Toxins

21 pages, 2893 KiB

Open AccessArticle

by Hong-Yan Zhao, Na He, Yan Sun, Yong-Chen Wang, Hao-Bing Zhang, Hui-Hui Chen, Ya-Qi Zhang and Jian-Fang Gao

Toxins 2023, 15(5), 350; https://doi.org/10.3390/toxins15050350 - 21 May 2023

Viewed by 1489

Abstract

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms [...] Read more.

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA₂ (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA₂ (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 2421 KiB

Open AccessEditor’s ChoiceArticle

Bioactives Overproduction through Operational Strategies in the Ichthyotoxic Microalga Heterosigma akashiwo Culture

by Adrián Macías-de la Rosa, Miguel Ángel González-Cardoso, María del Carmen Cerón-García, Lorenzo López-Rosales, Juan José Gallardo-Rodríguez, Sergio Seoane, Asterio Sánchez-Mirón and Francisco García-Camacho

Toxins 2023, 15(5), 349; https://doi.org/10.3390/toxins15050349 - 20 May 2023

Cited by 1 | Viewed by 1511

Abstract

The red tide-forming microalga Heterosigma akashiwo has been associated with massive events of fish deaths, both wild and cultured. Culture conditions are responsible for the synthesis or accumulation of some metabolites with different interesting bioactivities. H. akashiwo LC269919 strain was grown in a [...] Read more.

The red tide-forming microalga Heterosigma akashiwo has been associated with massive events of fish deaths, both wild and cultured. Culture conditions are responsible for the synthesis or accumulation of some metabolites with different interesting bioactivities. H. akashiwo LC269919 strain was grown in a 10 L bubble column photobioreactor artificially illuminated with multi-coloured LED lights. Growth and production of exopolysaccharides, polyunsaturated fatty acids (PUFAs), and carotenoids were evaluated under different culture modes (batch, fed-batch, semicontinuous, and continuous) at two irradiance levels (300 and 700 µE·s⁻¹·m⁻²). Continuous mode at the dilution rate of 0.2·day⁻¹ and 700 µE·s⁻¹·m⁻² provided the highest production of biomass, PUFAs (132.6 and 2.3 mg·L⁻¹·day⁻¹), and maximum fucoxanthin productivity (0.16 mg·L⁻¹·day⁻¹). The fed-batch mode accumulated exopolysaccharides in a concentration (1.02 g·L⁻¹) 10-fold over the batch mode. An extraction process based on a sequential gradient partition with water and four water-immiscible organic solvents allowed the isolation of bioactive fucoxanthin from methanolic extracts of H. akashiwo. Metabolites present in H. akashiwo, fucoxanthin and polar lipids (i.e., eicosapentaenoic acid (EPA)), or probably such as phytosterol (β-Sitosterol) from other microalgae, were responsible for the antitumor activity obtained. Full article

(This article belongs to the Section Marine and Freshwater Toxins)

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13 pages, 2888 KiB

Open AccessArticle

Biological Activity of Naphthoquinones Derivatives in the Search of Anticancer Lead Compounds

by Alexandra G. Durán, Nuria Chinchilla, Ana M. Simonet, M. Teresa Gutiérrez, Jorge Bolívar, Manuel M. Valdivia, José M. G. Molinillo and Francisco A. Macías

Toxins 2023, 15(5), 348; https://doi.org/10.3390/toxins15050348 - 20 May 2023

Cited by 2 | Viewed by 1398

Abstract

Naphthoquinones are a valuable source of secondary metabolites that are well known for their dye properties since ancient times. A wide range of biological activities have been described highlighting their cytotoxic activity, gaining the attention of researchers in recent years. In addition, it [...] Read more.

Naphthoquinones are a valuable source of secondary metabolites that are well known for their dye properties since ancient times. A wide range of biological activities have been described highlighting their cytotoxic activity, gaining the attention of researchers in recent years. In addition, it is also worth mentioning that many anticancer drugs possess a naphthoquinone backbone in their structure. Considering this background, the work described herein reports the evaluation of the cytotoxicity of different acyl and alkyl derivatives from juglone and lawsone that showed the best activity results from a etiolated wheat coleoptile bioassay. This bioassay is rapid, highly sensitive to a wide spectrum of activities, and is a powerful tool for detecting biologically active natural products. A preliminary cell viability bioassay was performed on cervix carcinoma (HeLa) cells for 24 h. The most promising compounds were further tested for apoptosis on different tumoral (IGROV-1 and SK-MEL-28) and non-tumoral (HEK-293) cell lines by flow cytometry. Results reveal that derivatives from lawsone (particularly derivative 4) were more cytotoxic on tumoral than in non-tumoral cells, showing similar results to those obtained with of etoposide, which is used as a positive control for apoptotic cell death. These findings encourage further studies on the development of new anticancer drugs for more directed therapies and reduced side effects with naphthoquinone skeleton. Full article

(This article belongs to the Special Issue Biological Activities and Potential Applications of Phytotoxins)

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18 pages, 14434 KiB

Open AccessArticle

The Potent Antitumor Activity of Smp43 against Non-Small-Cell Lung Cancer A549 Cells via Inducing Membranolysis and Mitochondrial Dysfunction

by Ze Deng, Yahua Gao, Tienthanh Nguyen, Jinwei Chai, Jiena Wu, Jiali Li, Mohamed A. Abdel-Rahman, Xueqing Xu and Xin Chen

Toxins 2023, 15(5), 347; https://doi.org/10.3390/toxins15050347 - 19 May 2023

Viewed by 1389

Abstract

Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its [...] Read more.

Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its impact on non-small-cell lung cancer (NSCLC) cell lines has not been previously investigated. This study aimed to determine the cytotoxicity of Smp43 towards various NSCLC cell lines, particularly A549 cells with an IC₅₀ value of 2.58 μM. The results indicated that Smp43 was internalized into A549 cells through membranolysis and endocytosis, which caused cytoskeleton disorganization, a loss of mitochondrial membrane potential, an accumulation of reactive oxygen species (ROS), and abnormal apoptosis, cell cycle distribution, and autophagy due to mitochondrial dysfunction. Additionally, the study explored the in vivo protective effect of Smp43 in xenograft mice. The findings suggest that Smp43 has potential anticarcinoma properties exerted via the inducement of cellular processes related to cell membrane disruption and mitochondrial dysfunction. Full article

(This article belongs to the Special Issue Animal Venom: Challenges and Perspectives in Drug Discovery)

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25 pages, 31522 KiB

Open AccessReview

Toxicity of House Plants to Pet Animals

by Zuzana Siroka

Toxins 2023, 15(5), 346; https://doi.org/10.3390/toxins15050346 - 19 May 2023

Cited by 1 | Viewed by 4516

Abstract

Cases of ingestion of indoor poisonous plants are relatively common among animals and lead to both acute cases of poisoning and long-term exposure to harmful substances and chronic damage to the animal’s health. Plants produce a large number of secondary metabolites, which serve [...] Read more.

Cases of ingestion of indoor poisonous plants are relatively common among animals and lead to both acute cases of poisoning and long-term exposure to harmful substances and chronic damage to the animal’s health. Plants produce a large number of secondary metabolites, which serve to protect the plant from attacks by insects, parasitic plants, fungi or, for example, during reproduction. However, these metabolites can be toxic if ingested by animals or humans. Toxicologically effective components found in plants are mainly alkaloids, glycosides, saponins, terpenes and others. This review article describes in detail the most common and popular indoor poisonous plants grown in Europe, the mechanisms of action of their active substances and clinical signs of the respective poisonings. This manuscript is supplemented with rich photographic documentation of these plants not found in similar articles, and also includes a description of the treatment of individual types of poisoning. Full article

(This article belongs to the Special Issue Animal Poisoning: Toxins from Plants or Feed)

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14 pages, 1986 KiB

Open AccessArticle

Antimicrobial Peptide Arsenal Predicted from the Venom Gland Transcriptome of the Tropical Trap-Jaw Ant Odontomachus chelifer

by Josilene J. Menk, Yan E. Matuhara, Henrique Sebestyen-França, Flávio Henrique-Silva, Milene Ferro, Renata S. Rodrigues and Célio D. Santos-Júnior

Toxins 2023, 15(5), 345; https://doi.org/10.3390/toxins15050345 - 18 May 2023

Cited by 1 | Viewed by 1603

Abstract

With about 13,000 known species, ants are the most abundant venomous insects. Their venom consists of polypeptides, enzymes, alkaloids, biogenic amines, formic acid, and hydrocarbons. In this study, we investigated, using in silico techniques, the peptides composing a putative antimicrobial arsenal from the [...] Read more.

With about 13,000 known species, ants are the most abundant venomous insects. Their venom consists of polypeptides, enzymes, alkaloids, biogenic amines, formic acid, and hydrocarbons. In this study, we investigated, using in silico techniques, the peptides composing a putative antimicrobial arsenal from the venom gland of the neotropical trap-jaw ant Odontomachus chelifer. Focusing on transcripts from the body and venom gland of this insect, it was possible to determine the gland secretome, which contained about 1022 peptides with putative signal peptides. The majority of these peptides (75.5%) were unknown, not matching any reference database, motivating us to extract functional insights via machine learning-based techniques. With several complementary methodologies, we investigated the existence of antimicrobial peptides (AMPs) in the venom gland of O. chelifer, finding 112 non-redundant candidates. Candidate AMPs were predicted to be more globular and hemolytic than the remaining peptides in the secretome. There is evidence of transcription for 97% of AMP candidates across the same ant genus, with one of them also verified as translated, thus supporting our findings. Most of these potential antimicrobial sequences (94.8%) matched transcripts from the ant’s body, indicating their role not solely as venom toxins. Full article

(This article belongs to the Special Issue Ant Venom)

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18 pages, 5856 KiB

Open AccessArticle

Effect of Monocerin, a Fungal Secondary Metabolite, on Endothelial Cells

by Tainah Colombo Gomes, Rafael Conrado, Rodrigo Cardoso de Oliveira, Priscila Jane Romano Gonçalves Selari, Itamar Soares de Melo, Welington Luiz Araújo, Durvanei Augusto Maria and Ana Olívia De Souza

Toxins 2023, 15(5), 344; https://doi.org/10.3390/toxins15050344 - 18 May 2023

Viewed by 1232

Abstract

This study reports the isolation and identification of the endophytic fungus Exserohilum rostratum through molecular and morphological analysis using optical and transmission electron microscopy (TEM), as well as the procurement of its secondary metabolite monocerin, an isocoumarin derivative. Considering the previously observed biological [...] Read more.

This study reports the isolation and identification of the endophytic fungus Exserohilum rostratum through molecular and morphological analysis using optical and transmission electron microscopy (TEM), as well as the procurement of its secondary metabolite monocerin, an isocoumarin derivative. Considering the previously observed biological activities of monocerin, this study was performed on human umbilical vein endothelial cells (HUVECs) that are widely used as an in vitro model for several different purposes. Important parameters, such as cell viability, senescence-associated β-galactosidase, cellular proliferation by using 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE), apoptosis analysis with annexin, cellular morphology through scanning electron microscopy (SEM), and laser confocal analysis were evaluated after exposing the cells to monocerin. After 24 h of exposure to monocerin at 1.25 mM, there was more than 80% of cell viability and a low percentage of cells in the early and late apoptosis and necrosis. Monocerin increased cell proliferation and did not induce cell senescence. Morphological analysis showed cellular integrity. The study demonstrates aspects of the mechanism of action of monocerin on endothelial cell proliferation, suggesting the possibility of its pharmaceutical application, such as in regenerative medicine. Full article

(This article belongs to the Collection Editorial Board Members’ Collection Series: Fungal Metabolites: From Toxins to Therapeutics)

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16 pages, 1707 KiB

Open AccessArticle

Behavioral and Physiological Alterations in Angus Steers Grazing Endophyte-Infected Toxic Fescue during Late Fall

by Ignacio M. Llada, Jeferson M. Lourenco, Mikayla M. Dycus, Jessica M. Carpenter, Garret Suen, Nicholas S. Hill and Nikolay M. Filipov

Toxins 2023, 15(5), 343; https://doi.org/10.3390/toxins15050343 - 18 May 2023

Cited by 1 | Viewed by 1248

Abstract

Fescue toxicosis is caused by grazing ergot alkaloid-producing endophyte (Epichloë coenophiala)-infected tall fescue (E+). Summer grazing of E+ leads to decreased productivity, associated impaired thermoregulation, and altered behavior. The goal of this study was to determine the role of E+ grazing-climate [...] Read more.

Fescue toxicosis is caused by grazing ergot alkaloid-producing endophyte (Epichloë coenophiala)-infected tall fescue (E+). Summer grazing of E+ leads to decreased productivity, associated impaired thermoregulation, and altered behavior. The goal of this study was to determine the role of E+ grazing-climate interaction on animal behavior and thermoregulation during late fall. Eighteen Angus steers were placed on nontoxic (NT), toxic (E+) and endophyte-free (E−) fescue pastures for 28 days. Physiological parameters, such as rectal temperature (RT), respiration rate (RR), ear and ankle surface temperature (ET, AT), and body weights, were measured. Skin surface temperature (SST) and animal activity were recorded continuously with temperature and behavioral activity sensors, respectively. Environmental conditions were collected using paddocks-placed data loggers. Across the trial, steers on E+ gained about 60% less weight than the other two groups. E+ steers also had higher RT than E− and NT, and lower SST than NT post-pasture placement. Importantly, animals grazing E+ spent more time lying, less time standing, and took more steps. These data suggest that late fall E+ grazing impairs core and surface temperature regulation and increases non-productive lying time, which may be partly responsible for the observed decreased weight gains. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 1912 KiB

Open AccessArticle

Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX^®) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis

by Joseph Jankovic, Jean Carruthers, Markus Naumann, Patricia Ogilvie, Terry Boodhoo, Mayssa Attar, Swati Gupta, Ritu Singh, John Soliman, Irina Yushmanova, Mitchell F. Brin and Jie Shen

Toxins 2023, 15(5), 342; https://doi.org/10.3390/toxins15050342 - 17 May 2023

Cited by 3 | Viewed by 2997

Abstract

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate [...] Read more.

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and post-treatment was tested and examined for impact on clinical safety and efficacy. Overall, 27 of the 5876 evaluable subjects (0.5%) developed NAbs after onabotulinumtoxinA treatment. At study exit, 16 of the 5876 subjects (0.3%) remained NAb positive. Due to the low incidence of NAb formation, no clear relationship was discernable between positive NAb results and gender, indication, dose level, dosing interval, treatment cycles, or the site of injection. Only five subjects who developed NAbs post-treatment were considered secondary nonresponders. Subjects who developed NAbs revealed no other evidence of immunological reactions or clinical disorders. This comprehensive meta-analysis confirms the low NAb formation rate following onabotulinumtoxinA treatment across multiple indications, and its limited clinical impact on treatment safety and efficacy. Full article

(This article belongs to the Special Issue Immunogenicity of Botulinum Toxin)

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20 pages, 2899 KiB

Open AccessArticle

Anxiolytic, Analgesic and Anti-Inflammatory Effects of Peptides Hmg 1b-2 and Hmg 1b-4 from the Sea Anemone Heteractis magnifica

by Irina N. Gladkikh, Anna A. Klimovich, Rimma S. Kalina, Yulia V. Kozhevnikova, Timur A. Khasanov, Dmitry I. Osmakov, Sergey G. Koshelev, Margarita M. Monastyrnaya, Yaroslav A. Andreev, Elena V. Leychenko and Sergey A. Kozlov

Toxins 2023, 15(5), 341; https://doi.org/10.3390/toxins15050341 - 15 May 2023

Cited by 1 | Viewed by 1573

Abstract

Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone [...] Read more.

Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone toxins, native Hmg 1b-2 and recombinant Hmg 1b-4, both related to APETx-like peptides, inhibited the transient current component of human ASIC3-Δ20 expressed in Xenopus laevis oocytes, but only Hmg 1b-2 inhibited the rat ASIC3 transient current. The Hmg 1b-4 action on rASIC3 as a potentiator was confirmed once again. Both peptides are non-toxic molecules for rodents. In open field and elevated plus maze tests, Hmg 1b-2 had more of an excitatory effect and Hmg 1b-4 had more of an anxiolytic effect on mouse behavior. The analgesic activity of peptides was similar and comparable to diclofenac activity in an acid-induced muscle pain model. In models of acute local inflammation induced by λ-carrageenan or complete Freund’s adjuvant, Hmg 1b-4 had more pronounced and statistically significant anti-inflammatory effects than Hmg 1b-2. It exceeded the effect of diclofenac and, at a dose of 0.1 mg/kg, reduced the volume of the paw almost to the initial volume. Our data highlight the importance of a comprehensive study of novel ASIC-targeting ligands, and in particular, peptide toxins, and present the slightly different biological activity of the two similar toxins. Full article

(This article belongs to the Special Issue Ion Channels, Venom, and Toxins)

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14 pages, 5467 KiB

Open AccessArticle

Functional Characterization of a New Degradation Peptide BmTX4-P1 from Traditional Chinese Scorpion Medicinal Material

by Chenhu Qin, Xuhua Yang, Yuanyuan Zhang, Gang Deng, Xin Huang, Zheng Zuo, Fang Sun, Zhijian Cao, Zongyun Chen and Yingliang Wu

Toxins 2023, 15(5), 340; https://doi.org/10.3390/toxins15050340 - 15 May 2023

Cited by 1 | Viewed by 1201

Abstract

Thermally processed Buthus martensii Karsch scorpion is an important traditional Chinese medical material that has been widely used to treat various diseases in China for over one thousand years. Our recent work showed that thermally processed Buthus martensii Karsch scorpions contain many degraded [...] Read more.

Thermally processed Buthus martensii Karsch scorpion is an important traditional Chinese medical material that has been widely used to treat various diseases in China for over one thousand years. Our recent work showed that thermally processed Buthus martensii Karsch scorpions contain many degraded peptides; however, the pharmacological activities of these peptides remain to be studied. Here, a new degraded peptide, BmTX4-P1, was identified from processed Buthus martensii Karsch scorpions. Compared with the venom-derived wild-type toxin peptide BmTX4, BmTX4-P1 missed some amino acids at the N-terminal and C-terminal regions, while containing six conserved cysteine residues, which could be used to form disulfide bond-stabilized α-helical and β-sheet motifs. Two methods (chemical synthesis and recombinant expression) were used to obtain the BmTX4-P1 peptide, named sBmTX4-P1 and rBmTX4-P1. Electrophysiological experimental results showed that sBmTX4-P1 and rBmTX4-P1 exhibited similar activities to inhibit the currents of hKv1.2 and hKv1.3 channels. In addition, the experimental electrophysiological results of recombinant mutant peptides of BmTX4-P1 indicated that the two residues of BmTX4-P1 (Lys²² and Tyr³¹) were the key residues for its potassium channel inhibitory activity. In addition to identifying a new degraded peptide, BmTX4-P1, from traditional Chinese scorpion medicinal material with high inhibitory activities against the hKv1.2 and hKv1.3 channels, this study also provided a useful method to obtain the detailed degraded peptides from processed Buthus martensii Karsch scorpions. Thus, the study laid a solid foundation for further research on the medicinal function of these degraded peptides. Full article

(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action v 2.0)

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6 pages, 277 KiB

Open AccessEditorial

Harmful Algae Impacting Aquatic Organisms: Recent Field and Laboratory Observations

by Juan José Dorantes-Aranda

Toxins 2023, 15(5), 339; https://doi.org/10.3390/toxins15050339 - 15 May 2023

Cited by 1 | Viewed by 1999

Abstract

Algal blooms formed by some phytoplankton species can produce toxins or alter environmental conditions that can affect aquatic organisms and water quality, with impacts on the aquaculture and fisheries industries that can pose a risk to public health [...] Full article

(This article belongs to the Special Issue Effects of Harmful Algal Blooms on Aquatic Organisms)

14 pages, 1483 KiB

Open AccessArticle

Retrospective Observational Study of Treatment Patterns and Efficacy of onabotulinumtoxinA Therapy in Patients with Refractory Overactive Bladder in Clinical Practice

by Kwang Jin Ko and Kyu-Sung Lee

Toxins 2023, 15(5), 338; https://doi.org/10.3390/toxins15050338 - 15 May 2023

Viewed by 1165

Abstract

This study aimed to evaluate the treatment patterns and long-term efficacy of onabotulinumtoxinA injections in a clinical setting. This single-center retrospective study was conducted on patients with refractory overactive bladder (OAB) aged 18 years or older who received onabotulinumtoxinA 100 IU administered between [...] Read more.

This study aimed to evaluate the treatment patterns and long-term efficacy of onabotulinumtoxinA injections in a clinical setting. This single-center retrospective study was conducted on patients with refractory overactive bladder (OAB) aged 18 years or older who received onabotulinumtoxinA 100 IU administered between April 2012 and May 2022. The primary endpoint was the treatment pattern, including the retreatment rate and OAB medication prescription pattern. The duration and effectiveness of onabotulinumtoxinA treatment were analyzed using the overactive bladder symptom score and voiding diaries. A total of 216 patients were enrolled in this study, and the overall patient satisfaction rate was 55.1%. After the first injection, 19.9% received a second treatment, and 6.1% received three or more injections. The median duration until the second injection was 10.7 months. Among the patients, 51.4% resumed OAB medications after 2.96 months. The presence of urodynamic detrusor overactivity was observed only in female patients (odds ratio, 23.65; 95% CI, 1.84 to 304.40), which was associated with a good response. In contrast to clinical trials, the degree of improvement and retreatment rate did not meet expectations. Our findings provide valuable insights into the effectiveness of onabotulinumtoxinA injections in patients with refractory OAB symptoms in real-world practice. Full article

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

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12 pages, 2203 KiB

Open AccessArticle

Automatic Pretreatment of Dispersive Liquid Liquid Microextraction Based on Immunomagnetic Beads Coupled with UPLC-FLD for the Determination of Zearalenone in Corn Oils

by Baoxia Ni, Jin Ye, Zhihong Xuan, Li Li, Xiangrui Wen, Zongwang Li, Hongmei Liu and Songxue Wang

Toxins 2023, 15(5), 337; https://doi.org/10.3390/toxins15050337 - 15 May 2023

Cited by 1 | Viewed by 1280

Abstract

Sample pretreatment is a vital step in the detection of mycotoxins, and traditional pretreatment methods are time-consuming, labor-intensive and generate much organic waste liquid. In this work, an automatic, high-throughput and environmentally friendly pretreatment method is proposed. Immunomagnetic beads technology and dispersive liquid–liquid [...] Read more.

Sample pretreatment is a vital step in the detection of mycotoxins, and traditional pretreatment methods are time-consuming, labor-intensive and generate much organic waste liquid. In this work, an automatic, high-throughput and environmentally friendly pretreatment method is proposed. Immunomagnetic beads technology and dispersive liquid–liquid microextraction technology are combined, and the zearalenone in corn oils is directly purified and concentrated under the solubilization effects of surfactant. The proposed pretreatment method allows for the batch pretreatment of samples without pre-extraction using organic reagents, and almost no organic waste liquid is produced. Coupled with UPLC-FLD, an effective and accurate quantitative detection method for zearalenone is established. The recovery of spiked zearalenone in corn oils at different concentrations ranges from 85.7 to 89.0%, and the relative standard deviation is below 2.9%. The proposed pretreatment method overcomes the shortcomings of traditional pretreatment methods and has broad application prospects. Full article

(This article belongs to the Special Issue Last Studies on Mycotoxins’ Fate during Food and Herbal Medicine Processing)

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12 pages, 563 KiB

Open AccessReview

Botulinum Toxin Treatment for Depression: A New Paradigm for Psychiatry

by Eric Finzi

Toxins 2023, 15(5), 336; https://doi.org/10.3390/toxins15050336 - 14 May 2023

Cited by 1 | Viewed by 3775

Abstract

Multiple randomized double-blind placebo-controlled trials have shown that botulinum toxin A (BoNT/A), when injected into the frown musculature, is an antidepressant. This review outlines the conceptual narrative behind this treatment modality, starting with theory developed by Charles Darwin. We develop the concept of [...] Read more.

Multiple randomized double-blind placebo-controlled trials have shown that botulinum toxin A (BoNT/A), when injected into the frown musculature, is an antidepressant. This review outlines the conceptual narrative behind this treatment modality, starting with theory developed by Charles Darwin. We develop the concept of emotional proprioception and discuss how the muscles of facial expression play an important role in relaying valenced information to the brain’s emotional neuroanatomical circuit. We review the role of facial frown musculature as the brain’s barometer and transmitter of negatively valanced emotional information. The direct connections between the corrugator muscles and the amygdala are reviewed, and these provide a neuroanatomical circuit that is a logical target for treatment with BoNT/A. The centrality of amygdala dysfunction in the pathogenesis of many psychiatric disorders, and the evidence that BoNT/A modulates amygdala activity, provides the mechanistic link between BoNT/A and its antidepressant activity. Animal models of BoNT/A’s antidepressant effects confirm the evolutionary conservation of this emotional circuit. The clinical and theoretical implications of this evidence, as it relates to the potential treatment of a broad range of psychiatric disorders by BoNT/A, is discussed. The ease of administration, long duration, and favorable side effect profile of this therapy is reviewed in the context of existing antidepressant treatments. Full article

(This article belongs to the Special Issue Treatment of Mental Health Disorders with Botulinum Toxin)

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14 pages, 1278 KiB

Open AccessArticle

Increasing the Passive Range of Joint Motion in Stroke Patients Using Botulinum Toxin: The Role of Pain Relief

by Carlo Trompetto, Lucio Marinelli, Laura Mori, Nicola Bragazzi, Giulia Maggi, Filippo Cotellessa, Luca Puce, Lucilla Vestito, Franco Molteni, Giulio Gasperini, Nico Farina, Luciano Bissolotti, Francesco Sciarrini, Marzia Millevolte, Fabrizio Balestrieri, Domenico Antonio Restivo, Carmelo Chisari, Andrea Santamato, Alessandra Del Felice, Paolo Manganotti, Carlo Serrati and Antonio Currà Show full author list Hide full author list

Toxins 2023, 15(5), 335; https://doi.org/10.3390/toxins15050335 - 13 May 2023

Cited by 3 | Viewed by 1830

Abstract

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle [...] Read more.

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3–6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment. Full article

(This article belongs to the Special Issue Botulinum Neurotoxins: From Toxin to Medicine)

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12 pages, 12383 KiB

Open AccessArticle

Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage

by Fan Wang, Fuhai Zhang, Juxingsi Song, Shuaijun Zou, Jie Li, Yichao Huang, Liming Zhang and Qianqian Wang

Toxins 2023, 15(5), 334; https://doi.org/10.3390/toxins15050334 - 13 May 2023

Viewed by 1615

Abstract

Tetrodotoxin (TTX) is a highly fatal marine biotoxin. Constantly increasing intoxications and the lack of specific antitoxic drugs in clinical applications highlight the need for further research into the toxic effects of TTX. Current reports on poisoning cases and the TTX toxicity mechanism [...] Read more.

Tetrodotoxin (TTX) is a highly fatal marine biotoxin. Constantly increasing intoxications and the lack of specific antitoxic drugs in clinical applications highlight the need for further research into the toxic effects of TTX. Current reports on poisoning cases and the TTX toxicity mechanism suggest that the blocking of voltage-gated sodium channels (VGSCs) by TTX is probably reversible, but direct evidence of this is lacking, as far as we are aware. This study explored the acute toxic effects of TTX at sub-lethal doses via different routes, analyzing variations in muscle strength and TTX concentration in the blood in mice. We found that the loss of muscle strength in mice caused by TTX was dose-dependent and reversible, and the death time and muscle strength variations after oral gavage with TTX appeared to occur later and were more variable than those after intramuscular injection. In conclusion, we systematically compared the acute toxic effects of TTX for two different administration routes at sub-lethal doses, directly verifying the reversible reaction of TTX blocking VGSCs and speculating that averting a complete block of VGSCs by TTX could be an effective strategy for preventing death from TTX poisoning. This work may provide data for the diagnosis and treatment of TTX poisoning. Full article

(This article belongs to the Special Issue Advances in Marine Toxins: Characterization, Analysis and Surveillance)

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16 pages, 1807 KiB

Open AccessArticle

Pain Reduction in Cervical Dystonia Following Treatment with IncobotulinumtoxinA: A Pooled Analysis

by Alberto Albanese, Jörg Wissel, Wolfgang H. Jost, Anna Castagna, Michael Althaus, Georg Comes, Astrid Scheschonka, Matteo Vacchelli and Hyder A. Jinnah

Toxins 2023, 15(5), 333; https://doi.org/10.3390/toxins15050333 - 12 May 2023

Cited by 3 | Viewed by 1892

Abstract

This analysis pooled pain severity data from four phase 3 and 4 studies of incobotulinumtoxinA (incoBoNT-A) for the treatment of cervical dystonia (CD) in adults. CD-related pain severity was assessed at baseline, each injection visit, and 4 weeks after each injection of incoBoNT-A [...] Read more.

This analysis pooled pain severity data from four phase 3 and 4 studies of incobotulinumtoxinA (incoBoNT-A) for the treatment of cervical dystonia (CD) in adults. CD-related pain severity was assessed at baseline, each injection visit, and 4 weeks after each injection of incoBoNT-A using the Toronto Western Spasmodic Torticollis Rating Scale pain severity subscale or a pain visual analog scale. Both were analyzed using a score range of 0–10 and pain was categorized as mild, moderate, or severe. Data for 678 patients with pain at baseline were assessed and sensitivity analyses evaluated pain responses in the subgroup not taking concomitant pain medication (n = 384 at baseline). At Week 4 after the first injection, there was a mean change of −1.25 (standard deviation 2.04) points from baseline pain severity (p < 0.0001), with 48.1% showing ≥ 30% pain reduction from baseline, 34.4% showing ≥50% pain reduction from baseline, and 10.3% becoming pain free. Pain responses were sustained over five injection cycles with a trend to incremental improvements with each successive cycle. Pain responses in the subgroup not taking concomitant pain medication demonstrated the lack of confounding effects of pain medications. These results confirmed the pain relief benefits of long-term treatment with incoBoNT-A. Full article

(This article belongs to the Special Issue Botulinum Neurotoxins: From Toxin to Medicine)

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20 pages, 1502 KiB

Open AccessEditor’s ChoiceSystematic Review

Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Maria Tiziana Corasaniti, Giacinto Bagetta, Pierluigi Nicotera, Assunta Tarsitano, Paolo Tonin, Giorgio Sandrini, Gary W. Lawrence and Damiana Scuteri

Toxins 2023, 15(5), 332; https://doi.org/10.3390/toxins15050332 - 12 May 2023

Cited by 3 | Viewed by 2112

Abstract

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the [...] Read more.

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010. This systematic review and meta-analysis appraises the safety of onabotulinumtoxin A treatment for chronic migraine and the occurrence of treatment-related adverse events (TRAEs) in randomized, clinical studies in comparison with placebo or other comparators and preventative treatments according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieved 888 total records. Nine studies are included and seven were eligible for meta-analysis. The present study demonstrates that toxin produces more TRAEs than placebo, but less than oral topiramate, supporting the safety of onabotulinumtoxin A, and highlights the heterogeneity of the studies present in the literature (I² = 96%; p < 0.00001). This points to the need for further, adequately powered, randomized clinical trials assessing the safety of onabotulinumtoxin A in combination with the newest treatment options. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin: Shared/Common Mechanisms in the Treatment of Pain, Spasticity and Movement Disorders)

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18 pages, 5148 KiB

Open AccessArticle

Characterization of the Molecular Diversity and Degranulation Activity of Mastoparan Family Peptides from Wasp Venoms

by Xiangdong Ye, Xin Liu, Xudong Luo, Fang Sun, Chenhu Qin, Li Ding, Wen Zhu, Huajun Zhang, Haimei Zhou and Zongyun Chen

Toxins 2023, 15(5), 331; https://doi.org/10.3390/toxins15050331 - 12 May 2023

Cited by 3 | Viewed by 1268

Abstract

Wasp stings have become an increasingly serious public health problem because of their high incidence and mortality rates in various countries and regions. Mastoparan family peptides are the most abundant natural peptides in hornet venoms and solitary wasp venom. However, there is a [...] Read more.

Wasp stings have become an increasingly serious public health problem because of their high incidence and mortality rates in various countries and regions. Mastoparan family peptides are the most abundant natural peptides in hornet venoms and solitary wasp venom. However, there is a lack of systematic and comprehensive studies on mastoparan family peptides from wasp venoms. In our study, for the first time, we evaluated the molecular diversity of 55 wasp mastoparan family peptides from wasp venoms and divided them into four major subfamilies. Then, we established a wasp peptide library containing all 55 known mastoparan family peptides by chemical synthesis and C-terminal amidation modification, and we systematically evaluated their degranulation activities in two mast cell lines, namely the RBL-2H3 and P815 cell lines. The results showed that among the 55 mastoparans, 35 mastoparans could significantly induce mast cell degranulation, 7 mastoparans had modest mast cell degranulation activity, and 13 mastoparans had little mast cell degranulation activity, suggesting functional variation in mastoparan family peptides from wasp venoms. Structure–function relationship studies found that the composition of amino acids in the hydrophobic face and amidation in the C-terminal region are critical for the degranulation activity of mastoparan family peptides from wasp venoms. Our research will lay a theoretical foundation for studying the mechanism underlying the degranulation activity of wasp mastoparans and provide new evidence to support the molecular design and molecular optimization of natural mastoparan peptides from wasp venoms in the future. Full article

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17 pages, 7971 KiB

Open AccessArticle

Investigation on Fermentation Characteristics and Microbial Communities of Wheat Straw Silage with Different Proportion Artemisia argyi

by Zhenyu Wang, Zhongfang Tan, Guofang Wu, Lei Wang, Guangyong Qin, Yanping Wang and Huili Pang

Toxins 2023, 15(5), 330; https://doi.org/10.3390/toxins15050330 - 11 May 2023

Cited by 1 | Viewed by 1365

Abstract

Mycotoxins, secondary metabolites of fungi, are a major obstacle to the utilization of animal feed for various reasons. Wheat straw (WS) is hollow, and miscellaneous bacteria can easy attach to its surface; the secondary fermentation frequency after silage is high, and there is [...] Read more.

Mycotoxins, secondary metabolites of fungi, are a major obstacle to the utilization of animal feed for various reasons. Wheat straw (WS) is hollow, and miscellaneous bacteria can easy attach to its surface; the secondary fermentation frequency after silage is high, and there is a risk of mycotoxin poisoning. In this study, a storage fermentation process was used to preserve and enhance fermentation quality in WS through the addition of Artemisia argyi (AA), which is an effective method to use WS resources and enhance aerobic stability. The storage fermentation of WS treated with AA had lower pH and mycotoxin (AFB1 and DON) values than the control due to rapid changes in microbial counts, especially in the 60% AA groups. Meanwhile, the addition of 60% AA improved anaerobic fermentation profiles, showing higher lactic acid contents, leading to increased efficiency of lactic acid fermentation. A background microbial dynamic study indicated that the addition of 60% AA improved the fermentation and aerobic exposure processes, decreased microbial richness, enriched Lactobacillus abundance, and reduced Enterobacter and Aspergillus abundances. In conclusion, 60% AA treatment could improve the quality by increase fermentation quality and improve the aerobic stability of WS silage by enhancing the dominance of desirable Lactobacillus, inhibiting the growth of undesirable microorganisms, especially fungi, and reducing the content of mycotoxins. Full article

(This article belongs to the Special Issue Mycotoxins in Animal Feed and Animal-Derived Food: Analytical Approach and Toxicology)

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17 pages, 1262 KiB

Open AccessArticle

LC-MS/MS Analysis of Cyanotoxins in Bivalve Mollusks—Method Development, Validation and First Evidence of Occurrence of Nodularin in Mussels (Mytilus edulis) and Oysters (Magallana gigas) from the West Coast of Sweden

by Julio César España Amórtegui, Heidi Pekar, Mark Dennis Chico Retrato, Malin Persson, Bengt Karlson, Jonas Bergquist and Aida Zuberovic-Muratovic

Toxins 2023, 15(5), 329; https://doi.org/10.3390/toxins15050329 - 11 May 2023

Cited by 1 | Viewed by 2149

Abstract

In this paper, an LC-MS/MS method for the simultaneous identification and quantification of cyanotoxins with hydrophilic and lipophilic properties in edible bivalves is presented. The method includes 17 cyanotoxins comprising 13 microcystins (MCs), nodularin (NOD), anatoxin-a (ATX-a), homoanatoxin (h-ATX) and cylindrospermopsin (CYN). A [...] Read more.

In this paper, an LC-MS/MS method for the simultaneous identification and quantification of cyanotoxins with hydrophilic and lipophilic properties in edible bivalves is presented. The method includes 17 cyanotoxins comprising 13 microcystins (MCs), nodularin (NOD), anatoxin-a (ATX-a), homoanatoxin (h-ATX) and cylindrospermopsin (CYN). A benefit to the presented method is the possibility for the MS detection of MC-LR-[Dha7] and MC-LR-[Asp3] as separately identified and MS-resolved MRM signals, two congeners which were earlier detected together. The performance of the method was evaluated by in-house validation using spiked mussel samples in the quantification range of 3.12–200 µg/kg. The method was found to be linear over the full calibration range for all included cyanotoxins except CYN for which a quadratic regression was used. The method showed limitations for MC-LF (R² = 0.94), MC-LA (R² ≤ 0.98) and MC-LW (R² ≤ 0.98). The recoveries for ATX-a, h-ATX, CYN, NOD, MC-LF and MC-LW were lower than desired (<70%), but stable. Despite the given limitations, the validation results showed that the method was specific and robust for the investigated parameters. The results demonstrate the suitability of the method to be applied as a reliable monitoring tool for the presented group of cyanotoxins, as well as highlight the compromises that need to be included if multi-toxin methods are to be used for the analysis of cyanotoxins with a broader range of chemical properties. Furthermore, the method was used to analyze 13 samples of mussels (Mytilus edulis) and oysters (Magallana gigas) collected in the 2020–2022 summers along the coast of Bohuslän (Sweden). A complementary qualitative analysis for the presence of cyanotoxins in phytoplankton samples collected from marine waters around southern Sweden was performed with the method. Nodularin was identified in all samples and quantified in bivalve samples in the range of 7–397 µg/kg. Toxins produced by cyanobacteria are not included in the European Union regulatory monitoring of bivalves; thus, the results presented in this study can be useful in providing the basis for future work including cyanotoxins within the frame of regulatory monitoring to increase seafood safety. Full article

(This article belongs to the Special Issue Advanced Research on Cyanotoxins: Toxic Mechanisms, Toxicological Effects, and Analytical Aspects)

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18 pages, 2023 KiB

Open AccessArticle

Gut-Faecal Microbial and Health-Marker Response to Dietary Fumonisins in Weaned Pigs

by Yarsmin Yunus Zeebone, Brigitta Bóta, Veronika Halas, Balázs Libisch, Ferenc Olasz, Péter Papp, Tibor Keresztény, Annamária Gerőcs, Omeralfaroug Ali, Melinda Kovács and András Szabó

Toxins 2023, 15(5), 328; https://doi.org/10.3390/toxins15050328 - 11 May 2023

Viewed by 1791

Abstract

This study investigated effects of dietary fumonisins (FBs) on gut and faecal microbiota of weaned pigs. In total, 18 7-week-old male pigs were fed either 0, 15 or 30 mg FBs (FB₁ + FB₂ + FB₃)/kg diet for 21 [...] Read more.

This study investigated effects of dietary fumonisins (FBs) on gut and faecal microbiota of weaned pigs. In total, 18 7-week-old male pigs were fed either 0, 15 or 30 mg FBs (FB₁ + FB₂ + FB₃)/kg diet for 21 days. The microbiota was analysed with amplicon sequencing of the 16S rRNA gene V3-V4 regions (Illumina MiSeq). Results showed no treatment effect (p > 0.05) on growth performance, serum reduced glutathione, glutathione peroxidase and malondialdehyde. FBs increased serum aspartate transaminase, gamma glutamyl-transferase and alkaline phosphatase activities. A 30 mg/kg FBs treatment shifted microbial population in the duodenum and ileum to lower levels (compared to control (p < 0.05)) of the families Campylobacteraceae and Clostridiaceae, respectively, as well as the genera Alloprevotella, Campylobacter and Lachnospiraceae Incertae Sedis (duodenum), Turicibacter (jejunum), and Clostridium sensu stricto 1 (ileum). Faecal microbiota had higher levels of the Erysipelotrichaceae and Ruminococcaceae families and Solobacterium, Faecalibacterium, Anaerofilum, Ruminococcus, Subdoligranulum, Pseudobutyrivibrio, Coprococcus and Roseburia genera in the 30 mg/kg FBs compared to control and/or to the 15 mg/kg FBs diets. Lactobacillus was more abundant in the duodenum compared to faeces in all treatment groups (p < 0.01). Overall, the 30 mg/kg FBs diet altered the pig gut microbiota without suppressing animal growth performance. Full article

(This article belongs to the Special Issue Effects of Feedborne Mycotoxins on Animal Health 2.0)

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14 pages, 1038 KiB

Open AccessArticle

Use of Botulinum Toxin as a Treatment of Hemiplegic Shoulder Pain Syndrome: A Randomized Trial

by Eduardo de Melo Carvalho Rocha, Marcelo Riberto, Rodrigo da Ponte Barbosa, Renan Miguel Porcini Geronimo and Mauricio Menezes-Junior

Toxins 2023, 15(5), 327; https://doi.org/10.3390/toxins15050327 - 11 May 2023

Viewed by 1711

Abstract

Objective: The primary objective of this paper is to assess whether the use of 200 units of abobotulinum in the pectoralis major and subscapularis muscles modifies the pain complaint assessed using the visual analog scale in subjects with shoulder pain after the onset [...] Read more.

Objective: The primary objective of this paper is to assess whether the use of 200 units of abobotulinum in the pectoralis major and subscapularis muscles modifies the pain complaint assessed using the visual analog scale in subjects with shoulder pain after the onset of spastic hemiplegia due to cerebrovascular disease when compared to the application of a placebo to the same muscles. Design: A prospective, double-blind, randomized, and placebo-controlled clinical trial study in two different rehabilitation centers. Setting: Two distinct outpatient neurological rehabilitation services. Participants: Patients older than 18 years who were included presented upper limb spasticity resulting from ischemic or hemorrhagic stroke and a diagnosis of Painful Hemiplegic Shoulder Syndrome (PHSS) that was independent of motor dominance. Interventions: Patients were divided into two groups, one of them underwent the application of botulinum toxin (TXB-A) in the pectoralis major and subscapularis muscles, at a total dose of 400 U. Main Outcome Measure: Patients were assessed for a change in pain using the Visual Analog Scale (VAS) for at least 13 mm. Results: An improvement in pain and spasticity levels in both groups, more intense in the toxin group, but without statistical significance. The comparison between the groups showed a reduction in pain by VAS (p = 0.52). Conclusions: The use of botulinum toxin in the subscapularis and pectoralis major muscles resulted in a reduction in shoulder pain in spastic hemiplegic patients without statistical significance. Full article

(This article belongs to the Section Bacterial Toxins)

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10 pages, 2097 KiB

Open AccessCommunication

Label-Free Direct Detection of Cylindrospermopsin via Graphene-Enhanced Surface Plasmon Resonance Aptasensor

by Stefan Jaric, Aabha Bajaj, Vladimir Vukic, Ivana Gadjanski, Ibrahim Abdulhalim and Ivan Bobrinetskiy

Toxins 2023, 15(5), 326; https://doi.org/10.3390/toxins15050326 - 10 May 2023

Cited by 2 | Viewed by 1440

Abstract

In this work, we report a novel method for the label-free detection of cyanotoxin molecules based on a direct assay utilizing a graphene-modified surface plasmon resonance (SPR) aptasensor. Molecular dynamic simulation of the aptamer’s interaction with cylindrospermopsin (CYN) reveals the strongest binding sites [...] Read more.

In this work, we report a novel method for the label-free detection of cyanotoxin molecules based on a direct assay utilizing a graphene-modified surface plasmon resonance (SPR) aptasensor. Molecular dynamic simulation of the aptamer’s interaction with cylindrospermopsin (CYN) reveals the strongest binding sites between C18–C26 pairs. To modify the SPR sensor, the wet transfer method of CVD monolayer graphene was used. For the first time, we report the use of graphene functionalized by an aptamer as a bioreceptor in conjunction with SPR for the detection of CYN. In a direct assay with an anti-CYN aptamer, we demonstrated a noticeable change in the optical signal in response to the concentrations far below the maximum tolerable level of 1 µg/L and high specificity. Full article

(This article belongs to the Special Issue Prospective Studies in Survey and Biosurvey of Cyanotoxins In Situ)

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13 pages, 908 KiB

Open AccessArticle

Natural Occurrence of Alternaria Toxins in Citrus-Based Products Collected from China in 2021

by Xiaomin Han, Wenjing Xu, Luxinyi Wang, Ruina Zhang, Jin Ye, Jing Zhang, Jin Xu and Yu Wu

Toxins 2023, 15(5), 325; https://doi.org/10.3390/toxins15050325 - 09 May 2023

Cited by 4 | Viewed by 1475

Abstract

A total of 181 citrus-based products, including dried fruits, canned fruits, and fruit juices, collected from China and from abroad in 2021 were analyzed for the four Alternaria toxins (ALTs): alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), and tenuazonic acid (TeA) via [...] Read more.

A total of 181 citrus-based products, including dried fruits, canned fruits, and fruit juices, collected from China and from abroad in 2021 were analyzed for the four Alternaria toxins (ALTs): alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), and tenuazonic acid (TeA) via ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC-ESI-MS). Although the concentrations of the four ALTs varied by product and geographically, TeA was the predominant toxin followed by AOH, AME, and TEN. Products made in China showed higher levels of ALTs than those made abroad. Maximum levels of TeA, AOH, and AME in analyzed domestic samples were 4.9-fold, 1.3-fold, and 1.2-fold, respectively, higher than those in imported products. Furthermore, 83.4% (151/181) of the analyzed citrus-based products were contaminated with at least two or more ALTs. There were significant positive correlations between AOH and AME, AME and TeA, and TeA and TEN in all analyzed samples. More importantly, the solid and the condensed liquid products had higher concentrations of ALTs than the semi-solid product samples, as well as tangerines, pummelos, and grapefruits compared to the other kinds of citrus-based products. In conclusion, co-contamination with ALTs in commercially available Chinese citrus-based products was universal. Extensive and systematic surveillance of ALTs in citrus-based products, both domestic and imported, is required to obtain more scientific data for the determination of the maximum allowable concentrations of ALTs in China. Full article

(This article belongs to the Topic Emerging Food Safety Issues Associated with Mycotoxins)

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10 pages, 1328 KiB

Open AccessArticle

Regional Targeted Subcutaneous Injection of Botulinum Neurotoxin Type A in Refractory Chronic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study

by Francesco Bono, Maria Rosaria Mazza, Giuseppe Magro, Giorgio Spano, Giovanni Idone, Vincenzo Laterza, Denise Tedeschi, Francesco Pucci, Antonio Gambardella and Alessia Sarica

Toxins 2023, 15(5), 324; https://doi.org/10.3390/toxins15050324 - 09 May 2023

Cited by 1 | Viewed by 1711

Abstract

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of an individualized technique of subcutaneous injection of botulinum toxin type A (BoNT-A) targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine (CM). Patients who had not [...] Read more.

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of an individualized technique of subcutaneous injection of botulinum toxin type A (BoNT-A) targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine (CM). Patients who had not previously responded to at least two treatments of intramuscular injections of BoNT-A were randomly assigned (2:1) to receive two subcutaneous administrations of BoNT-A (up to 200 units) with the SjBoT injection paradigm or placebo. Following the skin area where the maximum pain began, treatment was given in the trigeminal or occipital region bilaterally. The primary endpoint changed in monthly headache days from baseline to the last 4 weeks. Among 139 randomized patients, 90 received BoNT-A and 49 received placebo, and 128 completed the double-blind phase. BoNT-A significantly reduced monthly headache days versus placebo (−13.2 versus −1.2; p < 0.0001) in the majority of patients who had cutaneous allodynia. Other secondary endpoints, including measures for disability (Migraine Disability Assessment questionnaire from baseline 21.96 to 7.59 after treatment, p = 0.028), also differed. Thus, in non-responder patients with CM, BoNT-A significantly reduced migraine days when administered according to the “follow the origin of maximum pain” approach using SjBoT injection paradigm. Full article

(This article belongs to the Special Issue Botulinum Toxin and Migraine: Goals and Perspectives)

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19 pages, 3318 KiB

Open AccessArticle

Temporal Exposure to Bt Insecticide Causes Oxidative Stress in Larval Midgut Tissue

by Biko K. Muita and Simon W. Baxter

Toxins 2023, 15(5), 323; https://doi.org/10.3390/toxins15050323 - 07 May 2023

Cited by 1 | Viewed by 2028

Abstract

Bacillus thuringiensis (Bt) three-domain Cry toxins are highly successful biological pesticides; however, the mechanism through which they cause death to targeted larval midgut cells is not fully understood. Herein, we challenged transgenic Bt-susceptible Drosophila melanogaster larvae with moderate doses of activated Cry1Ac toxin [...] Read more.

Bacillus thuringiensis (Bt) three-domain Cry toxins are highly successful biological pesticides; however, the mechanism through which they cause death to targeted larval midgut cells is not fully understood. Herein, we challenged transgenic Bt-susceptible Drosophila melanogaster larvae with moderate doses of activated Cry1Ac toxin and assessed the midgut tissues after one, three, and five hours using transmission electron microscopy and transcriptome sequencing. Larvae treated with Cry1Ac showed dramatic changes to their midgut morphology, including shortened microvilli, enlarged vacuoles, thickened peritrophic membranes, and swelling of the basal labyrinth, suggesting water influx. Transcriptome analysis showed that innate immune responses were repressed, genes involved with cell death pathways were largely unchanged, and mitochondria-related genes were strongly upregulated following toxin exposure. Defective mitochondria produced after toxin exposure were likely to contribute to significant levels of oxidative stress, which represent a common physiological response to a range of toxic chemicals. Significant reductions in both mitochondrial aconitase activity and ATP levels in the midgut tissue supported a rapid increase in reactive oxygen species (ROS) following exposure to Cry1Ac. Overall, these findings support the role of water influx, midgut cell swelling, and ROS activity in response to moderate concentrations of Cry1Ac. Full article

(This article belongs to the Special Issue Mode of Action of Proteinaceous Toxins Produced by Bacillus thuringiensis)

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2 pages, 193 KiB

Open AccessCorrection

Correction: Degen et al. Citrinin Exposure in Germany: Urine Biomarker Analysis in Children and Adults. Toxins 2023, 15, 26

by Gisela H. Degen, Jörg Reinders, Martin Kraft, Wolfgang Völkel, Felicia Gerull, Rafael Burghardt, Silvia Sievering, Jennifer Engelmann, Yvonni Chovolou, Jan G. Hengstler and Hermann Fromme

Toxins 2023, 15(5), 322; https://doi.org/10.3390/toxins15050322 - 06 May 2023

Viewed by 723

Abstract

In the original publication [...] Full article

3 pages, 201 KiB

Open AccessEditorial

Botulinum Toxin Brings a Light to the Shadow of Functional Urology

by Hann-Chorng Kuo

Toxins 2023, 15(5), 321; https://doi.org/10.3390/toxins15050321 - 06 May 2023

Viewed by 1137

Abstract

Functional urology involves a large scale of lower urinary tract dysfunctions (LUTDs), including bladder dysfunctions and bladder outlet dysfunctions [...] Full article

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

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