Exosomes as mediators of signal transmitters in biotoxins toxicity: a comprehensive review.

Small membranes known as exosomes surround them and are released by several cell types both in vitro and in vivo. These membranes are packed with a variety of biomolecules, including proteins, lipids, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and non-coding RNA (ncRNA). As a source of biological nanomaterials, exosomes play a role in information and substance transmission between cells and have been identified as a general method of facilitating communication during interactions between the body, target organs, and toxins.. In order to understand the changes and mechanism of the composition and level of exosomes after biotoxin infection, this review focuses on current findings on the exosomes and highlights their novel uses in the toxicity mechanism. Exosomes are mainly used as a delivery carrier or mediated by receptors, and play an immune role after the toxin enters the body. This review expounds on the importance of exosomes in the toxicological mechanism of biotoxins and provides new insights for further diagnosis of toxic biomarkers, detoxification, and treatment development.

Research Progress of Safety of Zearalenone: A Review.

Zearalenone, a mycotoxin produced by fungi of the genus Fusarium, widely exists in animal feed and human food. The structure of zearalenone is similar to estrogen, so it mainly has estrogenic effects on various organisms. Products contaminated with zearalenone can pose risks to animals and humans. Therefore, it is imperative to carry out toxicological research on zearalenone and evaluate its risk to human health. This paper briefly introduces the production, physical, and chemical properties of zearalenone and the research progress of its toxicity kinetics, focusing on its genetic toxicity, reproductive toxicity, hepatotoxicity, immunotoxicity, carcinogenicity, endocrine interference, and its impact on intestinal health. Finally, the progress of the risk assessment of human exposure is summarized to provide a reference for the follow-up study of zearalenone.

Downregulation of m6A Methyltransferase in the Hippocampus of Tyrobp -/- Mice and Implications for Learning and Memory Deficits.

Loss-of-function mutations in the gene that encodes TYRO protein kinase-binding protein (TYROBP) cause Nasu-Hakola disease, a heritable disease resembling Alzheimer's disease (AD). Methylation of N6 methyl-adenosine (m6A) in mRNA plays essential roles in learning and memory. Aberrant m6A methylation has been detected in AD patients and animal models. In the present study, Tyrobp-/- mice showed learning and memory deficits in the Morris water maze, which worsened with age. Tyrobp-/- mice also showed elevated levels of total tau, Ser202/Thr205-phosphorylated tau and amyloid ß in the hippocampus and cerebrocortex, which worsened with aging. The m6A methyltransferase components METTL3, METTL14, and WTAP were downregulated in Tyrobp-/- mice, while expression of demethylases that remove the m6A modification (e.g., FTO and ALKBH5) were unaltered. Methylated RNA immunoprecipitation sequencing identified 498 m6A peaks that were upregulated in Tyrobp-/- mice, and 312 m6A peaks that were downregulated. Bioinformatic analysis suggested that most of these m6A peaks occur in sequences near stop codons and 3'-untranslated regions. These findings suggest an association between m6A RNA methylation and pathological TYROBP deficiency.

Regulation of apoptosis by Pacific oyster Crassostrea gigas reveals acclimation strategy to CO2 driven acidification.

Ocean acidification (OA) has posed formidable threats to marine calcifiers. In response to elevated CO2 levels, marine calcifiers have developed multiple strategies to survive, such as taking advantage of apoptosis, but its regulation mechanism remains largely unknown. Here, we used the Pacific oyster Crassostrea gigas as model to understand the apoptotic responses and regulation mechanism at short- (7 d) to long-term (56 d) CO2 exposure (pH = 7.50). The apoptosis of hemocytes was significantly induced after short-term treatment (7-21 d) but was suppressed under long-term CO2 exposure (42-56 d). Similarly, caspase-3 and caspase-9 were also increased post short-term exposure and fell back to normal levels after long-term exposure. These data together indicated diverse regulation mechanisms of apoptosis through different exposure periods. Through analysis of the B-cell lymphoma 2 (Bcl-2) family mitochondrial apoptosis regulators, we showed that only CgBcl-XL's expression kept at high levels after 42- and 56-day CO2 exposure. CgBcl-XL shared sequence, and structural similarity with its mammalian counterpart, and knockdown of CgBcl-XL in hemocytes via RNA interference promoted apoptosis. The protein level of CgBcl-XL was significantly increased after long-term CO2 exposure (28-56 d), and its distribution in hemocytes became more concentrated and dense. Therefore, CgBcl-XL serves as an essential anti-apoptotic protein for tipping the balance of cell apoptosis, which may play a key role in survival under long-term CO2 exposure. These results reveal a potential adaptation strategy of oysters towards OA and the variable environment changes through the modulation of apoptosis.