Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: Coronary heart disease (CHD) occurs when the arteries supplying blood to the heart become narrowed or blocked owing to plaque buildup, leading to reduced blood flow and potential heart attacks. N6-methyladenosine (mA) modification is a common form of post-transcriptional RNA modification. ALKB homolog 5 (ALKBH5) is an RNA demethylase that specifically removes the mA modification from RNA. This study aimed to investigate the role of ALKBH5 in CHD and the underlying mechanism.
Methods: Both cellular and animal CHD models were established. The expression levels of Alkbh5 and fibrosis-related markers were analyzed by qRT-PCR. Cell viability and cytotoxicity were assessed via cell counting kit-8. Inflammatory cytokines levels were detected by ELISA. Flow cytometry was used to detect pyroptosis. The interaction between ALKBH5/YTH N6-methyladenosine RNA binding protein (YTHDF)1 and SPEN transcriptional repressor (SPEN) was examined through RNA immunoprecipitation and dual-luciferase reporter assays.
Results: ALKBH5-mediated demethylation of mA was decreased in CHD rat heart tissues and oxidized low-density lipoprotein (ox-LDL)-treated H9c2 cells. In addition, Alkbh5 overexpression increased the cell viability and suppressed the inflammation, pyroptosis, and fibrosis in ox-LDL-treated H9c2 cells. In in vivo studies, Alkbh5 overexpression reduced myocardial injury and fibrosis in CHD rats by suppressing inflammation and pyroptosis. Mechanically, Alkbh5 overexpression decreased the stability of Spen mRNA. Additionally, ALKBH5/YTHDF1 mA axis regulated the expression of Spen. Moreover, Ythdf1 overexpression counteracted ALKBH5-mediated inhibition of inflammation, pyroptosis, and fibrosis in ox-LDL-treated H9c2 cells.
Conclusion: ALKBH5 regulated inflammation and pyroptosis of CHD by targeting SPEN in a YTHDF1-mediated manner, which could provide a reference for CHD treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10557-025-07746-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting NLRP3 inflammasome with curcumin: mechanisms and therapeutic promise in chronic inflammation.
Inflammopharmacology
September 2025
Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
The NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key molecular complex that amplifies inflammatory cascades by maturing interleukin‑1 beta (IL-1β) and interleukin‑18 (IL-18) and inducing pyroptosis. It serves as a major driver and co-driver of numerous diseases associated with chronic inflammation. Dysregulated NLRP3 activation contributes to the progression of disorders such as rheumatoid arthritis, inflammatory bowel disease, neurodegenerative diseases and atherosclerosis.
View Article and Find Full Text PDFEmerging regenerative strategies for spinal cord injury: exosome-derived mechanisms and therapeutic insights.
Front Neurosci
August 2025
First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Background: Spinal cord injury (SCI) often leads to severe motor and sensory impairments, and current treatment methods have not achieved complete neural repair. In recent years, exosomes have become a research focus in the treatment of nerve injuries due to their important roles in intercellular information transfer, immune regulation, and neural repair. Our study conducts a scientometric analysis to map the research landscape related to exosomes in SCI.
View Article and Find Full Text PDFCell death in multiple sclerosis.
Cell Death Differ
September 2025
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) characterized by inflammatory demyelination and progressive neurodegeneration. Although current disease-modifying therapies modulate peripheral autoimmune responses, they are insufficient to fully prevent tissue specific neuroinflammation and long-term neuronal and oligodendrocyte loss. Growing evidence implicates various regulated cell death (RCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, not only as downstream consequences of chronic inflammation, but also as active drivers of demyelination, axonal injury, and glial dysfunction in MS.
View Article and Find Full Text PDFMumps virus infection triggers early pro-inflammatory responses and impairs Leydig and Sertoli cell function in an ex vivo human testis model.
Hum Reprod
September 2025
Institut National de la Santé et de la Recherche Médicale, Ecole des Hautes Etudes en Santé Publique, Institut de recherche en santé, environnement et travail, Université de Rennes-UMR_S1085, Rennes, France.
Study Question: What is the direct effect of mumps virus (MuV) replication within the human testis on the tissue innate immune responses and testicular cell functions?
Summary Answer: MuV induces an early pro-inflammatory response in the human testis ex vivo and infects both Leydig cells and Sertoli cells, which drastically alters testosterone and inhibin B production.
What Is Known Already: Despite widespread vaccination efforts, orchitis remains a significant complication of MuV infection, especially in young men, which potentially results in infertility in up to 87% of patients with bilateral orchitis. Our understanding of MuV pathogenesis in the human testis has been limited by the lack of relevant animal models, impairing the development of effective treatments.
Superiority of ultrasound-extracted Flammulina velutipes polysaccharides over hot water-extracted ones in mitigating colonic cell pyroptosis: Discoveries into modulation of NLRP3 pathway.
Food Res Int
November 2025
College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, PR China. Electronic address:
Flammulina velutipes is a major edible fungus with abundant yield and mature industrial production technology. Its main functional component, Flammulina velutipes polysaccharide, has huge development and utilization value. In light of the current uncertainty regarding the mechanisms by which Flammulina velutipes polysaccharides prevent colonic cell pyroptosis, the mechanisms of ultrasound-extracted Flammulina velutipes polysaccharide (FVPU2) in inhibiting colonic cell pyroptosis in mice were investigated, and compared with Flammulina velutipes polysaccharide extracted via hot water extraction (FVPH2).
View Article and Find Full Text PDF