GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 1174 - 1186

Published: Jan. 13, 2025

This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator this process. A ferroptosis-related gene risk coefficient model was constructed using differential expression analysis GSE70362 dataset. The significant factor IVDD progression. shown to promote nucleus pulposus cells (NPCs) by regulating AKR1C3 through TLR2 pathway. In vitro vivo experiments demonstrated that knockdown reduced ferroptosis, improved cell viability, mitigated extracellular matrix degradation, whereas overexpression exacerbated these processes. Furthermore, found be crucial for GATA6-mediated modulation TLR2-AKR1C3 axis significantly impacted NPCs. These findings suggest targeting its downstream pathway may provide new therapeutic approaches IVDD.

Language: Английский

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Molecular mechanism of macrophage polarization regulating the cell senescence of nucleus pulposus during intervertebral disc degeneration

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114131 - 114131

Published: Feb. 6, 2025

Language: Английский

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Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

JOR Spine, Journal Year: 2023, Volume and Issue: 7(1)

Published: Dec. 22, 2023

Intervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained.

Language: Английский

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Molecular mechanism of mechanical pressure induced changes in the microenvironment of intervertebral disc degeneration

Inflammation Research, Journal Year: 2024, Volume and Issue: 73(12), P. 2153 - 2164

Published: Oct. 8, 2024

Language: Английский

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ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 28, 2025

Language: Английский

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The Significance of Cellular Senescence Hub Genes in the Diagnosis and Subtype Classification of a Comprehensive Database of Gene Expression in Intervertebral Disc Degeneration

JOR Spine, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 1, 2025

Intervertebral disc degeneration (IVDD) is a complex age-related physiological process, with cellular senescence (CS) being primary contributing factor. However, the precise role of CS and its associated genes in IVDD remains unclear. In this study, we performed differential expression analysis on GSE124272 GSE150408 datasets from GEO database identified 53 differentially expressed senescence-related (CSRGs). We then conducted Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses to explore their functions pathways. hub by constructing protein-protein interaction (PPI) network further validated these using clinical samples. explored functional prognostic significance support vector machine recursive feature elimination (SVM-RFE), random forest (RF), least absolute shrinkage selection operator (LASSO) algorithms. visualized correlation between levels four core immune cell infiltration heat maps histograms. Finally, graphene oxide 297 (DEGs) investigate IVDD. ultimately CSRGs DUSP3, MAPKAPK5, SP1, VEGFA, various algorithms Our results revealed that DUSP3 SP1 were upregulated IVDD, while MAPKAPK5 VEGFA downregulated. Immune demonstrated positively correlated levels, whereas negatively correlated. summary, play an important pathogenesis our study gene cluster may guide future therapeutic strategies for

Language: Английский

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Exploring the mechanisms of PANoptosis in osteoarthritis and the therapeutic potential of andrographolide through bioinformatics and single-cell analysis

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 31, 2025

Osteoarthritis (OA) is a degenerative joint disease marked by the breakdown of cartilage, where apoptosis plays key role. Although apoptosis-related genes in OA have been studied, detailed analysis PANoptosis-related and search for therapeutic drugs remains limited. We performed bioinformatics combined with single-cell RNA sequencing to examine gene expression cartilage. Key PANoptosis critical cell populations involved progression were identified. Drug prediction led selection Andrographolide (AG), whose effects validated through molecular docking, Western blotting, qRT-PCR chondrocyte models. Several genes, including CASP8, TLR3, CASP1, IL18, significantly differentially expressed OA. These are linked processes such as apoptosis, pyroptosis, inflammasome complex. Pathway revealed necroptosis, Toll-like receptor, signaling pathways important pathology. Single-cell identified HomC, EC, preHTC populations. AG was predicted regulate which confirmed experimentally, demonstrating AG's potential modulate cartilage degeneration. This study highlights identifies promising drug, offering new insights into treatment strategies.

Language: Английский

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Analysis of Nicotine Toxicity and Mechanisms of Senescence in Nucleus Pulposus Cells Using Network Toxicology and Molecular Docking Technique

JOR Spine, Journal Year: 2025, Volume and Issue: 8(2)

Published: March 31, 2025

ABSTRACT Aim Through the use of network toxicology, research sought to determine whether cellular senescence and associated molecular mechanisms in nicotine‐induced intervertebral disc degeneration (IVDD) were potentially harmful. Methods The primary chemical structure 105 targets action nicotine determined by using Swiss Target Prediction, Cell Age, PubChem databases. 855 IVDD genes found GEO Age datasets. Results After additional screening Cytoscape development, 9 key identified. Additionally, these targets' co‐expression pattern analysis protein interactions confirmed be identical. core primarily enriched positive regulation cell proliferation, telomere shortening, histone acetylation, senescence‐related processes, according gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG). KEGG signaling pathway also made it clear that Apelin route, nicotinate nicotinamide metabolism, cycle, apoptosis are all strongly linked senescence. We chose four with pathway—HDAC1, HDAC4, NAMPT, MYLK—for docking toxic substance nicotine. findings validated nicotine's strong affinity for targets. Conclusion All things considered, current indicates may contribute via controlling deacetylation process, pathway, pathways metabolism nicotinamide. theoretical foundation investigating is established.

Language: Английский

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Identification of aging-related biomarkers for intervertebral disc degeneration in whole blood samples based on bioinformatics and machine learning

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

Published: April 15, 2025

Aging is characterized by gradual structural and functional changes in the body over time, with intervertebral disc degeneration (IVDD) representing a key manifestation of spinal aging major contributor to low back pain (LBP). This study utilized bioinformatics machine learning approaches identify aging-related biomarkers associated IVDD whole blood samples. By analyzing GEO datasets alongside databases such as GeneCards, HAGR, AgeAnno, we identified 15 differentially expressed genes (AIDEGs). Correlation immune infiltration analyses were conducted on these AIDEGs, diagnostic models developed using WGCNA, logistic regression, random forest, support vector machine, k-nearest neighbors, LASSO regression genes. Among these, FCGR1A, CBS, FASLG emerged significant strong predictive capabilities for IVDD. Further exploration biological pathways involving AIDEGs provided insights into their potential roles pathogenesis. To further validate findings, collected human specimens vitro experiments. ELISA assays confirmed that CBS are crucial IVDD, distinct expression patterns patients moderate versus severe degeneration. These results highlight provide new perspective early intervention treatment strategies

Language: Английский

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Development and Validation of Early Alert Model for Diabetes Mellitus–Tuberculosis Comorbidity

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 919 - 919

Published: April 16, 2025

Diabetes mellitus (DM) and tuberculosis (TB) are two global health challenges that significantly impact population health, with DM increasing susceptibility to TB infections. However, early risk prediction methods for patients complicated (DM–TB) lacking. This study mined transcriptome data of DM–TB from the GEO database (GSE181143 GSE114192) used differential analysis, weighted gene co-expression network analysis (WGCNA), intersecting immune databases, combined ten machine learning algorithms, identify biomarkers associated DM–TB. An alert model was constructed based on identified core differentially expressed genes (DEGs) validated through a prospective cohort reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) expression levels. Furthermore, we performed detailed status using CIBERSORT algorithm. We 1090 DEGs further pinpointed CETP (cholesteryl ester transfer protein) (AUC = 0.804, CI: 0.744–0.864), TYROBP (TYRO protein tyrosine kinase binding 0.810, 0.752–0.867), SECTM1 (secreted transmembrane 1) 0.811, 0.757–0.864) as immune-related patients. developed these three 0.86, 0.813–0.907), sensitivity 0.80829 specificity 0.75758 at Youden index 0.56587. External validation GSE114192 dataset showed an AUC 0.901 (CI: 0.847–0.955). Population research RT-qPCR verified levels genes, demonstrating consistency trends seen in training set. KEGG enrichment revealed NF-κB MAPK signaling pathways play crucial roles pathogenic mechanism, infiltration significant suppression certain adaptive cells activation inflammatory potential DM–TB, assessment demonstrated predictive efficiency, providing screening strategy

Language: Английский

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