Toxins最新文献

Aflatoxin B1 (AFB1) contamination is a significant issue for the safety of edible oils. Biodegradation of mycotoxins represents a green and efficient approach. However, enzymes exhibit low catalytic activity and stability under harsh conditions, leading to rapid deactivation in edible oils. Zeolitic imidazolate frameworks (ZIFs) possess high specific surface areas, tunable pore sizes, and excellent thermal stability. Immobilizing enzymes on ZIFs can address the problem of enzyme inactivation during application. Although the stability of the enzyme can be enhanced after immobilization, the overall enzymatic activity remains limited. To overcome the issues of low catalytic activity and poor cycling stability associated with enzymes immobilized on ZIF-8 using 2-methylimidazole (2-mIM) as the ligand, this study optimized the ZIF structure through a ligand screening strategy. Both encapsulation efficiency and cycling stability were enhanced. This research found that the activity of Lac@ZIFs(IM), which uses imidazole (IM) as the ligand, was 2.16 times that of Lac@ZIF-8. The degradation efficiency of AFB1 reached 93% within 4 h in edible oil using Lac@ZIFs(IM) as the catalyst, which was 21-fold higher than that of free laccase. Lac@ZIFs(IM) exhibited excellent activity in the continuous flow system. After 20 h of continuous reaction, the activity of Lac@ZIFs(IM) was 6.6 times that of Lac@ZIF-8. This study provides a novel approach for the efficient enzymatic degradation of mycotoxins.

Chronic exposure to the cyanotoxin microcystin-LR is an emerging environmental driver of non-alcoholic fatty liver disease (NAFLD); however, the initiating molecular events at sub-lethal, environmentally relevant concentrations remain elusive. Current safety guidelines focus primarily on acute injury, potentially overlooking silent metabolic disruption. The present study investigates the early metabolic toxicity of chronic low-dose microcystin-LR (10 µg/L) in a 7-week rat model, specifically focusing on pre-symptomatic perturbations in lipid homeostasis. By integrating biochemical profiling with multivariate systems toxicology (LASSO and PLS-DA), we identified a specific phenotype of "Silent Hepatic Total Cholesterol Accumulation" (T-CHOL +16%, p = 0.01) occurring in the absence of systemic dyslipidemia or overt liver injury. Mechanistic analysis revealed a specific dual failure of cholesterol homeostasis, characterized by the paradoxical upregulation of the influx transporter Ldlr (LASSO coef +0.661) and the suppression of the efflux transporter Abcg1 (PLS1 loading -0.358). Crucially, Ldlr upregulation occurred despite the concomitant transcriptional downregulation of Srebp2 (Spearman ρ = -0.585), indicating a regulatory uncoupling mechanism. We propose that microcystin-LR-induced protein phosphatase 2A (PP2A) inhibition likely drives this uncoupling via a post-transcriptional override-possibly involving ERK/RSK-mediated Ldlr mRNA stabilization. Concurrently, this inhibition appears to block LXR-mediated Abcg1 expression through sustained AMPK hyperactivation resulting from the loss of dephosphorylation. These findings indicate liver-specific cholesterol accumulation as the critical first step of environmental NAFLD pathogenesis, suggesting that current WHO guidelines (1 µg/L) may require re-evaluation regarding metabolic safety. We propose the hepatic Ldlr/Abcg1 ratio as a potential early biomarker for revised risk assessment.

Extreme weather impacts the ecological niches of fungi, altering mycotoxin risks in wildlife. We analyzed mycotoxin carry-over into European fallow deer (Dama dama) milk across seasons and assessed how drought influences the shift from Fusarium to Aspergillus mycotoxins and affects physiological resilience. Samples were collected during 2021/2022 and a drought-stricken 2022/2023 from South Transdanubia and Northeastern Hungary. Aflatoxin B1/M1 (AFB1/AFM1), Fumonisin B1 (FB1), Deoxynivalenol (DON), Zearalenone (ZEN), and Body Condition Scores (BCS) were measured to evaluate the impact of exposure on health status. The severe drought significantly altered the mycotoxin profile: ZEN levels declined significantly (from a median of 0.28 to 0.00 ng/mL), consistent with the moisture requirements of Fusarium graminearum, whereas DON concentrations increased. Concurrently, AFM1 persisted, exhibiting increased variance and extreme outliers in the maize-dominated South Transdanubian region. Distinct pharmacokinetic patterns were observed, and positive correlations were observed between milk and feces for lipophilic toxins, validating milk as a possible biomarker. Hydrophilic DON showed no correlation despite its accumulation. Emergence of "Poor" BCS group carrying loads supports "condition-dependent foraging" hypothesis, as stressed individuals are forced to consume contaminated resources, exacerbating oxidative stress and metabolic deficits.

Background: Post-stroke spasticity (PSS) is a common complication in stroke survivors, significantly impairing functional recovery and quality of life. Despite its prevalence, Italy lacks national guidelines or structured good clinical practice documents, resulting in heterogeneous clinical management.

Methods: An Italian Delphi study was conducted to establish expert-based recommendations for PSS management. A panel of 93 rehabilitation medicine specialists and neurologists, each with over 5 years of experience in PSS management with botulinum toxin A (BoNT-A), participated in two rounds of voting on 47 statements drafted and approved by seven Key Opinion Leaders (KOLs), recognized for their national and international expertise. Consensus was defined as ≥75% of respondents answering 'strongly agree' or 'somewhat agree'.

Results: In Round 1, consensus was reached for 90% of statements; five items did not achieve the threshold. After revision and a second round, consensus was achieved for all items, including consideration of lesion site in clinical management and the role of adjuvant post-injection interventions. The panel's heterogeneity ensured broad representativeness.

Conclusion: This Delphi study provides the first structured Italian expert recommendations for PSS management. Full consensus was reached in all 47 statements and in the Symptoms domain, particularly regarding pain, stiffness and heaviness, which highlights the importance of a structured framework to support consistent, individualized care. By standardizing patient assessment, treatment planning, and follow-up strategies, these findings provide a practical reference for clinicians.

The biotransformation of nodularin (NOD) is one of the critical strategies for regulating their biological toxicity. To investigate the effects and mechanisms of the biotransformation pathway, this study synthesized six biotransformation products of nodulein-R (NODR-BTPs) and evaluated their inhibitory effects on protein phosphatase 1 (PP1) through protein phosphatase inhibition assays. The inhibitory effects of NODR-BTPs diminished as the molecular weight and polarity of the introduced biological thiols increased, indicating that biotransformation is an efficient mechanism for modulating the biological toxicity of NODR. Through ligand replacement and molecular docking techniques, the potential regulatory mechanisms underlying the primary interaction processes between NODR-BTPs and PP1 were further elucidated. The introduced biological thiols improved the hydrogen bonding for Glu₂₇₅ ← "Mdhb⁵"and enhanced the electropositive-electronegative interactions between "Mdhb⁵" and PP1. This resulted in an increase in the positive accessible surface area, negative accessible surface area, and polar surface area at the interface of "Mdhb⁵" and PP1. The biothiol moiety subsequently enhanced hydrogen bonds for Arg₉₆ → MeAsp¹ and Arg₉₆ → Glu⁴, thereby affecting the binding of these key interaction sites to PP1. This further diminished interactions between conserved amino acids in PP1 and Mn²⁺ ions, including the ionic bond for Asp₉₂-Mn₁²⁺ and metal bonds for Asp₆₄-Mn₁²⁺ and His₆₆-Mn₁²⁺, leading to increased exposure of Mn²⁺ ions. The regulatory mechanisms facilitated the restoration of PP1 catalytic activity.

Mycotoxin contamination represents a major public health and economic burden worldwide. Aflatoxins, particularly aflatoxin B₁, are the most detrimental for human health. In this review, we discuss the sources of exposure and geographic distribution. The prevalence of aflatoxin-albumin/lysine adduct detection in humans varies dramatically across the world, from 0% reported in two European studies to up to 100% reported in studies from parts of Africa and Asia. We also summarize the disease outcomes that aflatoxins are associated with in humans. We focus particularly on cancer outcomes, which aflatoxins can cause through mutagenic DNA adducts, oxidative stress, mitochondrial dysfunction, immune effects, and epigenetic changes. Synergy with hepatitis B virus and potentially with other mycotoxins can also increase risk. Minimization of aflatoxin exposure requires an integrative approach, beginning at the farm level and continuing through pre-harvest, post-harvest, storage, and the consumer level. New developments in technology, such as electrochemical biosensors and artificial intelligence algorithms, are being piloted and could help improve detection and decontamination efforts. Further, new tests for aflatoxin exposure in humans (e.g., blood spot assays) could assist biomonitoring efforts. Despite regulatory standards in most countries for the maximum allowable level of aflatoxins in food products and animal feed, exposure remains high in many parts of the world and might be increasing even in countries with historically low exposure. Integration of these tools in a One Health framework is essential to reduce the current and future burden of aflatoxin-related disease.

While harmful cyanobacterial blooms (HCBs) are extensively characterized in eutrophic lakes, the ecological dynamics of connected river networks remain oversimplified, obscuring the mechanisms of community assembly and toxin distribution across the lake-river interface. This study investigated the spatial heterogeneity of HCBs and microcystins (MCs) in the Lake Taihu watershed, revealing a complex functional divergence between lotic and lentic ecosystems. The rivers functioned as primary nutrient sources, with Total Nitrogen (3.35 ± 1.52 mg·L^-1) and Total Phosphorus (0.21 ± 0.22 mg·L^-1) concentrations being 1.7-fold and 1.8-fold higher, respectively, than those in the lake during peak periods. Conversely, the lake acted as a biological sink, supporting a peak cyanobacterial density (3.32 × 10⁷ cells·L^-1) nearly 1.5 times that of the river network. Phytoplankton community analysis revealed distinct ecological niches: while the lentic lake environment was almost exclusively dominated by colonial Microcystis (>90% relative abundance), the lotic river networks harbored a diverse assemblage with significant contributions from filamentous Oscillatoria and Dolichospermum. Correspondingly, intracellular MC (IMC) in the lake (up to 14.5 μg·L^-1) significantly exceeded riverine levels (generally <1.0 μg·L^-1). Despite these compositional differences, toxin dynamics exhibited strong bidirectional coupling (r > 0.75, p < 0.01), suggesting a spillover effect where the lake determines the watershed's toxin burden during rivers outflow period. Redundancy Analysis (RDA) further elucidated that limnetic blooms were primarily regulated by water temperature and pH, whereas riverine communities were strictly constrained by hydrodynamic flow. Consequently, the health risk assessment revealed a highly heterogeneous landscape where, beyond the northern lake bays, specific semi-lentic river segments emerged as cryptic hotspots. These findings demonstrate that while nutrients fuel the system, hydrodynamic conditions act as the ultimate ecological filter determining the spatiotemporal distribution of cyanobacterial risks, necessitating an integrated approach to monitoring the entire lake-river continuum.

Microplastics (MPs) and microcystins (MCs) frequently occur together in eutrophic environments. However, their interaction in aquatic systems is poorly understood. This study aimed to examine how MP particle size and salinity influence the adsorption behaviour of the cyanotoxin MC-LR onto polystyrene MPs (PS-MPs). Two particle size groups (180-500 µm and 700-1000 µm diameter) were mixed with a microcystin-LR (MC-LR) producing Microcystis aeruginosa lysate in either freshwater (salinity ≤ 0.05 g L^-1) or brackish water (salinity 16.00 g L^-1) and incubated at 25 °C in an orbital shaker for 48 h. MC-LR bound to PS-MPs was extracted and measured using triple quadrupole LC-MS/MS. The MC-LR adsorption rate exhibited a degree of oscillation throughout time, with peak adsorption observed for the smaller-sized PS-MPs at 1.60% in freshwater after 4 h and 4.60% in brackish water after 6 h. For the larger particle size of PS-MPs, peak adsorption occurred after 4 h, reaching 0.1% in freshwater and 1.3% in brackish water. This study provides evidence that PS-MPs have limited potential as vectors of MC-LR in eutrophic freshwater and brackish environments.

The introduction of botulinum neurotoxin (BoNT) to our therapeutic strategies has been an incredible success story [...].

ADP-ribosylation of nucleic acids is a modification found in both eukaryotes and bacteria, where it contributes to genome maintenance but can also serve as a toxic mechanism used by bacterial toxins to disrupt essential cellular processes. This modification is catalysed by ADP-ribosyltransferases and can be reversed by antagonistic ADP-ribosylgylcohydrolase enzymes. To date, ADP-ribosylation of nucleic acid bases has been described only for adenosine, guanosine, and thymidine. Here we report the ADP-ribosylation of cytidine, catalysed by members of the pierisin family of bacterial toxins-ScARP (SCO5461) and Scabin. We also show that ADP-ribosylation of cytidine is reversible through removal by certain NADAR family proteins, including NADAR proteins from the bacterium Streptomyces coelicolor (SCO5665) and the sponge Amphimedon queenslandica, as well as YbiA-type NADAR proteins. The conservation of cytidine de-ADP-ribosylating activity of NADAR proteins across phylogenetically distant species suggests that this modification may have important physiological significance.