Sphingosine 1-phosphate signaling during infection and immunity

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 92, P. 101251 - 101251

Published: Aug. 24, 2023

Language: Английский

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Nanotechnology-empowered combination therapy for rheumatoid arthritis: principles, strategies, and challenges

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 22, 2024

Abstract Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy frequently associated inadequate efficacy, drug resistance, severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers incomparable opportunity for developing advanced against RA. First, it allows co-delivering multiple drugs augmented physicochemical properties, targeted delivery capabilities, controlled release profiles. Second, enables therapeutic nanomaterials development, thereby expanding regimens include multifunctional nanomedicines. Lastly, facilitates the construction of all-in-one nanoplatforms assembled modalities, such as phototherapy, sonodynamic therapy, imaging. Thus, promising solution current bottleneck both RA treatment diagnosis. This review summarizes rationale, advantages, recent advances nano-empowered It also discusses safety considerations, drug–drug interactions, potential translation. Additionally, provides design tips outlook on future developments The objective this achieve comprehensive understanding mechanisms underlying unlock maximum nanotechnology, facilitating smooth transition research findings from laboratory practice.

Language: Английский

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L-selectin Promotes Migration, Invasion and Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via NF-kB Signaling Pathway

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by chronic inflammation of the synovium and progressive joint damage. Fibroblast-like synoviocytes (FLSs) exhibit excessive proliferative aggressive phenotypes play major role in pathophysiology RA. Previous studies have confirmed pathologic L-selectin cell adhesion migration. In rheumatoid models, regulates leukocyte homing, which leads to inflammation. Moreover, knockout mice, there reduction However, associations with FLSs RA remain unclear. This study aims reveal effect on RA-FLSs investigate molecular mechanism Our findings indicated that was significantly expressed synovial tissues RA-FLSs. silencing reduced migration invasion attenuated secretion pro-inflammatory cytokines TNF-α, IL-1β IL-6 vitro. investigations into mechanisms revealed activated nuclear factor kappa-B (NF-κB) signaling pathway while blocking this could compromise effects L-selectin. Finally, vivo experiments collagen-induced rat model alleviated inflammatory infiltration cartilage destruction, validated NF-κB pathways observed summary, we show enhances through activation pathways, ultimately worsening progression

Language: Английский

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Eupalinolide B alleviates rheumatoid arthritis through the promotion of apoptosis and autophagy via regulating the AMPK/mTOR/ULK-1 signaling axis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114179 - 114179

Published: Jan. 28, 2025

Language: Английский

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The dual anti-inflammatory and anticoagulant effects of Jianpi Huashi Tongluo prescription on Rheumatoid Arthritis through inhibiting the activation of the PI3K/AKT signaling pathway

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Background Rheumatoid arthritis (RA) is often accompanied by abnormal changes in inflammatory responses and coagulation-fibrinolysis indicators. Jianpi Huashi Tongluo Prescription - Xinfeng Capsule (XFC), a traditional Chinese medicine formulation comprising multiple herbal ingredients, widely used clinically for the treatment of RA. It exhibits dual anti-inflammatory anticoagulant effects. However, specific mechanisms underlying its actions remain to be further investigated. Objective This study aims elucidate XFC Methods A multidimensional methodological framework was employed. Firstly, through retrospective clinical data mining, combined with Apriori algorithm random walk models, an in-depth analysis conducted explore potential associations between improvements coagulation markers among RA patients. Secondly, adjuvant-induced rat model established directly observe effects vivo . Furthermore, bioinformatics network pharmacology techniques were applied decipher major active components their targets XFC. Lastly, co-culture system patient-derived peripheral blood mononuclear cells (RA-PBMCs) vascular endothelial (VECs) mimic microenvironment, validated vitro Results Data mining revealed abnormally elevated levels such as fibrinogen (FBG), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (Hs-CRP), rheumatoid factor (RF) patients (p < 0.001), emphasized close correlation improvement these including Hs-CRP, ESR, RF (confidence >60% lift >1). Animal experimental indicated that effectively reduced coagulant (IL-6, D-D, FBG, PAF, VEGF, TF) (AA) rats while enhancing expression factors (IL-10) 0.05). Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) results suggested pharmacodynamic mechanism may closely related regulation PI3K/AKT signaling pathway. Additionally, molecular docking show main XFC, namely, calycosin-7-O-beta-D-glucoside, calycosin, formononetin, exhibit excellent core HIF1A, PTGS2, MMP9. In showed inhibited RA-related hypercoagulable states suppressing activation Conclusion demonstrates exerts effects, at least part, inhibiting pathway, providing insights into targeted therapy

Language: Английский

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Drug Delivery Approaches for Rheumatoid Arthritis: Recent Advances and Clinical Translation Aspects

Critical Reviews in Therapeutic Drug Carrier Systems, Journal Year: 2025, Volume and Issue: 42(3), P. 1 - 54

Published: Jan. 1, 2025

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized with symmetrical progression of joint deformity that often diagnosed at chronic condition other associated pathological conditions such as pericarditis, keratitis, pulmonary granuloma. Despite the understanding RA pathophysiology in progression, current clinical treatment options disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, and non-steroidal anti-inflammatory (NSAIDs) provide only palliative therapy while causing adverse side effects off-target multi-organ toxicity risk infections. Further, available drug delivery strategies to treat pathogenicity does not successfully reach site action due various barriers phagocytosis first pass effect addition complexity unknown etiology, thereby leading development irreversible dysfunction. Therefore, novel effective remain an unmet need control maintain balance between pro- cytokines. This review provides comprehensive outlook on its corresponding progression. Contributions synoviocytes macrophages, fibroblast-like cells increasing invasiveness exacerbate damage also outlined this review, which could be potential future therapeutic target complement existing regimens controlling pathogenesis. smart approaches under research achieve maximum efficacy minimal have been discussed, turn emphasize challenges perspectives addressing complications.

Language: Английский

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Taurine is a potential therapy for rheumatoid arthritis via targeting FOXO3 through cellular senescence and autophagy

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0318311 - e0318311

Published: April 16, 2025

Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease closely related to aging with unclear pathogenic mechanisms. This study aims identify the biomarkers in RA, and autophagy using bioinformatics machine learning explore binding stability of taurine target utilizing computer-aided drug design (CADD). Methods We identified differentially expressed genes (DEGs) for then crossed gene libraries common (Co-genes). performed Gene Ontology (GO), Kyoto Encyclopedia Genome (KEGG), ClueGO analysis Co-genes. The Co-genes were subjected support vector machine-recursive feature elimination (SVM-RFE), Degree, Betweenness algorithms get hub genes, verified by an artificial neural network (ANN). After continuing perform least absolute shrinkage selection operator (LASSO) weighted co-expression (WGCNA) on Co-genes, results obtain which imported into various validation sets receiver operating characteristics (ROC) key genes. analyzed microRNA/TF network, enriched pathways, immune cell infiltration protein was CADD. Finally, we used Western blot vitro experimental verification. Results obtained 74 cellular senescence, regulation programmed death. model prediction works well ANN. (MMP9, CXCL10, IL15, FOXO3) tested ROC excellent efficacy. In FOXO3 expression down-regulated while MMP9, IL15 upregulated, negatively correlated IL15. Two miRNAs (hsa-mir-21-5p, hsa-mir-129-2-3p) four TFs (CTCF, KLF, FOXC1, TP53) associated cells positively Plasma cells, CD8 T memory-activated CD4 follicular helper aggregating RA. molecular docking dynamics simulation. experiments have indicated that can upregulate treat RA through FOXO3-Parkin signaling pathway. Conclusions are autophagy. Taurine might be promising against via targeting senescence FOXO3.

Language: Английский

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A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m

Life, Journal Year: 2024, Volume and Issue: 14(6), P. 751 - 751

Published: June 12, 2024

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys and cartilage, resulting in synovitis pannus formation. Timely detection effective management RA are pivotal for mitigating inflammatory consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents promising avenue diagnosis response to treatment assessment. Radiopharmaceutical such as technetium-99m (

Language: Английский

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The Combination of Hydrogels and Rutin-loaded Black Phosphorus Nanosheets Treats Rheumatoid Arthritis

Materials Today Bio, Journal Year: 2024, Volume and Issue: 29, P. 101264 - 101264

Published: Sept. 28, 2024

Language: Английский

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Recent developments in the synovial fibroblast pathobiology field in rheumatoid arthritis

Current Opinion in Rheumatology, Journal Year: 2023, Volume and Issue: 36(1), P. 69 - 75

Published: Sept. 12, 2023

Purpose of review Synovial fibroblasts are the central cells connective tissue homeostasis. In rheumatoid arthritis (RA) tissue, synovial activated because proinflammatory environment very early in disease. Epigenetic alterations RASF result a permanently stage, and involved many processes RA pathophysiology. Therefore, several recent findings last 18 months with focus on activation function summarized. Recent profoundly altered epigenome leads to an invasive phenotype increased migration, adhesion invasion into cartilage, which was further characterized studies. subtypes subtype dynamics were evaluated using high-resolution techniques better understand Many studies addressing interactions immune or stromal cell types have been published showing that interact different contributing not only their own pro-inflammatory response but also other cells. Summary Highly interesting revealing mechanisms functions published, subsets characterized, elucidated, all contribute understanding role development progression.

Language: Английский

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