CLINICA CHIMICA ACTA
·
2018
·
IF 2.926
Feiyan Liu,Luyang Xu,Changcheng Sheng,Xiaoyan Qiu,Ming Zhang,Zheng Jiao
Background The immunosuppressive agent mycophenolic acid (MPA) is a non-competitive, reversible inhibitor of inosine-5′-monophosphate dehydrogenase (IMPDH). Thus, IMPDH activity can serve as a potential pharmacodynamic biomarker to optimize dosing of MPA. Methods Peripheral blood mononuclear cells were isolated from 2 mL blood samples and an in vitro enzymatic reaction was subsequently performed for 120 min. To determine IMPDH activity in Chinese healthy volunteers and renal transplant patients, a high performance liquid chromatography assay was established and validated by subtracting adenosine monophosphate (AMP) from blank samples for eliminating exogenous AMP interference. Results The accuracy of our method ranged between −0.8% and 12.5%, and the precision ranged between 0.7% and 6.3%. The mean value of IMPDH activity across 11 healthy volunteers was 46.60 ± 14.28 μmol/s/mol AMP. A negative relationship between MPA concentration and IMPDH activity was observed in four renal transplant patients treated with MPA 13 days post-transplantation, while the inhibitory rate of IMPDH activity ranged from 24% to 42%. Conclusion A bioanalytical assay for IMPDH quantification was optimized and evaluated. The differences in the pharmacodynamics of MPA between Asians and Caucasians may provide some evidence for dosing differences among ethnicities.
研究领域:
药理学
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临床医学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2023
·
IF 2.8
Qingfeng Xie,Zhuo Cao,Weiling You,Xiaoping Cai,Mei Shen,Zhangyong Yin,Yiwei Jiang,Xin Wang,Siyu Ye
New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
研究领域:
肿瘤学
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药理学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Siwei Sun,Jiale Qi,Yun Zhou,Ke Li,Yu Rong,Jiao Bi,Weixin Hu,Jing Luan,Xueping Li
Mycophenolate mofetil (MMF) shows significant potential for precision immunotherapy in moderate to severe atopic dermatitis (AD). However, its clinical application is limited by inadequate delivery efficiency and dose related toxicities. Herein, we propose a straightforward and effective drug delivery strategy that involves coating MMF with polydopamine (PDA) to fabricate MMF nanoparticles (MMF NPs). A systematic investigation of their therapeutic efficacy and mechanism of action was also conducted in the AD model mice. Due to surface hydrophilicity and nanoscale effects mediated by PDA, MMF NPs demonstrate excellent stability, high drug loading capacity, and optimized pharmacokinetics. The prolonged circulation time and enhanced permeability retention effect reduce both toxicity and susceptibility to infections associated with MMF, which leads to a marked improvement in the therapeutic efficacy of AD. Finally, MMF NPs achieve precise immunotherapy through the synergistic effect by balancing systemic immunity and precisely targeting the local inflammatory microenvironment. This study not only presents a safe and effective treatment strategy for AD but also introduces a novel delivery approach for the clinical application of MMF in immune-mediated disorders.
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DOI
PubMed
高影响因子
TRANSPLANT INTERNATIONAL
·
2020
·Vol. 33
·期 4
·450-461
·
IF 3.177
Shoubao Wang,Yao Xiong,Yinmin Wang,Jingting Chen,Jun Yang,Binbin Sun
Summary Systemic immunosuppression is indispensable for vascularized composite allotransplantation (VCA). Daily administration of standard triple therapy regimen of tacrolimus (FK506), mycophenolate mofetil (MMF), and steroid has severe side effects and reduces the compliance of VCA recipients. To overcome these hurdles, FK506/MMF/prednisolone (PDNN) was loaded into PLGA microspheres (PGLA MS). A single injection of FK506/MMF/PDNN-PLGA MS significantly prolonged the survival time of allograft in a rat hind limb transplantation model with a median survival time (MST) of more than 150 days compared to 34.5 days in the group treated orally with FK506/MMF/PDNN and 11 days in the nontreatment allograft and MS control groups. Analysis of showed that FK506/MMF/PDNN-PLGA MS could maintain relatively higher plasma and tissue drug concentrations for a long time. Moreover, histopathology and flow cytometry of circulating mononuclear cells revealed significantly prolonged immunosuppression by the FK506/MMF/PDNN-PLGA MS compared with the orally given FK506/MMF/PDNN. In conclusion, a single injection of FK506/MMF/PDNN-PLGA MS may provide a new approach for long-term prevention of immune rejection in VCA.
研究领域:
移植免疫学
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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
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Yanjia Che,Yuanyang Chen,Zhiwei Wang,Sihao Zheng,Kai Xing,Shun Yuan,Xiaohan Zhong
Despite being the gold-standard treatment for end-stage heart disease, heart transplantation is associated with acute cardiac rejection within 1 year of transplantation. The continuous application of immunosuppressants may cause side effects such as hepatic and renal toxicity, infection, and malignancy. Developing new pharmaceutical strategies to alleviate acute rejection after heart transplantation effectively and safely is of critical importance. In this study, we performed a murine model of MHC-full mismatch cardiac transplantation and showed that the combination of Rhodosin (Rho) and mycophenolate mofetil (MMF) could prevent acute rejection and oxidative stress injury and prolong the survival time of murine heart transplants. The use of Rho plus MMF in allografts improved the balance of Tregs/Teff cells, which had a protective effect on allotransplantation. We also isolated bone marrow-derived dendritic cells (BMDCs) and determined that Rho inhibited DC maturation by promoting mitochondrial fusion mainly through the mitochondrial fusion-related protein MFN1. Herein, we demonstrated that Rho, an active ingredient isolated from the plant Rhodiola rosea with antioxidant and anti-inflammatory activities, could efficiently alleviate acute rejection and significantly prolong murine heart allograft survival when used with a low dose of MMF. More importantly, we found that Rho restrained DC maturation by promoting mitochondrial fusion and decreasing reactive oxygen species (ROS) levels, which then alleviated acute rejection in murine cardiac transplantation. Interestingly, as a novel immunosuppressant, Rho has almost no side effects compared with other traditional immunosuppressants. Taken together, these results suggest that Rho has good clinical auxiliary applications as an effective immunosuppressant and antioxidant, and this study provides an efficient strategy to overcome the side effects of immunosuppressive agents that are currently used in organ transplantation.
研究领域:
免疫学
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移植医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Small Methods
·
2023
·Vol. 7
·期 3
·2200925
·
IF 12.4
Tianliang Fang,Baoqi Li,Meng Li,Yuli Zhang,Zhangyan Jing,Yuan Li,Tianyuan Xue,Zhirang Zhang,Wenli Fang,Zhongda Lin,Fanqiang Meng,Liyan Li,Yang Yang,Xingding Zhang,Xin Liang,Shu-Na Chen,Jun Chen,Xudong Zhang
Immune intervention of B cell activation to blockade the production of autoantibodies provokes intense interest in the field of systemic lupus erythematosus (SLE) therapy development. Although the survival rate for SLE is improved, many patients die untimely. Engineered cell membrane vesicles manifest remarkable capacity of targeted drug delivery and immunomodulation of immune cells such as B cells. Herein, this work engineered cellular nanovesicles (NVs) presenting CD40 (CD40 NVs) that can blunt B cells and thus alleviate SLE. CD40 NVs disrupt the CD40/CD40 ligand (CD40L) costimulatory signal axis through the blockade of CD40L on CD4 + T cells. Therefore, the CD40 NVs restrain the generation of the germinal center structure and production of antibodies from B cells. Furthermore, immunosuppressive drug mycophenolate mofetil (MMF) is also encapsulated in the vesicles (MMF-CD40 NVs), which is employed to deplete immunocytes including B cells, T cells, and dendritic cells. Together, CD40 NVs are promising formulations for relieving autoimmunity and lupus nephritis in MRL/lpr mice.
研究领域:
免疫学
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药学
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生物技术
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Minhai Liu,Yan Zhang,Rui Cheng,Ting Tan,Lan Guo,Fan Liu,Yiqun Wan
An efficient and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MSMS) method was developed for simultaneous determination of 5 alternaria toxins (ATs) in edible and medicinal plant - peppermint using MOF-808-trifluoroacetic acid (MOF-808-TFA) as the adsorbent. Characterization methods such as scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and N 2 adsorption-desorption demonstrated that the synthesized MOF-808-TFA had a regular ortho-octahedral configuration and high specific surface area. Under the optimal conditions, the 5 ATs showed good linearity (R 2 ≥ 0.9993) in their respective concentration ranges. The limits of quantifications (LOQs) of the method ranged from 0.21 to 0.48 μg/L, and the recoveries were 77.8–118.2 %, with the relative standard deviations (RSDs) less than 8.9 %.
研究领域:
分析化学
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食品科学
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植物学
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产品关联
DOI
PubMed
高影响因子
Virulence
·
2024
·
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
·
病毒学
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免疫学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2018
·
IF 3.616
Lili Wu,Yulian Chen,Han Liu,Zhikun Zhan,Zhi Liang,Tao Zhang,Zheng Cai,Ling Ye,Menghua Liu,Jie Zhao,Shuwen Liu,Lan Tang
Aggravating effect of probenecid (a traditional anti-gout agent) on emodin-induced hepatotoxicity was evaluated in this study. 33.3% rats died in combination group, while no death was observed in rats treated with emodin alone or probenecid alone, indicating that emodin-induced (150 mg/kg) hepatotoxicity was exacerbated by probenecid (100 mg/kg). In toxicokinetics-toxicodynamics (TK-TD) study, aspartate aminotransferase (AST) and systemic exposure (area under the serum concentration-time curve, AUC ) of emodin and its glucuronide were significantly increased in rats after co-administrated with emodin and probenecid for 28 consecutive days. Results showed that the increased AUC (increased by 85.9%) of emodin was mainly caused by the decreased enzyme activity of UDP-glucuronosyltransferases (UGTs, decreased by 11.8%–58.1%). In addition, AUC of emodin glucuronide was increased 5-fold, which was attributed to the decrease of multidrug-resistant-protein 2 (MRP2) protein levels (decreased by 54.4%). Similarly, in vitro experiments proved that probenecid reduced the cell viability of emodin-treated HepG2 cells through inhibiting UGT1A9, UGT2B7 and MRP2. Our findings demonstrated that emodin-induced hepatoxicity was exacerbated by probenecid through inhibition of UGTs and MRP2 in vivo and in vitro , indicating that gout patients should avoid taking emodin-containing preparations in combination with probenecid for a long time.
研究领域:
药理学
·
毒理学
·
药学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xiangli He,Jiayan Cui,Hui Ma,Naijipu Abuduaini,Ying Huang,Lu Tang,Wanyan Wang,Yuanyuan Zhang,Yang Wang,Weiqiang Lu,Bo Feng,Jin Huang
Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting reaction in the de novo synthesis pathway of guanine nucleotides that is highly required for cancer cell outgrowth. Herein, we found that IMPDH isoform 2 (IMPDH2) is highly expressed in colorectal cancer (CRC) and is correlated with poor patient prognosis. Via structure-based virtual screening, we identified berberrubine, a critical ingredient of the medical plant Coptis chinensis, as a novel, selective, and competitive inhibitor of IMPDH2, which demonstrated over 15-fold selectivity to IMPDH2 than IMPDH1. Besides, we also confirmed the interaction between berberrubine and IMPDH2. Of note, berberrubine treatment significantly impairs the growth of human CRC cells in a dose-dependent manner, which can be rescued by supplementing with guanosine. Furthermore, oral administration of berberrubine remarkably reduced tumor volume and weight in a human cell line-derived xenograft model. Importantly, the anti-cancer activity of berberrubine was also confirmed by using the azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced spontaneous CRC mouse model. Taken together, our study highlights that berberrubine acts as a novel IMPDH2 inhibitor, suppressing the growth of CRC in vitro and in vivo , providing a fresh perspective for its potential application in the treatment of CRC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症生物学
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PubMed
高影响因子
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