Theranostics
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2021
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IF 11.556
Yuce Li,Yuchen Lou,Yu Chen,Jing Yang,Danqi Li,Biling Jiang,Jiajia Lan,Jingjing Wen,Yangxue Fu,Yamin Zhang,Juan Tao,Jintao Zhu
Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity. Methods: Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). The efficacy of these NPs for mediating immunosuppression and treatment of IMIDs was evaluated in imiquimod-induced psoriasis-like skin inflammation in Balb/c mice, a representative IMID model. Results: The MPA@Dex-MPA NPs exhibited high MPA loading efficiency, low albumin binding rates, and sustained MPA release, resulting in improved pharmacokinetics in vivo . Compared to free MPA, MPA@Dex-MPA NPs induced more robust therapeutic effects on IMIDs. Mechanistic studies indicated that MPA@Dex-MPA NPs were primarily distributed in dendritic cells (DCs) and significantly suppressed the overactivated DCs in vivo and in vitro . Furthermore, the recovered DCs rehabilitated the IL-23/Th17 axis function and significantly ameliorated imiquimod-induced psoriasis-like skin inflammation. Importantly, MPA@Dex-MPA NPs showed favorable safety and biocompatibility in vivo . Conclusion: Our results indicated the polysaccharide mycophenolate-based NPs to be highly promising for IMID treatment.
研究领域:
药学
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免疫学
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纳米技术
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2023
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IF 2.9
You Quan Shi,Zhao Xu,Le Wang,Kang Wang,Li Xu,Heng Zheng
It is particularly meaningful to therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) for transplant patients to maximize the drug efficacy and minimize the adverse effect. In this study, a novel fluorescence and colorimetric dual-readout probe was put forward to fast and reliable detect MPA. The blue fluorescence of MPA was largely enhanced in the presence of poly (ethylenimine) (PEI), while the red fluorescence of [email protected] 2 (silica-coated CdTe quantum dots) provided a reliable reference signal. Hence, combining PEI 70,000 and [email protected] 2 , a fluorescence and colorimetric dual-readout probe could be constructed. For fluorescence measurement of MPA, the linearity was obtained in the MPA concentration range of 0.5–50 μg/mL, with a limit of detection (LOD) of 33 ng/mL. For the visual detection, the fluorescent colorimetric card was established in the MPA concentration from 0.5 to 50 μg/mL corresponding to the fluorescence color from red to violet and then to blue, which could be used for semi-quantification. Furthermore, in the light of the ColorCollect APP by the smartphone, the ratio of blue and red brightness values was linear with the MPA concentration from 1 to 50 μg/mL; thus, quantification of MPA could be realized by APP with the LOD of 83 ng/mL. The developed method was successfully applied to the analysis of MPA in the plasma samples of three patients after oral administration of mycophenolate mofetil , which was the prodrug of MPA. The result was comparable to those obtained by the clinically widely-used enzyme multiplied immunoassay technique. The developed probe was fast, cost-effective and operational convenience, and possessed high potential for TDM of MPA.
研究领域:
分析化学
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临床化学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2023
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IF 5.9
Mingshi Deng,Wei Jin,Wenjuan Yang,Lingling Tian,Xinghua Gao,Xuefeng Wang,Lingyan Feng,Metini Janyasupab,Bingpu Zhou,Yuan Zhang
Mycophenolic acid (MPA), which is a potent immunosuppressant, has been widely used to prevent organ rejection after organ transplantation. In clinical practice, it is essential to monitor the free MPA concentration. Herein, convenient and fast electrochemical microsensing technology is developed for directly detecting the MPA concentration. To implement this method, ultrathin copper-based metal–organic framework (Cu–MOF) nanosheets with a thickness of about 6.6 nm are used to detect MPA. An analysis of electrochemical behavior reveals the direct electrochemical catalytic oxidation mechanism of MPA molecules on a Cu(II) tetrakis(4-carboxyphenyl)porphyrin (Cu–TCPP)-modified electrode. Furthermore, electrochemical testing results show that the ultrathin Cu–TCPP nanosheet-based microsensor exhibits high sensitivity and specificity for MPA in the nano- to micromolar range, with a detection limit of 10 nM. X-ray absorption spectroscopy (XAS) characterization reveals that the unsaturated metal ions in ultrathin nanosheets are the active sites responsible for boosting the catalytic oxidation of MPA molecules. High-performance liquid chromatography–tandem mass spectrometry further shows the catalytic oxidation product of MPA and that the phenolic hydroxyl group in the MPA molecule is the active site where the catalytic reaction occurs. The considerable sensing performance of the Cu–TCPP nanosheet-based microsensor proves that it is possible to develop a fast and convenient method for the direct high-frequency monitoring of immunosuppressive drugs.
研究领域:
分析化学
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生物医学工程
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药物分析
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 26
·期 1
·72
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IF 4.9
Chaoji Li,Min Zhang,Yanni Zhao,Dan Yang,Mei Zhao,Leyuan Shang,Xiaodong Sun,Shuo Zhang,Pengjiao Wang,Xiuli Gao
Mycophenolic acid (MPA) is a commonly used immunosuppressant. In the human body, MPA is metabolized into mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG) mainly through liver glucuronidation, which involves UDP-glucuronosyltransferase (UGTs) and transfer proteins. Research has indicated that the pharmaceutical excipient PEG400 can impact drug processes in the body, potentially affecting the pharmacokinetics of MPA. Due to the narrow therapeutic window of MPA, combination therapy is often used, and PEG400 is widely used in pharmaceutical preparations. Therefore, investigating the pharmacokinetic influence of PEG400 on MPA could offer valuable insights for optimizing MPA’s clinical use. In this study, we examined the impact of a single oral dose of PEG400 on the blood levels of MPA in rats through pharmacokinetic analysis. We also investigated the distribution of MPA in various tissues using mass spectrometry imaging. We explored the potential mechanism by which PEG400 affects the metabolism of MPA using hepatic and intestinal microsomes and the Caco-2 cellular transporter model. Our findings reveal that the overall plasma concentrations of MPA were elevated in rats following the co-administration of PEG400, with the AUC0-tof MPA and its metabolite MPAG increasing by 45.53% and 29.44%, respectively. Mass spectrometry imaging showed increased MPA content in tissues after PEG400 administration, with significant differences in the metabolites observed across different tissues. Microsomal and transport experiments showed that PEG400 accelerated the metabolism of MPA, promoted the uptake of MPA, and inhibited efflux. In conclusion, PEG400 alters the in vivo metabolism of MPA, potentially through the modulation of metabolic enzymes and transport.
研究领域:
药理学
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免疫抑制剂
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药物代谢
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药用辅料
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体内和体外研究
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产品关联
DOI
PubMed
高影响因子
Virulence
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2024
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IF 5.5
Xin Wang,Feiyang Pu,Xuanye Yang,Xili Feng,Jiayou Zhang,Kai Duan,Xuanxuan Nian,Zhongren Ma,Xiao-Xia Ma,Xiao-Ming Yang
Influenza A virus (IAV) poses threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of ten immunosuppressants, explored the antiviral mechanisms of immunosuppressants and demonstrated the combination effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibited viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibited IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG and filgotinib could be the preferential choices for patients who must take immunosuppressants but at risk of influenza virus infection.
研究领域:
药理学
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病毒学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2023
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IF 2.9
Yan Xiong,Shu Zhu,Hua Zhao,Jin Li,Yanting Li,Tao Gong,Yanru Tao,Jiangling Hu,Hongmei Wang,Xinhui Jiang
For patients receiving organ transplants, monitoring the blood concentration of MPA can provide timely information on whether MPA has reached the effective therapeutic window to better function while reducing the incidence of rejection or adverse reactions. In this study, an electrochemical sensor for the detection of MPA was built using a nanocomposite made of CS-MWCNT and AuNPs. At the same time, the high performance liquid phase (HPLC) method for MPA was established and compared with this sensor. The surface morphology, structure, and roughness of the material on the electrode were characterized by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), and atomic force microscopy (AFM). In addition, the electrochemical behavior of the modified electrode was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The standard curve was obtained in blank plasma, not pure buffer solution. The peak current was linearly related to the MPA concentration in the linear range of 0.001–0.1 mM with a detection limit of 0.05 μM and good anti-interference ability. Moreover, the sensor was employed with success for the determination of MPA in rat plasma with good recovery. The electrochemical sensor presented here is eco-friendly, and sensitive, and offers a great possibility for practical applicability.
研究领域:
电化学
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纳米技术
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分析化学
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生物医学工程
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药物分析
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产品关联
DOI
PubMed
高影响因子
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