Targeting FoxO1/3a, NF-κB, and mTOR signaling attenuates muscle atrophy in sepsis.

Donglin Fu, Min Zhou, Yingxiao Zhang, Pan Cheng, Yue Shu, Qian Xiao, Meng Zhang

Abstract read

In one paragraph

Article in Scientific reports, 2026. 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

7 authors.

Donglin FuDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Min ZhouDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Yingxiao ZhangDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Pan ChengDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Yue ShuDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Qian XiaoDepartment of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. xiaoqian1956@126.com.

Meng ZhangDepartment of Critical Care Medicine, Chongqing General Hospital, Chongqing University, Chongqing, 400013, China. 13883928801@163.com.

Funding

Chongqing Science and Health Joint Medical Scientific Research Surface Project 2024MSXM091

6 · The paper itself

Abstract

Sepsis frequently leads to skeletal muscle atrophy, but its molecular mechanisms remain unclear. Using a mouse model of cecal ligation and puncture and LPS-treated C2C12 myotubes, we found that sepsis activates autophagy, the ubiquitin-proteasome system (UPS), and calpain pathways, resulting in muscle wasting and functional decline. These changes were linked to upregulated FoxO1/3a and NF-κB signaling and suppressed mTOR activity. Pharmacological inhibition or genetic deletion of key components in these pathways, especially MuRF1, mitigated muscle atrophy and preserved function. Our findings reveal that sepsis-induced muscle loss is driven by coordinated activation of proteolytic systems regulated by the FoxO1/3a, NF-κB, and mTOR signaling pathway, offering potential therapeutic targets.

Indexed as

Forkhead Box Protein O1Forkhead Box Protein O3Muscular AtrophyNF-kappa BSepsisSignal TransductionTOR Serine-Threonine KinasesAnimalsAutophagyCell LineDisease Models, AnimalMaleMiceMuscle Fibers, SkeletalMuscle ProteinsProteasome Endopeptidase ComplexForkhead Box Protein O1Forkhead Box Protein O3Foxo1 protein, mouseFoxO3 protein, mousemTOR protein, mouseMuscle ProteinsNF-kappa BProteasome Endopeptidase ComplexTOR Serine-Threonine KinasesTrim63 protein, mouseTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID42168462

DOI10.1038/s41598-026-52665-7

PMCPMC13402580

What OpenQuestion holds

Textmetadata

LicenceCC BY-NC-ND

Read underepoch 390

Registered trials

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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.