Toxins

13 pages, 539 KiB

Open AccessReview

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

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)

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23 pages, 1059 KiB

Open AccessReview

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

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)

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12 pages, 1883 KiB

Open AccessArticle

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

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)

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15 pages, 2704 KiB

Open AccessArticle

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

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)

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11 pages, 2797 KiB

Open AccessArticle

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

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)

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14 pages, 2094 KiB

Open AccessReview

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

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

(This article belongs to the Special Issue 65 Years On from Aflatoxin Discovery—a Themed Issue in Honor of Professor John D. Groopman)

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23 pages, 1396 KiB

Open AccessReview

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

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 responsiveness 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

(This article belongs to the Special Issue Targeting Uremic Toxins in Chronic Kidney Disease: Novel Therapeutic Approaches)

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21 pages, 5193 KiB

Open AccessArticle

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

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)

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13 pages, 1612 KiB

Open AccessArticle

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

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 a_w) and incubation period (10, 20 and 30 days). There was no fungal growth at 0.85 a_w on any of the kernel types. At 0.92 a_w, 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 a_w and 20–35 °C. At 0.98 a_w, 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 a_w 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 a_w and reducing storage time would significantly decrease the risk of infestation and aflatoxin production by A. flavus. Full article

(This article belongs to the Special Issue Toxicity, Mitigation and Chemical Analysis of Aflatoxins and Other Toxic Metabolites Produced by Aspergillus)

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11 pages, 485 KiB

Open AccessArticle

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

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)

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13 pages, 1264 KiB

Open AccessArticle

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

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)

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Graphical abstract

22 pages, 1624 KiB

Open AccessArticle

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

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)

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40 pages, 7015 KiB

Open AccessReview

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

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, 136–138, 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

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8 pages, 919 KiB

Open AccessCase 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

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)

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17 pages, 1467 KiB

Open AccessReview

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

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)

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28 pages, 13740 KiB

Open AccessArticle

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

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)

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19 pages, 1790 KiB

Open AccessArticle

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

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

(This article belongs to the Special Issue The EuroBioTox Project: Progress Towards the Detection and Identification of Biotoxins via Standardization, Training, and Method Evaluation)

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17 pages, 3982 KiB

Open AccessSystematic 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

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

(This article belongs to the Special Issue Application of Botulinum Neurotoxin in Lower Urinary Tract Dysfunctions: Where Are We Now? II)

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31 pages, 1729 KiB

Open AccessReview

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

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)

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