Diabetic ferroptosis and chronic wounds

NewsBot · Aug 29, 2021

Members do not see these Ads. Sign Up.
Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound
Shuangwen Li, Yuan Li, Ziyu Wu, Zhongming Wu*, and Hongjuan Fang
23 AUG 2021

Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides, in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins, and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.
Click to expand...

NewsBot · Aug 29, 2021

Related Thread:
Biomarkers of Healing in Chronic Diabetic Foot Ulcers

NewsBot · Oct 14, 2022

Revealing the novel ferroptosis-related therapeutic targets for diabetic foot ulcer based on the machine learning
Xingkai Wang et al
Front Genet. 2022 Sep 26

Objectives: DFU is a serious chronic disease with high disability and fatality rates, yet there is no completely effective therapy. While ferroptosis is integrated to inflammation and infection, its involvement in DFU is still unclear. The study aimed to identify ferroptosis-related genes in DFU, providing potential therapeutic targets. Methods: In the GEO database, two DFU microarray datasets (GSE147890 and GSE80178) were collected. WGCNA was conducted to identify the modular genes most involved in DFU. Subsequently, enrichment analysis and PPI analysis were performed. To yield the DFU-associated ferroposis genes, the ferroposis genes were retrieved from the FerrDb database and overlapped with the modular genes. Eventually, an optimal DFU prediction model was created by combining multiple machine learning algorithms (LASSO, SVM-RFE, Boruta, and XGBoost) to detect ferroposis genes most closely associated with DFU. The accuracy of the model was verified by utilizing external datasets (GSE7014) based on ROC curves. Results: WGCNA yielded seven modules in all, and 1223 DFU-related modular genes were identified. GO analysis revealed that inflammatory response, decidualization, and protein binding were the most highly enriched terms. These module genes were also enriched in the ErbB signaling, IL-17 signaling, MAPK signaling, growth hormone synthesis, secretion and action, and tight junction KEGG pathways. Twenty-five DFU-associated ferroposis genes were obtained by cross-linking with modular genes, which could distinguish DFU patients from controls. Ultimately, the prediction model based on machine learning algorithms was well established, with high AUC values (0.79 of LASSO, 0.80 of SVM, 0.75 of Boruta, 0.70 of XGBoost). MAFG and MAPK3 were identified by the prediction model as the most highly associated ferroposis-genes in DFU. Furthermore, the external dataset (GSE29221) validation revealed that MAPK3 (AUC = 0.81) had superior AUC values than MAFG (AUC = 0.62). Conclusion: As the most related ferroptosis-genes with DFU, MAFG and MAPK3 may be employed as potential therapeutic targets for DFU patients. Moreover, MAPK3, with higher accuracy, could be the more potential ferroptosis-related biomarker for further experimental validation.
Click to expand...

NewsBot · Oct 4, 2024

Study on the mechanism of activating SIRT1/Nrf2/p62 pathway to mediate autophagy-dependent ferroptosis to promote healing of diabetic foot ulcers
Qinglin Han et al
Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep 25

Diabetic foot (DF), a prevalent and grave diabetes sequela, is considered as a notable clinical concern, with SIRT1 downregulation observed in DF patients' blood specimens. Nonetheless, the regulatory mechanisms of SIRT1 in diabetic foot ulcer (DFU) remain unclear. Thus, in the current study, we investigated the role and mechanisms of SIRT1 in alleviating DFU. Western blotting was used to detect the expression of autophagy and ferroptosis-related proteins, CCK8 assay was used to measure cell proliferation. Plate colony method was used to measure bacterial growth, and the inhibitory effect on intracellular and extracellular Staphylococcus aureus was observed after drug intervention. ELISA was used to detect inflammatory cytokines and oxidative stress markers levels. ROS, total iron, and Fe2+ levels were detected using corresponding assays. Additionally, HE staining detected the thickness of the epidermis and dermis of the rat wound tissue while the collagen deposition in the wound tissue was detected using Masson staining. In addition, Prussian blue staining was used to detect iron deposition, and C11 BODIPY 581/591 lipid peroxidation probe was used to detect lipid ROS. Our results suggested that the activation of SIRT1/Nrf2/p62 signaling affects cell proliferation, colony formation, ferroptosis, and the production of lipid ROS in DFU-infected cell model through autophagy. In vivo experiments indicated that activating SIRT1/Nrf2/p62 signaling affects oxidative stress, inflammation, and autophagy in wound tissue and promotes wound healing in DFU rats through mediating autophagy-dependent ferroptosis. Taken together, the activation of SIRT1/Nrf2/p62 pathway can promote DFU healing, which might be mediated by autophagy-dependent ferroptosis.
Click to expand...

NewsBot · Jan 29, 2025

Relationship between ferroptosis and healing of diabetic foot ulcer: a prospective clinical study
Qian Jiang et al
Front Endocrinol (Lausanne). 2025 Jan 14:15:1412373.

Objective: Diabetic foot ulcer (DFU) is one of the common complications in patients with diabetes mellitus (DM). In order to find a method to monitor and treat the refractory DFU, the ferroptosis level in DFU and traumatic wounds (TW) was monitored and the difference between them was analyzed. At the same time, this study further analyzed the correlation of ferroptosis levels with DM severity and DFU's healing.

Methods: A prospective cohort study was from January, 2021 to December, 2023 in the Second People's Hospital of Gansu province, which included 59 patients with DFU and 42 patients with TW. We then used the kit to detect the indicators related to ferroptosis, including 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA) and reactive oxygen species (ROS), in the wound exudate of the two groups of patients.

Results: The DFU group had higher ferroptosis level than the TW group (4-HNE: P = 0.003, MDA: P<0.001, ROS: P<0.001). The severity of diabetes was significantly associated with ferroptosis level in DFU patients(r = 0.936, P <0.001). The results of multiple regression analysis showed that 4-HNE (β = -0.182, P = 0.008), MDA (β = -0.478, P <0.001) and ROS (β = -0.394, P<0.001) significantly negatively predicted the healing rate of DFU.

Conclusion: As a new monitoring and therapeutic target, ferroptosis level plays an important role in predicting the healing rate of DFU and assisting clinical treatment decision-making.
Click to expand...

Diabetic ferroptosis and chronic wounds

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

SigmoidOxy - mobile perfusion tool for diabetic foot management

Healing of diabetic neuropathic foot ulcers receiving standard treatment

Nanozymes for the Treatment of Diabetic Foot Ulcers

Rapha® device for the treatment of diabetic foot ulcers

Cytoreg for the treatment of diabetic foot disease

COX-2 targeted therapy for diabetic foot ulcers

Healthcare-Seeking Intention Questionnaire in Diabetic High-Risk Foot

Share This Page

Diabetic ferroptosis and chronic wounds

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

SigmoidOxy - mobile perfusion tool for diabetic foot management

Healing of diabetic neuropathic foot ulcers receiving standard treatment

Nanozymes for the Treatment of Diabetic Foot Ulcers

Rapha® device for the treatment of diabetic foot ulcers

Cytoreg for the treatment of diabetic foot disease

COX-2 targeted therapy for diabetic foot ulcers

Healthcare-Seeking Intention Questionnaire in Diabetic High-Risk Foot

Share This Page

Useful Searches