The health risks associated with combined exposure to microplastics (MPs) and cyanobacteria toxins have gained increasing attention due to the large-scale prevalence of cyanobacterial blooms and accumulation of MPs in aquatic environments. Therefore, we explored the cardiovascular toxic effects of microcystin-LR (MC-LR, 1, 10, 100 mu g/L) in the presence of 5 mu m polystyrene microplastics (PS -MPs, 100 mu g/L) and 80 nm polystyrene nanoplastics (PS -NPs, 100 mu g/L) in zebrafish models. Embryos were exposed to certain PS -MPs and PS -NPs conditions in water between 3 h post -fertilization (hpf) and 168 hpf. Compared to MC-LR alone, a significant decrease in heart rate was observed as well as notable pericardial edema in the MC-LR + PS-MPs/NPs groups. At the same time, sinus venosus and bulbus arteriosus (SV-BA) distances were significantly increased. Furthermore, the addition of PS-MPs/NPs caused thrombosis in the caudal vein and more severe vascular damage in zebrafish larvae compared to MC-LR alone. Our findings revealed that combined exposure to PS -NPs and MC-LR could significantly decreased the expression of genes associated with cardiovascular development ( myh6, nkx2.5, tnnt2a, and vegfaa ), ATPase ( atp1a3b, atp1b2b, atp2a1l, atp2b1a, and atp2b4 ), and the calcium channel ( cacna1ab and ryr2a ) compared to exposure to MC-LR alone. In addition, co -exposure with PS-MPs/NPs exacerbated the MC-LR-induced reactive oxygen species (ROS) production, as well as the ROS-stimulated apoptosis and heightened inflammation. We also discovered that astaxanthin (ASTA) treatment partially attenuated these cardiovascular toxic effects. Our findings confirm that exposure to MC-LR and PS-MPs/NPs affects cardiovascular development through calcium signaling interference and ROS-induced cardiovascular cell apoptosis. This study highlights the potential environmental risks of the co -existence of MC-LR and PS-MPs/NPs for fetal health, particularly cardiovascular development.

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to β-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in β-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1β. These results suggest that the association of KDM4A and Wnt/β-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.

Emerging evidence indicates the critical roles of circular RNAs in the development of multiple cancers, containing hepatocellular carcinoma (HCC). Herein, our present research reported the biological function and mechanism of circ_0027791 in HCC progression. Circ_0027791, microRNA-496 (miR-496), programmed cell death ligand 1 (PDL1), and methyltransferase-like 3 (METTL3) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, invasion, and sphere formation ability were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, transwell, and sphere formation assays. Macrophage polarization was detected using flow cytometry assay. To understand the role of circ_0027791 during the immune escape, HCC cells were cocultured with peripheral blood mononuclear cells or cytokine-induced killer (CIK) cells in vitro. A xenograft mouse model was applied to assess the function of circ_0027791 in vivo. After prediction using circinteractome and miRDB, the binding between miR-496 and circ_0027791 or PDL1 was validated based on a dual-luciferase reporter assay. Interaction between METTL3 and circ_0027791 was determined using methylated RNA immunoprecipitation (MeRIP)-qPCR, RIP-qPCR, and RNA pull-down assays. Circ_0027791, PDL1, and METTL3 expression were upregulated, and miR-496 was decreased in HCC patients and cells. Moreover, circ_0027791 knockdown might repress proliferation, invasion, sphere formation, M2 macrophage polarization, and antitumor immune response. Circ_0027791 knockdown repressed HCC tumor growth in vivo. In mechanism, circ_0027791 functioned as a sponge for miR-496 to increase PDL1 expression. In addition, METTL3 mediated the m6A methylation of circ_0027791 and stabilized its expression. METTL3-induced circ_0027791 facilitated HCC cell progression partly regulating the miR-496/PDL1 axis, which provided a new prognostic and therapeutic marker for HCC.

Objective Microcystin-leucine-arginine(MC-LR) exposure induces lipid metabolism disorders in the liver. Secreted frizzled-related protein 5(SFRP5) is a natural antagonist of winglesstype MMTV integration site family, member 5A(Wnt5a) and an anti-inflammatory adipocytokine. In this study, we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5, which has anti-inflammatory effects, can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK) pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders. Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR, and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner. SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation. Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice, and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Background: Cyanobacterial blooms caused by eutrophication can not only worsen the water environment, but also produce cyanobacterial toxins when some toxic cyanobacterial blooms proliferate. Microcystin is one of the most abundant cyanobacterial toxins found in reservoirs worldwide. Among its isomer, microcystin-leucine-arginine (MC-LR) is the most abundant and most toxic variety. Various experiments have clearly shown that MC-LR has hepatotoxicity and carcinogenicity, but there are relatively few studies on its immune damage effect. Numerous studies have shown that microRNAs (miRNAs) are involved in a wide range of biological processes. Do miRNAs also play a role in immune disorders caused by microcystin exposure? This is the question to be discussed in this study. Objective: By reviewing the effects of microcystins on the immune system, the changes of miRNAs caused by microcystins exposure and the role of miRNAs in immune regulation, we further explore the possible important role of miRNAs in immune disorders induced by microcystins exposure. Methods: Firstly, evidence of the influence of microcystin on immune system was collected, then the influence of microcystin exposure on microRNAs expression was reviewed, and finally, the role of microRNAs in immune regulation was explored. Conclusions: Exposure to microcystin in vitro or in vivo can cause changes in the expression of miRNAs, as well as corresponding responses from the body's immune system. There has been evidence that miRNAs are involved in a variety of immune regulatory processes in the body, but there are still relatively few studies on the role of miRNAs in immune disorders caused by microcystins exposure.