Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Heart Failure with Preserved Ejection Fraction Through Regulating Macrophage Polarization Mediated by Alpha7nAChR

Cardiovascular Drugs and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

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The cardio‐renal‐metabolic role of the nod‐like receptor protein‐3 and senescence‐associated secretory phenotype in early sodium/glucose cotransporter‐2 inhibitor therapy in people with diabetes who have had a myocardial infarction

Diabetic Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Aims Following an acute myocardial infarction (AMI), individuals with type 2 diabetes (T2DM) have a 2‐to‐3 fold increased risk of mortality compared to those without diabetes, and globally cardiorenal complications account for 50% diabetes‐related deaths. The use sodium/glucose cotransporter‐2 inhibitors (SGLT2i) in people T2DM‐AMI is associated decreased inflammatory burden improved outcomes. mechanisms behind this protection are unclear form the basis study. Methods This single centre, prospective study randomisation will utilise plasma monocyte‐derived macrophages from patients T2DM who recently had AMI prescribed Empagliflozin either immediately following cardiac event or at 3 months post‐AMI. Results test hypothesis that provides anti‐inflammatory by suppressing systemic NOD‐like receptor protein‐3 (NLRP3) inflammasome activation pro‐inflammatory senescence‐associated secretory phenotype (SASP), perpetrators sterile (non‐pathogen evoked) inflammation linked poor clinical outcomes patients. also assess benefits early intervention on these parameters. Conclusions Elucidating role SGLT2i enhance understanding how they can be used effectively treat identify novel pathways future intervention. Furthermore, optimal timing when initiate therapy post‐AMI unclear. Correlating level onset T2DM, cardiovascular establish if greater benefit initiated earlier.

Language: Английский

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Neuregulin-1 reduces Doxorubicin-induced cardiotoxicity by upregulating YAP to inhibit senescence

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113278 - 113278

Published: Oct. 14, 2024

The cardiotoxicity of Doxorubicin (Dox) limits its clinical application, creating an urgent need to investigate underlying mechanism and develop effective therapies. Senescence plays important role in Dox-induced (DIC). Recently, Neuregulin-1 (NRG1) was found regulate Yes-associated protein (YAP), which reported inhibit senescence, suggesting that NRG1 might be used treat DIC by inhibiting senescence through YAP regulation. We examined the changes regulatory roles Dox whether could reduce chronic mice Dox-treated H9c2 cells. Our study revealed sustained small doses impaired cardiac function cell viability, induced myocardial inhibited expression. Conversely, high levels cells, indicating promotes YAP. In addition, we exogenous phosphorylation LATS1 MST1, thereby promote nuclear translocation YAP, attenuating cardiotoxicity. knockdown or inhibition binding TEA domain transcription factor （TEAD）blocks protective effects NRG1. conclusion, our suggests is one pathological mechanisms Additionally, reduces upregulating senescence.

Language: Английский

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Schaftoside improves HFpEF through regulation the autophagy-lysosome pathway by allosterically targeting CaMKII-δ

Redox Biology, Journal Year: 2024, Volume and Issue: 78, P. 103424 - 103424

Published: Nov. 13, 2024

Heart failure with preserved ejection fraction (HFpEF) presents a significant challenge to global healthcare systems due its complex presentation. HFpEF normal or near-normal left ventricular fraction, cardiac diastolic dysfunction, and metabolic profile characterized by impaired inflammation oxidative stress. There have been few valuable drug targets reported for date. Here, we discovered that schaftoside, an active component from licorice, has protective effect on the remodeling induced continuous infusion of angiotensin II (AngII), which leads phenotype. Mechanistically, schaftoside demonstrated ability ameliorate lysosomal dysfunction in both vitro vivo models, thereby activating autophagy. Bioinformatic analyses based proteome phosphoproteome suggested Ca

Language: Английский

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Identification of novel key genes and signaling pathways in hypertrophic cardiomyopathy: evidence from bioinformatics and next generation sequencing data analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Hypertrophic cardiomyopathy (HCM) is a global health problem characterized by left ventricle become thick and stiff with effect of indication including chest pain, fluttering, fainting shortness breath. In this investigation, we aimed to identify diagnostic markers analyzed the therapeutic potential essential genes. Next generation sequencing (NGS) dataset GSE180313 was obtained from Gene Expression Omnibus (GEO) database used differentially expressed genes (DEGs) in HCM. DEGs were screened using DESeq2 Rbioconductor tool. Then, Ontology (GO) REACTOME pathway enrichment analyses performed. Moreover, protein-protein interaction (PPI) network constructed, module analysis Next, miRNA-hub gene regulatory TF-hub constructed analyzed. Finally, values hub assessed receiver operating characteristic (ROC) curve analysis. By performing analysis, total 958 (479 up regulated 479 down genes) successfully identified GSE180313, respectively. GO revealed that functions signaling pathways significantly enriched response stimulus, multicellular organismal process, metabolism extracellular matrix organization. The FN1, SOX2, TUBA4A, RPS2, TUBA1C, ESR1, SNCA, LCK, PAK1 APLNR might be associated gens FN1 TPM3, together corresponding predicted miRNAs (e.g., hsa-mir-374a-5p hsa-miR-8052), SH3KBP1 ESR1 TFs (e.g PRRX2 STAT3) found correlated This investigation could serve as basis for further understanding molecular pathogenesis targets

Language: Английский

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Schaftoside Improves Hfpef Through Regulation the Autophagy-Lysosome Pathway by Allosterically Targeting Camkii-Δ

Published: Jan. 1, 2024

Language: Английский

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Can senolysis be used to overcome tumor immune evasion?

Journal of Stem Cell Research & Therapeutics, Journal Year: 2024, Volume and Issue: 9(1), P. 26 - 32

Published: Jan. 1, 2024

Tumor escape from immunologically mediated destruction is a well-studied phenomena and has been shown to utilize several pathways in common with physiological conditions such as pregnancy, well ocular or testicular immune privilege. Recent interest senescence revealed that senescent cells surrounding tumors contribute development of specific microenvironment may allow for escape. Senescent have reported possess “senescence associated secretory phenotype” (SASP) which produces inflammatory agents directly indirectly suppression T cell NK function. Exosomes secreted by can suppress activation, downregulate activity dendritic cells, are needed initiation immunity. Studies demonstrated reduction load increases tumor sensitivity variety therapies. We will overview supportive evidence use senolytics potentiate the efficacy immunotherapy cancer, discuss our preliminary findings regarding SenoVax™ (IND #30745), an autologous, polyvalent senolytic vaccine being developed treatment advanced non-small lung cancer.

Language: Английский

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