JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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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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产品关联
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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产品关联
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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产品关联
DOI
PubMed
高影响因子
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