New insights into FGF21 alleviates diabetic cardiomyopathy by suppressing ferroptosis: a commentary DOI Creative Commons
Kexin Chen, Si Wang

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 26, 2024

Diabetic cardiomyopathy (DCM) is a severe cardiovascular complication of diabetes characterized by myocardial hypertrophy, fibrosis, and impaired cardiac function. Fibroblast growth factor 21 (FGF21) has emerged as promising therapeutic target due to its antifibrotic, antioxidant, anti-inflammatory properties. Our commentary summarizes affirms the recent study Wang et al., which demonstrates significant role ferroptosis in DCM pathogenesis. FGF21 shown promise for DCM, potentially inhibiting ferroptosis, mitigating oxidative damage, protecting cardiomyocyte Mechanistically, identified ATF4 an upstream regulator revealing that directly interacts with ferritin extends half-life, thus DCM. These findings provide theoretical basis understanding pathogenesis treatment suggests future studies should explore non-cardiomyocyte cell types verify clinical samples, address comprehensive methods detection. Additionally, we discuss application potential FGF21-based therapies Such efforts may contribute advancing diagnosis treatment, fostering development innovative strategies.

Язык: Английский

Integrative single-cell and multi-omics analyses reveal ferroptosis-associated gene expression and immune microenvironment heterogeneity in gastric cancer DOI Creative Commons
Shupeng Zhang,

Zhaojin Li,

Gang Hu

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 17, 2025

Gastric cancer (GC), a prevalent malignancy worldwide, encompasses multitude of biological processes in its progression. Recently, ferroptosis, novel mode cell demise, has become focal point research. The microenvironment gastric is composed diverse populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood. Our study employed single-cell RNA sequencing to thoroughly investigate transcriptomic identify differential cancer, offering fresh insights into cellular diversity underlying molecular mechanisms this disease. We discovered set significantly differentially expressed genes GC, which may serve as valuable leads for future functional investigations. Subsequent analyses, including intersection enrichment, pinpointed implicated conducted comprehensive Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses elucidate roles. In selection model validation section, critical were identified using machine learning algorithms, constructing high predictive accuracy. Besides, distorted immune landscapes further RBL ssGSEA analysis such that complex features interaction networks infiltration by various types cells can be more clearly Correlation different subtypes showed CTSB an important regulator distributions infiltrating cells. Single-cell was utilized map composition microenvironment, provide information elucidating heterogeneity tumor regulation GC. Moreover, distribution FTH1, ZFP36 CIRBP at levels show new research prospects these promoters microenvironment. summary, present augments our knowledge tumorigenesisa scientific basis identifing targets biomarkers therapeutic diagnosis.

Язык: Английский

Процитировано

2
Identification of lipid metabolism-related genes in dapagliflozin treated rats with diabetic cardiomyopathy by bioinformatics DOI Creative Commons
Xun Huang,

Yunhong Wang,

Rong Wan

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 20, 2025

Background Diabetic cardiomyopathy (DCM) is a heart disease caused by the metabolic disorders of glucose and lipids associated with diabetes, leading to failure death in diabetic patients. Dapagliflozin (DAPA) serves as treatment for managing blood levels individuals type 2 diabetes mellitus (DM). However, specific mechanisms which DAPA treats DCM are not yet fully understood. Methods Sprague-Dawley (SD) rats (n = 5/group) were randomly divided into control, model, intervention groups. Lipid metabolism-related genes (LMRGs) gotten from publicly available database. Differential expression analysis model vs. control samples was performed obtain differentially expressed (DEGs), result recorded DEGs-Model DEGs-Intervention. The intersection opposing trends between DEGs-Intervention considered candidate genes. Subsequently, LMRGs intersected acquire hub genes, analyzed each group samples. Then, mechanism action these investigated through functional enrichment analysis, gene set (GSEA), predictive m6A binding sites. Results Ultimately, 68 590 derive (Acsbg1 Etnppl). Acsbg1 significantly increase compared group. RT-qPCR results confirmed obviously higher group, while Etnppl lower compare groups While Functional analyses indicated that fatty acid metabolism. findings GSEA might affect occurrence progression lysosome. And located at UCAGG RNA secondary structure. Conclusion This study identified Etnppl) potential new focal points diagnosing treating DCM.

Язык: Английский

Процитировано

0
DNA‐PKcs‐Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia‐Induced Cardiac Dysfunction in Type 1 Diabetes DOI Creative Commons
Junyan Wang, Xing Chang, Chun Li

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Abstract The DNA‐Dependent Protein Kinase catalytic subunit (DNA‐PKcs) acts as a principal executor in the DNA damage response (DDR), mediating phosphorylation of broad spectrum substrates integral to repair and apoptosis. This investigation seeks discern possible association mechanisms linking hyperglycemia‐induced ferroptosis DNA‐PKcs DCM. data exhibits substantial activation DNAPKcs‐ dependent DDR mice with streptozotocin‐induced However, deletion cardiomyocytes notably mitigates damage, enhances heart function dampens inflammatory response. Co‐IP/MS analysis subsequent validation experiments demonstrate that directly interacts phosphorylates YAP1 at Thr226. event facilitates nuclear retention YAP1, where it intensifies transcription ferroptosis‐associated genes. Knockin expressing nonphosphorylatable T226A mutant display decreased ferroptosis, reduced myocardial fibrosis improved function. Taken together, this study unravels an intracellular stress sensor, perceiving hyperglycemic conditions subsequently transmitting signal incite through interplay between YAP1. novel insight suggests DNA‐PKcs‐mediated could be promising therapeutic targets for management

Язык: Английский

Процитировано

0
New insights into FGF21 alleviates diabetic cardiomyopathy by suppressing ferroptosis: a commentary DOI Creative Commons
Kexin Chen, Si Wang

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 26, 2024

Diabetic cardiomyopathy (DCM) is a severe cardiovascular complication of diabetes characterized by myocardial hypertrophy, fibrosis, and impaired cardiac function. Fibroblast growth factor 21 (FGF21) has emerged as promising therapeutic target due to its antifibrotic, antioxidant, anti-inflammatory properties. Our commentary summarizes affirms the recent study Wang et al., which demonstrates significant role ferroptosis in DCM pathogenesis. FGF21 shown promise for DCM, potentially inhibiting ferroptosis, mitigating oxidative damage, protecting cardiomyocyte Mechanistically, identified ATF4 an upstream regulator revealing that directly interacts with ferritin extends half-life, thus DCM. These findings provide theoretical basis understanding pathogenesis treatment suggests future studies should explore non-cardiomyocyte cell types verify clinical samples, address comprehensive methods detection. Additionally, we discuss application potential FGF21-based therapies Such efforts may contribute advancing diagnosis treatment, fostering development innovative strategies.

Язык: Английский

Процитировано

0