Toxins

12 pages, 2855 KiB

Open AccessArticle

Mutation of a Threonine Residue in αD-β4 Loop of Cyt2Aa2 Protein Influences Binding on Fluid Lipid Membranes

by Chontida Tangsongcharoen, Jose L. Toca-Herrera, Boonhiang Promdonkoy and Sudarat Tharad

Toxins 2023, 15(2), 167; https://doi.org/10.3390/toxins15020167 - 19 Feb 2023

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Cyt proteins are insecticidal proteins originally from Bacillus thuringiensis. The lipid binding of the Cyt2Aa2 protein depends on the phase of the lipid bilayer. In this work, the importance of the conserved T144 residue in the αD-β4 loop for lipid binding on [...] Read more.

Cyt proteins are insecticidal proteins originally from Bacillus thuringiensis. The lipid binding of the Cyt2Aa2 protein depends on the phase of the lipid bilayer. In this work, the importance of the conserved T144 residue in the αD-β4 loop for lipid binding on fluid lipid membranes was investigated via atomic force microscopy (AFM). Lipid membrane fluidity could be monitored for the following lipid mixture systems: POPC/DPPC, POPC/SM, and DOPC/SM. AFM results revealed that the T144A mutant was unable to bind to pure POPC bilayers. Similar topography between the wildtype and T144A mutant was seen for the POPC/Chol system. Small aggregates of T144A mutant were observed in the POPC and DOPC domains of the lipid mixture systems. In addition, the T144A mutant had no cytotoxic effect against human colon cancer cells. These results suggest that alanine replacement into threonine 144 hinders the binding of Cyt2Aa2 on liquid lipid membranes. These observations provide a possibility to modify the Cyt2Aa2 protein to specific cells via lipid phase selection. Full article

(This article belongs to the Special Issue Bacterial Toxins: Protein Folding and Membrane Interactions)

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14 pages, 2588 KiB

Open AccessReview

Role of Urological Botulinum Toxin-A Injection for Overactive Bladder and Voiding Dysfunction in Patients with Parkinson’s Disease or Post-Stroke

by Ju-Chuan Hu, Lin-Nei Hsu, Wei-Chia Lee, Yao-Chi Chuang and Hung-Jen Wang

Toxins 2023, 15(2), 166; https://doi.org/10.3390/toxins15020166 - 17 Feb 2023

Cited by 5 | Viewed by 3330

Abstract

Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson’s disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor [...] Read more.

Botulinum toxin A (BoNT-A) paralyzes muscle by blocking acetylcholine release at the synaptic junction. BoNT-A has shown its therapeutic effects in neurological disorders such as Parkinson’s disease (PD) and post-stroke spasticity. A high proportion of patients with PD and post-stroke develop neurogenic detrusor overactivity (nDO) and then develop urinary incontinence and overactive bladder (OAB) symptoms. This study aimed to disclose the safety and efficacy of BoNT-A injection in treating bladder and voiding dysfunction in PD and post-stroke patients by reviewing the current evidence. At present, intradetrusor injection of BoNT-A is a Food and Drug Administration (FDA)-approved third-line therapy for nDO and idiopathic OAB. Although intradetrusor injection of onaBoNT-A 200 U is already approved for nDO treatment, most researchers would like to manage PD and post-stroke patients by using onaBoNT-A 100 U intradetrusor injection to achieve long-term efficacy and reduce adverse effects. However, in contrast to its inclusion in the International Continence Society guidelines for PD treatment, the clinical use of BoNT-A for post-stroke patients is limited to experimental use due to the development of urinary retention in about one-fifth of patients. For treating urethral pseudodyssynergia, half of patients may respond to onaBoNT-A 100 U urethral injection. However, refinement is needed to reduce unwanted urinary incontinence. 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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14 pages, 2093 KiB

Open AccessReview

A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin

by Nikolajs Sjakste and Goran Gajski

Toxins 2023, 15(2), 165; https://doi.org/10.3390/toxins15020165 - 17 Feb 2023

Cited by 2 | Viewed by 2076

Abstract

Envenomation by animal venoms remains a serious medical and social problem, especially in tropical countries. On the other hand, animal venoms are widely used as a source of biologically active compounds for the development of novel drugs. Numerous derivatives of animal venoms are [...] Read more.

Envenomation by animal venoms remains a serious medical and social problem, especially in tropical countries. On the other hand, animal venoms are widely used as a source of biologically active compounds for the development of novel drugs. Numerous derivatives of animal venoms are already used in clinical practice. When analysing the mechanisms of action of animal venoms, attention is usually focused on the main target of the venom’s enzymes and peptides such as neurotoxic, cytotoxic or haemorrhagic effects. In the present review, we would like to draw attention to the “hidden” effects of animal venoms and their derivatives in regard to DNA damage and/or protection against DNA damage. Alkaloids and terpenoids isolated from sponges such as avarol, ingenamine G or variolin B manifest the capability to bind DNA in vitro and produce DNA breaks. Trabectidin, isolated from a sea squirt, also binds and damages DNA. A similar action is possible for peptides isolated from bee and wasp venoms such as mastoparan, melectin and melittin. However, DNA lesions produced by the crude venoms of jellyfish, scorpions, spiders and snakes arise as a consequence of cell membrane damage and the subsequent oxidative stress, whereas certain animal venoms or their components produce a genoprotective effect. Current research data point to the possibility of using animal venoms and their components in the development of various potential therapeutic agents; however, before their possible clinical use the route of injection, molecular target, mechanism of action, exact dosage, possible side effects and other fundamental parameters should be further investigated. Full article

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

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11 pages, 1346 KiB

Open AccessReview

Type II Toxin–Antitoxin Systems in Pseudomonas aeruginosa

by Meng Li, Nannan Guo, Gaoyu Song, Yi Huang, Lecheng Wang, Yani Zhang and Tietao Wang

Toxins 2023, 15(2), 164; https://doi.org/10.3390/toxins15020164 - 17 Feb 2023

Cited by 1 | Viewed by 2801

Abstract

Toxin–antitoxin (TA) systems are typically composed of a stable toxin and a labile antitoxin; the latter counteracts the toxicity of the former under suitable conditions. TA systems are classified into eight types based on the nature and molecular modes of action of the [...] Read more.

Toxin–antitoxin (TA) systems are typically composed of a stable toxin and a labile antitoxin; the latter counteracts the toxicity of the former under suitable conditions. TA systems are classified into eight types based on the nature and molecular modes of action of the antitoxin component so far. The 10 pairs of TA systems discovered and experimentally characterised in Pseudomonas aeruginosa are type II TA systems. Type II TA systems have various physiological functions, such as virulence and biofilm formation, protection host against antibiotics, persistence, plasmid maintenance, and prophage production. Here, we review the type II TA systems of P. aeruginosa, focusing on their biological functions and regulatory mechanisms, providing potential applications for the novel drug design. Full article

(This article belongs to the Section Bacterial Toxins)

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18 pages, 2270 KiB

Open AccessArticle

First Identification of Amphidinols from Mexican Strains and New Analogs

by Lorena M. Durán-Riveroll, Jannik Weber and Bernd Krock

Toxins 2023, 15(2), 163; https://doi.org/10.3390/toxins15020163 - 16 Feb 2023

Cited by 1 | Viewed by 1418

Abstract

The genus Amphidinium has been the subject of recent attention due to the production of polyketide metabolites. Some of these compounds have shown significant bioactivities and could be related to species interactions in the natural benthic microenvironment. Among these compounds, amphidinols (AMs) are [...] Read more.

The genus Amphidinium has been the subject of recent attention due to the production of polyketide metabolites. Some of these compounds have shown significant bioactivities and could be related to species interactions in the natural benthic microenvironment. Among these compounds, amphidinols (AMs) are suspected to be related to fish kills and probably implicated in ciguatera symptoms associated with the occurrence of benthic harmful algal blooms (bHABs). Here, we present the first report of a variety of AMs produced by cultured strains from several species from the Mexican Pacific, the Gulf of California, and the Gulf of Mexico. Through ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), ten previously known AMs (AM02, -04, -05, -06, -07, -09, -11, -14, -15, and -17), four recently reported AMs (N7, N8/N9, N12, and N13), and three new variants (U1, U2, and U3) were identified. Of the twelve analyzed Amphidinium cultures, five were not AM producers, and the cell quotas of the remaining seven strains ranged from close to nondetectable to a maximum of 1694 fg cell⁻¹, with many intermediate levels in between. The cultures from the Mexican North Pacific coast produced AMs in a higher quantity and variety than those from worldwide locations. This is the first study of AMs from Mexican Amphidinium strains, and our results confirm the relevance of continuing the investigation of the genus bioactive metabolites. Full article

(This article belongs to the Special Issue New Frontiers in Monitoring, Detecting and Response to Marine and Freshwater Algal Toxins and Their Causative Organisms)

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2 pages, 613 KiB

Open AccessCorrection

Correction: Addante-Moya et al. Assessment of the Optimum Linker Tethering Site of Alternariol Haptens for Antibody Generation and Immunoassay Development. Toxins 2021, 13, 883

by Luis G. Addante-Moya, Antonio Abad-Somovilla, Antonio Abad-Fuentes, Consuelo Agulló and Josep V. Mercader

Toxins 2023, 15(2), 162; https://doi.org/10.3390/toxins15020162 - 16 Feb 2023

Viewed by 788

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Application of Novel Methods for Mycotoxins Analysis)

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19 pages, 3123 KiB

Open AccessArticle

Metabolome-Based Classification of Snake Venoms by Bioinformatic Tools

by Luis L. Alonso, Julien Slagboom, Nicholas R. Casewell, Saer Samanipour and Jeroen Kool

Toxins 2023, 15(2), 161; https://doi.org/10.3390/toxins15020161 - 15 Feb 2023

Viewed by 1648

Abstract

Snakebite is considered a neglected tropical disease, and it is one of the most intricate ones. The variability found in snake venom is what makes it immensely complex to study. These variations are present both in the big and the small molecules found [...] Read more.

Snakebite is considered a neglected tropical disease, and it is one of the most intricate ones. The variability found in snake venom is what makes it immensely complex to study. These variations are present both in the big and the small molecules found in snake venom. This study focused on examining the variability found in the venom’s small molecules (i.e., mass range of 100–1000 Da) between two main families of venomous snakes—Elapidae and Viperidae—managing to create a model able to classify unknown samples by means of specific features, which can be extracted from their LC–MS data and output in a comprehensive list. The developed model also allowed further insight into the composition of snake venom by highlighting the most relevant metabolites of each group by clustering similarly composed venoms. The model was created by means of support vector machines and used 20 features, which were merged into 10 principal components. All samples from the first and second validation data subsets were correctly classified. Biological hypotheses relevant to the variation regarding the metabolites that were identified are also given. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 1822 KiB

Open AccessEditor’s ChoiceArticle

Dispersive Magnetic Solid-Phase Extraction as a Novelty Sample Treatment for the Determination of the Main Aflatoxins in Paprika

by María García-Nicolás, Natalia Arroyo-Manzanares and Pilar Viñas

Toxins 2023, 15(2), 160; https://doi.org/10.3390/toxins15020160 - 15 Feb 2023

Cited by 3 | Viewed by 1905

Abstract

Dispersive magnetic solid-phase extraction (DMSPE) technique is proposed as a new sensitive and effective sample treatment method for the determination of aflatoxins in paprika samples. DMSPE was followed by ultrahigh-performance liquid chromatography and high-resolution mass spectrometry detection (UHPLC-HRMS) using a non-targeted acquisition mode [...] Read more.

Dispersive magnetic solid-phase extraction (DMSPE) technique is proposed as a new sensitive and effective sample treatment method for the determination of aflatoxins in paprika samples. DMSPE was followed by ultrahigh-performance liquid chromatography and high-resolution mass spectrometry detection (UHPLC-HRMS) using a non-targeted acquisition mode for the detection of main aflatoxins (aflatoxin G1, G2, B1 and B2) and derivatives. DMSPE was based on the use of magnetic nanocomposite coated with polypyrrole (PPy) polymer and the main experimental parameters influencing the extraction efficiency in adsorption and desorption steps have been studied and optimized. Analyses were performed using 250 µL magnetic PPy nanocomposite into the sample solution, adsorbing the analytes in 30 min and desorbing them with ethyl acetate (2 mL) in 15 min. The method has been validated, obtaining quantification limits between 3.5 and 4.7 µg kg⁻¹ and recoveries between 89.5–97.7%. The high recovery rate, wide detection range and the use for the first time of the reusable Fe₃O₄@PPy nanomaterial in suspension for solid food matrices, guarantee the usefulness of the method developed for adequate control of aflatoxins levels in paprika. The proposed methodology was applied for the analysis of 31 samples (conventional and organic) revealing the absence of aflatoxins in the samples. Full article

(This article belongs to the Collection Aflatoxins)

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12 pages, 1042 KiB

Open AccessReview

Harnessing the Power of Venomous Animal-Derived Toxins against COVID-19

by Isadora Oliveira, Isabela Ferreira, Beatriz Jacob, Kiara Cardenas, Felipe Cerni, Djane Baia-da-Silva, Eliane Arantes, Wuelton Monteiro and Manuela Pucca

Toxins 2023, 15(2), 159; https://doi.org/10.3390/toxins15020159 - 14 Feb 2023

Viewed by 2763

Abstract

Animal-derived venoms are complex mixtures of toxins triggering important biological effects during envenomings. Although venom-derived toxins are known for their potential of causing harm to victims, toxins can also act as pharmacological agents. During the COVID-19 pandemic, there was observed an increase in [...] Read more.

Animal-derived venoms are complex mixtures of toxins triggering important biological effects during envenomings. Although venom-derived toxins are known for their potential of causing harm to victims, toxins can also act as pharmacological agents. During the COVID-19 pandemic, there was observed an increase in in-depth studies on antiviral agents, and since, to date, there has been no completely effective drug against the global disease. This review explores the crosstalk of animal toxins and COVID-19, aiming to map potential therapeutic agents derived from venoms (e.g., bees, snakes, scorpions, etc.) targeting COVID-19. Full article

(This article belongs to the Special Issue Venom-Derived Toxins as Potential Pharmacologic Tools and Therapeutic Drugs: A Special Issue in Memory of Dr. Sérgio Henrique Ferreira)

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16 pages, 1941 KiB

Open AccessArticle

Children and Snakebite: Snake Venom Effects on Adult and Paediatric Plasma

by Christina N. Zdenek, Caroline F. B. Rodrigues, Lachlan A. Bourke, Anita Mitico Tanaka-Azevedo, Paul Monagle and Bryan G. Fry

Toxins 2023, 15(2), 158; https://doi.org/10.3390/toxins15020158 - 14 Feb 2023

Cited by 4 | Viewed by 3296

Abstract

Snakebite is a globally neglected tropical disease, with coagulation disturbances being the primary pathology of many deadly snake venoms. Age-related differences in human plasma have been abundantly reported, yet the effect that these differences pose regarding snakebite is largely unknown. We tested for [...] Read more.

Snakebite is a globally neglected tropical disease, with coagulation disturbances being the primary pathology of many deadly snake venoms. Age-related differences in human plasma have been abundantly reported, yet the effect that these differences pose regarding snakebite is largely unknown. We tested for differences in coagulotoxic effects (via clotting time) of multiple snake venoms upon healthy human adult (18+) and paediatric (median 3.3 years old) plasma in vivo and compared these effects to the time it takes the plasmas to clot without the addition of venom (the spontaneous clotting time). We tested venoms from 15 medically significant snake species (from 13 genera) from around the world with various mechanisms of coagulotoxic actions, across the three broad categories of procoagulant, pseudo-procoagulant, and anticoagulant, to identify any differences between the two plasmas in their relative pathophysiological vulnerability to snakebite. One procoagulant venom (Daboia russelii, Russell’s Viper) produced significantly greater potency on paediatric plasma compared with adult plasma. In contrast, the two anticoagulant venoms (Pseudechis australis, Mulga Snake; and Bitis cornuta, Many-horned Adder) were significantly more potent on adult plasma. All other procoagulant venoms and all pseudo-procoagulant venoms displayed similar potency across both plasmas. Our preliminary results may inform future studies on the effect of snake venoms upon plasmas from different age demographics and hope to reduce the burden of snakebite upon society. Full article

(This article belongs to the Special Issue Snakebite and Clinical Toxinology)

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14 pages, 2267 KiB

Open AccessArticle

Gymnodinium catenatum Paralytic Shellfish Toxin Production and Photobiological Responses under Marine Heat Waves

by Vanessa M. Lopes, Mélanie Court, Martim Costa Seco, Francisco O. Borges, Bernardo Vicente, Sandra Lage, Ana Catarina Braga, Bernardo Duarte, Catarina Frazão Santos, Ana Amorim, Pedro Reis Costa and Rui Rosa

Toxins 2023, 15(2), 157; https://doi.org/10.3390/toxins15020157 - 14 Feb 2023

Viewed by 1925

Abstract

Marine heatwaves (MHWs) have doubled in frequency since the 1980s and are projected to be exacerbated during this century. MHWs have been shown to trigger harmful algal blooms (HABs), with severe consequences to marine life and human populations. Within this context, this study [...] Read more.

Marine heatwaves (MHWs) have doubled in frequency since the 1980s and are projected to be exacerbated during this century. MHWs have been shown to trigger harmful algal blooms (HABs), with severe consequences to marine life and human populations. Within this context, this study aims to understand, for the first time, how MHWs impact key biological and toxicological parameters of the paralytic shellfish toxin (PST) producer Gymnodinium catenatum, a dinoflagellate inhabiting temperate and tropical coastal waters. Two MHW were simulated—category I (i.e., peak: 19.9 °C) and category IV (i.e., peak: 24.1 °C)—relative to the estimated baseline in the western coast of Portugal (18.5 °C). No significant changes in abundance, size, and photosynthetic efficiency were observed among treatments. On the other hand, chain-formation was significantly reduced under category IV MHW, as was PSP toxicity and production of some PST compounds. Overall, this suggests that G. catenatum may have a high tolerance to MHWs. Nevertheless, some sublethal effects may have occurred since chain-formation was affected, suggesting that these growth conditions may be sub-optimal for this population. Our study suggests that the increase in frequency, intensity, and duration of MHWs may lead to reduced severity of G. catenatum blooms. Full article

(This article belongs to the Special Issue Interactive Effects of Climate Change and Toxins in Marine Organisms: Current Knowledge and Research Gaps)

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16 pages, 2460 KiB

Open AccessArticle

Improved Production of Recombinant Carboxylesterase FumDM by Co-Expressing Molecular Chaperones in Pichia pastoris

by Lixiang Jiang, Xiao Guan, Hujun Liu, Xiaojiao Chang, Jing Sun, Changpo Sun and Chengcheng Zhao

Toxins 2023, 15(2), 156; https://doi.org/10.3390/toxins15020156 - 14 Feb 2023

Cited by 1 | Viewed by 1488

Abstract

Fumonisins (FBs) are mycotoxins that threaten public health and food safety worldwide. Enzymatic degradation of Fumonisin B1 (FB₁) through decarboxylation has attracted much attention, whereas application of FB₁ carboxylesterase in detoxification requires more effective expression of the recombinant carboxylesterase. In [...] Read more.

Fumonisins (FBs) are mycotoxins that threaten public health and food safety worldwide. Enzymatic degradation of Fumonisin B1 (FB₁) through decarboxylation has attracted much attention, whereas application of FB₁ carboxylesterase in detoxification requires more effective expression of the recombinant carboxylesterase. In this study, the carboxylesterase FumDM from Sphingopyxis sp. ASAG22 was codon-optimized and co-expressed with five different molecular chaperones (PDI, CPR5, ERO1, HAC1, and Bip) in order to improve the expression level of FumDM in Pichia pastoris (also known as Komagataella phaffii) GS115. The co-expression of different chaperones caused varying degrees of improvement in FumDM activity for FB₁. The enzyme activities of recombinant strains over-expressing PDI and CPR5 reached the highest levels of 259.47 U/mL and 161.34 U/mL, 635% and 357% higher than the original enzyme activity, respectively. Transcriptomic analysis of the two recombinant strains in comparison with the control strain showed that the correct folding of proteins assisted by molecular chaperones played a key role in the improvement of FumDM expression and its enzyme activity. This study demonstrated that co-expression of carboxylesterase FumDM and folding chaperones was an efficient strategy and therefore might inspire new perspectives on the improvement of carboxylesterase for detoxification of FB₁. Full article

(This article belongs to the Special Issue Strategies to Prevent Mycotoxin Contamination of Food and Feed)

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12 pages, 638 KiB

Open AccessArticle

Determination of Regulated and Emerging Mycotoxins in Organic and Conventional Gluten-Free Flours by LC-MS/MS

by Zoe Giannioti, Beatriz Albero, María Dolores Hernando, Luana Bontempo and Rosa Ana Pérez

Toxins 2023, 15(2), 155; https://doi.org/10.3390/toxins15020155 - 14 Feb 2023

Cited by 6 | Viewed by 2845

Abstract

Gluten-free cereal products have grown in popularity in recent years as they are perceived as “healthier” alternatives and can be safely consumed by celiac patients, and people with gluten intolerance or wheat allergies. Molds that produce mycotoxins contaminate cereal crops, posing a threat [...] Read more.

Gluten-free cereal products have grown in popularity in recent years as they are perceived as “healthier” alternatives and can be safely consumed by celiac patients, and people with gluten intolerance or wheat allergies. Molds that produce mycotoxins contaminate cereal crops, posing a threat to global food security. Maximum levels have been set for certain mycotoxins in cereal flours; however, little is known about the levels of emerging mycotoxins in these flours. The aim of this study was to develop an efficient, sensitive, and selective method for the detection of four emerging (beauvericin and enniatins A1, B, and B1) and three regulated (aflatoxin B1, zearalenone, and deoxynivalenol) mycotoxins in gluten-free flours. Ultrasound-assisted matrix solid-phase dispersion was used in the extraction of these mycotoxins from flour samples. The validated method was utilized for the LC-MS/MS analysis of conventional and organic wholegrain oat and rice flours. Six of the seven target mycotoxins were detected in these samples. Multi-mycotoxin contamination was found in all flour types, particularly in conventional wholegrain oat flour. Despite the low detection frequency in rice flour, one sample was found to contain zearalenone at a concentration of 83.2 μg/kg, which was higher than the level set by the European Commission for cereal flours. The emerging mycotoxins had the highest detection frequencies; enniatin B was present in 53% of the samples at a maximum concentration of 56 μg/kg, followed by enniatin B1 and beauvericin, which were detected in 46% of the samples, and at levels reaching 21 μg/kg and 10 μg/kg, respectively. These results highlight the need to improve the current knowledge and regulations on the presence of mycotoxins, particularly emerging ones, in gluten-free flours and cereal-based products. Full article

(This article belongs to the Special Issue Mycotoxins in Feed, Food, Nutraceuticals, and Functional Food)

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19 pages, 5551 KiB

Open AccessArticle

Isolation of the Main Pathogens Causing Postharvest Disease in Fresh Angelica sinensis during Different Storage Stages and Impacts of Ozone Treatment on Disease Development and Mycotoxin Production

by Jihui Xi, Dongyun Yang, Huali Xue, Zhiguang Liu, Yang Bi, Yuan Zhang, Xi Yang and Suqin Shang

Toxins 2023, 15(2), 154; https://doi.org/10.3390/toxins15020154 - 13 Feb 2023

Cited by 6 | Viewed by 1373

Abstract

Angelica sinensis, a Chinese herbal medicine, is susceptible to molds during storage, reducing its quality, and even generating mycotoxins with toxic effects on human health. Fresh A. sinensis was harvested from Min County of Gansu Province in China and kept at room [...] Read more.

Angelica sinensis, a Chinese herbal medicine, is susceptible to molds during storage, reducing its quality, and even generating mycotoxins with toxic effects on human health. Fresh A. sinensis was harvested from Min County of Gansu Province in China and kept at room temperature. Naturally occurring symptoms were observed during different storage stages. Molds were isolated and identified from the diseased A. sinensis using morphological and molecular biology methods. The impact of ozone treatment on postharvest disease development and mycotoxin production was investigated. The results indicated that A. sinensis decay began on day 7 of storage and progressed thereafter. Nine mold species were isolated and characterized: day 7, two Mucormycetes; day 14, Clonostachys rosea; day 21, two Penicillium species and Aspergillus versicolor; day 28, Alternaria alternata and Trichoderma atroviride; and day 49, Fusarium solani. Ozone treatment markedly inhibited the development of postharvest disease and the mycotoxin production (such as, patulin, 15-acetyl-deoxynivalenol, and sterigmatocystin) in the rotten tissue of A. sinensis inoculated with the nine isolates. Full article

(This article belongs to the Special Issue Detection, Control and Contamination of Mycotoxins (Volume II))

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0 pages, 3854 KiB

Open AccessEditor’s ChoiceArticle

Mixtures of Mycotoxins, Phytoestrogens, and Other Secondary Metabolites in Whole-Plant Corn Silages and Total Mixed Rations of Dairy Farms in Central and Northern Mexico

by Felipe Penagos-Tabares, Michael Sulyok, Juan-Ignacio Artavia, Samanta-Irais Flores-Quiroz, César Garzón-Pérez, Ezequías Castillo-Lopez, Luis Zavala, Juan-David Orozco, Johannes Faas, Rudolf Krska and Qendrim Zebeli

Toxins 2023, 15(2), 153; https://doi.org/10.3390/toxins15020153 - 13 Feb 2023

Cited by 3 | Viewed by 2126 | Correction

Abstract

Mycotoxins and endocrine disruptors such as phytoestrogens can affect cattle health, reproduction, and productivity. Most studies of mycotoxins in dairy feeds in Mexico and worldwide have been focused on a few (regulated) mycotoxins. In contrast, less known fungal toxins, phytoestrogens, and other metabolites [...] Read more.

Mycotoxins and endocrine disruptors such as phytoestrogens can affect cattle health, reproduction, and productivity. Most studies of mycotoxins in dairy feeds in Mexico and worldwide have been focused on a few (regulated) mycotoxins. In contrast, less known fungal toxins, phytoestrogens, and other metabolites have been neglected and underestimated. This study analyzed a broad spectrum (>800) of mycotoxins, phytoestrogens, and fungal, plant, and unspecific secondary metabolites in whole-plant corn silages (WPCSs) and total mixed rations (TMRs) collected from 19 Mexican dairy farms. A validated multi-metabolite liquid chromatography/electrospray ionization–tandem mass spectrometric (LC/ESI–MS/MS) method was used. Our results revealed 125 of >800 tested (potentially toxic) secondary metabolites. WPCSs/TMRs in Mexico presented ubiquitous contamination with mycotoxins, phytoestrogens, and other metabolites. The average number of mycotoxins per TMR was 24, ranging from 9 to 31. Fusarium-derived secondary metabolites showed the highest frequencies, concentrations, and diversity among the detected fungal compounds. The most frequently detected mycotoxins in TMRs were zearalenone (ZEN) (100%), fumonisin B1 (FB1) (84%), and deoxynivalenol (84%). Aflatoxin B1 (AFB1) and ochratoxin A (OTA), previously reported in Mexico, were not detected. All TMR samples tested positive for phytoestrogens. Among the investigated dietary ingredients, corn stover, sorghum silage, and concentrate proportions were the most correlated with levels of total mycotoxins, fumonisins (Fs), and ergot alkaloids, respectively. Full article

(This article belongs to the Special Issue Detection, Control and Contamination of Mycotoxins (Volume II))

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16 pages, 1158 KiB

Open AccessArticle

The Relationship between Pain and Spasticity and Tell-Tale Signs of Pain in Children with Cerebral Palsy

by Christian Wong

Toxins 2023, 15(2), 152; https://doi.org/10.3390/toxins15020152 - 13 Feb 2023

Cited by 2 | Viewed by 1869

Abstract

Pain and quality of life are closely interrelated in children with cerebral palsy (CCP). Even though 67% of CCP experience pain, it is overlooked and untreated. In this study, our purpose was two-fold: first, to examine the relationship between pain and spasticity by [...] Read more.

Pain and quality of life are closely interrelated in children with cerebral palsy (CCP). Even though 67% of CCP experience pain, it is overlooked and untreated. In this study, our purpose was two-fold: first, to examine the relationship between pain and spasticity by evaluating the effects of AbobotulinumtoxinA/Dysport (BoNT), and second, to describe the symptoms and location of pain in CCP. The subjects were 22 CCP in at least moderate pain. They were evaluated for spasticity by the modified Ashworth and Tardieu scale and for pain by the r-FLACC and the pediatric pain profile. After one injection of BoNT, the subjects were re-evaluated. We found a significant reduction in pain, but no significant relationship between the reduction of pain and spasticity. We found no association between the dose of BoNT and pain or spasticity. Pain in the lower extremity was located primarily in the hip region. The effect of ultrasound-guided intermuscular injections of BoNT suggests that pain in CCP has an extra-articular component. We found that pain in CCP manifests as specific tell-tale signs and problems in daily living. In conclusion, we found no relationship between pain and spasticity. Signs and manifestations of pain are described in detail. Lower extremity (hip) pain seems to have a soft tissue/extra-articular component. 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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15 pages, 1497 KiB

Open AccessArticle

Using Molecular Spectroscopic Techniques (NIR and ATR-FT/MIR) Coupling with Various Chemometrics to Test Possibility to Reveal Chemical and Molecular Response of Cool-Season Adapted Wheat Grain to Ergot Alkaloids

by Haitao Shi and Peiqiang Yu

Toxins 2023, 15(2), 151; https://doi.org/10.3390/toxins15020151 - 13 Feb 2023

Cited by 2 | Viewed by 1459

Abstract

The objectives of this study were to explore the possibility of using near infrared (NIR) and Fourier transform mid-infrared spectroscopy—attenuated total reflectance (ATR-FT/MIR) molecular spectroscopic techniques as non-invasive and rapid methods for the quantification of six major ergot alkaloids (EAs) in cool-season wheat. [...] Read more.

The objectives of this study were to explore the possibility of using near infrared (NIR) and Fourier transform mid-infrared spectroscopy—attenuated total reflectance (ATR-FT/MIR) molecular spectroscopic techniques as non-invasive and rapid methods for the quantification of six major ergot alkaloids (EAs) in cool-season wheat. In total, 107 wheat grain samples were collected, and the concentration of six major EAs was analyzed using the liquid chromatography-tandem mass spectrometry technique. The mean content of the total EAs—ergotamine, ergosine, ergometrine, ergocryptine, ergocristine, and ergocornine—was 1099.3, 337.5, 56.9, 150.6, 142.1, 743.3, and 97.45 μg/kg, respectively. The NIR spectra were taken from 680 to 2500 nm, and the MIR spectra were recorded from 4000–700 cm⁻¹. The spectral data were transformed by various preprocessing techniques (which included: FD: first derivative; SNV: standard normal variate; FD-SNV: first derivative + SNV; MSC: multiplicative scattering correction; SNV-Detrending: SNV + detrending; SD-SNV: second derivative + SNV; SNV-SD: SNV + first derivative); and sensitive wavelengths were selected. The partial least squares (PLS) regression models were developed for EA validation statistics. Results showed that the constructed models obtained weak calibration and cross-validation parameters, and none of the models was able to accurately predict external samples. The relatively low levels of EAs in the contaminated wheat samples might be lower than the detection limits of the NIR and ATR-FT/MIR spectroscopies. More research is needed to determine the limitations of the ATR-FT/MIR and NIR techniques for quantifying EAs in various sample matrices and to develop acceptable models. Full article

(This article belongs to the Special Issue Detection, Control and Contamination of Mycotoxins (Volume II))

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8 pages, 792 KiB

Open AccessCommunication

Correlation between Saliva Levels and Serum Levels of Free Uremic Toxins in Healthy Volunteers

by Nicolas Fabresse, Islam Amine Larabi, Emuri Abe, Elodie Lamy, Claire Rigothier, Ziad A. Massy and Jean-Claude Alvarez

Toxins 2023, 15(2), 150; https://doi.org/10.3390/toxins15020150 - 13 Feb 2023

Cited by 3 | Viewed by 1284

Abstract

The objective of the present study was to investigate the putative correlation between the saliva concentration and free serum concentration for 10 uremic toxins (UTs; eight protein-bound solutes: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid (HA), indole-3-acetic acid (3-IAA), indoxyl sulfate (I3S), kynurenic acid (KA), [...] Read more.

The objective of the present study was to investigate the putative correlation between the saliva concentration and free serum concentration for 10 uremic toxins (UTs; eight protein-bound solutes: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid (HA), indole-3-acetic acid (3-IAA), indoxyl sulfate (I3S), kynurenic acid (KA), kynurenine (KYN), p-cresyl glucuronide (pCG), and p-cresyl sulfate (pCS); two free, water-soluble, low-molecular weight solutes: phenylacetylglutamine (PAGN) and trimethylamine N-oxide (TMAO); and three precursors: tyrosine (Tyr), phenylalanine, and tryptophan). Saliva samples and blood samples were collected simultaneously from 18 healthy volunteers. After the addition of internal standards, 50 µL of saliva or serum were precipitated with methanol. UTs and precursors were quantified using a validated LC-MS/MS method. The saliva–serum correlation was statistically significant (according to Spearman’s coefficient) for six UTs (TMAO, HA, I3S, pCS, 3-IAA, and CMPF). Tyr presented a weak saliva-serum correlation (p = 0.08), whereas the other two precursors did not show a saliva–serum correlation. For three UTs (KYN, KA and pCG), we were unable to test the correlation since the saliva or serum levels were too low in many of the volunteers. The present study is the first to report on the saliva concentrations of TMAO, KYN, HA, PAGN, pCG, and 3-IAA. Full article

(This article belongs to the Section Uremic Toxins)

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16 pages, 5342 KiB

Open AccessArticle

Localization of Multiple Jellyfish Toxins Shows Specificity for Functionally Distinct Polyps and Nematocyst Types in a Colonial Hydrozoan

by Anna M. L. Klompen, Matthew K. Travert and Paulyn Cartwright

Toxins 2023, 15(2), 149; https://doi.org/10.3390/toxins15020149 - 13 Feb 2023

Cited by 1 | Viewed by 2273

Abstract

Hydractinia symbiolongicarpus is a colonial hydrozoan that displays a division of labor through morphologically distinct and functionally specialized polyp types. As with all cnidarians, their venoms are housed in nematocysts, which are scattered across an individual. Here, we investigate the spatial distribution of [...] Read more.

Hydractinia symbiolongicarpus is a colonial hydrozoan that displays a division of labor through morphologically distinct and functionally specialized polyp types. As with all cnidarians, their venoms are housed in nematocysts, which are scattered across an individual. Here, we investigate the spatial distribution of a specific protein family, jellyfish toxins, in which multiple paralogs are differentially expressed across the functionally specialized polyps. Jellyfish toxins (JFTs) are known pore-forming toxins in the venoms of medically relevant species such as box jellyfish (class Cubozoa), but their role in other medusozoan venoms is less clear. Utilizing a publicly available single-cell dataset, we confirmed that four distinct H. symbiolongicarpus JFT paralogs are expressed in nematocyst-associated clusters, supporting these as true venom components in H. symbiolongicarpus. In situ hybridization and immunohistochemistry were used to localize the expression of these JFTs across the colony. These expression patterns, in conjunction with known nematocyst type distributions, suggest that two of these JFTs, HsymJFT1c-I and HsymJFT1c-II, are localized to specific types of nematocysts. We further interpret JFT expression patterns in the context of known regions of nematogenesis and differential rates of nematocyst turnover. Overall, we show that JFT expression patterns in H. symbiolongicarpus are consistent with the subfunctionalization of JFT paralogs across a partitioned venom system within the colony, such that each JFT is expressed within a specific set of functionally distinct polyp types and, in some cases, specific nematocyst types. Full article

(This article belongs to the Special Issue Molecular Evolution of Toxins in Invertebrates)

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12 pages, 637 KiB

Open AccessArticle

Multi-Mycotoxin Method Development Using Ultra-High Liquid Chromatography with Orbitrap High-Resolution Mass Spectrometry Detection in Breakfast Cereals from the Campania Region, Italy

by Alfonso Narváez, Luana Izzo, Luigi Castaldo, Sonia Lombardi, Yelko Rodríguez-Carrasco and Alberto Ritieni

Toxins 2023, 15(2), 148; https://doi.org/10.3390/toxins15020148 - 12 Feb 2023

Cited by 4 | Viewed by 1314

Abstract

Breakfast cereals have been reported as one of the most susceptible cereal-based products to mycotoxin contamination. These products pose an even more concerning risk to human health since they are marketed as a ready-to-eat product and one of its main population targets is [...] Read more.

Breakfast cereals have been reported as one of the most susceptible cereal-based products to mycotoxin contamination. These products pose an even more concerning risk to human health since they are marketed as a ready-to-eat product and one of its main population targets is children. Therefore, the main goal of the present study was to conduct a monitoring study of multiple mycotoxins contained in breakfast cereals samples marketed in Italy through ultra-high performance liquid chromatography coupled to high-resolution Q-Orbitrap tandem mass spectrometry. An acetonitrile-based methodology was validated for quantifying 24 mycotoxins in breakfast cereals. The results showed that 93% of the samples contained at least one mycotoxin. Beauvericin was the most prevalent toxin (86% of samples; mean concentration: 30.66 µg/kg), although the main enniatins, zearalenone-derived forms and fumonisins B1 and B2 were also detected. Co-occurrence was observed in 73% of the positive samples with up to five mycotoxins simultaneously occurring, mainly due to the combination of beauvericin and enniatins. These results provided more evidence about the high impact of non-regulated mycotoxins, such as the emerging Fusarium toxins, in breakfast cereals, and encourages the development of analytical methodologies including these and zearalenone-derived forms that could be going unnoticed with current methodologies. Full article

(This article belongs to the Special Issue Mycotoxins in Feed, Food, Nutraceuticals, and Functional Food)

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14 pages, 515 KiB

Open AccessReview

Efficacy and Safety of Botulinum Toxin B in Focal Hyperhidrosis: A Narrative Review

by Anna Campanati, Federico Diotallevi, Giulia Radi, Emanuela Martina, Barbara Marconi, Ivan Bobyr and Annamaria Offidani

Toxins 2023, 15(2), 147; https://doi.org/10.3390/toxins15020147 - 11 Feb 2023

Cited by 5 | Viewed by 1955

Abstract

Botulinum toxin type B (BoNT-B), known as Myobloc^® in the United States and as Neurobloc^® in Europe, is a new therapeutically available serotype among the botulinum toxin family. During the last years several data have been reported in literature investigating its [...] Read more.

Botulinum toxin type B (BoNT-B), known as Myobloc^® in the United States and as Neurobloc^® in Europe, is a new therapeutically available serotype among the botulinum toxin family. During the last years several data have been reported in literature investigating its efficacy and safety, as well as defining the dosing and application regiments of BoNT-B in the treatment of hyperhidrosis. Moreover, recent studies have been examining its safety profile, which may be different from those known about BoNT-A. The aim of this review is to provide information about what is currently known about BoNT-B in regards to the treatment of focal hyperhidrosis. Full article

(This article belongs to the Special Issue Clinical and Anatomical Perspectives of Botulinum Neurotoxin)

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17 pages, 769 KiB

Open AccessReview

E-Nose Technology for Mycotoxin Detection in Feed: Ready for a Real Context in Field Application or Still an Emerging Technology?

by Federica Cheli, Matteo Ottoboni, Francesca Fumagalli, Sharon Mazzoleni, Luca Ferrari and Luciano Pinotti

Toxins 2023, 15(2), 146; https://doi.org/10.3390/toxins15020146 - 11 Feb 2023

Cited by 2 | Viewed by 2275

Abstract

Mycotoxin risk in the feed supply chain poses a concern to animal and human health, economy, and international trade of agri-food commodities. Mycotoxin contamination in feed and food is unavoidable and unpredictable. Therefore, monitoring and control are the critical points. Effective and rapid [...] Read more.

Mycotoxin risk in the feed supply chain poses a concern to animal and human health, economy, and international trade of agri-food commodities. Mycotoxin contamination in feed and food is unavoidable and unpredictable. Therefore, monitoring and control are the critical points. Effective and rapid methods for mycotoxin detection, at the levels set by the regulations, are needed for an efficient mycotoxin management. This review provides an overview of the use of the electronic nose (e-nose) as an effective tool for rapid mycotoxin detection and management of the mycotoxin risk at feed business level. E-nose has a high discrimination accuracy between non-contaminated and single-mycotoxin-contaminated grain. However, the predictive accuracy of e-nose is still limited and unsuitable for in-field application, where mycotoxin co-contamination occurs. Further research needs to be focused on the sensor materials, data analysis, pattern recognition systems, and a better understanding of the needs of the feed industry for a safety and quality management of the feed supply chain. A universal e-nose for mycotoxin detection is not realistic; a unique e-nose must be designed for each specific application. Robust and suitable e-nose method and advancements in signal processing algorithms must be validated for specific needs. Full article

(This article belongs to the Special Issue Improved and Innovative Actions for Mycotoxin Management in the Food and Feed Chain 2.0)

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16 pages, 1200 KiB

Open AccessReview

Antimicrobial Compounds from Skin Secretions of Species That Belong to the Bufonidae Family

by Rodrigo Ibarra-Vega, Alan Roberto Galván-Hernández, Hermenegildo Salazar-Monge, Rocio Zataraín-Palacios, Patricia Elizabeth García-Villalvazo, Diana Itzel Zavalza-Galvez, Laura Leticia Valdez-Velazquez and Juana María Jiménez-Vargas

Toxins 2023, 15(2), 145; https://doi.org/10.3390/toxins15020145 - 10 Feb 2023

Cited by 1 | Viewed by 1669

Abstract

Skin secretions of toads are a complex mixture of molecules. The substances secreted comprise more than 80 different compounds that show diverse pharmacological activities. The compounds secreted through skin pores and parotid glands are of particular interest because they help toads to endure [...] Read more.

Skin secretions of toads are a complex mixture of molecules. The substances secreted comprise more than 80 different compounds that show diverse pharmacological activities. The compounds secreted through skin pores and parotid glands are of particular interest because they help toads to endure in habitats full of pathogenic microbes, i.e., bacteria, fungi, viruses, and protozoa, due to their content of components such as bufadienolides, alkaloids, and antimicrobial peptides. We carried out an extensive literature review of relevant articles published until November 2022 in ACS Publications, Google Scholar, PubMed, and ScienceDirect. It was centered on research addressing the biological characterization of the compounds identified in the species of genera Atelopus, Bufo, Duttaphrynus, Melanophryniscus, Peltopryne, Phrynoidis, Rhaebo, and Rhinella, with antibacterial, antifungal, antiviral, and antiparasitic activities; as well as studies performed with analogous compounds and skin secretions of toads that also showed these activities. This review shows that the compounds in the secretions of toads could be candidates for new drugs to treat infectious diseases or be used to develop new molecules with better properties from existing ones. Some compounds in this review showed activity against microorganisms of medical interest such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Coronavirus varieties, HIV, Trypanosoma cruzi, Leishmania chagasi, Plasmodium falciparum, and against different kinds of fungi that affect plants of economic interest. Full article

(This article belongs to the Special Issue Biotechnological Potential of Animal Venom and Toxins)

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11 pages, 725 KiB

Open AccessArticle

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China

by Hong Gao, Na Zhu, Shuxiang Deng, Can Du, Yan Tang, Peng Tang, Shuaishuai Xu, Wenya Liu, Minxue Shen, Xinhua Xiao and Fei Yang

Toxins 2023, 15(2), 144; https://doi.org/10.3390/toxins15020144 - 10 Feb 2023

Viewed by 1412

Abstract

Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of [...] Read more.

Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose–response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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16 pages, 3156 KiB

Open AccessArticle

The Molecular Composition of Peptide Toxins in the Venom of Spider Lycosa coelestis as Revealed by cDNA Library and Transcriptomic Sequencing

by Xiangyue Wu, Yan Chen, Hao Liu, Xiangjin Kong, Xinyao Liang, Yu Zhang, Cheng Tang and Zhonghua Liu

Toxins 2023, 15(2), 143; https://doi.org/10.3390/toxins15020143 - 10 Feb 2023

Cited by 4 | Viewed by 1901

Abstract

In the so-called “struggle for existence” competition, the venomous animals developed a smart and effective strategy, envenomation, for predation and defense. Biochemical analysis revealed that animal venoms are chemical pools of proteinase, peptide toxins, and small organic molecules with various biological activities. Of [...] Read more.

In the so-called “struggle for existence” competition, the venomous animals developed a smart and effective strategy, envenomation, for predation and defense. Biochemical analysis revealed that animal venoms are chemical pools of proteinase, peptide toxins, and small organic molecules with various biological activities. Of them, peptide toxins are of great molecular diversity and possess the capacity to modulate the activity of ion channels, the second largest group of drug targets expressed on the cell membrane, which makes them a rich resource for developing peptide drug pioneers. The spider Lycosa coelestis (L. coelestis) commonly found in farmland in China is a dominant natural enemy of agricultural pests; however, its venom composition and activity were never explored. Herein, we conducted cDNA library and transcriptomic sequencing of the venom gland of L. coelestis, which identified 1131 high-quality expressed sequence tags (ESTs), grouped into three categories denoted as toxin-like ESTs (597, 52.79%), cellular component ESTs (357, 31.56%), and non-matched ESTs (177, 15.65%). These toxin-like ESTs encode 98 non-reductant toxins, which are artificially divided into 11 families based on their sequence homology and cysteine frameworks (2–14 cysteines forming 1–7 disulfide bonds to stabilize the toxin structure). Furthermore, RP-HPLC purification combined with off-line MALDI-TOF analysis have detected 147 different peptides physically existing in the venom of L. coelestis. Electrophysiology analysis confirmed that the venom preferably inhibits the voltage-gated calcium channels in rat dorsal root ganglion neurons. Altogether, the present study has added a great lot of new members to the spider toxin superfamily and built the foundation for characterizing novel active peptides in the L. coelestis venom. Full article

(This article belongs to the Section Animal Venoms)

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3 pages, 235 KiB

Open AccessEditorial

Editorial of the Special Issue “Toxins: Mr Hyde or Dr Jekyll?”

by Daniel Ladant, Gilles Prévost, Michel R. Popoff and Evelyne Benoit

Toxins 2023, 15(2), 142; https://doi.org/10.3390/toxins15020142 - 10 Feb 2023

Viewed by 989

Abstract

The 27th Annual Meeting of the French Society of Toxinology (SFET, http://sfet [...] Full article

(This article belongs to the Special Issue Toxins: Mr Hyde or Dr Jekyll?)

11 pages, 3507 KiB

Open AccessArticle

β-N-Methylamino-L-Alanine (BMAA) Modulates the Sympathetic Regulation and Homeostasis of Polyamines

by Milena Shkodrova, Milena Mishonova, Mariela Chichova, Iliyana Sazdova, Bilyana Ilieva, Dilyana Doncheva-Stoimenova, Neli Raikova, Milena Keremidarska-Markova and Hristo Gagov

Toxins 2023, 15(2), 141; https://doi.org/10.3390/toxins15020141 - 09 Feb 2023

Cited by 1 | Viewed by 1725

Abstract

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim [...] Read more.

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1–1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues—regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors. Full article

(This article belongs to the Special Issue Cyanobacterial Toxins: Toxins Production and Risk Assessment)

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22 pages, 3242 KiB

Open AccessArticle

Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells

by Éva Márton, Alexandra Varga, András Penyige, Zsuzsanna Birkó, István Balogh, Bálint Nagy and Melinda Szilágyi

Toxins 2023, 15(2), 140; https://doi.org/10.3390/toxins15020140 - 09 Feb 2023

Viewed by 1737

Abstract

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in [...] Read more.

Xenoestrogens are natural or synthetic compounds that mimic the effect of endogenous estrogens and might cause cancer. We aimed to compare the global transcriptomic response to zearalenone (ZEA; mycotoxin) and bisphenol A (BPA; plastic additive) with the effect of physiological estradiol (E2) in the PEO1 human ovarian cell line by mRNA and microRNA sequencing. Estrogen exposure induced remarkable transcriptomic changes: 308, 288 and 63 genes were upregulated (log₂FC > 1); 292, 260 and 45 genes were downregulated (log₂FC < −1) in response to E2 (10 nM), ZEA (10 nM) and BPA (100 nM), respectively. Furthermore, the expression of 13, 11 and 10 miRNAs changed significantly (log₂FC > 1, or log₂FC < −1) after exposure to E2, ZEA and BPA, respectively. Functional enrichment analysis of the significantly differentially expressed genes and miRNAs revealed several pathways related to the regulation of cell proliferation and migration. The effect of E2 and ZEA was highly comparable: 407 genes were coregulated by these molecules. We could identify 83 genes that were regulated by all three treatments that might have a significant role in the estrogen response of ovarian cells. Furthermore, the downregulation of several miRNAs (miR-501-5p, let-7a-2-3p, miR-26a-2-3p, miR-197-5p and miR-582-3p) was confirmed by qPCR, which might support the proliferative effect of estrogens in ovarian cells. Full article

(This article belongs to the Special Issue Omics Approaches to Study Toxins)

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20 pages, 4021 KiB

Open AccessArticle

Whole-Transcriptome Analysis Highlights Adenylyl Cyclase Toxins-Derived Modulation of NF-κB and ERK1/2 Pathways in Macrophages

by Taoran Zhao, Ruihua Li, Mengyin Qian, Meirong Wang, Xiaozheng Zhang, Yuhan Wang, Xinghui Zhao and Jun Xie

Toxins 2023, 15(2), 139; https://doi.org/10.3390/toxins15020139 - 09 Feb 2023

Viewed by 1346

Abstract

Edema toxin (ET), one of the main toxic factors of Bacillus anthracis (B. anthracis), is a kind of potent adenylate cyclase (AC). B. anthracis has adapted to resist macrophage microbicidal mechanisms in part by secreting ET. To date, there is limited [...] Read more.

Edema toxin (ET), one of the main toxic factors of Bacillus anthracis (B. anthracis), is a kind of potent adenylate cyclase (AC). B. anthracis has adapted to resist macrophage microbicidal mechanisms in part by secreting ET. To date, there is limited information on the pathogenic mechanisms used by ET to manipulate macrophage function, especially at the transcriptome level. We used RNA sequencing to study transcriptional changes in RAW264.7 cells treated with ET. We aimed to identify molecular events associated with the establishment of infection and followed changes in cellular proteins. Our results indicate that ET inhibited TNF-α expression in the RAW264.7 mouse macrophage cell line by activating the cAMP/PKA pathway. ET challenge of macrophages induced a differential expression of genes that participate in multiple macrophage effector functions such as cytokine production, cell adhesion, and the inflammatory response. Furthermore, ET influenced the expression of components of the ERK1/2, as well as the NF-αB signaling pathways. We also showed that ET treatments inhibit the phosphorylation of the ERK1/2 protein. ET also attenuated NF-αB subunit p65 phosphorylation and transcriptional activity of NF-αB via the cAMP/PKA pathway in macrophages. Since the observed modulatory effects were characteristic only of the bacterial exotoxin ET, we propose this may be a mechanism used by B. anthracis to manipulate macrophages and establish systemic infection. Full article

(This article belongs to the Collection Anthrax Toxins)

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14 pages, 3216 KiB

Open AccessArticle

Paenibacillus polymyxa Antagonism towards Fusarium: Identification and Optimisation of Antibiotic Production

by Junjian Ran, Youzhi Wu, Bo Zhang, Yiwei Su, Ninghai Lu, Yongchao Li, Xinhong Liang, Haixu Zhou and Jianrong Shi

Toxins 2023, 15(2), 138; https://doi.org/10.3390/toxins15020138 - 09 Feb 2023

Cited by 5 | Viewed by 1929

Abstract

An antibiotic produced by Paenibacillus polymyxa 7F1 was studied. The 7F1 strain was isolated from the rhizosphere of a wheat field. Response surface methodology was used to optimize the physicochemical parameters. The strain showed broad-spectrum activity against several plant pathogens. Identification of the [...] Read more.

An antibiotic produced by Paenibacillus polymyxa 7F1 was studied. The 7F1 strain was isolated from the rhizosphere of a wheat field. Response surface methodology was used to optimize the physicochemical parameters. The strain showed broad-spectrum activity against several plant pathogens. Identification of the strain was realized based on 16s rRNA gene and gyrB gene sequencing. The antibiotic was optimized by one-factor-at-a-time (OFAT) and response surface methodology (RSM) approaches. The suitable antibiotic production conditions were optimized using the one-factor-at-a-time method. The individual and interaction effects of three independent variables: culture temperature, initial pH, and culture time, were optimized by Box-Behnken design. The 16SrRNA gene sequence (1239 nucleotides) and gyrB gene (1111 nucleotides) were determined for strain 7F1 and shared the highest identities to those of Paenibacillus polymyxa. The results showed the optimal fermentation conditions for antibiotics produced by Paenibacillus polymyxa 7F1 were a culture temperature of 38 °C, initial pH of 8.0, and culture time of 8 h. The antibiotics produced by Paenibacillus polymyxa 7F1 include lipopeptides such as iturin A and surfactin. The results provide a theoretical basis for the development of bacteriostatic biological agents and the control of mycotoxins. Full article

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