Search

Triclocarban (TCC) is a broad-spectrum antibacterial agent used globally, and high concentrations of this harmful chemical exist in the environment. The human body is directly exposed to TCC through skin contact. Moreover, TCC is also absorbed through diet and inhaled through breathing, which results in its accumulation in the body. The safety profile of TCC and its potential impact on human health are still not completely clear; therefore, it becomes imperative to evaluate the reproductive toxicity of TCC. Here, we explored the effect of TCC on the early embryonic development of mice and its associated mechanisms. We found that acute exposure of TCC affected the early embryonic development of mice in a dose-dependent manner. Approximately 7600 differentially expressed genes (DEGs) were obtained by sequencing the transcriptome of 2-cell mouse embryos; of these, 3157 genes were upregulated and 4443 genes were downregulated in the TCC-treated embryos. GO and KEGG analysis revealed that the enriched genes were mainly involved in redox processes, RNA synthesis, DNA damage, apoptosis, mitochondria, endoplasmic reticulum, Golgi apparatus, cytoskeleton, peroxisome, RNA polymerase, and other components or processes. Moreover, the Venn analysis showed that the zygotic genome activation (ZGA) was affected and the degradation of maternal effector genes was inhibited. TCC induced changes in the epigenetic modification of 2-cell embryos. The level of DNA methylation increased significantly. Further, the levels of H3K27ac, H3K9ac, and H3K27me3 histone modifications decreased significantly, whereas those of H3K4me3 and H3K9me3 modifications increased significantly. Additionally, TCC induced oxidative stress and DNA damage in the 2-cell embryos. In conclusion, acute exposure of TCC affected early embryo development, destroyed early embryo gene expression, interfered with ZGA and maternal gene degradation, induced changes in epigenetic modification of early embryos, and led to oxidative stress and DNA damage in mouse early embryos.

Zinc Pyrithione (ZPT), a Food and Drug Administration (FDA) approved chemical, is widely used for topical antimicrobials and cosmetic consumer products, including anti-dandruff shampoos. ZPT and its degraded byproducts have detected in large quantities in the environment, and identified to pose healthy risks on aquatic organisms and human. However, so far, knowledge about ZPT effects on female reproduction, particularly oocyte maturation and quality, is limited. Herein, we investigated the adverse impact of ZPT on mouse oocyte maturation and quality in vitro and found exposure to ZPT significantly compromises oocyte maturation. The results revealed that ZPT disturbed the meiotic cell cycle by impairing cytoskeletal dynamics, kinetochore-microtubule attachment (K-MT), and causing spindle assembly checkpoints (SAC) continuous activation. Further, we observed the microtubule-organizing centers (MTOCs) associated proteins p-MAPK and Aurora-A were disrupted in ZPT-treated oocytes, signified by decreased expression and abnormal localization, responsible for the severe cytoskeletal defects. In addition, ZPT exposure induced a significant increase in the levels of H3K9me2, H3K9me3, H3K27me1, and H3K27me3, suggesting the alterations of epigenetic modifications. Moreover, the accumulation of zinc ions (Zn2+) was observed in ZPT-treated oocytes, which was detrimental because overmuch intracellular Zn2+ disrupted oocyte meiosis. Finally, these above alterations impaired spindle organization and chromosome alignment in metaphase-II (MII) oocytes, indicative of damaged oocytes quality. In conclusion, ZPT exposure influenced oocyte maturation and quality via involvement in MTOCs-associated proteins mediated spindle defects, altered epigenetic modifications and zinc accumulation.

Background & Aims: Immunodominance is an important feature of antiviral, antitumor, and antibacterial cellular immune responses, but it is not well demonstrated in the immune responses against Helicobacter pylori. Antigen-specific CD4+ T cells protect mice against infection with H pylori. We investigated the immunodominant CD4+ T-cell response to neuraminyllactose-binding hemagglutinin (HpaA), which is a conserved, H pylori–specific colonization factor that is being investigated as an antigen for vaccination strategies. Methods: HpaA-specific CD4+ T cells were expanded with autologous peripheral blood mononuclear cells that had been incubated with recombinant HpaA and characterized using overlapping synthetic peptides. We compared the percentage of CD4+ T cells with specificity for HpaA88–100, restricted to HLA-DRB1*1501, among 59 H pylori–infected subjects with different gastric diseases. Results: We identified and characterized several immunodominant CD4+ T-cell epitopes derived from HpaA. The immunodominant CD4+ T-cell responses specific to HpaA88–100 were observed in most H pylori–infected individuals who expressed HLA-DRB1*1501 and were significantly more abundant in patients with less severe diseases (P < .05). Conclusions: The HLA-DRB1*1501–restricted immunodominant CD4+ T-cell response to HpaA88–100 is associated with reduced risk of severe gastric diseases. Further study of these and other immunodominant CD4+ T-cell responses to H pylori will provide insight into mechanisms of protective immunity and aid in vaccine design. [ABSTRACT FROM AUTHOR]

Abstract: An epitope-based vaccine is a promising option for treating Helicobacter pylori (H. pylori) infection. Epitope mapping is the first step in designing an epitope-based vaccine. A pivotal role of CD4+ T cells in protection against H. pylori has been accepted, but few Th epitopes have been identified. In this study, two novel UreB CD4+ T cell epitopes were identified using PBMCs obtained from two H. pylori infected subjects. We determined the restriction molecules by antibody blocking and used various Epstein–Barr virus-transformed B lymphocyte cell lines (BLCLs) with different HLA alleles as APCs to present peptides to CD4+ T cells. These epitopes were DRB1*1404-restricted UreB373–385 and DRB1*0803-restricted UreB438–452. The T cells specific to these epitopes not only recognized autologous DCs loaded with recombinant UreB but also those pulsed with H. pylori whole cell lysates, suggesting that these epitope peptides are naturally processed. These epitopes have important value for designing an effective H. pylori vaccine. [Copyright &y& Elsevier]