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  1. AU="Cheng, Zhiluo"
  2. AU="Silva, Dândara Santos"
  3. AU="Timmann, Dagmar"
  4. AU="Jingping, Lin"
  5. AU="Yoon, Sangwook"
  6. AU="Sedor, John R."
  7. AU="Legrand, Julien"
  8. AU="Mintz, Kevin Todd"
  9. AU="Kösters, Markus"
  10. AU="Castano-Duque, Lina"
  11. AU="Lowry, Gregory V"
  12. AU="Gao, Xiaojuan"
  13. AU="Daniłowicz-Szymanowicz, Ludmiła"
  14. AU="Weber, Jesse N"
  15. AU="Fages-Masmiquel, Ester"
  16. AU="Macias Gil, Raul"
  17. AU="Planchat, Arnaud"
  18. AU="McElrath, Erin E"
  19. AU="Koji Ueda"
  20. AU="Pillas, Diana J"
  21. AU="Thomson, Jason J"
  22. AU="Mitra, Kalyan"
  23. AU="Sanjay Desai"
  24. AU=Cox David J AU=Cox David J
  25. AU="Grebenok, Robert J."
  26. AU="Blackburne, Brittney"
  27. AU="Bortoleti, Bruna Taciane da Silva"
  28. AU="Ehrbar, Martin"
  29. AU="Lepre, Davide"
  30. AU="Olszewska, Zuzanna"
  31. AU="Vojta, Leslie"
  32. AU=Wickstrom Eric AU=Wickstrom Eric
  33. AU="Gangavarapu, Sridevi"
  34. AU="Hussein, Hazem Abdelwaheb"
  35. AU=Cai Yixin AU=Cai Yixin
  36. AU="Hüls, Anke"
  37. AU="Poondru, Srinivasu"
  38. AU="Coca, Daniel"
  39. AU="Lebeau, Paul"
  40. AU="Dehghani, Sedigheh"
  41. AU="Ishibashi, Kenji"
  42. AU="Xu, Yanhua"
  43. AU="Matera, Katarzyna"
  44. AU="Ait-Ouarab, Slimane"
  45. AU="Nicola, Coppede"
  46. AU="Dewitt, John M"
  47. AU="Sorin M. Dudea"
  48. AU="Tanusha D. Ramdin"
  49. AU="Hao, Zehui"
  50. AU="Chauhan, Aman"

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  1. Artikel ; Online: Wnt/β-catenin signaling pathway promotes abnormal activation of fibroblast-like synoviocytes and angiogenesis in rheumatoid arthritis and the intervention of Er Miao San.

    Chen, Simeng / Wang, Jin / Wang, Jiayu / Jia, Xiaoyi / Xuan, Zihua / Cheng, Zhiluo / Meng, Xiangwen / Su, Wenrui

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Band 120, Seite(n) 155064

    Abstract: Background: Er Miao San (EMS) is an important herbal formula and a representative prescription for the treatment of the downwards flow of damp-heat syndrome. Clinical practice has proven that EMS can effectively treat rheumatoid arthritis (RA). Previous ...

    Abstract Background: Er Miao San (EMS) is an important herbal formula and a representative prescription for the treatment of the downwards flow of damp-heat syndrome. Clinical practice has proven that EMS can effectively treat rheumatoid arthritis (RA). Previous studies have demonstrated that EMS regulates the functions of T cells and dendritic cells and affects the polarization of macrophages. However, it is not clear whether the inhibitory effect of EMS on RA is related to the regulation of abnormal synovial activation and angiogenesis.
    Purpose: The aim of this study was to elucidate the effect and potential mechanisms of EMS on the abnormal activation and angiogenesis of fibroblast-like synoviocytes (FLSs) in RA.
    Methods: The effect of EMS on rats with adjuvant arthritis (AA) and MH7A cells was examined by X-ray, haematoxylin-eosin (HE) staining, immunohistochemistry (IHC), ELISA and western blotting. Angiogenesis in AA rats was measured by a small animal ultrasound imaging system, immunofluorescence (IF) analysis and ELISA. An exchange between MH7A cells and HUVECs was induced using conditioned media that mimicked the microenvironment in vivo. CCK-8, western blotting, and scratch healing and Transwell migration assays were used to evaluate the effect of EMS on the Wnt/β-catenin signaling pathway and angiogenesis in the inflammatory microenvironment of RA.
    Results: Our results showed that EMS had a protective effect on AA rats. On the one hand, there was a decrease in paw swelling, the arthritis index, organ indices and proinflammatory factor levels, as well as relief of joint damage. On the other hand, blood flow, the number of immature blood vessels and proangiogenic factors were decreased. Furthermore, EMS reduced the expression of the Wnt/β-catenin signaling pathway in the synovial tissue of AA rats and MH7A cells. In the inflammatory microenvonrment of RA, the results were consistent.
    Conclusion: This study demonstrated that EMS could protect against RA by inhibiting the abnormal activation and angiogenesis of FLSs, and the mechanism may be related to inhibiting the activation of the Wnt/β-catenin signaling pathway.
    Mesh-Begriff(e) Animals ; Rats ; Synoviocytes ; Wnt Signaling Pathway ; Arthritis, Rheumatoid/drug therapy ; Fibroblasts ; Synovial Membrane ; Arthritis, Experimental/drug therapy
    Sprache Englisch
    Erscheinungsdatum 2023-09-02
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.155064
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Exploring the effect of Er miao San-containing serum on macrophage polarization through miR-33/NLRP3 pathway

    Liu, Min / Wang, Jin / Chen, Simeng / Meng, Xiangwen / Cheng, Zhiluo / Wang, Jiayu / Tan, Yanan / Su, Wenrui / Lü, Zhiyuan / Zhang, Min / Jia, Xiaoyi

    Journal of Ethnopharmacology. 2023 May, v. 307 p.116178-

    2023  

    Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Er miao San (EMS) has been shown to have good anti-inflammatory effects and is widely used in the clinical treatment of RA. However, the exact mechanism is not completely understood. The ...

    Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Er miao San (EMS) has been shown to have good anti-inflammatory effects and is widely used in the clinical treatment of RA. However, the exact mechanism is not completely understood. The aim of this study was to explore that EMS-containing serum affects M1/M2 polarization of macrophages and may be mediated through the microRNA (miRNA)-33/NLRP3 pathway, thereby elucidating the molecular mechanism of EMS treatment of RA. We screened for safe concentrations of EMS-containing serum by using CCK-8 measurement. RAW264.7 cells were cultured with lipopolysaccharide (LPS) (100 ng/mL) and interferon-γ (20 ng/mL) for 24 h to induce M1-type macrophages. Adenosine triphosphate (ATP) (5 mM) was added in the last 30 min to activate NLRP3. The content of miR-33 was detected by RT‒qPCR after transfection of the miRNA-33 mimic. The protein expression levels of NLRP3, ASC, caspase-1, Inducible Nitric Oxide Synthase (iNOS) and Arginase-1 (Arg-1) were detected by Western blot. The contents of IL-1β, IL-10, TNF-α, TGF-β and IL-18 in serum and cell supernatant were determined by ELISA. The fluorescence intensity of CD86 and CD206 was detected by immunofluorescence. The results showed that EMS-containing serum promoted the protein expression level of Arg-1 and the secretion levels of TGF-β and IL-10, inhibited the levels of iNOS, IL-1β and TNF-α, and regulated the balance of pro-inflammatory factors and anti-inflammatory factors. RT‒qPCR results showed that EMS-containing serum could reduce the level of miRNA-33. EMS-containing serum could reduce the expression of NLRP3 inflammasome-related proteins and downregulate the expression levels of IL-1β and IL-18. These results suggest that EMS exerts its effect on macrophage polarization through the miRNA-33/NLRP3 pathway. EMS-containing serum inhibits the activation of the NLRP3 inflammasome by downregulating miRNA-33, thus preventing the polarization of M1-type macrophages.
    Schlagwörter Western blotting ; adenosine triphosphate ; blood serum ; caspase-1 ; fluorescence ; fluorescent antibody technique ; inducible nitric oxide synthase ; inflammasomes ; interleukin-10 ; interleukin-18 ; lipopolysaccharides ; macrophages ; microRNA ; protein synthesis ; rheumatoid arthritis ; secretion ; traditional medicine ; transfection ; M1-type macrophages ; miRNA-33 ; NLRP3 ; Er miao San
    Sprache Englisch
    Erscheinungsverlauf 2023-05
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel ; Online
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116178
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: MX2: Identification and systematic mechanistic analysis of a novel immune-related biomarker for systemic lupus erythematosus.

    Meng, Xiang-Wen / Cheng, Zhi-Luo / Lu, Zhi-Yuan / Tan, Ya-Nan / Jia, Xiao-Yi / Zhang, Min

    Frontiers in immunology

    2022  Band 13, Seite(n) 978851

    Abstract: Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs. However, the current SLE-related biomarkers still lack sufficient sensitivity, specificity and predictive power for clinical application. Thus, it is ... ...

    Abstract Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs. However, the current SLE-related biomarkers still lack sufficient sensitivity, specificity and predictive power for clinical application. Thus, it is significant to explore new immune-related biomarkers for SLE diagnosis and development.
    Methods: We obtained seven SLE gene expression profile microarrays (GSE121239/11907/81622/65391/100163/45291/49454) from the GEO database. First, differentially expressed genes (DEGs) were screened using GEO2R, and SLE biomarkers were screened by performing WGCNA, Random Forest, SVM-REF, correlation with SLEDAI and differential gene analysis. Receiver operating characteristic curves (ROCs) and AUC values were used to determine the clinical value. The expression level of the biomarker was verified by RT‒qPCR. Subsequently, functional enrichment analysis was utilized to identify biomarker-associated pathways. ssGSEA, CIBERSORT, xCell and ImmuCellAI algorithms were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Finally, the transcriptional regulatory network of the biomarker was constructed, and the corresponding therapeutic drugs were predicted.
    Results: Multiple algorithms were screened together for a unique marker gene, MX2, and expression analysis of multiple datasets revealed that MX2 was highly expressed in SLE compared to the normal group (all P < 0.05), with the same trend validated by RT‒qPCR (P = 0.026). Functional enrichment analysis identified the main pathway of MX2 promotion in SLE as the NOD-like receptor signaling pathway (NES=2.492, P < 0.001, etc.). Immuno-infiltration analysis showed that MX2 was closely associated with neutrophils, and single-cell and transcriptomic data revealed that MX2 was specifically expressed in neutrophils. The NOD-like receptor signaling pathway was also remarkably correlated with neutrophils (r >0.3, P < 0.001, etc.). Most of the MX2-related interacting proteins were associated with SLE, and potential transcription factors of MX2 and its related genes were also significantly associated with the immune response.
    Conclusion: Our study found that MX2 can serve as an immune-related biomarker for predicting the diagnosis and disease activity of SLE. It activates the NOD-like receptor signaling pathway and promotes neutrophil infiltration to aggravate SLE.
    Mesh-Begriff(e) Biomarkers ; Gene Regulatory Networks ; Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Myxovirus Resistance Proteins/genetics ; Myxovirus Resistance Proteins/immunology ; NLR Proteins/metabolism ; Transcriptome
    Chemische Substanzen Biomarkers ; MX2 protein, human ; Myxovirus Resistance Proteins ; NLR Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-08-18
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.978851
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Exploring the effect of Er miao San-containing serum on macrophage polarization through miR-33/NLRP3 pathway.

    Liu, Min / Wang, Jin / Chen, Simeng / Meng, Xiangwen / Cheng, Zhiluo / Wang, Jiayu / Tan, Yanan / Su, Wenrui / Lu, Zhiyuan / Zhang, Min / Jia, Xiaoyi

    Journal of ethnopharmacology

    2023  Band 307, Seite(n) 116178

    Abstract: Headings ethnopharmacological relevance: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Er miao San (EMS) has been shown to have good anti-inflammatory effects and is widely used in the clinical treatment of RA. However, the exact ... ...

    Abstract Headings ethnopharmacological relevance: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Er miao San (EMS) has been shown to have good anti-inflammatory effects and is widely used in the clinical treatment of RA. However, the exact mechanism is not completely understood.
    Aim of the study: The aim of this study was to explore that EMS-containing serum affects M1/M2 polarization of macrophages and may be mediated through the microRNA (miRNA)-33/NLRP3 pathway, thereby elucidating the molecular mechanism of EMS treatment of RA.
    Materials and methods: We screened for safe concentrations of EMS-containing serum by using CCK-8 measurement. RAW264.7 cells were cultured with lipopolysaccharide (LPS) (100 ng/mL) and interferon-γ (20 ng/mL) for 24 h to induce M1-type macrophages. Adenosine triphosphate (ATP) (5 mM) was added in the last 30 min to activate NLRP3. The content of miR-33 was detected by RT‒qPCR after transfection of the miRNA-33 mimic. The protein expression levels of NLRP3, ASC, caspase-1, Inducible Nitric Oxide Synthase (iNOS) and Arginase-1 (Arg-1) were detected by Western blot. The contents of IL-1β, IL-10, TNF-α, TGF-β and IL-18 in serum and cell supernatant were determined by ELISA. The fluorescence intensity of CD86 and CD206 was detected by immunofluorescence.
    Results: The results showed that EMS-containing serum promoted the protein expression level of Arg-1 and the secretion levels of TGF-β and IL-10, inhibited the levels of iNOS, IL-1β and TNF-α, and regulated the balance of pro-inflammatory factors and anti-inflammatory factors. RT‒qPCR results showed that EMS-containing serum could reduce the level of miRNA-33. EMS-containing serum could reduce the expression of NLRP3 inflammasome-related proteins and downregulate the expression levels of IL-1β and IL-18. These results suggest that EMS exerts its effect on macrophage polarization through the miRNA-33/NLRP3 pathway.
    Conclusion: EMS-containing serum inhibits the activation of the NLRP3 inflammasome by downregulating miRNA-33, thus preventing the polarization of M1-type macrophages.
    Mesh-Begriff(e) Humans ; Arthritis, Rheumatoid/metabolism ; Inflammasomes/metabolism ; Interleukin-10/metabolism ; Interleukin-18/metabolism ; Interleukin-18/pharmacology ; Lipopolysaccharides/pharmacology ; Macrophages ; MicroRNAs/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Transforming Growth Factor beta/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Drugs, Chinese Herbal
    Chemische Substanzen Inflammasomes ; Interleukin-10 (130068-27-8) ; Interleukin-18 ; Lipopolysaccharides ; MicroRNAs ; NLR Family, Pyrin Domain-Containing 3 Protein ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; Drugs, Chinese Herbal
    Sprache Englisch
    Erscheinungsdatum 2023-01-26
    Erscheinungsland Ireland
    Dokumenttyp Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2023.116178
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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