AP39, a novel mitochondria-targeted hydrogen sulfide donor, promotes cutaneous wound healing in an in vivo murine model of acute frostbite injury
Bibliographic record
Abstract
Frostbite injury refers to cold tissue injury which typically affects the peripheral areas of the body, and is associated with limb loss and high rates of morbidity. Historically, treatment options have been limited to supportive care, leading to suboptimal outcomes for affected patients. The pathophysiology of frostbite injury has been understood in recent years to share similarity with that of cold ischemia-reperfusion injury as seen in solid organ transplantation, of which mitochondria play an important contributing role. The present study investigated whether AP39, a novel mitochondria-targeted slow-releasing hydrogen sulfide donor, applied topically in a vehicle cream at 200 nM or 1 µM could mitigate frostbite injury and promote wound healing in mice. Frostbite injury was induced continuously for 3 min on the dorsal skin of C57BL/6 mice (Mus musculus) using magnets frozen on dry ice (-80 °C). AP39, delivered via a vehicle cream, was used daily to treat frostbite injury until animals were euthanized on day 15 after induction of frostbite injury. Wound tissues were stained with hematoxylin and eosin along with immunofluorescence staining with cleaved caspase-3, CD31, KI-67, CD163, fibronectin and cytokeratin. While 200 nM AP39 improved granulation tissue maturation (p < 0.001), angiogenesis (p < 0.01) and cell proliferation (p < 0.001) compared to vehicle control, 1 µM AP39 further increased granulation tissue formation compared to other frostbite groups (p < 0.001). Thus, AP39 promoted frostbite wound healing, and therefore could be considered as a treatment option for patients with frostbite injury.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".