Exposure to a Mixture of Endocrine-Disrupting Chemicals and Metabolic Outcomes in Belgian Adolescents.

Childhood exposure to endocrine-disrupting chemicals (EDCs), either alone or in mixtures, may affect metabolic outcomes, yet existing evidence remains inconclusive. In our study of 372 adolescents from the Flemish Environment and Health Study (FLEHS IV, 2017-2018), we measured 40 known and suspected EDCs and assessed metabolic outcomes, including body mass index z-score (zBMI), abdominal obesity (AO), total cholesterol (TC), and triglycerides (TG). We applied Bayesian kernel machine regression (BKMR) and Bayesian penalized horseshoe regression for variable selection and then built multivariate generalized propensity score (mvGPS) models to provide an overview of the effects of selected EDCs on metabolic outcomes. As a result, BKMR and horseshoe together identified five EDCs associated with zBMI, three with AO, three with TC, and five with TG. Through mvGPS analysis, monoiso-butyl phthalate (MIBP), polychlorinated biphenyl (PCB-170), and hexachlorobenzene (HCB) each showed an inverse association with zBMI, as did PCB-170 with AO. Copper (Cu) was associated with higher TC and TG, except in boys where it was linked to lower TG. Additionally, monoethyl phthalate (MEP) and monobenzyl phthalate (MBzP) were associated with higher TG. To conclude, our findings support the association between certain chemicals (Cu, MEP, and MBzP) and elevated lipid levels, aligning with prior studies. Further investigation is needed for sex-specific effects.

Prenatal Exposure to Metabolism-Disrupting Chemicals, Cord Blood Transcriptome Perturbations, and Birth Weight in a Belgian Birth Cohort.

Prenatal exposure to metabolism-disrupting chemicals (MDCs) has been linked to birth weight, but the molecular mechanisms remain largely unknown. In this study, we investigated gene expressions and biological pathways underlying the associations between MDCs and birth weight, using microarray transcriptomics, in a Belgian birth cohort. Whole cord blood measurements of dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyls 153 (PCB-153), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and transcriptome profiling were conducted in 192 mother-child pairs. A workflow including a transcriptome-wide association study, pathway enrichment analysis with a meet-in-the-middle approach, and mediation analysis was performed to characterize the biological pathways and intermediate gene expressions of the MDC-birth weight relationship. Among 26,170 transcriptomic features, we successfully annotated five overlapping metabolism-related gene expressions associated with both an MDC and birth weight, comprising BCAT2, IVD, SLC25a16, HAS3, and MBOAT2. We found 11 overlapping pathways, and they are mostly related to genetic information processing. We found no evidence of any significant mediating effect. In conclusion, this exploratory study provides insights into transcriptome perturbations that may be involved in MDC-induced altered birth weight.

Prenatal exposure to persistent organic pollutants and changes in infant growth and childhood growth trajectories.

BACKGROUND: Children are born with a burden of persistent organic pollutants (POPs) which may have endocrine disrupting properties and have been postulated to contribute to the rise in childhood obesity. The current evidence is equivocal, which may partly because many studies investigate the effects at one time point during childhood. We assessed associations between prenatal exposure to POPs and growth during infancy and childhood. METHODS: We used data from two Belgian cohorts with cord blood measurements of five organochlorines [(dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), polychlorinated biphenyls (PCB-138, -150, -180)] (N = 1418) and two perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)] (N = 346). We assessed infant growth, defined as body mass index (BMI) z-score change between birth and 2 years, and childhood growth, characterized as BMI trajectory from birth to 8 years. To evaluate associations between POP exposures and infant growth, we applied a multi-pollutant approach, using penalized elastic net regression with stability selection, controlling for covariates. To evaluate associations with childhood growth, we used single-pollutant linear mixed models with random effects for child individual, parametrized using a natural cubic spline formulation. RESULTS: PCB-153 was associated with increased and p,p'-DDE with decreased infant growth, although these results were imprecise. No clear association between any of the exposures and longer-term childhood growth trajectories was observed. We did not find evidence of effect modification by child sex. CONCLUSION: Our results suggest that prenatal exposure to PCB-153 and p,p'-DDE may affect infant growth in the first two years, with no evidence of more persistent effects.

Spatiotemporal Trends, Sources and Ecological Risks of Heavy Metals in the Surface Sediments of Weitou Bay, China.

Heavy metals are extremely harmful materials to marine ecosystems and human health. To determine the anthropogenic contributions and ecological risks in Weitou Bay, China, the spatiotemporal variations in the concentrations of heavy metals in surface sediment were investigated during spring 2008 and 2017. The results indicated that high concentrations of pollutants were generally located near the river mouths and along the coast of industrial areas. Principal component analysis indicated that heavy metal contents were mainly affected by industrial waste drainage, urban development, natural weathering and erosion, and interactions between organic matter and sulfides. The potential ecological risk assessment demonstrated that, in 2008, 82% of the sampling sites were at low risk, while 18% were at moderate risk. The situation had deteriorated slightly by 2017, with 73%, 18%, and 9% of stations in Waytou Bay at low, moderate, and very high risk, respectively. Cd was the most harmful metal, followed by Hg. These two elements accounted for more than 80% of the potential ecological risk index (RI) value. The present work analyzed the source of heavy metals, identified the major pollution elements and high risk areas, and provides guidance for pollution control and ecological restoration in Weitou Bay.

Synthesis of ß-cyclodextrin-PEG-G molecules to delay tumor growth and application of ß-cyclodextrin-PEG-G aggregates as drug carrier.

The clinical use of many chemotherapeutic drugs is considerably greatly limited due to their serious side effects. This problem can be solved by using a low-toxic or nontoxic drug carrier that exhibits excellent performance in entrapping chemotherapeutic drugs. Accordingly, ß-cyclodextrin-PEG-guanosine (ß-CD-PEG-G) molecule was first synthesized. The molecules can self-assemble into negatively charged spherical aggregates (called ß-CD-PEG-G aggregates) that can stably exist in an aqueous solution and entrap doxorubicin (Dox) to form ß-CD-PEG-G-Dox nanomedicine. Dox encapsulation efficiency is approximately 79 ± 6.3%. Dox from ß-CD-PEG-G-Dox nanomedicine exhibits sustained release and pH responsiveness. Cell and animal experiments showed that ß-CD-PEG-G-Dox nanomedicine could effectively induce cancer cell apoptosis to exert antitumor activity. Unexpectively, the animal experiment and tissue sections demonstrated that ß-CD-PEG-G aggregates exhibit certain antitumor activity that could delay the tumor growth. Therefore, the ß-CD-PEG-G molecule has high potential as a drug carrier candidate.

Preparation of ß-CD-DPPE-Dox Nanomedicine and Its' Application as the Anticancer and Antitumor Drug.

ß-CD-DPPE molecule was synthesized through the conjugation of ß-CD-NH2 and the DPPE molecule, and its' water-solubility was more excellent than the traditional phospholipid molecule. The spherical micelles was formed by ß-CD-DPPE molecule in aqueous solution, and the ß-CD-DPPE-Dox nanomedicine can be prepared through loading Dox (Doxorubicin) into the micelles, and the Dox loading ratio was about 82.3 ± 7.27%. At the same time the Dox release behavior from the nanomedicine was sustained-release and pH controlled release, and the release test in vitro showed that the release rate of the Dox at the lower pH was faster than that of normal pH (pH = 7.4), which indicated that the rate of release in the tumor microenvironment is faster than in the normal tissue. Biological test showed that the micelles was low cytotoxicity, and the cytotoxicity of ß-CD-DPPE-Dox nanomedicine was lower than the Dox under the same Dox concentration, and the ß-CD-DPPE-Dox nanomedicine could effectively induce cancer cell apoptosis and inhibit the tumor growth.

Plasmonic microgels of Au nanorods: Self-assembly and applications in chemophotothermo-synergistic cancer therapy.

Plasmonic microgels (PMgels) of the self-assembled gold nanorods (Au NRs) with side-by-side piles in ionic liquid microgels were prepared. Transmission electron microscopy (TEM) images revealed unique self-growth and self-arrangement of Au NRs in the microgel systems. The fabrication of PMgels occurs through co-assembling Au NRs and an ionic liquid microgel system, therefore differs from the fabrication of conventional plasmonic hybrid nanocomposites. These PMgels showed strong absorption in the near-infrared window and enhanced photothermal conversion efficiency, up to 52.8%, compared to the Au NRs (22%) as a result of the ordering and dense packing of Au NRs in the microgels. When the PMgels were exposed to a near-IR laser, the doxorubicin hydrochloride (Dox) released from PMgels and the resulting thermal effect can immensely inhibit tumor growth both in vitro and in vivo. The tests demonstrated that no tumor metastasis occurred. This platform of the PMgels with the laser-controlled delivery system could provide chemo-photothermal synergistic therapy for a wide spectrum of diseases.

A liposome preparation based on ß-CD-LPC molecule and its application as drug-delivery system.

AIM: The ß-CD-LPC molecule was synthesized based on the conjugation of LPC and ß-CD molecules and it could self-assemble into liposome which was used to encapsulate the Dox to form nanomedicine for the cancer therapy. MATERIALS & METHODS: The anticancer and antitumor effect of ß-CD-LPC-Dox nanomedicine was studied with the vitro and vivo experimental methods. RESULTS: The result showed that ß-CD-LPC liposome had high Dox drug-loading rate and a good sustained-release effect. Cell experiment showed that the ß-CD-LPC-Dox nanomedicine could effectively induce cancer cell apoptosis and in vivo experiments showed that ß-CD-LPC-Dox liposome could effectively inhibit tumor growth and had an effective anticancer activity with lower biotoxicity. CONCLUSION: The ß-CD-LPC-Dox nanomedicine could be applied as a candidate drug to therapy the cancer.