Annals of Translational Medicine
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2020
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IF 3.297
Li Li,Xingfeng He,Xingtong Wang,Yu Sun,Guosheng Wu,He Fang,Chen Wang,Pengfei Luo,Zhaofan Xia
Background Ruxolitinib is an inhibitor of Janus kinases (JAK) 1/2. It was authorised recently by the U.S. Food and Drug Administration (FDA) as a new Myelofibrosis treatment. In this study, we identified ruxolitinib as a new inhibitor of nitric oxide (NO) production in response to lipopolysaccharide (LPS)stimulation of RAW 264.7 cells. Methods In vitro direct effects of ruxolitinib were determined through NO production on RAW 264.7 cells. Also the expression level of iNOS, TNF-α and IL-6 were detected by Western Blotting and qRT-PCR. In vivo therapeutic effects of ruxolitinib on sepsis were evaluated by an endotoxemia model with C57 mice. The survival was calculated and histopathological damage of organs was observed by HE. Cytokines in serum were detected by Mouse Cytokine Array Panel. Results Ruxolitinib was found to significantly reduce NO production, inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 expression, suggesting that ruxolitinib blocks LPS signaling that leads to pro-inflammatory factor expression. Furthermore, the inhibitory effects of ruxolitinib contributed to the survival of septic mice by 70% and pro-inflammatory cytokines in serum declined apparently. The results taken together indicate that ruxolitinib can significantly suppress LPS-stimulated NO production and improve the survival of septic mice, perhaps by interfering with the NF-κB pathway. Conclusions These findings suggest ruxolitinib might be a possible therapeutic candidate for sepsis therapy.
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PubMed
高影响因子
Advanced Healthcare Materials
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2023
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IF 10
Shi Liu,Xinlin Jia,Jina Hao,Dapeng Zhang,Shengchao Yang,Bin Dai,Yuanqing Mao,Yongsheng Li
Cell senescence or apoptosis contributes to self-failure and functional loss in specialized cells, leading to incapacity of the body to repair specific damages. Senescent bone marrow mesenchymal stem cells (BMSCs) lose their proliferative abilities and secrete senescence-associated secretory phenotype (SASP), hindering their participation in bone defect repair. Hence, the effective suppression of cell senescence is crucial to restore the self-repair capacity of body to treat bone defects. Since the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is associated with SASP secretion, herein, we propose a new strategy to inhibit this pathway to suppress SASP secretion and enhance osteoblast activity based on a novel hierarchically biomimetic nanostructural electrospun scaffold with JAK inhibitors (JAKi, Ruxolitinib) loaded. As validated by in vitro and in vivo experiments, the JAKi loaded scaffold reduces SASP expression effectively and alleviates senescent cell burden, creating a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating the bone repair capacity. These findings offer insights into the regulatory role of cellular senescence in bone aging and provide a new and effective strategy to treat age-related bone defects by delivery of JAKi to locally aging bone defect sites. This article is protected by copyright. All rights reserved
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PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
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2023
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IF 2.9
Yao Liu,Zhichao He,Heng Liang,Minzhen Han,Jinxingyi Wang,Qian Liu,Yanping Guan
Rapidly developing UHPLC-MS/MS bioassays with high throughput and quality are challenging yet desired in routine clinics. Methods & results A high-throughput UHPLC-MS/MS bioassay has been built for simultaneously quantifying gefitinib , ruxolitinib , dasatinib , imatinib , ibrutinib , methotrexate , cyclophosphamide and paclitaxel . After the protein precipitation with methanol, samples were separated on an Acquity BEH C 18 column following a gradient elution system with methanol and 2 mM ammonium acetate in water at 40 °C with a run time of 3 min (flow rate 0.4 mL/min). Mass quantification in the positive ion SRM mode was then performed with electrospray ionization . The method of specificity, linearity, accuracy, precision, matrix effects, recovery, stability, dilution integrity and carryover were all validated as per the guideline of the China Food and Drug Administration whose values met the admissible limits. Application of the bioassay to therapeutic drug monitoring revealed important variability in the studied anti-tumour drugs. Conclusion This validated approach was shown to be reliable and effective in clinical management, being a valuable support in therapeutic drug monitoring and subsequent individualized dosing optimization.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Qi Chen,Yue Zhou,Xudong Zhu,Lei Xu,Ge Bai,Yaru Zhou,Nannan Zhang,Hongwen Liu,Yani Pan,Yu Liu,Lishan Wang,Xueni Fu,Jingjing Wei,Lina Zhou,Lu Xu,Yuxiang Sun,Zhangding Wang,Shanshan Shen,Yun Zhu,Lei Wang
Tumor-associated neutrophils (TANs), particularly the N2 phenotype, contribute to T cell exhaustion in cholangiocarcinoma (CCA), leading to low response rates to PD-1 inhibitor therapy. To address this issue, cancer-associated fibroblast (CAF)-derived extracellular vesicles loaded with ruxolitinib (CEVs@Ru) are developed to selectively target and reprogram N2 TANs, thereby modulating the immunosuppressive tumor microenvironment (TME). The combination of CEVs@Ru with anti-PD-1 antibody therapy significantly enhanced antitumor efficacy, reducing tumor weight by 89.86% and normalizing liver weight, without significant adverse effects. This approach improved the local concentration of ruxolitinib, increased CD8+ T cell infiltration, and reduced regulatory T cells, indicating a remodeled TME conducive to effective antitumor immunity. The findings provide a promising strategy for enhancing PD-1 inhibitor efficacy and improving patient outcomes in CCA and potentially other solid tumors.
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危险品化学品经营许可证（带存储）