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  • Chen, Jianhai  (7)
  • 1
    Online Resource
    Online Resource
    Genetically Engineered Biomimetic Nanoparticles for Targeted Delivery of mRNA to Treat Rheumatoid Arthritis
    Wiley ; 2023
    In:  Small Methods
    Details
    In: Small Methods, Wiley
    Abstract: In addition to inhibiting persistent inflammation, phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is known as an important therapeutic target for alleviating rheumatoid arthritis (RA) symptoms. Modulation of PTEN gene expression in synovial tissue using messenger RNA (mRNA) is a promising approach to combat RA. However, mRNA therapeutics are often hampered by unsatisfactory stability and inefficient localization in synovial tissue. In this study, a genetically engineered biomimetic membrane‐coated mRNA (MR@P‐mPTEN) carrier that effectively delivers mRNA‐PTEN (mPTEN) directly to the RA joint is presented. By overexpressing tumor necrosis factor (TNF‐α) receptors on macrophage biomimetic membranes via plasmid transfection, decoys that reduce inflammatory pathway activation are prepared for TNF‐α. The resulting construct, MR@P‐mPTEN, shows good stability and RA targeting based on in vivo fluorescence imaging. It is also found that MR@P‐mPTEN competitively binds TNF‐α and activates the PTEN pathway in vitro and in vivo, thereby inhibiting synovitis and joint damage. Clinical micro‐computed tomography and histological analyses confirm the treatment effects. These results suggest that the genetically engineered biomimetic therapeutic platform MR@P‐mPTEN both inhibits pro‐inflammatory cytokines and upregulates PTEN protein expression to alleviate RA damage, providing a new a new combination strategy for RA treatment.
    Type of Medium: Online Resource
    ISSN: 2366-9608 , 2366-9608
    URL: Article
    DOI: 10.1002/smtd.202300678
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2884448-8
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  • 2
    Online Resource
    Online Resource
    DataSheet1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Bioengineering and Biotechnology Vol. 9 ( 2021-11-12)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 9 ( 2021-11-12)
    Abstract: Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro . In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    URL: Article
    DOI: 10.3389/fbioe.2021.764212
    DOI: 10.3389/fbioe.2021.764212.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2719493-0
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  • 3
    Online Resource
    Online Resource
    Treatment of collagen-induced arthritis rat model by using Notch signalling inhibitor
    Elsevier BV ; 2021
    In:  Journal of Orthopaedic Translation Vol. 28 ( 2021-05), p. 100-107
    Details
    In: Journal of Orthopaedic Translation, Elsevier BV, Vol. 28 ( 2021-05), p. 100-107
    Type of Medium: Online Resource
    ISSN: 2214-031X
    URL: Article
    DOI: 10.1016/j.jot.2021.01.003
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2747531-1
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  • 4
    Online Resource
    Online Resource
    Repurposing of Pirfenidone (Anti-Pulmonary Fibrosis Drug) for Treatment of Rheumatoid Arthritis
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-3-5)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-3-5)
    Abstract: Clinical studies have shown that pirfenidone (PFD) effectively relieves joint pain in rheumatoid arthritis (RA) patients. However, the detailed mechanisms underlying the anti-RA effects of PFD have not been investigated. This study was undertaken to investigate the repurposing of PFD for the treatment of RA, and explore its anti-rheumatic mechanisms. A collagen-induced arthritis (CIA) rat model was used to observe joint pathological changes following PFD treatment. Based on bioinformatics to predict the mechanism of PFD anti-RA, using EA. hy926 and TNF-α-induced MH7A cells to establish in vitro model to explore its biological mechanism from the perspectives of synovial inflammation and angiogenesis. PFD significantly relieved pathological changes, including joint swelling, synovial hyperplasia, inflammatory cell infiltration and joint destruction. PFD was also associated with reduced expression of MMP-3 and VEGF in articular chondrocytes and synovial cells of CIA rats ( p & lt; 0.05). Using bioinformatic methods, we predicted that PFD inhibits cell inflammation and migration by interfering with the JAK2/STAT3 and Akt pathways. These results were verified using in vitro models. In particular, PFD effectively reduced the expression of pro-inflammatory, chondrogenic, and angiogenic cytokines, such as IL-1β, IL-6, IL-8, MMP-1/3/2/9 and VEGF ( p & lt; 0.05), in TNF-α-induced MH7A cells. In addition, PFD significantly reduced the production of MMP-2/9 and VEGF in EA. hy926 cells, thereby weakening migration and inhibiting angiogenesis ( p & lt; 0.05). These findings suggest that PFD may alleviate the pathological process in CIA rats, by inhibiting inflammation and angiogenesis through multiple pathways, and serve as a potential therapeutic drug for RA.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.631891
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    HIF-1α dependent RhoA as a novel therapeutic target to regulate rheumatoid arthritis fibroblast-like synoviocytes migration in vitro and in vivo
    Elsevier BV ; 2023
    In:  Journal of Orthopaedic Translation Vol. 40 ( 2023-05), p. 49-57
    Details
    In: Journal of Orthopaedic Translation, Elsevier BV, Vol. 40 ( 2023-05), p. 49-57
    Type of Medium: Online Resource
    ISSN: 2214-031X
    URL: Article
    DOI: 10.1016/j.jot.2023.05.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2747531-1
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  • 6
    Online Resource
    Online Resource
    Notch‐1 and Notch‐3 Mediate Hypoxia‐Induced Activation of Synovial Fibroblasts in Rheumatoid Arthritis
    Wiley ; 2021
    In:  Arthritis & Rheumatology Vol. 73, No. 10 ( 2021-10), p. 1810-1819
    Details
    In: Arthritis & Rheumatology, Wiley, Vol. 73, No. 10 ( 2021-10), p. 1810-1819
    Abstract: To investigate the molecular mechanism of hypoxia‐induced rheumatoid arthritis synovial fibroblast (RASF) activation via Notch‐1 and Notch‐3 signaling, and to evaluate its potential as a therapeutic target. Methods Expression of Notch‐1 intracellular domain (N1ICD), N3ICD, and hypoxia‐inducible factor 1α (HIF‐1α) was assessed by immunhistology in synovial tissue from patients with RA. RASFs were cultured under hypoxic conditions and normoxic conditions with or without small interfering RNAs (siRNAs), and N1ICD and N3ICD were overexpressed under normoxic conditions. Rats with collagen‐induced arthritis (CIA) were administered LY411575 (inhibitor of N1ICD and N3ICD) for 15 days and 28 days, and its therapeutic efficacy was assessed by histologic and radiologic evaluation of the rat synovial tissue, and by analysis of inflammatory cytokine production in the serum of rats. Results N1ICD, N3ICD, and HIF‐1α were expressed abundantly in the synovial tissue of RA patients. HIF‐1α was shown to directly regulate the expression of Notch‐1 and Notch‐3 genes under hypoxic conditions. Moreover, hypoxia‐induced N1ICD and N3ICD expression in RASFs was blocked by HIF‐1α siRNA. Notch‐1 siRNA and Notch‐3 siRNA inhibited hypoxia‐induced RASF invasion and angiogenesis in vitro, whereas overexpression of N1ICD and N3ICD promoted these processes. In addition, Notch‐1 was shown to regulate RASF migration and epithelial–mesenchymal transition under hypoxic conditions, whereas Notch‐3 was shown to regulate the processes of anti‐apoptosis and autophagy. Furthermore, in vivo studies in rats with CIA showed that the N1ICD and N3ICD inhibitor LY411575 had a therapeutic effect in terms of ameliorating the symptoms and severity of the disease. Conclusion This study identified a functional link between HIF‐1α, Notch‐1, and Notch‐3 signaling in regulating activation of RASFs and the processes involved in the pathogenesis of RA.
    Type of Medium: Online Resource
    ISSN: 2326-5191 , 2326-5205
    URL: Issue
    URL: Article
    DOI: 10.1002/art.v73.10
    DOI: 10.1002/art.41748
    RVK:
    XA 10000
    RVK:
    XA 30325
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2754614-7
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  • 7
    Online Resource
    Online Resource
    Biphasic Effect of Pirfenidone on Angiogenesis
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 12 ( 2022-1-5)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2022-1-5)
    Abstract: Pirfenidone (PFD), a synthetic arsenic compound, has been found to inhibit angiogenesis at high concentrations. However, the biphasic effects of different PFD concentrations on angiogenesis have not yet been elucidated, and the present study used an in vitro model to explore the mechanisms underlying this biphasic response. The effect of PFD on the initial angiogenesis of vascular endothelial cells was investigated through a Matrigel tube formation assay, and the impact of PFD on endothelial cell migration was evaluated through scratch and transwell migration experiments. Moreover, the expression of key migration cytokines, matrix metalloproteinase (MMP)-2 and MMP-9, was examined. Finally, the biphasic mechanism of PFD on angiogenesis was explored through cell signaling and apoptosis analyses. The results showed that 10–100 μM PFD has a significant and dose-dependent inhibitory effect on tube formation and migration, while 10 nM–1 μM PFD significantly promoted tube formation and migration, with 100 nM PFD having the strongest effect. Additionally, we found that a high concentration of PFD could significantly inhibit MMP-2 and MMP-9 expression, while low concentrations of PFD significantly promoted their expression. Finally, we found that high concentrations of PFD inhibited EA.hy926 cell tube formation by promoting apoptosis, while low concentrations of PFD promoted tube formation by increasing MMP-2 and MMP-9 protein expression predominantly via the EGFR/p-p38 pathway. Overall, PFD elicits a biphasic effect on angiogenesis through different mechanisms, could be used as a new potential drug for the treatment of vascular diseases.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.804327
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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