm29036 , and Gm47144 were potential downstream genes. In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation.
研究领域:
生殖生物学
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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
·
2023
·
IF 9.8
Xiaolong Yu,Huanhuan Xing,Jianteng Sun,Xiaodong Du,Guining Lu,Lizhong Zhu
Di-(2-ethylhexyl) phthalate (DEHP) as widely utilized plasticizer has aroused increasing concerns since its endocrine disrupting effects and continuous accumulation in biota. To date, the interaction mechanism between DEHP and rice plants has not been clearly illustrated at molecular level. Here, we investigated biological transformation and response of rice plants ( Oryza sativa L.) to DEHP at realistic exposure concentrations. Nontargeted screening by UPLC-QTOF-MS was used to verify 21 transformation products derived from phase I metabolism (hydroxylation and hydrolysis) and phase II metabolism (conjugation with amino acids, glutathione, and carbohydrates) in rice. MEHHP-asp, MEHHP-tyr, MEHHP-ala, MECPP-tyr and MEOHP-tyr as the conjugation products with amino acids are observed for the first time. Transcriptomics analyses unraveled that DEHP exposure had strong negative effects on genes associated with antioxidative components synthesis, DNA binding, nucleotide excision repair, intracellular homeostasis, and anabolism. Untargeted metabolomics revealed that metabolic network reprogramming in rice roots was induced by DEHP, including nucleotide metabolism, carbohydrate metabolism, amino acid synthesis, lipid metabolism, synthesis of antioxidant component, organic acid metabolism and phenylpropanoid biosynthesis. The integrated analyses of interaction between differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) endorsed that metabolic network regulated by DEGs was significantly interfered by DEHP, resulting in cell dysfunction of roots and visible growth inhibition. Overall, these finding generated fresh perspective for crops security caused by plasticizer pollution and enhanced the public focus on dietary risk.
研究领域:
环境科学
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植物科学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Jingbo Sun,Hongchen Li,Min Ouyang,Jing Cheng,Dong Xu,Xiaofeng Tan,Qinlu Lin
Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.
研究领域:
细胞生物学
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疾病诊断
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材料科学
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光学性质
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生物医学应用
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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）