Ferroptosis and endoplasmic reticulum stress in rheumatoid arthritis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 15, 2024

Ferroptosis is an iron-dependent mode of cell death distinct from apoptosis and necrosis. Its mechanisms mainly involve disordered iron metabolism, lipid peroxide deposition, imbalance the antioxidant system. The endoplasmic reticulum organelle responsible for protein folding, Ca

Язык: Английский

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Inhibition of ASIC1a reduces ferroptosis in rheumatoid arthritis articular chondrocytes via the p53/NRF2/SLC7A11 pathway

The FASEB Journal, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 6, 2025

The activation of acid-sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads an increase calcium influx, thereby exacerbating the degeneration articular chondrocytes rheumatoid arthritis (RA). It has been suggested that inhibition influx could potentially impede chondrocyte ferroptosis. cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator Recent studies suggest tumor suppressor gene p53 facilitates induction ferroptosis by suppressing upregulation SLC7A11. This process mediated nuclear factor erythroid 2-related 2 (NRF2), transcription integral maintenance cellular redox homeostasis and regulation inflammatory responses. study aims investigate role ASIC1a RA determine involvement p53/NRF2/SLC7A11 pathway its underlying mechanism. In vitro experiments revealed acidosis induces reduces expression NRF2 SLC7A11 chondrocytes. Moreover, significantly increased protein levels Pifithrin-α (PFN-α), inhibitor, mitigated acidosis-induced restored diminished Furthermore, PcTx-1, inhibited acidification-induced ferroptosis, enhanced NRF2, reduced expression. vivo demonstrated ASIC1a-specific inhibitor PcTx-1 ameliorated histopathological characteristics ankle joints collagen-induced (CIA) mice, decreased expression, These findings may mitigate RA, via pathway.

Язык: Английский

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Neutrophils: a Central Point of Interaction Between Immune Cells and Nonimmune Cells in Rheumatoid Arthritis

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Март 28, 2025

Язык: Английский

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Targeting BMAL1 reverses drug resistance of acute myeloid leukemia cells and promotes ferroptosis through HMGB1-GPX4 signaling pathway

Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 150(5)

Опубликована: Май 4, 2024

Abstract Purpose Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses serious threat to human health. Exploring alternative therapeutic strategies capable of inducing modes cell death, such as ferroptosis, holds great promise viable and effective intervention. Methods We analyzed online database data collected clinical samples verify the expression function BMAL1 in AML. conducted experiments on AML proliferation, cycle, chemotherapy resistance by overexpressing/knocking down using assays MDA detection BODIPY 581/591 C11 staining. validated transcriptional regulation HMGB1 through ChIP assay, luciferase RNA level detection, western blotting. Finally, we confirmed results our at animal level. Results up-regulation an observed phenomenon patients. Furthermore, there existed strong correlation between elevated levels inferior prognosis individuals with found knocking inhibited growth blocking cycle. Conversely, overexpressing promoted proliferation. Moreover, research revealed ferroptosis cells BMAL1-HMGB1-GPX4 pathway. can enhance efficacy certain first-line cancer drugs, including venetoclax, dasatinib, sorafenib. Conclusion Our suggest plays crucial regulatory role drug resistance, ferroptosis. could be potential important target for

Язык: Английский

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Molecular Mechanisms of Immunoinflammatory Infiltration and Ferroptosis in Arthritis Revealed by a Combination of Bioinformatics and Single-Cell Analysis

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 2409 - 2432

Опубликована: Фев. 1, 2025

Osteoarthritis (OA) is a widespread chronic inflammatory disease in orthopedics, and its molecular mechanisms are still poorly understood. The purpose of this work was to detect the immunological infiltration OA manner cell death utilizing bioinformatics single-cell analysis order provide guidelines for clinical therapy medicine. Ferroptosis -associated genes were sourced from ferroptosis Database, bioinformatic expression profiles chosen Gene Expression Comprehensive gene information taken GeneCards. To ascertain categorization status cells, conducted. Protein-protein interaction networks established by SRING analysis, functional enrichment examined Kyoto Encyclopedia Genes Genomes (KEGG) Ontology (GO) databases. important proteins immune-ferroptosis elucidated through co-analysis. Last but not least, network pharmacology docking support mechanism which resveratrol controls OA. development found be tightly related chondrocytes immune particularly T macrophage according profile. In patients with OA, also revealed notable B NK monocytes, macrophages. hub shown enriched responses, chemokine-mediated signaling pathways, analysis. main pathways included autophagy, ferroptosis, HIF-1 pathway, PI3K-Akt FoxO pathway. significant that contributes advancement osteoarthritis. lessened regulation GPX4, TFRC, SLC7A11. Various infiltrates, especially cells macrophages, play an role progression ameliorates modulating chondrocyte ferroptosis.

Язык: Английский

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Near-Infrared Fluorescent Lysosomal Viscosity Probe with Strong Solid Fluorescence for Rapid Imaging of Rheumatoid Arthritis

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Rheumatoid arthritis (RA) is a chronic disease of widespread concern worldwide, and there an urgent need to develop sensitive methods for the rapid detection RA. Previous studies have shown that RA closely related lysosomal dysfunction. Lysosomal viscosity important microenvironmental parameter reflecting state lysosomes, but due lack probes demonstrate correlation between RA, changes in during remain unclear. For this purpose, we report herein lysosome-targeted near-infrared fluorescent molecular rotor probe DSMP investigate This utilizes dicyanomethylene-4H-benzothiopyran as electron acceptor fluorophore piperazine unit donor targeting group lysosomes. In addition, shows strong solid fluorescence response can effectively target lysosomes detect live cells. Based on this, established mouse model using λ-carrageenan. Mice imaging show quickly image tissues exhibit signals significantly brighter than those normal joint tissues. indicates increase RA; therefore, serve indicator be effective tool research.

Язык: Английский

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Investigating ferroptosis-related genes NFE2L2 in neutrophils for ankylosing spondylitis: therapeutic potential of cassia twigs

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 10, 2025

We determined the relationship between ferroptosis and immune cells in ankylosing spondylitis role of Chinese herbal medicine Cassia twigs treating spondylitis. analyzed clinical data on spondylitis, transcriptome data, single-cell sequencing genes related to twigs. Clinical variables AS were selected through logistic regression analysis combined with machine learning. GSEA enrichment performed ferroptosis, drug-related genes, identify key drug targets AS, as well as, cells. Then, cell subtypes analyzed. Finally, interconnections intercellular communication. Five variables, including neutrophils, screened for analysis. The AUC experimental group was 0.859 that validation 0.807. Ferroptosis gene NFE2L2 identified final target AS; it upregulated downregulated control by immunohistochemical verification, both which statistically significant (P < 0.001). Neutrophils divided into two subgroups: high expression low NFE2L2. Through molecular docking, found effectively act important AS. herb can treat acting protein structure

Язык: Английский

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Identification biomarkers and therapeutic targets of disulfidptosis-related in rheumatoid arthritis via bioinformatics, molecular dynamics simulation, and experimental validation

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 13, 2025

The relationship between disulfidptosis and rheumatoid arthritis (RA) remains unclear. We aimed to identified biomarkers disulfidptosis-related in RA revealed potential targeted drugs. Two microarray datasets (GSE93272, GSE45291) related were downloaded from the Gene Expression Omnibus (GEO) database. Disulfidptosis-related genes(DRGs) extracted FerrDb GSE93272 was used identify DRGs, GSE45291 verify results. Multivariate Cox regression analysis candidate disulfidptosis-associated hub genes. differentiated values of DRGs determined by receiver operator characteristic (ROC) monofactor judge their quality as biomarkers. RT-qPCR validate expression Additionally, we analyzed connection genes filtration immune cells RA. made predictions about miRNAs, TFs possible drugs that regulate Subsequently, molecular docking carried out predict combination with targets. Finally, dynamics simulation conducted further findings. Oxoacyl-ACP Synthase Mitochondrial(OXSM) a biomarker high diagnostic value, an model based on OXSM for single gene constructed. showed accuracy distinguishing healthy controls (AUC = 0.802) validated external datasets, showing excellent power 0.982). Twelve against recognized comparative toxicogenomics database (CTD). Molecular results ICG 001 had highest binding affinity OXSM, simulations confirmed stability this complexes. Furthermore, CIBERSORT significant correlation cell infiltration regulatory network TFs-gene-miRNAs comprising 8 miRNAs 34 identified. significantly increased peripheral blood patients compared controls, consistent bioinformatics analysis. These studies suggest may be therapeutic target diagnosing RA, drug findings provide new avenues effective diagnosis treatment

Язык: Английский

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PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells

Current Cancer Drug Targets, Год журнала: 2024, Номер 24(10), С. 1047 - 1060

Опубликована: Фев. 1, 2024

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in head and neck. Elucidating molecular mechanisms underlying OSCC occurrence development important for therapy. Dysregulated palmitoylation-related enzymes have been reported several but OSCC.

Язык: Английский

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Chitosan-based self-healing thermosensitive hydrogel loaded with siHMGB1 for treatment of rheumatoid arthritis via macrophage repolarization

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 282, С. 137102 - 137102

Опубликована: Окт. 31, 2024

Язык: Английский

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