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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

I-motif Formed at Physiological pH Triggered by Spatial Confinement of Nanochannels: An Electrochemical Platform for pH Monitoring in Brain Microdialysates

Lu Shi,Feifei Cao,Limin Zhang,Yang Tian

The development of switches responding to specific pH changes was particularly useful in wide application fields. Owing to flexible switches simulated by pH, i-motif DNAs are widely used as a pH sensor. But its character of structure transition strongly dependent on acidic pH severely hampers the application of i-motif DNA in physiological media. Herein, we report the stable i-motif structure formed at a physiological pH triggered by spatial confinement of silica nanochannels. Three classic DNA chains containing 21-mer i-motif domain base-pairs and a single-stranded multiply (T)n spacer, 5′-COOH-(T)n-CCCTAACCCTAACCCTAACCC-3′, were employed to evaluate the enhanced stability of i-motif structure. Compared to their free states in a dilute solution, the transition pH of all i-motif DNAs decorated in nanochannels remarkably shifts toward a neutral pH. Moreover, the transition midpoint can be tuned sensitively over the physiologically relevant pH range through slightly varying the length of T base spacer. Density functional theory (DFT) calculations validate that the increased proton density in a nanochannel triggers the formation of an i-motif structure under a neutral pH. Finally, this i-motif DNA based nanochannels electrode was successfully employed to monitor pH in brain microdialysates followed by cerebral ischemia. The present approach is not limited by fundamental investigation for DNA conformation but may extend toward the manipulation of i-motif based structures for artificial molecular machines and signaling systems.

研究领域: 生物化学 · 分子生物学 · 医学检测
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ANALYTICAL CHEMISTRY · 2015 · IF 5.636

A Selective and Accurate Ratiometric Electrochemical Biosensor for Monitoring of Cu2+ Ions in a Rat Brain

Limin Zhang,Yingying Han,Fan Zhao,Guoyue Shi,Yang Tian

Metals are essential components of all living cells, and in many cases cells trigger and utilize dynamic metal movements for signaling purposes. So, it is very critical to develop the biosensors for determination of metal ions in living systems with high selectivity and accuracy. In this work, taking Cu2+ as a model, an accurate and selective ratiometric electrochemical biosensor was developed. First, the specific molecule, 2,2′,2″-(2,2′,2″-nitrilotris(ethane-2,1-diyl)-tris((pyridin-2-ylmethyl)azanediyl)triethanethiol (TPAASH), was designed and synthesized for specific recognition of Cu2+. Meanwhile, electroactive molecule, 6-(ferrocenyl)hexanethiol (FcHT) was coimmobilized with TPAASH at one electrode as inner reference molecule to provide a built-in correction for avoiding the environmental effects. Thus, the developed biosensor demonstrated high accuracy and remarkable selectivity toward Cu2+ against other metal ions, amino acids, and so on. In addition, the biosensor also showed high sensitivity due to the electrocatalytic activity of the nanostructured gold flowers. As a result, the present ratiometric electrochemical biosensor was successfully applied in detection of Cu2+ in brain microdialysates of normal rat brain and that followed by global cerebral ischemia.

研究领域: 生物传感技术 · 神经科学 · 分析化学
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XENOBIOTICA · 2017 · IF 1.932

Effect of ferulic acid on the brain pharmacokinetics of tetramethylpyrazine in conscious rats

Yinai Wu,Fengyun Liao,Weiguo Liao,Jianye Yu,Xingyun Deng,Huazhu Zheng,YingJiao Meng,Lisheng Wang

1. In traditional Chinese medicine, Angelica sinensis is often coprescribed with Ligusticum chuanxiong Hort for the treatment of ischemic cerebrovascular diseases. Tetramethylpyrazine (TMP) is one of the most important active ingredients isolated from Ligusticum chuanxiong Hort; ferulic acid (FA) is the main water-soluble component of Angelica sinensis.2. The purpose of this study is to investigate the possible effect of FA on the brain pharmacokinetics of TMP in conscious Sprague-Dawley rats. The pharmacokinetic parameters of TMP were investigated in brain microdialysates after oral and intravenous administration of TMP (4 mg/kg) to rats in the absence and presence of FA (5 mg/kg). Samples were collected at timed intervals for the measurement of TMP by a rapid and sensitive UPLC-MS/MS method.3. The pharmacokinetic parameters were calculated by noncompartmental analysis for brain microdialysates. The brain pharmacokinetic data for TMP showed significant increases in Cmax, t1/2, AUC0–inf and MRT0–inf after combination with FA. After intragastric administration with FA, there were significant decreases in the Tmax (from 38.33 ± 5.77 to 21 ± 5.48 min; p < 0.01) of TMP. This study indicated that potential drug–drug interaction between TMP and FA should be taken into consideration and the combined administration is beneficial in improving the bioavailability of TMP in the brain.

CAS / MDL: 723-46-6
研究领域: 药理学 · 中药学 · 神经科学
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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Target-Induced Horseradish Peroxidase Deactivation for Multicolor Colorimetric Assay of Hydrogen Sulfide in Rat Brain Microdialysis

Zhonghui Chen,Chaoqun Chen,Huawei Huang,Fang Luo,Longhua Guo,Lan Zhang,Zhenyu Lin,Guonan Chen

Hydrogen sulfide (H2S) is important for normal neural functions, which involves protecting neurons from oxidative stress and neuronal transmission modulation in brain. The detection of H2S is significant for revealing its role in the diagnosis of various disease. In this study, a novel multicolor colorimetric assay based on the etching of gold nanorods (Au NRs) is proposed to evaluate H2S level with the naked eye. This measurement relies on the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) via horseradish peroxidase (HRP) to produce TMB2+, which could etch the Au NRs quickly and accompany with a distinct color change. The vivid colors can be easily distinguished with the naked eye without any sophisticated instruments. The presence of H2S can cause the deactivation of HRP, which affects the amount of TMB2+ produced and consequently affects the color changing of the system. Based on this mechanism, a simple but sensitive multicolor colorimetric assay is developed for H2S detection with a linear range of 0.05–50 μM. The proposed method is demonstrated for monitoring extracellular H2S in rat brain coupled with microdialysate.

研究领域: 分析化学 · 神经科学 · 生物医学工程
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ANALYTICAL CHEMISTRY · 2014 · IF 5.825

Ratiometric Fluorescent Probe Based on Gold Nanoclusters and Alizarin Red-Boronic Acid for Monitoring Glucose in Brain Microdialysate

Lu-Liang Wang,Juan Qiao,Hui-Hui Liu,Jie Hao,Li Qi,Xiao-Ping Zhou,Dan Li,Zong-Xiu Nie,Lan-Qun Mao

Glucose monitoring with high sensitivity and accuracy in the cerebrospinal fluid is a challenge for evaluating the role of glucose in the physiological and pathological processes. In this work, a ratiometric fluorescent probe for sensing glucose was developed. In the probe, the gold nanoclusters protected by ovalbumin played the role as the reference of fluorophore and the Alizarin Red S-3-aminophenyl boronic acid immobilized on the poly(N-acryloxysuccinimide) acted as both the response signal and specific recognition unit for sensing glucose. Once the ratiometric fluorescent probe reacted with glucose in the biological system, its fluorescence intensity at 567 nm was quenched, while the fluorescence intensity at 610 nm was essentially unchanged. In addition, the prepared ratiometric fluorescent probe showed higher stability against environmental effects. As a result, the present ratiometric fluorescent probe was successfully used for monitoring of glucose in the rat brain following the cerebral calm/ischemia.

CAS / MDL: 9003-99-0 7440-38-2
研究领域: 分析化学 · 生物医学工程 · 神经科学
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ANALYTICAL CHEMISTRY · 2019 · IF 6.35

Sensitive Fluorescent Sensor for Hydrogen Sulfide in Rat Brain Microdialysis via CsPbBr3 Quantum Dots

Chaoqun Chen,Qing Cai,Fang Luo,Nuo Dong,Longhua Guo,Bin Qiu,Zhenyu Lin

The instability and insolubility of perovskite quantum dots in aqueous solution prohibit applications in polar solvents. As a highly toxic gas pollutant and also an endogenous gaseous signaling molecule existing in a variety of physiological processes, hydrogen sulfide (H2S), with high selectivity and high specificity, detection is of great significance. In this study, a simple device has been designed to separate H2S from aqueous solution and CsPbBr3 quantum dots (CsPbBr3 QDs) have been used as the detection probe to develop a novel fluorescent sensor for rapid H2S detection. The addition of hydrogen sulfide to the phosphoric acid solution results in the escape of H2S from the aqueous sample and hence it passing into the n-hexane solution containing CsPbBr3 QDs, resulting in the quenching of the fluorescence of CsPbBr3 QDs. The fluorescence intensity of the system has a linear relationship with the concentration of H2S in the range of 0–100 μM with the detection limit of 0.18 μM. The proposed system has been applied to detection of H2S in rat brain microdialysate with satisfying results. The potential mechanism regarding the quenching of fluorescence from CsPbBr3 QDs by H2S has been studied as well.

CAS / MDL: 1313-82-2
研究领域: 分析化学 · 生物化学 · 材料科学 · 毒理学
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Chinese Herbal Medicines · 2018 · IF 0

Comparative brain pharmacokinetic study of Jiaotai pills in normal and insomnic rats using brain microdialysis combinated with LC–MS/MS

Xiao-jun Zhang,Jia-hui Chen,Liang Luo,Wei He,Guang-hui Liu,Jing Gong,Yi-feng Zeng,Zhi-yong Xie,Qiong-feng Liao

Objective To compare the brain pharmacokinetics of five protoberberine-type alkaloids ( i.e. berberine , palmatine , coptisine , epiberberine, and jatrorrhizine), which were the main bioactive constituents of Jiaotai Pills (JTP), in normal and insomnic rats orally administrated with JTP. Methods The detection was conducted by a fully validated liquid chromatography-tandem mass spectrometry combinated with brain microdialysis method. Brain microdialysis probes were inserted into the hippocampus of rats. JTP extracts were administrated intragastrically and then brain microdialysates were collected at 30 min time intervals for 10 h. The separation of the five protoberberine-type alkaloids was carried out on a BDS Hypersil C 18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0) within 4 min. The quantification was performed by multiple reaction monitoring with the transitions of m / z 336.0-320.1 for berberine, m / z 352.0-336.1 for palmatine, m / z 338.0-322.1 for jatrorrhizine , m / z 336.0-320.1 for epiberberine, m / z 320.0-292.1 for coptisine and m / z 356.4-192.1 for IS. Results The lower limit of quantification for five protoberberine-type alkaloids was 0.05 ng/mL. Linearity, accuracy, precision, stability and matrix effect of five analytes were all satisfactory. Five protoberberine-type alkaloids were quickly distributed in the brain. Moreover, significant differences in the principal pharmacokinetic parameters such as AUC and T 1/2 of the analytes were observed between two groups. Conclusion The LC-MS/MS method combinated with microdialysis is useful in the brain pharmacokinetic study of five protoberberine-type alkaloids. The results indicated that the rates of analytes absorption in insomnic rats were significantly higher than those in normal rats. Besides, the protoberberine-type alkaloids could bring a direct effect on the neuron in the hippocampus.

CAS / MDL: 631-61-8
研究领域: 药理学 · 神经科学 · 分析化学
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Development of a dual-mode Ru-UiO-TPEA MOF probe for highly sensitive and accurate detection of Cu2+ in biological systems

Qian Long,Hanfeng Cui,Jing Zhang,Qiqi Fan,Ting Huang,Hai Shuai,Xiaocui Yin,Guobing Wei,Huanwen Chen,Hao Fan

Cu 2+ serves as a significant biomarker in various physiological processes. This study presents the development of a novel Ru-UiO-TPEA functionalized metal-organic framework (MOFs) probe for Cu 2+ detection, employing both electrochemiluminescence (ECL) and electrochemical (EC) methods. Employing a dual ligand-assisted energy transfer approach, we synthesized Ru-UiO with optimal ECL and EC properties by adjusting the synthesis ratio of biphenyldicarboxylic acid to Ru(dcbpy) 3 2+ . This was followed by its conjugation with N-(2-aminoethyl)-N, N′, N′-tris(pyridin-2-ylmethyl) ethane-1,2-diamine (AE-TPEA) to form the highly conjugated Ru-UiO-TPEA probe for Cu 2+ detection. As the Cu 2+ concentration increased, the probe exhibited a diminished ECL signal and an enhanced differential pulse voltammetry (DPV) signal. The dual-mode detection method enabled cross-validation of the ECL and EC signals, enhancing accuracy and effectively minimizing errors. The ECL and EC methods had detection limits of 0.26 nM (range: 1 nM to 10 μM) and 0.65 nM (range: 2 nM to 80 μM), respectively. Meanwhile, these two methods can effectively detect Cu 2+ in rat brain microdialysis fluid. Notably, the measured concentrations correlated well with those determined by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES), highlighting its potential in biological and clinical bioelectronic sensing applications.

研究领域: 分析化学 · 生物化学 · 生物医学工程 · 材料科学
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