{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:18:50Z","timestamp":1787167130208,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/04607\u20100"],"award-info":[{"award-number":["2020\/04607\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/14495\u20100"],"award-info":[{"award-number":["2022\/14495\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/16226\u20107"],"award-info":[{"award-number":["2022\/16226\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305494\/2022\u20108"],"award-info":[{"award-number":["305494\/2022\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mechanical inactivity rapidly induces diaphragm muscle fibres' contractile dysfunction and atrophy. Diaphragm weakness can impair respiratory function, quality of life and increase risks of morbidity and mortality. Muscle RING\u2010finger protein\u20101 (MuRF1) expression is upregulated during denervation and muscle inactivity and is known to target key muscle proteins for degradation. We previously reported that the small\u2010molecule targeting MuRF1 (MyoMed\u2010205) protects against diaphragm contractile dysfunction and atrophy after 12\u2009h of unilateral diaphragm denervation (UDD) in rats. In this study, we investigated the mechanisms by which MyoMed\u2010205 protects the diaphragm structure and function during early UDD in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were subjected to unilateral diaphragm denervation (UDD) for 12\u2009h. Immediately after UDD, rats received either a placebo (vehicle) or small\u2010molecule targeting MuRF1 (MyoMed\u2010205, 50\u2009mg\/kg bw), and outcomes were compared with sham\u2010operated controls. Diaphragm was used for histological, morphometric, transcriptomic (RNA\u2010seq) and protein content (Western blot) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      UDD induced diaphragm slow\u2010 (Type I:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) and fast\u2010twitch (Type IIa:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04; Type IIb\/x:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02) fibres atrophy after 12\u2009h, which was prevented by MyoMed\u2010205 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Mechanistically, UDD perturbed mechanisms involved with myofibre ultrastructure and contractility, mitochondrial function, proteolysis and tissue remodelling in the diaphragm. MyoMed\u2010205 enhanced the activation of mechanisms required for sarcomere integrity, calcium handling, antioxidant defence, chaperone\u2010mediated unfolded protein response and muscle growth. MyoMed\u2010205 also mitigated intramuscular fat deposition and pro\u2010fibrotic responses triggered by UDD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Small\u2010molecule targeting MuRF1 (MyoMed\u2010205) protects against diaphragm muscle contractile dysfunction and atrophy after 12\u2009h of UDD. Herein, we demonstrate that this protective effect involved augmented activation of signalling pathways controlling muscle structure and function, chaperone\u2010mediated unfolded protein and muscle growth, while mitigating intramuscular fat deposition and pro\u2010fibrotic responses triggered by UDD at the transcriptional and\/or protein level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70119","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:40:51Z","timestamp":1763358051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Small\u2010Molecule Targeting MuRF1 Protects Against Denervation\u2010Induced Diaphragmatic Dysfunction: Underlying Molecular Mechanisms"],"prefix":"10.1002","volume":"16","author":[{"given":"Fernando","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo\u00a0R.","family":"Jannig","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Biomedicum Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Labeit","sequence":"additional","affiliation":[{"name":"Department for Integrative Pathophysiology, DZHK Partner Site Mannheim\u2010Heidelberg, Medical Faculty Mannheim University of Heidelberg  Mannheim Germany"},{"name":"Myomedix GmbH  Neckargem\u00fcnd Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-4613","authenticated-orcid":false,"given":"Anselmo\u00a0S.","family":"Moriscot","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00002.2018"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1007236"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2012.tb00433.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2024"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.173.291"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043637"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.12.006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.77.3.1128"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01277.2005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.91247.2008"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00172.2010"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12319"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.4.1249"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4448"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.05.021"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601952"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/function\/zqab029"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186663"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12233"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12448"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12968"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102272"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042225"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201412-2214OC"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2025.102025"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1609707113"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00987-2"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241393598"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200202-088OC"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23272-z"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07718-5"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf7099"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.4.1196"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00040.2011"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.11.049"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13869-w"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00022.2013"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-020-00229-2"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-015-0252-x"}],"container-title":["Journal 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