Bioanalysis
·
2023
·Vol. 15
·期 6
·
IF 1.8
Juan Li,Yongjing Cao,Xiaojie Zhang,Min An,Juntao Zhang,Yanhua Liu
Background: Indocyanine2,3-dioxygenase (IDO) is an enzyme that can catalyze the metabolism of tryptophan (Trp) into kynurenine (Kyn), thus inhibiting the tumor immune microenvironment. Method: Based on its inhibitor, NLG919 (NLG), the authors developed a new immunomodulatory polymer micelle and established and verified an ultrahigh performance liquid chromatography–mass spectrometry method for the simultaneous determination of NLG, Trp and Kyn in mouse tumors through the ratio determination of Trp/Kyn tissue distribution and pharmacokinetics. The linear range of the method was 0.001–10 μg/ml. Results: Compared with NLG solution, the immunomodulatory polymeric drug-loaded micelles based on polystyrene-arginine showed higher Trp/Kyn ratio, more tumor aggregation and good pharmacokinetics. Conclusion: This method has been successfully applied to the simultaneous determination of Trp/Kyn and NLG in tumor tissues of mice.
研究领域:
药理学
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肿瘤学
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分析化学
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生物技术
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Tao Ke,Zhongyuan Zhao,Junhuan Lin,Fengting Ou,Kaikai Chen,Kui Zeng,Debo He,Shengqiang Tong,Xinyi Wang,Lushan Yu,Jing Chen
The aim of this study was to develop and fully validate a sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of pristinamycin ⅠA (PⅠA) and pristinamycin ⅡA (PⅡA) in plasma of beagle dogs after oral administration of pristinamycin tablets. PⅠA, PⅡA and quinupristin (internal standard, IS) were separated on an Agilent Eclipse Plus C 18 column (2.1 mm × 100 mm, 3.5 μm particle size) by using gradient elution consisting of methanol and water (0.1 % formic acid) at a flow rate of 0.4 mL/min in 4.0 min. Multiple reaction monitoring (MRM) mode was performed to quantify data under monitoring precursor-product ion transitions of m/z 867.6→134.1, 548.4→287.1 and 1022.7→133.9 for PⅠA, PⅡA and IS at positive ion mode, respectively. The method was developed at linearity ranging from 1.0 to 1000 ng/mL for all analytes.The accuracy of PⅠA and PⅡA was observed to range between −10.6 % and 7.1 %, while the precision was found to be within 8.9 %. No significant matrix effect was observed. PⅠA and PⅡA demonstrated stability during sample storage, preparation and analytic procedures. Furthermore, this method was successfully applied in the investigation of the pharmacokinetic profile of PⅠA and PⅡA in beagle dogs after oral administration of pristinamycin tablets (75 mg for PⅠA and 175 mg for PⅡA). The biological half-life (t 1/2 ) was determined to be 1.75 ± 0.07 h and 1.44 ± 0.31 h for PⅠA and PⅡA, respectively. The areas under curves (AUC 0-t ) of PⅠA and PⅡA were 80.7 ± 24.6 and 230 ± 94.8 μg/L·h, respectively.
研究领域:
分析化学
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药理学
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兽医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Junzhi,Lin Binyan,Zhang Ying,Hu Xiaochao,Liu Tongtong,Liu E-Hu,Liu Shijia
Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored.Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice.Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels.Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway.Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
研究领域:
药理学
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胃肠病学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Yunfeng Zhu,Fangkai Wang,Xin Wang,Ya Cheng,Xingyu Wang,Ali Fan,Jiawei Chang
Taletrectinib is a potent selective ROS and pan-NTRK tyrosine kinase inhibitor (TKI) and has been developed to treat non-small cell lung cancer (NSCLC). To facilitate pharmacokinetic and toxicokinetic studies of taletrectinib, we developed a procedure for ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to detect the plasma level of taletrectinib in dogs. This assay procedure was validated in compliance with FDA guidance. The dog plasma samples were spiked with internal standard (IS), followed by protein precipitation, and analyzed using a Waters ACQUITY BEH C 18 column coupled to a Thermo triple quadrupole mass spectrometer. Separation was executed using the acetonitrile-0.1 % formic acid solution with gradient elution, at a flow rate of 0.4 mL/min. Taletrectinib and IS were monitored by multiple reaction monitoring (MRM) with m / z 406.2 > 349.2 and m / z 441.2 > 138.1, respectively. The procedure demonstrated excellent linearity with a correlation coefficient greater than 0.999 within the concentration range of 0.2–200 ng/mL. The inter- and intra-day accuracy ranged from −5.25 % to 5.26 %, and the precision was below 6.39 %. Acetonitrile-mediated protein precipitation showed high extraction efficiency and a recovery above 85 %. The procedure was then applied to quantify taletrectinib in beagle dog plasma after oral and intravenous doses and achieved success. The obtained pharmacokinetic parameters indicated high bioavailability of taletrectinib (>85 %) and extensive tissue distribution (>40 L/kg).
研究领域:
药理学
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肿瘤学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Jianglin Hu,Jiayin Dai,Nan Sheng
Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding its hepatotoxicity biomarkers. In this study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA in mice serum reached a steady state by the 4th day. To assess its subacute hepatic effects and identify potential biomarkers, mice were administered HFPO-DA orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed that the lowest observed adverse effect levels were 0.5 mg/kg/d for hepatomegaly and 2.5 mg/kg/d for hepatic injury. Serum metabolomics analysis identified 34, 58, and 118 differential metabolites in the 0.1, 0.5, and 2.5 mg/kg/d groups, respectively, compared to the control group. Based on weighted gene coexpression network analysis, eight potential hepatotoxicity-related metabolites were identified; among them, kynurenic acid (KA) in mouse serum exhibited the highest correlation with liver injury. Furthermore, liver-targeted metabolomics analysis demonstrated that HFPO-DA exposure induced metabolic migration of the kynurenine pathway from KA to nicotinamide adenine dinucleotide, resulting in the activation of endoplasmic reticulum stress and the nuclear factor kappa-B signaling pathway. Notably, pretreatment with KA significantly attenuated liver injury induced by HFPO-DA exposure in mice, highlighting the pivotal roles of KA in the hepatotoxicity of HFPO-DA.
研究领域:
毒理学
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环境科学
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代谢学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Zilin Wang,Ying Feng,Yang Tian,Min Yang,Yanju He,Yujia He,Yue Wang,Chongying Shi,Liang Tao
This study aims to explore the enhancement effect of semi-solid fermentation of Monascus purpureus on the antioxidant properties of Moringa oleifera Lam. leaf (MOLL), as well as to analyze the potential antioxidant substances and their production mechanisms. In this study, the antioxidant activity of MOLL fermented with Monascus purpureus was evaluated in vitro . To gain further insight, we employed untargeted metabolomics to analyze the differentially abundant metabolites, and 30 key differentially expressed metabolites were identified. Notably, 15 of these metabolites were positively correlated with free radical scavenging activity. By utilizing a combination of KEGG topological and enrichment analyses, tryptophan metabolism was identified as a crucial pathway. Interestingly, Monascus purpureus fermentation significantly enhanced the conversion of tryptophan into metabolites with antioxidant properties, such as melatonin, kynurenine, and 3-hydroxyanthranilic acid, suggesting that fermentation with Monascus purpureus is a promising approach for enhancing the antioxidant properties of MOLL.
研究领域:
药理学
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生物化学
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代谢组学
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食品科学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Yaojun Lu,Hanhan Xie,Ketong Wu,Minyi Huang,Yuru Liu,Xingxing Li,Xiaofeng Guo,Jiahui Liu,Jundong Shao,Yongwen Luo,Lin Wang
Rising global dog ownership increases the risk of rabies, a viral disease with an almost 100% fatality rate. Current post-exposure prophylaxis (PEP) methods involving injections of human rabies immunoglobulin (HRIG) are invasive and painful, resulting in reduced compliance. Furthermore, delays associated with traditional methods can undermine their effectiveness during emergencies, highlighting the need for more efficient alternatives. This study explored microneedle (MN) patches as a less painful and more patient-friendly method for delivering HRIG. We developed a bilayer MN patch composed of a hyaluronic acid (HA) tip containing HRIG and a polyvinylpyrrolidone (PVP) base incorporating tazarotene (TA). The tip dissolved within two minutes, releasing effective doses of HRIG, while the base released TA to promote wound healing. The patch can be stored in blister packaging, maintaining stability without the need for cold-chain storage. Characterization confirmed the patch’s biocompatibility and its ability to enhance cell migration in vitro. In vivo testing using a rabies-infected mouse model demonstrated effective prevention of rabies and improved tissue repair following patch application. The patch’s portability, stability, and efficacy make it ideal for emergency scenarios, offering reduced discomfort compared to traditional methods. This approach also broadens the potential applications of microneedle in emergency care and vaccination.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Endocrinology
·
2024
·
IF 3.9
Chen Si-Ting,Ran Feng,Shi Wen-Wen,Liu Cheng-Kan,Wang Peng-Chao,Luo Hui-Na,Yang Zeng-Ming
Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy. Embryo implantation and decidualization were analysed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy. On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization. Hence, Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.
研究领域:
营养学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR NEUROSCIENCE
·
2025
·Vol. 75
·期 3
·1-14
·
IF 2.7
Fan Weihao,Ye Yi,Yang Hongkun,Wei Ying,Shi Kaiting,Yang Xinyu,Li Jian,Wang Zilong,Sun Yiming,Liao Linchuan
Ketamine is a synthesized anesthetic drug that was used extensively as a surgical anesthetic in the 1960s. Currently, ketamine is being investigated extensively for its potential as a treatment for depression. However, the addictive nature of ketamine has become an issue that cannot be ignored at this stage. As of now, there is no clear understanding of the changes in striatal metabolites and their relative metabolic pathways under the addictive effect of ketamine. In this study, a stable model of ketamine-induced conditioned place preference (CPP) was established. Non-targeted metabolomics and targeted metabolomics techniques, based on the ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-QE/MS) and the UHPLC-MS platform, were employed to uncover the metabolic characteristics and neurotransmitter profiles of the striatum after ketamine abuse in mice. Potential biomarkers and related differential metabolic pathways of this model have been revealed. In non-targeted metabolomics analysis, striatal differential metabolites mainly involve pathways related to arginine synthesis, purine metabolism, and morphine addiction. In targeted metabolism, the striatum of mice receiving ketamine showed an increase in the content of the neurotransmitter kynurenine (Kyn) and a decrease in the content of the neurotransmitter dopamine (DA). Our study suggested that Kyn and DA metabolism disturbances might be associated with ketamine-induced CPP phenotypes and provided a new perspective for investigating the addiction mechanisms of ketamine.
研究领域:
药理学
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神经科学
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代谢组学
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精神病学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2020
·
IF 4.848
Chen Zhongjian,Dai Yalan,Huang Xiancong,Chen Keke,Gao Yun,Li Na,Wang Ding,Chen Aiping,Yang Qingxia,Hong Yanjun,Zeng Su,Mao Weimin
Background: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with a poor prognosis. Although studies have shown metabolic reprogramming to be linked to ESCC development, no prognostic metabolic biomarkers or potential therapeutic metabolic targets have been identified.Method: The present study investigated some circulating metabolites associated with overall survival in 276 curatively resected ESCC patients using liquid chromatography/mass spectrometry metabolomics and Kaplan-Meier analysis. Tissue metabolomic analysis of 23-paired ESCC tissue samples was performed to discover metabolic dysregulation in ESCC cancerous tissue. A method consisting of support vector machine recursive feature elimination and LIMMA differential expression analysis was utilized to select promising feature genes within transcriptomic data from 179-paired ESCC tissue samples. Joint pathway analysis with genes and metabolites identified relevant metabolic pathways and targets for ESCC.Results: Four metabolites, kynurenine, 1-myristoyl-glycero-3-phosphocholine (LPC(14:0)sn-1), 2-piperidinone, and hippuric acid, were identified as prognostic factors in the preoperative plasma from ESCC patients. A risk score consisting of kynurenine and LPC(14:0)sn-1 significantly improved the prognostic performance of the tumor-node-metastasis staging system and was able to stratify risk for ESCC. Combined tissue metabolomic analysis and support vector machine recursive feature elimination gene selection revealed dysregulated kynurenine pathway as an important metabolic feature of ESCC, including accumulation of tryptophan, formylkynurenine, and kynurenine, as well as up-regulated indoleamine 2,3-dioxygenase 1 in ESCC cancerous tissue.Conclusions: This work identified for the first time four potential prognostic circulating metabolites. In addition, kynurenine pathway metabolism was shown to be up-regulated tryptophan-kynurenine metabolism in ESCC. Results not only provide a metabolite-based risk score system for prognosis, but also improve the understanding of the molecular basis of ESCC onset and progression, and as well as novel potential therapeutic targets for ESCC.
研究领域:
肿瘤学
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代谢组学
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生物标志物发现
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Peiling Wu,Wenjie Wang,Chuan Huang,Le Sun,Xiaoli Wu,Lijia Xu,Peigen Xiao
Background TRY-NAD metabolic network includes TRY (tryptophan), 5-HT (5-hydroxytryptamine), KYN (kynurenine), and NAD (nicotinamide adenine dinucleotide) pathway, which plays a significant role in neurological diseases and ageing. It is important to monitor these metabolites for studying the pathological anatomy of disease and treatment of responses evaluation. Although previous studies have reported quantitative methods for several metabolites in the network, the bottlenecks of simultaneously quantifying the whole metabolic network are their similar structures, diverse physico-chemical properties, and instability. Standardized protocols for the whole metabolic network are still missing, which hinders the in-depth study of TRY-NAD metabolic network in laboratory research and clinical screening. Results We developed a LC-MS/MS method for quantifying 28 metabolites in the TRY-NAD network simultaneously. Optimization was done for the mass spectral parameters, chromatographic conditions and sample pretreatment process. The developed method was fully validated in terms of standard curves, sensitivity, carryover, recovery, matrix effect, accuracy, precision, and stability. The pretreatment of 30 samples only takes 90 minutes, and the LC-MS/MS running time of one sample is only 13 minutes. With this method, we bring to light the chaos of global TRY-NAD metabolic network in sleep deprivation mice for the first time, including serum, clotted blood cells, hippocampus, cerebral cortex, and liver. NAD pathway levels in brain and blood decreased, whereas the opposite happened in the liver. The 5-HT pathway decreased and the concentration of KYN increased significantly in the brain. The concentration of many metabolites in KYN pathway (NAD + de novo synthesis pathway) increased in the liver. Significance This method is the first time to determine the metabolites of KYN, 5-HT and NAD pathway at the same time, and it is found that TRY-NAD metabolic network will be disordered after sleep deprivation. This work clarifies the importance of the pH of the extraction solution, the time and temperature control in pretreatment in standardized protocols building, and overcoming the problems of inconsistent sample pretreatment, separation, matrix effect interference and potential metabolite degradation. This method exhibits great prospects in providing more information on metabolic disturbances caused by sleep deprivation as well as neurological diseases and ageing.
研究领域:
分析化学
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神经科学
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药理学
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生物化学
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临床研究
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2024
·
IF 11.2
Zihe Hu,Gaoying Hong,Mumian Chen,Haiyan Wu,Weiying Lu,Yuewei Chen,Zhijian Xie,Changyu Shao,Jue Shi
Currently, commercial intraoral dressings have limitations as they only serve a single purpose and fail to meet various needs, such as hemostasis, wound protection, and dressing fixation. Here, we successfully fabricated a multifunctional polycaprolactone-chitosan Janus membrane (PCJM) with simultaneous hydrophobic and hydrophilic properties. The hydrophobic layer consists of a dense and disordered polycaprolactone, preventing bacterial adhesion, resisting fouling, and enhancing mechanical strength. The hydrophilic layer is a highly porous chitosan sponge, which facilitates cell and protein adhesion, as well as rapid absorption of blood and activation of the coagulation process. These results are confirmed by hemostasis experiments, which demonstrate that the PCJM had superior coagulation ability compared to commercial gelatin sponges and gauze, and by an early gingival healing model of beagle tooth extraction wounds, which exhibited excellent performance in promoting wound healing. Our work demonstrates the multifunctional PCJM wound dressing not only protects wounds from bacterial infections but also facilitates rapid hemostasis and early healing of beagle gingival soft tissue, which holds significant potential for clinical translation and large-scale production.
研究领域:
生物材料
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伤口愈合
·
组织工程
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生物医学工程
·
牙科材料
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）