Evidence map›Paper›PMID 41795141›Full record

Trial reportWound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

Folinic Acid Improves Healing of Diabetic Foot Ulcers.

Glenn D Hoke, Annjanette Stone, Michael A Bauer, Weleetka C Carter, Megan R Newsom, Joseph V Boykin

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Glenn D HokeDepartments of Surgery/Plastic Surgery, Richmond Department of Veterans Affairs, Medical Center, Richmond, Virginia, USA.
Annjanette StonePharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.ORCID https://orcid.org/0000-0001-8012-748X
Michael A BauerDepartment of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.ORCID https://orcid.org/0000-0003-2498-7295
Weleetka C CarterPharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.ORCID https://orcid.org/0000-0002-4808-9660
Megan R NewsomDepartments of Surgery/Plastic Surgery, Richmond Department of Veterans Affairs, Medical Center, Richmond, Virginia, USA.
Joseph V BoykinDepartments of Surgery/Plastic Surgery, Richmond Department of Veterans Affairs, Medical Center, Richmond, Virginia, USA.ORCID https://orcid.org/0000-0002-1583-7001

Funding

Department of Veterans Affairs (VA) Office of Research and Development (ORD)Medline Industries
6 · The paper itself

Abstract

A novel folinic acid (FA) wound treatment (FAWT) significantly (p < 0.05) improved healing (re-epithelialization) of chronic diabetic foot ulcers (DFUs). In a double-blind RCT, 10 (n = 10) chronic DFU subjects received daily topical treatment in either the Control group [(n = 5); PluroGel] or the FAWT group [(n = 5); PluroGel with FA 2.5%]. After 12 weeks, FAWT subjects experienced significantly (p < 0.05) greater %-DFU area reduction (88% [SD: 16]) vs. Control (40% [SD: 39]), respectively. Proteomic analysis of keratinocytes (KCs) pre- and post-FAWT, using Reverse Phase Proteomic Array (RPPA), documented significantly decreased levels of HMGB1 (High Mobility Group Box1) protein and activated IL-1B protein at 12 weeks after FAWT as compared to Control. RPPA also documented significantly decreased activating phosphorylation of SAP/JNK3 (T183/Y185) and p38 MAPK (T180/Y182) levels after FAWT as compared to Control. These findings suggested decreased activation and possible reduction of NFKB/p65 and p38 MAPK following FAWT that could decrease proinflammatory gene expression. Genomic DNA-methylation analysis of KCs identified significantly decreased FAWT-induced methylation at gene expression regulatory sites for multiple microRNAs (MiRNA) associated with regulating proinflammatory responses. FAWT-induced decreased methylation levels in MiRNAs suggested increased expression and their potential to inhibit protein translation. These MiRNAs are predicted to target multiple mitogen-activated protein kinase (MAPK) pathways. These MAPK pathways mediate signalling from proinflammatory cell surface receptors (such as RAGE, TLRs and IL1R), altering gene expression. FAWT-induced inhibition of MAPK-signalling may lessen NFKB/p65 and p38 MAPK induction of proinflammatory gene expression, reflected in the significantly decreased protein levels of HMGB1 and IL-1B. The data suggest FAWT-induced coordinated expression of multiple anti-inflammatory MiRNAs associated with impaired MAPK-signalling that resulted in decreased expression of HMGB1 and IL1B and this process may facilitate DFUs' transition from an inflammatory state to wound repair, enabling KCs to regulate their proliferative phase, migration and the promotion of DFU re-epithelialization.

Indexed as

Diabetic FootRe-EpithelializationWound HealingDouble-Blind MethodFemaleHMGB1 ProteinHumansKeratinocytesMaleMiddle AgedProteomicsHMGB1 Proteindiabetic foot ulcerdiabetic woundDNA methylationfolinic acidgenomicHMGB1inflammationmicroRNAproteomic

Identifiers

PMID41795141
PMCPMC12967698

What Socratic 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 Socratic graph.