Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 288, P. 117385 - 117385
Published: Nov. 23, 2024
Language: Английский
British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 20, 2025
Abstract Background and Purpose Chronic kidney disease (CKD) is characterised by inflammation, which can lead to tubular atrophy fibrosis. The molecular mechanisms are not well understood. In this study, we investigated the functional role of cyclic GMP–AMP synthase (cGAS)– stimulator interferon genes (STING) signalling in renal inflammation Experimental Approach Mice with global cGAS deficiency or myeloid cell‐specific STING wild‐type mice treated RU.521, a selective inhibitor, were used examine cGAS–STING fibrosis preclinical model obstructive nephropathy vivo. Bone marrow‐derived macrophages determine whether epithelial cell‐derived DNA activate vitro. Key Results Following injury, was activated kidneys during development exhibited significantly less macrophage proinflammatory activation, myofibroblast formation, total collagen deposition, extracellular matrix (ECM) protein production following injury. Pharmacological inhibition RU.521 reduced suppressed attenuated Mechanistically, double‐stranded released from damaged cells, induces inflammatory responses. Conclusions Implications Our study identifies pathway as critical regulator activation Therefore, may represent novel therapeutic strategy for CKD.
Language: Английский
Citations
6
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: July 10, 2024
Histone deacetylases (HDACs) are critical regulators of inflammatory gene expression, and the efficacy pan-HDAC inhibitors has been implicated in various disease conditions. However, it remains largely unclear how HDACs precisely regulate inflammation. To this end, evaluating isoform-specific function is critical, targeting could also circumvent off-target effects inhibitors. This review provides an overview roles HDAC3, a class I HDAC isoform, modulating responses discusses molecular mechanisms by which HDAC3 regulates inflammation associated with brain pathology, arthritis, cardiovascular diseases, lung allergic conditions, kidney disorders. The articles identify knowledge gaps field for future studies. Despite some conflicting reports, selective inhibition demonstrated to play beneficial role pathologies. Exploring potential improve prognosis promising avenue requiring further investigation.
Language: Английский
Citations
5
Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117842 - 117842
Published: Jan. 13, 2025
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: Feb. 19, 2025
The NLRP3 inflammasome and NF-κB signaling pathways play crucial roles in orchestrating inflammation immune defense. This review explores the intricate relationship between these epigenetic regulation, a field of growing importance understanding responses. Epigenetic modifications, including DNA methylation, histone non-coding RNAs (ncRNAs), significantly influence activity genes involved pathways, thereby modulating inflammatory provides comprehensive overview current research on how mechanisms interact with regulate pathways. It delves into advanced concepts such as RNA modifications 3D genome organization, their impact regulation. Furthermore, implications findings for developing novel therapeutic strategies targeting regulators diseases are discussed. By synthesizing recent advancements this rapidly evolving field, underscores critical role regulation highlights potential epigenetic-based therapies treating wide range conditions, autoimmune disorders cancer.
Language: Английский
Citations
0
Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Introduction Cholestatic liver diseases are highly prevalent and lack effective treatment, ultimately progressing to end-stage diseases. Our recent study indicates that the interplay between c-MYC lncRNA H19 exacerbates ductular reaction during cholestasis. This aims unveil underlying mechanisms of protective effects senkyunolide A (SenA) on cholangiocyte overproliferation in cholestatic Through comprehensive characterization using RNA sequencing, CHIP analysis, protein truncation, amino acid mutation or deletion, development SenA derivatives, we explored vivo bile duct ligation mice vitro primary cholangiocytes. We demonstrated effectively mitigates hyperproliferation by epigenetically suppressing expression disrupting downstream H19, Let-7a Lin28a. Mechanically, identified a potential interaction carbonyl group Arg483 TRAF6, TRAF6-HDAC3 complex. dissociation facilitates binding HDAC3 MYC promoter region, resulting enhanced histone deacetylation transcriptional suppression. highlight therapeutic elucidating its role epigenetic regulation.
Language: Английский
Citations
0
Seminars in Immunology, Journal Year: 2025, Volume and Issue: 78, P. 101957 - 101957
Published: April 26, 2025
Language: Английский
Citations
0
International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 2507 - 2520
Published: May 1, 2025
Chronic kidney disease (CKD) is influenced by inflammation, a critical factor in its progression. However, the underlying mechanism through which inflammation contributes to CKD still obscure. The Klotho protein, predominantly found kidneys, known for protective functions, including anti-inflammatory, anti-aging, antioxidant, and anti-fibrotic effects. A myriad of studies have suggested that leads decrease expression, diminishing protection capabilities exacerbating damage, thereby promoting These findings suggest deficiency could be crucial link between regarding their relationship unclear. reduction due may attributed epigenetic mechanisms, such as DNA methylation, histone deacetylation, transcription factor, microRNA (miRNA) regulation long non-coding RNA (lncRNA) or non-epigenetic factors, endoplasmic reticulum (ER) stress ER-associated degradation (ERAD), affect protein metabolism. Through these pathways, triggers further driving Notably, also exerts strong anti-inflammatory effect inhibiting key inflammatory factors suggesting there intricate crosstalk CKD. This review highlights how suppresses expression development exacerbation By focusing on interplay Klotho, present provides novel potential therapeutic strategies correcting abnormalities treating targeting this specific axis.
Language: Английский
Citations
0
Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown
Published: May 24, 2025
Abstract Nanoparticles have been investigated for extensive applications across scientific disciplines, including the medical field. Despite research aimed at enhancing understanding of their intracellular behavior and potential genomic side effects nanoparticles, scientists paid relatively little attention to nanoparticle‐induced epigenetic changes. This oversight is surprising given critical role mechanisms in shaping cellular function destiny. Epigenetic include procedures that modulate DNA or RNA influence production proteins as well extent which they are produced. Each cell type demonstrates unique profiles. changes can disrupt normal functions, potentially leading devastating outcomes. Investigating how nanoparticles impact these provides valuable insights into safe effective use applications. review a detailed overview enter cells on mechanisms, focusing current related studies different types cells.
Language: Английский
Citations
0
Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 715, P. 149997 - 149997
Published: April 24, 2024
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: July 8, 2024
Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with high mortality rate. Current first-line treatments for adult patients have limited efficacy significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies the potential treatment of HLH. Methods An open-label, single-center study was conducted to evaluate safety chidamide combination etoposide glucocorticoids HLH patients. Seventeen who fulfilled at least five eight HLH-2004 criteria were enrolled treated therapy. primary outcome overall response rate (ORR), secondary outcomes included survival, tolerability, changes laboratory indicators. Results A total 17 met inclusion this study, male female ratio 1.8:1. age range enrollment 31 71 years old, median 52 old. ORR 76.5% (13/17 patients), complete (CR) 17.6% (3/17 patients) partial (PR) 58.8% (10/17 patients). survival (OS) not achieved, OS 6 months 12 being 81% 65%, respectively. progression free (PFS) PFS 68% 55%, Hematologic toxicities most common. Safety profile favorable, very few cases grade 3/4 observed. results showed that levels sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, albumin these significantly improved 3 weeks after treatment. Conclusion addition may be promising new option HLH, ORR, manageable profile, improvement Further research needed confirm findings determine optimal dosing duration
Language: Английский
Citations
1