Next Issue
Volume 16, December
Previous Issue
Volume 16, October
 
 

Toxins, Volume 16, Issue 11 (November 2024) – 51 articles

Cover Story (view full-size image): The development of cyanobacterial harmful algal blooms (cHABs) in global water bodies leads to ecological and economic challenges. This study analyzes cyanotoxin production and cyanobiome dynamics across three key Great Lake regions using advanced molecular strategies. These include DNA sequencing and ELISA to identify site-specific variations in cyanobacterial taxa and cyanotoxin levels. The findings highlight the importance of regional cyanobacterial diversity in cHAB formation, which may help improve the development of targeted diagnostics and remediation strategies to preserve freshwater ecosystems. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
15 pages, 2039 KiB  
Article
Paralytic Shellfish Poisoning (PSP) Toxins in Bivalve Molluscs from Southern Italy Analysed by Liquid Chromatography Coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS/MS)
by Pasquale Gallo, Sara Lambiase, Ida Duro, Mauro Esposito and Angela Pepe
Toxins 2024, 16(11), 502; https://doi.org/10.3390/toxins16110502 - 20 Nov 2024
Viewed by 788
Abstract
A new method for simultaneous determination by liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS/MS) of 14 paralytic shellfish poisoning toxins (PSP), that is, Saxitoxin, Neosaxitoxin, Gonyautoxins and their respective variants, in bivalve molluscs, is herein described. The samples were extracted by [...] Read more.
A new method for simultaneous determination by liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS/MS) of 14 paralytic shellfish poisoning toxins (PSP), that is, Saxitoxin, Neosaxitoxin, Gonyautoxins and their respective variants, in bivalve molluscs, is herein described. The samples were extracted by acetic acid solution, then analysed by UHPLC coupled with a Q-Exactive Orbitrap Plus high resolution mass spectrometer, by electrospray ionization mode (ESI) with no further clean up step. The analysis was carried out by monitoring both the exact mass of the molecular precursor ion of each compound (in mass scan mode, resolution at 70,000 FWHM) and its respective fragmentation patterns (two product ions) with mass accuracy greater than 5 ppm. The analytical performance of the method was evaluated calculating trueness, as mean recoveries of each biotoxin, between 77.8% and 111.9%, a within-laboratory reproducibility (RSDR) between 3.6% and 12.2%, the specificity, the linearity of detector response, and the ruggedness for slight changes The results of the validation study demonstrate this method fits for the purposes of the official control of PSP toxins in molluscs. The results of two years of monitoring in local mussel farms are also reported, showing that no significant concerns for food safety in the monitored productions. Full article
Show Figures

Figure 1

13 pages, 539 KiB  
Review
Bee Venom Acupuncture for Shoulder Pain: A Literature Review of Clinical Studies
by Hyein Jeong, Soobin Jang, Jang-Kyung Park, Kyeong Han Kim, Jong Hyun Park, Gihyun Lee and Soo-Hyun Sung
Toxins 2024, 16(11), 501; https://doi.org/10.3390/toxins16110501 - 20 Nov 2024
Viewed by 734
Abstract
Managing shoulder pain typically involves the use of acetaminophen or oral nonsteroidal anti-inflammatory drugs, but prolonged use of these medications can lead to dependence and various side effects. To overcome the dose dependency and side effects of these conventional drugs, animal venoms have [...] Read more.
Managing shoulder pain typically involves the use of acetaminophen or oral nonsteroidal anti-inflammatory drugs, but prolonged use of these medications can lead to dependence and various side effects. To overcome the dose dependency and side effects of these conventional drugs, animal venoms have begun to be utilized. Among them, bee venom stands out for its powerful anti-inflammatory properties, which help relieve pain and treat chronic inflammatory conditions. This review evaluates the efficacy and safety of bee venom acupuncture (BVA) for shoulder pain. In March 2024, we searched 11 databases: 5 international and 6 Korean databases. We identified 23 clinical studies on BVA for shoulder pain. The causes of shoulder pain were post-stroke pain (43.5%), rotator cuff syndrome (17.4%), and brachial plexus palsy (13.0%). The BVA concentration and dosage per session were 0.005–1.0 mg/mL and 0.01–2.0 mL, respectively. All included clinical studies reported positive effects on pain outcomes. This review suggests that BVA, which involves injecting bee venom into acupuncture points, may serve as a viable alternative for pain management. However, the level of evidence in the included studies was low and adverse effects were reported infrequently, indicating that further research is needed. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
Show Figures

Figure 1

23 pages, 1059 KiB  
Review
Botulinum Toxin Type A for Trigeminal Neuralgia: A Comprehensive Literature Review
by Yan Tereshko, Simone Dal Bello, Christian Lettieri, Enrico Belgrado, Gian Luigi Gigli, Giovanni Merlino and Mariarosaria Valente
Toxins 2024, 16(11), 500; https://doi.org/10.3390/toxins16110500 - 20 Nov 2024
Viewed by 757
Abstract
Trigeminal neuralgia is a neuropathic pain syndrome responsive to botulinum toxin type A therapy. This review had the goal of analyzing the different studies published from 2002 to January 2024 to better define the techniques and the types of botulinum toxin type A [...] Read more.
Trigeminal neuralgia is a neuropathic pain syndrome responsive to botulinum toxin type A therapy. This review had the goal of analyzing the different studies published from 2002 to January 2024 to better define the techniques and the types of botulinum toxin type A used, the doses, the injection routes, and the different populations of trigeminal neuralgia patients treated. We considered only articles in which the therapy was administered to humans to treat trigeminal neuralgia. Case reports, case series, open-label, retrospective, and RCT studies were considered. The research was conducted on MEDLINE and the keywords included (trigeminal neuralgia) and (botulinum). Thirty-five articles were considered suitable for this review. Botulinum toxin type A was shown to be an effective therapy for TN pain in all the articles analyzed, albeit there is a lack of standardization in methods and outcomes. The techniques, the doses, and the injection approaches were very heterogeneous among the studies. Only two botulinum toxin type A formulations have been used in this setting: onabotulinumtoxinA and lanbotulinumtoxinA. There were 300 patients treated with onabotulinumtoxinA and 760 treated with lanbotulinumtoxinA overall (in 42 patients, the formulation was not specified). The distinction between etiological and clinical types of TN has been made by only a small portion of the studies. The main adverse event was transient facial asymmetry. Botulinum toxin type A is indeed a promising therapy that is clearly effective for trigeminal neuralgia. OnabotulinumtoxinA is the most common formulation used in Western countries; however, the meager sample of TN patients treated, and the lack of standardization are not sufficient for this therapy to be approved by the FDA or EMA. Indeed, more studies with standardized methods and larger samples are needed for this purpose. Full article
(This article belongs to the Collection Botulinum Toxins on Human Pain)
Show Figures

Figure 1

12 pages, 1883 KiB  
Article
Mycotoxin Prevalence and Microbiological Characteristics of Locally Produced Elected Freekeh Products
by Samer Mudalal
Toxins 2024, 16(11), 499; https://doi.org/10.3390/toxins16110499 - 20 Nov 2024
Viewed by 560
Abstract
Freekeh is produced from roasted, immature wheat grains. It is very popular in Middle Eastern and North African nations. This study aimed to evaluate the occurrence of different types of mycotoxins, physical impurities, and microbiological contamination in local freekeh products. Lateral flow competitive [...] Read more.
Freekeh is produced from roasted, immature wheat grains. It is very popular in Middle Eastern and North African nations. This study aimed to evaluate the occurrence of different types of mycotoxins, physical impurities, and microbiological contamination in local freekeh products. Lateral flow competitive immunochromatographic assay was used to evaluate the occurrence of mycotoxins. It was found that physical impurities for some tested products exceeded the permitted limit (>2% of straw and foreign grains). Moreover, our findings showed that total aerobic bacterial and fungal counts in Freekeh products varied from 1 to 4 logs and from 1.39 to 4.3 logs, respectively. The incidence ranges of aflatoxins and ochratoxin were 3.17–3.33 ppb and 4.63–8.17 ppb, respectively. The levels of deoxynivalenol (DON) and T2/HT2 (trichothecene T2 and deacetylated form HT2) were less than the limit of detection. More than 78% of Freekeh samples tested had aflatoxin and ochratoxin contents higher than the limit permitted by the European Commission (4 and 5 ppb). In conclusion, gaining knowledge about the quality, safety, and labeling of freekeh products can help increase their commercial potential. Further investigations are needed to evaluate the factors affecting contamination levels within the freekeh supply chain. Full article
(This article belongs to the Section Mycotoxins)
Show Figures

Figure 1

15 pages, 2704 KiB  
Article
Comparative Assessment of the Allergenicity of Hyaluronidases from Polistes dominula (Pol d 2), Vespula vulgaris (Ves v 2), and Apis mellifera Venom (Api m 2)
by Johannes Grosch, Bernadette Eberlein, Sebastian Waldherr, Mariona Pascal, Britta Dorn, Clara San Bartolomé, Federico De La Roca Pinzón, Maximilian Schiener, Ulf Darsow, Tilo Biedermann, Jonas Lidholm, Maria Beatrice Bilò, Thilo Jakob, Carsten B. Schmidt-Weber and Simon Blank
Toxins 2024, 16(11), 498; https://doi.org/10.3390/toxins16110498 - 19 Nov 2024
Viewed by 755
Abstract
Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes [...] Read more.
Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201. Full article
(This article belongs to the Section Animal Venoms)
Show Figures

Figure 1

11 pages, 2797 KiB  
Article
ScorpDb: A Novel Open-Access Database for Integrative Scorpion Toxinology
by Masoumeh Baradaran, Fatemeh Salabi, Masoud Mahdavinia, Elaheh Mohammadi, Babak Vazirianzadeh, Ignazio Avella, Seyed Mahdi Kazemi and Tim Lüddecke
Toxins 2024, 16(11), 497; https://doi.org/10.3390/toxins16110497 - 18 Nov 2024
Viewed by 832
Abstract
Scorpion stings are a significant public health concern globally, particularly in tropical and subtropical regions. Scorpion venoms contain a diverse array of bioactive peptides, and different scorpion species around the world typically exhibit varying venom profiles, resulting in a wide range of envenomation [...] Read more.
Scorpion stings are a significant public health concern globally, particularly in tropical and subtropical regions. Scorpion venoms contain a diverse array of bioactive peptides, and different scorpion species around the world typically exhibit varying venom profiles, resulting in a wide range of envenomation symptoms. Despite their harmful effects, scorpion venom peptides hold immense potential for drug development due to their unique characteristics. Therefore, the establishment of a comprehensive database that catalogs scorpions along with their known venom peptides and proteins is imperative in furthering research efforts in this research area. We hereby present ScorpDb, a novel database that offers convenient access to data related to different scorpion species, the peptides and proteins found in their venoms, and the symptoms they can cause. To this end, the ScorpDb database has been primarily advanced to accommodate data on the Iranian scorpion fauna. From there, we propose future community efforts to include a larger diversity of scorpions and scorpion venom components. ScorpDb holds the promise to become a valuable resource for different professionals from a variety of research fields, like toxinologists, arachnologists, and pharmacologists. The database is available at https://www.scorpdb.com/. Full article
(This article belongs to the Section Animal Venoms)
Show Figures

Figure 1

14 pages, 2094 KiB  
Review
65 Years on—Aflatoxin Biomarkers Blossoming: Whither Next?
by Thomas W. Kensler and David L. Eaton
Toxins 2024, 16(11), 496; https://doi.org/10.3390/toxins16110496 - 18 Nov 2024
Viewed by 700
Abstract
Aflatoxins are mycotoxins produced by Aspergillus flavus and several other related organisms and are common contaminants of numerous grains and nuts, especially maize (corn) and peanuts. Although, undoubtedly, aflatoxins have been present in the food of humans for millennia, their toxic effects were [...] Read more.
Aflatoxins are mycotoxins produced by Aspergillus flavus and several other related organisms and are common contaminants of numerous grains and nuts, especially maize (corn) and peanuts. Although, undoubtedly, aflatoxins have been present in the food of humans for millennia, their toxic effects were not discovered until 1960, first becoming evident as a non-infectious outbreak of poisoning of turkeys (Turkey X disease) arising from contaminated groundnut meal. The elucidation of specific chemical structures in 1963 led to the rapid characterization of aflatoxins as among the most potent chemical carcinogens of natural origin ever discovered. As a frontispiece to the Special Issue “65 Years on from Aflatoxin Discovery—A Themed Issue in Honor of Professor John D. Groopman”, we highlight many of Professor Groopman’s important contributions utilizing urinary (aflatoxin–N7–guanine) and, especially, serum (aflatoxin–albumin adducts) biomarkers; this work focused on over 40+ years of the development of analytical methods to measure biomarkers of aflatoxin exposure and their application in experimental and clinical studies. Collectively, this work serves as a template for using chemical-specific biomarkers as key tools to probe ‘exposure–disease relationships’—in this instance, dietary aflatoxins and liver cancer. New approaches to measuring carcinogen biomarkers will build upon this ‘aflatoxin paradigm’ to inform the public health implications of diverse exposures around the world. Full article
Show Figures

Figure 1

23 pages, 1396 KiB  
Review
Gut Dysbiosis and Its Role in the Anemia of Chronic Kidney Disease
by Elisabet Coll, Secundino Cigarran, Jose Portolés and Aleix Cases
Toxins 2024, 16(11), 495; https://doi.org/10.3390/toxins16110495 - 17 Nov 2024
Viewed by 925
Abstract
The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in [...] Read more.
The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the response to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments. Full article
Show Figures

Figure 1

21 pages, 5193 KiB  
Article
Proteomic Profiling of Venoms from Bungarus suzhenae and B. bungaroides: Enzymatic Activities and Toxicity Assessment
by Chenying Yang, Li Ding, Qiyi He, Xiya Chen, Haiting Zhu, Feng Chen, Wanzhou Yang, Yuexin Pan, Zhiyuan Tai, Wenhao Zhang, Zeyuan Yu, Zening Chen and Xiaodong Yu
Toxins 2024, 16(11), 494; https://doi.org/10.3390/toxins16110494 - 16 Nov 2024
Viewed by 1121
Abstract
Kraits are venomous snakes of the genus Bungarus from the family Elapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among the Bungarus species, Bungarus suzhenae and B. bungaroides have been poorly [...] Read more.
Kraits are venomous snakes of the genus Bungarus from the family Elapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among the Bungarus species, Bungarus suzhenae and B. bungaroides have been poorly studied, with little to no information available regarding their venom composition. In this study, a proteomic approach was employed using LC-MS/MS to identify proteins from trypsin-digested peptides. The analysis revealed 102 venom-related proteins from 18 distinct functional protein families in the venom of B. suzhenae, with the primary components being three-finger toxins (3-FTx, 25.84%), phospholipase A2 (PLA2, 40.29%), L-amino acid oxidase (LAAO, 10.33%), Kunitz-type serine protease inhibitors (KUN, 9.48%), and snake venom metalloproteinases (SVMPs, 6.13%). In the venom of B. bungaroides, 99 proteins from 17 families were identified, with primary components being 3-FTx (33.87%), PLA2 (37.91%), LAAO (4.21%), and KUN (16.60%). Enzymatic activity assays confirmed the presence of key venom enzymes. Additionally, the LD50 values for B. suzhenae and B. bungaroides were 0.0133 μg/g and 0.752 μg/g, respectively, providing a reference for toxicity studies of these two species. This research elucidates the proteomic differences in the venoms of these two species, offering a foundation for developing antivenoms and clinical treatments for envenomation. Full article
(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)
Show Figures

Figure 1

13 pages, 1612 KiB  
Article
The Effects of Kernel Type (Inshell, Shelled and Split Almonds) on the Growth and Aflatoxin Production of A. flavus Under Different Combinations of Water Activity and Temperature
by Barbara Szonyi, Guangwei Huang, Tim Birmingham and Dawit Gizachew
Toxins 2024, 16(11), 493; https://doi.org/10.3390/toxins16110493 - 16 Nov 2024
Viewed by 550
Abstract
Almonds are susceptible to infestation by Aspergillus flavus, an aflatoxin-producing fungus. The objective of this study was to investigate the effects of kernel type (inshell, shelled and split almonds) on the ability of A. flavus to grow and produce aflatoxins at different [...] Read more.
Almonds are susceptible to infestation by Aspergillus flavus, an aflatoxin-producing fungus. The objective of this study was to investigate the effects of kernel type (inshell, shelled and split almonds) on the ability of A. flavus to grow and produce aflatoxins at different combinations of temperature (20, 27 and 35 °C), water activity (0.85, 0.92, 0.95 and 0.98 aw) and incubation period (10, 20 and 30 days). There was no fungal growth at 0.85 aw on any of the kernel types. At 0.92 aw, only the split kernels supported growth and aflatoxin synthesis. The fungus was able to grow and produce aflatoxins on all three kernels at 0.95–0.98 aw and 20–35 °C. At 0.98 aw, high total aflatoxin concentrations (>300 µg/kg) were found on the shelled and split kernels at all temperatures. On the inshell nuts, the fungus produced up to 372 µg/kg of total aflatoxins at 0.98 aw and 27 °C. Regression analysis showed that significantly higher levels of aflatoxins were produced at 27 °C (as compared to at 20 and 35 °C) on shelled and split almonds. Incubation time was also a significant predictor of aflatoxin accumulation. The results of this study indicated that shipping almonds below 0.85 aw and reducing storage time would significantly decrease the risk of infestation and aflatoxin production by A. flavus. Full article
Show Figures

Figure 1

11 pages, 485 KiB  
Article
Co-Occurrence of Mycotoxins in the Diet and in the Milk of Dairy Cows from the Southeast Region of Brazil
by Aline Moreira Borowsky, Roice Eliana Rosim, Fernando Gustavo Tonin, Carlos Augusto Fernandes de Oliveira and Carlos Humberto Corassin
Toxins 2024, 16(11), 492; https://doi.org/10.3390/toxins16110492 - 15 Nov 2024
Viewed by 785
Abstract
Mycotoxins are toxic fungi secondary metabolites that develop on feedstuffs and can be transferred into milk, thus representing a public health risk. The objective of this study was to assess the co-occurrence of mycotoxins in the diet and in the milk of dairy [...] Read more.
Mycotoxins are toxic fungi secondary metabolites that develop on feedstuffs and can be transferred into milk, thus representing a public health risk. The objective of this study was to assess the co-occurrence of mycotoxins in the diet and in the milk of dairy cows from the southeast region of Brazil. Samples of total mixed ration (TMR, n = 70) and milk (n = 70) were collected in dairy farms and subjected to multi-mycotoxin analysis using liquid chromatography coupled to tandem mass spectrometry. The aflatoxins (AFs), ochratoxin A (OTA), and T-2 and HT-2 toxins were not detected in TMR samples. In contrast, fumonisins (FBs), zearalenone (ZEN), and deoxynivalenol (DON) were detected in 100, 93, and 24% of TMR samples at mean levels of 336.7 ± 36.98, 80.32 ± 16.06 µg/kg and 292.1 ± 85.68 µg/kg, respectively. Ninety-two percent of TMR samples exhibited co-occurring mycotoxins. In milk, 54% of samples (n = 38) had detectable levels of mycotoxin, while 43% (n = 30) contained two or more types of mycotoxins. DON, FB, and ZEN metabolites (α-zearalenol and β-zearalenol) were the most frequent mycotoxins detected in the milk samples analyzed, at mean concentrations of 0.562 ± 0.112, 2.135 ± 0.296 µg/kg, 2.472 ± 0.436 µg/kg, and 0.343 ± 0.062 µg/kg, respectively. However, none of the analyzed milk samples had levels higher than the maximum permitted limit for AFM1 in Brazil (0.5 µg/L). The results of this trial highlight the concern about the co-occurrence of multiple mycotoxins in TMR and in milk, due to the possible additive or synergistic effects of these compounds. The presence of co-occurring mycotoxins in milk underscores the need for stringent preventive practices to avoid mycotoxin contamination in the diet of dairy cows in Brazil. Full article
(This article belongs to the Special Issue Co-Occurrence of Mycotoxins and Their Combined Toxicity)
Show Figures

Figure 1

13 pages, 1264 KiB  
Article
Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model
by Zuzanna Tomkielska, Jorge Frias, Nelson Simões, Bernardo P. de Bastos, Javier Fidalgo, Ana Casas, Hugo Almeida and Duarte Toubarro
Toxins 2024, 16(11), 491; https://doi.org/10.3390/toxins16110491 - 15 Nov 2024
Viewed by 862
Abstract
Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila [...] Read more.
Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications. Full article
(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)
Show Figures

Graphical abstract

22 pages, 1624 KiB  
Article
Mycotoxin Challenge in Dairy Cows: Assessment of the Efficacy of an Anti-Mycotoxin Agent by Adopting an In Vitro Rumen Simulation Method
by Erica Fiorbelli, Marco Lapris, Michela Errico, Antonella Della Badia, Insaf Riahi, Gabriele Rocchetti and Antonio Gallo
Toxins 2024, 16(11), 490; https://doi.org/10.3390/toxins16110490 - 13 Nov 2024
Viewed by 1118
Abstract
To protect ruminants from the harmful effects of mycotoxins, anti-mycotoxin agents can be added to the dietary ration, thus guaranteeing animal health and production. Therefore, the objective of this study was to evaluate the in vitro ruminal initial sequestration (weak binding) and subsequent [...] Read more.
To protect ruminants from the harmful effects of mycotoxins, anti-mycotoxin agents can be added to the dietary ration, thus guaranteeing animal health and production. Therefore, the objective of this study was to evaluate the in vitro ruminal initial sequestration (weak binding) and subsequent desorption (strong binding) of an anti-mycotoxin agent based on a mixture of adsorbing material, turmeric and milk thistle extracts and yeast-based components to adsorb or bio-convert aflatoxins (AF), fumonisins B1 and B2 (FB), trichothecene deoxynivalenol (DON), T-2 and HT-2 toxins, and zearalenone (ZEN). Two doses were tested: Dose 1 simulated 30 mg/cow/d, while Dose 2 simulated 90 mg/cow/d of the anti-mycotoxin agent. Each treatment involved three analytical replicates at each of three incubation times (1, 4, and 24 h post-incubation), with two independent experimental runs providing experimental replicates. Analytical methods, including UHPLC-HRMS and multivariate analyses, were used to both quantify mycotoxin concentrations and reveal dose-dependent reductions, with statistical validations indicating significant changes in mycotoxin levels across both dose and time. The results indicated that the anti-mycotoxin agent was able to highly bind AFB1, T2, and HT-2 toxins since its concentration was always under the limit of detection (<1 ppb). Regarding ZEN (weak binding mean: 94.6%; strong binding mean: 62.4%) and FBs (weak binding mean: 58.7%; strong binding mean: 32.3%), orthogonal contrasts indicated that the anti-mycotoxin agent was able to effectively bind these toxins using Dose 1 (p < 0.05). This finding suggests that Dose 1 may be sufficient to achieve the targeted effect and that a further increase does not significantly improve the outcome. Regarding DON, a strong linear relationship was observed between dose and adsorption. However, the complex interactions between the mycotoxin, the ruminal environment, and the anti-mycotoxin agent made it difficult to establish a clear dose–effect relationship (p > 0.10). UHPLC-HRMS analysis identified over 1500 mass features in rumen samples, which were further analyzed to assess the effects of the anti-mycotoxin agent. Hierarchical clustering analysis (HCA) revealed significant changes in the untargeted metabolomic profiles of samples treated with mycotoxins compared to control samples, particularly after 24 h with the anti-mycotoxin treatments. Clear differences were noted between strong binding and weak binding samples. Further analysis using orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted distinct metabolomic profiles, with stronger predictive ability in the strong binding group (Q2 cumulative value of 0.57) compared to the weak binding group (0.30). The analysis identified 44 discriminant compounds in the strong binding model and 16 in the weak binding model. Seven compounds were common to both groups, while silibinin, known for its antioxidant and anti-inflammatory properties, was found among the unique compounds in the weak binding group. Overall, the findings suggest that both doses of the anti-mycotoxin agent significantly influenced the chemical profiles in the rumen, particularly enhancing the binding of mycotoxins, thereby supporting the role of phytogenic extracts in mitigating mycotoxin effects. Full article
(This article belongs to the Special Issue Mitigation and Detoxification Strategies of Mycotoxins)
Show Figures

Figure 1

40 pages, 7015 KiB  
Review
Antibacterial Activity and Antifungal Activity of Monomeric Alkaloids
by Amin Mahmood Thawabteh, Aseel Wasel Ghanem, Sara AbuMadi, Dania Thaher, Weam Jaghama, Rafik Karaman, Laura Scrano and Sabino A. Bufo
Toxins 2024, 16(11), 489; https://doi.org/10.3390/toxins16110489 - 12 Nov 2024
Viewed by 1502
Abstract
Scientists are becoming alarmed by the rise in drug-resistant bacterial and fungal strains, which makes it more costly, time-consuming, and difficult to create new antimicrobials from unique chemical entities. Chemicals with pharmacological qualities, such as antibacterial and antifungal elements, can be found in [...] Read more.
Scientists are becoming alarmed by the rise in drug-resistant bacterial and fungal strains, which makes it more costly, time-consuming, and difficult to create new antimicrobials from unique chemical entities. Chemicals with pharmacological qualities, such as antibacterial and antifungal elements, can be found in plants. Alkaloids are a class of chemical compounds found in nature that mostly consist of basic nitrogen atoms. Biomedical science relies heavily on alkaloid compounds. Based on 241 papers published in peer-reviewed scientific publications within the last ten years (2014–2024), we examined 248 natural or synthesized monomeric alkaloids that have antifungal and antibacterial activity against Gram-positive and Gram-negative microorganisms. Based on their chemical structure, the chosen alkaloids were divided into four groups: polyamine alkaloids, alkaloids with nitrogen in the side chain, alkaloids with nitrogen heterocycles, and pseudoalkaloids. With MIC values of less than 1 µg/mL, compounds 91, 124, 125, 136138, 163, 164, 191, 193, 195, 205 and 206 shown strong antibacterial activity. However, with MIC values of below 1 µg/mL, compounds 124, 125, 163, 164, 207, and 224 demonstrated strong antifungal activity. Given the rise in antibiotic resistance, these alkaloids are highly significant in regard to their potential to create novel antimicrobial drugs. Full article
Show Figures

Figure 1

8 pages, 919 KiB  
Case Report
Complete Improvement of Severe Forearm Complex Regional Pain Syndrome with Six High-Dose Incobotulinumtoxin A Injections: Clinical Implications with Respect to the Literature
by Harald Hefter, Marek Moll and Sara Samadzadeh
Toxins 2024, 16(11), 488; https://doi.org/10.3390/toxins16110488 - 10 Nov 2024
Viewed by 809
Abstract
There is some evidence that injections of botulinum neurotoxin effectively reduce pain in complex regional pain syndromes (CRPSs). But no or little experience appears to exist for the application of incobotulinum neurotoxin type A (incoBoNT/A) in complex pain disorders. Here, a case of [...] Read more.
There is some evidence that injections of botulinum neurotoxin effectively reduce pain in complex regional pain syndromes (CRPSs). But no or little experience appears to exist for the application of incobotulinum neurotoxin type A (incoBoNT/A) in complex pain disorders. Here, a case of CRPS type I, characterized by severe symptoms in the left forearm is presented, showed significant continuous improvement following a series of six repetitive (painful) injections into the finger, hand, and forearm muscles of incoBoNT/A every 3 months, administered at declining doses varying between 500 and 100 U. Remarkably, this treatment regimen led to the complete resolution of pain, vaso- and sudomotor symptoms, and hand dystonia. This highlights the possible efficacy of incoBoNT/A in the treatment of CRPS and encourages the further exploration of incoBoNT/A’s role in the successful management of complex pain disorders. Full article
(This article belongs to the Section Bacterial Toxins)
Show Figures

Figure 1

17 pages, 1467 KiB  
Review
Ochratoxin A in Poultry Supply Chain: Overview of Feed Occurrence, Carry-Over, and Pathognomonic Lesions in Target Organs to Promote Food Safety
by Elisabetta Bonerba, Alessio Manfredi, Michela Maria Dimuccio, Patrizio Lorusso, Annamaria Pandiscia, Valentina Terio, Angela Di Pinto, Sara Panseri, Edmondo Ceci and Giancarlo Bozzo
Toxins 2024, 16(11), 487; https://doi.org/10.3390/toxins16110487 - 10 Nov 2024
Viewed by 1043
Abstract
Ochratoxin A (OTA) is a mycotoxin produced by fungi species belonging to the genera Aspergillus spp. and Penicillium spp. The proliferation of OTA-producing fungal species may occur due to inadequate practices during both the pre-harvest and post-harvest stages of feed. Consequently, poultry species [...] Read more.
Ochratoxin A (OTA) is a mycotoxin produced by fungi species belonging to the genera Aspergillus spp. and Penicillium spp. The proliferation of OTA-producing fungal species may occur due to inadequate practices during both the pre-harvest and post-harvest stages of feed. Consequently, poultry species may be exposed to high concentrations of this mycotoxin that can be transferred to animal tissues due to its carry-over, reaching dangerous concentrations in meat and meat products. Therefore, this review aims to propose a comprehensive overview of the effects of OTA on human health, along with data from global studies on the prevalence and concentrations of this mycotoxin in avian feeds, as well as in poultry meat, edible offal, and eggs. Moreover, the review examines significant gross and histopathological lesions in the kidneys and livers of poultry linked to OTA exposure. Finally, the key methods for OTA prevention and decontamination of feed are described. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
Show Figures

Figure 1

28 pages, 13740 KiB  
Article
A Novel P-III Metalloproteinase from Bothrops barnetti Venom Degrades Extracellular Matrix Proteins, Inhibits Platelet Aggregation, and Disrupts Endothelial Cell Adhesion via α5β1 Integrin Receptors to Arginine–Glycine–Aspartic Acid (RGD)-Containing Molecules
by Pedro Henrique de Caires Schluga, Debora Larangote, Ana Maria de Melo, Guilherme Kamienski Lobermayer, Daniel Torrejón, Luciana Souza de Oliveira, Valeria Gonçalves Alvarenga, Dan Erick Vivas-Ruiz, Silvio Sanches Veiga, Eladio Flores Sanchez and Luiza Helena Gremski
Toxins 2024, 16(11), 486; https://doi.org/10.3390/toxins16110486 - 9 Nov 2024
Viewed by 1043
Abstract
Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of [...] Read more.
Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of the Peruvian snake Bothrops barnetti. Bar-III has a molecular mass of approximately 50 kDa and is a glycosylation-dependent functional metalloproteinase. Some biochemical properties of Bar-III, including the full amino acid sequence deduced from its cDNA, are reported. Its enzymatic activity is increased by Ca2+ ions and inhibited by an excess of Zn2+. Synthetic metalloproteinase inhibitors and EDTA also inhibit its proteolytic action. Bar-III degrades several plasma and ECM proteins, including fibrin(ogen), fibronectin, laminin, and nidogen. Platelets play a key role in hemostasis and thrombosis and in other biological process, such as inflammation and immunity, and platelet activation is driven by the platelet signaling receptors, glycoprotein (GP)Ib-IX-V, which binds vWF, and GPVI, which binds collagen. Moreover, Bar-III inhibits vWF- and convulxin-induced platelet aggregation in human washed platelets by cleaving the recombinant A1 domain of vWF and GPVI into a soluble ectodomain fraction of ~55 kDa (sGPVI). Bar-III does not reduce the viability of cultured endothelial cells; however, it interferes with the adhesion of these cells to fibronectin, vitronectin, and RGD peptides, as well as their migration profile. Bar-III binds specifically to the surface of these cells, and part of this interaction involves α5β1 integrin receptors. These results contribute to a better comprehension of the pathophysiology of snakebite accidents/incidents and could be used as a tool to explore novel and safer anti-venom therapeutics. Full article
(This article belongs to the Section Animal Venoms)
Show Figures

Figure 1

19 pages, 1790 KiB  
Article
International Proficiency Test Targeting a Large Panel of Botulinum Neurotoxin Sero- and Subtypes in Different Matrices
by Christine Rasetti-Escargueil, Michel Robert Popoff, Bettina Kampa, Sylvia Worbs, Maud Marechal, Daniel Guerin, Eléa Paillares, Werner Luginbühl and Emmanuel Lemichez
Toxins 2024, 16(11), 485; https://doi.org/10.3390/toxins16110485 - 8 Nov 2024
Viewed by 786
Abstract
Detection of botulinum neurotoxins (BoNTs) involves a combination of technical challenges that call for the execution of inter-laboratory proficiency tests (PTs) to define the performance and ease of implementation of existing diagnostic methods regarding representative BoNT toxin-types spiked in clinical, food, or environmental [...] Read more.
Detection of botulinum neurotoxins (BoNTs) involves a combination of technical challenges that call for the execution of inter-laboratory proficiency tests (PTs) to define the performance and ease of implementation of existing diagnostic methods regarding representative BoNT toxin-types spiked in clinical, food, or environmental matrices. In the framework of the EU project EuroBioTox, we organized an international proficiency test for the detection and quantification of the clinically relevant BoNT/A, B, E, and F sero- and subtypes including concentrations as low as 0.5 ng/mL. BoNTs were spiked in serum, milk, and soil matrices. Here, we evaluate the results of 18 laboratories participating in this PT. Participants have implemented a wide array of detection methods based on functional, immunological, and mass spectrometric principles. Methods implemented in this proficiency test notably included endopeptidase assays either coupled to mass spectrometry (Endopep-MS) or enzyme-linked immunosorbent assays (Endopep-ELISA). This interlaboratory exercise pinpoints the most effective and complementary methods shared by the greatest number of participants, also highlighting the importance of combining the training of selected methods and of distributing toxin reference material to reduce the variability of quantitative data. Full article
Show Figures

Figure 1

17 pages, 3982 KiB  
Systematic Review
Evaluating the Efficacy and Safety of Botulinum Toxin in Treating Overactive Bladder in the Elderly: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials
by Yu-Hsuan Chen, Jen-Hao Kuo, Yen-Ta Huang, Pei-Chun Lai, Yin-Chien Ou and Yu-Ching Lin
Toxins 2024, 16(11), 484; https://doi.org/10.3390/toxins16110484 - 8 Nov 2024
Viewed by 989
Abstract
Overactive bladder (OAB) significantly impairs quality of life in the elderly. Although the intradetrusor injection of botulinum toxin type A (BoNT-A) is a treatment option, its effects on older adults remain uncertain. This study aimed to evaluate the efficacy and safety of BoNT-A [...] Read more.
Overactive bladder (OAB) significantly impairs quality of life in the elderly. Although the intradetrusor injection of botulinum toxin type A (BoNT-A) is a treatment option, its effects on older adults remain uncertain. This study aimed to evaluate the efficacy and safety of BoNT-A intradetrusor injections in elderly OAB patients through a systematic review and meta-analysis. A comprehensive literature search was conducted using the PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases from inception to 30 May 2024. The primary outcomes were improvements in daily urinary incontinence (UI) episodes and patient-reported outcomes, while the secondary outcomes focused on potential adverse events. Four randomized controlled trials with 803 participants were included. BoNT-A injections significantly reduced daily UI episodes at 4–6 weeks (mean difference [MD]: −3.82; 95% confidence interval [CI]: −6.29 to −1.35) and at 12 weeks (MD: −2.17; 95% CI: −3.22 to −1.12). However, BoNT-A was associated with an increased risk of elevated post-void residual (Risk Difference [RD]: 0.154; 95% CI: 0.058 to 0.251) and urinary tract infection (RD: 0.111; 95% CI: 0.005 to 0.217), with no significant difference observed in the initiation of catheterization or hematuria. Trial sequential analysis confirmed a sufficient sample size and statistical power. In conclusion, while BoNT-A effectively manages OAB in the elderly, careful post-injection monitoring is warranted due to its potential risks. Full article
Show Figures

Figure 1

31 pages, 1729 KiB  
Review
Dietary Mycotoxins: An Overview on Toxicokinetics, Toxicodynamics, Toxicity, Epidemiology, Detection, and Their Mitigation with Special Emphasis on Aflatoxicosis in Humans and Animals
by James Kibugu, Leonard Munga, David Mburu, Fredrick Maloba, Joanna E. Auma, Delia Grace and Johanna F. Lindahl
Toxins 2024, 16(11), 483; https://doi.org/10.3390/toxins16110483 - 8 Nov 2024
Viewed by 1130
Abstract
Mycotoxins are secondary metabolites of filamentous fungi and ubiquitous dietary contaminants. Aflatoxins, a group of mycotoxins with high prevalence and toxicity, have raised a high level of public health concern, the most prevalent and toxic being aflatoxin B1 (AFB1). Many aspects appertaining to [...] Read more.
Mycotoxins are secondary metabolites of filamentous fungi and ubiquitous dietary contaminants. Aflatoxins, a group of mycotoxins with high prevalence and toxicity, have raised a high level of public health concern, the most prevalent and toxic being aflatoxin B1 (AFB1). Many aspects appertaining to AFB1 poisoning are not well understood. Yet this information is necessary to devise appropriate surveillance and mitigation strategies against human and animal aflatoxicosis. This review provides an in-depth update of work carried out on mycotoxin poisoning, particularly aflatoxicosis in humans and animals, to identify gaps in knowledge. Hypotheses explaining the functional significance of mycotoxins in fungal biology and their dietary epidemiological data are presented and briefly discussed. The toxicology of aflatoxins and the challenges of their mitigation are discussed in depth. It was concluded that the identification of potential mycotoxin-hazard-prone food items and quantification of the associated risk of cancer ailments in humans is a prime priority. There is a dearth of reliable sampling methodologies for estimating AFB1 in animal feed. Data update on AFB1 in animal feed and its implication in animal production, mitigation strategies, and elucidation of risk factors to this hazard is required. To reduce the burden of aflatoxins, surveillance employing predictive technology, and biocontrol strategies seem promising approaches. Full article
(This article belongs to the Special Issue Occurrence, Toxicity, Metabolism, Analysis and Control of Mycotoxins)
Show Figures

Figure 1

20 pages, 6584 KiB  
Article
Persistence of Microcystin in Three Agricultural Ponds in Georgia, USA
by Jaclyn E. Smith, James A. Widmer, Jennifer L. Wolny, Laurel L. Dunn, Matthew D. Stocker, Robert L. Hill, Oliva Pisani, Alisa W. Coffin and Yakov Pachepsky
Toxins 2024, 16(11), 482; https://doi.org/10.3390/toxins16110482 - 7 Nov 2024
Viewed by 686
Abstract
Cyanobacteria and their toxins can have multiple effects on agricultural productivity and water bodies. Cyanotoxins can be transported to nearby crops and fields during irrigation and may pose a risk to animal health through water sources. Spatial and temporal variations in cyanotoxin concentrations [...] Read more.
Cyanobacteria and their toxins can have multiple effects on agricultural productivity and water bodies. Cyanotoxins can be transported to nearby crops and fields during irrigation and may pose a risk to animal health through water sources. Spatial and temporal variations in cyanotoxin concentrations have been reported for large freshwater sources such as lakes and reservoirs, but there are fewer studies on smaller agricultural surface water bodies. To determine whether spatiotemporal patterns of the cyanotoxin microcystin occurred in agricultural waters used for crop irrigation and livestock watering, three agricultural ponds on working farms in Georgia, USA, were sampled monthly within a fixed spatial grid over a 17-month period. Microcystin concentrations, which ranged between 0.04 and 743.75 ppb, were determined using microcystin–ADDA ELISA kits. Temporal stability was assessed using mean relative differences between microcystin concentrations at each location and averaged concentrations across ponds on each sampling date. There were locations or zones in all three ponds that were consistently higher or lower than the average daily microcystin concentrations throughout the year, with the highest microcystin concentrations occurring in winter. Additionally, microcystin patterns were strongly correlated with the patterns of chlorophyll, phycocyanin, and turbidity. The results of this work showed that consistent spatiotemporal patterns in cyanotoxins can occur in produce irrigation and livestock watering ponds, and this should be accounted for when developing agricultural water monitoring programs. Full article
(This article belongs to the Special Issue Advances in Cyanotoxins: Latest Developments in Risk Assessment)
Show Figures

Figure 1

10 pages, 1862 KiB  
Article
Characterization of a Diaporthe toxica Strain: Growth, Spore Formation, Phomopsin-A, and Alkaloids Production on Lupins
by Francesco Buccioni, Chiara Rossi, Annalisa Serio, Federico Fanti and Antonello Paparella
Toxins 2024, 16(11), 481; https://doi.org/10.3390/toxins16110481 - 7 Nov 2024
Viewed by 788
Abstract
The growing interest in vegetable proteins, namely those derived from lupins, has raised concerns over potential safety risks associated with these food products. Lupin serves as the main host for the mycotoxin-producing fungus called Diaporthe toxica. This species, which is associated with [...] Read more.
The growing interest in vegetable proteins, namely those derived from lupins, has raised concerns over potential safety risks associated with these food products. Lupin serves as the main host for the mycotoxin-producing fungus called Diaporthe toxica. This species, which is associated with animal diseases, has been scarcely characterized. Recently, phomopsin-A (PHO-A), the main mycotoxin produced by D. toxica, was found to be harmful to humans. Therefore, this study aimed at characterizing D. toxica growth and spore formation both in vitro and on lupin samples. In addition, the production of PHO-A and alkaloids was investigated on lupin beans by using three different inoculation methods. Particularly, growth and spore production were evaluated on different media, while PHO-A and alkaloid production were determined by means of µSPE extraction followed by UHPLC-MS/MS and HPLC-MS/MS, respectively. The results have demonstrated differences in growth on different media, with potato and oat-flakes-based media being the best options. Conversely, D. toxica was not able to produce spores on agar media, but only on lupin beans. Moreover, a thorough analysis of PHO-A production revealed an increase over time, reaching values up to 1082.17 ppm after 21 days on artificially rehydrated samples. On the other side, the analysis of alkaloids revealed impressive results, as this species produced great quantities of the quinolizidine alkaloids (QA) that are normally present in lupin seeds such as lupanine, sparteine, multiflorine, and hydroxylupanine. On balance, considering these results, different metabolic pathways were demonstrated in D. toxica, which are not adequately described in the existing literature. These data are of paramount importance to deepen the knowledge about a fungal species that is important to ensure the safety of lupin and lupin-based products. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
Show Figures

Figure 1

6 pages, 241 KiB  
Opinion
Does the Diffusion Profile Differ Between Botulinum Toxin Type a Formulations? Implications for the Management of Post-Stroke Spasticity
by Alessandro Picelli, Stefano Tamburin, Rita Di Censo, Nicola Smania and Mirko Filippetti
Toxins 2024, 16(11), 480; https://doi.org/10.3390/toxins16110480 - 7 Nov 2024
Viewed by 1249
Abstract
Botulinum toxin type A is a first-line treatment for post-stroke spasticity, with selective action at nerve endings and minimal effects beyond the injection site. However, concerns about potential adverse reactions due to toxin diffusion and spread can significantly influence physicians’ therapeutic decisions in [...] Read more.
Botulinum toxin type A is a first-line treatment for post-stroke spasticity, with selective action at nerve endings and minimal effects beyond the injection site. However, concerns about potential adverse reactions due to toxin diffusion and spread can significantly influence physicians’ therapeutic decisions in managing post-stroke spasticity. Current evidence shows that while the main formulations of botulinum toxin type A have different molecular weights and sizes, they do not exhibit differing diffusion profiles. Instead, the key factors determining botulinum toxin type A diffusion and spread in post-stroke spasticity management are the dose (i.e., the actual amount of 150 kDa neurotoxin protein injected), dilution, and injection volume. Other injection-related factors, such as the needle gauge and injection speed, have also been suggested to have a secondary influence on botulinum toxin type A diffusion and spread. The needs of patients with post-stroke spasticity may vary, and depending on treatment goals, botulinum toxin type A diffusion and spread can be something to avoid or may offer therapeutic benefits by reaching a greater number of nerve terminals in the target muscle, enhancing the toxin’s effect. These factors should be carefully evaluated in spasticity clinics. Full article
32 pages, 4197 KiB  
Article
Chlorophyll-Amended Organoclays for the Detoxification of Ochratoxin A
by Johnson O. Oladele, Meichen Wang, Xenophon Xenophontos, Kendall Lilly, Phanourios Tamamis and Timothy D. Phillips
Toxins 2024, 16(11), 479; https://doi.org/10.3390/toxins16110479 - 6 Nov 2024
Viewed by 713
Abstract
Climate change has been associated with outbreaks of mycotoxicosis following periods of drought, enhanced fungal growth, and increased exposure to mycotoxins. For detoxification, the inclusion of clay-based materials in food and drinking water has resulted in a very promising strategy to reduce mycotoxin [...] Read more.
Climate change has been associated with outbreaks of mycotoxicosis following periods of drought, enhanced fungal growth, and increased exposure to mycotoxins. For detoxification, the inclusion of clay-based materials in food and drinking water has resulted in a very promising strategy to reduce mycotoxin exposure. In this strategy, mycotoxins are tightly sorbed to high-affinity clay particles in the gastrointestinal tract, thus decreasing bioavailability, uptake to blood, and potential toxicity. This study investigated the ability of chlorophyll and chlorophyllin-amended montmorillonite clays to decrease the toxicity of ochratoxin A (OTA). The sorption mechanisms of OTA binding to surfaces of sorbents, as well as binding parameters such as capacity, affinity, enthalpy, and free energy, were examined. Chlorophyll-amended organoclay (CMCH) demonstrated the highest binding (72%) and was better than the chlorophyllin-amended hydrophilic clay (59%), possibly due to the hydrophobicity of OTA (LogP 4.7). In silico studies using molecular dynamics simulations showed that CMCH improves OTA binding in comparison to parent clay in line with experiments. Simulations depicted that chlorophyll amendments on clay facilitated OTA molecules binding both directly, through enhancing OTA binding on the clay, or predominantly indirectly, through OTA molecules interacting with bound chlorophyll amendments. Simulations uncovered the key role of calcium ions in OTA binding, particularly in neutral conditions, and demonstrated that CMCH binding to OTA is enhanced under both neutral and acidic conditions. Furthermore, the protection of various sorbents against OTA-induced toxicity was carried out using two living organisms (Hydra vulgaris and Caenorhabditis elegans) which are susceptible to OTA toxicity. This study showed the significant detoxification of OTA (33% to 100%) by inclusion of sorbents. Organoclay (CMCH) at 0.5% offered complete protection. These findings suggest that the chlorophyll-amended organoclays described in this study could be included in food and feed as OTA binders and as potential filter materials for water and beverages to protect against OTA contaminants during outbreaks and emergencies. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
Show Figures

Figure 1

24 pages, 3424 KiB  
Review
Mycotoxin Biodegradation by Bacillus Bacteria—A Review
by Thanh Nguyen, Xiaojing Chen, Linlin Ma and Yunjiang Feng
Toxins 2024, 16(11), 478; https://doi.org/10.3390/toxins16110478 - 4 Nov 2024
Viewed by 1420
Abstract
Mycotoxins are toxic secondary metabolites produced by various types of fungi that are known to contaminate various food products; their presence in the food chain poses significant risks to human and animal health and leads to enormous economic losses in the food and [...] Read more.
Mycotoxins are toxic secondary metabolites produced by various types of fungi that are known to contaminate various food products; their presence in the food chain poses significant risks to human and animal health and leads to enormous economic losses in the food and feed industry worldwide. Ensuring food safety and quality by detoxifying mycotoxin is therefore of paramount importance. Several procedures to control fungal toxins have been extensively investigated, such as preventive measures, physical and chemical methods, and biological strategies. In recent years, microbial degradation of mycotoxins has attracted much attention due to its reliability, efficiency, and cost-effectiveness. Notably, bacterial species from the Bacillus genus have emerged as promising candidates for mycotoxin decontamination owing to their diverse metabolic capabilities and resilience in harsh environmental conditions. This review manuscript aims to provide a summary of recent studies on the biodegradation of fungal toxins by Bacillus bacteria, thereby illustrating their potential applications in the development of mycotoxin-degrading products. Full article
Show Figures

Figure 1

13 pages, 4807 KiB  
Article
The High-Efficiency Degradation of Multiple Mycotoxins by Lac-W Laccase in the Presence of Mediators
by Mengshuang Jia, Xiaohu Yu, Kun Xu, Xiaodan Gu, Nicholas J. Harmer, Youbao Zhao, Yuqiang Xiang, Xia Sheng, Chenglong Li, Xiang-Dang Du, Jiajia Pan and Wenbo Hao
Toxins 2024, 16(11), 477; https://doi.org/10.3390/toxins16110477 - 4 Nov 2024
Viewed by 773
Abstract
Mycotoxin cocontamination is a severe threat to health and economic security worldwide. The mycotoxins aflatoxin B1 (AFB1), zearalenone (ZEN), deoxynivalenol, T-2 toxin, fumonisin B1, and ochratoxin A are of particular concern due to their substantial toxicity. Lac-W is [...] Read more.
Mycotoxin cocontamination is a severe threat to health and economic security worldwide. The mycotoxins aflatoxin B1 (AFB1), zearalenone (ZEN), deoxynivalenol, T-2 toxin, fumonisin B1, and ochratoxin A are of particular concern due to their substantial toxicity. Lac-W is a laccase with the unique property of degrading these six mycotoxins in the absence of redox mediators. Nevertheless, their degradation rates are low. This work aims to improve the ability of Lac-W to degrade these six mycotoxins and to elucidate its detoxification mechanism. Including redox mediators increased the Lac-W degradation efficiency drastically, and completely degraded AFB1 and ZEN within one hour. Additionally, Lac-W-AS has good temperature, pH, and ions adaptability in ZEN degradation. Lac-W-AS reduced the ZEN toxicity because ZEN degradation products significantly restored the bioluminescence intensity of Vibrio fischeri. A Lac-W-AS-mediated oxidation product of ZEN was structurally characterized as 15-OH-ZEN by UHPLC-MS/MS. Linear sweep voltammetry showed that AS affected the potential of Lac-W and accelerated the oxidation of ZEN. Finally, the combination of mediators (acetosyringone and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate)) improved the degradation rate of mycotoxins. This work highlights that the combination of Lac-W with mediators serves as a good candidate for degrading multi-mycotoxin contaminants in food and feedstuff. Full article
Show Figures

Figure 1

10 pages, 2813 KiB  
Article
Design of a Duplex-to-Complex Structure-Switching Approach for the Homogeneous Determination of Marine Biotoxins in Water
by Awatef Al-Tabban, Amina Rhouati, Amjad Fataftah, Dana Cialla-May, Jürgen Popp and Mohammed Zourob
Toxins 2024, 16(11), 476; https://doi.org/10.3390/toxins16110476 - 4 Nov 2024
Viewed by 818
Abstract
In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein [...] Read more.
In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein (FAM). In parallel, complementary DNA (cDNA) sequences specific to each aptamer were conjugated to a fluorescence quencher BHQ1. In the absence of the target, an aptamer–cDNA duplex structure is formed, and the fluorescence is quenched. By adding the toxin, the aptamer tends to bind to its target and releases the cDNA. The fluorescence intensity is consequently restored after the formation of the complex aptamer–toxin, where the fluorescence recovery is directly correlated with the analyte concentration. Based on this principle, a highly sensitive detection of the six marine toxins was achieved, with the limits of detection of 0.15, 0.06, 0.075, 0.027, 0.041, and 0.026 nM for microcystin-LR, anatoxin-α, saxitoxin, cylindrospermopsin, okadaic acid, and brevetoxin, respectively. Moreover, each aptameric assay showed a very good selectivity towards the other five marine toxins. Finally, the developed technique was applied for the detection of the six toxins in spiked water samples with excellent recoveries. Full article
Show Figures

Figure 1

15 pages, 2138 KiB  
Article
Machine Learning Framework for Conotoxin Class and Molecular Target Prediction
by Duc P. Truong, Lyman K. Monroe, Robert F. Williams and Hau B. Nguyen
Toxins 2024, 16(11), 475; https://doi.org/10.3390/toxins16110475 - 3 Nov 2024
Viewed by 849
Abstract
Conotoxins are small and highly potent neurotoxic peptides derived from the venom of marine cone snails which have captured the interest of the scientific community due to their pharmacological potential. These toxins display significant sequence and structure diversity, which results in a wide [...] Read more.
Conotoxins are small and highly potent neurotoxic peptides derived from the venom of marine cone snails which have captured the interest of the scientific community due to their pharmacological potential. These toxins display significant sequence and structure diversity, which results in a wide range of specificities for several different ion channels and receptors. Despite the recognized importance of these compounds, our ability to determine their binding targets and toxicities remains a significant challenge. Predicting the target receptors of conotoxins, based solely on their amino acid sequence, remains a challenge due to the intricate relationships between structure, function, target specificity, and the significant conformational heterogeneity observed in conotoxins with the same primary sequence. We have previously demonstrated that the inclusion of post-translational modifications, collisional cross sections values, and other structural features, when added to the standard primary sequence features, improves the prediction accuracy of conotoxins against non-toxic and other toxic peptides across varied datasets and several different commonly used machine learning classifiers. Here, we present the effects of these features on conotoxin class and molecular target predictions, in particular, predicting conotoxins that bind to nicotinic acetylcholine receptors (nAChRs). We also demonstrate the use of the Synthetic Minority Oversampling Technique (SMOTE)-Tomek in balancing the datasets while simultaneously making the different classes more distinct by reducing the number of ambiguous samples which nearly overlap between the classes. In predicting the alpha, mu, and omega conotoxin classes, the SMOTE-Tomek PCA PLR model, using the combination of the SS and P feature sets establishes the best performance with an overall accuracy (OA) of 95.95%, with an average accuracy (AA) of 93.04%, and an f1 score of 0.959. Using this model, we obtained sensitivities of 98.98%, 89.66%, and 90.48% when predicting alpha, mu, and omega conotoxin classes, respectively. Similarly, in predicting conotoxins that bind to nAChRs, the SMOTE-Tomek PCA SVM model, which used the collisional cross sections (CCSs) and the P feature sets, demonstrated the highest performance with 91.3% OA, 91.32% AA, and an f1 score of 0.9131. The sensitivity when predicting conotoxins that bind to nAChRs is 91.46% with a 91.18% sensitivity when predicting conotoxins that do not bind to nAChRs. Full article
(This article belongs to the Special Issue Conotoxins: Evolution, Classifications and Targets)
Show Figures

Graphical abstract

11 pages, 904 KiB  
Review
Botulinum Toxin Effects on Freezing of Gait in Parkinson’s Disease: A Systematic Review
by Nicola Tambasco, Pasquale Nigro, Alessandro Mechelli, Michele Duranti and Lucilla Parnetti
Toxins 2024, 16(11), 474; https://doi.org/10.3390/toxins16110474 - 3 Nov 2024
Viewed by 764
Abstract
Freezing of gait is a frequent phenomenon and can be one of the most debilitating motor impairments in Parkinson’s disease, especially in the advanced stages. It is currently defined as a brief episodic absence or any marked reduction in the forward progression of [...] Read more.
Freezing of gait is a frequent phenomenon and can be one of the most debilitating motor impairments in Parkinson’s disease, especially in the advanced stages. It is currently defined as a brief episodic absence or any marked reduction in the forward progression of the feet, despite the intention to walk. Greater severity of freezing of gait has been associated with more frequent falls, postural instability, and executive dysfunction. However, botulinum neurotoxin is one of the most widely administered therapies for motor and non-motor symptoms, including freezing of gait, in parkinsonism. To date, the literature has had conflicting results on the use of botulinum toxin in the treatment of freezing of gait in Parkinson’s disease patients. In light of this, we reviewed the findings of past studies that specifically investigated the effects of botulinum toxin on freezing of gait in Parkinson’s disease in order to better understand this issue. Full article
(This article belongs to the Special Issue Advances in the Treatment of Movement Disorders with Botulinum Toxins)
Show Figures

Figure 1

17 pages, 2038 KiB  
Article
Integrated Approach to Cyclopiazonic Acid Cytotoxicity Using In Vitro (2D and 3D Models) and In Silico Methods
by Carmen Martínez-Alonso, Luana Izzo, Yelko Rodríguez-Carrasco and María-José Ruiz
Toxins 2024, 16(11), 473; https://doi.org/10.3390/toxins16110473 - 3 Nov 2024
Viewed by 856
Abstract
Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by Aspergillus and Penicillium genera present mainly in fruit, cereals and nuts. This study compares the cytotoxicity produced by CPA after 24, 48 and 72 h of exposure using both monolayers and 3D spheroids [...] Read more.
Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by Aspergillus and Penicillium genera present mainly in fruit, cereals and nuts. This study compares the cytotoxicity produced by CPA after 24, 48 and 72 h of exposure using both monolayers and 3D spheroids in human neuroblastoma SH-SY5Y cells. Furthermore, CPA toxicokinetics was evaluated using in silico models. Cytotoxicity increased dose- and time-dependently, as shown by the MTT assay. The lowest CPA IC50 values were found in the monolayer study compared to the 3D spheroids at all exposure times (24 h: 864.01 vs. 1132; 48 h: 437 vs. 1069; 72 h: 392 vs. 567 nM). The CPA exposure on SH-SY5Y spheroid organization and morphology was also studied. Morphological changes, including spheroid disaggregation, were observed after mycotoxin exposure. The in silico methods, SwissADME and admetSAR, were used for short and full ADMEt profiles of CPA. The ADMEt predictive profile shows high gastrointestinal absorption and ability to penetrate the blood–brain barrier. Including in silico studies emphasizes the comprehensive approach to understanding mycotoxin toxicity and risk assessment. By combining in vitro 3D spheroid models with computational simulations, this study aims to provide a holistic perspective on the effects of CPA, enhancing the accuracy and relevance of our findings. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop