SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Akkad Hazem)
 

Sökning: WFRF:(Akkad Hazem) > Ruxolitinib :

  • Addinsall, Alex B.Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Univ Copenhagen, Novo Nord Fdn Ctr Basic Metab Res, Copenhagen, Denmark. (författare)

Ruxolitinib : A new hope for ventilator-induced diaphragm dysfunction

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • John Wiley & Sons,2024
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-531603
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-531603URI
  • https://doi.org/10.1111/apha.14128DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:155311390URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Aim: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. Conclusion: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Cacciani, NicolaKarolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (författare)
  • Moruzzi, NoahKarolinska Institutet,Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, Stockholm, Sweden. (författare)
  • Akkad, HazemKarolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden. (författare)
  • Maestri, AliceKarolinska Institutet,Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Inst, Dept Med, Div Cardiovasc Med, Solna, Sweden. (författare)
  • Berggren, Per-OlofKarolinska Institutet,Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, Stockholm, Sweden. (författare)
  • Widgren, AnnaUppsala universitet,Analytisk kemi(Swepub:uu)gansc354 (författare)
  • Bergquist, JonasUppsala universitet,Analytisk kemi(Swepub:uu)jbe25356 (författare)
  • Tchkonia, TamaraViron Mol Med Inst, Muscle Biol Program, Boston, MA USA. (författare)
  • Kirkland, James L.Karolinska Institutet,Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA.;Mayo Clin, Div Gen Internal Med, Rochester, MN USA.,Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Viron Mol Med Inst, Muscle Biol Program, Boston, MA USA.;Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden. (författare)
  • Larsson, LarsKarolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Viron Mol Med Inst, Muscle Biol Program, Boston, MA USA.;Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol Grp, Solnavagen 9, S-17165 Solna, Sweden. (författare)
  • Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Univ Copenhagen, Novo Nord Fdn Ctr Basic Metab Res, Copenhagen, Denmark.Karolinska Inst, Dept Physiol & Pharmacol, Basic & Clin Muscle Biol, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Acta Physiologica: John Wiley & Sons240:51748-17081748-1716

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy