Advance in Drug Delivery for Ageing Skeletal Muscle

Li, Yang; Chen, Ming; Zhao, Yanpeng; Li, Ming; Qin, Yong; Cheng, Shi; Yang, Yanyu; Yin, Pengbin; Zhang, Licheng; Tang, Peifu

doi:10.3389/fphar.2020.01016

Cited by 12 publications

(11 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both L-carnitine and thiamine are potential nutrients that can be given as a dietary supplement countermeasure for skeletal muscle atrophy in spaceflight. There is no specific treatment for muscle atrophy, with only recent advances in the identification of treatments such as nanotechnology approaches [ 53 ]. However, ML based methods such as the GCN can be used to select drugs.…”

Section: Discussionmentioning

confidence: 99%

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Manian

Orozco-Sandoval

Díaz-Martínez

et al. 2022

Genes

View full text Add to dashboard Cite

Skeletal muscle atrophy is a common condition in aging, diabetes, and in long duration spaceflights due to microgravity. This article investigates multi-modal gene disease and disease drug networks via link prediction algorithms to select drugs for repurposing to treat skeletal muscle atrophy. Key target genes that cause muscle atrophy in the left and right extensor digitorum longus muscle tissue, gastrocnemius, quadriceps, and the left and right soleus muscles are detected using graph theoretic network analysis, by mining the transcriptomic datasets collected from mice flown in spaceflight made available by GeneLab. We identified the top muscle atrophy gene regulators by the Pearson correlation and Bayesian Markov blanket method. The gene disease knowledge graph was constructed using the scalable precision medicine knowledge engine. We computed node embeddings, random walk measures from the networks. Graph convolutional networks, graph neural networks, random forest, and gradient boosting methods were trained using the embeddings, network features for predicting links and ranking top gene-disease associations for skeletal muscle atrophy. Drugs were selected and a disease drug knowledge graph was constructed. Link prediction methods were applied to the disease drug networks to identify top ranked drugs for therapeutic treatment of skeletal muscle atrophy. The graph convolution network performs best in link prediction based on receiver operating characteristic curves and prediction accuracies. The key genes involved in skeletal muscle atrophy are associated with metabolic and neurodegenerative diseases. The drugs selected for repurposing using the graph convolution network method were nutrients, corticosteroids, anti-inflammatory medications, and others related to insulin.

show abstract

Section: Discussionmentioning

confidence: 99%

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Manian

Orozco-Sandoval

Díaz-Martínez

et al. 2022

Genes

View full text Add to dashboard Cite

show abstract

“…This strategy aims to properly expose the drug to the site of action of skeletal muscle, while sparing unwanted organs [ 114 , 115 ]. Adeno-associated virus, muscle-targeting delivery systems, nanoparticles, and extracellular vesicles are current promising drug delivery systems [ 116 ]. Gold nanoparticles conjugated to the IL-4 cytokine are more stable than soluble IL-4 in vitro and exhibit faster muscle regeneration in vivo [ 117 ].…”

Section: Discussionmentioning

confidence: 99%

Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

Yoon

Kwon

2021

Endocrinol Metab

View full text Add to dashboard Cite

Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

show abstract

“…Though bone engineering scaffolds provide stem cells with a platform for cell adhesion, migration, proliferation, and differentiation, the stem cells are also not ideal supplementary materials due to low survival rate, immunological rejection, tumorigenesis, and microthrombosis ( Brennan et al, 2020 ). The extracellular vesicles, such as exosomes, have been proven to present parental cells and deliver bioactive molecules (e.g., nucleic acids, proteins, lipids, and metabolites), thus having the ability of osteogenesis, angiogenesis, and inflammation modulation, which promise to be desirable components combining with bone engineering scaffolds to repair bone defects ( Huber et al, 2022 ; Li et al, 2020 ; Liu et al, 2018 ). The applications of exosomes and bone engineering scaffolds are still to be further researched, and there remain some problems to be solved.…”

Section: Introductionmentioning

confidence: 99%

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Zhang

Feng

et al. 2022

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

The treatment of bone defects is still an intractable clinical problem, despite the fact that numerous treatments are currently available. In recent decades, bone engineering scaffolds have become a promising tool to fill in the defect sites and remedy the deficiencies of bone grafts. By virtue of bone formation, vascular growth, and inflammation modulation, the combination of bone engineering scaffolds with cell-based and cell-free therapy is widely used in bone defect repair. As a key element of cell-free therapy, exosomes with bioactive molecules overcome the deficiencies of cell-based therapy and promote bone tissue regeneration via the potential of osteogenesis, angiogenesis, and inflammation modulation. Hence, this review aimed at overviewing the bone defect microenvironment and healing mechanism, summarizing current advances in bone engineering scaffolds and exosomes in bone defects to probe for future applications.

show abstract

Advance in Drug Delivery for Ageing Skeletal Muscle

Cited by 12 publications

References 89 publications

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

Bone Engineering Scaffolds With Exosomes: A Promising Strategy for Bone Defects Repair

Contact Info

Product

Resources

About