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Duchenne muscular dystrophy (DMD) is a disease that primarily affects males and causes a gradual loss of muscle strength. This results in a deterioration of motor skills and functional mobility, which can impact the performance of various occupations. Individuals with DMD often rely heavily on caregivers to assist with daily activities, which can lead to caregiver burden. A case study was conducted to explore and describe potential variations in the performance of a young adult diagnosed with DMD and his caregivers resulting from the integration of smart speakers (SS)-controlled Internet of Things (IoT) devices in the home environment. The study also examined the potential of SS as an environment control unit (ECU) and analysed variations in caregiver burden. Smart devices and SS were installed in the most frequently used spaces, namely, the bedroom and living room. The study employed WebQDA software to perform content analysis and Microsoft Excel to calculate the scores of the structured instruments. The implementation of the IoT-assisted environment compensated for previously physical tasks, resulting in a slight increase in independent performance and reduced demands on caregivers.

Sarcospan (SSPN) is a 25-kDa transmembrane protein that is broadly expressed at the cell surface of many tissues, including, but not limited to, the myofibers from skeletal and smooth muscles, cardiomyocytes, adipocytes, kidney epithelial cells, and neurons. SSPN is a core component of the dystrophin-glycoprotein complex (DGC) that links the intracellular actin cytoskeleton with the extracellular matrix. It is also associated with integrin α7β1, the predominant integrin expressed in skeletal muscle. As a tetraspanin-like protein with four transmembrane spanning domains, SSPN functions as a scaffold to facilitate protein-protein interactions at the cell membrane. Duchenne muscular dystrophy, Becker muscular dystrophy, and X-linked dilated cardiomyopathy are caused by the loss of dystrophin at the muscle cell surface and a concomitant loss of the entire DGC, including SSPN. SSPN overexpression ameliorates Duchenne muscular dystrophy in the mdx murine model, which supports SSPN being a viable therapeutic target. Other rescue studies support SSPN as a biomarker for the proper assembly and membrane expression of the DGC. Highly specific and robust antibodies to SSPN are needed for basic research on the molecular mechanisms of SSPN rescue, pre-clinical studies, and biomarker evaluations in human samples. The development of SSPN antibodies is challenged by the presence of its four transmembrane domains and limited antigenic epitopes. To address the significant barrier presented by limited commercially available antibodies, we aimed to generate a panel of robust SSPN-specific antibodies that can serve as a resource for the research community. We created antibodies to three SSPN protein epitopes, including the intracellular N- and C-termini as well as the large extracellular loop (LEL) between transmembrane domains 3 and 4. We developed a panel of rabbit antibodies (poly- and monoclonal) against an N-terminal peptide fragment of SSPN. We used several assays to show that the rabbit antibodies recognize mouse SSPN with a high functional affinity and specificity. We developed mouse monoclonal antibodies against the C-terminal peptide and the large extracellular loop of human SSPN. These antibodies are superior to commercially available antibodies and outperform them in various applications, including immunoblotting, indirect immunofluorescence analysis, immunoprecipitation, and an ELISA. These newly developed antibodies will significantly improve the quality and ease of SSPN detection for basic and translational research.

Periostin, a multifunctional 90 kDa protein, plays a pivotal role in the pathogenesis of fibrosis across various tissues, including skeletal muscle. It operates within the transforming growth factor beta 1 (Tgf-β1) signalling pathway and is upregulated in fibrotic tissue. Alternative splicing of Periostin\'s C-terminal region leads to six protein-coding isoforms. This study aimed to elucidate the contribution of the isoforms containing the amino acids encoded by exon 17 (e17+ Periostin) to skeletal muscle fibrosis and investigate the therapeutic potential of manipulating exon 17 splicing. We identified distinct structural differences between e17+ Periostin isoforms, affecting their interaction with key fibrotic proteins, including Tgf-β1 and integrin alpha V. In vitro mouse fibroblast experimentation confirmed the TGF-β1-induced upregulation of e17+ Periostin mRNA, mitigated by an antisense approach that induces the skipping of exon 17 of the Postn gene. Subsequent in vivo studies in the D2.mdx mouse model of Duchenne muscular dystrophy (DMD) demonstrated that our antisense treatment effectively reduced e17+ Periostin mRNA expression, which coincided with reduced full-length Periostin protein expression and collagen accumulation. The grip strength of the treated mice was rescued to the wild-type level. These results suggest a pivotal role of e17+ Periostin isoforms in the fibrotic pathology of skeletal muscle and highlight the potential of targeted exon skipping strategies as a promising therapeutic approach for mitigating fibrosis-associated complications.

Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder associated with muscle wasting and degeneration. The disease is caused by mutations in the gene that encodes dystrophin, a protein that links the cytoskeleton with cell membrane proteins. The current treatment methods aim to relieve the symptoms of the disease or partially rescue muscle functionality. However, they are insufficient to suppress disease progression. In recent years, studies have uncovered an important role for non-coding RNAs (ncRNAs) in regulating the progression of numerous diseases. ncRNAs, such as micro-RNAs (miRNAs), bind to their target messenger RNAs (mRNAs) to suppress translation. Understanding the mechanisms involving dysregulated miRNAs can improve diagnosis and suggest novel treatment methods for patients with DMD. This review presents the available evidence on the role of altered expression of miRNAs in the pathogenesis of DMD. We discuss the involvement of these molecules in the processes associated with muscle physiology and DMD-associated cardiomyopathy.

The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered the existence of a gut-muscle axis, revealing how alterations in the gut microbiota can disrupt regulatory mechanisms in muscular and adipose tissues, triggering immune-mediated inflammation. In the context of Duchenne muscular dystrophy (DMD), alterations in intestinal permeability stand as a potential origin of molecules that could trigger muscle degeneration via various pathways. Metabolites produced by gut bacteria, or fragments of bacteria themselves, may have the ability to migrate from the gut into the bloodstream and ultimately infiltrate distant muscle tissues, exacerbating localized pathologies. These insights highlight alternative pathological pathways in DMD beyond the musculoskeletal system, paving the way for nutraceutical supplementation as a potential adjuvant therapy. Understanding the complex interplay between the gut microbiota, immune system, and muscular health offers new perspectives for therapeutic interventions beyond conventional approaches to efficiently counteract the multifaceted nature of DMD.

Mutations in the DMD gene cause fatal Duchenne Muscular Dystrophy (DMD). An attractive therapeutic approach is autologous cell transplantation utilizing myogenic progenitors derived from induced pluripotent stem cells (iPSCs). Given that a significant number of DMD mutations occur between exons 45 and 55, we developed a gene knock-in approach to correct any mutations downstream of exon 44. We applied this approach to two DMD patient-specific iPSC lines carrying mutations in exons 45 and 51 and confirmed mini-DYSTROPHIN (mini-DYS) protein expression in corrected myotubes by western blot and immunofluorescence staining. Transplantation of gene-edited DMD iPSC-derived myogenic progenitors into NSG/mdx4Cv mice produced donor-derived myofibers, as shown by the dual expression of human DYSTROPHIN and LAMIN A/C. These findings further provide proof-of-concept for the use of programmable nucleases for the development of autologous iPSC-based therapy for muscular dystrophies.

Gene regulatory networks that act upstream of skeletal muscle fate determinants are distinct in different anatomical locations. Despite recent efforts, a clear understanding of the cascade of events underlying the emergence and maintenance of the stem cell pool in specific muscle groups remains unresolved and debated. Here, we invalidated Pitx2 with multiple Cre-driver mice prenatally, postnatally, and during lineage progression. We showed that this gene becomes progressively dispensable for specification and maintenance of the muscle stem (MuSC) cell pool in extraocular muscles (EOMs) despite being, together with Myf5, a major upstream regulator during early development. Moreover, constitutive inactivation of Pax7 postnatally led to a greater loss of MuSCs in the EOMs compared to the limb. Thus, we propose a relay between Pitx2, Myf5 and Pax7 for EOM stem cell maintenance. We demonstrate also that MuSCs in the EOMs adopt a quiescent state earlier that those in limb muscles and do not spontaneously proliferate in the adult, yet EOMs have a significantly higher content of Pax7+ MuSCs per area pre- and post-natally. Finally, while limb MuSCs proliferate in the mdx mouse model for Duchenne muscular dystrophy, significantly less MuSCs were present in the EOMs of the mdx mouse model compared to controls, and they were not proliferative. Overall, our study provides a comprehensive in vivo characterisation of MuSC heterogeneity along the body axis and brings further insights into the unusual sparing of EOMs during muscular dystrophy.