Search

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)2 and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers prenatal cortisol trajectories.

Despite growing interest in edible seaweeds, there is limited information on seaweed chemical contaminant levels in the Salish Sea. Without this knowledge, health-based consumption advisories can not be determined for consumers that include Tribes and First Nations, Asian and Pacific Islander community members, and recreational harvesters. We measured contaminant concentrations in edible seaweeds (Fucus distichus, F. spiralis, and Nereocystis luetkeana) from 43 locations in the Salish Sea. Metals were analyzed in all samples, and 94 persistent organic pollutants (POPs) (i.e. 40 PCBs, 15 PBDEs, 17 PCDD/Fs, and 22 organochlorine pesticides) and 51 PAHs were analyzed in Fucus spp. We compared concentrations of contaminants to human health-based screening levels calculated from the USEPA and to international limits. We then worked with six focal contaminants that either exceeded screening levels or international limits (Cd, total Hg, Pb, benzo[a]pyrene [BaP], and PCBs) or are of regional interest (total As). USEPA cancer-based screening levels were exceeded in 30 samples for the PCBs and two samples for BaP. Cadmium concentrations did not exceed the USEPA noncancer-based screening level but did exceed international limits at all sites. Lead exceeded international limits at three sites. Because there are no screening levels for total Hg and total As, and to be conservative, we made comparisons to methyl Hg and inorganic As screening levels. All samples were below the methyl Hg and above the inorganic As screening levels. Without knowledge of the As speciation, we cannot assess the health risk associated with the As. While seaweed was the focus, we did not consider contaminant exposure from consuming other foods. Other chemicals, such as contaminants of emerging concern (e.g., PFAS, pharmaceuticals and personal care products), should also be considered. Additionally, although we focused on toxicological aspects, there are cultural and health benefits of seaweed use that may affect consumer choice.

BackgroundAutologous engineered skin substitutes comprised of keratinocytes, fibroblasts, and biopolymers can serve as an adjunctive treatment for excised burns. However, engineered skin lacks a vascular plexus at the time of grafting, leading to slower vascularization and reduced rates of engraftment compared with autograft. Hypothetically, vascularization of engineered skin grafts can be improved by treatment with proangiogenic agents at the time of grafting. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase (sEH). EETs have multiple biological activities and have been shown to promote angiogenesis. Inhibitors of sEH (sEHIs) represent attractive therapeutic agents because they increase endogenous EET levels. We investigated sEHI administration, alone or combined with EET treatment, for improved vascularization of engineered skin after grafting to mice.MethodsEngineered skin substitutes, prepared using primary human fibroblasts and keratinocytes, were grafted to full-thickness surgical wounds in immunodeficient mice. Mice were treated with the sEHI 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), which was administered in drinking water throughout the study period, with or without topical EET treatment, and were compared with vehicle-treated controls. Vascularization was quantified by image analysis of CD31-positive areas in tissue sections.ResultsAt 2 weeks after grafting, significantly increased vascularization was observed in the TPPU and TPPU + EET groups compared with controls, with no evidence of toxicity.ConclusionsThe results suggest that sEH inhibition can increase vascularization of engineered skin grafts after transplantation, which may contribute to enhanced engraftment and improved treatment of full-thickness wounds.

Introduction The importance of TGF-β in preventing excessive T lymphocyte activation, proliferation, and development of autoimmunity is illustrated by the striking phenotype of [Tgfb1.sup.-/-] mice (1-3), as well as by [...], While there is evidence that specific T cell populations can promote the growth of established tumors, instances where T cell activity causes neoplasms to arise de novo are infrequent. Here, we employed two conditional mutagenesis systems to delete the TGF-βsignaling pathway component Smad4 in T cells and observed the spontaneous development of massive polyps within the gastroduodenal regions of mice. The epithelial lesions contained increased levels of transcripts encoding IL-11, IL-6, TGF-β, IL-1β, and TNF-α, and lamina propria cells isolated from lesions contained abundant [[IL-17A.sup.+]CD4.sup.+] T cells. Furthermore, we found that Smad4 deficiency attenuated TGF-β-mediated in vitro polarization of [[FoxP3.sup.+]CD4.sup.+] T cells, but not [[IL-17A.sup.+]CD4.sup.+] T cells, suggesting that the epithelial lesions may have arisen as a consequence of unchecked Th17 cell activity. Proinflammatory cytokine production likely accounted for the raised levels of IL-11, a cytokine known to promote gastric epithelial cell survival and hyperplasia. Consistent with IL-11 having a pathogenic role in this model, we found evidence of Stat3 activation in the gastric polyps. Thus, our data indicate that a chronic increase in gut Th17 cell activity can be associated with the development of premalignant lesions of the gastroduodenal region.

The article discusses the study that investigates engineered skin substitutes (ESS) as an in vitro organotypic keloid model to analyze changes in gene expression in response to wounding. It shows that keloid ESS 14 days after keratinocyte inoculation demonstrates a well-stratified epidermal layer. It suggests that the results are consistent with the hypothesis that an imbalance of extracellular matrix (ECM) production and degradation after wounding leads to keloid scarring.