Toxins

21 pages, 1231 KiB

Open AccessReview

Detection of Mycotoxins in Cereal Grains and Nuts Using Machine Learning Integrated Hyperspectral Imaging: A Review

by Md. Ahasan Kabir, Ivan Lee, Chandra B. Singh, Gayatri Mishra, Brajesh Kumar Panda and Sang-Heon Lee

Toxins 2025, 17(5), 219; https://doi.org/10.3390/toxins17050219 - 27 Apr 2025

Abstract

Cereal grains and nuts are the world’s most produced food and the economic backbone of many countries. Food safety in these commodities is crucial, as they are highly susceptible to mold growth and mycotoxin contamination in warm, humid environments. This review explores hyperspectral [...] Read more.

Cereal grains and nuts are the world’s most produced food and the economic backbone of many countries. Food safety in these commodities is crucial, as they are highly susceptible to mold growth and mycotoxin contamination in warm, humid environments. This review explores hyperspectral imaging (HSI) integrated with machine learning (ML) algorithms as a promising approach for detecting and quantifying mycotoxins in cereal grains and nuts. This study aims to (1) critically evaluate current non-destructive techniques for processing these foods and the applications of ML in identifying mycotoxins through HSI, and (2) highlight challenges and potential future research directions to enhance the reliability and efficiency of these detection systems. The ML algorithms showed effectiveness in classifying and quantifying mycotoxins in grains and nuts, with HSI systems increasingly adopted in industrial settings. Mycotoxins exhibit heightened sensitivity to specific spectral bands within HSI, facilitating accurate detection. Additionally, selecting only relevant spectral features reduces ML model complexity and enhances reliability in the detection process. This review contributes to a deeper understanding of the integration of HSI and ML for food safety applications in cereal grains and nuts. By identifying current challenges and future research directions, it provides valuable insights for advancing non-destructive mycotoxin detection methods in the food industry using HSI. Full article

(This article belongs to the Special Issue Mycotoxins in Food and Feeds: Human Health and Animal Nutrition)

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10 pages, 5505 KiB

Open AccessArticle

TM9SF2 Maintains Golgi Integrity and Regulates Ricin-Induced Cytotoxicity

by Yue Meng, Hongzhi Wan, Xinyu Wang, Lina Zhang, Ruozheng Xin, Lingyu Li, Yuhui Wang, Chengwang Xu, Hui Peng, Lu Sun, Bo Wang and Xiaotao Duan

Toxins 2025, 17(5), 218; https://doi.org/10.3390/toxins17050218 - 26 Apr 2025

Abstract

TM9SF2 belongs to a family of highly conserved nonaspanin proteins, and has been frequently identified as one of the important host factors for a plethora of lethal pathogens and toxins in previous genome-wide screening studies. We reported herein a novel molecular mechanism of [...] Read more.

TM9SF2 belongs to a family of highly conserved nonaspanin proteins, and has been frequently identified as one of the important host factors for a plethora of lethal pathogens and toxins in previous genome-wide screening studies. We reported herein a novel molecular mechanism of TM9SF2 in mediating the cytotoxicity of ricin, a type II ribosome-inactivating protein. We first showed that TM9SF2 displays a non-redundant requirement for ricin-induced cytotoxicity within the nonaspanin family. Then we found that genetic interference of TM9SF2 substantially affects/remodels intracellular cholesterol trafficking, which results in abnormal cholesterol accumulation in Golgi compartments and causes severe Golgi fragmentation. The disruption of Golgi integrity and network impedes the retrograde transport of ricin and thus attenuates ricin-induced cytotoxicity. We further verified this mechanism by pharmacological manipulation of cholesterol metabolism (e.g., by using A939572 and avasimibe, etc.), which well restores the integrity of the Golgi apparatus and reverses the ricin-resistant phenotype induced by TM9SF2 knockdown. Our finding provides new mechanistic insights into the pathology and toxicology of ricin and could potentially be applied to other ribosome-inactivating toxins. Full article

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19 pages, 17036 KiB

Open AccessArticle

The Uremic Toxins Inorganic Phosphate, Indoxylsulphate, p-Cresylsulphate, and TMAO Induce the Generation of Sulphated Glycosaminoglycans in Aortic Tissue and Vascular Cells via pAKT Signaling: A Missing Link in the “Gut–Matrix Axis”

by Christian Freise, Susanne Metzkow, Andreas Zappe, Monika Ebert, Nicola Stolzenburg, Julia Hahndorf, Jörg Schnorr, Kevin Pagel and Matthias Taupitz

Toxins 2025, 17(5), 217; https://doi.org/10.3390/toxins17050217 - 25 Apr 2025

Abstract

Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently [...] Read more.

Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently understood. Glycosaminoglycans (GAGs) as components of the extracellular matrix are known to interact with various ligands such as growth factors or receptors, thereby influencing (patho)physiological processes. We previously found that the UT inorganic phosphate (Pi) induces the synthesis and sulphation of the GAGs heparan sulphate and chondroitin sulphate in the rat vascular smooth muscle cell (VSMC) line A7r5 and in the human endothelial cell (EC) line EA.Hy926. The aim of this study was to investigate if other organic UTs modulate GAGs in vascular cells as well. We treated ex vivo cultures of rat aortic rings as well as primary rat VSMCs and human ECs with the UTs Pi, indoxylsulphate (IS), p-cresylsulphate (pCS), trimethylamine N-oxide (TMAO), and urea, and analyzed the samples by histological staining, qPCR, western blot, HPLC, and colorimetric assays. The UT treatment of aortic rings and cells increased contents of sulphated GAGs and hyaluronic acid. UT-treated cells contained higher amounts of 4S- and 6S-sulphated GAGs compared to controls. This was accompanied by altered expressions of genes and proteins relevant for GAG metabolism. Mechanistically, the effects of the UTs on GAGs involve the activation of the PI3K/Akt pathway and of the transcription factor NF-κB. In conclusion, the UT-induced remodeling of the cardiovascular matrix by upregulation of sulphated GAGs and hyaluronic acid in aortic tissue and vascular cells might be a missing link between gut-derived UT and pathophysiological alterations in the cardiovascular system in the sense of a gut–matrix axis. Full article

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13 pages, 1288 KiB

Open AccessArticle

Single-Dose IncobotulinumtoxinA in the Treatment of Early-Stage Knee Osteoarthritis: Results from a Preliminary Single-Arm Clinical Trial

by Sofia Durán-Hernández, Norma E. Herrera-González, Nayar Durán-Hernández, Martha Carnalla, Manuel de Jesús Castillejos-López and Citlaltepetl Salinas-Lara

Toxins 2025, 17(5), 216; https://doi.org/10.3390/toxins17050216 - 25 Apr 2025

Abstract

Osteoarthritis (OA) is the most prevalent rheumatologic disease and a leading cause of years lived with disability worldwide. There are no disease-modifying drugs available to treat it. This study aimed to evaluate the effect of a single dose of 100U botulinum neurotoxin-A (BoNT-A) [...] Read more.

Osteoarthritis (OA) is the most prevalent rheumatologic disease and a leading cause of years lived with disability worldwide. There are no disease-modifying drugs available to treat it. This study aimed to evaluate the effect of a single dose of 100U botulinum neurotoxin-A (BoNT-A) in patients with early knee OA. We designed a single-arm preliminary clinical trial in patients diagnosed with knee OA (KOA) grades I and II. 45 Patients received a single dose of 100U IncobotulinumtoxinA in the retro-patellar bursa and received nutritional and physical rehabilitation indications. Patients were evaluated at baseline and at days 5, 30, 60, and 90 after injection. The primary outcome was the reduction in pain using the visual analog scale (VAS). Knee function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We assessed secondary adverse effects and measured muscular strength in every consultation. Descriptive endpoint summaries and a generalized linear random-effect model were used to evaluate changes in each follow-up time compared to baseline. IncobotulinumtoxinA treatment significantly (p < 0.001) reduced pain in all treated patients at day 90 compared to day 0. Patients showed a significant reduction in total WOMAC score (p < 0.001), from a mean baseline of 44.6 (95% CI; 41.4, 47.8) to 4.4 at day 90 (95% CI; 0.2, 0.3). Our results show that IncobotulinumtoxinA applied in the retro-patellar bursa is a safe and effective treatment for pain in patients with early-stage KOA, offering a potential alternative for symptomatic control in KOA. Full article

(This article belongs to the Collection Botulinum Toxins on Human Pain)

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16 pages, 2089 KiB

Open AccessReview

Decoding Mycoplasma Nucleases: Biological Functions and Pathogenesis

by Xinchao Yi, Ying Huang, Xinru Li, Hao Xu, Chang Liu, Chao Li, Qianrui Zeng, Haodang Luo, Zufeng Ye, Jun He and Xiaoxing You

Toxins 2025, 17(5), 215; https://doi.org/10.3390/toxins17050215 - 24 Apr 2025

Abstract

Nucleases are critical metabolic enzymes expressed by mycoplasmas to acquire nucleic acid precursors from the host for their parasitic existence. Certain nucleases, either membrane-bound or secreted, not only contribute to the growth of mycoplasmas but also serve as key virulence factors due to [...] Read more.

Nucleases are critical metabolic enzymes expressed by mycoplasmas to acquire nucleic acid precursors from the host for their parasitic existence. Certain nucleases, either membrane-bound or secreted, not only contribute to the growth of mycoplasmas but also serve as key virulence factors due to their unique spatial structures and physiological activity. The pathogenesis includes, but is not limited to, degradation of host DNA and RNA, leading to disruptions of nucleic acid metabolism and the induction of host cell apoptosis; degradation of neutrophil extracellular traps (NETs), allowing escape from neutrophil-mediated killing; and upregulation of inflammatory molecules to modulate the immune response of the host. Understanding the biological functions of nucleases is essential for gaining deeper insights into the virulence and immune evasion strategies of mycoplasmas, which can inform the development of novel approaches for the prevention, diagnosis, and treatment of mycoplasma infections. Full article

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18 pages, 1955 KiB

Open AccessArticle

Evaluation of Untargeted Metabolomic and Mycotoxin Profiles in Corn Silage and High-Moisture Corn

by Marco Lapris, Valentina Novara, Mattia Masseroni, Michela Errico, Gabriele Rocchetti and Antonio Gallo

Toxins 2025, 17(5), 214; https://doi.org/10.3390/toxins17050214 - 24 Apr 2025

Abstract

Corn silage (CS) and high-moisture corn (HMC) represent fundamental ingredients in ruminant diets; however, their chemical complexity and susceptibility to mycotoxin contamination pose challenges for feed safety and quality assessment. This study applied an innovative approach combining untargeted metabolomics and mycotoxin profiling through [...] Read more.

Corn silage (CS) and high-moisture corn (HMC) represent fundamental ingredients in ruminant diets; however, their chemical complexity and susceptibility to mycotoxin contamination pose challenges for feed safety and quality assessment. This study applied an innovative approach combining untargeted metabolomics and mycotoxin profiling through ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to characterize the chemical profiles of CS (n = 19) and HMC (n = 13) samples collected from four farms in northern Italy over a period of two years. Fumonisin B1 (FB1) emerged as the most prevalent mycotoxin, with contamination levels significantly higher in HMC than CS, though all the detected levels complied with European Union (EU) guidance limits. Untargeted metabolomics distinguished CS and HMC based on their metabolic signatures: polyamines, amino acids, peptides, and phenolic acids typified CS, while HMC was primarily characterized by flavonoids and mycotoxins. Geographical origin significantly influenced both mycotoxin patterns and metabolite profiles, while the sampling season showed no significant impact. This study highlights the complementary value of metabolomics and mycotoxin screening to assess feed quality, identify biomarkers, and unravel the link between fungal contamination and biochemical composition, offering a robust strategy to support feed safety management in livestock production. Full article

(This article belongs to the Special Issue Mycotoxin Contaminants in Feed: Current Status and What Should We Do?)

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15 pages, 6359 KiB

Open AccessArticle

An Elastase Inhibitor ShSPI from Centipede Attenuates Bleomycin-Induced Pulmonary Fibrosis

by Xi Lian, Bin Liu, Dan Li, Xinyao Wang, Chengbo Long, Xing Feng, Qiong Liao and Mingqiang Rong

Toxins 2025, 17(5), 213; https://doi.org/10.3390/toxins17050213 - 24 Apr 2025

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive elastase levels in the lungs. ShSPI is an elastase inhibitor derived from centipede toxin. The present study evaluates the therapeutic effects of ShSPI in a bleomycin-induced idiopathic pulmonary fibrosis model. According to the results, ShSPI markedly reduced the weight loss, showing the improvement of health status in bleomycin-induced mice. Its robust antifibrotic effects were evidenced by the mitigation of alveolar structural damage, reduction in inflammatory cell infiltration, inhibition of collagen deposition, and suppression of fibrotic nodule formation. ShSPI effectively attenuated inflammatory responses by downregulating pro-inflammatory factors (IL-6, IL-1β, and MCP-1) and upregulating the anti-inflammatory factor interleukin-10 (IL-10). After delivered via inhalation, ShSPI exhibited favorable pharmacokinetic properties. It could be detected at 8 h at doses of 1 mg/kg and achieved maximum plasma concentrations (Cmax) of 188.00 ± 64.40 ng/mL in vivo. At high doses (160 mg/kg), ShSPI maintained a strong safety profile, with no detectable toxicity observed. This feature shows the therapeutic potential of ShSPI in the treatment of idiopathic pulmonary fibrosis and provides valuable evidence for its development as a novel peptide-based therapy. Full article

(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)

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22 pages, 2661 KiB

Open AccessArticle

The Efficacy of a Novel Water-Soluble Anti-Mycotoxin Solution in Improving Broiler Chicken Performance Under Mycotoxin Challenge

by Sayantani Sihi Arora, Anusuya Debnath, Amrita Kumar Dhara, Sudipto Haldar, Raquel Codina Moreno and Insaf Riahi

Toxins 2025, 17(5), 212; https://doi.org/10.3390/toxins17050212 - 23 Apr 2025

Abstract

Mycotoxins like aflatoxins (AFs), fumonisins (FBs), and ochratoxin A (OTA) pose serious health risks to humans and animals. Fruit pomace extracts, rich in natural nutrients and bioactive compounds, have the potential to enhance animal health and mitigate mycotoxin toxicity. This study evaluated a [...] Read more.

Mycotoxins like aflatoxins (AFs), fumonisins (FBs), and ochratoxin A (OTA) pose serious health risks to humans and animals. Fruit pomace extracts, rich in natural nutrients and bioactive compounds, have the potential to enhance animal health and mitigate mycotoxin toxicity. This study evaluated a novel liquid anti-mycotoxin solution (LAS), a combination of grape and olive pomace extract administered to broiler chickens through drinking water (2 L:1000 L) for 1–42 days under a natural multi-mycotoxin challenge. The 42-day trial with 288 one-day-old male Ross 308AP95 chicks included four experimental groups: a negative control (NC); NC+LAS; a positive control (PC) group fed a diet containing 80 μg/kg AFs, 1600 μg/kg FBs, and 50 μg/kg OTA; and PC+LAS. The growth performance, oxidative defense genes (liver), and stress biomarkers (blood) were analyzed. Mycotoxin exposure negatively affected body weight (BW), the feed conversion ratio (FCR), and the oxidative defense mechanism. LAS supplementation improved BW and the FCR, reduced Nrf-2 expression, and enhanced mycotoxin detoxification via lower EPHX1 expression. Though the LAS did not fully restore performance to NC levels, it significantly mitigated mycotoxin-induced damage. This study concluded that the LAS is a promising solution to improve broiler resilience against moderate to high mycotoxin exposure. Full article

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Graphical abstract

20 pages, 1936 KiB

Open AccessReview

Intravesical Onabotulinum Toxin A Injection Paradigms for Idiopathic Overactive Bladder: A Scoping Review of Clinical Outcomes, Techniques, and Implications for Practice and Future Research

by Ekene Enemchukwu, Hodan Mohamud, Shada Sinclair, Victoria Harbour, Raveen Syan, Michael Kennelly and Susanna Gunamany

Toxins 2025, 17(5), 211; https://doi.org/10.3390/toxins17050211 - 23 Apr 2025

Abstract

Introduction and Objectives: Onabotulinum toxin A (BTXA) is an effective treatment for refractory idiopathic overactive bladder (iOAB). Given the wide spectrum of patient factors and combination of symptoms, a tailored approach to management is needed. This scoping review assesses injection paradigms for iOAB. [...] Read more.

Introduction and Objectives: Onabotulinum toxin A (BTXA) is an effective treatment for refractory idiopathic overactive bladder (iOAB). Given the wide spectrum of patient factors and combination of symptoms, a tailored approach to management is needed. This scoping review assesses injection paradigms for iOAB. Prior studies have established the safety and efficacy of BTXA injections, and this review focuses on exploring variations in injection techniques that may inform more tailored approaches and support future research toward optimizing patient outcomes. Methods: We conducted a systematic literature search. Inclusion criteria included full-text English language and primary research studies assessing outcomes in adults undergoing BTXA for iOAB. Findings are summarized using narrative synthesis. Results: Forty-three articles were identified. Key findings include fewer injections (1–10 vs. 20–40) maintains efficacy while reducing procedure time, discomfort, and retreatment hesitancy. Durability appears to be lower with suburothelial and bladder base injections and higher with detrusor and bladder body injections, though these may carry an increased risk of urinary retention requiring clean intermittent catheterization. Trigone inclusion appears safe and effective without increased vesicoureteral reflux risk. Conclusions: Study heterogeneity and inconsistent reporting limit strong conclusions. Included injection paradigms demonstrated efficacy, high tolerability, symptom relief, and quality-of-life improvements with few adverse events. Further research is needed to refine optimal injection strategies to enhance patient comfort, maximize efficacy, and minimize adverse events. Future studies should ensure comprehensive data collection to clarify these associations. Full article

(This article belongs to the Special Issue Botulinum Toxin for Urinary Tract Disease: After a Decade from Approval)

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19 pages, 1929 KiB

Open AccessArticle

Molecular Diversity and Isoform Evolution in Tityus obscurus Venom: Insights from Proteomic Analysis

by Kemellyn Cristina Panchera, Lais Campelo Mendes, Ana Leonor Abrahão Nencioni, Daniel Carvalho Pimenta and Emídio Beraldo-Neto

Toxins 2025, 17(5), 210; https://doi.org/10.3390/toxins17050210 - 23 Apr 2025

Abstract

Over millions of years of evolution, natural selection has driven the specialization of predatory and defensive mechanisms in various animal species through the development of poisons and venoms. These venoms contain highly specific and selective molecules for several different targets according to the [...] Read more.

Over millions of years of evolution, natural selection has driven the specialization of predatory and defensive mechanisms in various animal species through the development of poisons and venoms. These venoms contain highly specific and selective molecules for several different targets according to the habitat and behavior of each species. In this work, we performed a comprehensive proteomic analysis of Tityus obscurus venom, identifying 45 proteins, including 8 toxins targeting K⁺ channels, 22 targeting Na⁺ channels, and 15 other venom components. Our study reveals seven novel isoforms of ion channel-targeting peptides characterized by amino acid substitutions which may influence their bioactivity and pharmacological properties. These findings contribute to our understanding of venom molecular diversity and evolution, providing new insights into peptide structure–function relationships. Considering the biomedical relevance of ion channel-modulating toxins, our work expands the repertoire of potential candidates for future drug development, particularly in the context of neuropharmacology and ion channel disorders. Full article

(This article belongs to the Special Issue New Insights into Structure and Function of Arthropod Toxins and Other Toxins: Tribute to Professor Hervé Rochat)

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14 pages, 3649 KiB

Open AccessArticle

Effectiveness of Unfocused vs. Focal Shock Waves Combined with Botulinum Toxin on Spasticity in Brain-Damaged Patients

by Antonio Déniz, Pedro Saavedra, Isabel Marrero, Samuel Barrera, Raúl Domínguez, Raúl Mendoza and Jorge Rodríguez

Toxins 2025, 17(5), 209; https://doi.org/10.3390/toxins17050209 - 22 Apr 2025

Abstract

Spasticity is a common complication in patients with neurological disorders, increasing disability and hampering quality of life. Combined treatment with focused shock waves (fESWT) and botulinum toxin (BoNT-A) has been shown to increase the effectiveness and duration of the effect of BoNT-A on [...] Read more.

Spasticity is a common complication in patients with neurological disorders, increasing disability and hampering quality of life. Combined treatment with focused shock waves (fESWT) and botulinum toxin (BoNT-A) has been shown to increase the effectiveness and duration of the effect of BoNT-A on spasticity in patients with brain injuries. We studied the effectiveness of the combination of unfocused shock waves (uESWT) and BoNT-A on spasticity. This prospective study with systematic randomization included 24 patients with brain injury, a small sample size due to clinical limitations, and spasticity was measured using the Ashworth scale (AS) for those with lower limb involvement; gait speed was assessed using the 10-m gait test (10MWT). To judge patient satisfaction with treatment, we used the Consumer Reports Effectiveness Scale-4 (CRES-4). Both uESWT and fESWT with BoNT-A resulted in a 3-point improvement in the median spasticity score, which was maintained from week 2 to week 26, and a statistically significant reduction in the 10MWT was observed. Furthermore, the proportion of patients who were very satisfied with the treatment was higher with uESWT (91%) than with fESWT (69.2%). To the authors’ knowledge, this is the first study to evaluate the added benefit of concurrent and combined treatment with uESWT and BoNT-A injections to improve spasticity in patients with stroke or multiple sclerosis and show higher patient satisfaction with the treatment. Full article

(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases (2nd Edition))

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12 pages, 1332 KiB

Open AccessArticle

Real-World Insights into the Effectiveness and Tolerability of OnabotulinumtoxinA in Chronic Migraine: A Long-Term Evaluation of up to 11 Years

by Antonio Santoro, Andrea Fontana, Massimiliano Copetti, Anna Maria Miscio and Giuseppe d’Orsi

Toxins 2025, 17(4), 208; https://doi.org/10.3390/toxins17040208 - 21 Apr 2025

Abstract

Background: Chronic migraine (CM) is a debilitating neurological disorder that imposes substantial burdens on individuals and society, including diminished quality of life and increased healthcare utilization. While the efficacy of botulinum neurotoxin type A (BoNT-A) has been demonstrated in controlled trials, this longitudinal, [...] Read more.

Background: Chronic migraine (CM) is a debilitating neurological disorder that imposes substantial burdens on individuals and society, including diminished quality of life and increased healthcare utilization. While the efficacy of botulinum neurotoxin type A (BoNT-A) has been demonstrated in controlled trials, this longitudinal, real-world study offers unprecedented evidence of its long-term benefits, with patients followed for a median of 15 months (interquartile range: 6–36 months) and up to 11 years. Methods: This retrospective analysis included 579 patients diagnosed with CM who were newly treated with BoNT-A, according to the PREEMPT protocol, receiving injections every 12 weeks at doses of 155–195 units across 31–39 sites. Outcomes were assessed through changes in monthly headache days, frequency, symptomatic medication use, and migraine-related disability using Migraine Disability Assessment (MIDAS) scores up to 60 months from recruitment. Safety was evaluated by recording treatment-emergent adverse events (TEAEs), with a focus on long-term tolerability and subgroup variability. Results: Patients showed sustained improvements, with the mean number of monthly headache days decreasing from 22.7 to 5.5, and symptomatic medication use dropping from 33.4 to 3.7 mean doses at 60 months. Additionally, over 60% of patients improved from severe (MIDAS Grade IV) to minimal disability (MIDAS Grade I). Subgroup analysis revealed variability in response rates, emphasizing the need for personalized approaches. TEAEs were predominantly mild, with no new adverse events reported after 36 months, supporting the long-term safety of BoNT-A in real-world settings. Conclusions: This real-world study provides significant evidence for the long-term efficacy, safety, and tolerability of BoNT-A in the preventive treatment of CM. The findings highlight the importance of real-world data to account for patient variability and tailoring treatment strategies. Full article

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13 pages, 252 KiB

Open AccessPerspective

Expert Opinions on Best Practices for Overactive Bladder Management with onabotulinumtoxinA

by Karyn S. Eilber, Benjamin M. Brucker, Andrea Pezzella, Vincent Lucente, Kevin Benson and Michael J. Kennelly

Toxins 2025, 17(4), 207; https://doi.org/10.3390/toxins17040207 - 21 Apr 2025

Abstract

OnabotulinumtoxinA is an FDA-approved treatment for adults with overactive bladder (OAB) who have an inadequate response to, or are intolerant of, oral pharmacotherapies including anticholinergics or beta-3 agonists. However, procedural practices of onabotulinumtoxinA intradetrusor injection vary among practitioners and can affect patient experience. [...] Read more.

OnabotulinumtoxinA is an FDA-approved treatment for adults with overactive bladder (OAB) who have an inadequate response to, or are intolerant of, oral pharmacotherapies including anticholinergics or beta-3 agonists. However, procedural practices of onabotulinumtoxinA intradetrusor injection vary among practitioners and can affect patient experience. To address this, a panel of six high-volume intravesical onabotulinumtoxinA providers with 100 years of combined experience convened to discuss the best office practices when treating patients with OAB. These key best practices include counseling patients on available OAB therapies, including onabotulinumtoxinA, at the initial consultation in accordance with established AUA and SUFU guidelines in a way that is easily understood. An office setting is preferred over a hospital or surgery center when performing the procedure. Staff involvement, from scheduling to post-procedure, is essential for establishing the relationships necessary to optimize patient experience and encourage compliance and retreatment. Experts generally recommend using a viscous lidocaine bladder instillation for an anesthetic 15 min prior to the reconstitution of onabotulinumtoxinA with 5 to 10 mL of normal saline. A range of one to 20 injection sites is acceptable, with a smaller number preferred. Starting in the lower bladder, experts recommend using a slower speed of injection to improve distribution and decrease patient discomfort. Subsequent treatments should be regularly scheduled at six-month intervals with the option of re-treating earlier if symptoms return, but no sooner than 12 weeks. For office intravesical onabotulinumtoxinA procedures, optimization of the patient experience by the physician and their staff, starting with the initial visit through the post-treatment follow-up, is key to long-term patient compliance. Full article

(This article belongs to the Special Issue Botulinum Toxin for Urinary Tract Disease: After a Decade from Approval)

14 pages, 1890 KiB

Open AccessArticle

Toxicokinetics of a Single Oral Dose of Aflatoxin B₁ in Plasma, Feces, and Urine of Male Donkeys

by Yulong Feng, Min Li, Yunduo Zheng, Honglei Qu, Pengshuai Li, Boying Dong, Yantao Wang, Guangyuan Liu, Bin Jia and Qiugang Ma

Toxins 2025, 17(4), 206; https://doi.org/10.3390/toxins17040206 - 20 Apr 2025

Abstract

Aflatoxin B₁ (AFB₁) is widely present in raw materials for food and feedstock, posing a significant threat to the health of humans and animals. This study explored the toxicokinetics of a single oral administration of AFB₁ at a dose [...] Read more.

Aflatoxin B₁ (AFB₁) is widely present in raw materials for food and feedstock, posing a significant threat to the health of humans and animals. This study explored the toxicokinetics of a single oral administration of AFB₁ at a dose of 100 µg·kg⁻¹ BW (body weight). Donkey blood samples were gathered at 0, 5, 10, 15, 20, 30, 45, and 60 min and at 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 6 h, 9 h, 12 h, 24 h, 48 h, 72 h, 96 h, and 120 h through jugular vein sampling needles at intervals. Fecal and urinary samples were collected at 0 h and every 6 h thereafter until 120 h. The concentrations of AFB₁ and AFM₁ in plasma, urine, and feces were quantitatively analyzed using LC-MS/MS. The maximum concentrations of AFB₁ and AFM₁ in plasma were 13.10 ± 6.35 µg·L⁻¹ and 0.72 ± 0.33 µg·L⁻¹, occurring at 1.38 ± 0.89 h and 2.25 ± 1.57 h after oral administration, respectively. The AFB₁ and AFM₁ elimination half-lives (T_1/2Elim) were 6.65 ± 2.84 h and 5.85 ± 3.00 h, respectively. The total clearances (CL) of AFB₁ and AFM₁ were 163 ± 52.2 L·kg⁻¹ BW⁻¹·h⁻¹ and 3210 ± 2450 L·kg⁻¹ BW⁻¹·h⁻¹, and the volumes of distribution (Vd) for AFB₁ were 1440 ± 417 L·kg⁻¹·BW and 22,400 ± 14,800 L·kg⁻¹·BW, respectively. In addition, the total amounts of AFB₁ and AFM₁ excreted over 120 h through urine and feces accounted for 3.38 ± 0.92% and 3.44 ± 1.45% of the total intake, respectively (calculated by material mass). Furthermore, the research showed that the absorption and metabolism of AFB₁ were rapid in male donkeys, with the tissue exhibiting a wide distribution and long duration. Full article

(This article belongs to the Section Mycotoxins)

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11 pages, 258 KiB

Open AccessArticle

Autonomic Dysfunction and Blood Pressure Variability in Botulinum Intoxication: A Prospective Observational Study from a Single-Center Italian Outbreak

by Giuseppe Miceli, Giuliano Cassataro, Vito Volpe, Emanuela Fertitta, Carmelinda Canale, Lucia Tomaiuolo, Melania Blasco, Mariagrazia Stella, Matteo Velardo and Maurizio Renda

Toxins 2025, 17(4), 205; https://doi.org/10.3390/toxins17040205 - 20 Apr 2025

Abstract

Botulinum neurotoxin (BoNT) intoxication is a rare but severe condition that is characterized by autonomic and neuromuscular dysfunction. This study aimed to evaluate autonomic impairment and blood pressure variability in patients with botulinum intoxication during an outbreak, compared to healthy controls, and to [...] Read more.

Botulinum neurotoxin (BoNT) intoxication is a rare but severe condition that is characterized by autonomic and neuromuscular dysfunction. This study aimed to evaluate autonomic impairment and blood pressure variability in patients with botulinum intoxication during an outbreak, compared to healthy controls, and to assess their progression over a six-month follow-up period. Methods: Twenty (n = 20) male patients diagnosed with BoNT intoxication and 34 age- and sex-matched healthy controls were enrolled. At baseline, all subjects underwent 24 h ambulatory blood pressure monitoring (ABPM), and clinostatic and orthostatic blood pressure measurements. Autonomic function parameters, including mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), SBP and DBP variability, SBP and DBP load, pulse pressure (PP), blood pressure variability ratio (BPVR), and morning surge, were analyzed. Follow-up assessments were conducted after six months. Results: Patients with botulinum intoxication exhibited significantly lower SBP, DBP, and blood pressure variability parameters compared to healthy controls. Orthostatic hypotension was present in 55% of patients at baseline, improving to 5% at follow-up. Respiratory failure occurred in 40% of cases, necessitating non-invasive ventilation in 35% and intubation in 20%. At six-month follow-up, mean SBP, DBP, heart rate, and blood pressure variability parameters increased significantly, indicating partial recovery of autonomic control. However, residual abnormalities in autonomic regulation persisted. Conclusions: BoNT intoxication leads to notable autonomic dysfunction, marked by impaired blood pressure regulation and a high prevalence of orthostatic hypotension. Although partial recovery occurs, long-term autonomic impairment persists, highlighting the necessity for ongoing cardiovascular monitoring and further research to accelerate autonomic recovery through targeted therapeutic interventions. Full article

(This article belongs to the Section Bacterial Toxins)

15 pages, 1265 KiB

Open AccessSystematic Review

Effectiveness of Bee Venom Injection for Parkinson’s Disease: A Systematic Review

by Hyein Jeong, Kyeong Han Kim and Seong-gyu Ko

Toxins 2025, 17(4), 204; https://doi.org/10.3390/toxins17040204 - 20 Apr 2025

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting over 8.5 million people as of 2019. While standard pharmacological treatments help alleviate symptoms, their long-term use can lead to side effects such as dyskinesia. Bee venom acupuncture (BVA) involves the [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide, affecting over 8.5 million people as of 2019. While standard pharmacological treatments help alleviate symptoms, their long-term use can lead to side effects such as dyskinesia. Bee venom acupuncture (BVA) involves the use of a natural toxin derived from bees that can be used for pain relief and treating neurological disorders. This study aimed to review the efficacy and safety of BVA for the treatment of PD. This review protocol was prospectively registered with PROSPERO (CRD420251000577). We searched eight databases in February 2025 and selected 12 studies involving 215 PD patients treated with BVA. Idiopathic Parkinson’s disease (IPD) is the most common diagnosis. The concentration and dosage per session ranged from 0.03 to 0.1 mg/mL and from 0.1 to 1.0 mL, respectively. Twenty-four different outcome measures were used, with the Unified PD Rating Scale employed in 91.7% of the studies. All studies reported improvements in outcomes. Mild adverse effects such as swelling and itching were noted in four studies (33.3%); however, no severe reactions such as anaphylactic shock occurred. These findings suggest that BVA has the potential for broader clinical applications in the treatment of PD. Full article

(This article belongs to the Special Issue Clinical Evidence for Therapeutic Effects and Safety of Animal Venoms)

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17 pages, 7461 KiB

Open AccessArticle

Apoptotic Effect of Combinations of T-2, HT-2, and Diacetoxyscirpenol on Human Jurkat T Cells

by Phattarawadee Wattanasuntorn, Saranya Poapolathep, Patchara Phuektes, Imourana Alassane-Kpembi, Johanna Fink-Gremmels, Isabelle P. Oswald and Amnart Poapolathep

Toxins 2025, 17(4), 203; https://doi.org/10.3390/toxins17040203 - 18 Apr 2025

Abstract

Trichothecene type A mycotoxins, such as T-2, HT-2, and diacetoxyscirpenol (DAS), are known to induce cytotoxicity and apoptosis in different cell types. As all three Fusarium toxins may occur concomitantly in a given food or feed commodity, there is growing interest in the [...] Read more.

Trichothecene type A mycotoxins, such as T-2, HT-2, and diacetoxyscirpenol (DAS), are known to induce cytotoxicity and apoptosis in different cell types. As all three Fusarium toxins may occur concomitantly in a given food or feed commodity, there is growing interest in the effect of such mycotoxin mixtures. This study aimed to identify the toxic interactions among T-2, HT-2, and DAS in a human Jurkat cell model. As a first step, an MTT assay was used to assess cytotoxicity after 24 h of cell exposure to individual mycotoxins and their mixtures. The results were used to calculate the combination index (CI), which indicates the nature of the mycotoxin interactions. In Jurkat T cells, the toxicity ranking for the individual mycotoxins was T-2 > HT-2 > DAS. The CI values of the dual and triple mycotoxin combinations calculated from the results of the MTT and reactive oxygen species assays showed synergistic effects at low concentrations and an apparent antagonism at very high concentrations for all combinations. The additional cytometric analyses confirmed the synergistic effects, as expected, following co-exposure to the three tested trichothecenes. As the lower toxin concentrations investigated reflect natural contamination levels in food and feeds, the synergistic effects identified should be considered in risk characterization for trichothecene exposure in humans and animals. Full article

(This article belongs to the Special Issue Alleviation of Mycotoxin-Induced Toxicity)

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12 pages, 239 KiB

Open AccessArticle

Efficacy and Predictive Factors of Intravesical Botulinum Toxin A Injection for Treating Neurogenic Detrusor Overactivity in Children: A Single-Center Retrospective Study

by Chun-Kai Hsu, Han-Yu Lin, Stephen Shei-Dei Yang, Wan-Ling Young and Shu-Yu Wu

Toxins 2025, 17(4), 202; https://doi.org/10.3390/toxins17040202 - 17 Apr 2025

Abstract

Neurogenic detrusor overactivity (NDO) is a complex condition associated with detrusor overactivity, reduced bladder compliance, and high intravesical pressures, potentially leading to urinary tract infections (UTIs) and renal impairment. This retrospective study evaluated the safety and potential efficacy of intravesical botulinum toxin A [...] Read more.

Neurogenic detrusor overactivity (NDO) is a complex condition associated with detrusor overactivity, reduced bladder compliance, and high intravesical pressures, potentially leading to urinary tract infections (UTIs) and renal impairment. This retrospective study evaluated the safety and potential efficacy of intravesical botulinum toxin A (BoNT/A) injections in children with NDO at a single institution. Eighteen pediatric patients (median age: 8.1 years) were followed for a median of 6.3 years. At follow-up, 77.8% achieved a global response assessment (GRA) score of ≥2. A statistically significant improvement was found in cystometric bladder capacity (p = 0.041), but it did not remain significant after Bonferroni correction, while other urodynamic trends were not statistically significant. Adverse events were infrequent, with only 11.8% experiencing mild febrile UTIs. While some patients with poorer baseline bladder conditions reported greater subjective improvement, no statistically significant predictors of success were identified. Overall, intravesical BoNT/A injection appears to be a safe and potentially effective option for managing pediatric NDO, though larger prospective studies are needed to confirm these findings. Full article

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

15 pages, 3663 KiB

Open AccessArticle

Trends in Mycotoxins Co-Occurrence in the Complete Feed for Farm Animals in Southern Romania During 2021–2024 Period

by Valeria Cristina Bulgaru, Mihail Alexandru Gras, Aglaia Popa, Gina Cecilia Pistol, Ionelia Taranu and Daniela Eliza Marin

Toxins 2025, 17(4), 201; https://doi.org/10.3390/toxins17040201 - 15 Apr 2025

Abstract

Mycotoxins are common natural contaminants of crops and fruits, associated with negative effects on human and animal health. Currently, more than 300 mycotoxins have been identified, but data on their effects and their limits in feed and food are still inconsistent. The European [...] Read more.

Mycotoxins are common natural contaminants of crops and fruits, associated with negative effects on human and animal health. Currently, more than 300 mycotoxins have been identified, but data on their effects and their limits in feed and food are still inconsistent. The European Commission, by directive EC 574/2011, established regulations concerning the maximum limit allowed in farm animals’ feed for aflatoxins, but for all other mycotoxins there are only recommendations (EC 1319/2016) and there are no established limits. Considering their variety and toxic effects, but also the fact that not many details are yet known about the cumulative effects of co-contamination with various mycotoxins, it is necessary to monitor the evolution of their presence in animal feed. The aim of our study was to analyze for a four-year period (2021–2024) the concentrations of six mycotoxins (total aflatoxins-AFT, fumonisins-FB, deoxynivalenol-DON, zearalenone-ZEA, T2/HT2 and ochratoxin (A + B)-OTA), the most frequently encountered in the south area of Romania in poultry, piglets and pig’s complete feed. Our results showed that the maximum highest concentrations were 5.8 ppb for AFT, 4.7 ppm for FB, 1.9 ppm for DON, 62.8 ppb for ZEA, 32.1 ppb for T2/HT2 and 19.7 ppb for OTA irrespective of the type of feed. It should be noted that AFT and ZEA were identified in all samples during the entire monitored period, and the only mycotoxin that exceeded the guidance value was DON, for which the recommendation of 0.9 ppm for pig feed was exceeded. Recent studies demonstrated that sub-chronic and chronic exposure to low concentrations of mycotoxins and specially co-contamination is more common than acute exposure, being able to affect animal health over time by lowering the defense capacity, inducing inflammatory reactions and affecting intestinal health, which in the long term could have important economic consequences. Our survey study can provide important data showing the degree of contamination with mycotoxins in pig and poultry feed including the simultaneous presence of different mycotoxins in this complete feed. Full article

(This article belongs to the Section Mycotoxins)

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