Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.

Use of a Mouse Model and Human Umbilical Vein Endothelial Cells to Investigate the Effect of Arsenic Exposure on Vascular Endothelial Function and the Associated Role of Calpains.

BACKGROUND: Arsenic (As) is a well-known environmental contaminant. Chronic exposure to As is known to increase the risk of cardiovascular diseases, including atherosclerosis, hypertension, diabetes, and stroke. However, the detailed mechanisms by which As causes vascular dysfunction involving endothelial integrity and permeability is unclear. OBJECTIVES: Our goal was to investigate how exposure to As leads to endothelial dysfunction. METHODS: Arsenic trioxide (ATO) was used to investigate the effects and mechanisms by which exposure to As leads to endothelial dysfunction using a mouse model and cultured endothelial cell monolayers. RESULTS: Compared with the controls, mice exposed chronically to As (10 ppb in drinking water supplied by ATO) exhibited greater vascular permeability to Evans blue dye and fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). In addition, endothelial monolayers treated with ATO ([Formula: see text] As) exhibited greater intracellular gaps and permeability to low-density lipoprotein or transmigrating THP-1 cells. Furthermore, activity and protein levels of calpain-1 (CAPN-1) were significantly higher in aortas and human umbilical vein endothelial cells (HUVECs) treated with ATO. These results were consistent with effects of ATO treatment and included a rapid increase of intracellular calcium ([Formula: see text]) and higher levels of CAPN-1 in the plasma membrane. Endothelial cell dysfunction and the proteolytic disorganization of vascular endothelial cadherin (VE-cadherin) in HUVECs in response to ATO were partially mitigated by treatment with a CAPN-1 inhibitor (ALLM) but not a CAPN-2 inhibitor (Z-LLY-FMK). CONCLUSIONS: This study found that in mice and HUVEC models, exposure to ATO led to CAPN-1 activation by increasing [Formula: see text] and CAPN-1 translocation to the plasma membrane. The study also suggested that inhibitor treatment may have a role in preventing the vascular endothelial dysfunction associated with As exposure. The findings presented herein suggest that As-induced endothelial dysfunction involves the hyperactivation of the CAPN proteolytic system. https://doi.org/10.1289/EHP4538.