Evidence map›Paper›PMID 40426903›Full record

ReviewBiomedicines2025

Diabetic Foot Ulcers: Pathophysiology, Immune Dysregulation, and Emerging Therapeutic Strategies.

John Dawi, Kevin Tumanyan, Kirakos Tomas, Yura Misakyan, Areg Gargaloyan, Edgar Gonzalez, Mary Hammi, Serly Tomas, Vishwanath Venketaraman

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biomedicines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Immunomodulatory Tissue-Engineering Strategies for Diabetic Foot Ulcer Management: A Systematic Review.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Pooled it
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. The Wound-Heart Axis: Can Chronic Wounds Contribute to Cardiac Dysfunction?International journal of molecular sciences · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Type 2 Diabetes Mellitus and Chronic Venous Disease of the Lower Extremities: A Narrative Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
  14. Article
  15. Review
  16. Article
  17. Review
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  20. Review

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

John DawiCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.ORCID 0009-0002-1860-3697
Kevin TumanyanCollege of Podiatric Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Kirakos TomasCollege of Podiatric Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Yura MisakyanCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Areg GargaloyanCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Edgar GonzalezCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Mary HammiCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Serly TomasOakland University William Beaumont School of Medicine, Rochester, MI 48309, USA.
Vishwanath VenketaramanCollege of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.ORCID 0000-0002-2586-1160

Funding

Glutathione depletion in the CNS and its effects on Mtb infectionR15HL143545 · NHLBI · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI VENKETARAMAN, VISHWANATH · 2019 to 2024
$852k
NHLBI NIH HHS R15 HL143545
6 · The paper itself

Abstract

Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15-25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged wound care, and frequent hospitalizations, accounting for billions in healthcare costs worldwide. The multifactorial pathophysiology of DFUs involves peripheral neuropathy, peripheral arterial disease, chronic inflammation, and impaired tissue regeneration. Recent studies underscore the importance of immune dysregulation-specifically macrophage polarization imbalance, regulatory T cell dysfunction, and neutrophil impairment-as central mechanisms in wound chronicity. These immune disruptions sustain a pro-inflammatory environment dominated by cytokines, such as TNF-α, IL-1β, and IL-6, which impair angiogenesis and delay repair. This review provides an updated synthesis of DFU pathogenesis, emphasizing immune dysfunction and its therapeutic implications. We examine emerging strategies in immunomodulation, regenerative medicine, and AI-based wound technologies, including SGLT2 inhibitors, biologics, stem cell therapies, and smart dressing systems. These approaches hold promise for accelerating healing, reducing amputation risk, and personalizing future DFU care.

Indexed as

advanced glycation end products (AGEs)macrophage polarization (M1/M2 imbalance)negative pressure wound therapy (NPWT)receptor for AGEs (RAGE) activationvascular endothelial growth factor (VEGF) therapy

Identifiers

PMID40426903
PMCPMC12109115

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.