Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Pharmacotherapy is a treatment for rheumatoid arthritis with limitations, such as poor drug targeting, low effective dosage at the inflammatory site, and high systemic toxicity. The combined application of drug-loaded nanobubbles ultrasound technology provides new technique treatment.
Language: Английский
Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice, Journal Year: 2025, Volume and Issue: 4, P. 4 - 14
Published: Jan. 17, 2025
Rheumatoid arthritis (RA) is a multifactorial incurable immune-inflammatory disease. Progression leads to joint deformation, cartilage and bone tissue destruction, subsequent disability. The primary goal of RA pharmacotherapy achieve disease remission. For this purpose, several classes drugs are used: basic anti-inflammatory (DMARDs), which large group synthetic biological that combined according their ability influence the pathogenetic mechanisms RA; glucocorticoids, recommended for use in combination with DMARDs; non-steroidal drugs, used relieve acute chronic pain. treatment long-term process, condition not always safe effective, discontinuation 20–50 % patients. Therefore, there need develop new pharmacological targets can increase drug effectiveness reduce toxicity. One promising therapeutic target proteinase-activated receptors (PARs), particularly PAR2, whose activation contributes occurrence inflammation, fibrosis, proliferation connective tissue. Experiments have demonstrated inhibition PAR2 activity prevents development pathogenesis positively modifies course search inhibit was carried out following directions: indirect blockade activity; creation monoclonal antibodies; inhibitors among peptide compounds; synthesis low-molecular-weight inhibitory substances.
Language: Английский
Citations
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Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 29, 2025
Overproduction of reactive oxygen species (ROS), elevated synovial inflammation, hyperplasia and fibrosis are the main characteristic microenvironment in rheumatoid arthritis (RA). Macrophages fibroblast-like synoviocytes (FLSs) play crucial roles progression RA. Hence, synergistic combination ROS scavenging, macrophage polarization from pro-inflammatory M1 phenotype towards M2 anti-inflammatory phenotype, restoring homeostasis FLSs will provide a promising therapeutic strategy for In this study, we successfully synthesized metformin-derived carbon dots (MCDs), investigated antirheumatic effect vivo vitro. Designed MCDs could target inflamed cells accumulate at inflammatory joints collagen-induced (CIA) rats. investigation suggested that reduced inflammation hyperplasia, ultimately prevented cartilage destruction, bone erosion, CIA addition, eliminated cellular macrophages RA through enzyme-like catalytic activity as well inhibiting NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, effectively polarizing them into to realize effect. Furthermore, inhibit proliferation, migration, FLSs. Mechanistically, restored while reducing level by blocking IL-6/gp130 pathway. Combined with preferable biocompatibility, offer prospective treatment approach
Language: Английский
Citations
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Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 3, 2025
Fibroblast-like synoviocytes (FLSs) and osteoclasts are central cells in the maintenance of joint homeostasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease joints that induces cytokine-activated FLSs progressive bone erosion. Interactions between other cells, such as T B have been recognized development RA. Here we hypothesized calcium released from by mature might activate FLSs, which also affected cytokines inflamed synovium. Osteoclastogenesis occurs presence cytokine-stimulated FLS medium, disc activates migration. We first investigated cytokine feedback loop osteoclast maturation. Moreover, addressing role sodium-bicarbonate cotransporter NBCn1 osteoclastogenesis, found inhibition attenuated infinite osteoclasts. In collagen-induced mouse model, NBC reduced RA pathological phenotype resorption area femur. These results suggest modulation crosstalk inhibiting could be considered to develop pioneering strategies combat severity dysregulated
Language: Английский
Citations
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Work, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 21, 2025
Background Individuals with arthritis often face significant challenges in their activities of daily living and work performance, resulting substantial effects on both personal professional lives. Objective This study aims to determine whether workers within the Canadian working-age population are more or less likely miss work, sustain injuries, experience activity limitations compared those without arthritis. Methods The analysis utilized data from Community Health Survey, focusing employed individuals over 20 two datasets: 2015–2016 (n = 107,705) 2017–2018 112,947). Logistic regression examined occupational health factors, while bivariate analyses via chi-squared tests (p < 0.01) filtered variables Tukey's HSD was used for post hoc 0.05). Multinomial models addressed complex responses, Wald's test differences between males females. Results 27,720) were difficulties functioning report injury non-arthritis counterparts. Women also joblessness. Men absences but women men. Conclusion Despite being heavily impacted terms functionality, there is a disconnect accommodations provided usage. Further research inclusive (e.g., ergonomic tools equipment, flexible arrangements) self-management strategies that can account problems faced by need be established.
Language: Английский
Citations
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Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 752, P. 151462 - 151462
Published: Feb. 12, 2025
Language: Английский
Citations
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MedComm, Journal Year: 2025, Volume and Issue: 6(3)
Published: March 1, 2025
Neutrophil extracellular traps (NETs) are unique fibrous structures released by neutrophils in response to various pathogens, exhibiting both anti-inflammatory and proinflammatory effects. In autoimmune conditions, NETs serve as crucial self-antigens triggering inflammatory cascades activating the inflammasome complement systems, disrupting self-tolerance mechanisms accelerating responses. Furthermore, play a pivotal role modulating immune cell activation, affecting adaptive This review outlines intricate relationship between diseases, including arthritis, systemic Behçet's disease, lupus erythematosus, kidney skin sclerosis, vasculitis, gouty arthritis. It highlights potential of targeting therapeutic strategy diseases. By examining dynamic balance NET formation clearance this offers critical insights theoretical foundation for future research on NET-related mechanisms. Advances systems biology, flow cytometry, single-cell multiomics sequencing have provided valuable tools exploring molecular NETs. These advancements renewed focus offering promising avenues further investigation into their clinical implications.
Language: Английский
Citations
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Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102481 - 102481
Published: March 1, 2025
Language: Английский
Citations
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Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13
Published: March 26, 2025
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes synovial joint inflammation as well bone destruction and erosion, typically characterized by pain, swelling, stiffness, with complications persistent pain after remission posing significant health burden for RA patients. The etiology of has not yet been fully elucidated, but large number studies have shown the initiation in closely related to T-cell activation, production variety pro-inflammatory cytokines, macrophage M1/M2 imbalance, homeostatic imbalance intestinal flora, fibroblast-like synoviocytes (FLSs) tissue macrophages (STMs) lumen joints exhibit an aggressive phenotype. While resolution less discussed, therefore, we provided systematic review relevant mechanisms including blocking T cell regulating polarization status, modulating signaling pathway FLSs, subpopulation STMs, inhibiting inflammatory factors, probable its management methods. Achieving crucial improving quality life long-term prognosis Thus, understanding these provide novel potential further drug development treatment RA.
Language: Английский
Citations
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Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: March 27, 2025
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction, with limited therapeutic options. This study investigated the potential of gastrodin (GAS), natural phenolic glycoside derived from Gastrodia elata, in targeting lysine acetyltransferase 8 (KAT8) to suppress histone H3K9 lactylation (H3K9la), novel post-translational modification linked inflammatory responses. Methods: The effect GAS on RA was verified constructing models vivo vitro . Molecular docking, surface plasmon resonance (SPR) assays, overexpression silencing experiments were used verify results. Results: In demonstrated that (10–20 μM) significantly inhibited lipopolysaccharide (LPS)-induced expression pro-inflammatory cytokines (IL-6, MMP1, MMP13) fibroblast-like synoviocytes (FLS) THP-1 macrophages downregulating glycolysis lactate production. docking assays confirmed KAT8 as direct target GAS, dissociation constant ( K D ) 413.72 μM. Overexpression revealed destabilized KAT8, thereby reducing H3K9la levels. , (20 mg/kg) ameliorated swelling hyperplasia Sprague-Dawley rat adjuvant-induced (AIA) model, correlating decreased IL-6 expression. Discussion: These findings establish promising agent for modulating KAT8-mediated lactylation, providing new insights into epigenetic regulation inflammation.
Language: Английский
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Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 8, 2025
Rhizomes of Drynaria quercifolia have long been traditionally used to manage rheumatic pain. However, there is limited research supporting this traditional practice and insufficient evidence demonstrating the molecular mechanisms action plant-derived bioactives in rheumatoid arthritis (RA). The current study aims identify effective components methanol rhizome extract (DME) their probable pharmacological alleviating Rheumatoid Arthritis (RA) using network-pharmacology, docking, molecular-dynamics simulations, gene expression-based validation. Gas chromatography-mass spectrometry (GC-MS) based screening identified 41 volatile phytocomponents from DME having drug-like potentiality. Network pharmacology-based revealed 117 therapeutic targets for RA which 11 as core targets. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis indicated that key target genes were mostly enriched inflammatory response associated with multiple signalling pathways. Molecular docking dynamics studies proteins like serine/threonine-protein kinase (AKT1), peroxisome proliferator-activated receptor alpha (PPARA), gamma (PPARG), exhibited strong binding affinity stable interactions present DME. For experimental verification FCA (Freund's complete adjuvant)-induced chronic model employed further investigation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results validated significantly (p ≤ 0.05) regulate expression AKT PPARG model. Moreover, confirmed downregulated pro-inflammatory mediators COX-2, IL-6 TNF-α at protein levels also normalized different oxidative stress parameters both low high dose groups DME-treated arthritic animals. In conclusion, network-based silico approach probably act a synergistic way modulate RA, was by studies. Therefore, could be potential alternative immunomodulatory therapies combat related conditions.
Language: Английский
Citations
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