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Toxins, Volume 14, Issue 12 (December 2022) – 75 articles

Cover Story (view full-size image): Ant venoms are an almost untouched source of biomolecules with translational potential. Several species are known to contain linear venom peptides with similarity to antimicrobial peptides (AMPs) in their venom. However, only a few AMP-like toxins have been studied so far. Here, we used an in silico approach to identify such toxins from venom gland transcriptomes of the two ants Myrmica rubra and Myrmica ruginodis. The peptides were synthesized and functionally studied. They imposed growth-reducing effects on several strains of bacteria, some of which are of clinical relevance. We therefore conclude that they have a principal function as an antimicrobial defense for the venom system and the colony and may be employed in allogrooming. View this paper
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13 pages, 1899 KiB  
Article
Cationic PLGA Nanoparticle Formulations as Biocompatible Immunoadjuvant for Serum Production and Immune Response against Bothrops jararaca Venom
by Emanuell dos Santos-Silva, Manoela Torres-Rêgo, Fiamma Gláucia-Silva, Renata Carvalho Feitosa, Ariane Ferreira Lacerda, Hugo Alexandre de Oliveira Rocha, Matheus de Freitas Fernandes-Pedrosa and Arnóbio Antônio da Silva-Júnior
Toxins 2022, 14(12), 888; https://doi.org/10.3390/toxins14120888 - 19 Dec 2022
Cited by 1 | Viewed by 1656
Abstract
Snakebite envenoming represents a worldwide public health issue. Suitable technologies have been investigated for encapsulated recombinant or native proteins capable of inducing an effective and long-lasting adaptive immune response. Nanoparticles are colloidal dispersions that have been used as drug delivery systems for bioactive [...] Read more.
Snakebite envenoming represents a worldwide public health issue. Suitable technologies have been investigated for encapsulated recombinant or native proteins capable of inducing an effective and long-lasting adaptive immune response. Nanoparticles are colloidal dispersions that have been used as drug delivery systems for bioactive biological compounds. Venom-loaded nanoparticles modulate the protein release and activate the immune response to produce specific antibodies. In this study, biocompatible cationic nanoparticles with Bothrops jararaca venom were prepared to be used as a novel immunoadjuvant that shows a similar or improved immune response in antibody production when compared to a conventional immunoadjuvant (aluminum hydroxide). We prepared stable, small-sized and spherical particles with high Bothrops jararaca venom protein association efficiency. The high protein loading efficiency, electrophoresis, and zeta potential results demonstrated that Bothrops jararaca venom is adsorbed on the particle surface, which remained as a stable colloidal dispersion over 6 weeks. The slow protein release occurred and followed parabolic diffusion release kinetics. The in vivo studies demonstrated that venom-loaded nanoparticles were able to produce an immune response similar to that of aluminum hydroxide. The cationic nanoparticles (CNp) as carriers of bioactive molecules, were successfully developed and demonstrated to be a promising immunoadjuvant. Full article
(This article belongs to the Special Issue Biotechnological Potential of Animal Venom and Toxins)
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19 pages, 2056 KiB  
Article
Assessment of Maize Hybrids Resistance to Aspergillus Ear Rot and Aflatoxin Production in Environmental Conditions in Serbia
by Tijana Barošević, Ferenc Bagi, Zagorka Savić, Nataša Ljubičić and Ivana Ivanović
Toxins 2022, 14(12), 887; https://doi.org/10.3390/toxins14120887 - 19 Dec 2022
Cited by 3 | Viewed by 1894
Abstract
Aflatoxin, a naturally occurring toxin produced by the fungus Aspergillus flavus, is the most economically important mycotoxin in the world, with harmful effects on human and animal health. Preventive measures such as irrigation and planting dates can minimize aflatoxin contamination most years. However, [...] Read more.
Aflatoxin, a naturally occurring toxin produced by the fungus Aspergillus flavus, is the most economically important mycotoxin in the world, with harmful effects on human and animal health. Preventive measures such as irrigation and planting dates can minimize aflatoxin contamination most years. However, no control strategy is completely effective when environmental conditions are extremely favorable for growth of the fungus. The most effective control method is growing maize hybrids with genetic resistance to aflatoxin contamination. The aim of this research was to evaluate the sensitivity of different maize hybrids to A. flavus infection and aflatoxin accumulation. Twenty commercial maize hybrids were evaluated in field trials with artificial inoculations using the colonized toothpicks method. The mycotoxin production potential of A. flavus isolates was confirmed by cluster amplification patterns (CAPs) analysis. The results of this research indicated the existence of significant differences in maize hybrids susceptibility to Aspergillus ear rot and aflatoxin B1 accumulation. No hybrid included in this research showed complete resistance in all conditions, but some hybrids showed partial resistance. Different hybrids also responded differently depending on the sowing date. This research showed that infection intensity is not always consistent with aflatoxin levels, and therefore visual evaluation is not enough to assess maize safety. Full article
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11 pages, 1055 KiB  
Article
Targeted Proteomics Analysis of Staphylococcal Superantigenic Toxins in Menstrual Fluid from Women with Menstrual Toxic Shock Syndrome (mTSS)
by Marie Courçon, Cédric Badiou, Mathilde Louwagie, Sibyle Etievant, Michel Jaquinod, Gérard Lina and Virginie Brun
Toxins 2022, 14(12), 886; https://doi.org/10.3390/toxins14120886 - 19 Dec 2022
Viewed by 1971
Abstract
Menstrual toxic shock syndrome (mTSS) is a rare life-threatening febrile illness that occurs in women using intravaginal menstrual protection. It is caused by toxic shock syndrome toxin 1 (TSST-1) produced by Staphylococcus aureus, triggering a sudden onset of rash and hypotension, subsequently [...] Read more.
Menstrual toxic shock syndrome (mTSS) is a rare life-threatening febrile illness that occurs in women using intravaginal menstrual protection. It is caused by toxic shock syndrome toxin 1 (TSST-1) produced by Staphylococcus aureus, triggering a sudden onset of rash and hypotension, subsequently leading to multiple organ failure. Detecting TSST-1 and S. aureus virulence factors in menstrual fluid could accelerate the diagnosis and improve therapeutic management of mTSS. However, menstrual fluid is a highly complex matrix, making detection of bacterial toxins challenging. Here, we present a mass-spectrometry-based proteomics workflow for the targeted, quantitative analysis of four S. aureus superantigenic toxins in menstrual fluids (TSST-1, SEA, SEC, and SED). This method was applied to characterize toxin levels in menstrual fluids collected from patients with mTSS and healthy women. Toxins were detectable in samples from patients with mTSS and one healthy donor at concentrations ranging from 0 to 0.46 µg/mL for TSST-1, and 0 to 1.07 µg/mL for SEC. SEA and SED were never detected in clinical specimens, even though many S. aureus strains were positive for the corresponding genes. The method presented here could be used to explore toxin production in vivo in users of intravaginal devices to improve the diagnosis, understanding, and prevention of mTSS. Full article
(This article belongs to the Special Issue Advances in Toxins and Virulence Analysis of Bacteria)
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14 pages, 3581 KiB  
Article
Substance P and Glucagon-like Peptide-17-36 Amide Mediate Anorexic Responses to Trichothecene Deoxynivalenol and Its Congeners
by Hui Jia, Zihui Qin, Ben Wei, Xinyi Guo, Huiping Xiao, Huayue Zhang, Zelin Li, Qinghua Wu, Ruibo Zheng and Wenda Wu
Toxins 2022, 14(12), 885; https://doi.org/10.3390/toxins14120885 - 18 Dec 2022
Cited by 2 | Viewed by 1453
Abstract
Type B trichothecenes commonly contaminate cereal grains and include five structurally related congeners: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), and nivalenol (NIV). These toxins are known to have negative effects on human and animal health, particularly affecting food intake. However, [...] Read more.
Type B trichothecenes commonly contaminate cereal grains and include five structurally related congeners: deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), and nivalenol (NIV). These toxins are known to have negative effects on human and animal health, particularly affecting food intake. However, the pathophysiological basis for anorexic effect is not fully clarified. The purpose of this study is to explore the potential roles of the brain-gut peptides substance P (SP) and glucagon-like peptide-17-36 amide (GLP-1) in anorexic responses induced by type B trichothecenes following both intraperitoneal (IP) and oral administration. SP and GLP-1 were elevated at 1 or 2 h and returned to basal levels at 6 h following exposure to DON and both ADONs. FX induced the production of both brain gut peptides with initial time at 1 or 2 h and duration > 6 h. Similar to FX, exposing IP to NIV caused elevations of SP and GLP-1 at 1 h and lasted more than 6 h, whereas oral exposure to NIV only increased both brain gut peptides at 2 h. The neurokinin-1 receptor (NK-1R) antagonist Emend® dose-dependently attenuated both SP- and DON-induced anorexic responses. Pretreatment with the GLP-1 receptor (GLP-1R) antagonist Exending9-39 induced a dose-dependent attenuation of both GLP-1- and DON-induced anorexic responses. To summarize, the results suggest that both SP and GLP-1 play important roles in anorexia induction by type B trichothecenes. Full article
(This article belongs to the Special Issue Remediation Strategies for Mycotoxin in Animal Feed)
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17 pages, 2822 KiB  
Review
Toxic Habits: An Analysis of General Trends and Biases in Snake Venom Research
by Ignazio Avella, Wolfgang Wüster, Luca Luiselli and Fernando Martínez-Freiría
Toxins 2022, 14(12), 884; https://doi.org/10.3390/toxins14120884 - 17 Dec 2022
Cited by 5 | Viewed by 2898
Abstract
Biases in snake venom research have been partially identified but seldomly quantified. Using the Google Scholar web search engine, we collected a total of 267 articles published between 1964 and 2021, and reviewed them to assess the main trends in this field of [...] Read more.
Biases in snake venom research have been partially identified but seldomly quantified. Using the Google Scholar web search engine, we collected a total of 267 articles published between 1964 and 2021, and reviewed them to assess the main trends in this field of study. We developed a 4-category classification of the harmful potential of each of the 298 snake species retrieved from the analysed publications, and tested whether taxonomy, realm of origin, and/or assigned hazard category could affect how often each of them appeared in the articles considered. Overall, viperids were significantly more represented than any other snake taxon retrieved. The Neotropics were the most represented biogeographic realm for number of studied species, whereas information about the country of origin of the analysed specimens was often incomplete. The vast majority of the publications focused on snake venom characterisation, whereas more ecology-related topics were rarely considered. Hazard category and biogeographic realm of origin of each species had a significant effect on the number of articles dedicated to it, suggesting that a snake’s harmful potential and place of origin influence its popularity in venom studies. Our analysis showed an overall positive trend in the number of snake venom studies published yearly, but also underlined severe neglect of snake families of supposedly minor medical relevance (e.g., Atractaspididae), underrepresentation of some of the areas most impacted by snakebite (i.e., Indomalayan and Afrotropic realms), and limited interest in the ecological and functional context of snake venom. Full article
(This article belongs to the Special Issue Recent Updates in Venomics and Applications)
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14 pages, 2626 KiB  
Article
Putative C2H2 Transcription Factor AflZKS3 Regulates Aflatoxin and Pathogenicity in Aspergillus flavus
by Liuke Liang, Haojie Yang, Shan Wei, Shuaibing Zhang, Liang Chen, Yuansen Hu and Yangyong Lv
Toxins 2022, 14(12), 883; https://doi.org/10.3390/toxins14120883 - 17 Dec 2022
Cited by 3 | Viewed by 1441
Abstract
Aflatoxin is a carcinogenic secondary metabolite that poses a serious threat to human and animal health. Some C2H2 transcription factors are associated with fungal growth and secondary metabolic regulation. In this study, we characterized the role of AflZKS3, a [...] Read more.
Aflatoxin is a carcinogenic secondary metabolite that poses a serious threat to human and animal health. Some C2H2 transcription factors are associated with fungal growth and secondary metabolic regulation. In this study, we characterized the role of AflZKS3, a putative C2H2 transcription factor based on genome annotation, in the growth and aflatoxin biosynthesis of A. flavus and explored its possible mechanisms of action. Surprisingly, the protein was found to be located in the cytoplasm, and gene deletion in A. flavus resulted in defective growth and conidia formation, as well as increased sensitivity to the fluorescent brightener Calcofluor white, Congo red, NaCl, and sorbitol stress. Notably, the biosynthesis of aflatoxin B1 was completely inhibited in the ΔAflZKS3 deletion strain, and its ability to infect peanut and corn seeds was also reduced. RNA sequencing showed that differentially expressed genes in the ΔAflZKS3 strain compared with the control and complementation strains were mainly associated with growth, aflatoxin biosynthesis, and oxidative stress. Thus, AflZKS3 likely contributes to growth, cell development, and aflatoxin synthesis in A. flavus. These findings lay the foundation for a deeper understanding of the roles of C2H2 transcription factors in A. flavus and provide a potential biocontrol target for preventing aflatoxin contamination. Full article
(This article belongs to the Section Mycotoxins)
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40 pages, 525 KiB  
Review
Potential Endocrine Disruption of Cyanobacterial Toxins, Microcystins and Cylindrospermopsin: A Review
by Antonio Casas-Rodriguez, Ana M. Cameán and Angeles Jos
Toxins 2022, 14(12), 882; https://doi.org/10.3390/toxins14120882 - 17 Dec 2022
Cited by 10 | Viewed by 3269
Abstract
Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of [...] Read more.
Microcystins (MCs) and cylindrospermopsin (CYN), although classified as hepatotoxins and cytotoxins, respectively, have been shown to also induce toxic effects in many other systems and organs. Among them, their potential endocrine disruption (ED) activity has been scarcely investigated. Considering the increasing relevance of ED on humans, mammals, and aquatic organisms, this work aimed to review the state-of-the-art regarding the toxic effects of MCs and CYN at this level. It has been evidenced that MCs have been more extensively investigated than CYN. Reported results are contradictory, with the presence or absence of effects, but experimental conditions also vary to a great extent. In general, both toxins have shown ED activity mediated by very different mechanisms, such as estrogenic responses via a binding estrogen receptor (ER), pathological changes in several organs and cells (testis, ovarian cells), and a decreased gonad-somatic index. Moreover, toxic effects mediated by reactive oxygen species (ROS), changes in transcriptional responses on several endocrine axes and steroidogenesis-related genes, and changes in hormone levels have also been reported. Further research is required in a risk assessment frame because official protocols for assessment of endocrine disrupters have not been used. Moreover, the use of advanced techniques would aid in deciphering cyanotoxins dose-response relationships in relation to their ED potential. Full article
(This article belongs to the Special Issue Toxicology Research on Cyanotoxins)
13 pages, 2749 KiB  
Article
A Thermostable Dissolving Microneedle Vaccine with Recombinant Protein of Botulinum Neurotoxin Serotype A
by Baohua Zhao, Zhiying Jin, Yunzhou Yu, Yue Li, Jing Wang, Wei Wan, Chenyi Hu, Xiaoyang Li, Yanwei Li, Wenwen Xin, Lin Kang, Hao Yang, Jinglin Wang and Shan Gao
Toxins 2022, 14(12), 881; https://doi.org/10.3390/toxins14120881 - 16 Dec 2022
Cited by 2 | Viewed by 1579
Abstract
Background: As a Class A bioterrorism agent, botulinum neurotoxin serotype A (BoNT/A) carries the risk of being used by terrorists to cause mass poisoning. The microneedle (MN) patch has a great potential for application as a novel vaccine delivery method. The aim of [...] Read more.
Background: As a Class A bioterrorism agent, botulinum neurotoxin serotype A (BoNT/A) carries the risk of being used by terrorists to cause mass poisoning. The microneedle (MN) patch has a great potential for application as a novel vaccine delivery method. The aim of this study is to develop a thermally stable, dissolving microneedle patch for the delivery of a recombinant protein vaccine using a recombinant C-terminal heavy chain of BoNT/A (Hc of BoNT/A, AHc) to prevent botulism. Methods: Fish gelatin, a natural non-toxic and bacteriostatic material, was selected as the microneedle matrix for the preparation of the dissolving microneedle vaccine. Subsequently, the mechanical performance, bacteriostatic properties, vaccination effect, and stability of the microneedle patches were evaluated using instruments such as the displacement-force test station and optical coherence tomography (OCT) scanner. Results: Fish gelatin matrix at high concentrations has good bacteriostatic properties, and excellent mechanical performance and vaccination effect, meeting the necessities of a vaccine. In both in vivo and in vitro neutralization experiments, MN vaccines containing different antigen doses achieved the same protective efficacy as subcutaneous vaccinations, protecting mice against 106 LD50 of BoNT/A injected intraperitoneally. Thermal stability analysis of the MN vaccines revealed that the fish gelatin matrix protected the AHc vaccine from protein denaturation even after 7 days of storage at 37 °C and enabled the vaccine patches to maintain good immunogenicity and protective efficacy even after 6 months of storage at room temperature. Conclusion: In this study, we successfully prepared a bacteriostatic MN patch using a fish gelatin matrix that not only has a good vaccination effect, but also obviates the need for a cold chain for the AHc vaccine, providing the possibility of rapid, painless, and large-scale vaccination. Full article
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4 pages, 468 KiB  
Editorial
Hypoxia and Cellular Senescence, Emerging Toxic Mechanisms of Mycotoxins and Toxins: A New Understanding of the Negative Immune Regulations
by Qinghua Wu, Li You, Wenda Wu and Xu Wang
Toxins 2022, 14(12), 880; https://doi.org/10.3390/toxins14120880 - 16 Dec 2022
Cited by 1 | Viewed by 1081
Abstract
Mycotoxin contamination is an important issue that has plagued the world [...] Full article
(This article belongs to the Section Mycotoxins)
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21 pages, 5339 KiB  
Article
Comparative Analysis of Aristolochic Acids in Aristolochia Medicinal Herbs and Evaluation of Their Toxicities
by Shu-Han Zhang, Yun Wang, Jing Yang, Dan-Dan Zhang, Yan-Lei Wang, Shu-Hui Li, Ying-Ni Pan, Hua-Min Zhang and Yi Sun
Toxins 2022, 14(12), 879; https://doi.org/10.3390/toxins14120879 - 16 Dec 2022
Cited by 4 | Viewed by 1636
Abstract
Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the Aristolochia genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in Aristolochia plants, except for AAs [...] Read more.
Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the Aristolochia genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in Aristolochia plants, except for AAs Ι and ΙΙ, still remain unclear. In this study, a total of 52 batches of three medicinal herbs belonging to the Aristolochia family were analyzed for their AA composition profiles and AA contents using the UPLC-QTOF-MS/MS approach. The studied herbs were A. mollissima Hance (AMH), A. debilis Sieb.etZucc (ADS), and A. cinnabaria C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the Aristolochia medicinal herbs. Additionally, cytotoxicity and genotoxicity of the selected AAs and the extracts of AMH and ADS were evaluated in a HepG2 cell line using the MTT method and a Comet assay, respectively. A total of 44 AAs, including 23 aristolochic acids and 21 aristolactams (ALs), were detected in A. mollissima. Moreover, 41 AAs (23 AAs and 18 ALs) were identified from A. debilis Sieb, and 45 AAs (29 AAs and 16 ALs) were identified in A. cinnabaria. Chemometrics results showed that 16, 19, and 22 AAs identified in AMH, ADS, and ACY, respectively, had statistical significance for distinguishing the three medicinal herbs of different origins. In the cytotoxicity assay, compounds AL-BΙΙ, AAΙ and the extract of AMH exhibited significant cytotoxicities against the HepG2 cell line with the IC50 values of 0.2, 9.7 and 50.2 μM, respectively. The results of the Comet assay showed that AAΙ caused relatively higher damage to cellular DNA (TDNA 40–95%) at 50 μM, while AAΙΙ, AMH and ADS extracts (ranged from 10 to 131 μM) caused relatively lower damage to cellular DNA (TDNA 5–20%). Full article
(This article belongs to the Section Plant Toxins)
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13 pages, 5997 KiB  
Article
Mechanism for the Potential Inhibition Effect of Microcystin-LR Disinfectant By-Products on Protein Phosphatase 2A
by Huiqun Yu, Yixue Xu, Jiyuan Cui and Wansong Zong
Toxins 2022, 14(12), 878; https://doi.org/10.3390/toxins14120878 - 16 Dec 2022
Cited by 1 | Viewed by 1239
Abstract
The secondary contamination of microcystin disinfection by-products (MC-DBPs) is of concern due to the residual structure similar to their original toxin. Based on identification and preparation, the potential inhibition effect of typical MCLR-DBPs (associated with the oxidation of Adda5) on PP2A [...] Read more.
The secondary contamination of microcystin disinfection by-products (MC-DBPs) is of concern due to the residual structure similar to their original toxin. Based on identification and preparation, the potential inhibition effect of typical MCLR-DBPs (associated with the oxidation of Adda5) on PP2A was confirmed in the sequence of MCLR > P1 > P4 > P3 ≈ P2 > P7 ≈ P6 ≈ P5 > P8. To elucidate the molecular mechanism underlying the inhibition effect, the interaction models for typical MCLR-DBPs and PP2A were constructed using a modeling-based-on-ligand-similarity approach, and the candidate interaction parameters between typical MCLR-DBPs and PP2A were obtained by molecular docking. By analyzing the correlation between inhibition data and candidate interaction parameters, the key interaction parameters were filtered as hydrogen bonds “Adda5”←Asn117, “Adda5”←His118, MeAsp3←Arg89, Arg4←Arg214, Arg4→Pro213; ionic bonds Glu6-Arg89, Asp85-Mn12+, Asp57-Mn22+; and metal bonds Glu6-Mn12+, Glu6-Mn22+. With the gradual intensification of chlorination, Adda5 was destroyed to varying degrees. The key interactions changed correspondingly, resulting in the discrepant inhibition effects of typical MCLR-DBPs on PP2A. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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9 pages, 273 KiB  
Article
Predictive Factors for a Successful Treatment Outcome in Patients with Different Voiding Dysfunction Subtypes Who Received Urethral Sphincter Botulinum Injection
by Yao-Lin Kao, Yin-Chien Ou, Kuen-Jer Tsai and Hann-Chorng Kuo
Toxins 2022, 14(12), 877; https://doi.org/10.3390/toxins14120877 - 15 Dec 2022
Viewed by 1291
Abstract
Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, [...] Read more.
Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, non-neurogenic voiding dysfunction. Patients who received urethral sphincter BoNT-A injection for refractory voiding dysfunction due to detrusor underactivity (DU) or urethral sphincter dysfunction were retrospectively reviewed. A successful outcome was defined as a marked improvement as reported in the global response assessment. The study evaluated the therapeutic efficacy of urethral sphincter BoNT-A injections and measured the changes in urodynamic parameters after the procedure in the patients. A total of 181 patients including 138 women and 43 men were included. The overall success rate was 64%. A lower success rate was noted in patients with DU compared to those with urethral sphincter dysfunction in both genders. In the multivariable analysis, recurrent urinary tract infection (UTI) and bladder voiding efficiency (BVE) were positive predictors for a successful outcome, while DU was a negative predictor. Urethral sphincter BoNT-A injection is an effective treatment for refractory non-neurogenic voiding dysfunction. Baseline BVE and history of recurrent UTI positively predict a successful outcome. DU is a negative outcome predictor. Full article
14 pages, 10906 KiB  
Article
Epigallocatechin Gallate and Glutathione Attenuate Aflatoxin B1-Induced Acute Liver Injury in Ducklings via Mitochondria-Mediated Apoptosis and the Nrf2 Signalling Pathway
by Yanan Wang, Jiayu Wu, Lingfeng Wang, Ping Yang, Zuhong Liu, Shahid Ali Rajput, Mubashar Hassan and Desheng Qi
Toxins 2022, 14(12), 876; https://doi.org/10.3390/toxins14120876 - 15 Dec 2022
Cited by 4 | Viewed by 1914
Abstract
Aflatoxin B1 (AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed [...] Read more.
Aflatoxin B1 (AFB1) exists widely in feed and food with severe hazards, posing a serious threat to human and animal health. Epigallocatechin gallate (EGCG) and glutathione (GSH) have been reported as having anti-oxidative and other functions. The present study aimed to investigate the detoxification effect of EGCG and GSH alone or in combination on AFB1 exposure in ducklings. Fifty one-day-old male ducklings were randomly assigned into five experimental groups (n = 10): 1. Control (CTR); 2. 0.3 mg/kg BW AFB1 (AFB1); 3. 0.3 mg/kg BW AFB1 + 100 mg/kg BW EGCG (AFB1 + EGCG); 4. 0.3 mg/kg BW AFB1 + 30 mg/kg BW GSH (AFB1 + GSH); 5. 0.3 mg/kg BW AFB1 + 100 mg/kg BW EGCG + 30 mg/kg BW GSH (AFB1 + EGCG + GSH). The experiment lasted for seven days. Compared with the CTR group, AFB1 reduced growth performance, total serum protein and albumin content, increased serum enzyme activity (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase), and caused pathological damage to the ducklings’ livers. AFB1 exposure increased malondialdehyde content and decreased superoxide dismutase, total antioxidant capacity, catalase, glutathione peroxidase activities, and glutathione content in the liver. EGCG and GSH alone or in combination mitigated these adverse effects. Meanwhile, EGCG and GSH attenuate apoptosis of hepatocytes, and regulated AFB1-induced changes in the abundance of genes contained in the Keap1/Nrf2 signalling and apoptotic pathways. Collectively, these results suggest that EGCG and GSH alleviate the hepatocyte injury induced by AFB1 by inhibiting oxidative stress and attenuating excessive mitochondria-mediated apoptosis. Full article
(This article belongs to the Special Issue Novel Strategies for Biodegradation and Detoxification of Mycotoxins)
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23 pages, 1247 KiB  
Review
Biological and Medical Aspects Related to South American Rattlesnake Crotalus durissus (Linnaeus, 1758): A View from Colombia
by Carlos A. Cañas
Toxins 2022, 14(12), 875; https://doi.org/10.3390/toxins14120875 - 15 Dec 2022
Cited by 2 | Viewed by 2295
Abstract
In Colombia, South America, there is a subspecies of the South American rattlesnake Crotalus durissus, C. d. cumanensis, a snake of the Viperidae family, whose presence has been reduced due to the destruction of its habitat. It is an enigmatic snake [...] Read more.
In Colombia, South America, there is a subspecies of the South American rattlesnake Crotalus durissus, C. d. cumanensis, a snake of the Viperidae family, whose presence has been reduced due to the destruction of its habitat. It is an enigmatic snake from the group of pit vipers, venomous, with large articulated front fangs, special designs on its body, and a characteristic rattle on its tail. Unlike in Brazil, the occurrence of human envenomation by C. durisus in Colombia is very rare and contributes to less than 1% of envenomation caused by snakes. Its venom is a complex cocktail of proteins with different biological effects, which evolved with the purpose of paralyzing the prey, killing it, and starting its digestive process, as well as having defense functions. When its venom is injected into humans as the result of a bite, the victim presents with both local tissue damage and with systemic involvement, including a diverse degree of neurotoxic, myotoxic, nephrotoxic, and coagulopathic effects, among others. Its biological effects are being studied for use in human health, including the possible development of analgesic, muscle relaxant, anti-inflammatory, immunosuppressive, anti-infection, and antineoplastic drugs. Several groups of researchers in Brazil are very active in their contributions in this regard. In this work, a review is made of the most relevant biological and medical aspects related to the South American rattlesnake and of what may be of importance for a better understanding of the snake C. d. cumanensis, present in Colombia and Venezuela. Full article
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14 pages, 2272 KiB  
Article
Candidalysin Is the Hemolytic Factor of Candida albicans
by Selene Mogavero, Sarah Höfs, Alexa N. Lauer, Rita Müller, Sascha Brunke, Stefanie Allert, Franziska Gerwien, Sabrina Groth, Edward Dolk, Duncan Wilson, Thomas Gutsmann and Bernhard Hube
Toxins 2022, 14(12), 874; https://doi.org/10.3390/toxins14120874 - 15 Dec 2022
Cited by 7 | Viewed by 3519
Abstract
Candida albicans produces an important virulence factor, the hypha-associated Ece1-derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. C. albicans has also long been known to be hemolytic, yet the hemolytic factor has not been clearly [...] Read more.
Candida albicans produces an important virulence factor, the hypha-associated Ece1-derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. C. albicans has also long been known to be hemolytic, yet the hemolytic factor has not been clearly identified. Here, we show that candidalysin is the hemolytic factor of C. albicans. Its hemolytic activity is modulated by fragments of another Ece1 peptide, P7. Hemolysis by candidalysin can be neutralized by the purinergic receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS). PPADS also affects candidalysin’s ability to intercalate into synthetic membranes. We also describe the neutralization potential of two anti-candidalysin nanobodies, which are promising candidates for future anti-Candida therapy. This work provides evidence that the historically proposed hemolytic factor of C. albicans is in fact candidalysin and sheds more light on the complex roles of this toxin in C. albicans biology and pathogenicity. Full article
(This article belongs to the Section Mycotoxins)
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16 pages, 759 KiB  
Review
Possible Mechanisms of the Interplay between Drugs and Mycotoxins—Is There a Possible Impact?
by Orphélie Lootens, An Vermeulen, Siska Croubels, Sarah De Saeger, Jan Van Bocxlaer and Marthe De Boevre
Toxins 2022, 14(12), 873; https://doi.org/10.3390/toxins14120873 - 14 Dec 2022
Cited by 5 | Viewed by 2538
Abstract
Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances—such as drugs—in the body by altering [...] Read more.
Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances—such as drugs—in the body by altering their pharmacokinetics and/or pharmacodynamics. The combined effects of chronic drug use and mycotoxin exposure need to be well understood in order to draw valid conclusions and, in due course, to develop guidelines. The aim of this review is to focus on food contaminants, more precisely on mycotoxins, and drugs. First, a description of relevant mycotoxins and their effects on human health and metabolism is presented. The potential for interactions of mycotoxins with drugs using in vitro and in vivo animal experiments is summarized. Predictive software tools for unraveling mycotoxin–drug interactions are proposed and future perspectives on this emerging topic are highlighted with a view to evaluate associated risks and to focus on precision medicine. In vitro and in vivo animal studies have shown that mycotoxins affect CYP450 enzyme activity. An impact from drugs on mycotoxins mediated via CYP450-enzymes is plausible; however, an impact of mycotoxins on drugs is less likely considering the much smaller dose exposure to mycotoxins. Drugs that are CYP450 perpetrators and/or substrates potentially influence the metabolism of mycotoxins, metabolized via these CYP450 enzymes. To date, very little research has been conducted on this matter. The only statistically sound reports describe mycotoxins as victims and drugs as perpetrators in interactions; however, more analysis on mycotoxin–drug interactions needs to be performed. Full article
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15 pages, 1722 KiB  
Article
Characterization of NanR Regulation of Sialidase Production, Sporulation and Enterotoxin Production by Clostridium perfringens Type F Strains Carrying a Chromosomal Enterotoxin Gene
by Jihong Li, Eric Mi, Arhat Pradhan and Bruce A. McClane
Toxins 2022, 14(12), 872; https://doi.org/10.3390/toxins14120872 - 13 Dec 2022
Cited by 1 | Viewed by 1415
Abstract
Clostridium perfringens type F food poisoning (FP) strains produce C. perfringens enterotoxin (CPE) to cause a common bacterial food-borne illness in the United States. During FP, CPE is synthesized in the intestines when C. perfringens sporulates. Besides CPE, FP strains also produce sialidases. [...] Read more.
Clostridium perfringens type F food poisoning (FP) strains produce C. perfringens enterotoxin (CPE) to cause a common bacterial food-borne illness in the United States. During FP, CPE is synthesized in the intestines when C. perfringens sporulates. Besides CPE, FP strains also produce sialidases. Most FP strains carry their cpe gene on the chromosome and all surveyed chromosomal cpe (c-cpe) FP strains produce NanH sialidase or both NanJ and NanH sialidases. NanR has been shown previously to regulate sialidase activity in non-FP strains. The current study investigated whether NanR also regulates sialidase activity or influences sporulation and CPE production for c-cpe FP strains SM101 and 01E809. In sporulation medium, the SM101 nanR null mutant showed lower sialidase activity, sporulation, and CPE production than its wild-type parent, while the 01E809 nanR null mutant showed roughly similar sialidase activity, sporulation, and CPE production as its parent. In vegetative medium, the nanR null mutants of both strains produced more spores than their parents while NanR repressed sialidase activity in SM101 but positively regulated sialidase activity in 01E809. These results demonstrate that NanR regulates important virulence functions of c-cpe strains, with this control varying depending on strain and culture conditions. Full article
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11 pages, 519 KiB  
Article
Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome
by Wan-Ru Yu, Yuan-Hong Jiang, Jia-Fong Jhang, Wei-Chuan Chang and Hann-Chorng Kuo
Toxins 2022, 14(12), 871; https://doi.org/10.3390/toxins14120871 - 11 Dec 2022
Cited by 4 | Viewed by 1448
Abstract
Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS [...] Read more.
Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome. Full article
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10 pages, 569 KiB  
Communication
Occurrence of Aflatoxin M1 in Cow, Goat, Buffalo, Camel, and Yak Milk in China in 2016
by Nan Zheng, Li Min, Dagang Li, Sheng Tan, Yanan Gao and Jiaqi Wang
Toxins 2022, 14(12), 870; https://doi.org/10.3390/toxins14120870 - 10 Dec 2022
Cited by 5 | Viewed by 1442
Abstract
In this present study, 195 cow milk, 100 goat milk, 50 buffalo milk, 50 camel milk, and 50 yak milk samples were collected in China in May and October 2016. The presence of aflatoxin M1 (AFM1) was determined using enzyme-linked immunosorbent assay method. [...] Read more.
In this present study, 195 cow milk, 100 goat milk, 50 buffalo milk, 50 camel milk, and 50 yak milk samples were collected in China in May and October 2016. The presence of aflatoxin M1 (AFM1) was determined using enzyme-linked immunosorbent assay method. For all cow milk samples, 128 samples (65.7%) contained AFM1 in concentrations ranging from 0.005 to 0.191 µg/L, and 6 samples (3.1%) from Sichuan province in October were contaminated with AFM1 above 0.05 µg/L (EU limit). For all goat milk samples, 76.0% of samples contained AFM1 in concentrations ranging from 0.005 to 0.135 µg/L, and 9 samples (9.0%) from Shanxi province in October were contaminated with AFM1 above 0.05 µg/L. For all buffalo milk samples, 24 samples (48.0%) contained AFM1 in concentrations ranging from 0.005 to 0.089 µg/L, and 2 samples collected in October were contaminated with AFM1 above 0.05 µg/L. Furthermore, 28.0% of samples contained AFM1 in concentrations ranging from 0.005 to 0.007 µg/L in camel milk samples, and 18.0% of samples contained AFM1 in concentrations ranging from 0.005 to 0.007 µg/L in yak milk samples. Our survey study has expanded the current knowledge of the occurrence of AFM1 in milk from five dairy species in China, in particular the minor dairy species. Full article
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13 pages, 1201 KiB  
Article
Green Pit Viper Envenomations in Bangkok: A Comparison of Follow-Up Compliance and Clinical Outcomes in Older and Younger Adults
by Rittirak Othong, Thanaphat Eurcherdkul and Prasit Chantawatsharakorn
Toxins 2022, 14(12), 869; https://doi.org/10.3390/toxins14120869 - 10 Dec 2022
Cited by 1 | Viewed by 1921
Abstract
We compared older and younger adults envenomated by the green pit viper (GPV) with regard to the following: follow-up compliance, elapsed time between envenomation and emergency department (ED) visit, and clinical/treatment outcomes. This was a two-site retrospective cohort study. We searched hospital electronic [...] Read more.
We compared older and younger adults envenomated by the green pit viper (GPV) with regard to the following: follow-up compliance, elapsed time between envenomation and emergency department (ED) visit, and clinical/treatment outcomes. This was a two-site retrospective cohort study. We searched hospital electronic medical databases between January 2011 and December 2021. Patients aged 15 and above were eligible if they had a history of snakebite and had at least two VCT and/or platelet count results in their medical records. After the search, 1550 medical records were reviewed and 760 cases were found to be eligible for analysis. In total, 205 cases (27.0%) were ≥60 years old. The median ages in the younger and older groups were 40 (26–51) and 68 (64–75) years, respectively. The median elapsed times from bite to the ED were 47 (30–118) vs. 69 (35–150) min (p-value = 0.001). Overall, 91.3% of all cases were managed as out-patient cases and were eligible for follow-up appointments. The rate of out-patient follow-up at 72 ± 12 h in the older patients was significantly higher (43.2%) than in the younger adult patients (32.4%) (p-value = 0.01). Regarding the clinical/treatment outcomes, the rates of coagulopathy, antivenom administration, and hospital admission were not statistically different between both groups. Full article
(This article belongs to the Special Issue Snakebite and Clinical Toxinology)
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7 pages, 1982 KiB  
Review
Anatomical Proposal for Botulinum Neurotoxin Injection Targeting the Platysma Muscle for Treating Platysmal Band and Jawline Lifting: A Review
by Kyu-Ho Yi, Ji-Hyun Lee, Kangwoo Lee, Hye-Won Hu, Hyung-Jin Lee and Hee-Jin Kim
Toxins 2022, 14(12), 868; https://doi.org/10.3390/toxins14120868 - 10 Dec 2022
Cited by 20 | Viewed by 14441
Abstract
The platysma muscle is a thin superficial muscle that covers the entire neck and lower part of the face. The platysma muscle is the primary target muscle for botulinum neurotoxin injection therapy aimed at treating platysmal band and lower facial lifting. In the [...] Read more.
The platysma muscle is a thin superficial muscle that covers the entire neck and lower part of the face. The platysma muscle is the primary target muscle for botulinum neurotoxin injection therapy aimed at treating platysmal band and lower facial lifting. In the procedure of botulinum neurotoxin injection therapy, a lack of knowledge of the anatomy of the platysma muscle and the properties of botulinum neurotoxin can lead to side effects such as dysphagia, dysphonia, and weakness of the neck muscles. Anatomically safe injection sites have been proposed for the platysma muscle, and the appropriate injection technique has been reviewed. We proposed optimal injection sites based on the external anatomical features of the mandible. The aim of these proposal was to standardize the procedure for the effective use of botulinum neurotoxin injections by minimizing the dose unit and injection points and thereby preventing adverse events. Full article
(This article belongs to the Special Issue Clinical and Anatomical Perspectives of Botulinum Neurotoxin)
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14 pages, 7400 KiB  
Article
Lysine Inhibits Hemolytic Activity of Staphylococcus aureus and Its Application in Food Model Contaminated with Staphylococcus aureus
by Yangli Wan, Xiaowen Wang, Tianyi Bai, Xuting Zheng, Liu Yang, Qianhong Li and Xin Wang
Toxins 2022, 14(12), 867; https://doi.org/10.3390/toxins14120867 - 09 Dec 2022
Cited by 3 | Viewed by 1544
Abstract
Alpha-hemolysin (Hla) is one of the important exotoxins of Staphylococcus aureus (S. aureus) and can be used as a target to reduce the virulence of S. aureus. This study explored the inhibitory effect of Lysine (Lys) on Hla and its application [...] Read more.
Alpha-hemolysin (Hla) is one of the important exotoxins of Staphylococcus aureus (S. aureus) and can be used as a target to reduce the virulence of S. aureus. This study explored the inhibitory effect of Lysine (Lys) on Hla and its application in food safety. Lys significantly inhibited the expression of Hla at sub-inhibitory concentrations and directly interacted with Hla to interfere with its oligomerization and thus significantly inhibited its hemolytic activity. Notably, Lys attenuated S. aureus damage to mouse small intestine and Caco-2 cells and delayed mouse mortality. In the food model, Lys inhibited the expression of Hla of S. aureus and had no significant effect on the sensory score. Moreover, Lys had no obvious damage effect on the main organs of mice, which indicated that Lys has good biocompatibility and has the potential to be used in the food industry as an anti-S. aureus preparation. Full article
(This article belongs to the Special Issue Foodborne Toxins: Advanced Detection and Toxicity)
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15 pages, 2595 KiB  
Article
Development of an Immunofluorescent Capillary Sensor for the Detection of Zearalenone Mycotoxin
by Krisztina Majer-Baranyi, Attila Barócsi, Patrik Gádoros, László Kocsányi, András Székács and Nóra Adányi
Toxins 2022, 14(12), 866; https://doi.org/10.3390/toxins14120866 - 09 Dec 2022
Cited by 1 | Viewed by 1279
Abstract
A capillary-based immunofluorescence sensor was developed and incorporated in a flow injection analysis system. The light-guiding capillary was illuminated axially by a 473 nm/5 mW solid state laser through a tailored optofluidic connector. High sensitivity of the system was achieved by efficiently collecting [...] Read more.
A capillary-based immunofluorescence sensor was developed and incorporated in a flow injection analysis system. The light-guiding capillary was illuminated axially by a 473 nm/5 mW solid state laser through a tailored optofluidic connector. High sensitivity of the system was achieved by efficiently collecting and detecting the non-guided fluorescence signal scattered out along the wall of the capillary. The excitation was highly suppressed with bandpass and dichroic filters by simultaneously exploiting the guiding effect inside the capillary. The glass capillary used as a measuring cell was silanized in liquid phase by 3-aminopropyltriethoxysilane (APTS), and the biomolecules were immobilized using glutaraldehyde inside the capillary. The applicability of the developed system was tested with a bovine serum albumin (BSA)—anti-BSA-IgG model-molecule pair, using a fluorescently labeled secondary antibody. Based on the results of the BSA–anti-BSA experiments, a similar setup using a primary antibody specific for zearalenone (ZON) was established, and a competitive fluorescence measurement system was developed for quantitative determination of ZON. For the measurements, 20 µg/mL ZON-BSA conjugate was immobilized in the capillary, and a 1:2500 dilution of the primary antibody stock solution and a 2 µg/mL secondary antibody solution were set. The developed capillary-based immunosensor allowed a limit of detection (LOD) of 0.003 ng/mL and a limit of quantification (LOQ) of 0.007 ng/mL for ZON in the competitive immunosensor setup, with a dynamic detection range of 0.01–10 ng/mL ZON concentrations. Full article
(This article belongs to the Special Issue Rapid Detection of Mycotoxin Contamination 2.0)
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13 pages, 714 KiB  
Article
Body Composition of Healthy Cats and Cats with Chronic Kidney Disease Fed on a Dry Diet Low in Phosphorus with Maintenance Protein
by Daniela P. Machado, Bruna Ruberti, Fabio A. Teixeira, Thiago H. A. Vendramini, Karina Pfrimer, Fernanda C. Chacar, Julio C. C. Balieiro, Cristiana F. F. Pontieri and Marcio A. Brunetto
Toxins 2022, 14(12), 865; https://doi.org/10.3390/toxins14120865 - 09 Dec 2022
Viewed by 2105
Abstract
The aim was to evaluate the effect of feeding a low-phosphorus and maintenance protein diet in healthy cats and cats with chronic kidney disease (CKD) with IRIS stages 1 (CKD-1) and 2 (CKD-2). Cats were initially fed a senior diet (30 days) followed [...] Read more.
The aim was to evaluate the effect of feeding a low-phosphorus and maintenance protein diet in healthy cats and cats with chronic kidney disease (CKD) with IRIS stages 1 (CKD-1) and 2 (CKD-2). Cats were initially fed a senior diet (30 days) followed by the renal diet (60 days). Body composition, body weight (BW), muscle mass score (MMS), and body condition score (BCS) were assessed before (T30) and after renal diet intake (T60). General mixed linear models were used to assess the effects of fixed groups and moments (T30 × T60), as well as their interaction, in addition to the random effects of animals within each group. Unlike healthy cats and cats with CKD-1, cats with CKD-2 had a loss of BW, lower BCS (p < 0.005), and lower MMS (p = 0.0008) after 60 days of consuming the renal diet. The fat mass and lean body mass (LBM), determined by the deuterium isotopes method, did not change in all cats between T0 and T60. In healthy cats and cats with CKD-1, the renal diet resulted in maintenance of BW, BCS and MMS; but cats with CKD-2 presented lower BCS and did not reduce phosphatemia after consumption. Full article
(This article belongs to the Special Issue Uremic Toxins Lowering Strategies in Chronic Kidney Disease)
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14 pages, 4033 KiB  
Article
Improving the In Vitro Removal of Indoxyl Sulfate and p-Cresyl Sulfate by Coating Diatomaceous Earth (DE) and Poly-vinyl-pyrrolidone-co-styrene (PVP-co-S) with Polydopamine
by Stefania Roberta Cicco, Maria Michela Giangregorio, Maria Teresa Rocchetti, Ighli di Bari, Claudio Mastropaolo, Rossella Labarile, Roberta Ragni, Loreto Gesualdo, Gianluca Maria Farinola and Danilo Vona
Toxins 2022, 14(12), 864; https://doi.org/10.3390/toxins14120864 - 08 Dec 2022
Cited by 2 | Viewed by 1613
Abstract
Polydopamine (PDA) is a synthetic eumelanin polymer mimicking the biopolymer secreted by mussels to attach to surfaces with a high binding strength. It exhibits unique adhesive properties and has recently attracted considerable interest as a multifunctional thin film coating. In this study, we [...] Read more.
Polydopamine (PDA) is a synthetic eumelanin polymer mimicking the biopolymer secreted by mussels to attach to surfaces with a high binding strength. It exhibits unique adhesive properties and has recently attracted considerable interest as a multifunctional thin film coating. In this study, we demonstrate that a PDA coating on silica- and polymer-based materials improves the entrapment and retention of uremic toxins produced in specific diseases. The low-cost natural nanotextured fossil diatomaceous earth (DE), an abundant source of mesoporous silica, and polyvinylpyrrolidone-co-Styrene (PVP-co-S), a commercial absorbent comprising polymeric particles, were easily coated with a PDA layer by oxidative polymerization of dopamine at mild basic aqueous conditions. An in-depth chemical-physical investigation of both the resulting PDA-coated materials was performed by SEM, AFM, UV-visible, Raman spectroscopy and spectroscopic ellipsometry. Finally, the obtained hybrid systems were successfully tested for the removal of two uremic toxins (indoxyl sulfate and p-cresyl sulfate) directly from patients’ sera. Full article
(This article belongs to the Special Issue New Strategies for the Reduction of Uremic Toxins (2022))
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16 pages, 2345 KiB  
Article
The Crystal Structure of Bacillus thuringiensis Tpp80Aa1 and Its Interaction with Galactose-Containing Glycolipids
by Hannah L. Best, Lainey J. Williamson, Magdalena Lipka-Lloyd, Helen Waller-Evans, Emyr Lloyd-Evans, Pierre J. Rizkallah and Colin Berry
Toxins 2022, 14(12), 863; https://doi.org/10.3390/toxins14120863 - 08 Dec 2022
Cited by 7 | Viewed by 2431
Abstract
Tpp80Aa1 from Bacillus thuringiensis is a Toxin_10 family protein (Tpp) with reported action against Culex mosquitoes. Here, we demonstrate an expanded target range, showing Tpp80Aa1 is also active against the larvae of Anopheles gambiae and Aedes aegypti mosquitoes. We report the first crystal [...] Read more.
Tpp80Aa1 from Bacillus thuringiensis is a Toxin_10 family protein (Tpp) with reported action against Culex mosquitoes. Here, we demonstrate an expanded target range, showing Tpp80Aa1 is also active against the larvae of Anopheles gambiae and Aedes aegypti mosquitoes. We report the first crystal structure of Tpp80Aa1 at a resolution of 1.8 Å, which shows Tpp80Aa1 consists of two domains: an N-terminal β-trefoil domain resembling a ricin B lectin and a C-terminal putative pore-forming domain sharing structural similarity with the aerolysin family. Similar to other Tpp family members, we observe Tpp80Aa1 binds to the mosquito midgut, specifically the posterior midgut and the gastric caecum. We also identify that Tpp80Aa1 can interact with galactose-containing glycolipids and galactose, and this interaction is critical for exerting full insecticidal action against mosquito target cell lines. Full article
(This article belongs to the Special Issue Bacillus thuringiensis: A Broader View of Its Biocidal Activity)
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16 pages, 2715 KiB  
Article
Residue Analysis and Assessment of the Risk of Dietary Exposure to Domoic Acid in Shellfish from the Coastal Areas of China
by Guanchao Zheng, Haiyan Wu, Hanyu Che, Xiaokang Li, Zhihua Zhang, Jixing Peng, Mengmeng Guo and Zhijun Tan
Toxins 2022, 14(12), 862; https://doi.org/10.3390/toxins14120862 - 08 Dec 2022
Cited by 5 | Viewed by 1974
Abstract
Harmful algal blooms in Chinese waters have caused serious domoic acid (DA) contamination in shellfish. Although shellfish are at particular risk of dietary exposure to DA, there have been no systematic DA risk assessments in Chinese coastal waters. A total of 451 shellfish [...] Read more.
Harmful algal blooms in Chinese waters have caused serious domoic acid (DA) contamination in shellfish. Although shellfish are at particular risk of dietary exposure to DA, there have been no systematic DA risk assessments in Chinese coastal waters. A total of 451 shellfish samples were collected from March to November 2020. The presence of DA and four of its isomers were detected using liquid chromatography–tandem mass spectrometry. The spatial-temporal distribution of DA occurrence and its potential health risks were examined. DA was detected in 198 shellfish samples (43.90%), with a maximum level of 942.86 μg/kg. DA was recorded in all 14 shellfish species tested and Pacific oysters (Crassostrea gigas) showed the highest average DA concentration (82.36 μg/kg). The DA concentrations in shellfish showed distinct spatial-temporal variations, with significantly higher levels of occurrence in autumn than in summer and spring (p < 0.01), and particularly high occurrence in Guangdong and Fujian Provinces. The detection rates and maximum concentrations of the four DA isomers were low. While C. gigas from Guangdong Province in September showed the highest levels of DA contamination, the risk to human consumers was low. This study improves our understanding of the potential risk of shellfish exposure to DA-residues. Full article
(This article belongs to the Section Marine and Freshwater Toxins)
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29 pages, 1541 KiB  
Review
Toxic Effects Produced by Anatoxin-a under Laboratory Conditions: A Review
by Cristina Plata-Calzado, Ana I. Prieto, Ana M. Cameán and Angeles Jos
Toxins 2022, 14(12), 861; https://doi.org/10.3390/toxins14120861 - 08 Dec 2022
Cited by 7 | Viewed by 2359
Abstract
The presence of cyanotoxins and its bioaccumulation in the food chain is an increasingly common problem worldwide. Despite the toxic effects produced by Anatoxin-a (ATX-a), this neurotoxin has been less studied compared to microcystins (MCs) and cylindrospermopsin (CYN). Studies conducted under laboratory conditions [...] Read more.
The presence of cyanotoxins and its bioaccumulation in the food chain is an increasingly common problem worldwide. Despite the toxic effects produced by Anatoxin-a (ATX-a), this neurotoxin has been less studied compared to microcystins (MCs) and cylindrospermopsin (CYN). Studies conducted under laboratory conditions are of particular interest because these provide information which are directly related to the effects produced by the toxin. Currently, the World Health Organization (WHO) considers the ATX-a toxicological database inadequate to support the publication of a formal guideline reference value. Therefore, the aim of the present work is to compile all of the in vitro and in vivo toxicological studies performed so far and to identify potential data gaps. Results show that the number of reports is increasing in recent years. However, more in vitro studies are needed, mainly in standardized neuronal cell lines. Regarding in vivo studies, very few of them reflect conditions occurring in nature and further studies with longer periods of oral exposure would be of interest. Moreover, additional toxicological aspects of great interest such as mutagenicity, genotoxicity, immunotoxicity and alteration of hormonal balance need to be studied in depth. Full article
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22 pages, 2138 KiB  
Article
Snake Venomics and Antivenomics of Cape Cobra (Naja nivea) from South Africa: Insights into Venom Toxicity and Cross-Neutralization Activity
by Choo Hock Tan, Kin Ying Wong, Li-Kun Huang, Kae Yi Tan, Nget Hong Tan and Wen-Guey Wu
Toxins 2022, 14(12), 860; https://doi.org/10.3390/toxins14120860 - 07 Dec 2022
Cited by 5 | Viewed by 2492
Abstract
Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, [...] Read more.
Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from South Africa. The major components in the venom are cytotoxins/cardiotoxins (~75.6% of total venom proteins) and alpha-neurotoxins (~7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A2 (PLA2) was undetected—this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom. Full article
(This article belongs to the Special Issue Recent Updates in Venomics and Applications)
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22 pages, 446 KiB  
Review
Crosstalk between Mycotoxins and Intestinal Microbiota and the Alleviation Approach via Microorganisms
by Daiyang Xia, Qianyuan Mo, Lin Yang and Wence Wang
Toxins 2022, 14(12), 859; https://doi.org/10.3390/toxins14120859 - 06 Dec 2022
Cited by 2 | Viewed by 2050
Abstract
Mycotoxins are secondary metabolites produced by fungus. Due to their widespread distribution, difficulty in removal, and complicated subsequent harmful by-products, mycotoxins pose a threat to the health of humans and animals worldwide. Increasing studies in recent years have highlighted the impact of mycotoxins [...] Read more.
Mycotoxins are secondary metabolites produced by fungus. Due to their widespread distribution, difficulty in removal, and complicated subsequent harmful by-products, mycotoxins pose a threat to the health of humans and animals worldwide. Increasing studies in recent years have highlighted the impact of mycotoxins on the gut microbiota. Numerous researchers have sought to illustrate novel toxicological mechanisms of mycotoxins by examining alterations in the gut microbiota caused by mycotoxins. However, few efficient techniques have been found to ameliorate the toxicity of mycotoxins via microbial pathways in terms of animal husbandry, human health management, and the prognosis of mycotoxin poisoning. This review seeks to examine the crosstalk between five typical mycotoxins and gut microbes, summarize the functions of mycotoxins-induced alterations in gut microbes in toxicological processes and investigate the application prospects of microbes in mycotoxins prevention and therapy from a variety of perspectives. The work is intended to provide support for future research on the interaction between mycotoxins and gut microbes, and to advance the technology for preventing and controlling mycotoxins. Full article
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