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
- Av författaren/redakt...
-
Addinsall, Alex ...
-
Cacciani, Nicola
-
Moruzzi, Noah
-
Akkad, Hazem
-
Maestri, Alice
-
Berggren, Per-Ol ...
-
visa fler...
-
Widgren, Anna
-
Bergquist, Jonas
-
Tchkonia, Tamara
-
Kirkland, James ...
-
Larsson, Lars
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Fysiologi
- Artiklar i publikationen
-
Acta Physiologic ...
- Av lärosätet
-
Uppsala universitet
-
Karolinska Institutet