Natural small molecules regulating the mitophagy pathway counteract the pathogenesis of diabetes and chronic complications

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Diabetes mellitus (DM) is a chronic metabolic disorder marked by sustained hyperglycemia. These disturbances contribute to extensive damage across various tissues and organs, giving rise severe complications such as vision loss, kidney failure, amputations, higher morbidity mortality rates. Furthermore, DM imposes substantial economic emotional burden on patients, families, healthcare systems. Mitophagy, selective process that targets the clearance of damaged or dysfunctional mitochondria, pivotal for sustaining cellular homeostasis through mitochondrial turnover recycling. Emerging evidence indicates mitophagy acts key pathogenic driver in pathogenesis its associated complications. Natural small molecules are particularly attractive this regard, offering advantages low toxicity, favorable pharmacokinetic profiles, excellent biocompatibility, broad range biochemical activities. This review systematically evaluates mechanistic roles natural molecules-including ginsenosides, resveratrol, berberine-in enhancing restoring via activation core signaling pathways (e.g., PINK1/Parkin, BNIP3/NIX, FUNDC1). collectively ameliorate pathological hallmarks DM, oxidative stress, inflammation, insulin resistance. integration nanotechnology with these compounds optimizes their bioavailability tissue-specific targeting, thereby establishing transformative therapeutic platform management. Current demonstrates modulation not only offers novel strategies but also advances foundation future drug development targeting disorders.

Language: Английский

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Unravelling the Molecular Footprints of Diabetic Foot Ulcers: In Silico Discovery of Key Protein and MicroRNA Signatures

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

Published: Nov. 12, 2024

Abstract Diabetic foot ulcers (DFUs) present a significant clinical challenge, characterized by chronic inflammation and impaired wound healing. This study employs Gene Ontology (GO) analysis to identify critical biological processes, molecular functions, cellular components, pathways associated with DFUs, aiming uncover novel therapeutic targets. The reveals enrichment in processes such as Positive Regulation of miRNA Transcription Transcription, highlighting the crucial role microRNAs, including hsa-miR-34a-5p, hsa-miR-155-5p, hsa-miR-17-5p, hsa-miR-29b-3p, hsa-miR-7-5p, hsa-miR-1-3p, hsa-miR-23b-3p, regulating healing inflammation. Enriched DNA-binding Activator Activity Protein Phosphatase Binding, suggest that targeting genes like TP53, GAPDH, AKT1, MYC, TNF, EGFR, STAT3, FN1, VEGFA, JUN could modulate improve DFU management. also identifies key Vesicle Platelet Alpha Granule Lumen, for transport signaling, suggesting interventions these components enhance repair. Furthermore, enriched Proteoglycans Cancer Human Cytomegalovirus Infection indicate potential mechanisms viral influences relevant DFUs. These findings provide comprehensive framework developing targeted therapies address multifaceted pathology offering promising avenues improving patient outcomes advancing strategies.

Language: Английский

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Adipose mesenchymal stem cell-derived extracellular vesicles regulate PINK1/parkin-mediated mitophagy to repair high glucose-induced dermal fibroblast senescence and promote wound healing in rats with diabetic foot ulcer

Acta Diabetologica, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Language: Английский

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Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and bioinformatics

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 15, 2024

Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet ISR remains unclear. This study aims to identify mitophagy-related biomarkers and explore their underlying molecular mechanisms. Through differential gene expression analysis between Control samples dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three (DEMRGs) identified by intersecting (MRGs) from GeneCards, functional enrichment indicated significant involvement biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) three machine learning algorithms (Logistic-LASSO, RF, SVM-RFE), LRRK2, ANKRD13A as ISR. The nomogram based on these two also exhibited promising diagnostic performance Set Enrichment (GSEA) well immune infiltration analyses showed that closely associated inflammatory responses Furthermore, potential small molecule compounds therapeutic implications predicted using connectivity Map (cMAP) database. systematically investigated functions, providing new insights into early diagnosis precision treatment strategies

Language: Английский

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