ArticleMolecular medicine (Cambridge, Mass.)2015
The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
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.
Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- JAK inhibition with tofacitinib rapidly increases contractile force in human skeletal muscle.Life science alliance · 2024Trial
- Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.Medical science monitor : international medical journal of experimental and clinical research · 2024Trial
- Muscle Dysfunction in Critical Illness: Established Mechanisms and the Potential Contribution of the NLRP3 Inflammasome.International journal of molecular sciences · 2026Review
- Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025Review
- Ultrasonographic changes and impact factors of diaphragmatic function in patients with obstructive sleep apnea-hypopnea syndrome.Sleep & breathing = Schlaf & Atmung · 2024Article
- Aberrant mitochondrial dynamics contributes to diaphragmatic weakness induced by mechanical ventilation.PNAS nexus · 2023Article
- Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis.Translational neurodegeneration · 2023Review
- Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway.Scientific reports · 2023Article
- Intensive Care Unit Acquired Weakness Is Associated with Rapid Changes to Skeletal Muscle Proteostasis.Cells · 2022Article
- Impact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise.The Journal of physiology · 2022Review
- Altered expression of microRNAs in the rat diaphragm in a model of ventilator-induced diaphragm dysfunction after controlled mechanical ventilation.BMC genomics · 2021Article
- Transcriptome profiling of the diaphragm in a controlled mechanical ventilation model reveals key genes involved in ventilator-induced diaphragmatic dysfunction.BMC genomics · 2021Article
- Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity.Antioxidants (Basel, Switzerland) · 2021Review
- Biological Network Model of Effect of Chronic Intermittent Hypoxia on Spermatogenesis in Rats.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Chaperone co-inducer BGP-15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model.Acta physiologica (Oxford, England) · 2020Article
- Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?Critical care research and practice · 2020Review
- Disturbances in Calcium Homeostasis Promotes Skeletal Muscle Atrophy: Lessons From Ventilator-Induced Diaphragm Wasting.Frontiers in physiology · 2020Review
- Ventilator-induced diaphragm dysfunction: translational mechanisms lead to therapeutical alternatives in the critically ill.Intensive care medicine experimental · 2019Review
- Mechanical ventilation causes diaphragm dysfunction in newborn lambs.Critical care (London, England) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients' need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined. We report here that the JAK-STAT pathway is activated in MV in the human diaphragm, as evidenced by significantly increased phosphorylation of JAK and STAT. Blockage of the JAK-STAT pathway by a JAK inhibitor in a rat MV model prevents diaphragm muscle contractile dysfunction (by ~85%, p < 0.01). We further demonstrate that activated STAT3 compromises mitochondrial function and induces oxidative stress in vivo, and, interestingly, that oxidative stress also activates JAK-STAT. Inhibition of JAK-STAT prevents oxidative stress-induced protein oxidation and polyubiquitination and recovers mitochondrial function in cultured muscle cells. Therefore, in ventilated diaphragm muscle, activation of JAK-STAT is critical in regulating oxidative stress and is thereby central to the downstream pathogenesis of clinical VIDD. These findings establish the molecular basis for the therapeutic promise of JAK-STAT inhibitors in ventilated ICU patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.