Toxicon最新文献

{"title":"Sirt1 Mitigates HT-2 Toxin-Induced Chondrocyte Injury Potentially via the Wnt/β-Catenin Signaling Pathway.","authors":"Haonan Li, Qi Zhang, Fang Qi, Qian Yu, Chenxi Wang, Ying Liu, Haoyu DU, Yue Zhao, Jun Yu","doi":"10.1016/j.toxicon.2025.108465","DOIUrl":"https://doi.org/10.1016/j.toxicon.2025.108465","url":null,"abstract":"<p><p>Sirt1 is crucial for cartilage homeostasis, and its dysregulation is implicated in Kashin-Beck disease (KBD), an osteochondropathy linked to HT-2 toxin exposure. This study investigated Sirt1's role in HT-2 toxin-induced chondrocyte injury. Human fetal chondrocytes treated with HT-2 toxin (0, 5, 10, 20ng/mL) for 48 hours showed dose-dependent viability reduction, extracellular matrix (ECM) degradation (↓Collagen II, ↓TIMP1, ↑MMP13), and senescence (↑P21, ↑β-galactosidase). HT-2 toxin suppressed Sirt1 while activating Wnt/β-catenin signaling (↑WNT3A, ↑β-catenin). Resveratrol (25μM), a Sirt1 agonist, restored TIMP1 and Collagen II levels and reduced P21 without affecting MMP13, while inhibiting the WNT3A/β-catenin pathway. These results demonstrate that Sirt1 activation mitigates HT-2 toxin-induced chondrocyte damage by inhibiting Wnt/β-catenin signaling.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"108465"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340432","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":"Exploring the Utility of Point-of-Care Testing for Diagnosing Snake Envenomation in Australian Snake Bites: A scoping review.","authors":"Madison Bailey, Clinton Gibbs, Clare Heal, Chloe E Gane, Leanne Hall","doi":"10.1016/j.toxicon.2025.108464","DOIUrl":"https://doi.org/10.1016/j.toxicon.2025.108464","url":null,"abstract":"<p><strong>Introduction: </strong>Most snake bites in Australia do not result in envenomation. However, when it does occur, envenomation can lead to a range of clinical syndromes, depending on the snake species involved. Diagnosis of envenomation, which relies primarily on laboratory investigations, poses a significant challenge when rapid identification of envenomation is essential for the timely administration of antivenom. Finding a solution to this challenge could enable earlier diagnosis and subsequent treatment of snake envenomation. This review assesses the existing literature on point-of-care testing methods for diagnosing snake envenomation across Australia.</p><p><strong>Methods: </strong>Six relevant databases were searched using appropriate subject headings and keywords, related to \"snake\" AND \"bite\" AND \"Australia\" with no time or language restrictions. Two reviewers screened titles and abstracts and full text articles. Data from included studies was extracted in duplicate.</p><p><strong>Results: </strong>1,260 articles were initially identified following removal of duplicates. After screening for eligibility, 12 relevant studies were identified. These articles explored four key areas of point-of-care testing in snake envenomation diagnosis: venom detection, coagulopathy detection, biomarker detection and cardiac assessment. No point-of-care test was found to sufficiently confirm envenomation to guide administration of antivenom in those with a suspected snake bite in Australia.</p><p><strong>Conclusion: </strong>This review underscores the need for continued research to explore novel approaches for the rapid diagnosis of snake envenomation. Improved diagnostic tools could enhance patient outcomes and potentially allow rural and remote areas without laboratory facilities to diagnose or rule out envenomation without patient transfer. However, the current literature is limited, and existing point-of-care methods lack sufficient accuracy to guide clinical practice.</p>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":" ","pages":"108464"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337046","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":"Immunization of rabbits with nanovenom composed of Dendroaspis polylepis venom and silica nanoparticles: a first in vivo approach","authors":"Federico G. Baudou ,&nbsp;María Herrera ,&nbsp;Mariángela Vargas ,&nbsp;Mauren Villalta ,&nbsp;Florencia S. Conti ,&nbsp;Exequiel Giorgi ,&nbsp;Laura Leiva ,&nbsp;José María Gutiérrez ,&nbsp;Adolfo R. de Roodt ,&nbsp;Mauricio de Marzi","doi":"10.1016/j.toxicon.2025.108462","DOIUrl":"10.1016/j.toxicon.2025.108462","url":null,"abstract":"<div><div><em>Dendroaspis polylepis</em> inflicts severe neurotoxic envenomings due to its high content of potent neurotoxins. The poor immunogenicity of these toxins represents a significant challenge in antivenom (AV) generation. Silica nanoparticles (SiNPs) have been proposed for use in medicine due to their ability to stimulate the immune system. This study explored the possible use of SiNPs as adjuvant (ADJ) mixed with <em>D. polylepis</em> venom (nanovenoms, NV) for immunization in rabbits, compared to venom emulsified with the traditional Freund ADJ and with venom alone. ELISA results show that sera from rabbits immunized with NV developed an antibody response similar to sera from rabbits immunized with Freund adjuvant, and did not develop significant lesions at the injection site. Western blot analysis indicates that NV sera group showed a strong recognition of neurotoxins and neutralized a challenge dose of venom (1.5 LD₅₀), increasing the survival time of mice. In conclusion, NV proved to be a good ADJ in immunization with <em>D. polylepis</em> venom and could be tested for AV industrial production.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108462"},"PeriodicalIF":2.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314139","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":"Localization modalities for botulinum neurotoxin injection","authors":"Barbara Illowsky Karp ,&nbsp;Ann Ly ,&nbsp;Katharine E. Alter","doi":"10.1016/j.toxicon.2025.108460","DOIUrl":"10.1016/j.toxicon.2025.108460","url":null,"abstract":"<div><div>Botulinum toxin is a targeted therapeutic that acts primarily at the site of injection. Various approaches have been taken to guide injection into the selected muscle, gland, organ or other body area. Guidance methodologies that can be used in the office setting for skeletal muscle and salivary gland percutaneous injection include uninstrumented manual needle placement, electromyography (EMG), electromyography with electrical stimulation (e-stim), ultrasound (US) and combined guidance (US + EMG or US + e-stim). This article reviews the advantages, disadvantages, and accuracy of each method and the impact of each guidance technique on therapeutic outcome for muscle and salivary gland injections. Overall, manual placement may suffice for large and superficial muscles, however, all instrumented techniques improve accuracy. Electromyography can uniquely provide information on muscle activity, while e-stim can aid injection in patients who cannot voluntarily activate a selected muscle. Ultrasound is the only technique that can visualize internal structures, allowing identification of a safe trajectory for injection of small or deep targets that might otherwise be inaccessible.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108460"},"PeriodicalIF":2.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320925","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":"Identification of effective inhibitors against epsilon toxin (ETX) of Clostridium perfringens: Virtual screening and molecular dynamics simulation","authors":"Atefe Panahipoor Javaherdehi ,&nbsp;Zahra Sadat Hashemi ,&nbsp;Sepideh Khaleghi ,&nbsp;Gholamreza Bayazian","doi":"10.1016/j.toxicon.2025.108463","DOIUrl":"10.1016/j.toxicon.2025.108463","url":null,"abstract":"<div><div>In spite of the potential for toxicity in humans, no therapeutics are approved against Epsilon toxin (ETX) for human use. Therefore, finding effective inhibitors for this toxin has garnered a lot of attention. In this regard, we performed an in silico study to find effective inhibitors against this toxin. To this end, the structure of ETX and an experimentally approved ETX inhibitor were prepared and docked as a control interaction and used for the determination of the binding site. An approved library of small molecules was obtained from the DrugBank database and prepared for virtual screening via size filtering and the addition of conformations. The top five molecules with the highest binding energy were used to draw their 2D interaction plots against ETX. A 100 ns MD simulation was performed on the Antrafenine-ETX complex as the best result of the screening stage in comparison to the control complex. The obtained results showed that among the 3849 molecules (which were analyzed by virtual screening), Cefotiam, Antrafenine, Ferric Derisomaltose, Mupirocin, and Salmeterol had the highest binding energies (binding energies respectively calculated to be −5.6, −5.8, −4.9, −4.9, and −4.6 kcal/mol). The 2D interaction plots also showed that the screened molecules had stronger interacting bonds with the ETX protein. MD simulations showed that the Antrafenine-ETX complex has a similar RMSD plot to the control complex, while its RMSF, hydrogen bond, and GR plots show better results for the Antrafenine-ETX complex. In light of these results, Antrafenine could be the best choice for ETX inhibition regarding strength, while based on the route of administration and drug applications, Cefotiam could also be considered for ETX inhibition. It seems that despite the promising results of the performed in silico studies, further empirical pieces of evidence would strengthen these conclusions in future studies.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108463"},"PeriodicalIF":2.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314138","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 co-existence of Microcoleus strains with gene variations in the anatoxin-a biosynthesis cluster can explain the different toxin profiles observed in freshwater benthic mats","authors":"Cecilio Valadez-Cano ,&nbsp;Adrian Reyes-Prieto ,&nbsp;Lindsay Johnston ,&nbsp;Yannan Huang ,&nbsp;Hannah Morris ,&nbsp;Lydia Zamlynny ,&nbsp;André M. Comeau ,&nbsp;Daniel G. Beach ,&nbsp;Rob C. Jamieson ,&nbsp;Janice Lawrence","doi":"10.1016/j.toxicon.2025.108461","DOIUrl":"10.1016/j.toxicon.2025.108461","url":null,"abstract":"<div><div>Distinct anatoxin profiles can occur in <em>Microcoleus</em>-dominated benthic mats. Metagenomic data from a dihydrohomoanatoxin-a-producing mat revealed two co-occurring <em>Microcoleus</em> strains with variations in the anatoxin biosynthesis gene cluster. One cluster contained an <em>anaK</em> (F₄₂₀-dependent oxidoreductase) similar to homologs from dihydroanatoxin-a-producing strains. The second contained the long <em>anaG</em> (polyketide-synthase) previously associated with homoanatoxin-a. Neither strain alone explained the observed toxin profile, suggesting that strain interaction contributes to the production of dihydrohomoanatoxin-a within benthic mats.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108461"},"PeriodicalIF":2.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310433","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":"First report of the medically significant Argentine scorpion Tityus carrilloi (Buthidae) in Paraguay: Epidemiological implications amid rising regional scorpionism","authors":"Adolfo Borges ,&nbsp;Camilo Caballero ,&nbsp;Antonieta Rojas de Arias ,&nbsp;Paul Smith ,&nbsp;Matthew Owen ,&nbsp;Aya Nishi ,&nbsp;Yasmine Maluff ,&nbsp;Tatiana Wieczorko","doi":"10.1016/j.toxicon.2025.108456","DOIUrl":"10.1016/j.toxicon.2025.108456","url":null,"abstract":"<div><div>We report the first record of the medically important scorpion <em>Tityus carrilloi</em> in Paraguay, from the metropolitan area of Encarnación, Itapúa Department, near the Argentine border. Known for causing severe and fatal envenomings across northern Argentina, the presence of this species in southeastern Paraguay highlights the risk of cross-border dispersion. Along with the regional spread of the Brazilian <em>Tityus serrulatus</em>, this finding has significant epidemiological implications and underscores the urgent need for improved surveillance, diagnostics, and coordinated public health responses in Paraguay and neighboring countries, within the evolving landscape of scorpionism in southern South America.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108456"},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295012","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":"Investigating the effect of acrylamide, penitrem A and 3-acetyldeoxynivalenol in SH-SY5Y human neuroblastoma cells: exploring the oxidative stress","authors":"Luna Bridgeman,&nbsp;Cristina Juan,&nbsp;Houda Berrada,&nbsp;Ana Juan-García","doi":"10.1016/j.toxicon.2025.108441","DOIUrl":"10.1016/j.toxicon.2025.108441","url":null,"abstract":"<div><div>Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds antioxidant defenses, causing cellular damage and contributing to several diseases. Research on ROS, lipid peroxidation (LPO), and glutathione (GSH/GSSG) balance in SH-SY5Y cells is reported in this study to understand the toxic effects of one food processed contaminant such as acrylamide (AA) and two mycotoxins belonging to food natural contaminants such as penitrem A (PEN A), and 3-acetyldeoxynivalenol (3-ADON). Understanding these interactions is crucial to mitigating the health risks associated with exposure to multiple contaminants; thus, the effect of AA, PEN A, and 3-ADON individually and in combination for the oxidative stress response in SH-SY5Y cells was studied. The results demonstrated a concentration-dependent increase in ROS for individual exposures, with a maximum increase of 26.9 % for 4 μM 3-ADON. Combined exposures generally reduced ROS levels compared to individual treatments but still showed significant increases, such as a 22.8 % rise with [PEN A + 3-ADON]. LPO also increased, with the highest elevation observed for [PEN A + 3-ADON] at 3.45-fold over control. The GSH/GSSG ratio was significantly reduced in all combinations, with decreases of up to 36.6 %, indicating pronounced oxidative stress. Cytotoxicity was also observed, with the tertiary combination [AA + PEN A + 3-ADON] reducing cell viability by 80 % at 24 h. Based on our findings, AA, PEN A, and 3-ADON cause damage to SH-SY5Y cells by increasing oxidative stress levels, ROS and LPO, as well as disrupting the antioxidant function of the glutathione system. Furthermore, this study highlights the importance of exploring food contaminants combinations, as the mixtures seemed to be more toxic than the individual contaminants. Altogether, these results emphasize the toxicological relevance of combined exposure to dietary contaminants and support the inclusion of mixture effects in neurotoxicity risk assessment frameworks within the field of food safety.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108441"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262191","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":"Training and educational needs for paediatric snakebite management among rural healthcare providers in Sri Lanka","authors":"Kavinda Dayasiri ,&nbsp;Gihan Gunarathna ,&nbsp;Anjana Silva ,&nbsp;Indika Gawarammana ,&nbsp;Shaluka Jayamanne","doi":"10.1016/j.toxicon.2025.108459","DOIUrl":"10.1016/j.toxicon.2025.108459","url":null,"abstract":"<div><div>This mixed-method study aimed to explore the educational and training needs of healthcare providers managing paediatric snakebites in regions with high burdens of snakebite envenomation in rural Sri Lanka. The goal was to identify gaps in current training practices and propose strategies to improve the clinical management of paediatric snakebite cases. A focus group discussion (FGD)-based approach was utilized to gather insights from healthcare providers involved in the management of paediatric snakebites. Participants included medical officers working in paediatric wards, paediatric emergency treatment units, paediatric intensive care units, as well as paediatric house officers and relief house officers. Using purposive sampling, participants were recruited from both tertiary referral centers and peripheral hospitals. Data were collected through six semi-structured FGDs, which were audio-recorded and transcribed. Thematic analysis was conducted following Braun and Clarke's six-step framework. The findings revealed significant gaps in knowledge and training related to paediatric snakebite management, particularly in more peripheral rural hospitals. Participants reported a lack of structured training, standardized institutional protocols, and exposure to paediatric-specific guidelines. Inconsistent knowledge among healthcare providers, particularly in peripheral settings, contributed to inappropriate treatments and delayed referrals. Recommendations for addressing these gaps included simulation-based training, mentorship programs, and standardized treatment protocols, particularly for junior doctors in resource-limited areas. The study highlights critical deficiencies in paediatric snakebite management training in rural Sri Lanka. To improve patient outcomes, there is a need for enhanced training programs, including hands-on experience, mentorship, and telemedicine support. Standardized, evidence-based guidelines should be disseminated and integrated into healthcare practices across all levels of the healthcare system.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108459"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280337","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":"Antimicrobial peptides from earthworms: Emerging candidates for novel therapeutic applications","authors":"Saravanakumar Venkatachalam,&nbsp;Johnson Retnaraj Samuel Selvan Christyraj,&nbsp;Reiya Bosco Don Bosco,&nbsp;Beryl Vedha Yesudhason","doi":"10.1016/j.toxicon.2025.108458","DOIUrl":"10.1016/j.toxicon.2025.108458","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) are small, naturally occurring peptides, play a crucial role in the innate immune system of many organisms, from bacteria to humans. Earthworms encompasses an array of antimicrobial peptides (AMPs) and its analogues, generated by their immune system confers to their survival against a wide range of pathogens. This review explores the different earthworm antimicrobials like, AMPs, extracts, powders and earthworm coelomic fluid (ECF) with experimental validation. This review highlights the earthworms innate immune response, harnessed to treat multiple co-infections, multiple drug resistance (MDR), antimicrobial resistance (AMR) and can address divergent diseases through their broad-spectrum applications. The implementations of earthworm extracts and AMPs are well addressed implying its attributes like anti-bacterial, anti-viral and anti-fungal properties, its role in wound healing and regeneration, anti-coagulation properties, anti-tumor properties and anti-inflammatory functions. The future scope of AMPs is detailed and the noteworthy attributes of earthworm antimicrobials face challenges, in being used for clinical applications. In addition, this review highlights the combination therapy where earthworm antimicrobials are administered in conjunction with other drugs. In such a manner the drawbacks of one are rectified by the other deducing powerful and novel antimicrobials. Further, the jeopardy of AMR in the current era is discussed and various tireless attempts to regulate its spread with the aid of novel antimicrobials including AMPs is also explored. This review contributes to explore the earthworm antimicrobials to clinical applications in the near future.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"264 ","pages":"Article 108458"},"PeriodicalIF":2.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262192","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}