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1. Intrauterine exposure to nicotine through maternal vaping disrupts embryonic lung and skeletal development via the Kcnj2 potassium channel

   https://doi.org/10.1016/j.ydbio.2023.06.002  

   Ozekin, Yunus H.; Saal, Maxwell L.; Pineda, Ricardo H.; Moehn, Kayla; Ordonez-Erives, Madison A.; Delgado Figueroa, Maria F.; Frazier, Caleb; Korth, Kamryn M.; Königshoff, Melanie; Bates, Emily A.; et al (September 2023, Developmental Biology)

   Smoking cigarettes during pregnancy is associated with adverse effects on infants including low birth weight, defective lung development, and skeletal abnormalities. Pregnant women are increasingly turning to vaping [use of electronic (e)-cigarettes] as a perceived safer alternative to cigarettes. However, nicotine disrupts fetal development, suggesting that like cigarette smoking, nicotine vaping may be detrimental to the fetus. To test the impact of maternal vaping on fetal lung and skeletal development in mice, pregnant dams were exposed to e-cigarette vapor throughout gestation. At embryonic day (E)18.5, vape exposed litter sizes were reduced and some embryos exhibited growth restriction compared to air exposed controls. Fetal lungs were collected for histology and whole transcriptome sequencing. Maternally nicotine vaped embryos exhibited histological and transcriptional changes consistent with impaired distal lung development. Embryonic lung gene expression changes mimicked transcriptional changes observed in adult mouse lungs exposed to cigarette smoke, suggesting that the developmental defects may be due to direct nicotine exposure. Fetal skeletons were analyzed for craniofacial and long bone lengths. Nicotine directly binds and inhibits the Kcnj2 potassium channel which is important for bone development. The length of the maxilla, palatal shelves, humerus, and femur were reduced in vaped embryos, which was further exacerbated by loss of one copy of the Kcnj2 gene. Nicotine vapor exposed Kcnj2KO/+ embryos also had significantly lower birth weights than unexposed animals of either genotype. Kcnj2 mutants had severely defective lungs with and without vape exposure, suggesting that potassium channels may be broadly involved in mediating the detrimental developmental effects of nicotine vaping. These data indicate that intrauterine nicotine exposure disrupts fetal lung and skeletal development likely through inhibition of Kcnj2. 

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2. PAH-pollution effects on sensitive and resistant embryos: Integrating structure and function with gene expression

   https://doi.org/10.1371/journal.pone.0249432  

   Bozinovic, Goran; Shea, Damian; Feng, Zuying; Hinton, David; Sit, Tim; Oleksiak, Marjorie F. (April 2021, PLOS ONE)

   Cao, Yi (Ed.)

   Polycyclic aromatic hydrocarbons (PAHs) are among the most widespread natural and anthropogenic pollutants, and some PAHs are proven developmental toxicants. We chemically characterized clean and heavily polluted sites and exposed fish embryos to PAH polluted sediment extracts during four critical developmental stages. Embryos were collected from Fundulus heteroclitus populations inhabiting the clean and heavily polluted Superfund estuary. Embryos of parents from the clean sites are sensitive to PAH pollutants while those of parents from the heavily polluted site are resistant. Chemical analysis of embryos suggests PAH accumulation and pollution-induced toxicity among sensitive embryos during development that ultimately kills all sensitive embryos before hatching, while remarkably, the resistant embryos develop normally. The adverse effects on sensitive embryos are manifested as developmental delays, reduced heart rates, and severe heart, liver, and kidney morphological abnormalities. Gene expression analysis of early somitogenesis, heartbeat initiation, late organogenesis, and pre-hatching developmental stages reveals genes whose expression significantly differs between sensitive and resistant embryo populations and helps to explain mechanisms of sensitivity and resistance to polluted environments during vertebrate animal development. 

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3. Multiphase reactivity of polycyclic aromatic hydrocarbons is driven by phase separation and diffusion limitations

   https://doi.org/10.1073/pnas.1902517116  

   Zhou, Shouming; Hwang, Brian C.; Lakey, Pascale S.; Zuend, Andreas; Abbatt, Jonathan P.; Shiraiwa, Manabu (January 2019, Proceedings of the National Academy of Sciences)

   Benzo[a]pyrene (BaP), a key polycyclic aromatic hydrocarbon (PAH) often associated with soot particles coated by organic compounds, is a known carcinogen and mutagen. When mixed with organics, the kinetics and mechanisms of chemical transformations of BaP by ozone in indoor and outdoor environments are still not fully elucidated. Using direct analysis in real-time mass spectrometry (DART-MS), kinetics studies of the ozonolysis of BaP in thin films exhibited fast initial loss of BaP followed by a slower decay at long exposure times. Kinetic multilayer modeling demonstrates that the slow decay of BaP over long times can be simulated if there is slow diffusion of BaP from the film interior to the surface, resolving long-standing unresolved observations of incomplete PAH decay upon prolonged ozone exposure. Phase separation drives the slow diffusion time scales in multicomponent systems. Specifically, thermodynamic modeling predicts that BaP phase separates from secondary organic aerosol material so that the BaP-rich layer at the surface shields the inner BaP from ozone. Also, BaP is miscible with organic oils such as squalane, linoleic acid, and cooking oil, but its oxidation products are virtually immiscible, resulting in the formation of a viscous surface crust that hinders diffusion of BaP from the film interior to the surface. These findings imply that phase separation and slow diffusion significantly prolong the chemical lifetime of PAHs, affecting long-range transport of PAHs in the atmosphere and their fates in indoor environments. 

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4. Evaluation of fireground exposures using urinary PAH metabolites

   https://doi.org/10.1038/s41370-021-00311-x  

   Hoppe-Jones, Christiane; Griffin, Stephanie C.; Gulotta, John J.; Wallentine, Darin D.; Moore, Paul K.; Beitel, Shawn C.; Flahr, Leanne M.; Zhai, Jing; Zhou, Jin J.; Littau, Sally R.; et al (September 2021, Journal of Exposure Science & Environmental Epidemiology)

   Abstract Background Firefighters have increased cancer incidence and mortality rates compared to the general population, and are exposed to multiple products of combustion including known and suspected carcinogens. Objective The study objective was to quantify fire response exposures by role and self-reported exposure risks. Methods Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAH-OHs) were measured at baseline and 2–4 h after structural fires and post-fire surveys were collected. Results Baseline urine samples were collected from 242 firefighters. Of these, 141 responded to at least one of 15 structural fires and provided a post-fire urine. Compared with baseline measurements, the mean fold change of post-fire urinary PAH-OHs increased similarly across roles, including captains (2.05 (95% CI 1.59–2.65)), engineers (2.10 (95% CI 1.47–3.05)), firefighters (2.83 (95% CI 2.14–3.71)), and paramedics (1.84 (95% CI 1.33–2.60)). Interior responses, smoke odor on skin, and lack of recent laundering or changing of hoods were significantly associated with increased post-fire urinary PAH-OHs. Significance Ambient smoke from the fire represents an exposure hazard for all individuals on the fireground; engineers and paramedics in particular may not be aware of the extent of their exposure. Post-fire surveys identified specific risks associated with increased exposure. 

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5. 1,25‐Dihydroxyvitamin D ₃ and dietary vitamin D reduce inflammation in mice lacking intestinal epithelial cell Rab11a

   https://doi.org/10.1002/jcp.30486  

   Goswami, Sayantani; Flores, Juan; Balasubramanian, Iyshwarya; Bandyopadhyay, Sheila; Joseph, Ivor; Bianchi‐Smak, Jared; Dhawan, Puneet; Mücahit, Derya M.; Yu, Shiyan; Christakos, Sylvia; et al (June 2021, Journal of Cellular Physiology)

   Abstract A number of studies have examined the effects of 1,25‐dihydroxyvitamin D₃(1,25(OH)₂D₃) on intestinal inflammation driven by immune cells, while little information is currently available about its impact on inflammation caused by intestinal epithelial cell (IEC) defects. Mice lacking IEC‐specificRab11aa recycling endosome small GTPase resulted in increased epithelial cell production of inflammatory cytokines, notably IL‐6 and early onset of enteritis. To determine whether vitamin D supplementation may benefit hosts with epithelial cell‐originated mucosal inflammation, we evaluated in vivo effects of injected 1,25(OH)₂D₃or dietary supplement of a high dose of vitamin D on the gut phenotypes of IEC‐specificRab11aknockout mice (Rab11a^ΔIEC). 1,25(OH)₂D₃administered at 25 ng, two doses per mouse, by intraperitoneal injection, reduced inflammatory cytokine production in knockout mice compared to vehicle‐injected mice. Remarkably, feeding mice with dietary vitamin D supplementation at 20,000 IU/kg spanning fetal and postnatal developmental stages led to improved bodyweights, reduced immune cell infiltration, and decreased inflammatory cytokines. We found that these vitamin D effects were accompanied by decreased NF‐κB (p65) in the knockout intestinal epithelia, reduced tissue‐resident macrophages, and partial restoration of epithelial morphology. Our study suggests that dietary vitamin D supplementation may prevent and limit intestinal inflammation in hosts with high susceptibility to chronic inflammation. 

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