Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L) from 2 h post-fertilization (hpf) to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab) might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8) and thyroid hormone synthesis (TSHβ, NIS and TG). However, the genes encoding proteins involved in TH transport (transthyretin, TTR) was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity.
Background: Tumor recurrence in patients after surgery severely reduces the survival rate of surgical patients. Targeting and killing recurrent tumor cells and tissues is extremely important for the cancer treatment. Results: Herein, we designed a nano-biomimetic photothermal-controlled drug-loading platform HepM-TSL with good targeting ability and immunocompatibility for the treatment of recurrent hepatocellular carcinoma. HepM-TSL can accurately target the recurrent tumor area with the aid of the cloaked homotypic cell membrane and release the chemotherapy drugs in a controlled manner. In vivo results have confirmed that HepM-TSL loaded with drugs and photosensitizer achieves the synergistic treatment of recurrent hepatocellular carcinoma with good therapeutic effect and slight side effects. Conclusion: Accordingly, HepM-TSL provides a sound photothermal-chemotherapy synergistic strategy for the treatment of other recurrent cancers besides of recurrent hepatocellular carcinoma.
Cardiovascular diseases (CVDs), which are associated with high morbidity and mortality worldwide, include atherosclerosis (AS), hypertension, heart failure (HF), atrial fibrillation, and myocardial fibrosis. CVDs are influenced by the diversity, distribution, and metabolites of intestinal microflora, and their risk can be reduced through physical activity (PA) such as regular exercise. PA benefits the metabolic changes that occur in the gut microbiota (GM). The major metabolites of the GM influence pathogenesis of CVDs through various pathways. However, the relationship between PA and GM is less well understood. In this review, we discuss the impacts of different types of PA on intestinal microflora including the diversity, distribution, metabolites, and intestinal barrier function including intestinal permeability, with a focus on the mechanisms by which PA affects GM. We also discuss how GM influences CVDs. Finally, we summarize current research and knowledge on the effects of PA on CVD via regulation of the GM and intestinal function. More understanding of relevant relationship between PA and GM may provide hope for the prevention or treatment of CVDs. Furthermore, a better understanding of regulation of the GM and intestinal function may lead to novel diagnostic and therapeutic strategies, improving the clinical care of CVD patients.
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