Search

Carboxymethyl starches are added to food products for thickening or tablet binding/filling purposes. Although they lack toxicity, their synthesis creates the chemical byproduct diglycolic acid (DGA), which is difficult to eliminate and whose toxicity is in question. A rare case of an accidental direct exposure to extremely high concentrations of DGA in a person revealed that DGA has the potential to be toxic to several organs, with the kidneys and liver being the most affected organs. Given that DGA is present in our food supply as a chemical byproduct of carboxymethyl starch food additives, we sought to perform in vitro testing of its potential hepatotoxicity to help complement a recent in vivo rat acute dose-response study that also tested for the potential hepatotoxic effects of daily DGA ingestion by oral gavage over a period of 28 days. Using the HepG2/C3A cellular in vitro model, we tested how escalating doses of DGA exposure over 24 h could induce hepatotoxicity. Both in vitro and in vivo testing systems revealed that DGA is indeed a hepatotoxin once a certain exposure threshold is reached. The concordance of these models highlights the utility of in vitro testing to support and help predict in vivo findings.

In this study, the effects of surface charge, dose, and cosmetic vehicle on the penetration of silver nanoparticles (AgNPs) into pig and human skin were compared. AgNPs (20 nm) with varying surface-charges (polyethylene glycol (PEG; neutral), citrate (CIT; negative), and branched polyethylenimine (bPEI; positive) were dosed onto skin in in vitro diffusion cells using an aqueous solution and an oil-in-water emulsion formulation. Samples were analyzed by inductively coupled plasma mass spectroscopy (ICP-MS) and transmission electron microscope (TEM) to assess AgNP skin penetration. The results showed that neutral and positive AgNPs penetrate human skin when applied in a high dose aqueous solution and less with the emulsion vehicle. A mass balance percutaneous penetration study in human skin found the majority of AgNPs were washed from the skin or remained mostly in the stratum corneum (3.4% of the applied dose for AgbPEI and 1.7% for AgPEG). Very little silver was found in the epidermis (1.2% AgbPEI and 0.3% AgPEG) and dermis (0.1% AgbPEI and none detected for AgPEG). These results indicate low dermal penetration of AgNPs that is not greatly affected by surface coating charge. The results will facilitate dermal exposure assessments by better understanding how nanoparticle properties affect skin absorption of nanoparticles found in personal care products.

BackgroundEnglish editing services are effective for improving manuscript quality as well as providing learning opportunities for non-native English-speaking authors. Herein, we describe the effects of a combined system of in-house and external editing services for handling large volumes of editing requests and providing personalized editing service in academic hospitals.MethodsWe established the Scientific Publications Team (SPT), an in-house editing team in Asan Medical Center in Seoul, Korea. The SPT is composed of two professional editors who manage editing requests sent to external companies while also providing one-on-one in-house editing services. We gathered author satisfaction data from 936 surveys between July 2017 and December 2018 and analyzed the number of editing requests and research publications by segmented regression analysis of interrupted time series data.ResultsThe SPT processed 3931 editing requests in 2017-2018, which was a marked increase compared with prior to its establishment (P = 0.0097). The authors were generally satisfied with the quality of editing services from both in-house and external editors. Upon conducting regular quality control, overall author satisfaction with one external company gradually increased over the course of one year (P for trend = 0.086). Author satisfaction survey results revealed that overall satisfaction of editing service was most strongly correlated with how well the edits conformed to the authors' intentions (R = 0.796), and was only weakly correlated with quick turnaround time (R = 0.355). We also observed a significant increase in the trend of the number of research publications (P = 0.0007) at one year after the establishment of the SPT.ConclusionProviding a combination of in-house and external editing services resulted in high author satisfaction and subsequent hospital-wide increases in manuscript writing and publication. Our model system may be adapted in academic hospitals to better address the editing needs of non-native English-speaking researchers.

Graphical abstract, Highlights • Diglycolic acid (DGA) is an indirect food additive. • DGA was tested for renal cell toxicity in vitro using HK-2 cells. • Evaluation of toxicity included cellular and mitochondrial effects. • In vitro data are highly concordant with in vivo outcomes., Diglycolic acid (DGA) is present in trace amounts in our food supply and is classified as an indirect food additive linked with the primary GRAS food additive carboxymethyl cellulose (CMC). Carboxymethyl starches are used as a filler/binder excipient in dietary supplement tablets and a thickening ingredient in many other processed foods. We sought to utilize the human proximal tubule HK-2 cell line as an in vitro cellular model system to evaluate its acute nephrotoxicity of DGA. We found that DGA was indeed toxic to HK-2 cells in all in vitro assays in our study, including a highly sensitive Luminex assay that measures levels of an in vitro biomarker of kidney-specific toxicity, Kidney Injury Molecule 1 (KIM-1). Interestingly, in vitro KIM-1 levels also correlated with in vivo KIM-1 levels in urine collected from rats treated with DGA by daily oral gavage. The use of in vitro and in vivo models towards understanding the effectiveness of an established in vitro system to predict in vivo outcomes would be particularly useful in rapidly screening compounds that are suspected to be unsafe to consumers. The merit of the HK-2 cell model in predicting human toxicity and accelerating the process of food toxicant screening would be especially important for regulatory purposes. Overall, our study not only revealed the value of HK-2 in vitro cell model for nephrotoxicity evaluation, but also uncovered some of the mechanistic aspects of the human proximal tubule injury that DGA may cause.

Background The widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag+) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs). Results The present study characterized transcriptomic changes induced by 5.0 µg/ml AgNPs during spontaneous differentiation of mouse ESCs, and compared them to those induced by Ag+ under identical conditions. After 24 h exposure, 101 differentially expressed genes (DEGs) were identified in AgNP-treated cells, whereas 400 genes responded to Ag+. Despite the large differences in the numbers of DEGs, functional annotation and pathway analysis of the regulated genes revealed overall similarities between AgNPs and Ag+. In both cases, most of the functions and pathways impacted fell into two major categories, embryonic development and metabolism. Nevertheless, a number of canonical pathways related to cancer were found for Ag+ but not for AgNPs. Conversely, it was noted that several members of the heat shock protein and the metallothionein families were upregulated by AgNPs but not Ag+, suggesting specific oxidative stress effect of AgNPs in ESCs. The effects of AgNPs on oxidative stress and downstream apoptosis were subsequently confirmed by flow cytometry analysis. Conclusions Taken together, the results presented in the current study demonstrate that both AgNPs and Ag+ caused transcriptomic changes that could potentially exert an adverse effect on development. Although transcriptomic responses to AgNPs and Ag+ were substantially similar, AgNPs exerted specific effects on ESCs due to their nanosized particulate form. Electronic supplementary material The online version of this article (doi:10.1186/s12951-017-0265-6) contains supplementary material, which is available to authorized users.

Highlights • Transcriptomics was used to study the effect of silver ion on developing thymus. • Maternal exposure to silver acetate was conducted during gestation and lactation. • Silver acetate up to 40.0 mg/kg did not adversely affect thymic development., Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Sperm-positive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs) in each dose group using a loose criterion of fold change (FC) >1.5 and unadjusted p

We found isolated or clustered trophoblasts in the chorionic connective tissue of the extraplacental membranes, and defined this novel histologic feature as the "trophoblast islands of the chorionic connective tissue" (TICCT). This study was conducted to determine the clinical significance of TICCT.Immunohistochemistry for cytokeratin-7 was performed on the chorioamniotic membranes (N = 2155) obtained from singleton pregnancies of 1199 uncomplicated term and 956 preterm deliveries. The study groups comprised 1236 African-American and 919 Hispanic women. Gestational age ranged from 24(+0) weeks to 41(+6) weeks. Multiple logistic regression analysis was performed to investigate the magnitude of association between patient characteristics and the presence of TICCT.The likelihood of TICCT was significantly associated with advancing gestational age both in term (OR: 1.29, 95% CI: 1.16-1.45, p0.001) and preterm deliveries (OR: 1.19, 95% CI: 1.07-1.32, p = 0.001) . Hispanic women were less likely than African-American women to have TICCT across gestation in term (OR: 0.23, 95% CI: 0.18-0.31, p0.001) and preterm pregnancies (OR: 0.41, 95% CI: 0.29-0.58, p0.001). Women with a female fetus were significantly more likely to have TICCT than women with a male fetus, in both term (OR: 1.64, 95% CI: 1.28-2.11, p0.001) and preterm gestations (OR: 2.04, 95% CI: 1.46-2.85, p0.001). TICCT was 40% less frequent in the presence of chronic placental inflammation [term (OR: 0.60, 95% CI: 0.45-0.81, p = 0.001) and preterm gestations (OR: 0.58, 95% CI: 0.40-0.84, p = 0.003)] and in parous women at term (OR: 0.60, 95% CI: 0.44-0.81, p = 0.001).Our findings suggest that the duration of pregnancy, fetal sex, and parity may influence the behavior of extravillous trophoblast and placental mesenchymal cells.

Paenibacillus alvei, a naturally occurring soil microorganism, may be used in the control and/or elimination of human/animal pathogens present on/within produce commodities associated with human consumption. The safety of oral exposure to P. alvei in male, nulliparous females, the pregnant dam and developing fetus was assessed. Adult male and female rats received a single oral dose (gavage) of P. alvei and tissues were collected at post exposure days 0, 3 and 14. To evaluate the effect of the test organism on fetal development, sperm positive female rats received the test organism every 3 days thereafter throughout gestation. As human exposure would be no more than 1 × 103 CFU/ml the following dose levels were evaluated in both study phases: 0 CFU/ml tryptic soy broth (negative control); 1 × 108 CFU/ml; 1 × 104 CFU/ml or 1 × 102 CFU/ml. Neither sex specific dose-related toxic effects (feed or fluid consumption, body weight gain, and histopathology) nor developmental/reproductive effects including the number of implantations, fetal viability, fetal weight, fetal length and effects on ossification centers were observed. The test organism did not cross the placenta and was not found in the amniotic fluid.

Background: Renal and hepatotoxicity of diglycolic acid (DGA) has been described with in vitro cellular models as well as in vivo animal and human systems. The possibility of DGA being toxic

Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis.Placental tissues were obtained from five groups of patients: 1) normal pregnancy at term without labor (n = 10); 2) normal pregnancy at term in labor (n = 10); 3) preterm labor without inflammation (n = 10); 4) preterm labor with acute chorioamnionitis and funisitis (n = 10); and 5) preterm labor with chronic chorioamnionitis (n = 10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n = 4) and human umbilical vein endothelial cells (HUVECs, n = 4) treated with IL-1β (1 and 10 ng/ml) and CXCL10 (0.5 and 1 or 5 ng/ml).1) Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton's jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment.IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton's jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis.

Background Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth. Methods and Findings This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p

Acute chorioamnionitis is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathological significance of chronic chorioamnionitis is unclear. This study was conducted to determine the frequency and severity of chronic chorioamnionitis in normal pregnancy and in various pregnancy complications. Placentas from the following patient groups were studied: (1) term not in labor (n=100), (2) term in labor (n=100), (3) preterm labor (n=100), (4) preterm prelabor rupture of membranes (n=100), (5) preeclampsia at term (n=100), (6) preterm preeclampsia (n=100), and (7) small-for-gestational-age at term (n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed using real-time quantitative reverse transcription-PCR. The frequency of chronic chorioamnionitis in the preterm labor group and the preterm prelabor rupture of membranes group was 34 and 39%, respectively, which was higher than that of normal-term placentas (term not in labor, 19%; term in labor, 8%; P