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Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient-specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC-derived myoblasts (MB) and 1774 CpG sites in differentiating SC-derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo- and hyper-methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP.

Cerebral palsy is a set of common, severe, motor disabilities categorized by a static, nondegenerative encephalopathy arising in the developing brain and associated with deficits in movement, posture, and activity. Spastic CP, which is the most common type, involves high muscle tone and is associated with altered muscle function including poor muscle growth and contracture, increased extracellular matrix deposition, microanatomic disruption, musculoskeletal deformities, weakness, and difficult movement control. These muscle-related manifestations of CP are major causes of progressive debilitation and frequently require intensive surgical and therapeutic intervention to control. Current clinical approaches involve sophisticated consideration of biomechanics, radiologic assessments, and movement analyses, but outcomes remain difficult to predict. There is a need for more precise and personalized approaches involving omics technologies, data science, and advanced analytics. An improved understanding of muscle involvement in spastic CP is needed. Unfortunately, the fundamental mechanisms and molecular pathways contributing to altered muscle function in spastic CP are only partially understood. In this review, we outline evidence supporting the emerging hypothesis that epigenetic phenomena play significant roles in musculoskeletal manifestations of CP.

Arabinoxylans (AX) are polysaccharides with antioxidant activity and emulsifying properties, which make them an attractive alternative for its potential application as a natural antioxidant in oils. Therefore, this work aimed to investigate the effect of ultrasonic treatment of AX on their antioxidant capacity and its ability to improve the oxidative stability of soybean oil. For this purpose, AX were exposed to ultrasonic treatment at 25% (100 W, AX-1) and 50% (200 W, AX-2) power and an operating frequency of 20 KHz during 15 min, and their macromolecular properties (weight average molecular weight (Mw), polydispersity index and intrinsic viscosity) were evaluated. The antioxidant capacity of AX was determined by the DPPH assay and Rancimat test. Results showed that ultrasonic treatment did not affect the molecular identity of the polysaccharide but modified its Mw distribution. AX-1 showed the highest antioxidant activity (75% inhibition) at 533 µg/mL by the DPPH method compared to AX and AX-2. AX at 0.25% ( w / v ) and AX-1 at 0.01% ( w / v ) exerted the highest protective effects on oxidative stability of soybean oil with induction periods of 7.69 and 5.54 h, respectively. The results indicate that AX could be a good alternative for the potential application as a natural antioxidant in oils., Competing Interests: The authors declare no conflict of interest.