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MOLECULES · 2014 ·Vol. 19 ·期 4 ·4857-4879 · IF 2.095

Identification of Absorbed Constituents in the Rabbit Plasma and Cerebrospinal Fluid after Intranasal Administration of Asari Radix et Rhizoma by HS-SPME-GC-MS and HPLC-APCI-IT-TOF-MSn

Chen Li,Feng Xu,De-Mei Xie,Yu Jing,Ming-Ying Shang,Guang-Xue Liu,Xuan Wang,Shao-Qing Cai

Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat numerous diseases for over two millennia. It has many advantages compared with other routes. In this article, headspace-solid phase microextraction-gas chromatography-mass spectrometry and high performance liquid chromatography-atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass spectrometry were applied for the first time to analyze the absorbed constituents in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14 monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nineN-alkylamides and eight lignans were tentatively identified in the rabbit plasma and CSF. Thirty-three absorbed constituents are found to have different bioactivities related to the pharmacological actions of AR through bibliography data retrieval. These indicated that many types of constituents of TCM can be absorbed at the nasal cavity into both rabbit blood and CSF. This is the first study to explore the absorption of AR, and comprehensively analyze the absorbed constituents after intranasal administration of TCM. These findings extend our understanding of the effective substances of AR, and inspire us to make a hypothesis on the mechanism of additive effect of multiple constituents of TCMs, which is very worthy of further investigation.Keywords:nasal therapy;Asarum heterotropoidesvar.mandshuricum;intranasal administration;effective substance;cerebrospinal fluid;absorption;SPME;GC-MS;LC-MS;additive effect

CAS / MDL: 6443-69-2
研究领域: 中药学 · 分析化学 · 药理学
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JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES · 2024 ·Vol. 79 ·期 3 · IF 4.3

PFASs May Risk Alzheimer’s Disease

Wang He-Ling,Fang Evandro F

We are now living in an aging society with increasingly older population, many of whom are suffering with or are at a high risk of developing dementia (1,2). Alzheimer’s disease (AD) is the world’s most common type of dementia, affecting about 50 million individuals worldwide currently, with that number set to rise to 82 million by 2023. There is a huge challenge in developing an anti-AD drug, and an enormous amount of effort has been devoted to this branch of research. It is encouraging that the 2 recently described anti-Aβ antibodies, lecanemab and donanemab, show clear benefits in slowing cognitive decline in patients with early-stage disease; however, rare but severe side effects (such as brain bleeding and swelling) still occur (10.1126/science.adj8110), indicating that there is likely a longway to go in developing a cure for AD (3,4).Although the hunt is on to develop an anti-AD drug to stop disease progression, it is also important and necessary to focus on prevention. It has been reported that lifestyle patterns and environmental toxins (natural and anthropogenic) increase the risk of dementia, with some estimates noting up to a 30% increase in AD risk. These factors are modifiable and reducing such risks could prevent or slow down the onset of dementia (5,6). Environmental toxins cover a broad spectrum of chemicals, including pesticides (organochlorine and organophosphate insecticides), toxic metals (such as aluminum), air pollutants, and especially industrial chemicals (6). Although we are exposed to trace amount of these contaminants during our daily lives, a lifelong accumulation could presumably reach to a toxic level, jeopardizing neuronal function and brain health.Per- and polyfluoroalkyl substances (PFASs) are a group of man-made chemicals that have been widely used in consumer products around the world since the 1950s. They have been very widely used and closely linked to our daily lives, being used, for example, on fabrics to provide stain resistance, and on cookware to keep food from sticking to it. While PFAS compounds facilitate our lives, they have brought environmental challenges with them, mainly due to their broad application, vast numbers (there are thousands of fluoroalkyl chemical compounds), and due to a chain of linked carbon and fluorine atoms that result in very slow breakdown over time, a long lifespan (7). Due to its widespread use, humans have been widely exposed to these chemicals, many of which can now be found in blood and cerebrospinal fluid (CSF) samples. In combination with data from laboratory animals, it is suggested these chemicals may cause a series of health issues, as summarized in Figure 1 (7,8).In this issue, Delcourt and colleagues (9) present a small human study showing patients with high CSF PFASs correlate with AD. Here, using the CSF samples from 8 patients hospitalized with suspected normal pressure hydrocephalus, they checked levels of 18 of the most common PFAS molecules. PFASs were detected in all 8 CSF samples, and a correlation was seen between high PFOS (perfluorooctane sulfonate) and cognitive impairment among the tested individuals. This discovery brings with it a sense of urgency in reducing exposure to PFASs in our daily lives and highlights the risks that it may bring in terms of our brain health. As this is a small-size proof-of-concept study, further large-size clinical validation and underlying molecular investigation are needed.E.F.F. is supported by Cure Alzheimer’s Fund (#282952), HELSE SØR-ØST (#2020001, #2021021, #2023093), the Research Council of Norway (#262175, #334361), Molecule AG/VITADAO (#282942), NordForsk Foundation (#119986), the National Natural Science Foundation of China (#81971327), Akershus University Hospital (#269901, #261973, #262960), the Civitan Norges Forskningsfond for Alzheimers sykdom (#281931), the Czech Republic-Norway KAPPA programme (with Martin Vyhnálek, #TO01000215), the Rosa sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society (#207819), and Wellcome Leap (#104617).E.F.F. is the co-owner of Fang-S Consultation AS (Organization number 931 410 717); he has an MTA with LMITO Therapeutics Inc. (South Korea), a CRADA arrangement with ChromaDex (United States), a commercialization agreement with Molecule AG/VITADAO; he is a consultant to Aladdin Healthcare Technologies (United Kingdom and Germany), the Vancouver Dementia Prevention Centre (Canada), Intellectual Labs (Norway), MindRank AI (China), and NYO3 (Norway and China). H-L.W. declares no conflict of interest.

研究领域: 神经科学 · 环境健康 · 医学
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STAR Protocols · 2025 · IF 1.3

Protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms

Hongyu Xu,Zetian Jia,Junhui Liu,Runming Liu,Wei Wei,Xiang Li

Summary Gut-microbiome-combined metabolomics studies in cerebrovascular disease highlight the microbiota-gut-brain axis in neurological disorders. Here, we present a protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms. We describe steps for sample collection, fecal genomic DNA extraction, rRNA PCR amplification, sequencing library construction, and rRNA sequencing. We then detail procedures for metabolite extraction, liquid chromatography-tandem mass spectrometry (LC-MS/MS) non-targeted metabolomics sequencing, and ELISA for cerebrospinal fluid and plasma samples. Finally, we perform combined multi-omics analysis. For complete details on the use and execution of this protocol, please refer to Xu et al. 1

CAS / MDL: 103616-89-3
研究领域: 神经病学 · 微生物组学 · 代谢组学
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FOOD AND CHEMICAL TOXICOLOGY · 2023 · IF 4.3

Oral exposure to an acceptable daily intake dose of aspartame induced a delayed proinflammatory cytokine response in the cerebrospinal fluid of rats

Xiaoyi He,Qianyi Zhong,Kai Yan,Guoying Li,Junhua Yang

This study aimed to investigate the effect of exposure to aspartame (ASP) at safe levels on proinflammatory cytokines in the cerebrospinal fluid (CSF) of rats. Sprague Dawley rats were sacrificed after 1, 2, 4 or 8 week(s) of continuous exposure to ASP (40 mg/kg body weight). Serum, CSF and brain tissue samples were prepared, and the levels of the IL-1β, IL-6 and TNF-α were analyzed by ELISA . In serum, the levels of all three cytokines showed a two-phase alteration, a decrease followed by an increase in the ASP group. In the brain, their levels increased from the second or fourth week compared with the control group. In CSF, the levels of these cytokines showed a similar change to that in brain tissue, but the increase appeared at a later time point. For each cytokine, there was a significant positive correlation between its levels in serum, brain tissue and CSF. This is the first discovery that ASP exposure increased the levels of proinflammatory cytokines in CSF in rats, which emerged later than in blood and brain tissue. This study suggests the necessity of conducting related clinical studies to evaluate potential neuroinflammatory effects induced by chronic ASP exposure through CSF analysis.

研究领域: 神经科学 · 免疫学 · 毒理学
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JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY · 2020 ·Vol. 71 ·期 6 · IF 2.644

New scheme for the preparation and use of artificial cerebrospinal fluid

W-H Zheng,C Yan,T Chen,D-Z Kang

This study aimed to explore a set of simplified schemes for the preparation and application of artificial cerebrospinal fluid (ACSF) to improve the experiment efficiency and neurosafety of ACSF. We prepared ACSF into parts A and B, according to the cerebrospinal fluid (CSF) data in rabbits. They were mixed in equal volumes to form ACSF, continous foaming with mixture gas (95% O 2 and 5% CO 2 ). Sampling inspection showed the chemical stability of ACSF in the three months after preparation. However, it needed to be kept continous foaming, as pH is correlated to the solubility of CO 2 . We further improved the application scheme by sealing the foamed ACSF in infusion bags filled with mixture gas, which could keep the pH stable for 24 hours. It was helpful in promoting the progress of clinical and experimental research relating to ACSF.

研究领域: 神经科学 · 实验医学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Determination of olverembatinib in human plasma and cerebrospinal fluid by an LC-MS/MS method: Validation and clinical application

Dong Xiang,Tinghui Zhao,Jue Wang,Yang Cao,Qiuxia Yu,Lu Liu,Hengyi Yu,Xiping Li,Ninghong Li,Yang Yi,Xuepeng Gong

A sensitive and robust LC-MS/MS method has been developed and validated for olverembatinib quantification in human plasma and cerebrospinal fluid (CSF). The method involved liquid-liquid extraction with methyl tertiary butyl ether for plasma pretreatment and precipitation enrichment with methanol for CSF pretreatment. Separation was achieved on the C18 column with gradient elutions of 10 mM ammonium formate in water and methanol-acetonitrile (50:50,v/v). Analyte detection was conducted by electrospray ionization (ESI) in a positive ion mode using multiple reaction monitoring (MRM). The m/z transitions were 533.4→433.2 for olverembatinib and m/z 502.4→394.2 for the internal standard (IS, Imatinib-d8). Calibration curves ranged from 0.500 to 50.0 ng/mL for plasma and from 0.0100 to 1.00 ng/mL for CSF. The intra- and inter-day precision and accuracy were < 15% for both plasma and CSF with four different quality control concentrations. The relative matrix effect was < 10% in plasma and artificial CSF. This method was successfully utilized for the measurement of olverembatinib concentrations in plasma and CSF from chronic myeloid leukemia patients.

CAS / MDL: 540-69-2
研究领域: 药理学 · 分析化学 · 肿瘤学
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Bioanalysis · 2025 · IF 1.8

LC-MS/MS quantification of nusinersen in rat cerebrospinal fluid and preclinical pharmacokinetics study application

Yujie Li,Shu Zhang,Xiayi Wang,Xiaochuan Li,Lizhong Guo

Background Background: An oligonucleotide drug named nusinersen sodium is used to treat Spinal Muscular Atrophy (SMA), requires accurate detection for therapeutic research. There are no published reports on liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting nusinersen in rat cerebrospinal fluid (CSF).Methods An LC-MS/MS method has been created and verified to detect nusinersen in Sprague-Dawley (SD) rat CSF. The method employed solid-phase extraction for post-extraction analysis and used dT20 as an internal standard. Negative ion multiple reaction monitoring (MRM) mode scanning and the electrospray ionization (ESI) source were used. The method was validated over a concentration range of 5–2000 ng/mL with a Lower Limit of Quantification (LLOQ) of for nusinersen at 5 ng/mL.Results and conclusions The method achieves extremely high accuracy and precision, good linearity, high extraction recovery, and provides a useful approach for evaluating the pharmacokinetics of nusinersen in rats.

研究领域: 分析化学 · 药代动力学 · 神经药理学 · 质谱分析
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2015 · IF 2.979

Preparation of a pipette tip-based molecularly imprinted solid-phase microextraction monolith by epitope approach and its application for determination of enkephalins in human cerebrospinal fluid

Hua Li,Dan Li

In this study, a novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of enkephalins was synthesized and prepared in a micropipette tip using epitope imprinting technique. The synthesized MIPs were characterized by scanning electron microscope (SEM) and infrared spectroscopy. A molecularly imprinted solid-phase microextraction (MISPME) method was developed for extraction of enkephalins in aqueous solutions. The parameters affecting MISPME were optimized. The results indicated that this MIP monolith exhibited specific recognition capability, high enrichment efficiency and excellent reusability for enkephalins. MALDI-TOF MS analysis demonstrated that this MIP monolith can act as a useful tool for highly selective purification and enrichment of enkephalin, a kind of low abundance protein, from high-abundance proteins in human cerebrospinal fluids (CSF). Employed this MIP monolith as solid-phase microextraction column, quantitative assay of enkephalins in human CSF was developed by HPLC–ultraviolet (UV) detection in this work. The detection limits were 0.05–0.08   nM. This MISPME/HPLC–UV method was used to quantify Met-enkephalin and Leu-enkephalin levels in the CSF of patients with cancer pain.

研究领域: 分析化学 · 医学 · 生物化学
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY · 2024 · IF 11.2

Janus orthogonal nanofiber membrane containing CPP@PDA for skull base reconstruction

Xiaomei Xia,Ziyang Liu,Hongshui Wang,Yazhou Hu,Werner E.G. Müller,Xiaohong Wang,Kun Qin,Jiantao Zheng,Huan Zhou,Lei Yang,Chunyong Liang

In neurosurgery procedures, cerebrospinal fluid leakage is a commonly encountered complication. Reconstructing skull base defects with patch materials can reduce the risk of cerebrospinal fluid leakage which can lead to serious issues such as infection, meningitis, arachnoiditis, and delayed wound healing. An ideal skull base reconstruction material should not only serve as a leak-proof barrier but also promote skull base bone regeneration. To fulfill this challenge, this research designed and fabricated a Janus orthogonal bilayer nanofiber membrane (OPCL/PG-PCPP). The aligned PCL (APCL) nanofibers were constituted as the top layer to resist cerebrospinal fluid leakage, while the perpendicular PCL/gelatin (APG) fibers with calcium polyphosphate encapsulated polydopamine nanoparticles (CPP@PDA, labeled as PCPP) were designed as the bottom layer (APG-PCPP) to facilitate osteoblast migration and osteogenic differentiation. Among these, APG-1%PCPP nanofibers demonstrated the most effective induction of osteogenic differentiation in bone marrow mesenchymal stem cells (rBMSCs). Subsequent in vivo animal experiments revealed that the bone surface area (BS), bone volume fraction (BV/TV), and number of trabeculae (Tb.N) in the APG-1%PCPP group were twice as high as those in the control group, which confirmed the good osteogenic potentials. Therefore, due to its unique leak-proof and osteoinductive properties, the OPCL/PG-PCPP membrane holds promise as an applicable skull base reconstruction material in the field of neurosurgery.

研究领域: 神经外科 · 生物材料学 · 组织工程学
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Materials Today Bio · 2025 · IF 10.2

Janus adhesive bio-patches with targeted drug delivery enabled anti-bacteria and pro-angiogenesis for dura mater repair

Yirizhati Aili,Pengfei Wei,Xueqiao Yu,Guofeng Fan,Nuerailijiang Maimaitiaili,Yunhuan Li,Siqi Liu,Yiqian Huang,Bo Zhao,Zengliang Wang,Hu Qin,Yongxin Wang

Dural injuries often result in severe complications such as cerebrospinal fluid (CSF) leakage, intracranial infections, and brain herniation, which significantly impact patient recovery and quality of life. Conventional dural repair materials, which rely on suturing to peripheral tissues, fail to promote tissue regeneration and provide sufficient CSF leakage prevention, leading to suboptimal outcomes. To address these limitations, we developed a Janus adhesive bio-patch with both antibacterial and pro-angiogenic properties to enhance dura mater repair. This bio-patch consisted of a polyacrylic acid (PAA) adhesive gel layer loaded with vancomycin and magnesium carbonate (MgCO 3 ), integrated onto a small intestinal submucosa (SIS) extracellular matrix. It exhibited a burst strength of 20.50±2.89kPa, effectively sealing CSF leaks, while demonstrating excellent antibacterial efficacy (∼99%) and significant enhanced angiogenesis (3.47-fold higher than the control). In rat, rabbit, and dog dural injury models, the bio-patch adhered seamlessly to the injury site, successfully preventing leaks and promoting tissue regeneration. These results highlighted the Janus adhesive bio-patch as a promising solution for improving dural repair in neurosurgery, offering a safer and more effective alternative to conventional suturing techniques.

研究领域: 神经外科 · 组织工程 · 再生医学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Asymmetric Janus fiber membrane for preventing cerebrospinal fluid leakage and promoting bone regeneration

Xiaomei Xia,Ziyang Liu,Hongshui Wang,Xianrui Zou,Lei Zhang,Kun Qin,Jiantao Zheng,Huan Zhou,Lei Yang,Chunyong Liang

Repairing skull base defects caused by pituitary tumor surgery remains challenging as it is difficult to restore its structural integrity and avoid cerebrospinal fluid leakage. To address this issue, this study aimed to prepare a Janus bilayer membrane with asymmetric wetting properties (hydrophobicity/super hydrophilicity) using polycaprolactone (PCL), gelatin (Gel), and polydopamine (PDA) through a layer-by-layer electrospinning technique. Randomly stacked hydrophobic PCL fibers were designed as the upper layer to control leakage of cerebrospinal fluid. Meanwhile, the bottom layer composed of hydrophilic PG-PDA nanofibers was utilized to promote the skull base bone repair. The experimental results showed that under a pressure of 200 mm water column, the Janus bilayer membrane could efficiently prevent leakage for several days. The prepared Janus PCL/PG-PDA membrane revealed excellent mechanical properties to mimic bone ECM and showed surface bioactivity to accelerate mineralization. The results of in vitro cell experiments indicated that the Janus membrane prepared in this study displays exceptional biocompatibility, with the PCL/PG-0.5%PDA fiber membrane demonstrating the highest capacity to promote osteogenic differentiation. These observations suggest that the asymmetric Janus fiber membrane (PCL/PG-PDA) has the potential to serve as a promising candidate for skull base repair.

研究领域: 生物材料学 · 再生医学 · 神经外科
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BIOMEDICAL CHROMATOGRAPHY · 2015 ·Vol. 29 ·期 8 ·1280-1289 · IF 1.723

Preparation and application of a novel molecularly imprinted solid-phase microextraction monolith for selective enrichment of cholecystokinin neuropeptides in human cerebrospinal fluid

Xiang Ji,Dan Li,Hua Li

A novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of cholecystokinin (CCK) neuropeptides was prepared in a micropipette tip. The MIPs were synthesized by epitope imprinting technique and the polymerization conditions were investigated and optimized. The synthesized MIPs were characterized by infrared spectroscopy, elemental analyzer and scanning electron microscope. A molecularly imprinted solid-phase microextraction (MI- μ -SPE) method was developed for the extraction of CCK neuropeptides in aqueous solutions. The parameters affecting MI- μ -SPE were optimized. The results indicated that this MIP monolith exhibited specific recognition capability and high enrichment efficiency for CCK neuropeptides. In addition, it showed excellent reusability. This MIP monolith was used for desalting and enrichment of CCK4, CCK5 and CCK8 from human cerebrospinal fluid prior to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and the results show that this MIP monolith can be a useful tool for effective purification and highly selective enrichment of multiple homologous CCK neuropeptides in cerebrospinal fluid simultaneously. By employing MI- μ -SPE combined with HPLC-ESI-MS/MS analysis, endogenous CCK4 in human cerebrospinal fluid was quantified. Copyright © 2015 John Wiley & Sons, Ltd.

研究领域: 分析化学 · 神经生物学 · 医学
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