Biomarkers of Healing in Chronic Diabetic Foot Ulcers

NewsBot · Sep 28, 2024

Biomarkers of local inflammation at the skin's surface may predict both pressure and diabetic foot ulcers
Pauline Wilson et al
J Wound Care. 2024 Sep 2;33(9):630-635

This commentary considers the similarities which exist between pressure ulcers (PUs) and diabetic foot ulcers (DFUs). It aims to describe what is known to be shared-both in theory and practice-by these wound types. It goes on to detail the literature surrounding the role of inflammation in both wound types. PUs occur following prolonged exposure to pressure or pressure in conjunction with shear, either due to impaired mobility or medical devices. As a result, inflammation occurs, causing cell damage. While DFUs are not associated with immobility, they are associated with altered mobility occurring as a result of complications of diabetes. The incidence and prevalence of both types of lesions are increased in the presence of multimorbidity. The prediction of either type of ulceration is challenging. Current risk assessment practices are reported to be ineffective at predicting when ulceration will occur. While systemic inflammation is easily measured, the presence of local or subclinical inflammation is harder to discern. In patients at risk of either DFUs or PUs, clinical signs and symptoms of inflammation may be masked, and systemic biomarkers of inflammation may not be elevated sufficiently to predict imminent damage until ulceration appears. The current literature suggests that the use of local biomarkers of inflammation at the skin's surface, namely oedema and temperature, may identify early tissue damage.
Click to expand...

NewsBot · Oct 7, 2024

Systematic review and meta-analysis of the diagnostic accuracy of inflammatory markers for infected diabetic foot ulcer
Hua Chen et al
J Tissue Viability. 2024 Sep 26

Background: The aim was to evaluate the diagnostic value of ESR, CPR, PCT, and WBC in patients with infected diabetic foot ulcer (DFU).

Methods: The MEDLINE, Embase, BIOSIS, Cochrane databases, and Web of Knowledge databases were searched, without language restriction, to July 2023. Original studies were selected that reported the performance of ESR, CPR, PCT, and WBC in diagnosing infected DFU. To assess the diagnostic value of biomarkers for infected DFU, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (ROC-AUC) were calculated.

Results: Ten studies with 765 patients were identified in our meta-analysis. The pooled sensitivity and specificity of ESR was 0.82 (95 % CI: 0.68-0.91) and 0.83 (95 % CI: 0.69-0.91) respectively. The pooled sensitivity and specificity of CRP was 0.81 (95 % CI: 0.65-0.91) and 0.91 (95 % CI: 0.79-0.96) respectively. The pooled sensitivity and specificity of PCT was 0.76 (95 % CI: 0.65-0.85) and 0.89 (95 % CI: 0.78-0.95) respectively. The pooled sensitivity and specificity of WBC was 0.75 (95 % CI: 0.64-0.83) and 0.79 (95 % CI: 0.67-0.88) respectively. CRP showed the best diagnostic accuracy at distinguishing infected DFU from noninfected DFU with an AUC of 0.93, followed by PCT (AUC of 0.89), ESR (AUC of 0.89), and WBC (AUC of 0.84).

Conclusion: CPR levels had high efficiency in distinguishing infected DFU from noninfected DFU, followed by PCT, ESR and WBC. All of these biomarkers could be helpful for early diagnosis of infected DFU. New biomarkers for improving medical decision in diagnosis of infected DFU are highly desirable.
Click to expand...

NewsBot · Nov 1, 2024

Neutrophil Migration is a Crucial Factor in Wound Healing and the Pathogenesis of Diabetic Foot Ulcers: Insights into Pharmacological Interventions
Adhi Shree R et al
Curr Vasc Pharmacol. 2024 Oct 30.

Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU.
Click to expand...

NewsBot · May 28, 2025

A Metabolic Signature Specific to the Patients with Type 2 Diabetes and its Association with the Pathogenesis of Diabetic-Foot Syndrome
Tao Wang et al
J Cardiovasc Transl Res. 2025 Apr 16.

Oxidative stress and protein nonenzymatic glycation are key factors in diabetic-foot syndrome pathogenesis. Type 2 diabetes (T2DM) progression involves excessive gluconolactone (GDL) production, linked to endothelial injury and diabetic arteriosclerosis. This study explored GDL's role in diabetic-foot syndrome using high-performance liquid chromatography-tandem mass spectrometry to analyze sera from 75 T2DM patients (including 32 with diabetic-foot) and 36 healthy controls. GDL levels were significantly higher in T2DM patients and correlated with increased hemoglobin A1c glycation and reactive oxygen species production in endothelial cells, suggesting GDL's role in accelerating macrovascular arteriosclerosis and diabetic-foot syndrome. These findings highlight GDL's potential as a diagnostic biomarker and therapeutic target for diabetic macrovascular complications.
Click to expand...

NewsBot · May 31, 2025

Exploring The Role of Serum Netrin 1 Levels in Diabetic Foot Syndrome And Uncomplicated Type 2 Diabetes Mellitus: A Comparative Analysis
D Chaitra et al
Clin Ter. 2025 Mar-Apr;176(2):201-206.

Purpose: Serum netrin levels have been implicated in diabetes and its complications, including diabetic foot syndrome. Netrin 1, a protein encoded by the Netrin gene, has been recognized for its role in various physiological processes ranging from nervous system development to angiogenesis, inflammation, and wound healing. In the context of diabetes, there is growing interest in understanding the relationship between serum netrin levels and the disease. Studies have suggested that netrin-1 may have a role in angiogenesis and inflammatory responses, both of which are relevant to diabetes and its complications. Research has indicated that may be involved in the pathophysiology of diabetic foot syndrome, a serious complication of diabetes characterized by issues such as foot ulcers and impaired wound healing. Therefore, comparing serum netrin levels in individuals with diabetes, especially those with complications like diabetic foot syndrome, to those with uncomplicated diabetes, may provide insights into the potential association between netrin and the disease.
Click to expand...

NewsBot · Jun 5, 2025

Evaluation of c-Myc and Phosphorylated Glucocorticoid Receptor (p-GR) for Predicting Diabetic Foot Ulcer Healing-A Diabetic Foot Consortium Study
Robert S Kirsner et al
Wound Repair Regen. 2025 May-Jun;33(3):e70044.

Diabetic foot ulcers (DFUs) are a serious clinical problem, leading to high rates of morbidity, disability, amputations, and mortality. Many DFUs fail to heal completely and a major challenge includes identifying non-healers early in treatment. However, effective predictive biomarkers for DFUs have not yet been validated. The goal of this study was to validate if two previously identified, objective and quantitative tissue biomarkers, c-Myc and phosphorylated glucocorticoid receptor (p-GR), could predict complete healing at week 12 in a multicenter observational cohort study of individuals with open DFUs, conducted by the NIDDK Diabetic Foot Consortium (DFC). Wound tissue collected at the initial visit was analysed for c-Myc and p-GR biomarkers by immunohistochemistry, quantifying their nuclear presence in full thickness epidermis and correlating with week 12 clinical outcomes. The primary analyses included AUC comparisons to assess the biomarkers' predictive capability for wound healing. Other analyses included descriptive measures and t-tests to evaluate the difference between biomarker quantification among healers and non-healers. Of 140 DFUs enrolled, 107 participants completed biomarker and clinical outcome data for analysis. The distributions of baseline c-Myc and p-GR between healed and not-healed DFUs by week 12 were not significantly different (p > 0.05). Although the two biomarkers did not yield significant predictability (ΔAUC = -0.006, 95% CI (-0.02, 0.01) and ΔAUC = -0.0002, 95% CI (-0.01, 0.01), p > 0.025) for each of c-Myc and p-GR respectively, this first DFC clinical study using a national consortium of DFU centres successfully created a unique resource of wound-related biomaterials coupled with the clinical outcomes, providing a platform for further biomarker discovery and validation.
Click to expand...

NewsBot · Jun 16, 2025

Are metabolic abnormalities the missing link between complete blood count-derived inflammatory markers and diabetic foot? Evidence from a large population study
Yang Zhang ,Shumin Zhou ,Xianbin Wang,Haiyan Zhou
June 12, 2025

Background
Diabetic foot is a serious complication of diabetes, and inflammation plays a key role in its pathogenesis. This population-based study investigates associations between complete blood count (CBC)-derived inflammatory markers and diabetic foot, while evaluating metabolic mediators in these relationships.

Methods
Data from 1,246 participants across three National Health and Nutrition Examination Survey (NHANES) cycles (1999–2004) were analyzed. Calculated inflammatory markers included monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), and systemic inflammatory response index (SIRI). Weighted logistic regression models assessed marker-diabetic foot associations, supplemented by subgroup and restricted cubic spline (RCS) analyses for nonlinearity. Mediation analysis quantified metabolic contributions.

Results
CBC-derived inflammatory markers demonstrated significant positive correlations with diabetic foot risk. Risk increased as quartiles for these markers increased. RCS analysis further revealed a significant nonlinear relationship between them. Serum creatinine (12.46%) and albumin (11.33%) mediated significant proportions of these associations.

Conclusions
CBC-derived inflammatory markers serve as accessible predictors of diabetic foot risk, with nonlinear patterns. The partial mediation by metabolic indicators highlights dual inflammatory-metabolic pathways in diabetic foot pathogenesis. Routine CBC-derived inflammatory markers monitoring could enable early risk stratification, while targeting metabolic abnormalities may amplify preventive strategies.
Click to expand...

NewsBot · Jul 26, 2025

The development of a direct co-culture-based model for diabetic foot ulcer mimicking inflammation and impaired phagocytosis
Mirella Ejiugwo et al
In Vitro Model. 2025 Apr 14;4(2):111-129.

Purpose: Diabetic foot ulcers (DFU) are characterized by delayed healing and high infection rates. DFU affect approximately 25% of individuals with diabetes. Secondary to hyperglycaemia, both chronic inflammation and defective phagocytosis have been identified as contributing factors to the non-healing status of DFU. Both inflammation and defective phagocytosis in DFU were sought to be modelled in vitro using pHRODO bioparticles for the first time. The pHRODO bioparticles, popularly used as phagocytic cargos, are chemically killed microorganisms conjugated to the pH-sensitive pHRODO dye that solely fluoresces within the acidic lysosomes where phagocytosis occurs.

Methods: The in vitro DFU model was developed by identifying which ratio of diabetic fibroblasts to THP-1-derived Mɸ, choice of pHRODO bioparticles, FBS concentration, and oxygen level exhibited both significant inflammation and reduced phagocytic ability. Inflammation was confirmed via simultaneous TNF-α and MCP-1 release by direct co-cultures of diabetic fibroblasts and THP-1-derived macrophages (Mɸ) following pHRODO bioparticle exposure using ELISA. Phagocytic activity, derived from the emitted fluorescence of ingested pHRODO bioparticles within acidic lysosomes, was quantified using an automated, whole-well, fluorescent imaging system. The kinase Bay 11-7085, shown to stimulate phagocytosis previously, was used to verify the usefulness of the developed in vitro DFU model.

Results: Inflammation and reduced phagocytic activity were observed maximally for a 1:4 ratio of diabetic dermal fibroblasts to THP-1-derived Mɸ upon 4-h incubation with 200 µg/ml pHRODO green Staphylococcus aureus bioparticles under hypoxia (2% oxygen) and low nutrient level (2% fetal bovine serum)-compared with the in vitro healthy wound model. When co-delivered with Bay 11-7085, significant increased uptake of pHRODO green S. aureus bioparticles was observed in the in vitro DFU model.

Conclusion: Optimized parameters for modeling inflammation and reduced phagocytic activity in DFU in vitro were identified. Modulating inflammation could be useful in stimulating phagocytosis in DFU based on the positive effect of Bay 11-7085 on the in vitro DFU model. This finding paves the way for screening and re-purposing immunomodulatory drugs to stimulate phagocytosis in DFU
Click to expand...

NewsBot · Nov 3, 2025

Annexin A1 as a potential anti-inflammatory marker in diabetic foot ulcer: A cross-sectional study
Shwetha Shetty Kalladka et al
Human Gene 31 October 2025, 201505

Background
Annexin A1 (AnxA1) is known to suppress inflammation by inhibiting the synthesis of pro-inflammatory molecules and promoting the release of immune-suppressive molecules. This suggests AnxA1 may be a vital marker for modulating inflammation and cell proliferation in Diabetic Foot Ulcer (DFU) patients. The current study aimed to investigate the expression and role of AnxA1 in relation to other key inflammatory molecules in DFU.
Methods
A cross-sectional study was conducted among 40 participants (20 DFU patients and 20 healthy subjects) to evaluate the expression of AnxA1, IL-10, IL-1β, IL-6, and TNF-α from both the blood and tissue samples.
Results
The mean relative expression of anti-inflammatory molecules such as AnxA1 (0.507, 0.442) and IL-10 (2.273, 0.602) were found to be downregulated in tissue and blood, respectively among DFU patients compared to healthy controls. Conversely, the pro-inflammatory molecules like IL-1β (2.393, 0.988), IL-6 (0.830, 0.748), and TNF-α (1.81, 1.099) were upregulated among DFU patients compared to healthy controls. The mean relative expression of AnxA1 and IL-1β was significantly higher in tissue and blood samples respectively of gangrenous DFU compared to non-gangrenous DFU (P < 0.05). Furthermore, AnxA1 expression showed a significant negative correlation with HbA1c and triglyceride levels (in blood and tissue) as well as wound grade and cholesterol levels (in tissue).
Conclusion
The relative down-expression of AnxA1 in DFU patients and its negative correlation with HbA1c, total cholesterol, and triglycerides indicate that AnxA1 has the potential to decrease inflammatory harm in DFU. These findings highlight AnxA1 as a promising target for novel therapeutic strategies against diabetic foot ulceration.
Click to expand...

NewsBot · Nov 7, 2025

Identification of Seven in absentia homolog 2 as a potential efferocytosis-related biomarker in diabetic foot ulcers
Jiangli Zhao , et al
Source

Introduction

Wound of diabetic foot ulcers (DFU) is chronic and hard to heal, characterized by impaired inflammatory response, dysfunction of keratinocyte and endothelial cells and improper removal of dying cells. Efferocytosis, as a trigger for phenotype switch of macrophages, plays a critical role in diabetic foot wound healing. Here, we showed the effect of efferocytosis in wound healing of diabetics and identified seven in absentia homolog 2 (SIAH2) as a potential efferocytosis-related biomarker.
Methods

Blood and skin samples were collected from 20 patients diagnosed type II diabetes at Qilu Hospital of Shandong University. Efferocytosis related genes in DFU were identified based on GSE147890, GSE80178 datasets as well as RNA-seq data of blood samples. Enrichment analysis, clustering analysis and protein-protein interaction network analysis were conducted based on the efferocytosis related genes in DFU. An array diagram was constructed and survival analysis of DFU was performed based on the associated clinical data. Single-cell sequencing data analysis combined with experiments in vitro, we analyzed the role of SIAH2 in wound healing of DFU as well as its correlation with efferocytosis signal.
Results

Overall efferocytosis and SIAH2 expression level were increased in DFU blood and tissue samples and associated with poor survival in patients. Single-cell analysis revealed elevated SIAH2 expression is positively associated with keratinocyte migration, angiogenesis and efferocytosis of macrophage in wound healing of DFU. SIAH2 involved in efferocytosis-related cell-to-cell communication, especially in “internalization” and “digestion” signals.
Conclusion

SIAH2 was identified to be one of the key efferocytosis genes and associated with poor prognosis of DFU. Protective upregulation of SIAH2 was involved in angiogenesis, keratinocyte migration and cell-to-cell communication mediated by efferocytosis in DFU wound healing.
Click to expand...

NewsBot · Nov 8, 2025

Ischemia Modified Albumin in Diabetic Foot Ulcers: Promising Marker or Incomplete Picture?
Seshadri Reddy Varikasuvu
Source

This letter critically appraises the study by Juttada et al, (doi: 10.1177/15347346251332708) which explored ischemia-modified albumin (IMA) as a marker of healing in diabetic foot ulcers (DFUs). We acknowledge the study's novel contribution through its serial IMA monitoring during treatment and compare it with a growing body of evidence. While the study demonstrates promising clinical applicability, there are important limitations regarding its predictive strength, albumin adjustment, and the influence of oxidative therapies. We suggest that future studies adopt a multi-biomarker approach and address variability in oxidative stress conditions such as those encountered during hyperbaric oxygen therapy.
Click to expand...

NewsBot · Dec 1, 2025

Ischemia-Modified Albumin in Diabetic Foot Ulcers: A Systematic Review and Bayesian Meta-Analysis
Seshadri Reddy Varikasuvu et al
Int J Low Extrem Wounds. 2025 Dec 1:15347346251399401.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, leading to significant morbidity, amputation risk, and healthcare burden. This systematic review and meta-analysis aimed to evaluate the association between circulating ischemia-modified albumin (IMA) levels and DFU. A comprehensive search of PubMed, Scopus, Cochrane Central and Google Scholar databases was conducted to identify eligible observational studies reporting IMA concentrations in DFU patients, diabetics without foot ulcers, and healthy controls. Meta-analyses were performed using both frequentist random-effects models and Bayesian approaches. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to express continuous outcomes. PET-PEESE regression analyses assessed publication bias and small-study effects. A total of six studies were included, with five eligible for meta-analysis. Compared to healthy controls, DFU patients exhibited significantly higher IMA levels [pooled SMD = 3.21 (95% CI: 1.40, 5.03)]. Similarly, DFU patients had higher IMA levels than diabetics without foot ulcers [pooled SMD = 1.21 (95% CI: 0.23, 2.20)]. Both frequentist and Bayesian analyses consistently supported these findings despite notable heterogeneity. Adjusted analyses of IMA for serum albumin further confirmed its discriminative value in DFU. PET-PEESE analyses did not detect significant publication bias. This meta-analysis highlights the potential of IMA as a biomarker for diagnosis, risk stratification, and monitoring in DFU management. Despite significant associations, high inter-study heterogeneity and the limited number of studies restrict generalizability. Future research should focus on standardizing measurement protocols, validating clinical cut-offs, and conducting large-scale prospective studies to confirm its utility.
Click to expand...

NewsBot · Dec 30, 2025

Identifying pyroptosis-related genes as novel therapeutic targets in diabetic foot ulceration
Diabetology & Metabolic Syndrome
Kang Liu, Lei Lei, Xin-lei Yang & Xin-he Zhang

Diabetic foot ulcer (DFU) is considered one of the most challenging chronic complications for individuals with diabetes, and its global incidence continues to rise, imposing a substantial burden on society. During the treatment of DFU, the locally intense inflammatory response induced by pyroptosis may adversely affect wound healing, making this phenomenon a focus of research. This study employed bioinformatics methods to systematically analyze the role of pyroptosis-related genes (PRGs) in the healing process of diabetic foot ulcers. Based on public datasets GSE147890 and GSE80178, we performed differential expression analysis, random forest, and LASSO regression to screen for key genes, and constructed and evaluated a multivariate logistic regression diagnostic model. We analyzed the GEO datasets GSE147890 and GSE80178, identifying 1336 and 2727 differentially expressed genes (DEGs), respectively. The intersection analysis with PRGs revealed 9 pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analysis associated these genes with pathways such as I-kappaB kinase/nuclear factor-kappaB (IKK/NF-κB) signaling and mitophagy. Six key PRDEGs (FSTL1, PINK1, HDAC3, ULK1, CPTP, and NOD2) were selected, and a diagnostic model was constructed using random forest and LASSO regression. The accuracy of the model was assessed through multivariate logistic regression, calibration curve analysis, decision curve analysis (DCA), and receiver operating characteristic (ROC) curve analysis. The model demonstrated excellent diagnostic performance, with an area under the curve (AUC) of 1.000 in both the training and validation sets. This study highlights the importance of PRGs in diabetic wound healing (DWH). Our findings not only elucidate the mechanisms of action of PRGs in diabetic wound healing but also provide a theoretical basis for the development of clinical early diagnosis and individualized treatment strategies, holding significant clinical application potential. Future research should validate these findings in larger populations and explore therapeutic interventions targeting these pathways to improve DWH outcomes.
Click to expand...

NewsBot · Jan 4, 2026

Cathepsin B as a potential serum biomarker for early diagnosis and progression of diabetic foot ulcer complicated with peripheral vascular disease
Ying Jin, Yaqi Yao, Yiqi Lin, Jianhua Zhong, Xinyi Kong, Yang Liu, Yuetong Li, Jie Qiao, Aixia Zhai & Changlong Bi
Scientific Reports volume 15, Article number: 42474 (2025)

The existing diagnostic methods of diabetic foot ulcer (DFU) complicated with peripheral vascular disease (PVD) lack sufficient potential for early identification, which leads to slow wound healing, amputation and even death. Thus, this study aimed to explore the potential serum biomarkers of DFU complicated with PVD. A target gene of DFU complicated with PVD was identified using single-cell transcriptome analysis. The immunohistochemistry, ELISA, clinical correlation analysis, tubulogenesis assay, CCK8 assay, and scratch assay were used to verify the correlation between this target gene and DFU complicated with PVD. The ELISA experiment was used to detect the target gene in serum. In this study, the result of PPI in single-cell transcriptomes showed that cathepsin B (CTSB) was enriched in vascular endothelial cells of DFU. The immunohistochemistry and ELISA results revealed that CTSB was highly expressed in the tissues and serum of patients with the combination of DFU and PVD, and this expression increased with the increase of the Wagner grade of DFU. Clinical correlation analysis indicated that CTSB expression is positively correlated with the clinical indicators of the combination of DFU and PVD. Knockdown of CTSB promoted tubulogenesis, proliferation and migration of vascular endothelial cells and overexpression of CTSB has the opposite effect. CTSB, a secretory protein, can be detected as a diagnostic biomarker in serum. Therefore, this study suggested that CTSB can be used as a potential serum diagnostic biomarker for DFU complicated with PVD, which is helpful for the early diagnosis of this disease, prognosis monitoring and adjustment of treatment plans.
Click to expand...

NewsBot · Jan 9, 2026

Identify Diagnostic Biomarkers Related to Taurine Metabolism in Diabetic Foot Ulcers Using Bulk RNA-seq and ScRNA-seq Analysis
Mengrong He, Jiamin Chen
J Diabetes. 2026 Jan;18(1):e70166.

Background: Diabetic foot ulcers (DFU) are severe complications with complex pathogenesis involving inflammation and impaired healing. Taurine, a key antioxidant amino acid, shows therapeutic potential in diabetes, but its role in DFU remains unclear and warrants investigation.

Methods: This integrated multi-omics study analyzed DFU using GEO transcriptomics data (training: GSE68183/GSE80178; validation: GSE37265/GSE134431; scRNA-seq: GSE223964). Limma identified DEGs that intersected with taurine metabolism -related genes. Key modules (MCODE) and a LASSO-based diagnostic signature were established. Immune infiltration was profiled via ssGSEA, CIBERSORT, and MCP-Counter. Regulatory networks (TFs/miRNAs) were predicted (miRNet/NetworkAnalyst), and therapeutic agents were screened (DSigDB). Seurat-processed scRNA-seq defined nine cell types, with CellChat analyzing intercellular communication.

Results: This study identified a three-gene diagnostic signature (HMOX1, MAPK3, TXN) for DFU with near-perfect accuracy (training AUC = 1, validation AUC ≥ 0.98). Multi-omics analyses revealed significant immune dysregulation (increased B cells/CD8+T cells/M1 macrophages in DFS), collagen-centric signaling dominance, and two molecular subtypes. Single-cell RNA-seq uncovered cell-type-specific dysfunction: fibroblasts and endothelial cells expanded in DFS, while HMOX1 localized to Mono-macrophages and MAPK3 to endothelium.

Conclusion: This study deeply analyzed DFU immune microenvironment characteristics, intercellular communication networks, and molecular regulatory mechanisms, revealing a dysregulated metabolic-immune repair network framework, providing new insights for understanding DFU pathological mechanisms and developing targeted diagnostic and therapeutic strategies.
Click to expand...

NewsBot · Jan 15, 2026

Distinct urine and plasma metabolic signatures in diabetic foot: early diagnostic biomarkers and predictive modeling
Feilin lian, Jinping Gu, Jinxin Huan, Yaxin Liu, Wei Lin, Xiaoling Lai, Xiaoqi Zheng, Luyao Li, Wanglong Li, Xinhuang Hou, Fanggang Cai & Changwei Yang
BMC Endocrine Disorders

Background and Objective

Diabetic foot (DF), a limb-threatening complication associated with high risk of amputation, currently lacks reliable early diagnostic biomarkers. This study aims to identify novel DF-specific metabolic biomarkers and develop predictive models for early diagnosis by integrating serum and urine metabolomic profiling.
Methods

Serum and urine samples were collected from patients with diabetic foot and those with diabetes mellitus without foot complications. Metabolomic and lipoprotein profiles were quantitatively analyzed using multivariate statistical methods to identify metabolic alterations associated with DF. Differential metabolites were used to construct a machine learning-based predictive model for early DF diagnosis.
Results

Distinct metabolic profiles differentiated DF from DM patients. Serum analysis revealed significantly lower hemoglobin, albumin, calcium, and apolipoprotein A1 levels in DF (P < 0.05). Urine metabolomics identified elevated N-isovaleroylglycine (OR = 12.89) and valine (OR = 2.23) as key DF-associated metabolites (P < 0.05). Lipidomics demonstrated increased triglyceride-rich LDL subtypes (L2TG, L4TG) and reduced high-density lipoprotein components (H4CH, H4PL) in DF. A predictive model integrating urinary metabolites (N-isovaleroylglycine, valine) and clinical profiles (albumin, apolipoprotein A1, calcium) achieved robust diagnostic accuracy (AUC = 0.91).
Conclusion

This study reveals distinct metabolic disturbances in DF through integrated metabolomic analysis. The combination of urinary metabolites and clinical biomarkers provides a non-invasive approach for early detection of DF, highlighting the potential utility of metabolomics in improving early diagnosis and management of diabetic foot.
Click to expand...

NewsBot · Jan 17, 2026

Biomarkers in Diabetic Foot

Biomarkers of Healing in Chronic Diabetic Foot Ulcers

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.

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.

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.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Biomarkers for diabetic foot amputation prediction

Cellular Biomarkers for the Diagnosis and Treatment of Diabetic Foot Ulcer

Biomarkers for peripheral artery disease

Fespixon Cream in Diabetic Foot Ulcer Healing

Comprehensive Therapy vs. Standard Treatment in Diabetic Foot Ulcer Healing

Injury Afoot: 30 Things You Can Do to Relieve Heel Pain and Speed Healing of Plantar Fasciitis

Healing of diabetic neuropathic foot ulcers receiving standard treatment

Share This Page

Biomarkers of Healing in Chronic Diabetic Foot Ulcers

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.

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.

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.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Biomarkers for diabetic foot amputation prediction

Cellular Biomarkers for the Diagnosis and Treatment of Diabetic Foot Ulcer

Biomarkers for peripheral artery disease

Fespixon Cream in Diabetic Foot Ulcer Healing

Comprehensive Therapy vs. Standard Treatment in Diabetic Foot Ulcer Healing

Injury Afoot: 30 Things You Can Do to Relieve Heel Pain and Speed Healing of Plantar Fasciitis

Healing of diabetic neuropathic foot ulcers receiving standard treatment

Share This Page

Useful Searches