Muscle stem cell dysfunction in rhabdomyosarcoma and muscular dystrophy

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2024, Volume and Issue: unknown, P. 83 - 121

Published: Jan. 1, 2024

Language: Английский

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Radiomics with Ultrasound Radiofrequency Data for Improving Evaluation of Duchenne Muscular Dystrophy

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Duchenne muscular dystrophy (DMD) is a rare and severe genetic neuromuscular disease, characterized by rapid progression high mortality, highlighting the need for accurate ambulatory function assessment tools. Ultrasound imaging methods have been widely used quantitative analysis. Radiomics, which converts medical images into data, combined with machine learning (ML), offers promising solution. This study aimed at utilizing radiomics to analyze different stages of data generated during B-mode image processing evaluate DMD patients. The included 85 participants, categorized non-ambulatory groups based on their functional status. scans were utilized capture backscattered radiofrequency then processed generate envelope, normalized, images. Radiomics analysis involved manual segmentation grayscale automatic feature extraction using specialized software, followed selection maximal relevance minimal redundancy method. selected features input five ML algorithms, model evaluation conducted via area under receiver operating characteristic curve (AUROC). To ensure robustness, both leave-one-out cross-validation repeated splitting employed. Additionally, multiple models constructed tested assess performance. intensity values across all types increased as walking ability declined, significant differences observed between (p < 0.001). These exhibited similar diagnostic performance levels, AUROC below 0.8. However, (RF) outperformed other when was applied, notably achieving an value 0.906. combining algorithms yielded higher 0.912 RF input. surpasses conventional ultrasound-derived in evaluating DMD. Moreover, integrating further enhances classification proposed method this framework improving accuracy reliability clinical follow-up evaluations, supporting more effective management code available https://github.com/Goldenyan/radiomicsUS .

Language: Английский

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Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3579 - 3579

Published: April 10, 2025

Abnormalities in X chromosomes, either numerical or structural, cause X-linked disorders, such as Duchenne muscular dystrophy (DMD). Recent molecular and cytogenetic techniques can help identify DMD gene mutations. The accurate diagnosis of is crucial, directly impacting patient treatment management, genetics, the establishment effective prevention strategies. This review provides an overview chromosomal disorders affecting discusses how mutations Dystrophin domains impact detection accuracy. Firstly, efficiency use for genetic disease have, thus, become increasingly important. Secondly, artificial intelligence (AI) will be instrumental developing future therapies by enabling aggregation synthesis extensive heterogeneous datasets, thereby elucidating underlying mechanisms. However, despite advances diagnostic technology, understanding role remains a challenge. Therefore, this aims to synthesize complex information significantly advance it could affect care.

Language: Английский

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How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?

Proteomes, Journal Year: 2024, Volume and Issue: 12(1), P. 4 - 4

Published: Jan. 16, 2024

This perspective article is concerned with the question of how proteomics, which a core technique systems biology that deeply embedded in multi-omics field modern bioresearch, can help us better understand molecular pathogenesis complex diseases. As an illustrative example monogenetic disorder primarily affects neuromuscular system but characterized by plethora multi-system pathophysiological alterations, muscle-wasting disease Duchenne muscular dystrophy was examined. Recent achievements dystrophinopathy research are described special reference to proteome-wide complexity changes and body-wide alterations/adaptations. Based on description current applications top-down versus bottom-up proteomic approaches their technical challenges, future biological outlined. The envisaged holistic integromic bioanalysis would encompass integration diverse omics-type studies including inter- intra-proteomics as disciplines for systematic protein evaluations, sophisticated biomolecular analyses, physiology, biology, biochemistry histochemistry. Integrated findings promise be instrumental improving our detailed knowledge pathogenic mechanisms dysfunction, widening available biomarker signature improved diagnostic/prognostic procedures, advancing identification novel therapeutic targets treat dystrophy.

Language: Английский

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Revolutionizing genetic diagnostics: Innovative techniques for inherited disease detection

Gene Reports, Journal Year: 2024, Volume and Issue: 36, P. 101963 - 101963

Published: June 27, 2024

Language: Английский

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Cellular interactions and microenvironment dynamics in skeletal muscle regeneration and disease

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 22, 2024

Skeletal muscle regeneration relies on the intricate interplay of various cell populations within niche—an environment crucial for regulating behavior stem cells (MuSCs) and ensuring postnatal tissue maintenance regeneration. This review delves into dynamic interactions among key players this process, including MuSCs, macrophages (MPs), fibro-adipogenic progenitors (FAPs), endothelial (ECs), pericytes (PCs), each assuming pivotal roles in orchestrating homeostasis Dysfunctions these can lead not only to pathological conditions but also exacerbate muscular dystrophies. The exploration cellular molecular crosstalk both physiological dystrophic provides insights multifaceted communication networks governing Furthermore, discusses emerging strategies modulate muscle-regenerating niche, presenting a comprehensive overview current understanding innovative approaches.

Language: Английский

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Molecular pathways involved in the control of contractile and metabolic properties of skeletal muscle fibers as potential therapeutic targets for Duchenne muscular dystrophy

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 9, 2024

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, a subsarcolemmal protein whose absence results increased susceptibility of muscle fiber membrane to contraction-induced injury. This calcium influx, oxidative stress, and mitochondrial dysfunction, leading chronic inflammation, myofiber degeneration, reduced regenerative capacity. Fast glycolytic fibers have been shown be more vulnerable mechanical stress than slow both DMD patients mouse models. Therefore, remodeling skeletal toward slower, phenotype may represent relevant therapeutic approach protect dystrophic muscles from deterioration improve effectiveness cell-based therapies. The resistance slow, myofibers pathology attributed, part, their higher expression Utrophin; there are, however, other characteristics that might contribute enhanced injury, including contractile speed, fatigue, capillary density, activity, decreased cellular energy requirements. review focuses on signaling pathways regulatory factors genetic or pharmacologic modulation has ameliorate preclinical models while promoting transition towards slower phenotype.

Language: Английский

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Circadian Clock in Muscle Disease Etiology and Therapeutic Potential for Duchenne Muscular Dystrophy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4767 - 4767

Published: April 27, 2024

Circadian clock and clock-controlled output pathways exert temporal control in diverse aspects of skeletal muscle physiology, including the maintenance mass, structure, function, metabolism. They have emerged as significant players understanding disease etiology potential therapeutic avenues, particularly Duchenne muscular dystrophy (DMD). This review examines intricate interplay between circadian rhythms highlighting how disruptions regulation may contribute to pathophysiology specific mechanisms linking dysregulation with DMD. Moreover, we discuss recent advancements chronobiological research that shed light on function its relevance Understanding involved mass offers novel insights into pathogenesis DMD unveils promising avenues for interventions. We further explore chronotherapeutic strategies targeting ameliorate degeneration which inform drug development efforts dystrophy.

Language: Английский

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Spectrinopathies in rare neurological and neuromuscular diseases : large-scale efforts towards the identification of novel molecular causes

Published: Jan. 1, 2024

Rare inherited neurological and neuromuscular diseases affect the central nervous system, peripheral skeletal muscles.About 80% of rare are estimated to have an underlying genetic etiology, yet only approximately 50% patients receive a diagnosis, which is often described as diagnostic gap.Determining cause patients' disease ends their years-long odyssey, has important consequences regarding counselling be offered patients, enables availability pre-implantation testing, increasingly so, determines access clinical trials gene-specific therapies.From research point view, closing gap great impact on discovery critical neuronal pathways, oftentimes leading overarching pathomechanisms between acquired neuropathies resulting in shared therapy development.The overall aim this PhD thesis gain novel insights into architecture diseases, including spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP), myopathies.The objective can divided two main parts: [1] application large-scale variant identification, using both 'classical' single-nucleotide identification bio-informatic approach identify copy number variation whole exome sequencing [2] characterization phenotypical spectrum associated with mutations SPTAN1 gene, identified approaches [1].SPTAN1 display intriguingly wide spectrum.Prior thesis, SPTAN1-associated included epileptic syndromes, intellectual disability, motor neuropathy.Chapter 2 describes de novo dominantly variants HSP SCA, thereby widening system phenotypes variants.This study relied screening more than 10,000 NGS datasets relevant phenotype, indicative efforts currently needed find causes for diseases.Chapter 3 Copy Number Variants (CNVs) repurposed Whole Exome Sequencing (WES).This analysis was performed within setting Solve-RD consortium, enabling participation 42 groups across Europe studying diseases.Three different CNV calling algorithms compared study, limited pre-defined set diseaseassociated genes reduce interpretation burden submitting centers.Chapter 4 presents deeper dive one families techniques Chapter 3, where we show that 9q34 deletion full gene causative myopathy phenotype.This not provided diagnosis long-standing unsolved family, but also further defines include myopathy.A general discussion presented 5, focus commonalities data sharing necessary current challenges remain implement upcoming technologies like long read short genome sequencing.Een discussie van dit proefschrift wordt gepresenteerd Hoofdstuk met nadruk op overeenkomsten pathomechanismen die ten grondslag liggen aan zeldzame erfelijke neurologische en neuromusculaire ziekten, het grote schaal delen gegevens nodig zijn om nieuwe oorzaken voor ziekten te identificeren huidige uitdagingen nog resteren vooraleer technologieën zoals klaar implementatie.

Language: Английский

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ECM components are essential for proper in vitro myogenesis

European Journal of Therapeutics, Journal Year: 2024, Volume and Issue: 30(5), P. 675 - 681

Published: Aug. 6, 2024

Objective: In vitro models of skeletal muscle often utilize primary myoblast cells or cell lines. Myoblasts require adhesion to the extracellular matrix (ECM) grow, proliferate, migrate, and differentiate in their natural environments vivo. To meet needs adhesive under conditions, culture surfaces are coated with various biological synthetic compounds. Within scope study, differentiation potential H2K myoblasts, a line resembling were comparatively evaluated through morphological analysis on ECM materials. Methods: The fibronectin laminin, major proteins ECM; gelatin, molecular derivative collagen; matrigel, an extract; PLL, poly-amino acid. Cells allowed each medium for 4 days capacity adhere surface rates from myotube by analysis. Results: uncoated environment, could only attach 30-50% development was limited not aligned other. On no observed 30-40% surface. Myotube alignment similar all components. components covered entire exhibited development. However, both compared other mean diameters fibronectin, PLL+laminin gelatin 49.71µm (±16.3µm), 52.31µm (±15.7µm), 51.9µm (±15.3µm), 53.06µm (±14.2µm) 35.25µm (±11.4µm), respectively. Conclusion: it revealed that coating cationic material such as PLL does support myogenesis needed viability differentiation.

Language: Английский

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