Emodin mitigates rheumatoid arthritis through direct binding to TNF-α

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 26, 2025

Emodin has shown certain anti-rheumatoid arthritis (RA) activity in preliminary studies. However, the precise mechanisms of emodin's anti-RA effects, particularly its direct targets, remain unclear. This study aimed to evaluate emodin and elucidate potential mechanisms, with a specific focus on identifying molecular targets. Employing collagen-induced (CIA) rat model, along transcriptomic analysis, thermal proteome profiling (TPP) TNF-α-induced L929 cell was confirmed, TNF-α as target. Techniques such drug affinity responsive target stability (DARTS), cellular shift assay (CETSA), Affinity ultrafiltration-liquid chromatography/mass spectrometry (AUF-LC/MS), surface plasmon resonance (SPR) bio-layer interferometry (BLI) validated binding TNF-α. Molecular dynamics simulation, ELISA BLI further revealed that stabilizes asymmetric trimeric structure TNF-α, disrupting TNF-α-TNFR1 interaction. In vitro assays, including luciferase reporter gene MH7A demonstrated this disruption inhibits NF-κB activation, leading downregulation inflammatory mediators IL-6, IL-1β, COX2. conclusion, directly targets stabilizing blocking interaction, which subsequently suppresses downstream pathway activation contributes potent properties.

Язык: Английский

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Advancements in rheumatoid arthritis therapy: a journey from conventional therapy to precision medicine via nanoparticles targeting immune cells

Nanoscale, Год журнала: 2024, Номер 16(32), С. 14975 - 14993

Опубликована: Янв. 1, 2024

Rheumatoid arthritis (RA) is a progressive autoimmune disease that mainly affects the inner lining of synovial joints and leads to chronic inflammation. While RA not known as lethal, recent research indicates it may be silent killer because its strong association with an increased risk lung heart diseases. Patients develop these systemic consequences due regular uptake heavy drugs such disease-modifying antirheumatic medications (DMARDs), glucocorticoids (GCs), nonsteroidal anti-inflammatory medicines (NSAIDs),

Язык: Английский

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Cannabidiol regulates L-carnitine and butanoic acid metabolism by modulating the gut microbiota to ameliorate collagen-induced arthritis

Phytomedicine, Год журнала: 2024, Номер 136, С. 156270 - 156270

Опубликована: Ноя. 19, 2024

Язык: Английский

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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

Science China Life Sciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Язык: Английский

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Potential Mechanisms Underlying the Protective Effects of Lily Bulbs Extract and Characteristic Ingredients Against LPS-induced Inflammation in HaCaT Cells

Food Bioscience, Год журнала: 2025, Номер unknown, С. 106142 - 106142

Опубликована: Фев. 1, 2025

Язык: Английский

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Increased Alleviation of Bone Destruction in Individuals with Rheumatoid Arthritis via the Coinhibition of the METTL3 and YTHDF1 Axis by the Combination of Triptolide and Medicarpin

Engineering, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Transcriptomics of Various Diseases Reveals the Core Role of Immune System Pathways in Retinal Damage Repair and Nerve Regeneration

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Язык: Английский

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USP22 enhances atherosclerotic plaque stability and macrophage efferocytosis by stabilizing PPARγ

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Апрель 29, 2025

Atherosclerosis is a chronic inflammatory disease that strongly threatens human health, and macrophages play pivotal role in its pathogenesis. Ubiquitin-specific peptidase 22 (USP22) involved the regulation of macrophage inflammation. However, atherosclerotic microenvironment remains unclear. In this study, we found USP22 overexpression alleviated atherosclerosis progression ApoE-/- mice. vitro, silencing enhanced inflammation foam cell formation, efferocytosis was significantly impaired. Mechanistically, bound to peroxisome proliferator-activated receptor γ (PPARγ) inhibited ubiquitination, thereby stabilizing PPARγ promoting efferocytosis. addition, intraperitoneal injection inhibitor USP22i-S02 exacerbated summary, these findings indicate may be potential therapeutic target for treatment atherosclerosis.

Язык: Английский

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IGF2BP2 Drives Subchondral Bone Damage in Temporomandibular Joint Osteoarthritis through PPARγ/C-FOS-regulated Dual Pathways: NFATC1 Signaling and ATG16L2-Mediated Autophagy

American Journal Of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Unveiling the molecular mechanisms of stigmasterol on diabetic retinopathy: BNM framework construction and experimental validation

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Май 9, 2025

Background Diabetic retinopathy (DR), one of the most common complications diabetes, severely impacts patients’ quality life. The combined use traditional Chinese medicines Astragalus, Fructus ligustris, and Cornus officinalis has yielded considerable therapeutic effects in clinical DR treatment. Methods In this study, a multimodule framework (BNM) encompassing bioinformatics, network pharmacology, machine learning (ML) based on molecular fingerprints was innovatively developed to thoroughly investigate mechanisms medicine treating DR. Results A total 40 active components 12 core targets were identified. Enrichment analysis identified key pathways such as VEGF signaling pathway, TNF pathway HIF-1 pathway. Prediction models using targets, PPARG, constructed from GEO database validated via immune infiltration docking, revealing that PPARG may be potential target for Moreover, component medicine, stigmasterol, ML model fingerprints. vivo experiments demonstrated stigmasterol can regulate glucose lipid metabolism, improve systemic inflammatory levels, ameliorate ocular vascular changes by modulating expression PPARG. Conclusion BNM suggests an important treatment DR, with its mechanism potentially related VEGF/VEGFR

Язык: Английский

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