Articles: function.
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Induced pluripotent stem cell (iPSC) technology has emerged as a powerful tool for disease modeling, providing an innovative platform for investigating disease mechanisms. iPSC-derived organoids, including retinal organoids, offer patient-specific models that closely replicate in vivo cellular environments, making them ideal for studying retinal neurodegenerative diseases where retinal ganglion cells (RGCs) are impacted. N6-methyladenosine (m6A), a prevalent internal modification in eukaryotic mRNAs, plays a critical role in RNA metabolic processes such as splicing, stability, translation, and transport. Given the high energy demands of RGCs, mitochondrial dysfunction, which leads to impaired ATP production and increased ROS levels, is often central to the progression of retinal neurodegenerative disorders. However, the epigenetic mechanisms underlying m6A modification and their contributions to these conditions remain unclear. ⋯ These findings suggest that differential m6A modifications may play pivotal roles in the pathogenesis of retinal neurodegenerative diseases and affect the progression of the disease in affected individuals.
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Semin Respir Crit Care Med · Dec 2024
Advances in Disease-Modifying Therapeutics for Chronic Neuromuscular Disorders.
Neuromuscular disorders can cause respiratory impairment by affecting the muscle fibers, neuromuscular junction, or innervation of respiratory muscles, leading to significant morbidity and mortality. Over the past few years, new disease-modifying therapies have been developed and made available for treating different neuromuscular disorders. Some of these therapies have remarkable effectiveness, resulting in the prevention and reduction of respiratory complications. ⋯ For late-onset Pompe disease (LOPD), avalglucosidase alfa has shown a greater improvement in respiratory function, ambulation, and functional outcomes in comparison to alglucosidase alfa, and cipaglucosidase alfa combined with miglustat has shown improvement in respiratory and motor function in a cohort of enzyme replacement therapy-experienced LOPD patients. Amyotrophic lateral sclerosis (ALS) remains a challenge. The two most recent FDA-approved medications, namely sodium phenylbutyrate and tofersen, may slow down the disease by a few months in a selected population but do not stop the progression of the disease.
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In the PROTECTION trial, intravenous amino acids (AA) decreased the occurrence of acute kidney injury (AKI) in cardiac surgery patients with cardiopulmonary bypass (CPB). Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease (CKD) have diminished renal functional reserve, and AA may be less protective in such patients. Thus, a separate investigation of such patients is warranted. ⋯ AA infusion protected CKD patients undergoing CPB from developing AKI, with an absolute risk reduction of 7% and a NNT of 14 in a cohort with a >45% rate of AKI. Moreover, it delivered a >50% relative risk reduction in severe AKI.