Search

Increasing concerns surround nanoplastic's health risks owing to global exposure emphasize clear understanding of their dynamic distribution and organ-specific molecular effects. We assessed the health risks associated with nanoplastics (100 nm) following oral ingestion. Using a fluorescent tracking system, we demonstrated their recyclability through gastrointestinal tract-liver-gallbladder axis, with specific accumulation in the gallbladder. Pathological alterations in the gallbladder and single-cell RNA sequencing data indicated that short-term (three weeks) exposure induces gallbladder epithelial hyperplasia, whereas long-term exposure (six weeks) induces progressive hyperplasia, epithelial-mesenchymal transition (EMT), and fibrosis. Nanoplastic exposure facilitates neutrophil extracellular trap (NET) formation. Various nanoplastics were identified in human gallbladder bile samples using scanning electron microscopy (SEM) and Raman spectroscopy. Consistently, epithelial hyperplasia and neutrophil infiltration were observed in the gallbladder tissues, alongside nanoplastic detection in the bile. Our findings offer insights into the understanding of the enterohepatic-biliary recycling route of nanoplastics and their potential toxic consequences. [Display omitted] • Nanoplastics following oral ingestion pass through gastrointestine-liver-biliary axis, with specific accumulation in the gallbladder and recyled. • Short-termexposure induces gallbladder epithelial hyperplasia, whereas long-term exposure induces epithelial mesenchymal transition (EMT), and fibrosis. • Nanoplastic exposure facilitates neutrophil extracellular trap (NET) formation. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p’-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. [ABSTRACT FROM AUTHOR]

Associations between polycyclic aromatic hydrocarbons (PAHs) and respiratory diseases have been widely studied, but the effects of PAH on liver toxicity in adolescents are unclear. Here, 3194 adolescents with NHANES data from 2003 to 2016 were selected. PAH exposure was assessed by measuring PAH metabolites in urine. The outcome variables were the levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transpeptidase (GGT). The association between PAH exposure and liver function was evaluated by the weighted quantile sum (WQS) and logistic regression, and the associations between PAHs and inflammation and blood lipids were evaluated by linear regression. Covariates were adjusted for age, ethnicity, BMI, physical activity, family income, cotinine, and urinary creatinine. The results showed that for females, mixed PAH exposure was related to an increased ALT level (OR = 2.33, 95% CI 1.15, 4.72), and 2-fluorene contributed the most (38.6%). Urinary 2-fluorene was positively associated with an elevated ALT level (OR = 2.19 95% 1.12, 4.27, p for trend = 0.004). Mechanistically, 2-fluorene can cause a 3.56% increase in the white blood cell count, a 6.99% increase in the triglyceride level, and 1.70% increase in the total cholesterol level. PAHs may have toxic effects, possibly mediated by inflammation and blood lipids, on the adolescent female liver. Additional confirmatory studies are needed. [Display omitted] • Urinary PAHs mixtures may be risk factors for hepatotoxicity. • Urinary 2-fluorene positively associated with increased risk of ALT. • Each increment of one unit (ng/L) in the 2-fluorene was associated with a 3.56% increase in white blood cells count. Exposure to a mixture of polycyclic aromatic hydrocarbons (PAHs) is positively related to elevated alanine aminotransferase (ALT) level. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is an emerging organic pollutant (EOP) hazardous to human health. Effects of maternal PFOA exposure on offspring as well as the underlying mechanisms remain unclear. In this study, ICR mouse models of gestational low PFOA exposure (0.05 mg/kg/day) were established to investigate the roles on metabolic disorders of offspring. Body weight, body composition, hepatic lipid levels, transcriptome and metabolome were analyzed. Expression of genes related to lipid metabolism, inflammasome formation and gut barrier integrity were measured. Furthermore, oral administration of chlorogenic acid (CGA) (100 mg/kg/day) was performed to observe the rescue effect on lipid disorders caused by PFOA exposure. Our findings demonstrated that gestational exposure to PFOA resulted in obesity, hepatic inflammation, disorders of lipid metabolism, and disruption of gut barrier integrity in male offspring. Notably, these adverse effects were attenuated by CGA supplementation. These data suggested that PFOA exposure during early life stage induced potential risks for later onset of obesity and metabolic disorder which could be ameliorated by CGA treatment. Image 1 • Low-dose gestational perfluorooctanoic acid (PFOA) exposure induces obesity in male offspring. • Low-dose gestational PFOA exposure impairs hepatic lipid metabolism and gut barrier integrity in male offspring. • Chlorogenic acid (CGA) attenuates adverse effects in male offspring induced by PFOA. Chlorogenic acid (CGA) ameliorates gestational PFOA exposure induced obesity and metabolic disorder in male offspring. [ABSTRACT FROM AUTHOR]

The biomimetic pancreatic microenvironment improves the differentiation efficiency and function of human embryonic stem cell-derived β-cells (S C-β cells). Thus, a laminin subunit alpha 2-gelatin methacrylate (LAMA2-GelMA) hybrid hydrogel as a bionics carrier for the formation and maturation of endocrine lineage was developed in our research, based on pancreas proteomics analysis of postnatal mice. Pancreatic endocrine cells cultured on the hybrid hydrogel in vitro , which was composed of 0.5 μg/mL LAMA2 protein and 4% GelMA, the expression of transcription factors (TFs), including NKX6.1, NKX6.2, and NEUROD1 were upregulated. Single-cell transcriptomics was performed after LAMA2 knockdown during the early differentiation of pancreatic progenitor (PP) cells, a marked decrease in the forkhead box protein A2 (FOXA2+)/GATA-binding factor 6 (GATA6+) cluster was detected. Also, we clarified that as a receptor of LAMA2, integrin subunit alpha 7 (ITGA7) participated in Integrin-AKT signaling transduction and influenced the protein levels of FOXA2 and PDX1. In vivo experiments showed that, PP cells encapsulated in the LAMA2-GelMA hydrogel exhibited higher serum C -peptide levels compared to the GelMA and Matrigel groups in nude mice and reversed hyperglycemia more quickly in STZ-induced diabetic nude mice. Taken together, our findings highlighted the feasibility of constructing a pancreas-specific microenvironment based on proteomics and tissue engineering for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below: 4,4′-thiodiphenol (TDP) < bisphenol S (BPS) < 4,4′-dihydroxybenzophenone (DHBP) < tetrabromobisphenol A (TBBPA) < tetrachlorobisphenol A (TCBPA) < bisphenol E (BPE) < bisphenol F (BPF) < bisphenol B (BPB) < bisphenol AF (BPAF) < bisphenol A (BPA) < bisphenol C (BPC) < tetramethylbisphenol A (TMBPA) < bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs. • A high-content screening assay was performed to evaluate the hepatic lipid accumulation of 13 bisphenols in vitro. • BPE, BPF, BPB, BPAF, BPA, BPC, TMBPA, and BPAP exhibited the significant effects on lipid deposition. • BPAP, BPA, and BPAF significantly regulated genes involved in lipid β-oxidation, lipogenesis and nuclear receptor genes. [ABSTRACT FROM AUTHOR]