Background. Facioscapulohumeral muscular dystrophy type 2 (FSHD2) poses a significant challenge within the domain of neuromuscular disorders, marked by a progressive decline in muscle strength accompanied by tissue wasting. FSHD2 results from chromosomal deletions triggering the activation of a dormant gene known as DUX4. While DUX4 typically regulates early embryonic development, its activation in adult muscle cells leads to premature cell death. Despite this understanding, the exact pathology of FSHD2 remains unclear. To date, no effective treatment for FSHD2 exists. Method. We acquired single-cell RNA sequencing (RNA-Seq) data (GSE143452) from primary myoblasts for FSHD2 from the United States National Institutes of Health (NIH) portal website. Our analysis encompassed a comprehensive examination of differentially expressed genes, alongside associated compounds sourced from the Chemical Entities of Biological Interest (ChEBI) database. Employing rigorous statistical methods, we pinpointed the most prominently upregulated and downregulated genes. Subsequently, we determined the compounds capable of modulating the expression of these top genes, either enhancing or reducing their activity. Results. Bisphenol S (BPS) can upregulate 52 of 100 top downregulated genes in FSHD2 without downregulating any other genes and Bisphenol F (BPF) can upregulate 45 of 100 downregulated genes with downregulating only one other gene. The enrichment analysis of both sets of 52 genes related to BPS and 45 genes corresponding to BPF highlights their significant involvement in various aspects of muscle biology, particularly as pertaining to the function and dysfunction of cardiac and skeletal muscle. Conclusions. Leveraging single-cell RNA-Seq data and computational analysis, we identified key dysregulated genes in FSHD2 and elucidated their modulation by compounds such as BPS and BPF. While effective treatments for FSHD2 remain elusive, our study provides valuable insights into potential therapeutic targets and pathways for further investigation in the pursuit of effective interventions for this debilitating condition. However, more research is needed to understand whether the roles of BPS and F are constructive or destructive.

中文翻译：

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解锁 2 型面肩肱型肌营养不良症的治疗方法：双酚的联系

背景。2 型面肩肱型肌营养不良症 (FSHD2) 在神经肌肉疾病领域提出了重大挑战，其特点是肌肉力量进行性下降并伴有组织消耗。FSHD2 是由于染色体缺失触发休眠基因 DUX4 的激活而产生的。虽然 DUX4 通常调节早期胚胎发育，但它在成年肌肉细胞中的激活会导致细胞过早死亡。尽管有这样的认识，FSHD2 的确切病理学仍不清楚。迄今为止，尚无针对 FSHD2 的有效治疗方法。方法。我们从美国国立卫生研究院 (NIH) 门户网站获取了原代成肌细胞 FSHD2 的单细胞 RNA 测序 (RNA-Seq) 数据 (GSE143452)。我们的分析包括对差异表达基因以及源自生物活性化学实体 (ChEBI) 数据库的相关化合物的全面检查。采用严格的统计方法，我们确定了最显着的上调和下调基因。随后，我们确定了能够调节这些顶级基因表达、增强或降低其活性的化合物。结果。双酚 S (BPS) 可以上调 FSHD2 中 100 个最下调基因中的 52 个，而不下调任何其他基因；双酚 F (BPF) 可以上调 100 个下调基因中的 45 个，仅下调一个其他基因。对两组与 BPS 相关的 52 个基因和与 BPF 对应的 45 个基因的富集分析强调了它们在肌肉生物学各个方面的重要参与，特别是与心肌和骨骼肌的功能和功能障碍有关。结论。利用单细胞 RNA-Seq 数据和计算分析，我们确定了 FSHD2 中关键的失调基因，并阐明了 BPS 和 BPF 等化合物对它们的调节作用。虽然 FSHD2 的有效治疗方法仍然难以捉摸，但我们的研究为潜在的治疗靶点和途径提供了宝贵的见解，可用于进一步研究，以寻求针对这种衰弱疾病的有效干预措施。然而，需要更多的研究来了解 BPS 和 F 的作用是建设性的还是破坏性的。