Evidence mapPaperPMID 40655077Full record

ArticleBurns & trauma2025

Flufenamic acid inhibits pyroptosis in ischemic flaps via the AMPK-TRPML1-Calcineurin signaling pathway.

Liang Chen, Ningning Yang, Kongbin Chen, Yingying Huang, Xian Liu, Gaoxiang Yu, Fulin Wang, Yong Gou, Yi Wang, Xiaolang Lu and 4 more

Abstract read
In one paragraph

Article in Burns & trauma, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Liang ChenDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Ningning YangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Kongbin ChenDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Yingying HuangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Xian LiuDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Gaoxiang YuDepartment of Hand Surgery, Ningbo Sixth Hospital, No. 1059 Zhongshan East Road, Jiangdong District, Ningbo 315042, China.
Fulin WangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Yong GouDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Yi WangDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Xiaolang LuDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Yuqi WangSchool of nursing, Wenzhou medical university, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.
Lipeng ZhuThe Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfu Front Street, Zhengzhou 450015, China.
Weiyang GaoDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.ORCID https://orcid.org/0000-0002-6987-5206
Jian DingDepartment of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No. 109 WestXueyuan Road, Lucheng District, Wenzhou 325027, China.ORCID https://orcid.org/0009-0003-0618-8876

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Ischemic injury is a primary cause of distal flap necrosis. Previous studies have shown that Flufenamic acid (FFA) can reduce inflammation, decrease oxidative stress (OS), and promote angiogenesis, suggesting its potential role in protecting flaps from ischemic damage. This study investigated the effects and mechanisms of FFA in enhancing the survival of ischemic flaps. Methods: The viability of ischemic flaps was evaluated using laser doppler blood flow (LDBF) and survival rates. We examined levels of pyroptosis, OS, transcription factor E3 (TFE3)-induced autophagy, and elements of the AMPK-TRPML1-Calcineurin pathway through western blotting (WB), immunofluorescence, molecular docking, cellular thermal shift assay (CETSA) and surface plasmon resonance. Results: The findings suggest that FFA significantly enhances the viability of ischemic flaps. The improvement in flap survival associated with FFA can be attributed to increased autophagy, diminished OS, and the suppression of pyroptosis. Notably, the promotion of autophagy flux and an augmented resistance to OS are instrumental in curbing pyroptosis in these flaps. Activation of TFE3 by FFA promoted autophagy and diminished oxidative damage. The therapeutic effects of FFA were negated when TFE3 levels were decreased using adeno-associated virus (AAV)-TFE3shRNA. Additionally, FFA modified TFE3 activity through the AMPK-TRPML1-Calcineurin pathway. Conclusions: FFA promotes ischemic flap survival via induction of autophagy and suppression of OS by activation of the AMPK-TRPML1-Calcineurin-TFE3 signaling pathway. These findings could have therapeutic implications.

Indexed as

AutophagyFFAIschemic flapsOxidative stressTFE3

Identifiers

PMID40655077
PMCPMC12253954

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.