Metrnl Ameliorates Ferroptosis in Model of Diabetic Foot Ulcer Through the Inhibition of Mitochondrial Damage via LKB1/AMPK Signaling

Experimental and Clinical Endocrinology & Diabetes, Journal Year: 2025, Volume and Issue: 133(03), P. 120 - 132

Published: March 1, 2025

Abstract Diabetic foot ulcer (DFU) represents a severe complication of diabetes, mainly caused by peripheral vascular occlusion and infection, presenting significant clinical challenges in treatment potentially resulting gangrene, amputation, or even fatality. This study aimed to investigate the involvement underlying mechanisms Meteorin-like (Metrnl) pathogenic process DFU. Mice underwent diabetes induction streptozotocin, while human umbilical vein endothelial cells (HUVECs) were exposed 5.5, 10, 20 40 mM glucose. HUVECs transfected with negative Metrnl si-nc si-Metrnl plasmids via Lipofectamine 2000. The expression was down-regulated both patients murine model Elevated glucose levels diminished through enhanced ubiquitination. suppression exacerbated mouse alleviated oxidative stress ferroptosis DFU inhibiting mitochondrial damage. induced liver kinase B1 (LKB1)/AMP-activated protein (AMPK) signaling model. LKB1 attenuated effects on data cumulatively demonstrate that ameliorates damage LKB1/AMPK signaling, suggesting targeting may emerge as potential preventive approach against other diabetes.

Language: Английский

---

Critical Understanding of Apoptosis’ Function in Diabetes and Diabetic Wound Healing: Prospective Therapeutic Opportunities

Journal of Stem Cell Therapy and Transplantation, Journal Year: 2025, Volume and Issue: 9(2), P. 012 - 026

Published: Feb. 24, 2025

Apoptosis, or programmable necrosis, can be induced by miscellaneous factors such as radiation, chemicals, and physiological pathological conditions. Apoptosis is required for many processes, the turning over of normal cells, growth immune system functions, unfair apoptosis either too little much has been linked to several clinical circumstances, accompanied cancer, diabetes, neurodegenerative spoiling. The harm β-cell cytoplasm owing pancreatic cells dying (T2DM) a complicated etiology Non-insulin-dependent diabetes mellitus (type II). To halt progression cell disorders, it may modulate proliferation processes these cells. complex process with four major components: induction, detection, effectors, eradication. Each step necessitates coordinated action multiple molecules, most noteworthy which are caspases, Bcl-2 protein family, p53 (tumor suppressor gene).

Language: Английский

---

The role of programmed cell death in diabetic foot ulcers

International Wound Journal, Journal Year: 2023, Volume and Issue: 21(2)

Published: Sept. 22, 2023

Diabetic foot ulcer, is a chronic complication afflicting individuals with diabetes, continue to increase worldwide, immensely burdening society. Programmed cell death, which includes apoptosis, autophagy, ferroptosis, necroptosis and pyroptosis, has been increasingly implicated in the pathogenesis of diabetic ulcer. This review based on an exhaustive examination literature 'programmed death' 'diabetic ulcers' via PubMed. The findings revealed that natural bioactive compounds, noncoding RNAs certain proteins play crucial roles healing ulcers through various forms programmed including ferroptosis pyroptosis.

Language: Английский

---

Identification of CGNL1 as a diagnostic marker in fibroblasts of diabetic foot ulcers: Insights from single cell RNA sequencing and bulk sequencing data

International Journal of Immunopathology and Pharmacology, Journal Year: 2024, Volume and Issue: 38

Published: Jan. 1, 2024

Objectives This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and role ferroptosis in diabetic foot ulcers (DFUs). Methods The GEO (Gene Expression Omnibus) was searched obtain DFUs single-cell datasets. After identifying cell types by classic marker genes, integrated dataset used run trajectory inference, RNA velocity, ligand-receptor interaction analysis. Next, bulk RNA-seq datasets were analyzed key genes. Results Here, we profile 83529 single transcriptomes from samples utilizing sequencing (scRNA-seq) data DFU database identified 12 types, with exhibiting elevated levels activity substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, healing-enriched functional annotations. Trajectory inference cell-cell communication analysis revealed two major fates subpopulations altered interactions. Bulk CGNL1 as a distinctive diagnostic signature fibroblasts. Notably, positively correlated pro-inflammatory Conclusions Overall, our delineated heterogeneity present populations DFUs, showing distinct characterized their own features enrichment functions. will help us better understand pathogenesis identifies potential target for therapies.

Language: Английский

---

Features of apoptotic and proliferative processes in experimental infected radiation-induced skin ulcer under conditions of photodynamic therapy and the use of platelet-rich plasma

Polski Merkuriusz Lekarski, Journal Year: 2024, Volume and Issue: 52(1), P. 54 - 59

Published: Jan. 1, 2024

Aim: The purpose of the study was to identify features apoptotic and proliferative processes in experimental Staphylococcus aureus-infected radiation skin ulcer under conditions photodynamic therapy use platelet-rich plasma. Materials Methods: An conducted on 95 six-month-old male rats WAG population, which were divided into three groups. Group 1 included 25 animals that simulated a thigh area with subsequent application its surface 7th day after irradiation 0.2 ml suspension aureus (ATCC 25923) reference strain (0.5 million microbial cells/cm2). 2 ulcer, subjected infection. 3 45 ulcers, which, infection, received first half day, second periphery wound defect injected material for underlying soft tissues from exposure. Histological, immunohistochemical, morphometric statistical methods used. Results: In cases simultaneous plasma, compared alone, ofapoptosis proliferation more balanced, active, shift proliferative-apoptotic ratio towards met needs regenerative process. From 10th 22nd experiment these increased, indicated active healing processes, that, during survey microscopy manifested by complete filling cavity granulation connective presence an epithelial layer regenerate. 45th experiment, decrease rate regeneration recorded, as evidenced intensity processes. latter sufficient, led restoration original structure skin. Conclusions: Photodynamic combination plasma balancedly activates predominance lumen leads

Language: Английский

---

THE ROLE OF INTRACELLULAR SIGNALING PATHWAYS IN THE DEVELOPMENT OF TROPHIC PATHOLOGIES OF THE LOWER EXTREMITIES AND THEIR REGENERATION UNDER TYPE 2 DIABETES (PART 1)

Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії, Journal Year: 2024, Volume and Issue: 24(3), P. 217 - 226

Published: Nov. 11, 2024

Introduction. This review article addresses the critical issue of development and regeneration chronic trophic ulcers in context type 2 diabetes. pathological process is associated with inhibited cell proliferation, impaired differentiation various types, disrupted mechanisms that regulate death. An analysis recent scientific literature also highlights involvement key intracellular signaling pathways ulcerative pathologies lower extremities, as observed both experimental animal models patients II Despite advancements, this remains insufficiently explored theory practice, underscoring its ongoing relevance. The aim study to identify roles pathways—transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt), Wnt/β-catenin—in inflammatory response, regenerative mechanisms, healing processes soft tissue damage animals Materials Methods. based on an current topic. Results. It has been found out changes content activity molecules lead disruption carbohydrate homeostasis occurrence structural functional dysfunction damaged tissues against background These include TGF-β, PI3K, Akt β-catenin. Analysis data demonstrated under conditions diabetes endocrine disease, there increase level TGF-β. At same time PI3K/Akt pathway above-mentioned studied groups was reduced. relationship between Wnt/β-catenin established. Suppression accompanied by Conclusion. Thus, mechanism peptic ulcer pathology, a cascades. concerns following cellular systems such Wnt/β-catenin. They can be considered potential therapeutic targets for newest methods treatment order accelerate recovery volumetric extremities.

Language: Английский

---

Bulk and Single‐Cell Transcriptome Analyses Unravel Gene Signatures of Mitochondria‐Associated Programmed Cell Death in Diabetic Foot Ulcer

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(24)

Published: Dec. 1, 2024

Mitochondrial programmed cell death (PCD) plays a critical role in the pathogenesis of diabetic foot ulcers (DFU). In this study, we performed comprehensive transcriptome analysis to identify potential hub genes and key types associated with PCD mitochondria DFU. Using intersection PCD- mitochondria-related genes, identified candidate through protein-protein interaction random forest analysis. At single-cell level, were further validated based on expression genes. Additionally, explored transcription factors (TFs) regulating gene cellular heterogeneity Finally, TFs was clinical specimens. Our results BCL2 LIPT1 as significantly downregulated DFU, Keratinocytes, type. Immunohistochemistry confirmed downregulation DFU samples (p < 0.05). CEBPD IRF1 upregulated by real-time polymerase chain reaction

Language: Английский

---