Heterogeneity effects of bisphenol A and its substitute, fluorene-9-bisphenol, on intestinal homeostasis.

Bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) are used in consumer products; however, their toxic effects on intestinal epithelium remain largely unknown. In this study, we combined intestinal organoids and single-cell RNA sequencing to investigate the impact of BPA and BHPF exposure on intestinal cell composition, differentiation, and function. Both compounds inhibited the growth of small intestinal organoids, with BHPF exhibiting a more potent inhibitory effect.

Cadmium exposure causes transcriptomic dysregulation in adipose tissue and associated shifts in serum metabolites.

Cadmium (Cd) is a toxic heavy metal found in natural and industrial environments. Exposure to Cd can lead to various metabolic disturbances, notably disrupting glucose and lipid homeostasis. Despite this recognition, the direct impact of Cd exposure on lipid metabolism within adipose tissue, and the mechanisms underlying these effects, have not been fully elucidated.

Saturated fatty acids synergizes cadmium to induce macrophages M1 polarization and hepatic inflammation.

Exposure to the toxic metal cadmium (Cd) is a well-established risk factor for hepatic inflammation, but it remains unclear how metabolic components, such as different fatty acids (FAs), interact with Cd to influence this process. Understanding these interactions is essential for identifying potential preventative and therapeutic targets for this disorder. To address this question, we conducted in vitro and in vivo studies to investigate the combinatorial effect of Cd and saturated FAs on hepatic inflammation.

Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.

Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages' function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro-inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8 T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor.

Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function.

Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8 T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse.

The intervention of valproic acid on the tumorigenesis induced by an environmental carcinogen of PAHs.

This study investigated whether valproic acid (VPA, a histone deacetylase inhibitor) can interfere with the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). A typical representative compound of PAHs, 7,12-Dimethylbenz[a]anthracene (DMBA), was used to induce rat breast cancer. The results showed that therapeutic concentration of VPA (50 and 100 mg/kg) delayed the occurrence of tumors, reduced tumor formation rate and attenuated tumors growth, and have a protective effect on normal tissues.