JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2024
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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
Materials Science & Engineering C-Materials for Biological Applications
·
2018
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IF 5.08
Yada Li,Weiqiang Wang,Huiying Liu,Jingwu Lei,Jingying Zhang,Hongzhi Zhou,Min Qi
A novel “cortex-like” micro/nano dual-scale structured TiO 2 coating was prepared on a titanium surface by micro-arc oxidation (MAO) with tetraborate electrolytes. This structure, which combines microslots with nanopores, exhibits super hydrophilicity. This coating modified the surface structure, chemistry, and hydrophilicity in a one-step treatment. Evolution of the coating together with its surface and structure properties was studied. We propose a forming mechanism of the dual-scale structure in which the oxides formed during the MAO discharge dissolve in the tetraborate electrolytes, leaving little or no deposition outside the discharge channels. We performed in vitro tests using human bone marrow-derived mesenchymal stem cells (hBMSCs) that compared this coating with a “volcano-like” MAO coating and a commercial sandblasted, large-grit and acid-etched (SLA) coating. The adhesion, morphology, proliferation, and differentiation of hBMSCs, together with the matrix mineralization, were investigated. Results suggest that the “cortex-like” structure significantly promotes the adhesion, spreading, and differentiation of cells and increases the matrix mineralization. In vivo tests with mongrel dogs showed an excellent osseointegration of the “cortex-like” coating. The combination of the dual-scale structure and the hydrophilicity of the “cortex-like” TiO 2 coating synergistically resulted in an outstanding cytocompatibility and osseointegration, which may facilitate a higher level of implant success.
研究领域:
生物材料
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组织工程
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生物医学工程
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材料科学
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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
Bioactive Materials
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2022
·
IF 16.874
Yilin Wang,Shanshan Wang,Xueqin He,Yupei Li,Tao Xu,Lin Xu,Bo Yang,Xinnian Fan,Weifeng Zhao,Changsheng Zhao
The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The “anticoagulant + column” realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and “anticoagulant + column” cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.
研究领域:
生物医学工程
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肝病学
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药理学
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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
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2024
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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
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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
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Xinhao Song,Mengjuan Lin,Tian Fang,Jiahao Gong,Junqi Wang,Shasha Gao,Xiaolin Xu,Xin Lv,Xiuge Gao,Junren Zhang,Shanxiang Jiang,Dawei Guo
Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.
研究领域:
药学
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癌症研究
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纳米技术
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兽医学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2024
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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.
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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
Bioactive Materials
·
2021
·
IF 14.593
Xiyu Li,Juan Wu,Danxue Li,Qin Zou,Yi Man,Ling Zou,Wei Li
Insufficient early osteogenesis seriously affects the later stage osteogenic quality and osseointegration of dental implants. To promote early osteogenesis, we first designed a Ti dental implant with a built-in magnet (mTi) to produce a local static magnetic field (SMF). Then, a dental implantation system comprising the mTi implant and the superparamagnetic hydroxyapatite (HA:Yb/Ho–Fe, named HYH-Fe) particles was implanted into the alveolar bone of beagles. The results showed that the mTi + HYH-Fe group displayed better early osteogenesis and later stage osseointegration than the Ti + HA and mTi + HA groups. A combination of the local SMF (mTi) and superparamagnetic HYH-Fe particles had a positive effect on the pro-osteogenesis of Ti implants. The results also indicated that week 10 could be adopted as the key time point to evaluate the early osteogenic effect of the mTi + HYH-Fe implantation system, which would be a promising prospect for promotion of osteogenesis, in vivo tracking investigation of material-bone relationships, and clinical applications.
研究领域:
牙科学
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生物材料
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生物医学工程
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骨科学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 20
·10184-10195
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IF 5.396
Zhenyang Gu,Wenlong Pei,Yonghua Shen,Lijuan Wang,Jun Zhu,Yi Zhang,Shengxian Fan,Qian Wu,Lei Li,Zhan Zhang
Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that Akkermansia muciniphila (Akk), a promising probiotic, could protect against colitis via the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between Akk and three Trp metabolites. Live Akk, pasteurised Akk and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live Akk, pasteurised Akk and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live Akk, pasteurised Akk and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised Akk significantly elevated the serum levels of indole acrylic acid (IA). In addition, live Akk, pasteurised Akk and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including CYP1A1, IL-10 and IL-22, suggesting that Akk could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.
研究领域:
微生物学
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免疫学
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胃肠病学
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代谢组学
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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）