Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mice and, for the first time, demonstrated similar and differential effects of ectoine.
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http://dx.doi.org/10.3390/ijms23179567 | DOI Listing |
Paediatr Drugs
December 2024
Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
New drugs for Duchenne muscular dystrophy (DMD) are emerging rapidly. However, we and others believe these drugs are achieving regulatory approval prematurely. It is the cardiorespiratory complications of DMD that cause the disease's major morbidities and that determine survival.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Hepatobiliary Surgery, First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang, China.
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder primarily affecting cardiac and skeletal muscles, with gastrointestinal obstruction being an infrequent complication.
Case Report: We present a 17-year-old boy with DMD (G-to-T transversion at c.4150 in the gene encoding dystrophin protein) who developed severe colonic obstruction due to fecal impaction.
Neurol Genet
February 2025
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton, NY.
Skelet Muscle
December 2024
Ottawa Hospital Research Institute Regenerative Medicine Program, Ottawa, ON, Canada.
Intramuscular injection of Wnt7a has been shown to accelerate and augment skeletal muscle regeneration and to ameliorate dystrophic progression in mdx muscle, a model for Duchenne muscular dystrophy (DMD). Here, we assessed muscle regeneration and function in wild type (WT) and mdx mice where Wnt7a was deleted in muscle using a conditional Wnt7a floxed allele and a Myf5-Cre driver. We found that both WT and mdx mice lacking Wnt7a in muscle, exhibited marked deficiencies in muscle regeneration at 21 d following cardiotoxin (CTX) induced injury.
View Article and Find Full Text PDFNeurobiol Dis
December 2024
Université Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay, 91400 Saclay, France. Electronic address:
Duchenne muscular dystrophy (DMD) is associated with a range of cognitive and behavioral problems. Brain-related comorbidities show clinical heterogeneity depending on the position of the mutation within the multi-promoter dystrophin (DMD) gene, likely due to the differential impact of mutations on the expression of distinct brain dystrophins. A deficiency of the full-length brain dystrophin, Dp427, has been associated with enhanced stress reactivity, characterized by abnormal fear responses in both patients and mdx mouse model.
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