Clinical Report: Investigation of Lactylation-Associated Genes in DFUs

Overview

This study identifies lactylation-related genes CHD4, EEF1A1, and EEF1G as significantly downregulated in diabetic foot ulcers (DFUs) and associated with immune dysregulation. The findings suggest that lactylation may play a crucial role in the pathogenesis of DFUs and highlight potential biomarkers for therapeutic strategies.

Background

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, often resulting in chronic wounds and increased amputation risk. Understanding the molecular mechanisms underlying DFU development is essential for improving patient outcomes. Lactylation, a post-translational modification linked to immune response regulation, has emerged as a potential factor in the pathogenesis of DFUs.

Data Highlights

Key Findings

• 1,234 differentially expressed genes (DEGs) identified in DFUs.
• 38 DEGs overlapped with lactylation-related genes; 27 were significantly downregulated.
• Machine learning identified CHD4, EEF1A1, and EEF1G as core lactylation-associated genes.
• These genes showed positive correlation with natural killer cells and negative correlation with neutrophil infiltration.
• Experimental validation confirmed reduced expression of these genes in DFU tissues and high-glucose-stimulated macrophages.

Clinical Implications

The identification of lactylation-associated genes in DFUs suggests new avenues for biomarker development and therapeutic strategies. Clinicians should consider the role of lactylation in immune dysregulation when managing DFUs, potentially leading to improved treatment outcomes.

Conclusion

This study underscores the significance of lactylation in the pathogenesis of diabetic foot ulcers and its potential as a target for future therapeutic interventions.

References

1. American Diabetes Association, Standards of Care in Diabetes—2026
2. npj Digital Medicine, A Blood Transcriptomic Profile Utilizing Machine Learning for Digital Diagnosis and Classification of Alzheimer’s Disease
3. npj Digital Medicine, Spatial Multi-Omics Enhanced by Machine Learning Reveals Lactate-Driven Therapeutic Targets and Reprogramming of the Tumor Microenvironment in Cancer
4. Infection, The Impact of Bacterial Presence and Sampling Techniques on Outcomes in Diabetic Foot Infections
5. BJS (British Journal of Surgery) — 19 Antimicrobial Peptide-Enhanced Gelatin-Modified Hyaluronic Acid Hydrogels for the Management of Chronic Wounds
6. The American Diabetes Association Releases “Standards of Care in Diabetes—2026” | American Diabetes Association
7. [Single-cell transcriptomic analysis reveals immune dysregula-tion and macrophage reprogramming in diabetic foot ulcers].
8. Efficacy and Safety of Negative Pressure Wound Therapy in Diabetic Foot Ulcers: A Cross-Sectional Analysis of Overlapping Meta-Analyses - PubMed