Citations

ABSTRACT Premature infants often require supplemental oxygen therapy, however, exposure to supraphysiological oxygen (hyperoxia) can disrupt normal lung development and contribute to bronchopulmonary dysplasia (BPD). Mitochondrial dysfunction is increasingly recognized as a contributor to hyperoxia-induced BPD. However, the effects of hyperoxia on mitochondrial function and mucociliary differentiation in the developing upper airway epithelium remain poorly understood. This study tested the hypothesis that hyperoxia impairs neonatal airway mucociliary differentiation by disrupting mitochondrial bioenergetic function. Neonatal tracheal airway epithelial cells (nTAECs) from term infants (n=5) were cultured in a 3D air-liquid interface (ALI) model and exposed to 60% O₂ during the mid-phase of differentiation (ALI day 7-14). Cellular phenotype was assessed using immunofluorescence staining and gene expression analyses. Mitochondrial function was evaluated through Seahorse metabolic flux analysis, and global protein changes were characterized by quantitative proteomics. Hyperoxia exposure significantly impaired terminal epithelial differentiation, characterized by reductions in ciliated and goblet cells. Seahorse assay revealed a decrease in baseline oxygen consumption and mitochondrial ATP production, accompanied by a compensatory increase in glycolytic ATP production. Quantitative proteomics identified disruption of mitochondrial Complex I as a central feature of the hyperoxic response. Downstream proteomic pathway analyses further confirmed the metabolic shift from mitochondrial to glycolytic ATP production and demonstrated altered epithelial differentiation pathways, including NOTCH and TGF-β signaling. These findings reveal that moderate hyperoxia impairs mitochondrial bioenergetics and alters metabolic programming, leading to disrupted mucociliary differentiation. Future in vivo studies should evaluate mitochondrial oxidative fitness as a therapeutic target in neonatal lung disease. NEW & NOTEWORTHY We report that moderate hyperoxia during a critical window of mucociliary differentiation disrupts terminal maturation in neonatal airway epithelial cells cultured in a 3D model. Hyperoxia induced mitochondrial bioenergetic dysfunction and metabolic reprogramming, with proteomic analysis identifying Complex I disruption as a key driver of impaired differentiation. Overall, these findings reveal a previously underrecognized link between mitochondrial bioenergetics and airway epithelial development, positioning metabolic dysfunction as an early trigger of hyperoxia-induced neonatal airway injury.

ABSTRACTMonoclonal gammopathy of undetermined significance (MGUS) is the term used for a minimal clonal expansion of plasma cells that is most typically detected by the presence of a small serum monoclonal protein. For most—but not all—patients, the presence of a small monoclonal protein will have no clinical significance at the time of recognition or even over time. It is imperative, therefore, that a careful—but sensible—evaluation be performed both at the time of recognition and subsequently because these monoclonal may represent significant pathology including diseases such as multiple myeloma, low grade lymphoma or any of the diseases captured under the moniker of monoclonal gammopathy of clinical significance (MGCS), which includes—but is not limited to—immunoglobulin light chain amyloidosis and POEMS syndrome. Herein is a discussion of the diagnosis and follow‐up MGUS and MGCS.