Toxins

Snakebite-related fatalities disproportionately affect populations in impoverished socio-economic regions, marked by limited access to adequate healthcare and constrained antivenom availability. Early medical intervention is pivotal in mitigating mortality and morbidity associated with snakebite envenoming (SBE). While clinical assessment remains fundamental in treating SBE, this review aims to spotlight objective parameters that could also affect outcomes. Selected studies that identify factors associated with poor outcomes are predominantly region-specific, single-site, and observational, yet collectively reveal similar findings. They consistently report factors such as treatment delays, susceptibility in vulnerable groups such as children and pregnant women, as well as various biochemical and haematological abnormalities. Acute kidney injury (AKI), low platelets, leucocytosis, abnormal coagulation, and elevated creatine kinase (CK) all show an association with poor outcomes. Furthermore, recognising rare and unusual SBE presentations such as adrenal insufficiency, severe hypertension, intracranial haemorrhage, acute angle closure glaucoma, and bowel ischaemia also has a bearing on outcomes. Despite the integration of these parameters into clinical decision tools and guidelines, the validation of this evidence is limited. This review underscores the imperative for high-quality, multi-centre studies aligned with consensus-driven Core Outcome Sets (COS) and Patient-Reported Outcome Measures (PROMS) to validate and strengthen the current evidence. Full article

Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp., which commonly and severely contaminate food/feed. ZEN severely affects food/feed safety and reduces economic losses owing to its carcinogenicity, genotoxicity, reproductive toxicity, endocrine effects, and immunotoxicity. To explore efficient methods to detoxify ZEN, we identified and characterized an efficient ZEN-detoxifying microbiota from the culturable microbiome of Pseudostellaria heterophylla rhizosphere soil, designated Bacillus amyloliquefaciens D-1. Its highest ZEN degradation rate reached 96.13% under the optimal condition. And, D-1 can almost completely remove ZEN (90 μg·g⁻¹) from coix semen in 24 h. Then, the D-1 strain can detoxify ZEN to ZEM, which is a new structural metabolite, through hydrolyzation and decarboxylation at the ester group in the lactone ring and amino acid esterification at C2 and C4 hydroxy. Notably, ZEM has reduced the impact on viability, and the damage of cell membrane and nucleus DNA and can significantly decrease the cell apoptosis in the HepG2 cell and TM4 cell. In addition, it was found that the D-1 strain has no adverse effect on the HepG2 and TM4 cells. Our findings can provide an efficient microbial resource and a reliable reference strategy for the biological detoxification of ZEN. Full article

Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom—polyclonal antibodies isolated from the plasma of hyperimmunised animals—which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability. Full article

An analysis methodology was optimised and validated for the quantification of opium alkaloids (OAs) in ground poppy seeds. This involved ultrasound-assisted extraction (UAE) and solid-phase extraction (SPE) purification before analysis using a high-performance liquid chromatography mass spectrometry detector (HPLC-MS/MS). UAE was optimised through the design of experiments with three factors and a three-level full factorial design. For SPE optimisation, a commercial material was compared with a previously synthesised material of SBA-15 silica functionalised with sulfonic groups (SBA-15-SO₃⁻). The synthesised material demonstrated superior efficiency with only 25 mg and proved to be reusable for up to four cycles. The methodology was properly validated in terms of linearity, limits of detection and quantification, and selectivity. Matrix effects were negligible; adequate recovery values (85–100%) and inter-day and intra-day precision (≤15%) were obtained. The greenness of the method was evaluated with the AGREEprep metric scale, being more environmentally friendly compared to OA analysis methods. Finally, the method was applied to different samples of ground poppy seeds and revealed a concentration of 140 mg/kg of morphine equivalents in one of the samples, surpassing the legislatively established limits by sevenfold. This highlights the need to analyse these types of samples to mitigate potential public health issues. Full article

Introduction: In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021. Results: During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by Nerium oleander (n = 186, 71%), followed by the Datura genus (4.2%), Ricinus communis (3.8%), Taxus baccata (1.9%), Digitalis purpurea (1.2%), Aconitum nape (1.9%), Myristica fragans (1.5%), and Pyracantha coccine (1.2%). Through the 262 plants poisonings, 19 patients among the 186 Nerium oleander poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving Nerium oleander. Discussion: The first involved species was Nerium oleander (71% of all plants poisonings), then Datura sp and Ricinus communis. It is explained by this native local species’ important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose. Material and Methods: This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS). Full article

Humans are constantly exposed to mixtures of different xenobiotics through their diet. One emerging concern is the Alternaria mycotoxin alternariol (AOH), which can occur in foods typically contaminated by the process contaminant acrylamide (AA). AA is a byproduct of the Maillard reaction produced in carbohydrate-rich foods during thermal processing. Given the genotoxic properties of AOH and AA as single compounds, as well as their potential co-occurrence in food, this study aimed to assess the cytotoxic, genotoxic, and mutagenic effects of these compounds in combination. Genotoxicity was assessed in HepG2 cells by quantifying the phosphorylation of the histone γ-H2AX, induced as a response to DNA double-strand breaks (DSBs). Mutagenicity was tested in Salmonella typhimurium strains TA98 and TA100 by applying the Ames microplate format test. Our results showed the ability of AOH and AA to induce DSBs and increase revertant numbers in S. typhimurium TA100, with AOH being more potent than AA. However, no synergistic effects were observed during the combined treatments. Notably, the results of the study suggest that the compounds exert mutagenic effects primarily through base pair substitutions. In summary, the data indicate no immediate cause for concern regarding synergistic health risks associated with the consumption of foods co-contaminated with AOH and AA. Full article

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, β3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5–17 years, while β3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children. Full article

The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches. Full article

Aspergillus flavus can cause mildew in corn, peanuts, and other foods as well as animal feed, which seriously endangers human and livestock health; thus, preventing A. flavus contamination is imperative. Previous studies have found that the secondary metabolites of Bacillus subtilis BS-Z15 have broad-spectrum-inhibiting fungal activity, further confirming that the main active inhibiting fungal substance is Mycosubtilin (Myco). In this paper, corn and peanuts were treated with 0, 100, and 200 μg/mL BS-Z15 secondary metabolites (BS-Z15-SMA) for 7 days, and the aflatoxin contamination prevention effect was examined. The results showed that with increasing BS-Z15-SMA concentration, the aflatoxin contamination prevention effect was significantly enhanced. The above toxicity phenomena became more significant with extended BS-Z15-SMA treatment time. Scanning electron microscopy showed that 4 μg/mL Myco treatment resulted in a dented A. flavus surface and breakage of both the conidial stem and the mycelium. Transcriptome results showed that Myco significantly affected gene expression in A. flavus spores. The downregulated genes were significantly enriched in cell wall synthesis, transcription and translation, transmembrane transport pathways, and pathways related to key enzymes for aflatoxin synthesis. These results suggest that Myco could be used as a new bioactive material to prevent aflatoxin synthesis and contamination. Full article

Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A total of 88 patients were included in the study, with chronic kidney disease stage 2 to 5 (without kidney replacement). We analysed the total concentrations of eight uremic toxins (trimethylamine N-oxide -TMAO-, Indoxyl Sulfate, P-cresyl-sulfate, Indole 3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid -CMPF-, Kynurenine, Hippuric acid and Phenylacetylglutamine) and three precursors of uremic toxins (Tyrosine, Phenylalanine and Tryptophan) in the saliva using LC-MS/MS. We observed, for the first time, the association between various dental scores: DMFT, FST, CPITN, and OHIS, and saliva uremic toxins and precursors: TMAO, indoxyl sulfate, or hippuric acid. Further prospective interventional studies are required to confirm our results. Full article

Harmful algal blooms (HABs) caused by lake eutrophication and climate change have become one of the most serious problems for the global water environment. Timely and comprehensive data on HABs are essential for their scientific management, a need unmet by traditional methods. This study constructed a novel digital twin lake framework (DTLF) aiming to integrate, represent and analyze multi-source monitoring data on HABs and water quality, so as to support the prevention and control of HABs. In this framework, different from traditional research, browser-based front ends were used to execute the video-based HAB monitoring process, and real-time monitoring in the real sense was realized. On this basis, multi-source monitored results of HABs and water quality were integrated and displayed in the constructed DTLF, and information on HABs and water quality can be grasped comprehensively, visualized realistically and analyzed precisely. Experimental results demonstrate the satisfying frequency of video-based HAB monitoring (once per second) and the valuable results of multi-source data integration and analysis for HAB management. This study demonstrated the high value of the constructed DTLF in accurate monitoring and scientific management of HABs in lakes. Full article

The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify secondary metabolites found in water samples collected in the IRL. Water samples from 20 sites of the IRL were collected during the wet and dry seasons over a three-year period. A panel of cell lines was used to test cytotoxicity. Hemagglutination, hemolysis, and inhibition of protein phosphatase 2A (PP2A) were also measured. Cytotoxic blooms were seen both in the south (Microcystis) and the north (Pyrodinium) of the IRL. Each toxin induced a consistent pattern of cytotoxicity in the panel of human cell lines assayed. During blooms, cytotoxicity due to a single type of toxin is obvious from this pattern. In the absence of blooms, the cytotoxicity seen reflected either a mixture of toxins or it was caused by an unidentified toxin. These observations suggest that other toxins with the potential to be harmful to human health may be present in the IRL. Moreover, the presence of toxins in the IRL is not always associated with blooms of known toxin-producing organisms. Full article

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation. Full article

Brucellosis is a notorious zoonotic disease caused by Brucella, which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS) are the main virulence factor of Brucella. LPS derived from Brucella are different and non-classical and are less toxic and less active than LPS isolated from E. coli. However, the effects and possible mechanisms of Brucella LPS-caused pregnancy loss remain to be revealed. In the present study, we investigated the effects of Brucella suis S2 LPS on early pregnancy loss in mice. The results indicated that embryo implantation failure was induced by Brucella LPS treatment in a dose-dependent manner. The injection of Brucella LPS mainly resulted in fibrinolysis in the decidual area of the uterus on the 6th day post coition (dpc), infiltration of large granular cells among the decidual cells near the embryo on the 8th dpc, a large number of gaps in the decidual area, and cell necrosis around the embryo. In addition, the expression of Cyclin D3 mRNA in the uterus on the 7th and 8th dpc and IGFBP-1 mRNA and the progesterone receptor in the uterus on the 6th and 7th dpc were also inhibited. Moreover, the expression of decidualization marker Cyclin D3 and decidualization prolactin-associated protein (dPRP) in endometrial stromal cells were also inhibited by Brucella LPS treatment in vitro. In summary, Brucella LPS affect the process of endometrial decidualization in mice by affecting the structure of the decidua and the expression of decidual marker factors in endometrial stromal cells. Full article

The presence of yessotoxins (YTXs) was analyzed in 10,757 samples of Galician bivalves from 2014 to 2022. Only YTX and 45-OH YTX were found. YTX was detected in 31% of the samples, while 45-OH YTX was found in 11.6% of them. Among the samples containing YTX, 45-OH YTX was detected in 37.3% of cases. The maximum recorded levels were 1.4 and 0.16 mg of YTX-equivalentsg⁻¹, for YTX and 45-OH YTX, respectively, which are well below the regulatory limit of the European Union. The YTX and 45-OH YTX toxicities in the raw extracts and extracts subjected to alkaline hydrolysis were strongly and linearly related. Due to the lack of homo-YTX in Galician samples, the effect of alkaline hydrolysis on homo-YTX and 45OH-Homo-YTX was only checked in 23 additional samples, observing no negative effect but a high correlation between raw and hydrolyzed extracts. Hydrolyzed samples can be used instead of raw ones to carry out YTXs determinations in monitoring systems, which may increase the efficiency of those systems where okadaic acid episodes are very frequent and therefore a higher number of hydrolyzed samples are routinely analyzed. The presence of YTX in the studied bivalves varied with the species, with mussels and cockles having the highest percentages of YTX-detected samples. The presence of 45-OH YTX was clearly related to YTX and was detected only in mussels and cockles. Wild populations of mussels contained proportionally more 45-OH YTX than those that were raft-cultured. Spatially, toxin toxicities varied across the sampling area, with higher levels in raft-cultured mussels except those of Ría de Arousa. Ría de Ares (ARE) was the most affected geographical area, although in other northern locations, lower toxin levels were detected. Seasonally, YTX and 45-OH YTX toxicities showed similar patterns, with higher levels in late summer and autumn but lower toxicities of the 45-OH toxin in August. The relationship between the two toxins also varied seasonally, in general with a minimum proportion of 45-OH YTX in July–August but with different maximum levels for raft-cultured and wild mussel populations. Interannually, the average toxicities of YTX decreased from 2014 to 2017 and newly increased from 2018 to 2021, but decreased slightly in 2022. The relationship between 45-OH YTX and YTX also varied over the years, but neither a clear trend nor a similar trend for wild and raft mussels was observed. Full article

Aflatoxin B₁ (AFB₁) is one of the most toxic and harmful fungal toxins to humans and animals, and the fundamental way to prevent its entry into humans is to detect its presence in advance. In this paper, the monoclonal antibody mAbA2-2 was obtained via three-step sample amplification and multi-concentration standard detection using a subcloning method based on the limited dilution method with AFB₁ as the target. A dynamic and pseucdo-homogeneous magnetic beads enzyme-linked immunosorbent assay (MBs-icELISA) was established using the prepared antibody as the recognition element and immunomagnetic beads as the antigen carrier. The MBs-icELISA showed good linear correlation in the concentration range of 0.004–10 ng/mL with R² = 0.99396. The limit of detection (LOD) of the MBs-icELISA for AFB₁ was 0.0013 ng/mL. This new ELISA strategy significantly shortened AFB₁ detection time through improved sensitivity compared to the conventional ELISA method. Full article

The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity. In 1984, the waters of the Great Salt Lake occupied 8500 km². Nearly four decades later, the waters occupy 2500 km²—a reduction in surface area of 71%. With predominantly westerly winds, there is a potential for the adjacent metropolitan residents to the east to be exposed to airborne cyanobacteria- and cyanotoxin-containing dust. During the summer and fall months of 2022, air and dried sediment samples were collected and assessed for the presence of BMAA which has been identified as a risk factor for ALS. Collection of air samples equivalent to a person breathing for 1 h resulted in BMAA and isomers being found in some air samples, along with their presence in exposed lakebed samples. There was no clear relationship between the presence of these toxins in airborne and adjacent lakebed samples, suggesting that airborne toxins may originate from diffuse rather than point sources. These findings confirm that continued low water levels in the Great Salt Lake may constitute an increasing health hazard for the 2.5 million inhabitants of communities along the Wasatch Front. Full article

Colombia encompasses three mountain ranges that divide the country into five natural regions: Andes, Pacific, Caribbean, Amazon, and Orinoquia. These regions offer an impressive range of climates, altitudes, and landscapes, which lead to a high snake biodiversity. Of the almost 300 snake species reported in Colombia, nearly 50 are categorized as venomous. This high diversity of species contrasts with the small number of studies to characterize their venom compositions and natural history in the different ecoregions. This work reviews the available information about the venom composition, isolated toxins, and potential applications of snake species found in Colombia. Data compilation was conducted according to the PRISMA guidelines, and the systematic literature search was carried out in Pubmed/MEDLINE. Venom proteomes from nine Viperidae and three Elapidae species have been described using quantitative analytical strategies. In addition, venoms of three Colubridae species have been studied. Bioactivities reported for some of the venoms or isolated components—such as antibacterial, cytotoxicity on tumoral cell lines, and antiplasmodial properties—may be of interest to develop potential applications. Overall, this review indicates that, despite recent progress in the characterization of venoms from several Colombian snakes, it is necessary to perform further studies on the many species whose venoms remain essentially unexplored, especially those of the poorly known genus Micrurus. Full article

Microbial interactions including competition, mutualism, commensalism, parasitism, and predation, which can be triggered by nutrient acquisition and chemical communication, are universal phenomena in the marine ecosystem. The interactions may influence the microbial population density, metabolism, and even their environmental functions. Herein, we investigated the interaction between a heterotrophic bicosoecid flagellate, Pseudobodo sp. (Bicoecea), and a dinoflagellate, Gambierdiscus balechii (Dinophyceae), which is a well-known ciguatera food poisoning (CFP) culprit. The presence of Pseudobodo sp. inhibited the algal proliferation and decreased the cardiotoxicity of zebrafish in the algal extract exposure experiment. Moreover, a significant difference in microbiome abundance was observed in algal cultures with and without Pseudobodo sp. Chemical analysis targeting toxins was performed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with molecular networking (MN), showing a significant alteration in the cellular production of gambierone analogs and some super-carbon chain compounds. Taken together, our results demonstrated the impact of heterotrophic flagellate on the photosynthetic dinoflagellates, revealing the complex dynamics of algal toxin production and the ecological relationships related to dinoflagellates in the marine environment. Full article