American Journal of Translational Research
·
2024
·Vol. 16
·期 12
·8008
·
IF 1.7
Yalan Zuo,Peidan Yang,Ruixia Yang,Juan Hou,Rui Feng,Ping Liang,Jiang Liu
Objectives: The aim of this study was to establish an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the detection of osimertinib in rat plasma, lung and brain tissues. Methods: Forty-eight rats were randomly divided into an experimental group (receiving osimertinib at doses of 5, 8, and 10 mg/kg) and a control group. After continuous intragastric administration for 15 days, samples of blood, lung, and brain tissue were collected. Chromatographic separation was achieved using a BEH C18 column with gradient elution, employing a mobile phase of water (containing 0.1% (v/v) formic acid) and acetonitrile. The concentration of osimertinib in the samples was determined using an AB SCIEX 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) mode. Results: A UPLC-MS/MS analytical method for determining osimertinib concentrations was successfully established and validated. A linear relationship was observed for osimertinib concentrations in plasma within the range of 1-300 ng/mL, and in lung and brain tissues within the range of 0.5-50 ng/mL. The selectivity, accuracy, precision, matrix effect, extraction recovery, and stability all meet the requirements of methodological validation criteria. Conclusions: A rapid and sensitive UPLC-MS/MS method was developed and validated for quantifying osimertinib concentrations in rat plasma, lung, and brain tissues, providing a valuable tool for pharmacokinetic and tissue distribution studies.
研究领域:
药理学
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分析化学
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药物代谢动力学
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DOI
PubMed
高影响因子
XENOBIOTICA
·
2024
·
IF 1.3
Danqing Wu,Rui Luo,Yangnan Chen,Zhiyun Zheng,Shuangying Gui,Ning He
This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson’s disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson’s disease, a long-term chronic condition.
研究领域:
药理学
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神经科学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Yongyin Zhou,Hui Li,Hongjun Luo,Zhexuan Lin,Wenhong Luo
An untargeted UHPLC-MS method was developed for the preliminary screening of differential amino acids between two mouse brain tissue samples, and a targeted UHPLC-MS/MS method was developed for the quantitative determination of amino acids in mouse brain tissue samples. The sample processing procedure, chromatographic conditions and MS parameters were optimized. The mouse brain tissue samples were homogenized with HCl solution (0.01 mol/L), protein precipitated with methanol and centrifugation. For the untargeted method, one sample was derivatized with butanol (D0) and another sample was derivatized with deuterated butanol (D9), then combined together and analyzed with UHPLC-MS. Chromatographic peak area ratio for each amino acid was then used for differential analyses between two samples. Results showed good accuracy with standard spiked samples (83.4–113.0 %). For the targeted quantitative method, the sample supernatants were dried and residues were derivatized with butanol (D0). Internal standards of amino acids derivatized with deuterated butanol (D9) were added before analyzed with UHPLC-MS/MS. The intra- and inter-day precisions were in the intervals of 0.5–8.1 % and 0.3–9.1 %. The LOD and the LOQ were ranged from 0.03 × 10 −3 to 0.92 × 10 −3 µg mL −1 and 0.08 × 10 −3 to 3.08 × 10 −3 µg mL −1 , respectively. Spiked recoveries were from 96.8 % to 111.7 %. Both methods were applied to analyze amino acids in brain tissue of C57BL/6 mice treated and untreated with piperine and the result showed that the levels of glutamic acid, aspartic acid, histidine, asparagine, γ-aminobutyric acid, alanine, leucine and isoleucine significantly decreased in the piperine treated group comparing with the untreated group.
研究领域:
分析化学
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神经生物学
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药理学
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产品关联
DOI
高影响因子
Analytical Methods
·
2015
·Vol. 7
·期 5
·1971-1976
·
IF 1.821
Yahong Chen,Gongke Li,Yufei Hu
In this paper, a novel electrochemical method is proposed for the determination of 5-hydroxytryptophan (5-HTP) based on a carbon nanosheets (CNSs)-modified electrode. The CNSs were prepared by a one-step flowing electrolysis using a home-made device. The surface morphology and composition of the CNSs were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The cyclic voltammetry method was used to study the electrochemical behavior of 5-HTP on the CNSs-modified electrode. The results suggested that the modified electrode exhibited high electrocatalytic activity, and that the anodic peak current of 5-HTP was significantly enhanced on the modified electrode. A differential pulse voltammetry method was developed for the determination 5-HTP at the modified electrode. In the optimum experimental conditions, the linear calibration range varied from 5 × 10−8 mol L−1 to 1 × 10−6 mol L−1, with a detection limit of 3 × 10−8 mol L−1. The proposed method was further successfully applied for the determination of 5-HTP in rats' brain tissue samples, with the recovery ranging from 90.3% to 98.0%.
研究领域:
分析化学
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神经生物学
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产品关联
DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2023
·Vol. 415
·期 23
·5575-5588
·
IF 4.3
Liu Yuanyuan,Han Yutong,Zhu Wenjie,Luo Qingming,Yuan Jing,Liu Xin
Glycosylation is one of the most common types of post-translational modifications in mammals. It is well known that N-glycans play a key role in cell adhesion, differentiation, synapsis, and myelination during the development of the mammalian central nervous system (CNS). Neuropathological symptoms (such as epilepsy and Alzheimer’s disease) are usually accompanied by N-glycosylation changes. In this study, we extracted N-glycan chains from eight regions of the mouse brain, and combined high-throughput, high-resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) with the Fmoc N-hydroxysuccinimide ester (Fmoc-OSU) derivatization method to improve the sensitivity of glycan detection to characterize the total N-glycans in the mouse brain. A total of 96 N-glycan moieties were detected. An exhaustive examination of the relative abundance of N-glycans, coupled with a comparative analysis of differences, has uncovered discernible variations of statistical significance, including high mannose, fucosylated, sialylated, and galactosylated N-glycans. According to our investigations, a thorough and regionally specific cartography of glycans within the brain can facilitate the investigation of glycan-mediated mechanisms related to both the developmental trajectory and functional output of the brain. Additionally, this approach may serve as a basis for identifying potential biomarkers that are relevant to various brain-associated pathologies. Graphical Abstract
研究领域:
生物化学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 8
·3569
·
IF 4.9
Fu Zeng,Lian Huang,Ding Han,Renjie Liu,Kongjia Zhang,Yuwen Su,Tong Su,Yarong Lin,Jianbo Xiu
Recent advances in tissue clearing chemistry have revolutionized three-dimensional imaging by enabling whole-organ antibody labeling, even in thick human tissue samples. However, these techniques face limitations, including reduced clearance efficiency in thick tissue blocks, prolonged processing times, and other challenges specific to formalin-fixed human brain tissue, such as autofluorescence due to the presence of lipofuscin, neuromelanin pigments, and residual blood. To address these challenges, we have developed an improved SHANEL procedure, iSHANEL, which is compatible with brain tissue from multiple species, including nonrodents. iSHANEL significantly enhances the tissue transparency. It effectively removes lipids, particularly sphingolipids, from brain tissue across different species. For brain vasculature imaging, it offers the better visualization of vascular structures at high magnification, reducing light scattering and background noise. Moreover, iSHANEL can be effectively applied to large tissue from pigs and cynomolgus monkeys, and it preserves protein immunogenicity well, as evidenced by immunostaining with the microglia-specific marker IBA-1. We also investigated methods to reduce blood vessel autofluorescence. Overall, iSHANEL provides an improved procedure for the high-resolution 3D imaging of brain tissue across multiple species.
研究领域:
神经科学
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生物化学
·
显微成像
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产品关联
DOI
PubMed
高影响因子
Cell Reports Methods
·
2024
·
IF 4.3
Weiwei Xue,Huijuan Li,Jinhong Xu,Xiao Yu,Linlin Liu,Huihui Liu,Rui Zhao,Zhicheng Shao
Human brain tissue models and organoids are vital for studying and modeling human neurological disease. However, the high cost of long-term cultured organoids inhibits their wide-ranging application. It is therefore urgent to develop methods for the cryopreservation of brain tissue and organoids. Here, we establish a method using methylcellulose, ethylene glycol, DMSO, and Y27632 (termed MEDY) for the cryopreservation of cortical organoids without disrupting the neural cytoarchitecture or functional activity. MEDY can be applied to multiple brain-region-specific organoids, including the dorsal/ventral forebrain, spinal cord, optic vesicle brain, and epilepsy patient-derived brain organoids. Additionally, MEDY enables the cryopreservation of human brain tissue samples, and pathological features are retained after thawing. Transcriptomic analysis shows that MEDY can protect synaptic function and inhibit the endoplasmic reticulum-mediated apoptosis pathway. MEDY will enable the large-scale and reliable storage of diverse neural organoids and living brain tissue and will facilitate wide-ranging research, medical applications, and drug screening.
研究领域:
神经科学
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生物技术
·
疾病建模
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2020
·
IF 8.352
Youguo Liao,Qiulin He,Feifei Zhou,Yi Hong,Xinyu Wu,Haoyu Wu,Xianzhu Zhang,Varitsara Bunpetch,Jingwei Zhang,Guo Ye,Weiliang Shen,Shufang Zhang,Hongwei Ouyang
Large area skull defects accompanied by craniocerebral injury are life-threating diseases that are difficult to treat due to the large area of damage and intracranial hypertension. An autologous bone is an ideal source for the regeneration of bone, including skull defects. However, two-step treatment, including craniectomy and cranioplasty, is the main strategy in clinical practice to stabilize intracranial pressure, but still remains a huge obstacle in both the preservation of auto-bone fragments and protection of exposed brain tissue. In this study, an elastic auto-bone patch was developed to provide a new and one-step method for repairing large skull defects which are currently repaired with two stages of surgery. The elastic auto-bone patch is formed by bonding auto-bone fragments together using hydrogels, which is then re-implanted to bone defects to repair large skull defects. The auto-bone patch could adapt to changes in intracranial pressure to protect brain tissue for damage, integrate well with surrounding bone tissues, and promote bone regeneration. After 8 weeks implantation, the large-size skull defect is filled with new formed bone tissues in the group of treating with auto-bone patch. This study introduced a new procedure on the application of elastic auto-bone patch to repair large area skull defects.
研究领域:
医学
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生物材料学
·
神经科学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Yan Zhou,Jia Liu,Tingting Zheng,Yang Tian
The aggregation of Aβ has been reported to closely correlate with Alzheimer’s disease (AD). However, clear monitoring of the entire aggregation process of Aβ from monomer to fibril has been scarcely reported until now. Herein, we developed a label-free ratiometric surface enhanced Raman spectroscopic (SERS) platform for real-time monitoring of the entire process of Aβ aggregation in neurons and brain tissues. Different gold nanoparticles, generated in situ with Aβ monomer and fibril as templates separately, were served as effective SERS substrates to achieve a high sensitivity with a limit of detection (LOD) down to 70 ± 4 pM and 3.0 ± 0.5 pM for Aβ40 monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of Aβ monomer and fibril (I1244/I1268) realized real-time monitoring of the entire aggregation process of Aβ monomer with high accuracy and selectivity against other proteins and amino acids. The significant analytical performance of the developed platform, together with good biocompatibility, long-term stability, and remarkable spatial resolution, enabled the present SERS platform imaging and real-time monitoring and imaging of Aβ aggregation influenced by different metal ions (Cu2+, Zn2+, and Fe3+) in neurons and brain tissues at the single cell level. Our results suggested that Cu2+ and Zn2+ ion of low concentration (10 μM) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 μM) showed inhibition of fibrosis.
研究领域:
生物化学
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医学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Bin Jiao,Huimin Ye,Xinwei Liu,Jiexun Bu,Junhan Wu,Wenpeng Zhang,Yunfeng Zhang,Zheng Ouyang
The development of miniature mass spectrometry (MS) systems with simple analysis procedures is important for the transition of applying MS analysis outside traditional analytical laboratories. Here, we present Mini 14, a handheld MS instrument with disposable sample cartridges designed based on the ambient ionization concept for intrasurgical tissue analysis and surface analysis. The instrumentation architecture consists of a single-stage vacuum chamber with a discontinuous atmospheric interface and a linear ion trap. A major effort in this study for technical advancement is on making handheld MS systems capable of automatically adapting to complex conditions for in-field analysis. Machine learning is used to establish the model for autocorrecting the mass offsets in the mass scale due to temperature variations and a new strategy is developed to extend the dynamic concentration range for analysis. Mini 14 weighs 12 kg and can operate on battery power for more than 3 h. The mass range exceeds m/z 2000, and the full peak width at half-maximum is Δm/z 0.4 at a scanning speed of 700 Th/s. The direct analysis of human brain tissue for identifying glioma associated with isocitrate dehydrogenase mutations has been achieved and a limit of detection of 5 ng/mL has been obtained for analyzing illicit drugs in blood.
研究领域:
分析化学
·
医学技术
·
人工智能应用
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MASS SPECTROMETRY
·
2022
·Vol. 57
·期 3
·e4813
·
IF 2.394
Liutian Wu,Keke Qi,Minggao Xu,Chengyuan Liu,Yang Pan
Desorption electrospray ionization/post-photoionization (DESI/PI) is a newly developed ionization method by the combination of DESI and post-photoionization for the simultaneous imaging of polar and nonpolar compounds in biological tissues. Dopants are of great importance in DESI/PI for the enhancement of signal intensities through ion–molecule reactions. In this work, to evaluate the performance of dopants in DESI/PI, an efficient homogenate model was developed, and four kinds of dopants (toluene, chlorobenzene, bromobenzene, and anisole) were tested using homogenate of mouse brain tissue as target sample. The influences of the dopants on the signal enhancements of different compounds were explained reasonably by the ionization mechanism. Then, the dopants with their optimum volume contents were applied to the mass spectrometry imaging (MSI). For a comprehensive imaging of various compounds with different polarities, methanol/toluene/formic acid (7:3:0.1) was chosen as the best choice. Finally, the stronger quantitative ability of DESI/PI with toluene as dopant for a few compounds in mouse brain tissue was demonstrated.
研究领域:
分析化学
·
生物医学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Hong Huang,Huiru Li,Yong Zhang,Xuhan Xia,Ningwen Zhang,Haixin Fan,Longhua Guo,Yongyong Cao,Hu Pan,Ruijie Deng,Yangang Wang,Rodrigo Ledesma-Amaro,Jianguo Xu
Cellular redox homeostasis and energy metabolism in the central nervous system are associated with neurodegenerative diseases. However, their real-time and concurrent monitoring in thick tissues remains challenging. Herein, a single dual-emission two-photon fluorescent probe (named DST ) is designed for the simultaneous tracking of tyrosinase (TYR) and adenosine triphosphate (ATP), thereby enabling the real-time monitoring of both neurocellular redox homeostasis and energy metabolism in brain tissue. The developed DST probe exhibits excellent sensitivity and selectivity toward TYR and ATP, with distinctive responses in the blue and red fluorescence channels being observed without spectra crosstalk. Using this probe, the correlation and regulatory mechanism between TYR and ATP during oxidative stress are uncovered. Additionally, the two-photon nature of this probe allows alterations in the TYR and ATP levels to be monitored across different brain regions in an Alzheimer's disease (AD) mouse model. Notably, a significant decrease in ATP levels is revealed within the somatosensory cortex (S1BF) and caudate putamen brain regions of an AD mouse, alongside an increase in TYR levels within the S1BF and laterodorsal thalamic nucleus brain regions. These findings indicate the potential of applying the spatially resolved regulation of neurocellular redox homeostasis and energy metabolism to treat neurodegenerative diseases.
研究领域:
神经科学
·
分析化学
·
医学
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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）