Toxins

20 pages, 780 KiB

Open AccessReview

Peptides Isolated from Amphibian Skin Secretions with Emphasis on Antimicrobial Peptides

by Xi Chen, Songcai Liu, Jiayuan Fang, Shuo Zheng, Zhaoguo Wang, Yingying Jiao, Peijun Xia, Hongyan Wu, Ze Ma and Linlin Hao

Toxins 2022, 14(10), 722; https://doi.org/10.3390/toxins14100722 - 21 Oct 2022

Cited by 13 | Viewed by 3430

Abstract

The skin of amphibians is a tissue with biological functions, such as defense, respiration, and excretion. In recent years, researchers have discovered a large number of peptides in the skin secretions of amphibians, including antimicrobial peptides, antioxidant peptides, bradykinins, insulin-releasing peptides, and other [...] Read more.

The skin of amphibians is a tissue with biological functions, such as defense, respiration, and excretion. In recent years, researchers have discovered a large number of peptides in the skin secretions of amphibians, including antimicrobial peptides, antioxidant peptides, bradykinins, insulin-releasing peptides, and other peptides. This review focuses on the origin, primary structure, secondary structure, length, and functions of peptides secreted from amphibians’ skin. We hope that this review will provide further information and promote the further study of amphibian skin secretions, in order to provide reference for expanding the research and application of amphibian bioactive peptides. Full article

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12 pages, 2604 KiB

Open AccessArticle

Cyclosporin A as a Source for a Novel Insecticidal Product for Controlling Spodoptera frugiperda

by Chengxian Sun, Shunjia Li, Kai Wang, Hongqiang Feng, Caihong Tian, Xiaoguang Liu, Xiang Li, Xinming Yin, Yanmei Wang, Jizhen Wei and Shiheng An

Toxins 2022, 14(10), 721; https://doi.org/10.3390/toxins14100721 - 21 Oct 2022

Cited by 4 | Viewed by 2122

Abstract

The fall armyworm (FAW), Spodoptera frugiperda, causes substantial annual agricultural production losses worldwide due to its resistance to many insecticides. Therefore, new insecticides are urgently needed to more effectively control FAW. Cyclosporin A (CsA) is a secondary metabolite of fungi; little is [...] Read more.

The fall armyworm (FAW), Spodoptera frugiperda, causes substantial annual agricultural production losses worldwide due to its resistance to many insecticides. Therefore, new insecticides are urgently needed to more effectively control FAW. Cyclosporin A (CsA) is a secondary metabolite of fungi; little is known about its insecticidal activity, especially for the control of FAW. In this study, we demonstrate that CsA shows excellent insecticidal activity (LC₅₀ = 9.69 μg/g) against FAW through significant suppression of calcineurin (CaN) activity, which is a new target for pest control. Combinations of CsA and indoxacarb, emamectin benzoate, or Vip3Aa showed independent or synergistic toxicity against FAW; however, the combination of CsA and chlorantraniliprole showed no toxicity. Sublethal doses of CsA led to decreases in FAW larval and pupal weight, pupation, emergence, mating rates, adult longevity, extended development of FAW larvae and pupae and the pre-oviposition period of adults, and increases in the proportion of pupal malformation. Importantly, CsA treatment reduced FAW ovarian size and female fecundity, which suggests that it has great potential to suppress FAW colony formation. Taken together, these results indicate that CsA has high potential as an insecticide for controlling FAW. Full article

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14 pages, 2009 KiB

Open AccessArticle

Cytotoxic Effects of Cannabidiol on Neonatal Rat Cortical Neurons and Astrocytes: Potential Danger to Brain Development

by Damijana Mojca Jurič, Klara Bulc Rozman, Metoda Lipnik-Štangelj, Dušan Šuput and Miran Brvar

Toxins 2022, 14(10), 720; https://doi.org/10.3390/toxins14100720 - 21 Oct 2022

Cited by 6 | Viewed by 4325

Abstract

The influence of cannabidiol (CBD) on brain development is inadequately understood. Since CBD is considered a non-intoxicating drug, it has attracted great interest concerning its potential medical applicability, including in pregnant women and children. Here, we elucidated the response of perinatal rat cortical [...] Read more.

The influence of cannabidiol (CBD) on brain development is inadequately understood. Since CBD is considered a non-intoxicating drug, it has attracted great interest concerning its potential medical applicability, including in pregnant women and children. Here, we elucidated the response of perinatal rat cortical neurons and astrocytes to CBD at submicromolar (0.1, 0.5, 1, 5 µM) concentrations attainable in humans. The effect of CBD was concentration- and time-dependent and cell-specific. In neurons, 0.1 µM CBD induced an early and transient change in mitochondrial membrane potential (ΔΨm), ATP depletion, and caspase-8 activation, followed by rapid ATP recovery and progressive activation of caspase-9 and caspase-3/7, resulting in early apoptotic cell death with reduction and shortening of dendrites, cell shrinkage, and chromatin condensation. The decrease in neuronal viability, ATP depletion, and caspase activation due to CBD exposure was prevented by transient receptor potential vanilloid 1 (TRPV1) antagonist. In astrocytes, 0.5 µM CBD caused an immediate short-term dysregulation of ΔΨm, followed by ATP depletion with transient activation of caspase-8 and progressive activation of caspase-9 and caspase-3/7, leading to early apoptosis and subsequent necroptosis. In astrocytes, both TRPV1 and cannabinoid receptor 1 (CB₁) antagonists protected viability and prevented apoptosis. Given that CBD is a non-intoxicating drug, our results clearly show that this is not the case during critical periods of brain development when it can significantly interfere with the endogenous cannabinoid system. Full article

(This article belongs to the Collection Toxic and Pharmacological Effect of Plant Toxins)

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21 pages, 1996 KiB

Open AccessReview

French Scorpionism (Mainland and Oversea Territories): Narrative Review of Scorpion Species, Scorpion Venom, and Envenoming Management

by Jules-Antoine Vaucel, Sébastien Larréché, Camille Paradis, Arnaud Courtois, Jean-Marc Pujo, Narcisse Elenga, Dabor Résière, Weniko Caré, Luc de Haro, Jean-Christophe Gallart, Romain Torrents, Corinne Schmitt, Johan Chevalier, Magali Labadie, Hatem Kallel and French PCC Research Group

Toxins 2022, 14(10), 719; https://doi.org/10.3390/toxins14100719 - 21 Oct 2022

Cited by 6 | Viewed by 6952

Abstract

Sixty-seven scorpion species have been described in France and its territories, where they have been found to be heterogeneously distributed. Indeed, only one species can be found on Réunion Island, while 38 species exist in French Guiana. The number of stings is also [...] Read more.

Sixty-seven scorpion species have been described in France and its territories, where they have been found to be heterogeneously distributed. Indeed, only one species can be found on Réunion Island, while 38 species exist in French Guiana. The number of stings is also heterogenous, with up to 90 stings per 100,000 inhabitants occurring annually. Scorpion species can frequently be determined through simple visual factors, including species of medical importance (i.e., Buthus, Centruroides and Tityus). Scorpion venom is composed of local enzymes and peptides with a cysteine-stabilized α/β motif (NaTxs, Ktxs, Calcines), which allow for venom diffusion and the prey’s incapacitation, respectively. Harmful scorpion species are limited to Centruroides pococki in the French West Indies, which can induce severe envenoming, and the Tityus obscurus and Tityus silvestris in French Guiana, which can cause fatalities in children and can induce severe envenoming, respectively. Envenomation by one of these scorpions requires hospital monitoring as long as systemic symptoms persist. Typical management includes the use of a lidocaine patch, pain killers, and local antiseptic. In the case of heart failure, the use of dobutamine can improve survival, and pregnant women must consult an obstetrician because of the elevated risk of preterm birth or stillbirth. France does not have scorpion antivenom, as scorpion stings are generally not fatal. Full article

(This article belongs to the Section Animal Venoms)

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11 pages, 2050 KiB

Open AccessArticle

Co-Occurrence of Staphylococcus aureus and Ochratoxin A in Pasteurized Milk

by Zhenzhen Zhang, Yanmin Song, Liyan Ma, Kunlun Huang and Zhihong Liang

Toxins 2022, 14(10), 718; https://doi.org/10.3390/toxins14100718 - 21 Oct 2022

Cited by 8 | Viewed by 2247

Abstract

Pathogens and mycotoxins are serious public health risks for humans and food safety in milk. This study concentrated on detecting Staphylococcus aureus and Ochratoxin A (OTA) in 210 pasteurized milk from ten urban Beijing districts to suggest the co-occurrence of S. aureus with [...] Read more.

Pathogens and mycotoxins are serious public health risks for humans and food safety in milk. This study concentrated on detecting Staphylococcus aureus and Ochratoxin A (OTA) in 210 pasteurized milk from ten urban Beijing districts to suggest the co-occurrence of S. aureus with toxin-producing genes and OTA in milk and the possible risk. S. aureus was identified by physiological and biochemical experiments and molecular biology experiments, and enterotoxin genes were identified by PCR. OTA was detected by LC-MS/MS. The study found 29 isolates of S. aureus, of which 17.24% had the sea gene encoding enterotoxin A. OTA was detected in 31 out of 120 samples and the maximum amount of detection was 18.8 μg/kg. The results of this study indicate that when failing to guarantee the cold chain, the presence of S. aureus with enterotoxin genes in milk will present a risk to food safety. Furthermore, the high detection rates and levels of OTA in milk suggest that OTA is a hidden risk. The co-occurrence of S. aureus and OTA in milk is a food safety concern and there is a need to control the occurrence of these two biohazards in milk. Full article

(This article belongs to the Special Issue Advanced Research on Mycotoxins: Detection and Removal)

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19 pages, 5647 KiB

Open AccessArticle

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro

by Tienthanh Nguyen, Ruiyin Guo, Jinwei Chai, Jiena Wu, Junfang Liu, Xin Chen, Mohamed A. Abdel-Rahman, Hu Xia and Xueqing Xu

Toxins 2022, 14(10), 717; https://doi.org/10.3390/toxins14100717 - 21 Oct 2022

Cited by 17 | Viewed by 2716

Abstract

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the [...] Read more.

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment. Full article

(This article belongs to the Special Issue Advanced Research on Animal Venoms in China)

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14 pages, 1581 KiB

Open AccessArticle

Comparative Venom Proteomics of Iranian, Macrovipera lebetina cernovi, and Cypriot, Macrovipera lebetina lebetina, Giant Vipers

by Parviz Ghezellou, Melissa Dillenberger, Seyed Mahdi Kazemi, Daniel Jestrzemski, Bernhard Hellmann and Bernhard Spengler

Toxins 2022, 14(10), 716; https://doi.org/10.3390/toxins14100716 - 20 Oct 2022

Cited by 6 | Viewed by 3150

Abstract

Envenoming by Macrovipera lebetina subspecies causes severe life-threatening difficulties for people living in North Africa and the Middle East. To better understand the pathophysiology of envenoming and improve patient management, knowledge about the venom components of the subspecies is essential. Here, the venom [...] Read more.

Envenoming by Macrovipera lebetina subspecies causes severe life-threatening difficulties for people living in North Africa and the Middle East. To better understand the pathophysiology of envenoming and improve patient management, knowledge about the venom components of the subspecies is essential. Here, the venom proteomes of Macrovipera lebetina lebetina from Cyprus and Macrovipera lebetina cernovi from Iran were characterized using RP-HPLC separation of the crude venom proteins, SDS-PAGE of fractionated proteins, and LC-MS/MS of peptides obtained from in-gel tryptic digestion of protein bands. Moreover, we also used high-resolution shot-gun proteomics to gain more reliable identification, where the whole venom proteomes were subjected directly to in-solution digestion before LC-HR-MS/MS. The data revealed that both venoms consisted of at least 18 protein families, of which snake venom Zn²⁺-dependent metalloprotease (SVMP), serine protease, disintegrin, phospholipase A2, C-type lectin-like, and L-amino acid oxidase, together accounted for more than 80% of the venoms’ protein contents. Although the two viper venoms shared mostly similar protein classes, the relative occurrences of these toxins were different in each snake subspecies. For instance, P-I class of SVMP toxins were found to be more abundant than P-III class in the venoms of M. l. cernovi compared to M. l. lebetina, which gives hints at a more potent myonecrotic effect and minor systemic hemorrhage following envenoming by M. l. cernovi than M. l. lebetina. Moreover, single-shot proteomics also revealed many proteins with low abundance (<1%) within the venoms, such as aminopeptidase, hyaluronidase, glutaminyl-peptide cyclotransferase, cystatin, phospholipase B, and vascular endothelial growth factor. Our study extends the in-depth understanding of the venom complexity of M. lebetina subspecies, particularly regarding toxin families associated with envenoming pathogenesis and those hard-detected protein classes expressed in trace amounts. Full article

(This article belongs to the Special Issue Evolution, Genomics and Proteomics of Venom)

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11 pages, 1186 KiB

Open AccessReview

Microcystin-LR in Primary Liver Cancers: An Overview

by Shen Gu, Mingxuemei Jiang and Bo Zhang

Toxins 2022, 14(10), 715; https://doi.org/10.3390/toxins14100715 - 20 Oct 2022

Cited by 16 | Viewed by 3305

Abstract

The cyanobacterial blooms produced by eutrophic water bodies have become a serious environmental issue around the world. After cellular lysing or algaecide treatment, microcystins (MCs), which are regarded as the most frequently encountered cyanobacterial toxins in fresh water, are released into water. Among [...] Read more.

The cyanobacterial blooms produced by eutrophic water bodies have become a serious environmental issue around the world. After cellular lysing or algaecide treatment, microcystins (MCs), which are regarded as the most frequently encountered cyanobacterial toxins in fresh water, are released into water. Among all the variants of MCs, MC-LR has been widely studied due to its severe hepatotoxicity. Since 1992, various studies have identified the important roles of MC-LR in the origin and progression of primary liver cancers (PLCs), although few reviews have focused on it. Therefore, this review aims to summarize the major achievements and shortcomings observed in the past few years. Based on the available literature, the mechanisms of how MC-LR induces or promotes PLCs are elucidated in this review. This review aims to enhance our understanding of the role that MC-LR plays in PLCs and provides a rational approach for future applications. Full article

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

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9 pages, 721 KiB

Open AccessArticle

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

by Ilaria Chiminelli, Leon J. Spicer, Excel Rio S. Maylem and Francesca Caloni

Toxins 2022, 14(10), 714; https://doi.org/10.3390/toxins14100714 - 20 Oct 2022

Cited by 9 | Viewed by 2215

Abstract

The emerging Fusarium mycotoxins enniatins (ENNs) have been the focus of new research because of their well-documented existence in various cereal and grain products. Research findings indicate that reproductive disorders may be caused by exposure to Fusarium mycotoxins, but little work has evaluated [...] Read more.

The emerging Fusarium mycotoxins enniatins (ENNs) have been the focus of new research because of their well-documented existence in various cereal and grain products. Research findings indicate that reproductive disorders may be caused by exposure to Fusarium mycotoxins, but little work has evaluated ENNs on reproductive function. Therefore, to determine the effects of ENNA on the proliferation and steroidogenesis of granulosa cells (GC), experiments were conducted using bovine GC cultures. In vitro, ENNA (1–5 μM) inhibited (p < 0.05) hormone-induced GC progesterone and estradiol production. The inhibitory effect of ENNA on estradiol production was more pronounced in small- than large-follicle GC. In large-follicle GC, 0.3 μM ENNA had no effect (p > 0.10) whereas 1 and 3 μM ENNA inhibited GC proliferation. In small-follicle GC, ENNA (1–5 μM) dramatically decreased (p < 0.05) GC proliferation. Using cell number data, the IC₅₀ of ENNA was estimated at 2 μM for both follicle sizes. We conclude that ENNA can directly inhibit ovarian function in cattle, decreasing the proliferation and steroid production of GC. Full article

(This article belongs to the Special Issue Cellular Toxicity of the Mycotoxins: From In Vitro Testing to Single Cell Analysis)

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10 pages, 1657 KiB

Open AccessArticle

Nanobody-Nanoluciferase Fusion Protein-Enabled Immunoassay for Ochratoxin A in Coffee with Enhanced Specificity and Sensitivity

by Kunlu Bao, Xing Liu, Yujing Liao, Zilong Liu, Hongmei Cao, Long Wu and Qi Chen

Toxins 2022, 14(10), 713; https://doi.org/10.3390/toxins14100713 - 19 Oct 2022

Cited by 10 | Viewed by 2390

Abstract

Ochratoxin A (OTA), one of the best-known mycotoxins, causes problems concerning food safety with potential toxic effects in humans and animals. So, it is crucial to develop simple and sensitive methods for the detection of OTA. Herein, a nanoluciferase–nanobody fusion protein (Nb28-Nluc)-retaining antibody [...] Read more.

Ochratoxin A (OTA), one of the best-known mycotoxins, causes problems concerning food safety with potential toxic effects in humans and animals. So, it is crucial to develop simple and sensitive methods for the detection of OTA. Herein, a nanoluciferase–nanobody fusion protein (Nb28-Nluc)-retaining antibody recognition and enzymatic activity was first prepared, which was then applied as a bifunctional tracer to construct a one-step bioluminescent enzyme-linked immunosorbent assay (BLEIA) for OTA in coffee samples. On the basis of Nb28-Nluc, the BLEIA can be completed with a one-step incubation and detection, with only a substrate replacement from 3,3′,5,5′-tetramethylbenzidine (TMB) to a Nluc assay reagent (Furimazine). Under the optimal experimental conditions, the proposed one-step BLEIA achieved a detection limit of 3.7 ng/mL (IC₁₀) within 3 h. Moreover, the BLEIA method showed good repeatability and accuracy in the spike recovery experiments with recoveries of 83.88% to 120.23% and relative standard deviations (RSDs) of 5.2% to 24.7%, respectively. Particularly, the BLEIA displayed superior performances, such as fewer operations and more rapid and sensitive detection as compared with Nb28-based enzyme-linked immunosorbent assay. Therefore, the proposed one-step BLEIA has great potential for the sensitive and accurate screening of OTA in food samples. Full article

(This article belongs to the Special Issue Emerging Strategies for Extraction and Analysis of Mycotoxins in Food)

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23 pages, 706 KiB

Open AccessArticle

Investigating the Toxicity of Compounds Yielded by Staphylococci on Vero Cells

by Margaret Selina Modimola, Ezekiel Green, Patrick Njobeh, Jeremiah Senabe, Gerda Fouche, Lyndy McGaw, Sanah Malomile Nkadimeng, Kgama Mathiba and Julian Mthombeni

Toxins 2022, 14(10), 712; https://doi.org/10.3390/toxins14100712 - 18 Oct 2022

Cited by 7 | Viewed by 2900

Abstract

Bacterial secondary metabolites play a major role in the alleviation of diseases; however, the cytotoxicity of other metabolites cannot be ignored as such metabolites could be detrimental to human cells. Three Staphylococci strains Staphylococcus aureus, staphylococcus epidermidis and staphylococcus saprophyticus were used [...] Read more.

Bacterial secondary metabolites play a major role in the alleviation of diseases; however, the cytotoxicity of other metabolites cannot be ignored as such metabolites could be detrimental to human cells. Three Staphylococci strains Staphylococcus aureus, staphylococcus epidermidis and staphylococcus saprophyticus were used in the experiments. These strains are well known to cause hospital and community-acquired infections. Secondary metabolites from S. aureus isolated from milk of cows with clinical features of mastitis (swollen udders and the production of watery clotted milk), S. saprophyticus (ATCC 35552), and S. epidermidis (ATCC 51625) were exposed to a minimal medium then screened using Gas Chromatography High-Resolution Time-of-flight Mass Spectrometry (GC-HRTOF-MS) and identified with Nuclear Magnetic Resonance (NMR). From S. epidermidis, two compounds were isolated: oleamide and methyl palmitate; three from S. aureus, including fluoranthene, 3-methyl-2-phenyl-1H-pyrrole, and cyclo(L-Leu-L-Propyl); while S. saprophyticus yielded succinic acid, 1,2,6-hexantriol, veratramine, and 4-methyl-pentyl-amine. The secondary metabolites were tested for cytotoxicity using the Vero cell line. Fluoranthene exhibited toxicity with an LC₅₀ of 0.0167 mg/mL to Vero cells, while the other metabolites did not. Methyl palmitate was the least toxic of all of the metabolites. The results imply that none of the compounds, except fluoranthene, pose any danger to human cells. Full article

(This article belongs to the Collection Staphylococcus aureus Toxins)

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21 pages, 9718 KiB

Open AccessArticle

Clostridium botulinum C3 Toxin for Selective Delivery of Cargo into Dendritic Cells and Macrophages

by Maximilian Fellermann, Mia Stemmer, Reiner Noschka, Fanny Wondany, Stephan Fischer, Jens Michaelis, Steffen Stenger and Holger Barth

Toxins 2022, 14(10), 711; https://doi.org/10.3390/toxins14100711 - 18 Oct 2022

Cited by 5 | Viewed by 4108

Abstract

The protein toxin C3bot from Clostridium botulinum is a mono-ADP-ribosyltransferase that selectively intoxicates monocyte-derived cells such as macrophages, osteoclasts, and dendritic cells (DCs) by cytosolic modification of Rho-A, -B, and -C. Here, we investigated the application of C3bot as well as its non-toxic [...] Read more.

The protein toxin C3bot from Clostridium botulinum is a mono-ADP-ribosyltransferase that selectively intoxicates monocyte-derived cells such as macrophages, osteoclasts, and dendritic cells (DCs) by cytosolic modification of Rho-A, -B, and -C. Here, we investigated the application of C3bot as well as its non-toxic variant C3bot_E174Q as transporters for selective delivery of cargo molecules into macrophages and DCs. C3bot and C3bot_E174Q facilitated the uptake of eGFP into early endosomes of human-monocyte-derived macrophages, as revealed by stimulated emission depletion (STED) super-resolution microscopy. The fusion of the cargo model peptide eGFP neither affected the cell-type selectivity (enhanced uptake into human macrophages ex vivo compared to lymphocytes) nor the cytosolic release of C3bot. Moreover, by cell fractionation, we demonstrated that C3bot and C3bot_E174Q strongly enhanced the cytosolic release of functional eGFP. Subsequently, a modular system was created on the basis of C3bot_E174Q for covalent linkage of cargos via thiol–maleimide click chemistry. The functionality of this system was proven by loading small molecule fluorophores or an established reporter enzyme and investigating the cellular uptake and cytosolic release of cargo. Taken together, non-toxic C3bot_E174Q is a promising candidate for the cell-type-selective delivery of small molecules, peptides, and proteins into the cytosol of macrophages and DCs. Full article

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

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12 pages, 4373 KiB

Open AccessArticle

A Highly Sensitive Fluorescence and Screen-Printed Electrodes—Electrochemiluminescence Immunosensor for Ricin Detection Based on CdSe/ZnS QDs with Dual Signal

by Shasha Feng, Wei Hu, Fubin Pei, Zhiwei Liu, Bin Du, Xihui Mu, Bing Liu, Qingli Hao, Wu Lei and Zhaoyang Tong

Toxins 2022, 14(10), 710; https://doi.org/10.3390/toxins14100710 - 17 Oct 2022

Cited by 3 | Viewed by 1922

Abstract

A sensitive dual-readout immunosensor for fluorescence and electrochemiluminescence (ECL) detection of ricin was established, which was combined with a streptavidin–biotin signal amplification system. CdSe/ZnS quantum dots with fine fluorescence and ECL properties were used as the dual-signal function probes of the sandwich immunocomplex. [...] Read more.

A sensitive dual-readout immunosensor for fluorescence and electrochemiluminescence (ECL) detection of ricin was established, which was combined with a streptavidin–biotin signal amplification system. CdSe/ZnS quantum dots with fine fluorescence and ECL properties were used as the dual-signal function probes of the sandwich immunocomplex. Under the optimum experimental conditions, the dual signal intensity increased significantly with the rise in ricin concentration. The fluorescence intensity of the senor exhibited a good liner relationship toward the ricin concentrations with 0.1~100 ng/mL and the limit of detection (LOD) was 81.7 pg/mL; taking ECL as the detection signal, the sensor showed a linear relationship with the ricin concentrations ranging from 0.01 ng/mL to 100 ng/mL and the LOD was 5.5 pg/mL. The constructed sensor with high sensitivity had been successfully applied to the detection of ricin in complex matrices with satisfactory recoveries. The proposed immunosensor model can be extended to the analysis and detection of others target proteins. Full article

(This article belongs to the Section Plant Toxins)

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40 pages, 4004 KiB

Open AccessReview

Mechanisms of Action of the Peptide Toxins Targeting Human and Rodent Acid-Sensing Ion Channels and Relevance to Their In Vivo Analgesic Effects

by Clément Verkest, Miguel Salinas, Sylvie Diochot, Emmanuel Deval, Eric Lingueglia and Anne Baron

Toxins 2022, 14(10), 709; https://doi.org/10.3390/toxins14100709 - 17 Oct 2022

Cited by 12 | Viewed by 3985

Abstract

Acid-sensing ion channels (ASICs) are voltage-independent H⁺-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly [...] Read more.

Acid-sensing ion channels (ASICs) are voltage-independent H⁺-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly pH-dependent gating properties. This review provides an update on the pharmacological profiles of animal peptide toxins targeting ASICs, including PcTx1 from tarantula and related spider toxins, APETx2 and APETx-like peptides from sea anemone, and mambalgin from snake, as well as the dimeric protein snake toxin MitTx that have all been instrumental to understanding the structure and the pH-dependent gating of rodent and human cloned ASICs and to study the physiological and pathological roles of native ASICs in vitro and in vivo. ASICs are expressed all along the pain pathways and the pharmacological data clearly support a role for these channels in pain. ASIC-targeting peptide toxins interfere with ASIC gating by complex and pH-dependent mechanisms sometimes leading to opposite effects. However, these dual pH-dependent effects of ASIC-inhibiting toxins (PcTx1, mambalgin and APETx2) are fully compatible with, and even support, their analgesic effects in vivo, both in the central and the peripheral nervous system, as well as potential effects in humans. Full article

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

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18 pages, 3672 KiB

Open AccessArticle

Botulinum Neurotoxin Type A Directly Affects Sebocytes and Modulates Oleic Acid-Induced Lipogenesis

by Karen Brami-Cherrier, Alex Chernavsky, Hui You, Sergei A. Grando, Amy Brideau-Andersen and Birgitte Sondergaard

Toxins 2022, 14(10), 708; https://doi.org/10.3390/toxins14100708 - 15 Oct 2022

Cited by 3 | Viewed by 4244

Abstract

Excess sebum (seborrhea) results in oily skin and is associated with large pore size and acne. Studies in healthy, seborrheic volunteers have reported that intradermal injection of commercial preparations of botulinum neurotoxin type A (BoNT/A) (onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA) reduced sebum production, and [...] Read more.

Excess sebum (seborrhea) results in oily skin and is associated with large pore size and acne. Studies in healthy, seborrheic volunteers have reported that intradermal injection of commercial preparations of botulinum neurotoxin type A (BoNT/A) (onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA) reduced sebum production, and thus, skin oiliness and pore size. The mechanism for these effects has not been fully elucidated; however, several theories involving direct or indirect effects of BoNT/A on neuronal and/or dermal cells (e.g., sebocytes) have been proposed. In the present study, we evaluated the direct effect of native research grade BoNT/A complex, a commercial preparation of BoNT/A (onabotA), and BoNT/A variants on sebocyte lipogenesis using an in vitro sebocyte cell model. We show that picomolar concentrations of BoNT/A (BoNT/A complex: half maximal effective concentration [EC₅₀] = 24 pM; BoNT/A 150 kDa: EC₅₀ = 34 pM) modulate sebocyte lipogenesis and reduce oleic acid-induced sebocyte differentiation, lipogenesis, and holocrine-like secretion. Comparative studies with the binding domain of BoNT/A, which lacks enzymatic activity, show that this effect is independent of the enzymatic activity of BoNT/A and likely occurs via sebocyte cell surface receptors (e.g., fibroblast growth factor receptors). Overall, these results shed light on the potential mechanism of action and rationale for use of BoNT/A for treatment of sebum-related conditions. Full article

(This article belongs to the Special Issue Structure and Function of Clostridial and Botulinum-Like Neurotoxins)

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15 pages, 2513 KiB

Open AccessEditor’s ChoiceReview

The Efficacy of Additives for the Mitigation of Aflatoxins in Animal Feed: A Systematic Review and Network Meta-Analysis

by Oluwatobi Kolawole, Wipada Siri-Anusornsak, Awanwee Petchkongkaw, Julie Meneely and Christopher Elliott

Toxins 2022, 14(10), 707; https://doi.org/10.3390/toxins14100707 - 15 Oct 2022

Cited by 10 | Viewed by 4020

Abstract

The contamination of animal feed with aflatoxins is an ongoing and growing serious issue, particularly for livestock farmers in tropical and subtropical regions. Exposure of animals to an aflatoxin-contaminated diet impairs feed efficiency and increases susceptibility to diseases, resulting in mortality, feed waste, [...] Read more.

The contamination of animal feed with aflatoxins is an ongoing and growing serious issue, particularly for livestock farmers in tropical and subtropical regions. Exposure of animals to an aflatoxin-contaminated diet impairs feed efficiency and increases susceptibility to diseases, resulting in mortality, feed waste, and increased production costs. They can also be excreted in milk and thus pose a significant human health risk. This systematic review and network meta-analysis aim to compare and identify the most effective intervention to alleviate the negative impact of aflatoxins on the important livestock sector, poultry production. Eligible studies on the efficacy of feed additives to mitigate the toxic effect of aflatoxins in poultry were retrieved from different databases. Additives were classified into three categories based on their mode of action and composition: organic binder, inorganic binder, and antioxidant. Moreover, alanine transaminase (ALT), a liver enzyme, was the primary indicator. Supplementing aflatoxin-contaminated feeds with different categories of additives significantly reduces serum ALT levels (p < 0.001) compared with birds fed only a contaminated diet. Inorganic binder (P-score 0.8615) was ranked to be the most efficient in terms of counteracting the toxic effect of aflatoxins, followed by antioxidant (P-score 0.6159) and organic binder (P-score 0.5018). These findings will have significant importance for farmers, veterinarians, and animal nutrition companies when deciding which type of additives to use for mitigating exposure to aflatoxins, thus improving food security and the livelihoods of smallholder farmers in developing countries. Full article

(This article belongs to the Special Issue Mycotoxins: Decontamination and Adsorption)

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15 pages, 1557 KiB

Open AccessArticle

Programmed Aptamer Screening, Characterization, and Rapid Detection for α-Conotoxin MI

by Han Guo, Bowen Deng, Luming Zhao, Yun Gao, Xiaojuan Zhang, Chengfang Yang, Bin Zou, Han Chen, Mingjuan Sun, Lianghua Wang and Binghua Jiao

Toxins 2022, 14(10), 706; https://doi.org/10.3390/toxins14100706 - 14 Oct 2022

Cited by 5 | Viewed by 2108

Abstract

Conotoxins (CTXs) are a variety of mixed polypeptide toxins, among which α-conotoxin MI (CTX-MI) is the most toxic. Serious toxic symptoms, a lack of counteracting drugs, and cumbersome detection processes have made CTX-MI a hidden danger for humans. One of the obstacles to [...] Read more.

Conotoxins (CTXs) are a variety of mixed polypeptide toxins, among which α-conotoxin MI (CTX-MI) is the most toxic. Serious toxic symptoms, a lack of counteracting drugs, and cumbersome detection processes have made CTX-MI a hidden danger for humans. One of the obstacles to resolving this problem is the absence of specific recognition elements. Aptamers have shown great advantages in the fields of molecule detection, drug development, etc. In this study, we screened and characterized aptamers for CTX-MI through a programmed process. MBMI-01c, the isolated aptamer, showed great affinity, with an affinity constant (K_D) of 0.524 μM, and it formed an antiparallel G-quadruplet (GQ) structure for the specific recognition of CTX-MI. Additionally, an aptasensor based on the biolayer interferometry (BLI) platform was developed and displayed high precision, specificity, and repeatability with a limit of detection (LOD) of 0.26 μM. This aptasensor provides a potential tool for the rapid detection of CTX-MI in 10 min. The aptamer can be further developed for the enrichment, detoxification, and biological studies of CTX-MI. Additionally, the programmed process is applicable to screening and characterizing aptamers for other CTXs. Full article

(This article belongs to the Special Issue Advanced Technology for Toxins Detection: Current Status and Future Perspectives)

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16 pages, 2084 KiB

Open AccessArticle

Variability of Microcystin-LR Standards Available from Seven Commercial Vendors

by Donna Hill, Johnsie Lang, James McCord, Mark Strynar, Charlita Rosal, Judith Schmid, Thanh-Thao Le and Neil Chernoff

Toxins 2022, 14(10), 705; https://doi.org/10.3390/toxins14100705 - 14 Oct 2022

Cited by 2 | Viewed by 2198

Abstract

Microcystins (MCs) are a large group of heptapeptide cyanobacterial toxins commonly produced in harmful algal blooms (HABs) and associated with adverse health effects in wildlife, livestock, pets, and humans. MC chemical standards are extracted from cyanobacteria biomass rather than produced synthetically and are [...] Read more.

Microcystins (MCs) are a large group of heptapeptide cyanobacterial toxins commonly produced in harmful algal blooms (HABs) and associated with adverse health effects in wildlife, livestock, pets, and humans. MC chemical standards are extracted from cyanobacteria biomass rather than produced synthetically and are used in water assessment methods and toxicological studies. MC standards are generally supplied in less than 1 mg quantities, and verification of the mass can only be accomplished by analytical chemistry methods using a certified reference of the specific MC for comparison. Analytical quantification of MCs in environmental samples and toxicology studies using accurate doses of test chemicals administered to experimental animals rely on the availability and accuracy of chemical standards. To check the accuracy and purity of available standards, seven individual microcystin-LR (MCLR) standards were purchased from separate commercial vendors and analyzed to determine the actual mass supplied and identify the presence of potential contaminants. To determine the effect of varying toxin mass in toxicological studies, each MCLR standard was administered to CD-1 mice in doses based on mass purchased, by a single 40 µg/kg intraperitoneal injection. The measured mass purchased varied from the vendor label mass by more than 35% for two of the seven MCLR standards. Contaminants, including trifluoroacetic acid (TFA), were identified in four of the seven samples. Comparative in vivo hepatotoxicity between vendor samples closely reflected the actual amount of MCLR present in each standard and demonstrated the toxicological impact of varying cyanotoxin mass. Full article

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

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12 pages, 697 KiB

Open AccessReview

Botulinum Neurotoxins beyond Neurons: Interplay with Glial Cells

by Siro Luvisetto

Toxins 2022, 14(10), 704; https://doi.org/10.3390/toxins14100704 - 13 Oct 2022

Cited by 13 | Viewed by 4847

Abstract

In recent years, numerous studies have highlighted the significant use of botulinum neurotoxins (BoNTs) in the human therapy of various motor and autonomic disorders. The therapeutic action is exerted with the selective cleavage of specific sites of the SNARE’s protein complex, which plays [...] Read more.

In recent years, numerous studies have highlighted the significant use of botulinum neurotoxins (BoNTs) in the human therapy of various motor and autonomic disorders. The therapeutic action is exerted with the selective cleavage of specific sites of the SNARE’s protein complex, which plays a key role in the vesicular neuroexocytosis which is responsible for neural transmission. The primary target of the BoNTs’ action is the peripheral neuromuscular junction (NMJ), where, by blocking cholinergic neurons releasing acetylcholine (ACh), they interfere with neural transmission. A great deal of experimental evidence has demonstrated that BoNTs are also effective in blocking the release of other neurotransmitters or neuromodulators, such as glutamate, substance-P, and CGRP, and they can interfere with the function of glial cells, both at the peripheral and central level. The purpose of this review is to provide an update on the available experimental data from animal models that suggest or confirm the direct interactions between BoNTs and glial cells. From the data collected, it appears evident that, through mechanisms that are not yet fully understood, BoNTs can block the activation of spinal glial cells and their subsequent release of pro-inflammatory factors. BoNTs are also able to promote peripheral regeneration processes after nerve injury by stimulating the proliferation of Schwann cells. The data will be discussed in consideration of the possible therapeutic implications of the use of BoNTs on those pathological conditions where the contribution of glial cell activation is fundamental, such as in peripheral and central neuropathies. Full article

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

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2 pages, 474 KiB

Open AccessCorrection

Correction: Panjideh et al. Improved Therapy of B-Cell Non-Hodgkin Lymphoma by Obinutuzumab-Dianthin Conjugates in Combination with the Endosomal Escape Enhancer SO1861. Toxins 2022, 14, 478

by Hossein Panjideh, Nicole Niesler, Alexander Weng and Hendrik Fuchs

Toxins 2022, 14(10), 703; https://doi.org/10.3390/toxins14100703 - 13 Oct 2022

Viewed by 1397

Abstract

The authors wish to make corrections to their paper [...] Full article

(This article belongs to the Special Issue Immunotoxin and beyond—Past, Present and Future Perspectives)

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17 pages, 2711 KiB

Open AccessArticle

Quantitative Proteomic Analysis of Zearalenone-Induced Intestinal Damage in Weaned Piglets

by Lulu Ma, Yanping Jiang, Fuguang Lu, Shujing Wang, Mei Liu, Faxiao Liu, Libo Huang, Yang Li, Ning Jiao, Shuzhen Jiang, Xuejun Yuan and Weiren Yang

Toxins 2022, 14(10), 702; https://doi.org/10.3390/toxins14100702 - 13 Oct 2022

Cited by 12 | Viewed by 2500

Abstract

Zearalenone (ZEN), also known as the F-2 toxin, is a common contaminant in cereal crops and livestock products. This experiment aimed to reveal the changes in the proteomics of ZEN-induced intestinal damage in weaned piglets by tandem mass spectrometry tags. Sixteen weaned piglets [...] Read more.

Zearalenone (ZEN), also known as the F-2 toxin, is a common contaminant in cereal crops and livestock products. This experiment aimed to reveal the changes in the proteomics of ZEN-induced intestinal damage in weaned piglets by tandem mass spectrometry tags. Sixteen weaned piglets either received a basal diet or a basal diet supplemented with 3.0 mg/kg ZEN in a 32 d study. The results showed that the serum levels of ZEN, α-zearalenol, and β-zearalenol were increased in weaned piglets exposed to ZEN (p < 0.05). Zearalenone exposure reduced apparent nutrient digestibility, increased intestinal permeability, and caused intestinal damage in weaned piglets. Meanwhile, a total of 174 differential proteins (DEPs) were identified between control and ZEN groups, with 60 up-regulated DEPs and 114 down-regulated DEPs (FC > 1.20 or <0.83, p < 0.05). Gene ontology analysis revealed that DEPs were mainly involved in substance transport and metabolism, gene expression, inflammatory, and oxidative stress. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that DEPs were significantly enriched in 25 signaling pathways (p < 0.05), most of which were related to inflammation and amino acid metabolism. Our study provides valuable clues to elucidate the possible mechanism of ZEN-induced intestinal injury. Full article

(This article belongs to the Special Issue Effects of Mycotoxins on Animals)

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22 pages, 2459 KiB

Open AccessReview

How Does Botulinum Toxin Inhibit Itch?

by Parisa Gazerani

Toxins 2022, 14(10), 701; https://doi.org/10.3390/toxins14100701 - 12 Oct 2022

Cited by 3 | Viewed by 10739

Abstract

Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized [...] Read more.

Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined. Full article

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

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14 pages, 1490 KiB

Open AccessArticle

Aflatoxin Contamination of Maize, Groundnut, and Sorghum Grown in Burkina Faso, Mali, and Niger and Aflatoxin Exposure Assessment

by Titilayo D. O. Falade, Adama Neya, Saïdou Bonkoungou, Karim Dagno, Adamou Basso, Amadou Lamine Senghor, Joseph Atehnkeng, Alejandro Ortega-Beltran and Ranajit Bandyopadhyay

Toxins 2022, 14(10), 700; https://doi.org/10.3390/toxins14100700 - 12 Oct 2022

Cited by 9 | Viewed by 3673

Abstract

Aflatoxin contamination of staple crops by Aspergillus flavus and closely related fungi is common across the Sahel region of Africa. Aflatoxins in maize, groundnut, and sorghum collected at harvest or from farmers’ stores within two weeks of harvest from Burkina Faso, Mali, and [...] Read more.

Aflatoxin contamination of staple crops by Aspergillus flavus and closely related fungi is common across the Sahel region of Africa. Aflatoxins in maize, groundnut, and sorghum collected at harvest or from farmers’ stores within two weeks of harvest from Burkina Faso, Mali, and Niger were quantified. Thereafter, aflatoxin exposure values were assessed using per capita consumption rates of those crops. Mean aflatoxin concentrations in maize were high, 128, 517, and 659 µg/kg in Mali, Burkina Faso, and Niger, respectively. The estimated probable daily intake (PDI) of aflatoxins from maize ranged from 6 to 69, 29 to 432, and 310 to 2100 ng/kg bw/day in Mali, Burkina Faso, and Niger, respectively. Similarly, mean aflatoxin concentrations in sorghum were high, 76 and 259 µg/kg in Mali and Niger, respectively, with an estimated PDI of 2–133 and 706–2221. For groundnut, mean aflatoxin concentrations were 115, 277, and 628 µg/kg in Mali, Burkina Faso, and Niger, respectively. Aflatoxin exposure values were high with an estimated 9, 28, and 126 liver cancer cases/100,000 persons/year in Mali, Burkina Faso, and Niger, respectively. Several samples were extremely unsafe, exceeding manyfold regulatory levels of diverse countries (up to 2000 times more). Urgent attention is needed across the Sahel for integrated aflatoxin management for public health protection, food and nutrition security, and access to trade opportunities. Full article

(This article belongs to the Special Issue Mycotoxin Exposure: Assessment, Corresponding Adverse Health Outcomes and Control Plans)

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13 pages, 2502 KiB

Open AccessArticle

Mycotoxin Production and the Relationship between Microbial Diversity and Mycotoxins in Pyrus bretschneideri Rehd cv. Huangguan Pear

by Huimin Li, Yang Zhang, Congcong Gao, Qi Gao, Yudou Cheng, Min Zhao and Junfeng Guan

Toxins 2022, 14(10), 699; https://doi.org/10.3390/toxins14100699 - 11 Oct 2022

Cited by 6 | Viewed by 2357

Abstract

Mycotoxins are generated by a series of fungal pathogens in postharvest fruit, resulting in serious health threat to consumers and great economic loss to the fruit storage industry. The microbial differences between rotten and healthy fruit during storage and their relationship with mycotoxin [...] Read more.

Mycotoxins are generated by a series of fungal pathogens in postharvest fruit, resulting in serious health threat to consumers and great economic loss to the fruit storage industry. The microbial differences between rotten and healthy fruit during storage and their relationship with mycotoxin production have not been fully studied. In this study, differences in microbial diversity between rotten and healthy fruit after 30 days of storage at ambient temperature were investigated using high-throughput sequencing technology in ‘Huangguan’ pear (Pyrus bretschneideri Rehd cv. Huangguan) harvested from five different producing regions of Hebei province, China. The bacterial genus Gluconobacter was much more abundant in rotten fruit (76.24%) than that in healthy fruit (32.36%). In addition, Komagataeibacter and Acetobacter were also relatively higher in abundance in rotten fruit. In contrast, bacterial genera Pantoea, Alistipes, Muribaculaceae, Lactobacillus, and Ruminococcaceae_UCG were found to be more abundant in healthy fruit. Fungal genera including Botryosphaeria, Colletotrichum, Valsa, Alternaria, Rosellinia, Fusarium, and Trichothecium were found to be abundant in rotten fruit. The results of principal coordinate analysis (PCoA) showed that there were significant differences in the microbial diversity of different regions. PAT (patulin) was detected in all rotten fruit samples, while tenuazonic acid (TeA), alternariol (AOH), and alternariolmonomethyl ether (AME) were only detected in samples collected from one region (Weixian). Canonical correlation analysis (CCA) and Pearson correlation analysis showed that the abundance of Alistipes and Pantoea were negatively correlated with the contents of PAT, suggesting that bacterial genera Alistipes and Pantoea have potential in reducing mycotoxin production in ‘Huangguan’ pear. Full article

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

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12 pages, 2951 KiB

Open AccessArticle

Corynebacterium sp. 2-TD Mediated Toxicity of 2-Tridecanone to Helicoverpa armigera

by Meng Gu, Zhaoxiang Xue, Shenglan Lv, Yuhao Cai, Lei Zhang and Xiwu Gao

Toxins 2022, 14(10), 698; https://doi.org/10.3390/toxins14100698 - 11 Oct 2022

Cited by 9 | Viewed by 2161

Abstract

Cotton bollworm (Helicoverpa armigera) is a Lepidopteran noctuid pest with a global distribution. It has a wide range of host plants and can harm cotton, tomato, tobacco, and corn, as well as other crops. H. armigera larvae damage the flower buds, [...] Read more.

Cotton bollworm (Helicoverpa armigera) is a Lepidopteran noctuid pest with a global distribution. It has a wide range of host plants and can harm cotton, tomato, tobacco, and corn, as well as other crops. H. armigera larvae damage the flower buds, flowers, and fruits of tomato and cause serious losses to tomato production. Tomato uses the allelochemical 2-tridecanone to defend against this damage. So far, there have been no reports on whether the adaptation of H. armigera to 2-tridecanone is related to its symbiotic microorganisms. Our study found that Corynebacterium sp. 2-TD, symbiotic bacteria in H. armigera, mediates the toxicity of the 2-tridecanone to H. armigera. Corynebacterium sp. 2-TD, which was identified by 16S rDNA gene sequence analysis, was screened out using a basal salt medium containing a unique carbon source of 2-tridecanone. Then, Corynebacterium sp. 2-TD was confirmed to be distributed in the gut of H. armigera by quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). The survival rate of H. armigera increased by 38.3% under 2-tridecanone stress after inoculation with Corynebacterium sp. 2-TD. The degradation effect of Corynebacterium sp. 2-TD on 2-tridecanone was verified by ultra-high-performance liquid chromatography (UPLC). Our study is the first to report the isolation of gut bacteria that degrade 2-tridecanone from the important agricultural pest H. armigera and to confirm bacterial involvement in host adaptation to 2-tridecanone, which provides new insights into the adaptive mechanism of agricultural pests to host plants. Full article

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20 pages, 4203 KiB

Open AccessArticle

Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone Heteractis magnifica

by Rimma S. Kalina, Igor E. Kasheverov, Sergey G. Koshelev, Oksana V. Sintsova, Steve Peigneur, Ernesto Lopes Pinheiro-Junior, Roman S. Popov, Victoria E. Chausova, Margarita M. Monastyrnaya, Pavel S. Dmitrenok, Marina P. Isaeva, Jan Tytgat, Sergey A. Kozlov, Emma P. Kozlovskaya, Elena V. Leychenko and Irina N. Gladkikh

Toxins 2022, 14(10), 697; https://doi.org/10.3390/toxins14100697 - 11 Oct 2022

Cited by 6 | Viewed by 2136

Abstract

The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Met_ox and Hmg 1b-5, were [...] Read more.

The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Met_ox and Hmg 1b-5, were isolated from the sea anemone Heteractis magnifica and characterized as novel nAChR ligands and acid-sensing ion channel (ASIC) modulators. All peptides competed with radiolabeled α-bungarotoxin for binding to Torpedo californica muscle-type and human α7 nAChRs. Hmg 1b-2 potentiated acetylcholine-elicited current in human α7 receptors expressed in Xenopus laevis oocytes. Moreover, the multigene family coding APETx-like peptides library from H. magnifica was described and in silico surface electrostatic potentials of novel peptides were analyzed. To explain the 100% identity of some peptide isoforms between H. magnifica and H. crispa, 18S rRNA, COI, and ITS analysis were performed. It has been shown that the sea anemones previously identified by morphology as H. crispa belong to the species H. magnifica. Full article

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

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20 pages, 2625 KiB

Open AccessArticle

Evaluation of a Novel Synthetic Peptide Derived from Cytolytic Mycotoxin Candidalysin

by Pedro Henrique de Oliveira Cardoso, Ana Paula de Araújo Boleti, Patrícia Souza e Silva, Lincoln Takashi Hota Mukoyama, Alexya Sandim Guindo, Luiz Filipe Ramalho Nunes de Moraes, Caio Fernando Ramalho de Oliveira, Maria Ligia Rodrigues Macedo, Cristiano Marcelo Espínola Carvalho, Alinne Pereira de Castro and Ludovico Migliolo

Toxins 2022, 14(10), 696; https://doi.org/10.3390/toxins14100696 - 11 Oct 2022

Cited by 5 | Viewed by 3176

Abstract

The importance of neuroinflammation in neurology is becoming increasingly apparent. In addition to neuroinflammatory diseases such as multiple sclerosis, the role of neuroinflammation has been identified in many non-inflammatory neurological disorders such as stroke, epilepsy, and cancer. The immune response within the brain [...] Read more.

The importance of neuroinflammation in neurology is becoming increasingly apparent. In addition to neuroinflammatory diseases such as multiple sclerosis, the role of neuroinflammation has been identified in many non-inflammatory neurological disorders such as stroke, epilepsy, and cancer. The immune response within the brain involves the presence of CNS resident cells; mainly glial cells, such as microglia, the CNS resident macrophages. We evaluated the peptide Ca-MAP1 bioinspired on the C. albicans immature cytolytic toxin candidalysin to develop a less hemolytic peptide with anti-neuroinflammatory, antibacterial, and cytotoxic activity against tumor cells. In silico and in vitro studies were performed at various concentrations. Ca-MAP1 exhibits low hemolytic activity at lower concentrations and was not cytotoxic to MRC-5 and BV-2 cells. Ca-MAP1 showed activity against Acinetobacter baumannii, Escherichia coli ATCC, E. coli KPC, Klebsiella pneumoniae ATCC, Pseudomonas aeruginosa, and Staphylococcus aureus ATCC. Furthermore, Ca-MAP1 exhibits anti-neuroinflammatory activity in the BV-2 microglia model, with 93.78% inhibition of nitrate production at 18.1 µM. Ca-MAP1 presents cytotoxic activity against tumor cell line NCI-H292 at 36.3 μM, with an IC₅₀ of 38.4 µM. Ca-MAP1 demonstrates results that qualify it to be evaluated in the next steps to promote the control of infections and provide an alternative antitumor therapy. Full article

(This article belongs to the Special Issue Mycotoxins and Fungal Toxins: Current Status and Future Perspectives)

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12 pages, 2870 KiB

Open AccessArticle

Possible Reaction Mechanisms Involved in Degradation of Patulin by Heat-Assisted Cysteine under Highly Acidic Conditions

by Enjie Diao, Kun Ma, Minghua Li, Hui Zhang, Peng Xie, Shiquan Qian, Huwei Song, Ruifeng Mao and Liming Zhang

Toxins 2022, 14(10), 695; https://doi.org/10.3390/toxins14100695 - 10 Oct 2022

Cited by 2 | Viewed by 2090

Abstract

Patulin (PAT) is one of mycotoxins that usually contaminates apple juice, and it is not easily detoxified by cysteine (CYS) at room temperature due to the highly acidic conditions based on the Michael addition reaction. However, it could be effectively degraded by a [...] Read more.

Patulin (PAT) is one of mycotoxins that usually contaminates apple juice, and it is not easily detoxified by cysteine (CYS) at room temperature due to the highly acidic conditions based on the Michael addition reaction. However, it could be effectively degraded by a heating treatment at 120 °C for 30 min in the presence of cysteine. In our study, a total of eight degradation products (DP A–H) were characterized and identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in a negative ion mode, and their structures and formulas were proposed based on their accurate mass data. The fragmentation patterns of PAT and its degradation products were obtained from the MS/MS analysis. Meanwhile, the possible reaction mechanisms involved in the degradation of PAT were established and explained for the first time. According to the relation between the structure and toxicity of PAT, it could be deduced that the toxic effects of PAT degradation products were potentially much less than those of PAT-self. Full article

(This article belongs to the Special Issue Innovative Mycotoxin Detoxification: Discoveries, Mechanisms and Applications)

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19 pages, 1076 KiB

Open AccessArticle

Early Adverse Reactions to Snake Antivenom: Poison Center Data Analysis

by Charuwan Sriapha, Panee Rittilert, Taksa Vasaruchapong, Sahaphume Srisuma, Winai Wananukul and Satariya Trakulsrichai

Toxins 2022, 14(10), 694; https://doi.org/10.3390/toxins14100694 - 9 Oct 2022

Cited by 11 | Viewed by 3165

Abstract

Antivenom is an essential treatment for snake envenomation; however, early adverse reactions (EARs) are major limitations to its use. We performed a retrospective cross-sectional study using Ramathibodi Poison Center data (January 2016 to December 2017) to clarify the incidence and severity of EARs [...] Read more.

Antivenom is an essential treatment for snake envenomation; however, early adverse reactions (EARs) are major limitations to its use. We performed a retrospective cross-sectional study using Ramathibodi Poison Center data (January 2016 to December 2017) to clarify the incidence and severity of EARs following different F(ab’)₂ antivenoms. Among 1006 envenomed patients, 684 (68%) received antivenom therapy with a total of 1157 doses, mostly green pit viper antivenom. The overall EAR incidence and rate were 22. 5% (154/684) and 15% (173/1157), respectively. The EAR rate following each type of antivenom was >10%, except for Russell’s viper antivenom (2.9%); the severe reaction rate was 2.6% (30/1157). Malayan pit viper bites caused a high incidence of EARs (37.8%) and the highest EAR rate (22.3%). Fifty-two cases developed anaphylaxis. All EARs occurred within 2 h after treatment initiation. No deaths were attributed to EARs. The duration of administration was significantly different between doses of antivenom that induced EARs and those that did not. In conclusion, all types and every dose of antivenom should be infused for 30–60 min. Preparation of resuscitation equipment and continuous clinical observation are crucial for at least 2 h after administration, and prompt treatment should be provided when EARs occur. Full article

(This article belongs to the Section Animal Venoms)

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17 pages, 906 KiB

Open AccessReview

Ochratoxin A in Dry-Cured Ham: OTA-Producing Fungi, Prevalence, Detection Methods, and Biocontrol Strategies—A Review

by Yuanshan Chen, Jiang Chen, Qiujin Zhu and Jing Wan

Toxins 2022, 14(10), 693; https://doi.org/10.3390/toxins14100693 - 9 Oct 2022

Cited by 11 | Viewed by 3341

Abstract

Traditional dry-cured hams are easily contaminated by toxigenic fungi during the fermentation and ripening stages. The detection and positive rates of ochratoxin A (OTA) are the highest among mycotoxins detected in traditional dry-cured hams, indicating that OTA in hams is a potential safety [...] Read more.

Traditional dry-cured hams are easily contaminated by toxigenic fungi during the fermentation and ripening stages. The detection and positive rates of ochratoxin A (OTA) are the highest among mycotoxins detected in traditional dry-cured hams, indicating that OTA in hams is a potential safety hazard to human health. This review addresses the mycotoxin-producing fungal species, the toxigenic conditions causing OTA contamination worldwide, the prevalence of OTA contamination in dry-cured hams, and the detection methods applied in OTA analysis. Additionally, this study introduces methods to prevent and control OTA in traditional dry-cured hams. The growth of common mycotoxin-producing fungi and the accumulation of mycotoxins in dry-cured ham can be controlled by a microbial starter. This review provides an important theoretical foundation for the research and control of OTA in traditional dry-cured hams. Full article

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