Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway

Ni, Rongrong; Song, Guojing; Fu, Xiaohong; Song, Ruifeng; Li, Lanlan; Pu, Wendan; Gao, Jining; Hu, Jun; Liu, Qin; He, Fengtian; Zhang, Dinglin; Huang, Gang

doi:10.1016/j.biomaterials.2019.119730

Cited by 96 publications

(64 citation statements)

References 42 publications

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“…It was reported that CCR5 silencing suppresses in ammatory response, inhibits viability, and promotes apoptosis of synovial cells in RA rats by inhibiting MAPK pathway [100]. TNF-a is a major cytokine implicated in RA [101]. Recently article revealed that miR-17 overexpression inhibited TRAF2 expression and its association with cIAP2, thereby suppressing TNF-a signaling pathways and downstream in ammatory proteins in RA SFs [102].…”

Section: Discussionmentioning

confidence: 99%

“…Genes in the TNF family have been associated with RA, and may be a potential therapeutic target [113]. A plenty of evidences illustrated that TNF perpetuate synovial in ammation via activates RA-FLS inducing in a constellation of genes [101]. All these provide strong evidences for the prediction of ELP treat RA via intervention these key targets, but it is necessary to further validate the claims using molecular biological methods.…”

Section: Discussionmentioning

confidence: 99%

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WITHDRAWN: Elucidating the mechanisms of Tibetan medicine Ershiwuwei Lvxue Pill in the treatment of rheumatoid arthritis via a system pharmacological approach

Liu

Fan

Zhong

et al. 2020

Preprint

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Background: Ershiwuwei Lvxue Pill (ELP, མགྲིན་མཚལ་ཉེར་ལྔ།), a traditional Tibetan medicine preparation, has been used hundreds of years for the clinical treatment of rheumatoid arthritis (RA) in Tibet, China. Nevertheless, its chemical compositions and therapeutic mechanism are unclear. Methods: In this work, a system pharmacological approach based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), network pharmacology and molecular docking simulation was proposed for exploring the promising bioactive compounds and mechanisms for the treatment of RA.Results: For the first time, the compounds database of ELP was successfully established and 96 compounds were identified based on UPLC-Q-TOF/MS analysis. Among them, 22 bioactive compounds were screened according to ADME, oral bioavailability and drug likeness. Screening based on relevant databases and topological analysis revealed that 22 bioactive ingredients participated in 46 potential target proteins and 12 signaling pathways in RA. The functional enrichment analysis indicated that ELP exerted the anti-RA effects via synergistically regulating multiple biological nodes of the disease network. In that, 10 targets with high degree value including IL6, TNF, TP53, AKT1, JUN, VEGFA, MAPK3, STAT3, IL1β and PTGS2. The pathways with greater p-value contribution are PI3K-Akt signaling pathway, Cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, MAPK signaling pathway, TNF signaling pathway and Toll-like receptor signaling pathway. In addition, good molecular docking scores were highlighted between five promising bioactive compounds (ellagic acid, quercetin, kaempferol, galangin, coptisine) and five core targets (PTGS2, STAT3, VEGFA, MAPK3, TNF). Conclusion: Overall, the present work revealed the material basis and potential mechanism of ELP treatment on RA and provides insight for further research. However, further studies are needed to validate the biological processes and effect pathways of ELP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Elucidating the mechanisms of Tibetan medicine Ershiwuwei Lvxue Pill in the treatment of rheumatoid arthritis via a system pharmacological approach

Liu

Fan

Zhong

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…After intraperitoneal injection in AIA rats, the ROS-responsive micellar nanotherapy significantly inhibited the levels of inflammatory cytokines (IL-1 and IL-6) and reduced the bone destruction, with much better efficacy than berberine. In other cases, ROS-responsive and FA-targeting liposomes and nanoparticles were investigated for targeted RA treatment [ 339 , 340 ], and both systems notably reinforced in vivo efficacies of loaded drugs in CIA mice.…”

Section: Treatment Of Inflammatory Diseases By Bioresponsive Drug Delmentioning

confidence: 99%

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Ding

et al. 2020

Journal of Controlled Release

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140

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Inflammation is intimately related to the pathogenesis of numerous acute and chronic diseases like cardiovascular disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative diseases. Therefore anti-inflammatory therapy is a very promising strategy for the prevention and treatment of these inflammatory diseases. To overcome the shortcomings of existing anti-inflammatory agents and their traditional formulations, such as nonspecific tissue distribution and uncontrolled drug release, bioresponsive drug delivery systems have received much attention in recent years. In this review, we first provide a brief introduction of the pathogenesis of inflammation, with an emphasis on representative inflammatory cells and mediators in inflammatory microenvironments that serve as pathological fundamentals for rational design of bioresponsive carriers. Then we discuss different materials and delivery systems responsive to inflammation-associated biochemical signals, such as pH, reactive oxygen species, and specific enzymes. Also, applications of various bioresponsive drug delivery systems in the treatment of typical acute and chronic inflammatory diseases are described. Finally, crucial challenges in the future development and clinical translation of bioresponsive anti-inflammatory drug delivery systems are highlighted.

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“…An anti-inflammatory mechanism study revealed that Dex/FA-Oxi-αCD inhibits the expression of iRhom2, TNF-α, and BAFF in vitro and in vivo. FA modification accumulates the biodistribution of Dex/FA-Oxi-αCD in the inflamed joints of RA, and the therapeutic efficacy is significantly improved compared to free Dex (Ni et al, 2020). Chung et al (2015) fabricated an inflammatory microenvironment ultrasensitive ROS-responsive gas-generating carrier for the treatment of osteoarthritis.…”

Section: Application Of Ros-responsive Nps For Inflammation Treatmentmentioning

confidence: 99%

Biomedical Application of Reactive Oxygen Species–Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases

Liu

Chen

et al. 2020

Front. Chem.

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Numerous pathological conditions, including cancer, inflammatory diseases, and neurodegenerative diseases, are accompanied by overproduction of reactive oxygen species (ROS). This makes ROS vital flagging molecules in disease pathology. ROS-responsive drug delivery platforms have been developed. Nanotechnology has been broadly applied in the field of biomedicine leading to the progress of ROS-responsive nanoparticles. In this review, we focused on the production and physiological/pathophysiological impact of ROS. Particular emphasis is put on the mechanisms and effects of abnormal ROS levels on oxidative stress diseases, including cancer, inflammatory disease, and neurodegenerative diseases. Finally, we summarized the potential biomedical applications of ROS-responsive nanocarriers in these oxidative stress diseases. We provide insights that will help in the designing of new ROS-responsive nanocarriers for various applications.

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Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway

Cited by 96 publications

References 42 publications

WITHDRAWN: Elucidating the mechanisms of Tibetan medicine Ershiwuwei Lvxue Pill in the treatment of rheumatoid arthritis via a system pharmacological approach

WITHDRAWN: Elucidating the mechanisms of Tibetan medicine Ershiwuwei Lvxue Pill in the treatment of rheumatoid arthritis via a system pharmacological approach

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

Biomedical Application of Reactive Oxygen Species–Responsive Nanocarriers in Cancer, Inflammation, and Neurodegenerative Diseases

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