Toxicon最新文献

{"title":"Hepatoprotective effects of dandelion against AFB1-induced liver injury are associated with activation of bile acid-FXR signaling in chicks","authors":"Zhe Peng ,&nbsp;Jiang Deng ,&nbsp;Ze-Jing Xu ,&nbsp;Qin-Jian Niu ,&nbsp;Lamesgen Dessalegn ,&nbsp;Alainaa Refaie ,&nbsp;Lv-Hui Sun ,&nbsp;Yan-Ping Feng ,&nbsp;Meng Liu","doi":"10.1016/j.toxicon.2025.108419","DOIUrl":"10.1016/j.toxicon.2025.108419","url":null,"abstract":"<div><div>This study aimed to investigate the protective effects of dandelion against AFB₁-induced hepatotoxicity through the regulation of the FXR signaling pathway in chicks. A total of 144 one-day-old male broilers were randomly assigned to three groups and received a basal diet (BD), and BD supplemented with 0.5 mg/kg of AFB₁ or 0.5 mg/kg AFB₁ with 0.4 % dandelion for 3 weeks. The results showed that the AFB₁ treatment caused liver injury and decreased the concentrations of albumin and alkaline phosphatase in serum and increased the total bile acid concentration in serum and liver. Dietary AFB₁ supplementation also induced hepatocyte swelling, necrosis, neutrophils infiltration and lipid deposition in the liver. Notably, dietary dandelion supplementation alleviated these alterations induced by AFB₁. Additionally, dietary dandelion supplementation alleviated AFB₁-induced changes in ileum microbiota and decreased the abundance of <em>Lactobacillus</em>, <em>L. vaginalis</em>, and <em>L. acidophilus</em> compared to the AFB₁ treatment. Furthermore, AFB₁ downregulated <em>Baat</em>, <em>Ntcp</em>, <em>Acc</em>, FXR, SHP, and SREBP-1c expression, and upregulated <em>Cyp8b1</em>, <em>Bacs</em>, <em>Fas</em>, <em>Pparα</em>, <em>Lxrα</em> and CYP7A1 expression in liver. Meanwhile, AFB₁ also downregulated <em>Fgf19</em>, <em>Ostα</em>, <em>Ostβ</em> and FXR expression and upregulated SHP expression in the ileum. Conclusively, dietary dandelion supplementation protected broilers from AFB₁-induced hepatotoxicity, potentially due to the activation of bile acid-FXR signaling pathway.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108419"},"PeriodicalIF":2.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A decade of toxicity research on sea urchins: A review","authors":"Petra Burić,&nbsp;Ines Kovačić,&nbsp;Kornelija Ilić,&nbsp;Dora Šižgorić Winter,&nbsp;Moira Buršić","doi":"10.1016/j.toxicon.2025.108420","DOIUrl":"10.1016/j.toxicon.2025.108420","url":null,"abstract":"<div><div>Sea urchins have been used extensively in toxicity studies worldwide. In this review, toxicity studies that used sea urchins as the organism of choice during the last decade (from 2014 to 2023) were assessed. The selected articles were analysed for the following main points: (i) the world regions where sea urchins are predominantly utilized in toxicological studies, (ii) the sea urchin species most frequently employed, (iii) the most frequently used toxicological assays, and (iv) the chemical under examination. The results indicate that the scientists in Europe most often decide to work with this organism. Specifically, sea urchins were sampled from the Tyrrhenian Sea and the Atlantic coast of Spain and Portugal for the toxicity studies. The most frequently selected species of sea urchin is <em>Paracentrotus lividus</em>, followed by <em>Arbacia lixula</em> and <em>Strongylocentrotus purpuratus</em>. Furthermore, the toxicity experimental method that is most often applied is the embryotoxicity that includes a version of the sea urchin embryo-larval development test endpoints. Currently metals are the most frequently researched pollutant of this species as target organism, followed by environmental samples (e.g. sediment or wastewaters), plastics and nanoparticles (metal and metal oxide nanoparticles, silicate nanoparticles, polystyrene nanoparticles and carbon nanotubes). At the end, the obtained results were discussed and recommendations for further work with sea urchins in toxicological studies were proposed.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108420"},"PeriodicalIF":2.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxins under a Rock: Proteo-transcriptomic analysis reveals the venom composition of the Pseudoscorpion Ammogarypus lawrencei (Pseudoscorpiones: Garypidae)","authors":"Jonas Krämer ,&nbsp;Tim Lüddecke ,&nbsp;Danilo Harms ,&nbsp;Sabine Hurka ,&nbsp;Reinhard Predel","doi":"10.1016/j.toxicon.2025.108417","DOIUrl":"10.1016/j.toxicon.2025.108417","url":null,"abstract":"<div><div>Pseudoscorpions represent one of the venomous animal groups least investigated with respect to their venom composition. So far, the venom of only a few species of these tiny arachnids has been analyzed, among which only the cosmopolitan species <em>Chelifer cancroides</em> and the Australian <em>Synsphyronus apimelus</em> have been investigated in more detail. Here, we advance the current understanding on pseudoscorpion toxins by unveiling the venom composition of the African species <em>Ammogarypus lawrencei</em> via proteo-transcriptomics-guided venomics. Belonging to the same family as <em>S</em>. <em>apimelus</em> whose venom was analyzed solely by a transcriptomic approach, we found the highest similarities between putative venom compounds in these species. Instead of an enzyme-rich venom predicted for <em>S. apimelus</em>, we found the venom of <em>A</em>. <em>lawrencei</em> to be dominated by Cysteine-rich peptides (CRPs). Many of these peptides show moderate similarity to neurotoxins found primarily in other arachnids, although a large proportion could not be annotated in more detail due to their high sequence disparity. Enzymes are a minor component in the venom of <em>A</em>. <em>lawrencei</em> and classified mostly as peptidases and triacylglycerol lipases, likely fulfilling a predigestive function or acting as spreading factors. Lastly, we identified a range of linear and putatively antimicrobial peptides in the <em>A</em>. <em>lawrencei</em> venom, which seem to be unrelated to the previously identified checacin-type linear peptides identified in the venom of <em>C. cancroides</em>. Our study provides valuable insights into the molecular diversity encoded in pseudoscorpion venom glands and identifies a range of novel biomolecules with putative translational potential.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108417"},"PeriodicalIF":2.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deoxynivalenol induces pyroptosis and IL-1β secretion via P2X7R signal in murine RAW264.7 macrophages","authors":"Zihui Qin ,&nbsp;Huayue Zhang ,&nbsp;Jie Zhang ,&nbsp;Tushuai Li ,&nbsp;Kamil Kuca ,&nbsp;Jiaguo Liu ,&nbsp;Wenda Wu","doi":"10.1016/j.toxicon.2025.108418","DOIUrl":"10.1016/j.toxicon.2025.108418","url":null,"abstract":"<div><div>Deoxynivalenol (DON), a trichothecene mycotoxin, exerts pro-inflammatory and immunomodulatory activity. Interleukin (IL)-1β serves a crucial part as a gate keeper of inflammation in DON-induced macrophages, but an overview of how DON exposure elicits IL-1β secretion from RAW264.7 cells has not been fully illustrated. Here we found that the cellular phenomenon, involved with a type of programmed cell death known as pyroptosis, contains: 1) increase of pro-IL-1β expression, 2) motivation of caspase-1, 3) caspase-1-dependent maturement of IL-1β, 4) caspase-1 fragmentation of gasdermin D (GSDMD), and 5) IL-1β secretion through GSDMD pore. Mechanistically, the present study certified that DON both as first and second signals engaged in IL-1β release is mediated by purinergic P2X7 receptor (P2X7R)-Src signaling. During this process, P2X7R signal is required for GSDMD pore forming course in ASC-independent manner. Moreover, blocking of K⁺ efflux, ROS formation, as well as cathepsin B activity decreases IL-1β export. Our data show that exposure to DON does cause pyroptosis and IL-1β secretion via P2X7R signal in RAW264.7 macrophages. Overall, these results provide new mechanistic clue for DON as a pro-inflammatory factor in innate immune signaling events.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108418"},"PeriodicalIF":2.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracerebral hemorrhage (hemorrhagic stroke) secondary to Bothrops spp. snakebite envenomation in a horse","authors":"Ana Lívia Vasconcelos de Sousa ,&nbsp;Davi Emanuel Ribeiro de Sousa ,&nbsp;Isabel Luana de Macêdo ,&nbsp;Liz de Albuquerque Cerqueira ,&nbsp;Yasmin Nunes Godoy da Fonseca ,&nbsp;Andressa Barbosa Oliveira ,&nbsp;Letícia Vilela Silva das Chagas ,&nbsp;Geisiana Barbosa Gonçalves ,&nbsp;Hennrique Caetano Veado ,&nbsp;Kelly Moura Keller ,&nbsp;Antônio Carlos Lopes Câmara ,&nbsp;Mizael Machado ,&nbsp;Márcio Botelho de Castro","doi":"10.1016/j.toxicon.2025.108408","DOIUrl":"10.1016/j.toxicon.2025.108408","url":null,"abstract":"<div><div>This report describes the first documented case of intracerebral hemorrhage (ICH) in a horse following <em>Bothrops</em> snakebite envenomation. A 3-year-old mare developed acute kidney injury, systemic hemorrhage, and neurological signs before euthanasia. Postmortem findings confirmed massive ICH with intralesional venom identified by immunohistochemistry. Delayed treatment and insufficient antivenom likely contributed to the outcome. This case highlights the potential for cerebrovascular complications following <em>Bothrops</em> snakebite envenomation in horses, which may present as subtle neurological signs.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108408"},"PeriodicalIF":2.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in paediatric snakebite management: physician perspectives from rural Sri Lanka","authors":"Kavinda Dayasiri ,&nbsp;Indika Gawarammana ,&nbsp;Shaluka Jayamanne","doi":"10.1016/j.toxicon.2025.108410","DOIUrl":"10.1016/j.toxicon.2025.108410","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to explore the challenges encountered by paediatric emergency care teams in managing snakebite cases in children across three major referral hospitals in Sri Lanka.</div></div><div><h3>Methods</h3><div>A qualitative exploratory study was conducted using focus group discussions (FGDs) with physicians who manage paediatric snakebites from Polonnaruwa and Trincomalee District General Hospitals, Kurunegala Teaching Hospital, and peripheral hospitals in the same districts. Thematic analysis was used to identify key challenges related to clinical decision-making, access to healthcare services, availability of antivenom and medical supplies, capacity building, interdisciplinary collaboration, and policy-related issues.</div></div><div><h3>Results</h3><div>Several challenges were identified, including delays in seeking medical care due to community misconceptions, limited access to antivenom in peripheral hospitals, inadequate intensive care facilities, and gaps in clinical training. Variability in clinical decision-making and the absence of standardized paediatric treatment guidelines further complicated management. Participants emphasized the need for interdisciplinary collaboration, improved referral networks, and targeted educational interventions to address these gaps.</div></div><div><h3>Conclusions</h3><div>Paediatric snakebite management in Sri Lanka is hindered by systemic, infrastructural, and educational challenges. Strengthening healthcare infrastructure, ensuring equitable access to antivenom, implementing standardized treatment protocols, and enhancing training programs for healthcare providers are crucial steps in improving patient outcomes. Policy-level interventions and community education initiatives are necessary to mitigate delays in care-seeking and enhance awareness.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108410"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling long-term outcomes in patients with post-stroke spasticity with or without BoNT-A treatment on all-cause mortality and secondary cardiovascular events","authors":"Klemens Fheodoroff","doi":"10.1016/j.toxicon.2025.108409","DOIUrl":"10.1016/j.toxicon.2025.108409","url":null,"abstract":"<div><div>App. 25 % of stroke survivors develop post-stroke spasticity (PSS) over the first year after a stroke, and they also experience motor weakness, which may prevent effective recovery by restricting mobility and participating in exercise programmes. Patients generally experience rapid improvement with Botulinum Toxin Type A (BoNT-A) therapy for PSS. Unfortunately, clinical trials demonstrating benefits from BoNT-A treatment are of short duration. Consequently, it is not known if treatment-related improvements in mobility could also contribute to lowering the risks of secondary cardiovascular (CV) events and all-cause death.</div><div>To assess if BoNT-A injections could also have an impact on long-term outcomes, we developed a 10-year survival model comparing the effects of AbobotulinumtoxinA (aboBoNT-A) injections and rehabilitation therapy (aboBoNT-A+RT) with rehabilitation therapy (RT) alone. The Functional Independence Measure (FIM) appeared to be the only functional outcome allowing us to model the effect of aboBoNT-A injections on all-cause mortality. Stroke survivors who reported better improvement in FIM score during rehabilitation had lower risk of all-cause mortality during follow-up. Patients treated with aboBoNT-A injections + RT showed better improvement in FIM score than patients treated without aboBoNT-A injections. Our modelling results showed that the addition of aboBoNT-A injections to RT led to a reduction of 8.8 % in the risk of all-cause mortality, and a relative increase of 12.8 % in discounted life-years.</div><div>The addition of aboBoNT-A injections to RT led to an increase in total costs of £42.329 over 10 years (based on National Health Service (NHS) UK cost collection 2018/2019). In the base-case scenario, incremental costs were driven by the increased number of hours of home care and RT for patients treated with aboBoNT-A injections compared with RT alone. Assuming an incremental cost-effectiveness ratio (ICER) threshold of £30.000, the probabilistic sensitivity analysis found a 73 % likelihood that aboBoNT-A + RT demonstrated cost-effectiveness compared with RT alone.</div><div>Our work advocates for the need to consider and to capture the impact of BoNT-A injections on all-cause mortality and secondary events, such as CV events and recurrent stroke, which are prevalent in stroke survivors.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108409"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kraits of Indian subcontinent: Natural history, risks, venom variation, lethality and treatment strategies – A comprehensive review","authors":"Amit Talukdar ,&nbsp;Surajit Giri ,&nbsp;Robin Doley","doi":"10.1016/j.toxicon.2025.108406","DOIUrl":"10.1016/j.toxicon.2025.108406","url":null,"abstract":"<div><div>The World Health Organization (WHO) has re-classified “Snakebite” as a Neglected Tropical Disease in 2017, and estimated that as many as 5.4 million people suffer from snakebites every year. Out of this large number of snakebites, envenoming occurs in about 50 % of the cases, and the number of resulting deaths could be as high as 138,000. The genus <em>Bungarus</em> commonly known as kraits are medically important elapid snakes widely distributed in the Indian subcontinent, southern China and the Southeast Asian countries (except Philippines). The Indian subcontinent (India, Bangladesh, Bhutan, Nepal, Pakistan, Sri Lanka and Maldives) is home to 8–9 krait species, among which <em>B. caeruleus</em> and <em>B. niger</em> are highly venomous. This review presents the current state of knowledge on krait bites in the Indian subcontinent. The risk of envenomation by kraits, the venom lethality and krait bite management in the Indian subcontinent have been critically analyzed. Moreover, the issue of dry bites from kraits and their management has also been reviewed. Furthermore, critical aspects, such as knowledge of snakebite management among healthcare workers, clinical symptoms of snakebite patients, and treatment in healthcare facilities including antivenom administration and their clinical efficacy, have helped us in identifying the critical knowledge gaps. Proposed preventive measures will help to reduce krait bite associated mortality and morbidity. Moreover, development and accessibility to affordable treatment options may help in the effective management of krait bites.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108406"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The double-banded false coralsnake Erythrolamprus bizona (Dipsadidae, Xenodontinae, Xenodontini) has a metalloproteinase-rich venom with proteolytic activity towards azocasein and α-fibrinogen","authors":"Kristian A. Torres-Bonilla ,&nbsp;Juan D. Bayona-Serrano ,&nbsp;Paula A. Sáenz-Suarez ,&nbsp;Luis M. Muñoz-Gómez ,&nbsp;Manuel H. Bernal-Bautista ,&nbsp;Stephen Hyslop","doi":"10.1016/j.toxicon.2025.108407","DOIUrl":"10.1016/j.toxicon.2025.108407","url":null,"abstract":"<div><div>The venom of the double-banded false coralsnake, <em>Erythrolamprus bizona</em>, is proteolytic and attenuates neuromuscular contractile activity <em>in vitro</em>. Here, we examined the Duvernoy's venom gland histology and general composition of <em>E. bizona</em> venom using a combination of chromatographic, electrophoretic, enzymatic and proteomic analyses. Histologically, the venom gland consisted of serous epithelium-lined secretory tubules and a supralabial gland that stained positively for mucopolysaccharide. SDS-PAGE showed that the venom had a simple composition, with proteins in the range of 15–60 kDa. This simple composition was confirmed by RP-HPLC that revealed 15 main protein peaks. The venom (1–10 μg) was highly proteolytic towards azocasein, but was devoid of esterase, phospholipase (PLA₂), and L-amino acid oxidase activities. The venom also degraded casein and gelatin in zymographic assays, with activity towards gelatin being particularly potent and detected over the range of 18.7 ng–30 μg of venom; gelatinolytic activity was also detected in four of the RP-HPLC peaks. The venom (10 μg) selectively degraded the α-chain of fibrinogen. All proteolytic activity was inhibited by EDTA (metalloproteinase inhibitor) but not by AEBSF (serine proteinase inhibitor). SDS-PAGE followed by in-gel digestion of the main electrophoretic bands coupled with LC-MS/MS analysis revealed the presence of five toxin families: C-type lectin-like proteins (CTL), cysteine-rich secretory proteins (CRiSP), phospholipase B (PLB), snake venom matrix metalloproteinases (svMMP), and snake venom metalloproteinases (SVMP). These findings extend our knowledge of the toxinology of <em>E. bizona</em> and suggest that the local manifestations (pain, edema, erythema, and ecchymosis) seen in human envenomation by this species are probably mediated by venom metalloproteinases.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"263 ","pages":"Article 108407"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Widespread occurrence of botulinum and tetanus neurotoxin genes in ancient DNA","authors":"Shyan Mascarenhas ,&nbsp;Harold P. Hodgins ,&nbsp;Andrew C. Doxey","doi":"10.1016/j.toxicon.2025.108405","DOIUrl":"10.1016/j.toxicon.2025.108405","url":null,"abstract":"<div><h3>Background</h3><div>Ancient DNA collected from archaeological specimens not only provides a window into ancient human genetic diversity but also contains a rich mixture of associated microbial DNA including potential pathogens. In recent work, we identified <em>C. tetani</em> and tetanus neurotoxin (TeNT) genes in ancient DNA datasets collected from human archaeological specimens. However, the reasons underlying the occurrence of these toxin genes and the extent to which other toxin genes are present in ancient DNA is unclear.</div></div><div><h3>Methods</h3><div>Here, we performed a large-scale analysis of 6435 ancient DNA (aDNA) sequencing datasets including human and non-human sources, searching for 49 clostridial neurotoxin types and subtypes, and 3 additional unrelated toxins.</div></div><div><h3>Results</h3><div>Our search identified a total of 105 ancient DNA datasets (1.6 %) containing significant matches to one or more neurotoxin genes. Consistent with our earlier work, TeNT genes were most common, found in 50 ancient DNA datasets. In addition, we identified sequences encoding diverse botulinum neurotoxins including BoNT/C (40 samples), BoNT/D (6 samples), BoNT/B (4 samples), BoNT/E (1 sample), and the <em>Enterococcus</em>-associated BoNT/En (10 samples). TeNT genes were detected in a broad range of ancient samples including human and animal (horse, wild bear, chimpanzee, gorilla, dog) remains, whereas the largest diversity of toxins was detected in aDNA from Egyptian mummies. Phylogenetic and sequence analysis of the identified matches revealed close identity to modern forms of these toxins. Damage analysis revealed several toxin genes with hallmarks of ancient DNA associated damage, indicative of an ancient origin.</div></div><div><h3>Conclusions</h3><div>Our work reveals that clostridial neurotoxin genes occur frequently in aDNA samples, including human and animal-associated toxin variants. We conclude that the frequent association of these genes with aDNA likely reflects a strong ecological association of pathogenic clostridia with decaying human and animal remains and possible post-mortem colonization of these samples.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"262 ","pages":"Article 108405"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}