Toxins最新文献

{"title":"Fumonisin B₁ Exposure Causes Intestinal Tissue Damage by Triggering Oxidative Stress Pathways and Inducing Associated CYP Isoenzymes.","authors":"Changyu Cao, Weiping Hua, Runxi Xian, Yang Liu","doi":"10.3390/toxins17050239","DOIUrl":"10.3390/toxins17050239","url":null,"abstract":"<p><p>Fumonisin B₁ (FB₁) is considered the most toxic fumonisin produced by fungi and is commonly found in contaminated feed and crops. Fumonisin and its metabolites extensively exist in feed and crops, where FB₁-polluted crop ingestion can do harm to livestock and poultry, causing poultry intestinal toxicity in the latter. For investigating FB₁-mediated intestinal toxicity, we assessed the function of FB₁ exposure in quail intestines and explored its possible molecular mechanisms. In total, 120 quail pups were classified into two groups, where those in the control group were given a typical control diet, and those in the experimental group were given a typical diet that contained 30 mg/kg FB₁. We evaluated the histopathological and ultrastructural changes in quails' intestines on days 14, 28, and 42, and studied the molecular mechanisms by assessing oxidative stress, inflammation, and nuclear xenobiotic receptors (NXRs). Our results suggest that FB₁ exposure causes intestinal inflammation by triggering oxidative stress pathways and modulating NXRs to induce Cytochrome P450 proteins (CYP) isoforms, leading to intestinal histopathological damage. The results of this study shed novel light on the molecular mechanism underlying FB₁-induced intestinal injury in juvenile quails.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of Venom-Derived Compounds for the Development of New Antimicrobial Agents.","authors":"Esraa Yasser Rabea, Esraa Dakrory Mahmoud, Nada Khaled Mohamed, Erada Rabea Ansary, Mahmoud Roushdy Alrouby, Rabab Reda Shehata, Youssef Yasser Mokhtar, Prakash Arullampalam, Ahmed M Hegazy, Ahmed Al-Sabi, Tarek Mohamed Abd El-Aziz","doi":"10.3390/toxins17050238","DOIUrl":"10.3390/toxins17050238","url":null,"abstract":"<p><p>The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, and <i>Pseudomonas aeruginosa</i> pose significant public health threats, as they are increasingly resistant to common antibiotics, leading to more severe and difficult-to-treat infections. These pathogens are part of the ESKAPE group, which includes <i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, and <i>Enterobacter</i> species. Animal venoms, derived from a wide range of species such as snakes, scorpions, spiders, bees, wasps, and ants, represent a rich source of bioactive peptides. Venoms have been a valuable source for drug discovery, providing unique compounds with therapeutic potential. Venom-derived drugs are known for their increased bioactivity, specificity, and stability compared to synthetic alternatives. These compounds are being investigated for various conditions, including treatments for diabetes, pain relief, cancer, and infections, showcasing their remarkable antimicrobial efficacy. In this review, we provide a comprehensive investigation into the potential of venom-derived compounds for developing new antimicrobial agents, including antibacterial, antifungal, antiviral, and antiparasitic therapeutics. Key venom components, including melittin from bee venom, phospholipase A₂ from snake venom, and chlorotoxin from scorpion venom, exhibit potent antimicrobial effects through mechanisms such as membrane disruption, enzymatic inhibition, and immune modulation. We also explore the challenges related to the development and clinical use of venom-derived antimicrobials, including toxicity, stability, and delivery mechanisms. These compounds hold immense promise as transformative tools against resistant pathogens, offering a unique avenue for groundbreaking advancements in antimicrobial research and therapeutic development.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snake Venom: Toxicology and Associated Countermeasures.","authors":"Nicholas J Youngman","doi":"10.3390/toxins17050237","DOIUrl":"10.3390/toxins17050237","url":null,"abstract":"<p><p>This Special Issue aims to provide insight into the understudied toxicological effects induced by snakebite envenoming, as well as to highlight current and future countermeasures for reducing the extreme morbidity and mortality associated with this globally neglected tropical disease [...].</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive Variation in Thermal Responses and Toxin Content Among 40 Strains of the Cold-Water Diatom <i>Pseudo-nitzschia seriata</i>-In a Global Warming Context.","authors":"Caroline Weber, Anna Junker Olesen, Robert G Hatfield, Bernd Krock, Nina Lundholm","doi":"10.3390/toxins17050235","DOIUrl":"10.3390/toxins17050235","url":null,"abstract":"<p><p>Phytoplankton are single-celled microorganisms with short generation times that may comprise high diversity in genetic and phenotypic traits, allowing them to acclimate to changes rapidly. High intraspecific genetic variation is well known in phytoplankton, but less is known about variation in physiological traits. To investigate variability and plasticity in genetic, morphological, and physiological traits of the toxigenic diatom genus <i>Pseudo-nitzschia</i> in a global warming scenario, we exposed 40 strains of the cold-water <i>P. seriata</i> to different temperatures (2 °C, 6 °C and 10 °C). The maximum growth rate and cellular toxin content showed extensive intraspecific variation, whereas morphological and genetic variation was minor. Thermal reaction norms showed a general increase in growth rate with increasing temperature; however, three distinct types of thermal responses were found among the 40 strains. All 40 strains contained toxins (domoic acid) in both exponential and stationary growth phase, and toxin content increased significantly with temperature. Most strains (>87%) contained measurable levels of domoic acid at all three temperatures. In conclusion, <i>P. seriata</i> shows extensive intraspecific variation in measured physiological traits like growth and toxin content, a variation exceeding the response of each strain to increases in temperature. Intraspecific variation in harmful species thus needs attention for the future understanding of food web dynamics, as well as the management and forecasting of harmful blooms.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Preclinical Testing of a Novel Neurodenervant in the Rat: C3 Transferase Mitigates Botulinum Toxin's Adverse Effects on Muscle Mechanics.","authors":"Cemre Su Kaya Keles, Zeynep D Akdeniz Dogan, Can A Yucesoy","doi":"10.3390/toxins17050234","DOIUrl":"10.3390/toxins17050234","url":null,"abstract":"<p><p>Spasticity, characterized by elevated muscle tone, is commonly managed with botulinum toxin type A (BTX-A). However, BTX-A can paradoxically increase passive muscle forces, narrow muscles' length range of force exertion (l_range), and elevate extracellular matrix (ECM) stiffness. C3 transferase, known to inhibit myofibroblast and fascial tissue contractility, may counteract ECM stiffening. This study investigated whether combining BTX-A with C3 transferase reduces active forces without altering passive forces or l_range. Additionally, we examined the isolated effects of C3 transferase on muscle levels. Male Wistar rats received injections into the tibialis anterior (TA): Control (<i>n</i> = 7, saline) and C3 + BTX-A (<i>n</i> = 7, 2.5 µg C3 + 0.1U BTX-A). TA forces were measured one month post-injection, and isolated C3 transferase effects were assessed in separate groups (Control and C3, <i>n</i> = 6 each). Active forces were 43.5% lower in the C3 + BTX-A group compared to the Control group. No differences between groups in passive forces (<i>p</i> = 0.33) or l_range (<i>p</i> = 0.19) were observed. C3 transferase alone had no significant effect on relative muscle mass (<i>p</i> = 0.298) or collagen content (<i>p</i> = 0.093). Supplementing BTX-A with C3 transferase eliminates BTX-A's adverse effects at the muscle level. C3 transferase alone causes no atrophy or collagen increase, which are key factors in BTX-A-induced ECM stiffening. This novel neurodenervant formula shows promise for advancing spasticity management.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Biocontrol Agents on the Metabolome of <i>Penicillium nordicum</i> Strains and Its Relation to Ochratoxin A Production on Dry-Cured Ham.","authors":"Eva Cebrián, Elia Roncero, João Luz, Mar Rodríguez, Marta Sousa Silva, Carlos Cordeiro, Félix Núñez","doi":"10.3390/toxins17050236","DOIUrl":"10.3390/toxins17050236","url":null,"abstract":"<p><p>Throughout the process of dry-cured ham, moulds such as <i>P. nordicum</i>, a producer of ochratoxin A (OTA), grow on its surface. The use of combined biocontrol agents (BCAs) is a promising strategy for controlling this hazard. The goal of this study is to assess the effect of <i>D. hansenii</i>, <i>S. xylosus</i>, and <i>P. chrysogenum</i> as BCAs on the metabolome of two strains of <i>P. nordicum</i> and to understand the differences between both strains. Each ochratoxigenic strain was inoculated both individually and in combination with the BCAs onto ham for 30 days under the environmental conditions experienced during traditional ripening. Untargeted metabolomics was performed through mass spectrometry using a Q-Exactive Plus Orbitrap. The BCAs caused alterations in the metabolomes of both ochratoxigenic moulds, mainly in phenylalanine catabolism and the valine, leucine, and isoleucine biosynthesis pathways, although with some differences. In the absence of the BCAs, the metabolomes of both types of <i>P. nordicum</i> were globally changed, despite these being moulds of the same species. In conclusion, these data help us to understand the differences between OTA-producing strains in dry-cured ham and confirm the need to demonstrate the efficacy of BCAs against a wide range of toxigenic moulds before they can be used to minimise OTA contamination in the meat industry.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure, Toxicity, Prevalence, and Degradation of Six Understudied Freshwater Cyanopeptides.","authors":"Blake B Stringer, Regina G Szlag Silva, Jeremy J Kodanko, Judy A Westrick","doi":"10.3390/toxins17050233","DOIUrl":"10.3390/toxins17050233","url":null,"abstract":"<p><p>Anthropogenic influences have increased global warming and eutrophication, escalating the frequency and severity of harmful cyanobacterial blooms (cHABs) in freshwater ecosystems. These blooms release cyanopeptides, a diverse class of bioactive compounds with varying acute and chronic toxicities upon ingestion. To date, research has prioritized acutely toxic cyanopeptides like microcystins. As a result, significantly less is known about other freshwater cyanopeptides. This review highlights six understudied cyanopeptide classes, anabaenopeptins, cyanopeptolins, aeruginosamides, aeruginosins, microginins, and cyclamides, and provides a comprehensive overview of their molecular structures, toxicological profiles, environmental concentrations, and known degradation pathways. Given the potential toxicity, increased environmental abundance, and environmental stability of many cyanopeptides in freshwater sources, further research is needed to understand if degraded cyanopeptides are still biologically active prior to entering drinking water to ensure public health.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Strategies and Artificial Intelligence Methods for the Mitigation of Toxigenic Fungi and Mycotoxins in Foods.","authors":"Fernando Mateo, Eva María Mateo, Andrea Tarazona, María Ángeles García-Esparza, José Miguel Soria, Misericordia Jiménez","doi":"10.3390/toxins17050231","DOIUrl":"10.3390/toxins17050231","url":null,"abstract":"<p><p>The proliferation of toxigenic fungi in food and the subsequent production of mycotoxins constitute a significant concern in the fields of public health and consumer protection. This review highlights recent strategies and emerging methods aimed at preventing fungal growth and mycotoxin contamination in food matrices as opposed to traditional approaches such as chemical fungicides, which may leave toxic residues and pose risks to human and animal health as well as the environment. The novel methodologies discussed include the use of plant-derived compounds such as essential oils, classified as Generally Recognized as Safe (GRAS), polyphenols, lactic acid bacteria, cold plasma technologies, nanoparticles (particularly metal nanoparticles such as silver or zinc nanoparticles), magnetic materials, and ionizing radiation. Among these, essential oils, polyphenols, and lactic acid bacteria offer eco-friendly and non-toxic alternatives to conventional fungicides while demonstrating strong antimicrobial and antifungal properties; essential oils and polyphenols also possess antioxidant activity. Cold plasma and ionizing radiation enable rapid, non-thermal, and chemical-free decontamination processes. Nanoparticles and magnetic materials contribute advantages such as enhanced stability, controlled release, and ease of separation. Furthermore, this review explores recent advancements in the application of artificial intelligence, particularly machine learning methods, for the identification and classification of fungal species as well as for predicting the growth of toxigenic fungi and subsequent mycotoxin production in food products and culture media.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BLF1 Affects ATP Hydrolysis Catalyzed by Native and Mutated eIF4A1 and eIF4A2 Proteins.","authors":"Min An, Xin Cheng, Yu Zhang, Jiang Gu, Xuhu Mao","doi":"10.3390/toxins17050232","DOIUrl":"10.3390/toxins17050232","url":null,"abstract":"<p><p><i>Burkholderia</i> lethal factor 1 (BLF1), a toxin derived from <i>Burkholderia pseudomallei</i>, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on cancer treatment outcomes. To understand the molecular mechanism by which BLF1 modulates eIF4A isoforms in cancer cells, we investigated its effects on eIF4A-mediated adenosine 5'-triphosphate (ATP) hydrolysis. We found that eIF4A1 has a higher ATP-binding affinity compared to eIF4A2 (K_m = 6.55 ± 0.78 μM vs. K_m = 11.61 ± 2.33 μM). Meanwhile, we also found that eIF4A1 is more sensitive to changes in temperature, pH, and Mg²⁺ concentration. Through N-terminal swapping and single amino acid mutations, we found that leucine 98 (L98) and alanine 100 (A100) play important roles in the ATPase activities of eIF4A isoforms. Moreover, BLF1 treatment significantly enhanced eIF4A2-mediated ATP hydrolysis at all tested ATP concentrations. These differences in BLF1-regulated eIF4A isoforms may explain its selective cytotoxicity against cancer cells. Our findings provide molecular insights into the functional difference between eIF4A isoforms and suggest that BLF1 might be of promising value for anticancer therapies.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evaluation of Botulinum Toxin Type E (TrenibotulinumtoxinE) Using the Mouse Digit Abduction Score (DAS) Assay.","authors":"Gregory S Nicholson, David Canty, Annemarie Southern, Kevin Whelan, Amy D Brideau-Andersen, Ron S Broide","doi":"10.3390/toxins17050230","DOIUrl":"10.3390/toxins17050230","url":null,"abstract":"<p><p>TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24-27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}