A Preconception Paternal Fish Oil Diet Prevents Toxicant-Driven New Bronchopulmonary Dysplasia in Neonatal Mice

New bronchopulmonary dysplasia is a developmental lung disease associated with placental dysfunction and impaired alveolarization. Risk factors for new BPD include prematurity, delayed postnatal growth, the dysregulation of epithelial-to-mesenchymal transition (EMT), and parental exposure to toxicants. Our group previously reported that a history of paternal toxicant exposure increased the risk of prematurity and low birth weight in offspring. A history of paternal toxicant exposure also increased the offspring’s risk of new BPD and disease severity was increased in offspring who additionally received a supplemental formula diet, which has also been linked to poor lung development. Risk factors associated with new BPD are well-defined, but it is unclear whether the disease can be prevented. Herein, we assessed whether a paternal fish oil diet could attenuate the development of new BPD in the offspring of toxicant exposed mice, with and without neonatal formula feeding. We investigated the impact of a paternal fish oil diet preconception because we previously reported that this intervention reduces the risk of TCDD associated placental dysfunction, prematurity, and low birth weight. We found that a paternal fish oil diet significantly reduced the risk of new BPD in neonatal mice with a history of paternal toxicant exposure regardless of neonatal diet. Furthermore, our evidence suggests that the protective effects of a paternal fish oil diet are mediated in part by the modulation of small molecules involved in EMT.

Trace analysis of emerging and regulated mycotoxins in infant stool by LC-MS/MS

Infants are sensitive to negative effects caused by food contaminants such as mycotoxins. To date, analytical methods assessing mycotoxin mixture exposure in infant stool are absent. Herein, we present a novel multi-mycotoxin LC-MS/MS assay capable of detecting 30+ analytes including the regulated mycotoxin classes (aflatoxins, trichothecenes, ochratoxins, zearalenone, citrinin), emerging Alternaria and Fusarium toxins, and several key metabolites. Sample preparation consisted of a ‘dilute, filter, and shoot’ approach. The method was in-house validated and demonstrated that 25 analytes fulfilled all required criteria despite the high diversity of chemical structures included. Extraction recoveries for most of the analytes were in the range of 65–114% with standard deviations below 30% and limits of detection between 0.03 and 11.3 ng/g dry weight. To prove the methods’ applicability, 22 human stool samples from premature Austrian infants (n = 12) and 12-month-old Nigerian infants (n = 10) were analyzed. The majority of the Nigerian samples were contaminated with alternariol monomethyl ether (8/10) and fumonisin B1 (8/10), while fumonisin B2 and citrinin were quantified in some samples. No mycotoxins were detected in any of the Austrian samples. The method can be used for sensitive human biomonitoring (HBM) purposes and to support exposure and, potentially, risk assessment of mycotoxins. Moreover, it allows for investigating potential associations between toxicant exposure and the infants’ developing gut microbiome. Graphical abstract

Effects of IQOS health warnings and modified risk claims among young adult cigarette smokers and non-smokers

IntroductionHeated tobacco products, including Marlboro IQOS, are available globally. In the USA, IQOS was authorised to be advertised with claims about reduced toxicant exposure relative to cigarettes. The effects of such modified risk claims and health warnings have not been studied among young adult cigarette smokers and non-smokers.MethodsIn 2020, US young adult (18–30 years, n=1328) cigarette smokers and non-smokers viewed an IQOS ad in a 4 (modified risk claim variations or none) by 3 (warning variations or none) between-subjects experiment. Outcome measures assessed perceived credibility and effectiveness of the health or risk message for discouraging IQOS use, perceived harms, efficacy beliefs, and IQOS use intentions.ResultsSmokers reported significantly higher (p<0.05) perceived credibility, lower perceived effectiveness, higher efficacy beliefs about switching to IQOS and higher intentions to use IQOS than non-smokers. Among smokers, health warnings increased perceived credibility (p<0.001) and effectiveness (p<0.05), but claims did not affect outcomes examined. Among non-smokers, warnings and claims increased perceived credibility, and warnings increased perceived effectiveness (p<0.003). The reduced exposure claim increased non-smokers’ intentions to use IQOS (b=0.40, 95% CI 0.07 to 0.73).ConclusionsAmong young adult smokers, health warnings increased perceived effectiveness at discouraging IQOS use and perceived credibility. Among non-smokers, warnings and claims increased perceived credibility and warnings increased perceived effectiveness, but the Food and Drug Administration-authorised reduced exposure claim increased intentions to use IQOS. Research is warranted to understand how the content of modified risk claims and health warnings for IQOS affects IQOS use in this population.

Hsp40 Affinity to Identify Proteins Destabilized by Cellular Toxicant Exposure

Environmental toxins and toxicants can damage proteins and threaten cellular proteostasis. Most current methodologies to identify misfolded proteins in cells survey the entire proteome for sites of changed reactivity. We describe and apply a quantitative proteomics methodology to identify destabilized proteins based on their binding to the human Hsp40 chaperone DNAJB8. These protein targets are validated by an orthogonal limited proteolysis assay using parallel reaction monitoring. We find that brief exposure of HEK293T cells to meta-arsenite increases the affinity of two dozen proteins to DNAJB8, including known arsenite-sensitive proteins. In particular, arsenite treatment destabilizes both the pyruvate dehydrogenase complex E1 subunit and several RNA-binding proteins. This platform can be used to explore how environmental toxins impact cellular proteostasis, and to identify the susceptible proteome.