ACS Sensors
·
2017
·
IF 0
Shushu Ding,Sumei Cao,Yingzi Liu,Ying Lian,Anwei Zhu,Guoyue Shi
Sensitive and selective monitoring of sialic acid (SA) in cerebral nervous system is of great importance for studying the role that SA plays in the pathological process of Alzheimer’s disease (AD). In this work, we first reported an electrochemical biosensor based on a novel stimuli-responsive copolymer for selective and sensitive detection of SA in mouse brain. Notably, through synergetic hydrogen-bonding interactions, the copolymer could translate the recognition of SA into their conformational transition and wettability switch, which facilitated the access and enrichment of redox labels and targets to the electrode surface, thus significantly improving the detection sensitivity with the detection limit down to 0.4 pM. Besides amplified sensing signals, the proposed method exhibited good selectivity toward SA in comparison to potential interference molecules coexisting in the complex brain system due to the combination of high affinity between phenylboronic acid (PBA) and SA and the directional hydrogen-bonding interactions in the copolymer. The electrochemical biosensor with remarkable analytical performance was successfully applied to evaluate the dynamic change of SA level in live mouse brain with AD combined with in vivo midrodialysis. The accurate concentration of SA in different brain regions of live mouse with AD has been reported for the first time, which is beneficial for progressing our understanding of the role that SA plays in physiological and pathological events in the brain.
研究领域:
神经科学
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分析化学
·
生物医学工程
✓ 已验证
DOI
ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
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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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Na Wei,Xian-En Zhao,Shuyun Zhu,Yongrui He,Longfang Zheng,Guang Chen,Jinmao You,Shu Liu,Zhiqiang Liu
This paper, for the first time, reported a simple, rapid, sensitive and environmental friendly ultrasonic-assisted in situ derivatization-dispersive liquid–liquid microextraction ( in situ UAD-DLLME) method followed by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of dopamine (DA), serotonin (5-HT) and their biosynthesis precursors and metabolites in rat brain microdialysates. In this work, a commercial reagent, Lissamine rhodamine B sulfonylchloride (LRSC), was proposed as a derivatization reagent. The ionization efficiency of neurotransmitters was greatly enhanced through the introduction of a permanent charged moiety of LRSC into their derivatives during electrospray ionization MS (ESI–MS) analysis. Parameters of in situ UAD-DLLME and UHPLC-MS/MS conditions were all optimized in detail. The optimum conditions of in situ UAD-DLLME were found to be as follows: a mixture of 150 μL of acetonitrile (dispersant) containing LRSC (derivatization reagents) and 50 μL of low toxic bromobenzene (extractant) was rapidly injected into an aqueous sample containing 30 μL of microdialysate and 800 μL of NaHCO 3 -Na 2 CO 3 buffer solution (pH 10.5) at 37 °C. After ultrasonication for 3 min and centrifuging for 2 min, the sedimented phase was conveniently injected for UHPLC–MS/MS analysis. Under the optimized conditions, good linearity was observed with the limits of detection (LODs, S/N>3) and limits of quantification (LOQs, S/N>10) in the range of 0.002–0.008 and 0.015–0.040 nmol/L, respectively. Meanwhile, it also brought good results of precision (3.2–13.0%, peak area RSDs %), accuracy (86.4–112%), recovery (73.9–105%), matrix effect (86.2–105%), and stability (3.1–8.8%, peak area RSDs %). The developed method was successfully applied for the simultaneous determination of multiple neurotransmitters, their precursors and metabolites in brain microdialysates of normal and L -DOPA induced dyskinesias (LID) rats.
研究领域:
神经科学
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分析化学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 2
·553
·
IF 4.6
Meng Yang,Jianxia Meng,Lu Han,Xiaoyan Yu,Zhimin Fan,Yongfang Yuan
Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the “first pass effect” of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components ofTripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin–blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three−layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.Keywords:triptolide;transdermal drug delivery;nanoemulsion gel;multiscale mathematical modeling;synchronous microdialysis
研究领域:
药剂学
·
药物代谢动力学
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中药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2013
·Vol. 138
·期 10
·3046-3052
·
IF 3.969
Xuming Zhuang,Dalei Wang,Lifen Yang,Ping Yu,Wei Jiang,Lanqun Mao
Simple and effective measurement of Mg2+ in the brain of living animals is of great physiological and pathological importance. In this study, we report a facile yet highly selective colorimetric method for effective sensing of cerebral Mg2+. The method is based on rational design of surface chemistry of gold nanoparticles (Au-NPs) with functional molecules including 1,4-dithiothreitol (DTT) and cysteine, enabling the fine tuning of the surface chemistry of Au-NPs in such a way that the addition of Mg2+ into the Au-NPs dispersion could selectively trigger the change of the dispersion/aggregation states of Au-NPs. The strong chelation interaction between Mg2+ and the hydroxyls in 1,4-dithiothreitol and the co-existence of cysteine on the surface of Au-NPs could, on one hand, enable the selective colorimetric detection of Mg2+ and, on the other hand, avoid the aggregation of Au-NPs induced by DTT itself. As a result, the addition of Mg2+ into the dispersion of the Au-NPs containing both cysteine and DTT results in the changes in both the color and the UV-vis spectra of the Au-NPs dispersion. The signal readout shows a linear relationship of Mg2+ within the concentration range from 1 μM to 40 μM with a detection limit of 800 nM (S/N = 3). Moreover, the assay demonstrated here is free from the interference of some physiological species commonly existing in rat brain. Although Ca2+ could interfere with the detection of Mg2+ because of its strong chelation with DTT, it could be selectively masked by masking agent (i.e., ethyleneglcol-bis (2-aminoethylether) tetraacetic acid). By combining the microdialysis technique, the basal dialysate level of Mg2+ is determined to be 299.2 ± 41.1 μM (n = 3) in the cerebral systems. The method essentially offers a new method for the detection of Mg2+ in the cerebral system.
研究领域:
神经化学
·
分析化学
·
纳米生物技术
·
分子探针
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金属离子传感
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活体分析
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2014
·
IF 5.825
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.
研究领域:
分析化学
·
生物医学工程
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
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.
研究领域:
分析化学
·
生物化学
·
材料科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Jinpeng,Cui Xinyuan,Zhao Shuo,Chang Zenghui,Zhang Junshuo,Chen Yufeng,Liu Jiale,Sun Guohao,Wang Yiyuan,Liu Yuanyuan
Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer’s disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model.Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group.Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.
研究领域:
药理学
·
神经科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2022
·Vol. 189
·期 2
·1-7
·
IF 6.408
Luo Fang,Zhang Yating,Zu Yexin,Li Shiqing,Chen Yiting,Chen Zhonghui,Huang Da,Qiu Bin,Lin Zhenyu
A good water-soluble and stable nanocomposite has been facilely prepared by the encapsulation of CsPbBr 3 QDs via cetyltrimethylammonium bromide and mineral oil through sonication, namely CsPbBr 3 @CMO nanocomposite. Such method is very quick and simple without complicated instruments and strict conditions. The results reveal that the synthesized CsPbBr 3 @CMO nanocomposite is spherical with uniform size and shows remarkably good solubility and stability in water. Specifically, the fluorescent intensity of CsPbBr 3 @CMO nanocomposite in water is decreased by 0.76% after 3 h; this result is comparable with those in earlier studies, and the good stability in water might be owned to the hydrophobic core of the CsPbBr 3 @CMO nanocomposite. The prepared CsPbBr 3 @CMO nanocomposite has been applied as a sensitive fluorescent probe for monitoring hydrogen sulfide (H 2 S), and the fluorescence intensity (~ 524 nm) has a linear relationship with the concentration of H 2 S in the range 0.15–105 µM with a detection limit of 53 nM, demonstrating application for monitoring H 2 S in rat brain coupled with microdialysis apparatus with satisfied results. The present study not only provides a simple but sensitive approach for the detection of H 2 S in living body, but also paves the way for expanding the application of CsPbBr 3 QDs to aqueous medium. Graphical abstract
研究领域:
纳米技术
·
材料科学
·
分析化学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2018
·
IF 0
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.
研究领域:
药理学
·
神经科学
·
分析化学
✓ 已验证
产品关联
DOI
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Yihui Hu,Wenjing Guo,Yubin Ding,Hanjun Cheng,Hui Wei
The detection of heparin (Hep) and its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance in clinics but remains challenging. Here, we report a sensitive and selective time-resolved luminescence (TRL) biosensing system for Hep by modulating the photoluminescence of Tb 3+ with guanine-rich ssDNA and Hep-specific AG73 peptide (RKRLQVQLSIRT). With the developed system, Hep including both unfractionated Hep (UFH) and the low molecular weight Hep (LMWH) has been successfully detected with a satisfactory detection limit. Owing to the highly specific interaction between Hep and AG73 peptide, major interfering substances in Hep detection, such as Hep analogs of chondrotin sulfate (Chs) and hyaluronic acid (HA), did not interfere with Hep detection. The established TRL sensing system was then successfully used for monitoring Hep metabolism in living rats by microdialysis . Moreover, the proposed TRL sensing system was further applied to analyze OSCS contaminant in Hep with heparinases treatment by exploring the inhibition effects of OSCS on the activity of heparinases. As low as 0.002% of OSCS in Hep was identified.
研究领域:
分析化学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Yu Du,Chang Li,Shouchao Xu,Jiehong Yang,Haitong Wan,Yu He
Background Astragali Radix-Safflower combination (ARSC) is widely utilized in clinic to treat cerebral ischemia/reperfusion injury (CI/RI). Whereas, there is no in-depth research of the pharmacokinetics (PK) and pharmacodynamics (PD) analysis of ARSC after intragastric administration in rats with CI/RI. Purpose The purpose of this research is to investigate the PK characteristics of eight active ingredients (astragaloside IV, calycosin , calycosin-7-O-β-glucoside, formononetin , ononin , hydroxysafflor yellow A, syringin and vernine) of ARSC, and the regulation of neurotransmitters disorders, revealing the pharmacodynamic substance basis and the mechanism of ARSC in treating CI/RI from the molecular level. Methods We established a new method which based on blood-brain dual channel microdialysis (MD) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to continuously gather, and determine the components of ARSC and neurotransmitters related to CI/RI in vivo . The collected data were analyzed by sigmoid-E max function. The neurotransmitters primarily regulated in CI/RI rat were discussed by principal component analysis and the compound most associated with total pharmacodynamics was chosen by partial least squares regression . Results The validated LC-MS/MS method had specificity and selectivity to simultaneously analyze the concentration of eight active components of ARSC extract and five neurotransmitters of CI/RI rats. The recovery rates of brain MD probe and blood MD probe were stable within six hours. The MD probes recovery rates decreased with the increase of flow rates, but the solution concentration had little effect on the probes recovery rates. It was feasible to correct the recovery rates of probes in vivo by using reverse dialysis method. All eight active ingredients of ARSC could pass across the blood brain barrier after CI/RI. ARSC regulated the release of glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT) and aspartic acid (Asp). Notably, astragaloside IV and hydroxysafflor yellow A might have better regulatory effect on neurotransmitters in comparison with other six measured components of ARSC, and Glu was the neurotransmitter mainly regulated in CI/RI rats. Conclusion The ARSC was able to treat CI/RI through ameliorating neurotransmitters disorders. There was a hysteresis between the peaked drug concentration and maximum therapeutic effect of ARSC. The drug effective concentrations range of ASIV, calycosin, calycosin-7-O-β-glucoside, syringin and vernine in blood microdialysate and calycosin, syringin, vernine in brain microdialysate were narrow, which need be paid attention in clinical use.
研究领域:
药理学
·
神经科学
·
分析化学
·
中医药学
✓ 已验证
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）