UNASSIGNED: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.
UNASSIGNED: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.
UNASSIGNED: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P<0.05).
UNASSIGNED: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.

Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.

The presence of microplastics in the aquatic environment has attracted widespread attention. A large number of studies have assessed the effects of microplastics on the respiratory system of aquatic animals, but the results are not directly comparable across studies due to inconsistent evaluation criteria. Therefore, we adopted an integrated research approach that can integrate and parse complex data to improve reliability, conducted a systematic review and meta-analysis of 35 published studies, and elucidated the mechanisms of microplastic damage to cells. The results showed that PE had the greatest impact on aquatic animals, and fish were the most sensitive to the effects caused by microplastics, with oxidative stress induced by exposure concentrations exceeding 1000 µg/L or exposure times exceeding 28 days, leading to depletion of antioxidant defenses, cellular damage, inflammatory responses, and behavioral abnormalities. As this review is based on existing studies, there may be limitations in terms of literature quality, data availability and timeliness. In conclusion, we suggest to combat microplastic pollution by limiting plastic use, promoting plastic substitution and recycling, and enhancing microplastic capture degradation technologies.

Rare earth elements (REEs) are a new type of material resource which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. The long-term, large-scale mining and utilization of rare earths has caused serious environmental pollution and constitutes a global health issue, which has raised concerns regarding the safety of human health. However, the toxicity profile of suspended particulate matter in REEs in the environment, which interacts with the human body, remains largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.

The toxic effects of tire wear particles (TWPs) on organisms have attracted widespread concerns over the past decade. However, the underlying toxicity mechanism of TWPs, especially aged TWPs to marine microalgae remains poorly understood. This study investigated the physiological and metabolic responses of Phaeodactylum tricornutum to different concentrations of TWPs (Experiment 1), virgin and differently aged TWPs (Experiment 2) as well as their leachates and leached particles (Experiment 3). Results demonstrated that TWPs promoted the growth of microalgae at low concentrations (0.6 and 3 mg L-1) and inhibited their growth at high concentrations (15 and 75 mg L-1). Moreover, aged TWPs induced more profound physiological effects on microalgae than virgin TWPs, including inhibiting microalgae growth, decreasing the content of Chla, promoting photosynthetic efficiency, and causing oxidative damage to algal cells. Untargeted metabolomics analysis confirmed that aged TWPs induced more pronounced metabolic changes than virgin TWPs. This study represented the first to demonstrate that both particulate- and leachate-induced toxicity of TWPs was increased after aging processes, which was confirmed by the changes in the surface morphology of TWPs and enhanced release of additives. Through the significant correlations between the additives and the microalgal metabolites, key additives responsible for the shift of microalgal metabolites were identified. These results broaden the understanding of the toxicity mechanism of aged TWPs to microalgae at the physiological and metabolic levels and appeal for considering the effects of long-term aging on TWP toxicity in risk assessment of TWPs.

Pollution from microplastics (MPs) and nanoplastics (NPs) has gained significant public attention and has become a serious environmental problem worldwide. This review critically investigates MPs/NPs\' ability to pass through biological barriers in vertebrate models and accumulate in various organs, including the brain. After accumulation, these particles can alter individuals\' behaviour and exhibit toxic effects by inducing oxidative stress or eliciting an inflammatory response. One major concern is the possibility of transgenerational harm, in which toxic consequences are displayed in offspring who are not directly exposed to MPs/NPs. Due to their large and marked surface hydrophobicity, these particles can easily absorb and concentrate various environmental pollutants, which may increase their toxicity to individuals and subsequent generations. This review systematically provides an analysis of recent studies related to the toxic effects of MPs/NPs, highlighting the intricate interplay between co-contaminants in vitro and in vivo. We further delve into mechanisms of MPs/NPs-induced toxicity and provide an overview of potential therapeutic approaches to lessen the negative effects of these MPs/NPs. The review also emphasizes the urgency of future studies to examine the long-term effects of chronic exposure to MPs/NPs and their size- and type-specific hazardous dynamics, and devising approaches to safeguard the affected organisms.

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

The clinical effectiveness of nux-vomica in treating rheumatism and arthralgia is noteworthy; however, its nephrotoxicity has sparked global concerns. Hence, there is value in conducting studies on detoxification methods based on traditional Chinese medicine compatibility theory. Blood biochemistry, enzyme-linked immunosorbent assay, and pathological sections were used to evaluate both the nephrotoxicity of nux-vomica and the efficacy of the Jian Pi Tong Luo (JPTL) compound in mitigating this toxicity. Kidney metabolomics, using ultra-high-performance liquid chromatography-quadrupole-time-of-flight-MS (UPLC-Q-TOF-MS), was applied to elucidate the alterations in small-molecule metabolites in vivo. In addition, network pharmacology analysis was used to verify the mechanism and pathways underlying the nephrotoxicity associated with nux-vomica. Finally, essential targets were validated through molecular docking and western blotting. The findings indicated significant nephrotoxicity associated with nux-vomica, while the JPTL compound demonstrated the ability to alleviate this toxicity. The mechanism potentially involves nux-vomica activating the \"PTGS2/CYP2C9-phosphatidylcholine-arachidonic acid metabolic pathway.\" This study establishes a scientific foundation for the clinical use of nux-vomica and lays groundwork for further research and safety assessment of toxic Chinese herbal medicines.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility\'s central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment.

The ubiquitous presence of emerging contaminants (ECs) in the environment and their associated adverse effects has raised concerns about their potential risks. The increased toxicity observed during the environmental transformation of ECs is often linked to the formation of their transformation products (TPs). However, comprehension of their formation mechanisms and contribution to the increased toxicity remains an unresolved challenge. To address this gap, by combining quantum chemical and molecular simulations with photochemical experiments in water, this study investigated the formation of TPs and their molecular interactions related to estrogenic effect using the photochemical degradation of benzylparaben (BZP) preservative as a representative example. A non-targeted analysis was carried out and three previously unknown TPs were identified during the transformation of BZP. Noteworthy, two of these novel TPs, namely oligomers BZP-o-phenol and BZP-m-phenol, exhibited higher estrogenic activities compared to the parent BZP. Their IC50 values of 0.26 and 0.50 μM, respectively, were found to be lower than that of the parent BZP (6.42 μM). The binding free energies (ΔGbind) of BZP-o-phenol and BZP-m-phenol (-29.71 to -23.28 kcal·mol-1) were lower than that of the parent BZP (-20.86 kcal·mol-1), confirming their stronger binding affinities toward the estrogen receptor (ER) α-ligand binding domain. Subsequent analysis unveiled that these hydrophobic residues contributed most favorably to ER binding, with van der Waals interactions playing a significant role. In-depth examination of the formation mechanisms indicated that these toxic TPs primarily originated from the successive cleavage of ester bonds (OCH2C6H5 and COO group), followed by their combination with BZP*. This study provides valuable insight into the mechanisms underlying the formation of toxic TPs and their binding interactions causing the endocrine-disrupting effects. It offers a crucial framework for elucidating the toxicological patterns of ECs with similar structures.