Deciphering hub genes and immune landscapes related to neutrophil extracellular traps in rheumatoid arthritis: insights from integrated bioinformatics analyses and experiments

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Neutrophil extracellular traps (NETs), microreticular structure formed after neutrophil death, have recently been implicated in RA pathogenesis pathological mechanisms. However, the underlying molecular mechanisms key genes involved NET formation remain largely unknown. We obtained single-cell RNA sequencing data of tissues from Gene Expression Omnibus (GEO) database performed cellular annotation intercellular communication analyses. Subsequently, three microarray datasets were collected for training cohort correlated with bulk RNA-seq dataset associated NETs. Differentially expressed identified, weighted gene correlation network analysis was used to characterize association. Using machine learning techniques, we identified most important hub develop evaluate nomogram diagnostic model. CIBERSORT elucidate relationship between immune cells. An external validation verify pivotal expression construct co-regulatory networks using NetworkAnalyst platform. further investigated immunohistochemistry (IHC) an adjuvant-induced rat model real-time quantitative polymerase chain reaction (RT-qPCR) clinical cohort. Seven subpopulations through downscaling clustering, neutrophils likely crucial cell clusters RA. Intercellular highlighted fibroblasts. In this context, 4 (CRYBG1, RMM2, MMP1, SLC19A2) NETs identified. A value developed evaluated. Immune infiltration indicated associations landscape IHC RT-qPCR findings showed high CRYBG1, MMP1 neutrophilic cells, lower SLC19A2. Correlation emphasized close laboratory markers patients This study first elucidated heterogeneity microenvironment SLC19A2 validated as potential NET-associated biomarkers, offering insights tools immunotherapeutic strategies

Language: Английский

---

Paeoniflorin Attenuates APAP-Induced Liver Injury via Intervening the Crosstalk Between Hepatocyte Pyroptosis and NETs

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1493 - 1493

Published: Feb. 11, 2025

(1) Liver injury caused by an overdose of acetaminophen (APAP) represents a major public health concern. Paeoniflorin (PF) has been reported to have anti-inflammatory and liver-protective effects, but the underlying mechanisms remain unclear. This study aimed investigate effect PF on crosstalk between pyroptosis NETs in AILI. (2) APAP-treated C57BL/6J mice were used demonstrate protective liver injury. HepG2 dHL-60 cells cultured effects hepatocyte neutrophil extracellular traps (NETs) vitro. Moreover, cell co-culture experiments performed, treated with NETs-depleting agent inhibitor improvement AILI induced through regulating NETs. (3) significantly alleviated Additionally, inhibited expression pyroptosis-related proteins, high-mobility group box 1 (HMGB1), NETs-associated proteins vitro vivo. The demonstrated that not only triggered pyroptosis, also suppressed In depleted neutrophils, level notably decreased, indicating diminished impact PF. Similarly, formation was reduced receiving compared APAP group. Compared DNase I alone, reduction combined serum ALT AST levels decreased from 46.857% 39.927% 44.347% 33.419%, respectively. DSF 45.347% 36.419%, (4) therapeutic Its mechanism involves regulation research substantiates pharmacological promise as intervention for acute

Language: Английский

---

Application of Nanomaterials Targeting Immune Cells in the Treatment of Chronic Inflammation

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 13925 - 13946

Published: Dec. 1, 2024

Chronic inflammation is a common characteristic of all kinds diseases, including autoimmune metabolic and tumors. It distinguished by the presence low concentrations inflammatory factors stimulating body for an extended period, resulting in persistent state infection. This condition manifested aggregation infiltration mononuclear cells, lymphocytes, other immune leading to tissue hyperplasia lesions. Although various anti-inflammatory medications, glucocorticoids non-steroidal drugs (NSAIDs), have shown strong therapeutic effects, they lack specificity targeting ability, require high dosages, which can lead severe adverse reactions. Nanoparticle drug delivery mechanisms possess capacity minimize effect on healthy cells or tissues due their capabilities sustained release properties. However, most nanosystems only target sites rather than specific types leaving room further improvement effects nanomaterials. article reviews current research progress role diverse inflammation, focusing functions neutrophils macrophages during inflammation. provides overview domestic international applications nanomaterials targeted therapy aiming establish conceptual foundation utilization treatment chronic offer new perspectives avoidance management

Language: Английский

---

Application of Single‐Cell Genomics to Animal Models of Periodontitis and Peri‐Implantitis

Journal Of Clinical Periodontology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

This narrative review aims to synthesize current knowledge on integrating single-cell genomics technologies with animal models of periodontitis and peri-implantitis.

Language: Английский

---