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Toxins, Volume 16, Issue 7 (July 2024) – 41 articles

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13 pages, 963 KiB  
Article
Effects of Different Shelling Methods on Data Variability during Field Screening for Reduced Aflatoxin Contamination in Maize
by Alison Adams, Daniel Jeffers, Shien Lu, Baozhu Guo, W. Paul Williams and Jake C. Fountain
Toxins 2024, 16(7), 324; https://doi.org/10.3390/toxins16070324 - 19 Jul 2024
Viewed by 158
Abstract
Non-genetic variation limits the identification of novel maize germplasm with genetic markers for reduced Aspergillus flavus infection and aflatoxin contamination. Aflatoxin measurements can vary substantially within fields containing the same germplasm following inoculation with A. flavus. While some variation is expected due [...] Read more.
Non-genetic variation limits the identification of novel maize germplasm with genetic markers for reduced Aspergillus flavus infection and aflatoxin contamination. Aflatoxin measurements can vary substantially within fields containing the same germplasm following inoculation with A. flavus. While some variation is expected due to microenvironmental differences, components of field screening methodologies may also contribute to variability in collected data. Therefore, the objective of this study is to test the effects of three different shelling methods (whole ear (WE), ear end removal (EER), and inoculation site-surrounding (ISS)) to obtain bulk samples from maize on aflatoxin measurements. Five ears per row of three inbred lines and two hybrids were inoculated with A. flavus, then shelled using the three different methods, and aflatoxin was quantified. Overall, EER and ISS resulted in reduced coefficients of variance (CVs) in comparison to WE for both inbred and hybrid maize lines, with two exceptions. Susceptible B73 showed increased CVs with both EER and ISS compared to WE, and resistant Mp719’s EER CVs marginally increased compared to WE. While WE is the standard practice for most breeding programs due to its technical simplicity, EER and ISS may allow for finely phenotyping parental lines for further breeding applications. Full article
(This article belongs to the Section Mycotoxins)
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18 pages, 1077 KiB  
Review
Gait Reconstruction Strategy Using Botulinum Toxin Therapy Combined with Rehabilitation
by Takatoshi Hara, Toru Takekawa and Masahiro Abo
Toxins 2024, 16(7), 323; https://doi.org/10.3390/toxins16070323 - 19 Jul 2024
Viewed by 167
Abstract
Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have [...] Read more.
Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function. Full article
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16 pages, 8494 KiB  
Article
Identification of a Chimera Mass Spectrum of Isomeric Lipid A Species Using Negative Ion Tandem Mass Spectrometry
by Ágnes Dörnyei, Anikó Kilár and Viktor Sándor
Toxins 2024, 16(7), 322; https://doi.org/10.3390/toxins16070322 - 18 Jul 2024
Viewed by 265
Abstract
The toxic nature of bacterial endotoxins is affected by the structural details of lipid A, including the variety and position of acyl chains and phosphate group(s) on its diglucosamine backbone. Negative-ion mode tandem mass spectrometry is a primary method for the structure elucidation [...] Read more.
The toxic nature of bacterial endotoxins is affected by the structural details of lipid A, including the variety and position of acyl chains and phosphate group(s) on its diglucosamine backbone. Negative-ion mode tandem mass spectrometry is a primary method for the structure elucidation of lipid A, used independently or in combination with separation techniques. However, it is challenging to accurately characterize constitutional isomers of lipid A extracts by direct mass spectrometry, as the elemental composition and molecular mass of these molecules are identical. Thus, their simultaneous fragmentation leads to a composite, so-called chimera mass spectrum. The present study focuses on the phosphopositional isomers of the classical monophosphorylated, hexaacylated Escherichia coli-type lipid A. Collision-induced dissociation (CID) was performed in an HPLC-ESI-QTOF system. Energy-resolved mass spectrometry (ERMS) was applied to uncover the distinct fragmentation profiles of the phosphorylation isomers. A fragmentation strategy applying multi-levels of collision energy has been proposed and applied to reveal sample complexity, whether it contains only a 4′-phosphorylated species or a mixture of 1- and 4′-phosphorylated variants. This comparative fragmentation study of isomeric lipid A species demonstrates the high potential of ERMS-derived information for the successful discrimination of co-ionized phosphorylation isomers of hexaacylated lipid A. Full article
(This article belongs to the Topic Application of Analytical Technology in Metabolomics)
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13 pages, 1462 KiB  
Article
Citrinin Provoke DNA Damage and Cell-Cycle Arrest Related to Chk2 and FANCD2 Checkpoint Proteins in Hepatocellular and Adenocarcinoma Cell Lines
by Darija Stupin Polančec, Sonja Homar, Daniela Jakšić, Nevenka Kopjar, Maja Šegvić Klarić and Sanja Dabelić
Toxins 2024, 16(7), 321; https://doi.org/10.3390/toxins16070321 - 17 Jul 2024
Viewed by 226
Abstract
Citrinin (CIT), a polyketide mycotoxin produced by Penicillium, Aspergillus, and Monascus species, is a contaminant that has been found in various food commodities and was also detected in house dust. Several studies showed that CIT can impair the kidney, liver, heart, [...] Read more.
Citrinin (CIT), a polyketide mycotoxin produced by Penicillium, Aspergillus, and Monascus species, is a contaminant that has been found in various food commodities and was also detected in house dust. Several studies showed that CIT can impair the kidney, liver, heart, immune, and reproductive systems in animals by mechanisms so far not completely elucidated. In this study, we investigated the CIT mode of action on two human tumor cell lines, HepG2 (hepatocellular carcinoma) and A549 (lung adenocarcinoma). Cytotoxic concentrations were determined using an MTT proliferation assay. The genotoxic effect of sub-IC50 concentrations was investigated using the alkaline comet assay and the impact on the cell cycle using flow cytometry. Additionally, the CIT effect on the total amount and phosphorylation of two cell-cycle-checkpoint proteins, the serine/threonine kinase Chk2 and Fanconi anemia (FA) group D2 (FANCD2), was determined by the cell-based ELISA. The data were analyzed using GraphPad Prism statistical software. The CIT IC50 for HepG2 was 107.3 µM, and for A549, it was >250 µM. The results showed that sensitivity to CIT is cell-type dependent and that CIT in sub-IC50 and near IC50 induces significant DNA damage and cell-cycle arrest in the G2/M phase, which is related to the increase in total and phosphorylated Chk2 and FANCD2 checkpoint proteins in HepG2 and A549 cells. Full article
(This article belongs to the Section Mycotoxins)
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11 pages, 515 KiB  
Article
Treatment of Primary Axillary Hyperhidrosis with Two Doses of Botulinum Toxin A—Observational Study
by María Jesús Antón Andrés, Ernesto Domingo Candau Pérez and María Pilar Bermejo de la Fuente
Toxins 2024, 16(7), 320; https://doi.org/10.3390/toxins16070320 - 16 Jul 2024
Viewed by 280
Abstract
Hyperhidrosis (HH) is defined as the production of more sweat than is necessary for its thermoregulatory function, negatively affecting patients’ quality of life and interfering with their social, work and family life. In this context, the aim of thisstudy was to evaluate the [...] Read more.
Hyperhidrosis (HH) is defined as the production of more sweat than is necessary for its thermoregulatory function, negatively affecting patients’ quality of life and interfering with their social, work and family life. In this context, the aim of thisstudy was to evaluate the efficacy of two different doses of botulinum toxin type A (50 or 100 units) in each axilla in severe primary axillary hyperhidrosis. A descriptive, observational, cross-sectional and post-authorisation study was conducted onpatients referred to our department.Thirty-one patients with severe primary axillary hyperhidrosis were included, some of whom received more than one infiltration during the follow-up period, performing a total of 82 procedures. They were assigned by simple random sampling to two types of treatment: infiltration of 50 or 100 units (U) of botulinum toxin A per axilla.Hyperhidrosis severity was assessed using the Hyperhidrosis Disease Severity Scale (HDSS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. Onabotulinum toxin A infiltration reduced the severity of hyperhidrosis and improved the quality of life of the treated patients, with no significant differences between the two groups. Full article
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21 pages, 3584 KiB  
Article
Metabolome and Its Mechanism Profiling in the Synergistic Toxic Effects Induced by Co-Exposure of Tenuazonic Acid and Patulin in Caco-2 Cells
by Yuxian Qin, Hongyuan Zhou, Yulian Yang, Ting Guo, Ying Zhou, Yuhao Zhang and Liang Ma
Toxins 2024, 16(7), 319; https://doi.org/10.3390/toxins16070319 - 15 Jul 2024
Viewed by 318
Abstract
Tenuazonic acid (TeA), usually found in cereals, fruits, vegetables, oil crops, and their products, was classified as one of the highest public health problems by EFSA as early as 2011, but it has still not been regulated by legislation due to the limited [...] Read more.
Tenuazonic acid (TeA), usually found in cereals, fruits, vegetables, oil crops, and their products, was classified as one of the highest public health problems by EFSA as early as 2011, but it has still not been regulated by legislation due to the limited toxicological profile. Moreover, it has been reported that the coexistence of TeA and patulin (PAT) has been found in certain agricultural products; however, there are no available data about the combined toxicity. Considering that the gastrointestinal tract is the physiological barrier of the body, it would be the first target site at which exogenous substances interact with the body. Thus, we assessed the combined toxicity (cell viability, ROS, CAT, and ATP) in Caco-2 cells using mathematical modeling (Chou-Talalay) and explored mechanisms using non-targeted metabolomics and molecular biology methods. It revealed that the co-exposure of TeA + PAT (12.5 μg/mL + 0.5 μg/mL) can induce enhanced toxic effects and more severe oxidative stress. Mechanistically, the lipid and amino acid metabolisms and PI3K/AKT/FOXO signaling pathways were mainly involved in the TeA + PAT-induced synergistic toxic effects. Our study not only enriches the scientific basis for the development of regulatory policies but also provides potential targets and treatment options for alleviating toxicities. Full article
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14 pages, 1672 KiB  
Article
Aspergillus and Fusarium Mycotoxin Contamination in Maize (Zea mays L.): The Interplay of Nitrogen Fertilization and Hybrids Selection
by Muhoja Sylivester Nyandi and Péter Pepó
Toxins 2024, 16(7), 318; https://doi.org/10.3390/toxins16070318 - 13 Jul 2024
Viewed by 316
Abstract
Maize plays a significant global role as a food source, feed, and as a raw material in industry. However, it is affected by toxin-producing fungi, mainly Fusarium graminearum, Fusarium verticillioides, and Aspergillus flavus, which compromise its quality. This study, conducted [...] Read more.
Maize plays a significant global role as a food source, feed, and as a raw material in industry. However, it is affected by toxin-producing fungi, mainly Fusarium graminearum, Fusarium verticillioides, and Aspergillus flavus, which compromise its quality. This study, conducted in 2022 and 2023 at the Látókép long-term research site of the University of Debrecen, Hungary, investigated the effects of different nitrogen fertilization rates (0, 90 and 150 Kgha−1 N) on mycotoxin contamination (DON vs. FB vs. AFB1) in the kernels of three (3) maize hybrids: DKC4590 (tolerant), GKT376 (sensitive), and P9610 (undefined). The results showed a significant (p = 0.05) influence of nitrogen fertilization and maize genotype on mycotoxin levels. Sole nitrogen impacts were complex and did not define a clear trend, contrary to the hybrids selected, which followed superiority to resistance. Increased nitrogen fertilization was associated with higher DON production, while hybrid selection demonstrated a clearer trend in resistance to mycotoxins. Therefore, to maximize yield and minimize mycotoxin contamination, future research should focus on optimizing nitrogen application rates and breeding for resistance to balance yield and mycotoxin management. These results suggest that while nitrogen fertilization is crucial for maximizing yield, selecting less susceptible maize hybrids remains vital for minimizing mycotoxin contamination. Full article
(This article belongs to the Section Mycotoxins)
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12 pages, 6015 KiB  
Article
Ultrasound-Guided Botulinum Neurotoxin Injection for Alleviating Cricopharyngeus Muscle Spasticity: A Cadaveric Feasibility Study with Nerve Ending Analysis
by Ji-Hyun Lee, Hyung-Jin Lee and Bo Hae Kim
Toxins 2024, 16(7), 317; https://doi.org/10.3390/toxins16070317 - 12 Jul 2024
Viewed by 287
Abstract
Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study [...] Read more.
Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler’s staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases. Full article
(This article belongs to the Special Issue The Botulinum Toxin and Spasticity: Exploring New Horizons)
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19 pages, 3628 KiB  
Article
7-Phenylheptanoic Acid-Hydroxypropyl β-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice
by Kindness Lomotey Commey, Airi Enaka, Ryota Nakamura, Asami Yamamoto, Kenji Tsukigawa, Koji Nishi, Masaki Otagiri and Keishi Yamasaki
Toxins 2024, 16(7), 316; https://doi.org/10.3390/toxins16070316 - 12 Jul 2024
Viewed by 269
Abstract
The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the [...] Read more.
The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease. Full article
(This article belongs to the Section Uremic Toxins)
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26 pages, 548 KiB  
Review
Resistance of Lepidopteran Pests to Bacillus thuringiensis Toxins: Evidence of Field and Laboratory Evolved Resistance and Cross-Resistance, Mode of Resistance Inheritance, Fitness Costs, Mechanisms Involved and Management Options
by Muhammad Babar Shahzad Afzal, Mamuna Ijaz, Naeem Abbas, Sarfraz Ali Shad and José Eduardo Serrão
Toxins 2024, 16(7), 315; https://doi.org/10.3390/toxins16070315 - 12 Jul 2024
Viewed by 581
Abstract
Bacillus thuringiensis (Bt) toxins are potential alternatives to synthetic insecticides for the control of lepidopteran pests. However, the evolution of resistance in some insect pest populations is a threat and can reduce the effectiveness of Bt toxins. In this review, we [...] Read more.
Bacillus thuringiensis (Bt) toxins are potential alternatives to synthetic insecticides for the control of lepidopteran pests. However, the evolution of resistance in some insect pest populations is a threat and can reduce the effectiveness of Bt toxins. In this review, we summarize the results of 161 studies from 20 countries reporting field and laboratory-evolved resistance, cross-resistance, and inheritance, mechanisms, and fitness costs of resistance to different Bt toxins. The studies refer mainly to insects from the United States of America (70), followed by China (31), Brazil (19), India (12), Malaysia (9), Spain (3), and Australia (3). The majority of the studies revealed that most of the pest populations showed susceptibility and a lack of cross-resistance to Bt toxins. Factors that delay resistance include recessive inheritance of resistance, the low initial frequency of resistant alleles, increased fitness costs, abundant refuges of non-Bt, and pyramided Bt crops. The results of field and laboratory resistance, cross-resistance, and inheritance, mechanisms, and fitness cost of resistance are advantageous for predicting the threat of future resistance and making effective strategies to sustain the effectiveness of Bt crops. Full article
(This article belongs to the Special Issue Advances in Bacillus thuringiensis Toxins)
15 pages, 2223 KiB  
Article
Three Ecological Models to Evaluate the Effectiveness of Trichoderma spp. for Suppressing Aflatoxigenic Aspergillus flavus and Aspergillus parasiticus
by Nataliia Voloshchuk, Zilfa Irakoze, Seogchan Kang, Joshua J. Kellogg and Josephine Wee
Toxins 2024, 16(7), 314; https://doi.org/10.3390/toxins16070314 - 12 Jul 2024
Viewed by 425
Abstract
Chemical pesticides help reduce crop loss during production and storage. However, the carbon footprints and ecological costs associated with this strategy are unsustainable. Here, we used three in vitro models to characterize how different Trichoderma species interact with two aflatoxin producers, Aspergillus flavus [...] Read more.
Chemical pesticides help reduce crop loss during production and storage. However, the carbon footprints and ecological costs associated with this strategy are unsustainable. Here, we used three in vitro models to characterize how different Trichoderma species interact with two aflatoxin producers, Aspergillus flavus and Aspergillus parasiticus, to help develop a climate-resilient biological control strategy against aflatoxigenic Aspergillus species. The growth rate of Trichoderma species is a critical factor in suppressing aflatoxigenic strains via physical interactions. The dual plate assay suggests that Trichoderma mainly suppresses A. flavus via antibiosis, whereas the suppression of A. parasiticus occurs through mycoparasitism. Volatile organic compounds (VOCs) produced by Trichoderma inhibited the growth of A. parasiticus (34.6 ± 3.3%) and A. flavus (20.9 ± 1.6%). The VOCs released by T. asperellum BTU and T. harzianum OSK-34 were most effective in suppressing A. flavus growth. Metabolites secreted by T. asperellum OSK-38, T. asperellum BTU, T. virens OSK-13, and T. virens OSK-36 reduced the growth of both aflatoxigenic species. Overall, T. asperellum BTU was the most effective at suppressing the growth and aflatoxin B1 production of both species across all models. This work will guide efforts to screen for effective biological control agents to mitigate aflatoxin accumulation. Full article
(This article belongs to the Special Issue Impact of Climate Change on Fungal Population and Mycotoxins)
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14 pages, 2717 KiB  
Review
General ADP-Ribosylation Mechanism Based on the Structure of ADP-Ribosyltransferase–Substrate Complexes
by Hideaki Tsuge, Noriyuki Habuka and Toru Yoshida
Toxins 2024, 16(7), 313; https://doi.org/10.3390/toxins16070313 - 11 Jul 2024
Viewed by 331
Abstract
ADP-ribosylation is a ubiquitous modification of proteins and other targets, such as nucleic acids, that regulates various cellular functions in all kingdoms of life. Furthermore, these ADP-ribosyltransferases (ARTs) modify a variety of substrates and atoms. It has been almost 60 years since ADP-ribosylation [...] Read more.
ADP-ribosylation is a ubiquitous modification of proteins and other targets, such as nucleic acids, that regulates various cellular functions in all kingdoms of life. Furthermore, these ADP-ribosyltransferases (ARTs) modify a variety of substrates and atoms. It has been almost 60 years since ADP-ribosylation was discovered. Various ART structures have been revealed with cofactors (NAD+ or NAD+ analog). However, we still do not know the molecular mechanisms of ART. It needs to be better understood how ART specifies the target amino acids or bases. For this purpose, more information is needed about the tripartite complex structures of ART, the cofactors, and the substrates. The tripartite complex is essential to understand the mechanism of ADP-ribosyltransferase. This review updates the general ADP-ribosylation mechanism based on ART tripartite complex structures. Full article
(This article belongs to the Special Issue ADP-Ribosylation and Beyond)
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18 pages, 5697 KiB  
Article
A Glycoprotein-Based Surface-Enhanced Raman Spectroscopy–Lateral Flow Assay Method for Abrin and Ricin Detection
by Lan Xiao, Li Luo, Jia Liu, Luyao Liu, Han Han, Rui Xiao, Lei Guo, Jianwei Xie and Li Tang
Toxins 2024, 16(7), 312; https://doi.org/10.3390/toxins16070312 - 11 Jul 2024
Viewed by 336
Abstract
Abrin and ricin, both type II ribosome-inactivating proteins, are toxins of significant concern and are under international restriction by the Chemical Weapons Convention and the Biological and Toxin Weapons Convention. The development of a rapid and sensitive detection method for these toxins is [...] Read more.
Abrin and ricin, both type II ribosome-inactivating proteins, are toxins of significant concern and are under international restriction by the Chemical Weapons Convention and the Biological and Toxin Weapons Convention. The development of a rapid and sensitive detection method for these toxins is of the utmost importance for the first emergency response. Emerging rapid detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA), have garnered attention due to their high sensitivity, good selectivity, ease of operation, low cost, and disposability. In this work, we generated stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for SERS-LFA. We then constructed a sandwich-style lateral flow test strip using a pair of glycoproteins, asialofetuin and concanavalin A, as the core affinity recognition molecules, capable of trace measurement for both abrin and ricin. The limit of detection for abrin and ricin was 0.1 and 0.3 ng/mL, respectively. This method was applied to analyze eight spiked white powder samples, one juice sample, and three actual botanic samples, aligning well with cytotoxicity assay outcomes. It demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins. Full article
(This article belongs to the Special Issue Natural Toxins Detected via Different Methods)
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21 pages, 2525 KiB  
Article
A Novel Cytotoxic Mechanism for Triple-Negative Breast Cancer Cells Induced by the Type II Heat-Labile Enterotoxin LT-IIc through Ganglioside Ligation
by Natalie D. King-Lyons, Aryana S. Bhati, John C. Hu, Lorrie M. Mandell, Gautam N. Shenoy, Hugh J. Willison and Terry D. Connell
Toxins 2024, 16(7), 311; https://doi.org/10.3390/toxins16070311 - 11 Jul 2024
Viewed by 555
Abstract
Triple-negative breast cancer (TNBC), which constitutes 10–20 percent of all breast cancers, is aggressive, has high metastatic potential, and carries a poor prognosis due to limited treatment options. LT-IIc, a member of the type II subfamily of ADP-ribosylating—heat-labile enterotoxins that bind to a [...] Read more.
Triple-negative breast cancer (TNBC), which constitutes 10–20 percent of all breast cancers, is aggressive, has high metastatic potential, and carries a poor prognosis due to limited treatment options. LT-IIc, a member of the type II subfamily of ADP-ribosylating—heat-labile enterotoxins that bind to a distinctive set of cell-surface ganglioside receptors—is cytotoxic toward TNBC cell lines, but has no cytotoxic activity for non-transformed breast epithelial cells. Here, primary TNBC cells, isolated from resected human tumors, showed an enhanced cytotoxic response specifically toward LT-IIc, in contrast to other enterotoxins that were tested. MDA-MB-231 cells, a model for TNBC, were used to evaluate potential mechanisms of cytotoxicity by LT-IIc, which induced elevated intracellular cAMP and stimulated the cAMP response element-binding protein (CREB) signaling pathway. To dissect the role of ADP-ribosylation, cAMP induction, and ganglioside ligation in the cytotoxic response, MDA-MB-231 cells were exposed to wild-type LT-IIc, the recombinant B-pentamer of LT-IIc that lacks the ADP-ribosylating A polypeptide, or mutants of LT-IIc with an enzymatically inactivated A1-domain. These experiments revealed that the ADP-ribosyltransferase activity of LT-IIc was nonessential for inducing the lethality of MDA-MB-231 cells. In contrast, a mutant LT-IIc with an altered ganglioside binding activity failed to trigger a cytotoxic response in MDA-MB-231 cells. Furthermore, the pharmacological inhibition of ganglioside expression protected MDA-MB-231 cells from the cytotoxic effects of LT-IIc. These data establish that ganglioside ligation, but not the induction of cAMP production nor ADP-ribosyltransferase activity, is essential to initiating the LT-IIc-dependent cell death of MDA-MB-231 cells. These experiments unveiled previously unknown properties of LT-IIc and gangliosides in signal transduction, offering the potential for the targeted treatment of TNBC, an option that is desperately needed. Full article
(This article belongs to the Section Bacterial Toxins)
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29 pages, 3388 KiB  
Article
Kinetics and Mechanism of Cyanobacteria Cell Removal Using Biowaste-Derived Activated Carbons with Assessment of Potential Human Health Impacts
by Irina Kandić, Milan Kragović, Sanja Živković, Jelena Knežević, Stefana Vuletić, Stefana Cvetković and Marija Stojmenović
Toxins 2024, 16(7), 310; https://doi.org/10.3390/toxins16070310 (registering DOI) - 9 Jul 2024
Viewed by 477
Abstract
Harmful cyanobacteria blooms and the escalating impact of cyanotoxins necessitates the effective removal of cyanobacteria from water ecosystems before they release cyanotoxins. In this study, cyanobacteria removal from water samples taken from the eutrophic Aleksandrovac Lake (southern Serbia) was investigated. For that purpose, [...] Read more.
Harmful cyanobacteria blooms and the escalating impact of cyanotoxins necessitates the effective removal of cyanobacteria from water ecosystems before they release cyanotoxins. In this study, cyanobacteria removal from water samples taken from the eutrophic Aleksandrovac Lake (southern Serbia) was investigated. For that purpose, novel activated carbons derived from waste biomass—date palm leaf stalk (P_AC), black alder cone-like flowers (A_AC), and commercial activated carbon from coconut shell (C_AC) as a reference were used. To define the best adsorption conditions and explain the adsorption mechanism, the influence of contact time, reaction volume, and adsorbent mass, as well as FTIR analysis of the adsorbents before and after cyanobacteria removal, were studied. The removal efficiency of P_AC and A_AC achieved for the applied concentration of 10 mg/mL after 15 min was ~99%, while for C_AC after 24 h was only ~92% for the same concentration. To check the safety of the applied materials for human health and the environment, the concentrations of potentially toxic elements (PTEs), the health impact (HI) after water purification, and the toxicity (MTT and Comet assay) of the materials were evaluated. Although the P_AC and A_AC achieved much better removal properties in comparison with the C_AC, considering the demonstrated genotoxicity and cytotoxicity of the P_AC and the higher HI value for the C_AC, only the A_AC was further investigated. Results of the kinetics, FTIR analysis, and examination of the A_AC mass influence on removal efficiency indicated dominance of the physisorption mechanism. Initially, the findings highlighted the superior performance of A_AC, with great potential to be globally commercialized as an effective cyanobacteria cell adsorbent. Full article
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15 pages, 1654 KiB  
Opinion
Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine
by Dilara Onan, Fatemeh Farham and Paolo Martelletti
Toxins 2024, 16(7), 309; https://doi.org/10.3390/toxins16070309 - 7 Jul 2024
Viewed by 430
Abstract
OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle [...] Read more.
OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin. Full article
(This article belongs to the Section Bacterial Toxins)
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14 pages, 2196 KiB  
Article
Synthesis, Characterization, and Study of the Antimicrobial Potential of Dimeric Peptides Derived from the C-Terminal Region of Lys49 Phospholipase A2 Homologs
by Gabriel F. H. Bicho, Letícia O. C. Nunes, Louise Oliveira Fiametti, Marcela N. Argentin, Vitória T. Candido, Ilana L. B. C. Camargo, Eduardo M. Cilli and Norival A. Santos-Filho
Toxins 2024, 16(7), 308; https://doi.org/10.3390/toxins16070308 - 5 Jul 2024
Viewed by 462
Abstract
Currently, the search for new alternatives to conventional antibiotics to combat bacterial resistance is an urgent task, as many microorganisms threaten human health due to increasing bacterial resistance to traditional medicines. Thus, new molecules such as antimicrobial peptides have emerged as promising alternatives [...] Read more.
Currently, the search for new alternatives to conventional antibiotics to combat bacterial resistance is an urgent task, as many microorganisms threaten human health due to increasing bacterial resistance to traditional medicines. Thus, new molecules such as antimicrobial peptides have emerged as promising alternatives because of their low induction of resistance and broad spectrum of action. In this context, in the past few years, our research group has synthesized and characterized a peptide derived from the C-terminal region of the Lys49 PLA2-like BthTX-I, named p-BthTX-I. After several studies, the peptide (p-BthTX-I)2K was proposed as the molecule with the most considerable biotechnological potential. As such, the present work aimed to evaluate whether the modifications made on the peptide (p-BthTX-I)2K can be applied to other molecules originating from the C-terminal region of PLA2-like Lys49 from snake venoms. The peptides were obtained through the solid-phase peptide synthesis technique, and biochemical and functional characterization was carried out using dichroism techniques, mass spectrometry, antimicrobial activity against ESKAPE strains, hemolytic activity, and permeabilization of lipid vesicles. The antimicrobial activity of the peptides was promising, especially for the peptides (p-AppK)2K and (p-ACL)2K, which demonstrated activity against all strains that were tested, surpassing the model molecule (p-BthTX-I)2K in most cases and maintaining low hemolytic activity. The modifications initially proposed for the (p-BthTX-I)2K peptide were shown to apply to other peptides derived from Lys49 PLA2-like from snake venoms, showing promising results for antimicrobial activity. Future assays comparing the activity of the dimers obtained through this strategy with the monomers of these peptides should be carried out. Full article
(This article belongs to the Section Animal Venoms)
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22 pages, 2744 KiB  
Review
Shining a Light on Venom-Peptide Receptors: Venom Peptides as Targeted Agents for In Vivo Molecular Imaging
by Chun Yuen Chow and Glenn F. King
Toxins 2024, 16(7), 307; https://doi.org/10.3390/toxins16070307 - 4 Jul 2024
Viewed by 761
Abstract
Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest [...] Read more.
Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest in real time. Ion channels play a fundamental role in cellular signalling, and they are implicated in diverse pathological conditions, making them an attractive target in the field of molecular imaging. Many venom peptides exhibit exquisite selectivity and potency towards ion channels, rendering them ideal agents for molecular imaging applications. In this review, we illustrate the use of fluorescently-labelled venom peptides for disease diagnostics and intraoperative imaging of brain tumours and peripheral nerves. Finally, we address challenges for the development and clinical translation of venom peptides as nerve-targeted imaging agents. Full article
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18 pages, 895 KiB  
Review
Understanding Clinical Effectiveness and Safety Implications of Botulinum Toxin in Children: A Narrative Review of the Literature
by Salvatore Crisafulli, Francesco Ciccimarra, Zakir Khan, Francesco Maccarrone and Gianluca Trifirò
Toxins 2024, 16(7), 306; https://doi.org/10.3390/toxins16070306 - 4 Jul 2024
Viewed by 688
Abstract
Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range [...] Read more.
Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range of neuromuscular, otolaryngologic, orthopedic, gastrointestinal, and urologic disorders. Approved pediatric indications of use include the treatment of blepharospasm associated with dystonia, strabismus, lower-limb spasticity, focal spasticity in patients with cerebral palsy, and neurogenic detrusor overactivity. Alongside these approved indications, botulinum toxin is extensively used off-label. Although several clinical studies have shown that botulinum toxin is effective and well-tolerated in children, uncertainties persist regarding its long-term effects on growth and appropriate dosing in this population. As such, further research is needed to better define the botulinum toxin risk–benefit profile and expand approved uses in pediatrics. This narrative review aimed to provide a broad overview of the evidence concerning the clinical effectiveness and safety of BoNT with respect to its principal authorized and non-authorized pediatric therapeutic indications, as well as to describe perspectives on its future use in children. Full article
(This article belongs to the Special Issue Botulinum Toxins and Children’s Health)
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20 pages, 4165 KiB  
Article
Bioremediation of Aflatoxin B1 by Meyerozyma guilliermondii AF01 in Peanut Meal via Solid-State Fermentation
by Wan Zhang, Changpo Sun, Wei Wang and Zhongjie Zhang
Toxins 2024, 16(7), 305; https://doi.org/10.3390/toxins16070305 - 4 Jul 2024
Viewed by 652
Abstract
The use of microorganisms to manage aflatoxin contamination is a gentle and effective approach. The aim of this study was to test the removal of AFB1 from AFB1-contaminated peanut meal by a strain of Meyerozyma guilliermondii AF01 screened by the [...] Read more.
The use of microorganisms to manage aflatoxin contamination is a gentle and effective approach. The aim of this study was to test the removal of AFB1 from AFB1-contaminated peanut meal by a strain of Meyerozyma guilliermondii AF01 screened by the authors and to optimize the conditions of the biocontrol. A regression model with the removal ratio of AFB1 as the response value was established by means of single-factor and response surface experiments. It was determined that the optimal conditions for the removal of AFB1 from peanut meal by AF01 were 75 h at 29 °C under the natural pH, with an inoculum of 5.5%; the removal ratio of AFB1 reached 69.31%. The results of simulating solid-state fermentation in production using shallow pans and fermentation bags showed that the removal ratio of AFB1 was 68.85% and 70.31% in the scaled-up experiments, respectively. This indicated that AF01 had strong adaptability to the environment with facultative anaerobic fermentation detoxification ability. The removal ratio of AFB1 showed a positive correlation with the growth of AF01, and there were no significant changes in the appearance and quality of the peanut meal after fermentation. This indicated that AF01 had the potential to be used in practical production. Full article
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10 pages, 538 KiB  
Article
Enhancing Botulinum Toxin Injection Precision: The Efficacy of a Single Cadaveric Ultrasound Training Intervention for Improved Anatomical Localization
by Camille Heslot, Omar Khan, Alexis Schnitzler, Chloe Haldane, Romain David and Rajiv Reebye
Toxins 2024, 16(7), 304; https://doi.org/10.3390/toxins16070304 - 2 Jul 2024
Viewed by 540
Abstract
Ultrasound guidance can enhance existing landmark-based injection methods, even through a brief and single exposure during a cadaveric training course. A total of twelve participants were enrolled in this training program, comprising nine physical medicine and rehabilitation specialists, one pediatrician, and two physician [...] Read more.
Ultrasound guidance can enhance existing landmark-based injection methods, even through a brief and single exposure during a cadaveric training course. A total of twelve participants were enrolled in this training program, comprising nine physical medicine and rehabilitation specialists, one pediatrician, and two physician assistants. For each participant, one upper-limb muscle and one lower-limb muscle were randomly chosen from the preselected muscle group. Subsequently, participants were tasked with injecting both of their chosen cadaveric muscles with 1 mL of acrylic paint using a manual needle palpation technique, relying solely on their knowledge of anatomic landmarks. Participants then underwent a personalized, one-to-one ultrasound teaching session, lasting approximately five minutes, conducted by two highly experienced instructors. Following this instructive phase, participants were tasked with a second round of injections, targeting the same two muscles in the lower and upper limbs. However, this time, the injections were performed using anatomical landmarks and ultrasound guidance. To facilitate differentiation from the initial injections, a distinct color of acrylic paint was employed. When employing the anatomical landmark-based approach, the overall success rate for injections was 67%, with 16 out of 24 targeted muscles accurately injected. With the incorporation of ultrasound guidance, the success rate was 92%, precisely targeting 22 out of the 24 muscles under examination. There was an improvement in injection accuracy achievable through the integration of ultrasound guidance, even with minimal training exposure. Our single cadaveric ultra-sound training program contributes valuable insights to the utilization of ultrasound for anatomy training to help optimize the targeting of BoNT-A. Full article
(This article belongs to the Special Issue Uses of Botulinum Toxin Injection in Medicine)
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12 pages, 993 KiB  
Article
Long-Term Adherence to Onabotulinum Toxin-A Intradetrusor Injections for Neurogenic Dysfunction in Children—A Retrospective Single-Center Evaluation
by Chiara Pellegrino, Valentina Forlini, Maria Luisa Capitanucci, Gessica Della Bella and Giovanni Mosiello
Toxins 2024, 16(7), 303; https://doi.org/10.3390/toxins16070303 - 1 Jul 2024
Viewed by 515
Abstract
Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric [...] Read more.
Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric patients are present. The aim of this study is to share our long-term experience of BTX-A adherence in children. This study is a retrospective review of 230 refractory NB patients treated with BTX-A. The inclusion criteria were ≥3 treatments and the first injection performed ≥10 years before the study endpoint. Fifty-four patients were included. Mean follow-up was 10.2 years; mean treatment number was 6.4 for each patient. During follow-up, 7% did not need BTX-A anymore; 76% discontinued therapy, with a prevalence of acquired NB (64% acquired vs. 34% congenital; p = 0.03); sex-based and urodynamic findings did not influence the discontinuation rate (p = 0.6, p = 0.2, respectively). Considering those who withdrew from the therapy, 43% were lost to follow-up/died after a mean of 7.5 years (although 33% still experienced clinical efficacy); 33% changed therapy after a mean of 5.8 years (with reduced efficacy in 22%, persistent efficacy in 11%). BTX-A is a safe and effective therapy for pediatric patients. The treatment abandonment rate is higher for children than for adults; no specific reasons were highlighted. It is necessary to evaluate any age-specific factors to explain these data. Full article
(This article belongs to the Special Issue Botulinum Toxins and Children’s Health)
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15 pages, 2195 KiB  
Article
Increased Dissemination of Aflatoxin- and Zearalenone-Producing Aspergillus spp. and Fusarium spp. during Wet Season via Houseflies on Dairy Farms in Aguascalientes, Mexico
by Erika Janet Rangel-Muñoz, Arturo Gerardo Valdivia-Flores, Carlos Cruz-Vázquez, María Carolina de-Luna-López, Emmanuel Hernández-Valdivia, Irene Vitela-Mendoza, Leticia Medina-Esparza and Teódulo Quezada-Tristán
Toxins 2024, 16(7), 302; https://doi.org/10.3390/toxins16070302 - 1 Jul 2024
Viewed by 722
Abstract
Crops contamination with aflatoxins (AFs) and zearalenone (ZEA) threaten human and animal health; these mycotoxins are produced by several species of Aspergillus and Fusarium. The objective was to evaluate under field conditions the influence of the wet season on the dissemination of [...] Read more.
Crops contamination with aflatoxins (AFs) and zearalenone (ZEA) threaten human and animal health; these mycotoxins are produced by several species of Aspergillus and Fusarium. The objective was to evaluate under field conditions the influence of the wet season on the dissemination of AF- and ZEA-producing fungi via houseflies collected from dairy farms. Ten dairy farms distributed in the semi-arid Central Mexican Plateau were selected. Flies were collected in wet and dry seasons at seven points on each farm using entomological traps. Fungi were isolated from fly carcasses via direct seeding with serial dilutions and wet chamber methods. The production of AFs and ZEA from pure isolates was quantified using indirect competitive ELISA. A total of 693 Aspergillus spp. and 1274 Fusarium spp. isolates were obtained, of which 58.6% produced AFs and 50.0% produced ZEA (491 ± 122; 2521 ± 1295 µg/kg). Houseflies and both fungal genera were invariably present, but compared to the dry season, there was a higher abundance of flies as well as AF- and ZEA-producing fungi in the wet season (p < 0.001; 45.3/231 flies/trap; 8.6/29.6% contaminated flies). These results suggest that rainy-weather conditions on dairy farms increase the spread of AF- and ZEA-producing Aspergillus spp. and Fusarium spp. through houseflies and the incorporation of their mycotoxins into the food chain. Full article
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15 pages, 6499 KiB  
Article
Toxic Peptides from the Mexican Scorpion Centruroides villegasi: Chemical Structure and Evaluation of Recognition by Human Single-Chain Antibodies
by Lidia Riaño-Umbarila, Timoteo Olamendi-Portugal, José Alberto Romero-Moreno, Gustavo Delgado-Prudencio, Fernando Z. Zamudio, Baltazar Becerril and Lourival D. Possani
Toxins 2024, 16(7), 301; https://doi.org/10.3390/toxins16070301 - 1 Jul 2024
Viewed by 534
Abstract
Alternative recombinant sources of antivenoms have been successfully generated. The application of such strategies requires the characterization of the venoms for the development of specific neutralizing molecules against the toxic components. Five toxic peptides to mammals from the Mexican scorpion Centruroides villegasi were [...] Read more.
Alternative recombinant sources of antivenoms have been successfully generated. The application of such strategies requires the characterization of the venoms for the development of specific neutralizing molecules against the toxic components. Five toxic peptides to mammals from the Mexican scorpion Centruroides villegasi were isolated by chromatographic procedures by means of gel filtration on Sephadex G-50, followed by ion-exchange columns on carboxy-methyl-cellulose (CMC) resins and finally purified by high-performance chromatography (HPLC) columns. Their primary structures were determined by Edman degradation. They contain 66 amino acids and are maintained well packed by four disulfide bridges, with molecular mass from 7511.3 to 7750.1 Da. They are all relatively toxic and deadly to mice and show high sequence identity with known peptides that are specific modifiers of the gating mechanisms of Na+ ion channels of type beta-toxin (β-ScTx). They were named Cv1 to Cv5 and used to test their recognition by single-chain variable fragments (scFv) of antibodies, using surface plasmon resonance. Three different scFvs generated in our laboratory (10FG2, HV, LR) were tested for recognizing the various new peptides described here, paving the way for the development of a novel type of scorpion antivenom. Full article
(This article belongs to the Section Animal Venoms)
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21 pages, 4910 KiB  
Article
Qualitative Profiling of Venom Toxins in the Venoms of Several Bothrops Species Using High-Throughput Venomics and Coagulation Bioassaying
by Dimoetsha J. C. Weekers, Luis L. Alonso, Anniek X. Verstegen, Julien Slagboom and Jeroen Kool
Toxins 2024, 16(7), 300; https://doi.org/10.3390/toxins16070300 - 1 Jul 2024
Viewed by 658
Abstract
Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The Bothrops genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into Bothrops venom composition [...] Read more.
Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The Bothrops genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into Bothrops venom composition is important to aid in the development of safer and more effective snakebite treatments. In addition, the discovery of Bothrops toxins that could potentially be used for medical or diagnostic purposes is of interest to the pharmaceutical industry. This study aimed to employ high-throughput (HT) venomics to qualitatively analyze venom composition while utilizing coagulation bioassays for identifying coagulopathic toxins and characterizing coagulopathic activity in various Bothrops venoms. Using the recently demonstrated HT venomics workflow in combination with post-column coagulopathic bioassaying, focus was placed at anticoagulant toxins. Well-known procoagulant toxins were also investigated, taking into account that using the HT venomics workflow, procoagulant toxins are especially prone to denaturation during the reversed-phase chromatographic separations performed in the workflow. The findings revealed that the venoms of B. atrox and B. jararaca harbored procoagulant toxins, whereas those of B. alternatus and B. neuwiedi contained both procoagulant and anticoagulant toxins. In general, anticoagulation was associated with phospholipases A2s, while procoagulation was associated with snake venom metalloproteinases and snake venom serine proteases. These results showed the identification of coagulopathic venom toxins in the Bothrops venoms analyzed using multiple analytical methods that complement each other. Additionally, each venom underwent qualitative characterization of its composition. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
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8 pages, 2121 KiB  
Review
Strategies for Safe Transurethral Injections of Botulinum Toxin into the Bladder Wall
by Matthias Oelke
Toxins 2024, 16(7), 299; https://doi.org/10.3390/toxins16070299 - 30 Jun 2024
Viewed by 445
Abstract
Introduction: Transurethral injections into the bladder wall with botulinum toxin are an established treatment for refractory overactive bladder or detrusor overactivity. With the current injection technique, an average of approx. 18% and up to 40% of botulinum toxin is injected next to the [...] Read more.
Introduction: Transurethral injections into the bladder wall with botulinum toxin are an established treatment for refractory overactive bladder or detrusor overactivity. With the current injection technique, an average of approx. 18% and up to 40% of botulinum toxin is injected next to the bladder wall, potentially causing reduced efficacy or non-response. The article aims to evaluate the reasons for incorrect injections and propose strategies for complete delivery of the entire botulinum toxin fluid into the bladder wall. Material and Methods: Unstructured literature search and narrative review of the literature. Results: Incorrect injection of botulinum toxin fluid next to the bladder wall is caused by pushing the injection needle too deep and through the bladder wall. Bladder wall thickness decreases with increasing bladder filling and has a thickness of less than 2 mm beyond 100 mL in healthy individuals. Ultrasound imaging of the bladder wall before botulinum toxin injection can verify bladder wall thickness in individual patients. Patient movements during the injection therapy increase the chance of incorrect placement of the needle tip. Conclusions: Based on the literature search, it is helpful and recommended to (1) perform pretreatment ultrasound imaging of the bladder to estimate bladder wall thickness and to adjust the injection depth accordingly, (2) fill the bladder as low as possible, ideally below 100 mL, (3) use short needles, ideally 2 mm, and (4) provide sufficient anesthesia and pain management to avoid patient movements during the injection therapy. Full article
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21 pages, 1754 KiB  
Review
Residual Kidney Function in Hemodialysis: Its Importance and Contribution to Improved Patient Outcomes
by Yoshitsugu Obi, Jochen G. Raimann, Kamyar Kalantar-Zadeh and Mariana Murea
Toxins 2024, 16(7), 298; https://doi.org/10.3390/toxins16070298 - 28 Jun 2024
Viewed by 394
Abstract
Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of [...] Read more.
Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF. Full article
(This article belongs to the Special Issue Kidney Replacement Therapy by Hemodialysis: 21st Century Challenges)
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20 pages, 354 KiB  
Article
Vitamin 25(OH)D3, E, and C Supplementation Impact the Inflammatory and Antioxidant Responses in Piglets Fed a Deoxynivalenol-Contaminated Diet and Challenged with Lipopolysaccharides
by Béatrice Sauvé, Younes Chorfi, Marie-Pierre Létourneau-Montminy and Frédéric Guay
Toxins 2024, 16(7), 297; https://doi.org/10.3390/toxins16070297 - 28 Jun 2024
Viewed by 341
Abstract
Using alternative ingredients or low-quality grain grades to reduce feeding costs for pig diets can introduce mycotoxins such as deoxynivalenol (DON) into feed, which is known to induce anorexia, inflammation, and oxidative stress. Adding vitamin 25(OH)D3 or vitamins E and C to [...] Read more.
Using alternative ingredients or low-quality grain grades to reduce feeding costs for pig diets can introduce mycotoxins such as deoxynivalenol (DON) into feed, which is known to induce anorexia, inflammation, and oxidative stress. Adding vitamin 25(OH)D3 or vitamins E and C to the feed could increase piglets’ immune system to alleviate the effects of DON. This study used 54 pigs (7.8 ± 0.14 kg) in 27 pens (2 pigs/pen) with a vitamin 25(OH)D3 or vitamin E-C supplementation, or their combination, in DON-contaminated (5.1 mg/kg) feed ingredients over 21 days followed by a lipopolysaccharide (LPS) challenge (20 µg/kg BW) 3 h prior to euthanasia for 1 piglet per pen. DON contamination induced anorexia, which reduced piglet growth. DON also induced immunomodulation, oxidative stress, and downregulated vitamin D status. The vitamin E and C supplementation and the combination of vitamins E, C, and 25(OH)D3 provided protection against DON contamination by not only decreasing blood and liver oxidative stress markers, but also by increasing antioxidant enzymes and tocopherol levels in blood, indicating improved antioxidant defense mechanisms. The combination of vitamins also restored the vitamin D status. After LPS challenge, DON contamination decreased intestinal and liver antioxidant statuses and increased inflammation markers. The addition of vitamins E and C to DON-contaminated feed reduced markers of inflammation and improved the antioxidant status after the LPS immune stimulation. The combination of all these vitamins also reduced the oxidative stress markers and the inflammation in the intestine and mesenteric lymph nodes, suggesting an anti-inflammatory effect. Full article
15 pages, 646 KiB  
Article
Validation of a UPLC-MS/MS Method for Multi-Matrix Biomonitoring of Alternaria Toxins in Humans
by Lia Visintin, María García Nicolás, Sarah De Saeger and Marthe De Boevre
Toxins 2024, 16(7), 296; https://doi.org/10.3390/toxins16070296 - 28 Jun 2024
Viewed by 323
Abstract
Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds [...] Read more.
Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds the threshold of toxicological concern in some European populations, especially infants and toddlers. Despite this, regulatory standards for Alternaria toxins remain absent. The lack of toxicokinetic parameters, reference levels, and sensitive detection methods complicates risk assessment and highlights the necessity for advanced biomonitoring (HBM) techniques. This study addresses these challenges by developing and validating ultra-high performance liquid chromatography method coupled with tandem mass spectrometry to quantify AOH, AME, TeA, and their conjugates in multiple biological matrices. The validated method demonstrates robust linearity, precision, recovery (94–111%), and sensitivity across urine (LOD < 0.053 ng/mL), capillary blood (LOD < 0.029 ng/mL), and feces (LOD < 0.424 ng/g), with significantly lower LOD for TeA compared to existing methodologies. The application of minimally invasive microsampling techniques for the blood collection enhances the potential for large-scale HBM studies. These advancements represent a step toward comprehensive HBM and exposure risk assessments for Alternaria toxins, facilitating the generation of data for regulatory authorities. Full article
(This article belongs to the Special Issue Multi Methods for Detecting Natural Toxins)
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12 pages, 455 KiB  
Systematic Review
Onabotulinumtoxina in the Prevention of Migraine in Pediatric Population: A Systematic Review
by Artemis Mavridi, Aine Redmond, Paraschos Archontakis-Barakakis, Petya Bogdanova-Mihaylova, Christina I. Deligianni, Dimos D. Mitsikostas and Theodoros Mavridis
Toxins 2024, 16(7), 295; https://doi.org/10.3390/toxins16070295 - 28 Jun 2024
Viewed by 754
Abstract
Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children [...] Read more.
Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy. OnabotulinumtoxinA is a known and approved treatment for the management of chronic migraine in people older than 18 years. Several studies examine its role in the pediatric population with positive results; however, the clear-cut benefit is still unclear. OnabotulinumtoxinA seems not only to improve disability scores (PedMIDAS) but also to improve the quality, characteristics, and frequency of migraines in the said population. This systematic review aims to summarize the evidence on the efficacy, dosing, administration, long-term outcomes, and safety of onabotulinumtoxinA in pediatric and adolescent migraine. Eighteen studies met the eligibility criteria and were included in this review. The mean monthly migraine days (MMDs), decreased from of 21.2 days per month to 10.7 after treatment. The reported treatment-related adverse effects were mild and primarily injection site related and ranged from 0% to 47.0%. Thus, this review provides compelling evidence suggesting that OnabotulinumtoxinA may represent a safe and effective preventive treatment option for pediatric migraine. Full article
(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives (Volume II))
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