E3 Ubiquitin Ligase FBXO32 Promotes Sepsis-Induced Cardiomyopathy by Regulating ANXA1/PI3K/AKT Signaling DOI Creative Commons
De Chen, Xuan Liang, Lei Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Abstract Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are great significance. This study investigated the role F-box-only protein 32 (FBXO32) in pathogenesis. models were established rats H9c2 cells using lipopolysaccharide. The effects FBXO32 on myocardial apoptosis mitochondrial structure function determined electron microscopy, reactive oxygen species detection, JC-1 staining. molecular mechanism was elucidated western blotting co-immunoprecipitation. results showed elevated expression both vivo vitro models. knockdown alleviated cardiac dysfunction. Mechanistic analysis revealed that promoted ubiquitination degradation annexin A1 (ANXA1), inhibiting phosphatidylinositol 3-kinase (PI3K) kinase B (AKT) pathways. Rescue experiments demonstrated ANXA1 reversed knockdown. suggests exacerbates progression by mediating PI3K/AKT signaling pathway.

Language: Английский

Exploring the role of OIP5-AS1 in the mechanisms of delayed fracture healing: functional insights and clinical implications DOI Creative Commons
Yu Hu,

M. Cen,

Yi Hu

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 10, 2025

Language: Английский

Citations

1
Lipid Nanoparticle-Mediated Oip5-as1 Delivery Preserves Mitochondrial Function in Myocardial Ischemia/Reperfusion Injury by Inhibiting the p53 Pathway DOI
Xiaowei Niu, Jing Zhang, Jingjing Zhang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(45), P. 61565 - 61582

Published: Nov. 1, 2024

Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. may have potential target for MI/R injury its upregulated expression has been associated reduced infarct size improved cardiac function animal models, although how effectively safely overexpress vivo remains unclear. Lipid nanoparticles (LNPs) are versatile technology targeted drug delivery numerous applications. Herein, we aimed assess the efficacy safety of LNPs coloaded cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) murine model injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. structural components were physicochemically analyzed. A hypoxia/reoxygenation (H/R) HL-1 cells coronary artery ligation mice used simulate Our results demonstrated that designed cardiomyocyte targeting efficient successfully synthesized. In cells, treatment significantly mitochondrial apoptosis caused by H/R model, intravenous administration decreased function. Mechanistic investigations revealed inhibited p53 signaling pathway. However, cardioprotective effects abrogated administrating Nutlin-3a, activator. Furthermore, no signs organ damage detected after injection. study reveals mitigating These findings pave way advanced treatments cardiovascular diseases, emphasizing promise lncRNA-based therapies.

Language: Английский

Citations

5
E3 Ubiquitin Ligase FBXO32 Promotes LPS-Induced Cardiac Injury by Regulating ANXA1/PI3K/AKT Signaling DOI Creative Commons
Chen De, Xuan Liang, Lei Zhang

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are great significance. This study investigated the role F-box-only protein 32 (FBXO32) in pathogenesis. LPS-induced cardiac injury models were established rats H9c2 cells using lipopolysaccharide. The effects FBXO32 on myocardial apoptosis mitochondrial structure function determined electron microscopy, reactive oxygen species detection, JC-1 staining. molecular mechanism was elucidated western blotting co-immunoprecipitation. results showed elevated expression both vivo vitro models. Fbxo32 knockdown alleviated dysfunction. Mechanistic analysis revealed that promoted ubiquitination degradation annexin A1 (ANXA1), inhibiting phosphatidylinositol 3-kinase (PI3K) kinase B (AKT) pathways. Rescue experiments demonstrated Anxa1 reversed knockdown. suggests exacerbates progression by mediating ANXA1 PI3K/AKT signaling pathway.

Language: Английский

Citations

0
Angelica sinensis Polysaccharide Suppresses Pyroptosis in Myocardial Ischemia/Reperfusion Injury via the FN1/NF-κB/NLRP3 Pathway DOI Creative Commons
Xiaowei Niu, Wenjun Zhang, Fei Zhao

et al.

Natural Product Communications, Journal Year: 2024, Volume and Issue: 19(9)

Published: Sept. 1, 2024

Background Pyroptosis, a form of inflammatory programmed cell death, has recently emerged as pivotal factor in the pathogenesis myocardial ischemia/reperfusion (MI/R) injury. Despite its significance, effective therapeutic strategies targeting MI/R-induced pyroptosis remain elusive current clinical practice. Previous studies have demonstrated promising anti-inflammatory effects Angelica sinensis polysaccharide (ASP) context certain disorders. Objectives We aimed to investigate ASP on MI/R injury and elucidate potential molecular mechanisms by combining transcriptomic analysis with complementary vivo vitro experiments. Materials methods H9c2 cells were used establish hypoxia/reoxygenation (H/R) model, was induced rats ligating releasing left anterior coronary artery. Myocardial tissue samples harvested for sequencing bioinformatic analyses. Cardioprotective evaluated through electrocardiography, echocardiography, histological examination. Enzyme-linked immunosorbent assay (ELISA) employed quantify levels mediators. Biochemical assays conducted assess biomarkers Caspase-1 activity. Western blotting performed analyze protein expression Fibronectin 1 (FN1), Nuclear kappa B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Nod-like receptor 3 (NLRP3), Gasdermin-D (GSDMD). Results Pretreatment conferred potent cardioprotective rat model injury, evidenced significant attenuation infarct size, enzyme levels, ST-segment elevation alongside notable improvements cardiac function. Transcriptomic profiling unveiled that differentially expressed genes modulated treatment predominantly implicated pyroptosis-elicited response. Concordantly, both experiments substantiated effectively attenuated pyroptosis, manifested diminished pyroptosis-related indicators, encompassing proportion TUNEL-positive cells, activation, GSDMD cleavage, liberation pro-inflammatory cytokines. Further mechanistic investigations revealed inhibition FN1/NF-κB/NLRP3 signaling pathway. Conclusions Our investigation, leveraging system-level profiling, demonstrates confers against suppression cardiomyocyte culminating from downregulation

Language: Английский

Citations

0
The Role of Long Non-Coding RNAs in Cardiovascular Diseases: A Comprehensive Review DOI Creative Commons
Xuena Xie,

Mei‐Wen Huang,

Shudong Ma

et al.

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 11, P. 158 - 187

Published: Dec. 28, 2024

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, posing significant challenges to healthcare systems. Despite advances in medical interventions, molecular mechanisms underlying CVDs not yet fully understood. For decades, protein-coding genes have been focus CVD research. However, recent genomics highlighted importance long non-coding RNAs (lncRNAs) cardiovascular health disease. Changes lncRNA expression specific tissues may result from various internal or external factors, tissue damage, organ dysfunction, In this review, we provide a comprehensive discussion regulatory lncRNAs their roles pathogenesis progression CVDs, such as coronary heart disease, atherosclerosis, failure, arrhythmias, cardiomyopathies, diabetic cardiomyopathy, explore potential therapeutic targets diagnostic biomarkers.

Language: Английский

Citations

0
E3 Ubiquitin Ligase FBXO32 Promotes Sepsis-Induced Cardiomyopathy by Regulating ANXA1/PI3K/AKT Signaling DOI Creative Commons
De Chen, Xuan Liang, Lei Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 3, 2024

Abstract Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis. Therefore, understanding SIC pathogenesis and developing new therapeutic targets are great significance. This study investigated the role F-box-only protein 32 (FBXO32) in pathogenesis. models were established rats H9c2 cells using lipopolysaccharide. The effects FBXO32 on myocardial apoptosis mitochondrial structure function determined electron microscopy, reactive oxygen species detection, JC-1 staining. molecular mechanism was elucidated western blotting co-immunoprecipitation. results showed elevated expression both vivo vitro models. knockdown alleviated cardiac dysfunction. Mechanistic analysis revealed that promoted ubiquitination degradation annexin A1 (ANXA1), inhibiting phosphatidylinositol 3-kinase (PI3K) kinase B (AKT) pathways. Rescue experiments demonstrated ANXA1 reversed knockdown. suggests exacerbates progression by mediating PI3K/AKT signaling pathway.

Language: Английский

Citations

0