The effects of maternal obesity on lung development have been recognized, and speculation is that these diseases are not simply because of accelerated pulmonary decline with aging but with a failure to achieve optimal lung development during early life. These studies tested the hypothesis that maternal obesity alters signaling pathways during the course of lung development that may affect life-long pulmonary health. Adult female mice were fed 60% fat [high-fat diet (HFD)] or 10% fat [control diet (CD)] for 8 wk before mating and through weaning. Pup lung tissues were collected at postnatal days ( PN) 7, 21, and 90 (after receiving HFD or CD as adults). At PN7, body weights from HFD were greater than CD but lung weight-to-body weight ratios were lower. In lung tissues, NFκB-mediated inflammation was greater in HFD pups at PN21 and phospho-/total STAT3, phospho-/total VEGF receptor 2, and total AKT protein levels were lower with maternal HFD and protein tyrosine phosphatase B1 levels were increased. Decreased platelet endothelial cell adhesion molecule levels were observed at PN21 and at PN90 in the pups exposed to maternal HFD. Morphometry indicated that the pups exposed to maternal or adult HFD had fewer alveoli, and the effect was additive. Decreases in pulmonary resistance, elastance, and compliance were observed because of adult HFD diet and decreases in airway resistance and increases in inspiratory capacity because of maternal HFD. In conclusion, maternal HFD disrupts signaling pathways in the early developing lung and may contribute to deficiencies in lung function and increased susceptibility in adults.

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BackgroundElectronic cigarette usage is increasing at an alarming rate primarily because of reports implicating their use as safer than traditional cigarettes. However, little is known about the acute effects on lung injury and inflammation. These studies tested the hypothesis that acute exposure to e‐cigarette vapor would result in lung inflammation and injury.MethodsC57Bl/6 mice were exposed to e‐cigarette vapor consisting of 10 mg/mL nicotine in a 50/50 mixture of propylene glycol/vegetable glycerin (PG/VG) or PG/VG alone for 6 hr/day, 5 days/week for either 1 or 2 weeks. Lungs were excised and snap‐frozen for analysis. Lung homogenates were analyzed by western blot for pAKT, pSTAT3, PECAM, BCL‐2, and BAX. RNA was isolated for measurement of MMP9, KC, and VEGF by RT‐PCR.ResultspAKT protein expression was decreased (0.54 vs 1.0 relative density, p=0.02) and pSTAT3 was increased (1.7 vs 1.0 relative density, p=0.02) in the e‐cigarette exposed mice vs PG/VG exposed mice after 1 week of exposure. At 2 weeks, pSTAT3 remained increased (1.9 vs 1.0 relative density, p=0.01) and both BCL‐2 (2.5 vs 1.0 relative density, p=0.02) and BAX (1.7 vs 1.0 relative density, p<0.05) were increased in the exposed mice compared to mice exposed to PG/VG alone. No differences were observed in PECAM, MMP9, KC, or VEGF.ConclusionsAcute exposure to e‐cigarette vapor caused changes in signaling molecules associated with apoptosis. While we did not observe differences in the inflammatory pathways tested, additional inflammatory and apoptotic markers may yield insights into the acute effects of e‐cigarette vapor exposure on the lung.Support or Funding InformationNIH NHLBI R01 HL139348 02This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Drug overdose death rates continue to rise – more Americans and Coloradans are dying of drug overdoses than ever before. Despite efforts to shift the narrative, our society continues to struggle to acknowledge substance use disorders as medical conditions worthy of medical care. Rural settings are no exception. In this piece, a University of Colorado medical student describes her experience working to fight stigma surrounding opioid use disorder in both lay and healthcare professional populations. By designing and employing the use of lapel pins, students are leading a grassroots campaign to combat opioid use disorder stigma among healthcare professionals at the outset of their careers. Using real experiences from a rural clinic, the authors explore barriers to addiction care, including how stigma can perpetuate sub-optimal care for treatable medical conditions.

BackgroundBronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication for preterm infants, but the mechanisms associated with altered lung development remain poorly understood. Our mouse model of perinatal inflammation mimics the pathophysiology observed in infants with severe BPD. We have previously reported decreased pulmonary miR‐29b expression, and that restoration of miR‐29b expression improves lung development. The current studies tested the hypothesis that decreased expression of miR‐29b was associated with decreases in expression of key protein methyltransferases (PRMTs), and that restoration of miR‐29b would restore expression.MethodsPregnant C3H/HeN mice received an intraperitoneal LPS injection on E16 and newborn pups were exposed in 85% oxygen from birth to 14 days of life. On postnatal day 3, PBS containing a liposomal preparation of miR‐29b or an empty liposome was administered intranasally. On postnatal 28, mouse lung tissues were analyzed for changes in PRMT‐1, PRMT‐5, and symmetrical and asymmetrical dimethylation of histone 4, arginine 3 by western blot.ResultsPerinatal inflammation resulted in decreased expression of PRMT‐1 and PRMT‐5 which led to a decrease in histone 4, arginine 3 symmetrical dimethylation. Liposomal delivery of miR‐29b restored PRMT‐1 and PRMT‐5 expression and partially attenuated the decrease in histone 4 symmetrical methylation.ConclusionOur data suggest that restoration of miR‐29b may prevent aberrant expression of matrix proteins by increasing histone 4, arginine 3 dimethylation and promoting gene silencing.Support or Funding InformationThe authors gratefully acknowledge funding from the NIH/NICHD R01HD0880833This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.