Journal of Xenobiotics最新文献

High doses of the antibiotic azithromycin in freshwater environments can impact planktonic organisms at both the individual and community levels, influencing interactions at the base of the food web. This study investigated the effects of azithromycin on the natural rotifer community feeding on phytoplankton from a eutrophic water body and its potential impacts on rotifer fitness (impaired mastax movement: slow, irregular or reduced frequency), grazing and mortality following acute exposure. The natural plankton community was exposed to three azithromycin concentrations based on the EC₅₀ value (EC₅₀, 1/2 EC₅₀ and 1/3 EC₅₀) and assessed at different exposure times (24, 48 and 72 h) in the microcosm experiments. The results showed that all azithromycin concentrations reduced the fitness of the rotifers, as indicated by impaired mastax movement and/or slow, irregular or reduced movement frequency. Impairment of mastax movement altered rotifer grazing and the abundance of phytoplankton. The rotifers in the control group suppressed abundant phytoplankton growth, suggesting that azithromycin impairs interspecific interactions between plankton species. Rotifer mortality occurred at 48 h after azithromycin exposure in all treated samples. These findings show that the effects of azithromycin can be observed at different trophic levels, affecting both phytoplankton and zooplankton through altered biotic interactions and suppressed grazing.

Background: Beta-lactamase inhibitors (BLIs) are widely used with beta-lactam antibiotics to combat resistant infections, yet their safety profiles, especially for newer agents, remain underexplored. This study aimed to identify potential adverse event (AE) signals associated with BLIs using the USFDA Adverse Event Reporting System (USFDA AERS).

Methods: The USFDA AERS was queried for AE reports involving FDA-approved BLIs from March 2004 to March 2024. After removing duplicates, only reports with BLIs listed as primary suspects were included. Disproportionality analysis was conducted using frequentist and Bayesian approaches, with statistical significance assessed by chi-square testing.

Results: A total of 12,456 unique reports were analyzed. Common AEs across BLIs included hematologic disorders, hypersensitivity reactions, emergent infections, organ dysfunction, and neurological complications. Signal detection revealed specific associations: septic shock and respiratory failure with avibactam; lymphadenopathy and congenital anomalies with clavulanic acid; antimicrobial resistance and epilepsy with relebactam; disseminated intravascular coagulation and cardiac arrest with sulbactam; and agranulocytosis and conduction abnormalities with tazobactam. For vaborbactam, no distinct AE signals were identified apart from off-label use. Mortality was significantly more frequent with avibactam and relebactam (p < 0.0001).

Conclusions: This analysis highlights a spectrum of AE signals with BLIs, including unexpected associations warranting further investigation. While some events may reflect comorbidities or concomitant therapies, these findings underscore the importance of continued pharmacovigilance and targeted clinical studies to clarify causality and ensure the safe use of BLIs in practice.

Heavy metals, nitrogen, and phosphorus play a significant role in the marine ecosystem and human health. In this work, the concentrations of heavy metals, inorganic nitrogen, and phosphorus were determined to assess the distribution characteristics, risk levels, and possible sources in seawater from Taizhou Bay. The concentration ranges of Cu, Pb, Zn, Cd, Hg, As, ammonia, nitrate, nitrite, and phosphate were 1.87-3.65 μg/L, 0.10-0.95 μg/L, 2.98-16.80 μg/L, 0.07-0.38 μg/L, 0.011-0.043 μg/L, 0.93-2.06 μg/L, 0.011-0.608 mg-N/L, 0.012-0.722 mg-N/L, 0.001-0.022 mg-N/L, and 0.004-0.044 mg-P/L, respectively. The ecological risks were evaluated by the single factor index, Nemerow pollution index, and risk quotient. The results indicated that Taizhou Bay is not currently facing ecological risk related to heavy metals, nitrogen, and phosphorus, but the RQ values emphasized the urgency of strengthening continuous monitoring of As, Cu, and Zn. The results of Pearson's correlation indicated that salinity and chemical oxygen demand had a significant impact on nitrogen and phosphorus but little impact on heavy metals. Principal component analysis was then applied to analyze the probable origins of heavy metals and inorganic pollutants, suggesting that these pollutants were mainly derived from human activities along the bay.

Air pollution, particularly exposure to fine particulate matter (PM_2.5), poses a substantial risk to human health. Diesel exhaust particles (DEPs), a major constituent of PM_2.5, contain chemically reactive components that promote inflammation, oxidative stress, and immune dysfunction. Although the acute toxicity of PM_2.5 and DEPs has been extensively studied, their effects under "sub-toxic" conditions-defined here as exposures that do not cause measurable cytotoxicity based on LDH release but still impair cellular function-remain poorly understood. This study investigated the impact of low-toxicity exposure to DEPs and PM_2.5 on dendritic cell (DC) function using the human plasmacytoid DC-like cell line PMDC05. Cells exposed to DEPs or PM_2.5 exhibited minimal cytotoxicity but accumulated intracellular particles, resulting in impaired endocytosis, phagocytosis, and interferon gene expression upon TLR7 stimulation. These functional impairments were not observed following TLR4 stimulation, suggesting a selective disruption of endolysosomal signalling. The findings demonstrate that DEPs and PM_2.5 can impair innate immune responses without inducing cell death, likely through lysosomal overload and altered intracellular trafficking. This study identifies a non-cytotoxic pathway through which particulate air pollution may compromise antiviral immunity, thereby increasing susceptibility to infection in polluted environments. Strategies aimed at preserving lysosomal integrity and dendritic cell function may help mitigate the immunotoxic effects of airborne particles.

Children are more vulnerable to the adverse effects of pesticides due to physiological factors and behavioral habits. This study aimed to evaluate the impact of pesticide exposure on telomere length (TL) and the enzymatic activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and β-glucuronidase (β-Glu) in children ages 6 to 12 from an agricultural area in Mexico. A cross-sectional, descriptive, and analytical study was conducted involving 471 children. Blood samples were collected to assess TL through qPCR and enzymatic activity using established protocols. A pesticide exposure index (PEI) was developed incorporating biomarker levels, urinary dialkylphosphates (DAP), and proximity to farmland. No significant differences were observed in AChE activity across communities; however, BuChE activity was significantly higher in agricultural communities, while β-Glu activity varied among communities. Notably, children aged 6 in agricultural areas showed TL values similar to 12-year-old children in the reference community. Adjusted regression models revealed significantly shorter TL in children from agricultural communities and in children with moderate to high PEI. The findings indicate that chronic pesticide exposure was associated with telomere shortening in children, suggesting accelerated biological aging and potential genomic instability during critical developmental periods.

Due to the growing emergence of bacterial and fungal resistance, there is an urgent need for novel antimicrobial compounds. Cationic surfactants are effective antimicrobial agents; however, traditional quaternary ammonium compounds (QACs) are increasingly scrutinized due to their cytotoxicity, poor biodegradability, and harmful effects on aquatic ecosystems. While the antimicrobial efficacy of many new biocides, including QACs, has been extensively studied, comprehensive experimental strategies that simultaneously assess antimicrobial activity, mammalian cell toxicity, and ecotoxicity remain limited. Recent studies have reported that amino-acid-based surfactants containing arginine-phenylalanine and arginine-tryptophan exhibit excellent antibacterial activity and are biodegradable. This work extends their biological characterization to evaluate their potential applications. Specifically, we examined how variations in the head group architecture and hydrophobic moiety influence antifungal and antibiofilm activity. We also assessed how these structural parameters impact cytotoxicity and ecotoxicity. These compounds demonstrated strong activity against a wide range of Candida strains. Their hydrophobic character primarily influenced both antifungal efficacy and cytotoxicity. Importantly, these surfactants exhibited potent antimicrobial and antibiofilm effects at non-cytotoxic concentrations. Notably, their aquatic toxicity was significantly lower than that of conventional QACs.

Curcumin, the principal active component of turmeric, is a polyphenol that has been used in various countries for the treatment of numerous conditions due to its wide range of health benefits. Curcumin exhibits bifunctional antioxidant properties: the first is attributed to its chemical structure, which enables it to directly neutralize reactive oxygen species (ROS); the second is related to its ability to induce the expression of antioxidant enzymes via the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Both ROS and Nrf2 are closely associated with mitochondrial function and metabolism, and their dysregulation may lead to mitochondrial dysfunction, potentially contributing to the development of various pathological conditions. Therefore, curcumin treatment appears highly promising and is strongly associated with the preservation of mitochondrial function. The aim of this review is to summarize the current literature on the impact of curcumin's antioxidant properties on mitochondrial function. Specifically, studies conducted in different biological models are included, with emphasis on aspects such as mitochondrial respiration, antioxidant enzyme activity, interactions with mitochondrial membranes, and the role of curcumin in the regulation of intrinsic apoptosis.

Glyphosate Oxidoreductase (Gox) is an enzyme known to degrade glyphosate, an intensively used wide-spectrum herbicide. Although it was first reported back in 1995, much remains unknown about its role in bacteria, its distribution across the bacterial kingdom, and its structure. This information would be valuable for better understanding the degradation pathway of glyphosate and for discovering new enzymes with the same potential. In the present study, a holistic evolutionary analysis has been performed towards identifying homologue proteins within the FAD-dependent/binding oxidoreductases family and extracting critical characteristics related to conserved protein domains and motifs that play a key role in this enzyme's function. A total of 2220 representative protein sequences from 843 species and 10 classes of bacteria were analyzed, from which 4 protein domains, 2 characteristic/functional regions, and 8 conserved motifs were identified based on multiple sequence alignment and the annotated information from biological databases. The major goal of this study is the presentation of a novel phylogenetic tree for the Gox-related proteins to identify the major protein clusters and correlate them based on their sequence, structural, and functional information towards identifying new possible pharmacological targets that are related to this specific enzyme function. Considering the lack of information about Gox, the aim of this paper is to fill in these knowledge gaps, which can help determine the biological role of Gox and consequently better understand its function.

The extensive utilization of amorphous silica nanoparticles (SiNPs) has raised concerns regarding the potential health risks. Previous studies have indicated that SiNPs could trigger both the activation of heat shock proteins (HSPs) and epithelial-mesenchymal transition (EMT) in BEAS-2B cells; however, the underlying mechanisms require further elucidation. This study aimed to investigate how SiNPs activate the heat shock response (HSR) in BEAS-2B cells, which subsequently triggers EMT. Firstly, we observed that SiNPs were internalized by BEAS-2B cells and localized in the endoplasmic reticulum (ER), inducing ER stress. The ER stress led to the activation of SIRT1 by phosphorylation, which enhanced the nuclear transcriptional activity of HSF1 via deacetylation. HSF1 was found to upregulate the levels of HSP70 and HSP27 proteins, which further affected EMT-related genes and, ultimately, induced EMT. Additionally, 4-phenylbutyric acid (4-PBA) inhibited ER stress, which attenuated the SIRT1/HSF1 signaling pathway. The knockdown of SIRT1 and HSF1 using siRNA effectively suppressed the EMT progression. In summary, these results suggested that SiNPs activated the SIRT1/HSF1/HSPs pathway through ER stress, thereby triggering EMT in BEAS-2B cells. The present study identified a novel mechanism of SiNP-induced EMT, which has provided valuable insights for future toxicity studies and risk assessments of SiNPs.

This study investigated whether the Endocrine Disruptome and VirtualToxLab in silico platforms are suitable for predicting the endocrine disrupting effects of per- and polyfluoroalkyl substances (PFASs)-in particular, for interactions with oestrogen receptors (ERs) and androgen receptor (AR). Compounds included in the U.S. Environmental Protection Agency's PFAS working list were analysed with both models, and the results were compared with the available in vitro data regarding their modulation of nuclear receptors. Based on the identified prediction parameters, such as sensitivity, specificity, accuracy, and Mathews' correlation coefficient, VirtualToxLab was found to be a reliable model for predicting the reactivity of PFASs with AR, while a positive consensus approach of both platforms provided reliable predictions of the PFAS reactivity with ERα and ERβ. This study provides the evidence that Endocrine Disruptome and VirtualToxLab can be used as a tier 1 screening tool for assessment of the endocrine disrupting effect of PFASs. Furthermore, it demonstrates that the likelihood of endocrine disrupting properties increases with the lipophilicity of PFASs and identifies the understudied PFHpS, PFNS, PFDS, 9-Cl, NMeFOSAA, NEtFOSAA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 6:2 monoPAP, 8:2 monoPAP, and 5:3 acid as potential ligands of AR and/or ERs.