Toxins

18 pages, 7789 KiB

Open AccessEditor’s ChoiceArticle

Environmental Conditions Affecting Ochratoxin A during Solar Drying of Grapes: The Case of Tunnel and Open Air-Drying

by Charalampos Templalexis, Paola Giorni, Diamanto Lentzou, Sabrina Mesisca, Dimitrios I. Tsitsigiannis, Paola Battilani and Georgios Xanthopoulos

Toxins 2021, 13(6), 400; https://doi.org/10.3390/toxins13060400 - 3 Jun 2021

Cited by 8 | Viewed by 2801

Abstract

Drying optimization, to mitigate fungal growth and Ochratoxin A (OTA) contamination is a key topic for raisin and currant production. Specific indicators of environmental conditions and drying properties were analyzed using two seedless grape varieties (Crimson—red and Thompson—white), artificially inoculated [...] Read more.

Drying optimization, to mitigate fungal growth and Ochratoxin A (OTA) contamination is a key topic for raisin and currant production. Specific indicators of environmental conditions and drying properties were analyzed using two seedless grape varieties (Crimson—red and Thompson—white), artificially inoculated with Aspergillus carbonarius under open air and tunnel drying. The air temperature (T), relative humidity, grape surface temperature (T_s) and water activity throughout the drying experiment, the grapes’ moisture content and the fungal colonization and OTA contamination during the drying process and their interactions were recorded and critically analyzed. Drying properties such as the water diffusivity (D_eff) and peel resistance to water transfer were estimated. The grapes T_s was 5–7 °C higher in tunnel vs. open air–drying; the infected grapes had higher maximum T_s vs. the control (around 4–6 °C). OTA contamination was higher in tunnel vs. open air–dried grapes, but fungal colonies showed the opposite trend. The D_eff was higher in tunnel than in the open air–drying by 54%; the infected grapes had more than 70% higher D_eff than the control, differences explained by factors affecting the water transport. This study highlighted CFU and OTA indicators that affect the water availability between red and white grapes during open air and tunnel drying, estimated by the D_eff and peel resistance. This raises new issues for future research. Full article

(This article belongs to the Special Issue Occurrence and Integrated Management of Mycotoxins)

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11 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors

by Yin-Chien Ou, Kuan-Hsun Huang, Hau-Chern Jan, Hann-Chorng Kuo, Yao-Lin Kao and Kuen-Jer Tsai

Toxins 2021, 13(6), 398; https://doi.org/10.3390/toxins13060398 - 2 Jun 2021

Cited by 10 | Viewed by 3270

Abstract

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving [...] Read more.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes. Full article

(This article belongs to the Special Issue Botulinum Toxins: Old and New Applications in Humans and Animals for the Treatment of Lower Urinary Tract Conditions)

21 pages, 4995 KiB

Open AccessEditor’s ChoiceArticle

Cyanobacterial Toxins and Peptides in Lake Vegoritis, Greece

by Sevasti-Kiriaki Zervou, Kimon Moschandreou, Aikaterina Paraskevopoulou, Christophoros Christophoridis, Elpida Grigoriadou, Triantafyllos Kaloudis, Theodoros M. Triantis, Vasiliki Tsiaoussi and Anastasia Hiskia

Toxins 2021, 13(6), 394; https://doi.org/10.3390/toxins13060394 - 1 Jun 2021

Cited by 21 | Viewed by 4865

Abstract

Cyanotoxins (CTs) produced by cyanobacteria in surface freshwater are a major threat for public health and aquatic ecosystems. Cyanobacteria can also produce a wide variety of other understudied bioactive metabolites such as oligopeptides microginins (MGs), aeruginosins (AERs), aeruginosamides (AEGs) and anabaenopeptins (APs). This [...] Read more.

Cyanotoxins (CTs) produced by cyanobacteria in surface freshwater are a major threat for public health and aquatic ecosystems. Cyanobacteria can also produce a wide variety of other understudied bioactive metabolites such as oligopeptides microginins (MGs), aeruginosins (AERs), aeruginosamides (AEGs) and anabaenopeptins (APs). This study reports on the co-occurrence of CTs and cyanopeptides (CPs) in Lake Vegoritis, Greece and presents their variant-specific profiles obtained during 3-years of monitoring (2018–2020). Fifteen CTs (cylindrospermopsin (CYN), anatoxin (ATX), nodularin (NOD), and 12 microcystins (MCs)) and ten CPs (3 APs, 4 MGs, 2 AERs and aeruginosamide (AEG A)) were targeted using an extended and validated LC-MS/MS protocol for the simultaneous determination of multi-class CTs and CPs. Results showed the presence of MCs (MC-LR, MC-RR, MC-YR, dmMC-LR, dmMC-RR, MC-HtyR, and MC-HilR) and CYN at concentrations of <1 μg/L, with MC-LR (79%) and CYN (71%) being the most frequently occurring. Anabaenopeptins B (AP B) and F (AP F) were detected in almost all samples and microginin T1 (MG T1) was the most abundant CP, reaching 47.0 μg/L. This is the first report of the co-occurrence of CTs and CPs in Lake Vegoritis, which is used for irrigation, fishing and recreational activities. The findings support the need for further investigations of the occurrence of CTs and the less studied cyanobacterial metabolites in lakes, to promote risk assessment with relevance to human exposure. Full article

(This article belongs to the Special Issue Cyanotoxins in Bloom: Ever-Increasing Occurrence and Global Distribution of Freshwater Cyanotoxins from Planktic and Benthic Cyanobacteria)

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17 pages, 929 KiB

Open AccessEditor’s ChoiceArticle

Post-Contrast Acute Kidney Injury in Patients with Various Stages of Chronic Kidney Disease—Is Fear Justified?

by Inga Chomicka, Marlena Kwiatkowska, Alicja Lesniak and Jolanta Malyszko

Toxins 2021, 13(6), 395; https://doi.org/10.3390/toxins13060395 - 1 Jun 2021

Cited by 6 | Viewed by 3690

Abstract

Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We [...] Read more.

Post-contrast acute kidney injury (PC-AKI) is one of the side effects of iodinated contrast media, including those used in computed tomography. Its incidence seems exaggerated, and thus we decided to try estimate that number and investigate its significance in our clinical practice. We analyzed all computed tomographies performed in our clinic in 2019, including data about the patient and the procedure. In each case, we recorded the parameters of kidney function (serum creatinine concentration and eGFR) in four time intervals: before the test, immediately after the test, 14–28 days after the test, and over 28 days after the test. Patients who did not have a follow-up after computed tomography were excluded. After reviewing 706 CT scans performed in 2019, we included 284 patients undergoing contrast-enhanced CT and 67 non-enhanced CT in the final analysis. On this basis, we created two comparable groups in terms of age, gender, the severity of chronic kidney disease, and the number of comorbidities. We found that AKI was more common in the non-enhanced CT population (25.4% vs. 17.9%). In terms of our experience, it seems that PC-AKI is not a great risk for patients, even those with chronic kidney disease. Consequently, the fear of using contrast agents is not justified. Full article

(This article belongs to the Special Issue Uremic Toxins and Urinary Acute Kidney Injury Biomarkers)

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14 pages, 1779 KiB

Open AccessEditor’s ChoiceArticle

Physiological Effects of Deoxynivalenol from Naturally Contaminated Corn on Cerebral Tryptophan Metabolism, Behavioral Response, Gastrointestinal Immune Status and Health in Pigs Following a Pair-Feeding Model

by Yan-Bin Shen, Alexandra C. Weaver and Sung Woo Kim

Toxins 2021, 13(6), 393; https://doi.org/10.3390/toxins13060393 - 30 May 2021

Cited by 13 | Viewed by 4298

Abstract

This study investigated the impact of deoxynivalenol (DON) from naturally contaminated feed on pig growth, immune status, organ health, brain serotonin (5-Hydroxytryptamine, 5-HT) and behavior. Sixteen individually housed pigs (25.57 ± 0.98 kg, age 9 weeks) were randomly allotted to two dietary treatments: [...] Read more.

This study investigated the impact of deoxynivalenol (DON) from naturally contaminated feed on pig growth, immune status, organ health, brain serotonin (5-Hydroxytryptamine, 5-HT) and behavior. Sixteen individually housed pigs (25.57 ± 0.98 kg, age 9 weeks) were randomly allotted to two dietary treatments: without DON (CON) or with 3.8 mg/kg of DON (MT). Pigs were pair-fed to eliminate differences in feed intake (equal tryptophan (Trp) intake). Pigs fed CON received a daily ration based on the ad libitum feed consumption of their MT pair-mate. Performance was determined over 21 days and blood collected for immunological and oxidative stress parameters. Behavior was recorded for 12 h on days 0, 7, 14 and 21. After 21 days, pigs were euthanized to collect tissues for immune parameters, gut morphology and brain serotonin levels. Overall, pigs fed MT had greater weight gain compared with CON. Immunological and oxidative stress parameters were unaffected, but pigs fed MT had reduced villus height, crypt depth and villus-to-crypt ratio in the jejunum. Pigs consuming MT had reduced concentration of 5-HT and increased 5-HT turnover in the hypothalamus. Mycotoxin-fed pigs spent more time lying and sitting, and less time standing and drinking. In conclusion, consumption of DON impacted gastrointestinal tract structure, altered behavior and changed Trp metabolism through increasing 5-HT turnover in hypothalamus. Full article

(This article belongs to the Special Issue Risk Assessment of Mycotoxins in Feed and Food)

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25 pages, 1824 KiB

Open AccessEditor’s ChoiceReview

Analytical Separation of Carcinogenic and Genotoxic Alkenylbenzenes in Foods and Related Products (2010–2020)

by Huynh N. P. Dang and Joselito P. Quirino

Toxins 2021, 13(6), 387; https://doi.org/10.3390/toxins13060387 - 28 May 2021

Cited by 7 | Viewed by 4343

Abstract

Alkenylbenzenes are potentially toxic (genotoxic and carcinogenic) compounds present in plants such as basil, tarragon, anise star and lemongrass. These plants are found in various edible consumer products, e.g., popularly used to flavour food. Thus, there are concerns about the possible health consequences [...] Read more.

Alkenylbenzenes are potentially toxic (genotoxic and carcinogenic) compounds present in plants such as basil, tarragon, anise star and lemongrass. These plants are found in various edible consumer products, e.g., popularly used to flavour food. Thus, there are concerns about the possible health consequences upon increased exposure to alkenylbenzenes especially due to food intake. It is therefore important to constantly monitor the amounts of alkenylbenzenes in our food chain. A major challenge in the determination of alkenylbenzenes in foods is the complexity of the sample matrices and the typically low amounts of alkenylbenzenes present. This review will therefore discuss the background and importance of analytical separation methods from papers reported from 2010 to 2020 for the determination of alkenylbenzenes in foods and related products. The separation techniques commonly used were gas and liquid chromatography (LC). The sample preparation techniques used in conjunction with the separation techniques were various variants of extraction (solvent extraction, liquid-liquid extraction, liquid-phase microextraction, solid phase extraction) and distillation (steam and hydro-). Detection was by flame ionisation and mass spectrometry (MS) in gas chromatography (GC) while in liquid chromatography was mainly by spectrophotometry. Full article

(This article belongs to the Special Issue Detection and Control of Plant and Fungal Metabolites: An Application in Human Life)

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21 pages, 4015 KiB

Open AccessEditor’s ChoiceArticle

Changes in the Intestinal Histomorphometry, the Expression of Intestinal Tight Junction Proteins, and the Bone Structure and Liver of Pre-Laying Hens Following Oral Administration of Fumonisins for 21 Days

by Ewa Tomaszewska, Halyna Rudyk, Piotr Dobrowolski, Janine Donaldson, Izabela Świetlicka, Iwona Puzio, Daniel Kamiński, Dariusz Wiącek, Volodymyr Kushnir, Oksana Brezvyn, Viktor Muzyka, Renata Doraczyńska, Siemowit Muszyński and Ihor Kotsyumbas

Toxins 2021, 13(6), 375; https://doi.org/10.3390/toxins13060375 - 25 May 2021

Cited by 20 | Viewed by 4214

Abstract

Fumonisins (FB) are metabolites found in cereal grains (including maize), crop products, and pelleted feed. There is a dearth of information concerning the effects of FB intoxication on the intestinal histomorphometry, the expression of intestinal tight junction proteins, and the bone structure and [...] Read more.

Fumonisins (FB) are metabolites found in cereal grains (including maize), crop products, and pelleted feed. There is a dearth of information concerning the effects of FB intoxication on the intestinal histomorphometry, the expression of intestinal tight junction proteins, and the bone structure and liver in pre-laying hens. The current experiment was carried out on hens from the 11th to the 14th week of age. The hens were orally administered an extract containing fumonisin B1 (FB1) and fumonisin B2 (FB2) at doses of 0.0 mg/kg b.w. (body weight), 1.0 mg/kg b.w., 4.0 mg/kg b.w., and 10.9 mg/kg b.w. for 21 days. Following FB intoxication, the epithelial integrity of the duodenum and jejunum was disrupted, and dose-dependent degenerative changes were observed in liver. An increased content of immature collagen was observed in the bone tissue of FB-intoxicated birds, indicating intensified bone turnover. A similar effect was observed with regards to the articular cartilage, where enhanced fibrillogenesis was observed mainly in the group of birds that received the FB extract at a dose of 10.9 mg/kg b.w. In conclusion, FB intoxication resulted in negative structural changes in the bone tissue of the hens, which could result in worsened bone mechanics and an increase in the risk of bone fractures. Fumonisin administration, even at a dose of 1.0 mg/kg b.w., can lead to degradation of the intestinal barrier and predispose hens to intestinal disturbances later in life. Full article

(This article belongs to the Special Issue Removal and Control of Mycotoxins Contamination)

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26 pages, 1627 KiB

Open AccessEditor’s ChoiceSystematic Review

Impact of Fusarium-Derived Mycoestrogens on Female Reproduction: A Systematic Review

by Carolyn W. Kinkade, Zorimar Rivera-Núñez, Ludwik Gorcyzca, Lauren M. Aleksunes and Emily S. Barrett

Toxins 2021, 13(6), 373; https://doi.org/10.3390/toxins13060373 - 24 May 2021

Cited by 34 | Viewed by 5289

Abstract

Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has [...] Read more.

Contamination of the world’s food supply and animal feed with mycotoxins is a growing concern as global temperatures rise and promote the growth of fungus. Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium fungi, is a common contaminant of cereal grains and has also been detected at lower levels in meat, milk, and spices. ZEN’s synthetic derivative, zeranol, is used as a growth promoter in United States (US) and Canadian beef production. Experimental research suggests that ZEN and zeranol disrupt the endocrine and reproductive systems, leading to infertility, polycystic ovarian syndrome-like phenotypes, pregnancy loss, and low birth weight. With widespread human dietary exposure and growing experimental evidence of endocrine-disrupting properties, a comprehensive review of the impact of ZEN, zeranol, and their metabolites on the female reproductive system is warranted. The objective of this systematic review was to summarize the in vitro, in vivo, and epidemiological literature and evaluate the potential impact of ZEN, zeranol, and their metabolites (commonly referred to as mycoestrogens) on female reproductive outcomes. We conducted a systematic review (PROSPERO registration CRD42020166469) of the literature (2000–2020) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data sources were primary literature published in English obtained from searching PubMed, Web of Science, and Scopus. The ToxR tool was applied to assess risk of bias. In vitro and in vivo studies (n = 104) were identified and, overall, evidence consistently supported adverse effects of mycoestrogens on physiological processes, organs, and tissues associated with female reproduction. In non-pregnant animals, mycoestrogens alter follicular profiles in the ovary, disrupt estrus cycling, and increase myometrium thickness. Furthermore, during pregnancy, mycoestrogen exposure contributes to placental hemorrhage, stillbirth, and impaired fetal growth. No epidemiological studies fitting the inclusion criteria were identified. Full article

(This article belongs to the Special Issue Toxic Effect of Mycotoxins)

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11 pages, 619 KiB

Open AccessEditor’s ChoiceArticle

Early Botulinum Toxin Type A Injection for Post-Stroke Spasticity: A Longitudinal Cohort Study

by Alessandro Picelli, Andrea Santamato, Michela Cosma, Alessio Baricich, Carmelo Chisari, Marzia Millevolte, Cristina Del Prete, Ilenia Mazzù, Paolo Girardi and Nicola Smania

Toxins 2021, 13(6), 374; https://doi.org/10.3390/toxins13060374 - 24 May 2021

Cited by 24 | Viewed by 5665

Abstract

Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke [...] Read more.

Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke onset and initial BoNT-A injection has an effect on outcomes after PSS treatment. This multicenter, longitudinal, cohort study included stroke patients (time since onset <12 months) with PSS who received BoNT-A for the first time according to routine practice. The main outcome was the modified Ashworth scale (MAS). Patients were evaluated before BoNT-A injection and then at 4, 12, and 24 weeks of follow-up. Eighty-three patients with PSS were enrolled. MAS showed a significant decrease in PSS at 4 and 12 weeks but not at 24 weeks after treatment. Among the patients with a time between stroke onset and BoNT-A injection >90 days, the MAS were higher at 4 and 12 weeks than at 24 weeks compared to those injected ≤90 days since stroke. Our findings suggest that BoNT-A treatment for PSS should be initiated within 3 months after stroke onset in order to obtain a greater reduction in muscle tone at 1 and 3 months afterwards. Full article

(This article belongs to the Special Issue Botulinum Toxin Treatment for Spasticity and Pain)

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14 pages, 1823 KiB

Open AccessEditor’s ChoiceArticle

Controlled Production of Zearalenone-Glucopyranoside Standards with Cunninghamella Strains Using Sulphate-Depleted Media

by Jeroen Peters, Edward Ash, Arjen Gerssen, Ruud Van Dam, Maurice C. R. Franssen and Michel W. F. Nielen

Toxins 2021, 13(6), 366; https://doi.org/10.3390/toxins13060366 - 21 May 2021

Cited by 4 | Viewed by 2835

Abstract

In recent years, conjugated mycotoxins have gained increasing interest in food safety, as their hydrolysis in human and animal intestines leads to an increase in toxicity. For the production of zearalenone (ZEN) glycosides reference standards, we applied Cunninghamellaelegans and Cunninghamella echinulata fungal [...] Read more.

In recent years, conjugated mycotoxins have gained increasing interest in food safety, as their hydrolysis in human and animal intestines leads to an increase in toxicity. For the production of zearalenone (ZEN) glycosides reference standards, we applied Cunninghamellaelegans and Cunninghamella echinulata fungal strains. A sulphate-depleted medium was designed for the preferred production of ZEN glycosides. Both Cunninghamella strains were able to produce zearalenone-14-β-D-glucopyranoside (Z14G), zearalenone-16-β-D-glucopyranoside (Z16G) and zearalenone-14-sulphate (Z14S). In a rich medium, Cunninghamellaelegans preferably produced Z14S, while Cunninghamellaechinulata preferably produced Z14G. In the sulphate-depleted medium a dramatic change was observed for Cunninghamellaelegans, showing preferred production of Z14G and Z16G. From 2 mg of ZEN in sulphate-depleted medium, 1.94 mg of Z14G and 0.45 mg of Z16G were produced. Following preparative Liquid Chromatography-Mass Spectrometry (LC-MS) purification, both fractions were submitted to ¹H and ¹³C NMR and High-Resolution Mass Spectrometry (HRMS). These analyses confirmed that the purified fractions were indeed Z14G and Z16G. In conclusion, the presented research shows that a single Cunninghamella strain can be an effective and efficient tool for the controlled biotransformation of ZEN glycosides and other ZEN metabolites. Additionally, the biotransformation method was extended to zearalanone, β-zearalenol and other mycotoxins. Full article

(This article belongs to the Special Issue Metabolism of Mycotoxins by Animals and Microbes)

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15 pages, 5035 KiB

Open AccessEditor’s ChoiceReview

The Role of Ultrasound for the Personalized Botulinum Toxin Treatment of Cervical Dystonia

by Urban M. Fietzek, Devavrat Nene, Axel Schramm, Silke Appel-Cresswell, Zuzana Košutzká, Uwe Walter, Jörg Wissel, Steffen Berweck, Sylvain Chouinard and Tobias Bäumer

Toxins 2021, 13(5), 365; https://doi.org/10.3390/toxins13050365 - 20 May 2021

Cited by 18 | Viewed by 6579

Abstract

The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among [...] Read more.

The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among experts that some of the most relevant muscles in this indication can be safely injected under visual US guidance. This review will explore the method from basic technical considerations, current evidence to conceptual developments of the phenomenology of cervical dystonia. We will review the implications of introducing US to our understanding of muscle function and anatomy of common cervical dystonic patterns. We suggest a flow chart for the use of US to achieve a personalized treatment of people with CD. Thus, we hope to contribute a resource that is useful in clinical practice and that stimulates the ongoing development of this valuable technique. Full article

(This article belongs to the Special Issue Botulinum Toxin for the Treatment of Neurological Disorders—Where We Are and Where We Need to Go)

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15 pages, 2361 KiB

Open AccessEditor’s ChoiceArticle

Different Biological Activities of Histidine-Rich Peptides Are Favored by Variations in Their Design

by Morane Lointier, Candice Dussouillez, Elise Glattard, Antoine Kichler and Burkhard Bechinger

Toxins 2021, 13(5), 363; https://doi.org/10.3390/toxins13050363 - 20 May 2021

Cited by 10 | Viewed by 3426

Abstract

The protein transduction and antimicrobial activities of histidine-rich designer peptides were investigated as a function of their sequence and compared to gene transfection, lentivirus transduction and calcein release activities. In membrane environments, the peptides adopt helical conformations where the positioning of the histidine [...] Read more.

The protein transduction and antimicrobial activities of histidine-rich designer peptides were investigated as a function of their sequence and compared to gene transfection, lentivirus transduction and calcein release activities. In membrane environments, the peptides adopt helical conformations where the positioning of the histidine side chains defines a hydrophilic angle when viewed as helical wheel. The transfection of DNA correlates with calcein release in biophysical experiments, being best for small hydrophilic angles supporting a model where lysis of the endosomal membrane is the limiting factor. In contrast, antimicrobial activities show an inverse correlation suggesting that other interactions and mechanisms dominate within the bacterial system. Furthermore, other derivatives control the lentiviral transduction enhancement or the transport of proteins into the cells. Here, we tested the transport into human cell lines of luciferase (63 kDa) and the ribosome-inactivating toxin saporin (30 kDa). Notably, depending on the protein, different peptide sequences are required for the best results, suggesting that the interactions are manifold and complex. As such, designed LAH4 peptides assure a large panel of biological and biophysical activities whereby the optimal result can be tuned by the physico-chemical properties of the sequences. Full article

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

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16 pages, 3695 KiB

Open AccessEditor’s ChoiceReview

by Kensei Taguchi, Kei Fukami, Bertha C. Elias and Craig R. Brooks

Toxins 2021, 13(5), 361; https://doi.org/10.3390/toxins13050361 - 19 May 2021

Cited by 25 | Viewed by 5963

Abstract

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually [...] Read more.

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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22 pages, 698 KiB

Open AccessEditor’s ChoiceReview

Dissecting the Environmental Consequences of Bacillus thuringiensis Application for Natural Ecosystems

by Maria E. Belousova, Yury V. Malovichko, Anton E. Shikov, Anton A. Nizhnikov and Kirill S. Antonets

Toxins 2021, 13(5), 355; https://doi.org/10.3390/toxins13050355 - 16 May 2021

Cited by 36 | Viewed by 9297

Abstract

Bacillus thuringiensis (Bt), a natural pathogen of different invertebrates, primarily insects, is widely used as a biological control agent. While Bt-based preparations are claimed to be safe for non-target organisms due to the immense host specificity of the bacterium, the [...] Read more.

Bacillus thuringiensis (Bt), a natural pathogen of different invertebrates, primarily insects, is widely used as a biological control agent. While Bt-based preparations are claimed to be safe for non-target organisms due to the immense host specificity of the bacterium, the growing evidence witnesses the distant consequences of their application for natural communities. For instance, upon introduction to soil habitats, Bt strains can affect indigenous microorganisms, such as bacteria and fungi, and further establish complex relationships with local plants, ranging from a mostly beneficial demeanor, to pathogenesis-like plant colonization. By exerting a direct effect on target insects, Bt can indirectly affect other organisms in the food chain. Furthermore, they can also exert an off-target activity on various soil and terrestrial invertebrates, and the frequent acquisition of virulence factors unrelated to major insecticidal toxins can extend the Bt host range to vertebrates, including humans. Even in the absence of direct detrimental effects, the exposure to Bt treatment may affect non-target organisms by reducing prey base and its nutritional value, resulting in delayed alleviation of their viability. The immense phenotypic plasticity of Bt strains, coupled with the complexity of ecological relationships they can engage in, indicates that further assessment of future Bt-based pesticides’ safety should consider multiple levels of ecosystem organization and extend to a wide variety of their inhabitants. Full article

(This article belongs to the Special Issue The Pivotal Role of Toxins in Insects-Bacteria Interactions)

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15 pages, 1882 KiB

Open AccessEditor’s ChoiceReview

Shining a Light on Colibactin Biology

by Michael W. Dougherty and Christian Jobin

Toxins 2021, 13(5), 346; https://doi.org/10.3390/toxins13050346 - 12 May 2021

Cited by 42 | Viewed by 9633

Abstract

Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this [...] Read more.

Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks⁺ E. coli in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin’s structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine. Full article

(This article belongs to the Special Issue Escherichia coli Toxins and Intestinal Diseases)

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13 pages, 584 KiB

Open AccessEditor’s ChoiceArticle

Duvernoy’s Gland Transcriptomics of the Plains Black-Headed Snake, Tantilla nigriceps (Squamata, Colubridae): Unearthing the Venom of Small Rear-Fanged Snakes

by Erich P. Hofmann, Rhett M. Rautsaw, Andrew J. Mason, Jason L. Strickland and Christopher L. Parkinson

Toxins 2021, 13(5), 336; https://doi.org/10.3390/toxins13050336 - 6 May 2021

Cited by 10 | Viewed by 5005

Abstract

The venoms of small rear-fanged snakes (RFS) remain largely unexplored, despite increased recognition of their importance in understanding venom evolution more broadly. Sequencing the transcriptome of venom-producing glands has greatly increased the ability of researchers to examine and characterize the toxin repertoire of [...] Read more.

The venoms of small rear-fanged snakes (RFS) remain largely unexplored, despite increased recognition of their importance in understanding venom evolution more broadly. Sequencing the transcriptome of venom-producing glands has greatly increased the ability of researchers to examine and characterize the toxin repertoire of small taxa with low venom yields. Here, we use RNA-seq to characterize the Duvernoy’s gland transcriptome of the Plains Black-headed Snake, Tantilla nigriceps, a small, semi-fossorial colubrid that feeds on a variety of potentially dangerous arthropods including centipedes and spiders. We generated transcriptomes of six individuals from three localities in order to both characterize the toxin expression of this species for the first time, and to look for initial evidence of venom variation in the species. Three toxin families—three-finger neurotoxins (3FTxs), cysteine-rich secretory proteins (CRISPs), and snake venom metalloproteinases (SVMPIIIs)—dominated the transcriptome of T. nigriceps; 3FTx themselves were the dominant toxin family in most individuals, accounting for as much as 86.4% of an individual’s toxin expression. Variation in toxin expression between individuals was also noted, with two specimens exhibiting higher relative expression of c-type lectins than any other sample (8.7–11.9% compared to <1%), and another expressed CRISPs higher than any other toxin. This study provides the first Duvernoy’s gland transcriptomes of any species of Tantilla, and one of the few transcriptomic studies of RFS not predicated on a single individual. This initial characterization demonstrates the need for further study of toxin expression variation in this species, as well as the need for further exploration of small RFS venoms. Full article

(This article belongs to the Section Animal Venoms)

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19 pages, 5267 KiB

Open AccessEditor’s ChoiceArticle

Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

by Jessica Matos Kleiz-Ferreira, Nuria Cirauqui, Edson Araujo Trajano, Marcius da Silva Almeida and Russolina Benedeta Zingali

Toxins 2021, 13(5), 328; https://doi.org/10.3390/toxins13050328 - 30 Apr 2021

Cited by 3 | Viewed by 4076

Abstract

Studies on 3FTxs around the world are showing the amazing diversity in these proteins both in structure and function. In Brazil, we have not realized the broad variety of their amino acid sequences and probable diversified structures and targets. In this context, this [...] Read more.

Studies on 3FTxs around the world are showing the amazing diversity in these proteins both in structure and function. In Brazil, we have not realized the broad variety of their amino acid sequences and probable diversified structures and targets. In this context, this work aims to conduct an in silico systematic study on available 3FTxs found in Micrurus species from Brazil. We elaborated a specific guideline for this toxin family. First, we grouped them according to their structural homologue predicted by HHPred server and further curated manually. For each group, we selected one sequence and constructed a representative structural model. By looking at conserved features and comparing with the information available in the literature for this toxin family, we managed to point to potential biological functions. In parallel, the phylogenetic relationship was estimated for our database by maximum likelihood analyses and a phylogenetic tree was constructed including the homologous 3FTx previously characterized. Our results highlighted an astonishing diversity inside this family of toxins, showing some groups with expected functional similarities to known 3FTxs, and pointing out others with potential novel roles and perhaps structures. Moreover, this classification guideline may be useful to aid future studies on these abundant toxins. Full article

(This article belongs to the Section Animal Venoms)

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45 pages, 1100 KiB

Open AccessEditor’s ChoiceReview

Algal Toxic Compounds and Their Aeroterrestrial, Airborne and other Extremophilic Producers with Attention to Soil and Plant Contamination: A Review

by Georg Gӓrtner, Maya Stoyneva-Gӓrtner and Blagoy Uzunov

Toxins 2021, 13(5), 322; https://doi.org/10.3390/toxins13050322 - 29 Apr 2021

Cited by 37 | Viewed by 7672

Abstract

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. [...] Read more.

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. There is a growing body of evidence that algal toxins and their producers occur in all general types of extreme habitats, and cyanobacteria/cyanoprokaryotes dominate in most of them. Altogether, 55 toxigenic algal genera (47 cyanoprokaryotes) were enlisted, and our analysis showed that besides the “standard” toxins, routinely known from different waterbodies (microcystins, nodularins, anatoxins, saxitoxins, cylindrospermopsins, BMAA, etc.), they can produce some specific toxic compounds. Whether the toxic biomolecules are related with the harsh conditions on which algae have to thrive and what is their functional role may be answered by future studies. Therefore, we outline the gaps in knowledge and provide ideas for further research, considering, from one side, the health risk from phycotoxins on the background of the global warming and eutrophication and, from the other side, the current surge of interest which phycotoxins provoke due to their potential as novel compounds in medicine, pharmacy, cosmetics, bioremediation, agriculture and all aspects of biotechnological implications in human life. Full article

(This article belongs to the Special Issue Ecology of Aerophytic and Freshwater Cyanobacteria and Algae with Special Reference to Toxic Species)

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14 pages, 1366 KiB

Open AccessEditor’s ChoiceArticle

In-Host Emergence of Linezolid Resistance in a Complex Pattern of Toxic Shock Syndrome Toxin-1-Positive Methicillin-Resistant Staphylococcus aureus Colonization in Siblings with Cystic Fibrosis

by Agathe Boudet, Alexandre Jay, Catherine Dunyach-Remy, Raphaël Chiron, Jean-Philippe Lavigne and Hélène Marchandin

Toxins 2021, 13(5), 317; https://doi.org/10.3390/toxins13050317 - 28 Apr 2021

Cited by 5 | Viewed by 3027

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) can cause chronic lung infections in patients with Cystic Fibrosis (CF). One option for managing them is the use of linezolid. We hereby report the in-host emergence of linezolid resistance (LR) in MRSA in CF siblings via a population [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause chronic lung infections in patients with Cystic Fibrosis (CF). One option for managing them is the use of linezolid. We hereby report the in-host emergence of linezolid resistance (LR) in MRSA in CF siblings via a population analysis. A collection of 171 MRSA strains from 68 samples were characterized by determining their linezolid Minimal Inhibitory Concentrations (MICs), analyzing the locus of staphylococcal protein A (spa) and whole genome sequencing. Courses of linezolid were retraced. Strains belonged to three spa types (t002, t045, t127) and two sequence types (ST1, ST5). Emergence of LR occurred under treatment, one year apart in both siblings, in the CC5-MRSA-I Geraldine clone harboring the toxic shock syndrome toxin-1-encoding gene. Resistance was related to a G2576T substitution present in a variable number of 23S rRNA gene copies. Susceptible and resistant strains were co-isolated within samples. Single Nucleotide Polymorphism-based analysis revealed complex colonizations by highly diversified, clonally related populations. LR remains rare in MRSA and there are very few longitudinal analyses documenting its emergence. Analyzing a large MRSA collection revealed new aspects of LR emergence: it emerges in specific subclonal lineages resulting from adaptive diversification of MRSA in the CF lung and this heterogeneity of intra-sample resistance may contribute to compromising antibiotic management. Full article

(This article belongs to the Special Issue Resistance to Staphylococcus aureus Toxins)

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23 pages, 2092 KiB

Open AccessEditor’s ChoiceReview

Development and Limitations of Exposure Biomarkers to Dietary Contaminants Mycotoxins

by Paul C. Turner and Jessica A. Snyder

Toxins 2021, 13(5), 314; https://doi.org/10.3390/toxins13050314 - 28 Apr 2021

Cited by 33 | Viewed by 3859

Abstract

Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated [...] Read more.

Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated exposure biomarkers better tools for informing epidemiological investigations. While biomarkers of exposure have served important roles for understanding the public health impact of mycotoxins such as aflatoxins (AF), the science of biomarkers must continue advancing to allow for better understanding of mycotoxins’ roles in the etiology of disease and the effectiveness of mitigation strategies. This review will discuss mycotoxin biomarker development approaches over several decades for four toxins of significant public health concerns, AFs, fumonisins (FB), deoxynivalenol (DON), and ochratoxin A (OTA). This review will also highlight some knowledge gaps, key needs and potential pitfalls in mycotoxin biomarker interpretation. Full article

(This article belongs to the Special Issue Biomonitoring of Mycotoxins)

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26 pages, 557 KiB

Open AccessEditor’s ChoiceReview

Shiga Toxin-Associated Hemolytic Uremic Syndrome: Specificities of Adult Patients and Implications for Critical Care Management

by Benoit Travert, Cédric Rafat, Patricia Mariani, Aurélie Cointe, Antoine Dossier, Paul Coppo and Adrien Joseph

Toxins 2021, 13(5), 306; https://doi.org/10.3390/toxins13050306 - 26 Apr 2021

Cited by 24 | Viewed by 4855

Abstract

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. [...] Read more.

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a form of thrombotic microangiopathy secondary to an infection by an enterohemorrhagic E. coli. Historically considered a pediatric disease, its presentation has been described as typical, with bloody diarrhea at the forefront. However, in adults, the clinical presentation is more diverse and makes the early diagnosis hazardous. In this review, we review the epidemiology, most important outbreaks, physiopathology, clinical presentation and prognosis of STEC-HUS, focusing on the differential features between pediatric and adult disease. We show that the clinical presentation of STEC-HUS in adults is far from typical and marked by the prevalence of neurological symptoms and a poorer prognosis. Of note, we highlight knowledge gaps and the need for studies dedicated to adult patients. The differences between pediatric and adult patients have implications for the treatment of this disease, which remains a public health threat and lack a specific treatment. Full article

(This article belongs to the Special Issue Pathogenesis of Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections)

13 pages, 317 KiB

Open AccessEditor’s ChoiceArticle

Mycotoxin Occurrence and Risk Assessment in Gluten-Free Pasta through UHPLC-Q-Exactive Orbitrap MS

by Josefa Tolosa, Yelko Rodríguez-Carrasco, Giulia Graziani, Anna Gaspari, Emilia Ferrer, Jordi Mañes and Alberto Ritieni

Toxins 2021, 13(5), 305; https://doi.org/10.3390/toxins13050305 - 25 Apr 2021

Cited by 15 | Viewed by 3751

Abstract

Celiac disease (CD) is a genetic-based autoimmune disorder which is characterized by inflammation in the small intestinal mucosa due to the intolerance to gluten. Celiac people should consume products without gluten, which are elaborated mainly with maize or other cereals. Contamination of cereals [...] Read more.

Celiac disease (CD) is a genetic-based autoimmune disorder which is characterized by inflammation in the small intestinal mucosa due to the intolerance to gluten. Celiac people should consume products without gluten, which are elaborated mainly with maize or other cereals. Contamination of cereals with mycotoxins, such as fumonisins (FBs) and aflatoxins (AFs) is frequently reported worldwide. Therefore, food ingestion is the main source of mycotoxin exposure. A new analytical method was developed and validated for simultaneous analysis of 21 mycotoxins in gluten-free pasta, commonly consumed by celiac population as an alternative to conventional pasta. Ultrahigh-performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was used for analyte separation and detection. The mycotoxins included in this work were those widely reported to occur in cereal samples, namely, ochratoxin-A (OTA), aflatoxins (AFB1, AFB2, AFG1 and AFG2), zearalenone (ZON), deoxynivalenol (DON), 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol (3-AcDON and 15-AcDON, respectively), nivalenol (NIV), neosolaniol (NEO), fusarenone-X, (FUS-X), T-2 toxin (T-2) and HT-2 toxin (HT-2), fumonisin B1 and B2 (FB1 and FB2, respectively), enniatins (ENN A, ENN A1, ENN B and ENN B1) and beauvericin (BEA). The validated method was successfully applied to 84 gluten-free pasta samples collected from several local markets of Campania region (Italy) during September to November 2020 to monitor the occurrence of mycotoxins and to assess the exposure to these food contaminants. A significant number of samples (95%) showed mycotoxin contamination, being Fusarium mycotoxins (FB1, ZON and DON) the most commonly detected ones. Regarding the risk assessment, the higher exposures were obtained for NIV, DON and FB1 for children and teenagers age group which can be explained due to their lower body weight. Full article

(This article belongs to the Special Issue Mycotoxins and Food)

20 pages, 3256 KiB

Open AccessEditor’s ChoiceArticle

Anticoagulant Activity of Naja nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib

by Taline D. Kazandjian, Arif Arrahman, Kristina B. M. Still, Govert W. Somsen, Freek J. Vonk, Nicholas R. Casewell, Mark C. Wilkinson and Jeroen Kool

Toxins 2021, 13(5), 302; https://doi.org/10.3390/toxins13050302 - 23 Apr 2021

Cited by 21 | Viewed by 4353

Abstract

Bites from elapid snakes typically result in neurotoxic symptoms in snakebite victims. Neurotoxins are, therefore, often the focus of research relating to understanding the pathogenesis of elapid bites. However, recent evidence suggests that some elapid snake venoms contain anticoagulant toxins which may help [...] Read more.

Bites from elapid snakes typically result in neurotoxic symptoms in snakebite victims. Neurotoxins are, therefore, often the focus of research relating to understanding the pathogenesis of elapid bites. However, recent evidence suggests that some elapid snake venoms contain anticoagulant toxins which may help neurotoxic components spread more rapidly. This study examines the effects of venom from the West African black-necked spitting cobra (Naja nigricollis) on blood coagulation and identifies potential coagulopathic toxins. An integrated RPLC-MS methodology, coupled with nanofractionation, was first used to separate venom components, followed by MS, proteomics and coagulopathic bioassays. Coagulation assays were performed on both crude and nanofractionated N. nigricollis venom toxins as well as PLA₂s and 3FTx purified from the venom. Assays were then repeated with the addition of either the phospholipase A₂ inhibitor varespladib or the snake venom metalloproteinase inhibitor marimastat to assess whether either toxin inhibitor is capable of neutralizing coagulopathic venom activity. Subsequent proteomic analysis was performed on nanofractionated bioactive venom toxins using tryptic digestion followed by nanoLC-MS/MS measurements, which were then identified using Swiss-Prot and species-specific database searches. Varespladib, but not marimastat, was found to significantly reduce the anticoagulant activity of N. nigricollis venom and MS and proteomics analyses confirmed that the anticoagulant venom components mostly consisted of PLA₂ proteins. We, therefore, conclude that PLA₂s are the most likely candidates responsible for anticoagulant effects stimulated by N. nigricollis venom. Full article

(This article belongs to the Section Animal Venoms)

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13 pages, 291 KiB

Open AccessEditor’s ChoiceReview

Electrical Stimulation of Injected Muscles to Boost Botulinum Toxin Effect on Spasticity: Rationale, Systematic Review and State of the Art

by Alessandro Picelli, Mirko Filippetti, Giorgio Sandrini, Cristina Tassorelli, Roberto De Icco, Nicola Smania and Stefano Tamburin

Toxins 2021, 13(5), 303; https://doi.org/10.3390/toxins13050303 - 23 Apr 2021

Cited by 12 | Viewed by 4345

Abstract

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has [...] Read more.

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms “electric stimulation”, “muscle spasticity” and “botulinum toxins” and strings “electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A” was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake. Full article

(This article belongs to the Special Issue Enhancing the Effect of Botulinum Toxin in Neurology, Neurorehabilitation and Pain Medicine)

9 pages, 8761 KiB

Open AccessEditor’s ChoiceReview

Two Gut Microbiota-Derived Toxins Are Closely Associated with Cardiovascular Diseases: A Review

by Tomoya Yamashita, Naofumi Yoshida, Takuo Emoto, Yoshihiro Saito and Ken-ichi Hirata

Toxins 2021, 13(5), 297; https://doi.org/10.3390/toxins13050297 - 22 Apr 2021

Cited by 19 | Viewed by 3896

Abstract

Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and [...] Read more.

Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and renal functions of the host via the production of bioactive metabolites. This review investigated the evidence from several clinical and experimental studies that indicated an association between the gut microbiota-derived toxins and CVDs. We mainly focused on the pro-inflammatory gut microbiota-derived toxins, namely lipopolysaccharides, derived from Gram-negative bacteria, and trimethylamine N-oxide and described the present status of research in association with these toxins, including our previous research findings. Several clinical studies aimed at exploring the effectiveness of reducing the levels of these toxins to inhibit cardiovascular events are currently under investigation or in the planning stages. We believe that some of the methods discussed in this review to eliminate or reduce the levels of such toxins in the body could be clinically applied to prevent CVDs in the near future. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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22 pages, 4393 KiB

Open AccessEditor’s ChoiceArticle

A Comprehensive Study Monitoring the Venom Composition and the Effects of the Venom of the Rare Ethiopian Endemic Snake Species Bitis parviocula

by Vladimír Petrilla, Magdaléna Polláková, Barbora Bekešová, Zuzana Andrejčáková, Radoslava Vlčková, Dana Marcinčáková, Monika Petrillová, Eva Petrovová, Drahomíra Sopková and Jaroslav Legáth

Toxins 2021, 13(5), 299; https://doi.org/10.3390/toxins13050299 - 22 Apr 2021

Cited by 3 | Viewed by 3653

Abstract

The Ethiopian endemic snake of the species Bitis parviocula, recognized for its colorful patterns, might be more interesting as we look deeper into the venom activity. We assayed the effects of venoms from the most widespread venomous African Bitis arietens and closely related [...] Read more.

The Ethiopian endemic snake of the species Bitis parviocula, recognized for its colorful patterns, might be more interesting as we look deeper into the venom activity. We assayed the effects of venoms from the most widespread venomous African Bitis arietens and closely related species Bitis parviocula using The Hen’s Egg Test—Chorioallantoic membrane test (HET-CAM) and Chicken embryotoxicity screening test (CHEST), acetylcholinesterase (AChE) analysis, cytotoxicity assay performed on cell lines and protein analysis of selected venoms. Our results indicated that B. parviocula venom contains vasoactive compounds that have a direct effect on blood vessels. The AChE analysis showed significant ability inhibiting AChE activity in embryonic tissue. Cytotoxicity observed on A549 ATCC^® CCL-185™ cells indicates the possible presence of cytotoxic agents in B. parviocula venom. We proved previously described differences in the composition of venom obtained from B. arietans and B. parviocula by using electrophoresis and total protein concentration. Based on similarities in vasoactive effects observed after administration of venoms onto a chicken chorioallantoic membrane, we suggest that venom from B. arietans and B. parviocula might share certain venom proteins responsible for haemotoxicity. The main active components of B. parviocula venom are unknown. Our results suggest that it might be worth performing proteomic analysis of B. parviocula venom as it might contain medically valuable compounds. Full article

(This article belongs to the Special Issue Venom-Induced Tissue Damage)

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21 pages, 2749 KiB

Open AccessEditor’s ChoiceArticle

A Novel Microbial Zearalenone Transformation through Phosphorylation

by Yan Zhu, Pascal Drouin, Dion Lepp, Xiu-Zhen Li, Honghui Zhu, Mathieu Castex and Ting Zhou

Toxins 2021, 13(5), 294; https://doi.org/10.3390/toxins13050294 - 21 Apr 2021

Cited by 21 | Viewed by 2978

Abstract

Zearalenone (ZEA) is a mycotoxin widely occurring in many agricultural commodities. In this study, a purified bacterial isolate, Bacillus sp. S62-W, obtained from one of 104 corn silage samples from various silos located in the United States, exhibited activity to transform the mycotoxin [...] Read more.

Zearalenone (ZEA) is a mycotoxin widely occurring in many agricultural commodities. In this study, a purified bacterial isolate, Bacillus sp. S62-W, obtained from one of 104 corn silage samples from various silos located in the United States, exhibited activity to transform the mycotoxin ZEA. A novel microbial transformation product, ZEA-14-phosphate, was detected, purified, and identified by HPLC, LC-MS, and NMR analyses. The isolate has been identified as belonging to the genus Bacillus according to phylogenetic analysis of the 16S rRNA gene and whole genome alignments. The isolate showed high efficacy in transforming ZEA to ZEA-14-phosphate (100% transformation within 24 h) and possessed advantages of acid tolerance (work at pH = 4.0), working under a broad range of temperatures (22–42 °C), and a capability of transforming ZEA at high concentrations (up to 200 µg/mL). In addition, 23 Bacillus strains of various species were tested for their ZEA phosphorylation activity. Thirteen of the Bacillus strains showed phosphorylation functionality at an efficacy of between 20.3% and 99.4% after 24 h incubation, suggesting the metabolism pathway is widely conserved in Bacillus spp. This study established a new transformation system for potential application of controlling ZEA although the metabolism and toxicity of ZEA-14-phosphate requires further investigation. Full article

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

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21 pages, 23036 KiB

Open AccessEditor’s ChoiceReview

Predicted Aflatoxin B₁ Increase in Europe Due to Climate Change: Actions and Reactions at Global Level

by Marco Camardo Leggieri, Piero Toscano and Paola Battilani

Toxins 2021, 13(4), 292; https://doi.org/10.3390/toxins13040292 - 20 Apr 2021

Cited by 56 | Viewed by 6997

Abstract

Climate change (CC) is predicted to increase the risk of aflatoxin (AF) contamination in maize, as highlighted by a project supported by EFSA in 2009. We performed a comprehensive literature search using the Scopus search engine to extract peer-reviewed studies citing this study. [...] Read more.

Climate change (CC) is predicted to increase the risk of aflatoxin (AF) contamination in maize, as highlighted by a project supported by EFSA in 2009. We performed a comprehensive literature search using the Scopus search engine to extract peer-reviewed studies citing this study. A total of 224 papers were identified after step I filtering (187 + 37), while step II filtering identified 25 of these papers for quantitative analysis. The unselected papers (199) were categorized as “actions” because they provided a sounding board for the expected impact of CC on AFB₁ contamination, without adding new data on the topic. The remaining papers were considered as “reactions” of the scientific community because they went a step further in their data and ideas. Interesting statements taken from the “reactions” could be summarized with the following keywords: Chain and multi-actor approach, intersectoral and multidisciplinary, resilience, human and animal health, and global vision. In addition, fields meriting increased research efforts were summarized as the improvement of predictive modeling; extension to different crops and geographic areas; and the impact of CC on fungi and mycotoxin co-occurrence, both in crops and their value chains, up to consumers. Full article

(This article belongs to the Special Issue Mycotoxins in Relation to Climate Change)

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20 pages, 1068 KiB

Open AccessEditor’s ChoiceReview

Muscle Tone Physiology and Abnormalities

by Jacky Ganguly, Dinkar Kulshreshtha, Mohammed Almotiri and Mandar Jog

Toxins 2021, 13(4), 282; https://doi.org/10.3390/toxins13040282 - 16 Apr 2021

Cited by 75 | Viewed by 20301

Abstract

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia [...] Read more.

The simple definition of tone as the resistance to passive stretch is physiologically a complex interlaced network encompassing neural circuits in the brain, spinal cord, and muscle spindle. Disorders of muscle tone can arise from dysfunction in these pathways and manifest as hypertonia or hypotonia. The loss of supraspinal control mechanisms gives rise to hypertonia, resulting in spasticity or rigidity. On the other hand, dystonia and paratonia also manifest as abnormalities of muscle tone, but arise more due to the network dysfunction between the basal ganglia and the thalamo-cerebello-cortical connections. In this review, we have discussed the normal homeostatic mechanisms maintaining tone and the pathophysiology of spasticity and rigidity with its anatomical correlates. Thereafter, we have also highlighted the phenomenon of network dysfunction, cortical disinhibition, and neuroplastic alterations giving rise to dystonia and paratonia. Full article

(This article belongs to the Special Issue Botulinum Toxin for the Treatment of Neurological Disorders—Where We Are and Where We Need to Go)

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16 pages, 6347 KiB

Open AccessEditor’s ChoiceArticle

Morphological Analysis Reveals a Compartmentalized Duct in the Venom Apparatus of the Wasp Spider (Argiope bruennichi)

by Henrike Schmidtberg, Björn M. von Reumont, Sarah Lemke, Andreas Vilcinskas and Tim Lüddecke

Toxins 2021, 13(4), 270; https://doi.org/10.3390/toxins13040270 - 9 Apr 2021

Cited by 6 | Viewed by 5120

Abstract

Spiders are one of the most successful groups of venomous animals, but surprisingly few species have been examined in sufficient detail to determine the structure of their venom systems. To learn more about the venom system of the family Araneidae (orb-weavers), we selected [...] Read more.

Spiders are one of the most successful groups of venomous animals, but surprisingly few species have been examined in sufficient detail to determine the structure of their venom systems. To learn more about the venom system of the family Araneidae (orb-weavers), we selected the wasp spider (Argiope bruennichi) and examined the general structure and morphology of the venom apparatus by light microscopy. This revealed morphological features broadly similar to those reported in the small number of other spiders subject to similar investigations. However, detailed evaluation of the venom duct revealed the presence of four structurally distinct compartments. We propose that these subunits facilitate the expression and secretion of venom components, as previously reported for similar substructures in pit vipers and cone snails. Full article

(This article belongs to the Section Animal Venoms)

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14 pages, 1006 KiB

Open AccessEditor’s ChoiceArticle

Susceptibility of Oocytes from Gilts and Sows to Beauvericin and Deoxynivalenol and Its Relationship with Oxidative Stress

by Eric J. Schoevers, Regiane R. Santos and Bernard A. J. Roelen

Toxins 2021, 13(4), 260; https://doi.org/10.3390/toxins13040260 - 6 Apr 2021

Cited by 5 | Viewed by 3069

Abstract

Beauvericin (BEA) and deoxynivalenol are toxins produced by Fusarium species that can contaminate food and feed. The aim of this study was to assess the effects of these mycotoxins on the maturation of oocytes from gilts and sows. Furthermore, the antioxidant profiles in [...] Read more.

Beauvericin (BEA) and deoxynivalenol are toxins produced by Fusarium species that can contaminate food and feed. The aim of this study was to assess the effects of these mycotoxins on the maturation of oocytes from gilts and sows. Furthermore, the antioxidant profiles in the oocytes’ environment were assessed. Cumulus-oocyte-complexes (COCs) from gilts and sows were exposed to beauvericin (BEA) or deoxynivalenol (DON) and matured in vitro. As an extra control, these COCs were also exposed to reactive oxygen species (ROS). The maturation was mostly impaired when oocytes from gilts were exposed to 0.02 μmol/L DON. Oocytes from sows were able to mature even in the presence of 5 μmol/L BEA. However, the maturation rate of gilt oocytes was already impaired by 0.5 μmol/L BEA. It was observed that superoxide dismutase (SOD) and glutathione (GSH) levels in the follicular fluid (FF) of gilt oocytes was higher than that from sows. However, the expression of SOD1 and glutathione synthetase (GSS) was higher in the oocytes from sows than in those from gilts. Although DON and BEA impair cell development by diverse mechanisms, this redox imbalance may partially explain the vulnerability of gilt oocytes to these mycotoxins. Full article

(This article belongs to the Section Mycotoxins)

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16 pages, 2264 KiB

Open AccessEditor’s ChoiceArticle

Sphingomyelinase D Activity in Sicarius tropicus Venom: Toxic Potential and Clues to the Evolution of SMases D in the Sicariidae Family

by Priscila Hess Lopes, Caroline Sayuri Fukushima, Rosana Shoji, Rogério Bertani and Denise V. Tambourgi

Toxins 2021, 13(4), 256; https://doi.org/10.3390/toxins13040256 - 1 Apr 2021

Cited by 4 | Viewed by 4427

Abstract

The spider family Sicariidae includes three genera, Hexophthalma, Sicarius and Loxosceles. The three genera share a common characteristic in their venoms: the presence of Sphingomyelinases D (SMase D). SMases D are considered the toxins that cause the main pathological effects of [...] Read more.

The spider family Sicariidae includes three genera, Hexophthalma, Sicarius and Loxosceles. The three genera share a common characteristic in their venoms: the presence of Sphingomyelinases D (SMase D). SMases D are considered the toxins that cause the main pathological effects of the Loxosceles venom, that is, those responsible for the development of loxoscelism. Some studies have shown that Sicarius spiders have less or undetectable SMase D activity in their venoms, when compared to Hexophthalma. In contrast, our group has shown that Sicarius ornatus, a Brazilian species, has active SMase D and toxic potential to envenomation. However, few species of Sicarius have been characterized for their toxic potential. In order to contribute to a better understanding about the toxicity of Sicarius venoms, the aim of this study was to characterize the toxic properties of male and female venoms from Sicarius tropicus and compare them with that from Loxosceles laeta, one of the most toxic Loxosceles venoms. We show here that S. tropicus venom presents active SMases D. However, regarding hemolysis development, it seems that these toxins in this species present different molecular mechanisms of action than that described for Loxosceles venoms, whereas it is similar to those present in bacteria containing SMase D. Besides, our results also suggest that, in addition to the interspecific differences, intraspecific variations in the venoms’ composition may play a role in the toxic potential of venoms from Sicarius species. Full article

(This article belongs to the Special Issue Toxinologic and Pharmacological Investigation of Venomous Arthropods)

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23 pages, 964 KiB

Open AccessEditor’s ChoiceReview

The Impact of CKD on Uremic Toxins and Gut Microbiota

by Jacek Rysz, Beata Franczyk, Janusz Ławiński, Robert Olszewski, Aleksanda Ciałkowska-Rysz and Anna Gluba-Brzózka

Toxins 2021, 13(4), 252; https://doi.org/10.3390/toxins13040252 - 31 Mar 2021

Cited by 175 | Viewed by 17194

Abstract

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of [...] Read more.

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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14 pages, 2834 KiB

Open AccessEditor’s ChoiceArticle

Citrinin Determination in Food and Food Supplements by LC-MS/MS: Development and Use of Reference Materials in an International Collaborative Study

by Emmanuel K. Tangni, François Van Hove, Bart Huybrechts, Julien Masquelier, Karine Vandermeiren and Els Van Hoeck

Toxins 2021, 13(4), 245; https://doi.org/10.3390/toxins13040245 - 30 Mar 2021

Cited by 8 | Viewed by 2850

Abstract

The development of incurred reference materials containing citrinin (CIT) and their successful application in a method validation study (MVS) in order to harmonize CIT determination in food and food supplements are demonstrated. CIT-contaminated materials made of red yeast rice (RYR), wheat flour, and [...] Read more.

The development of incurred reference materials containing citrinin (CIT) and their successful application in a method validation study (MVS) in order to harmonize CIT determination in food and food supplements are demonstrated. CIT-contaminated materials made of red yeast rice (RYR), wheat flour, and Ginkgo biloba leaves (GBL), as well as food supplements made of red yeast rice (FS-RYR) and Ginkgo biloba leaves (FS-GBL), were manufactured in-house via fungal cultivation on collected raw materials. The homogeneity and stability from randomly selected containers were verified according to the ISO 13528. CIT was found to be homogenously distributed and stable in all contaminated materials, with no significant degradation during the timescale of the MVS when storage was performed up to +4 °C. Next, an MVS was organized with eighteen international laboratories using the provided standard operating procedure and 12 test materials, including three RYRs (blank, <50 µg/kg, <2000 µg/kg), two wheat flours (blank, <50 µg/kg), two GBL powders (blank, <50 µg/kg), three FS-RYRs (blank, <50 µg/kg, <2000 µg/kg), and two FS-GBLs (blank, <50 µg/kg). The results of seven CIT-incurred materials showed acceptable within-laboratory precision (RSDr) varying from 6.4% to 14.6% and between-laboratory precision (RSDR) varying from 10.2% to 37.3%. Evidenced by HorRat values < 2.0, the results of the collaborative trial demonstrated that the applied analytical method could be standardized. Furthermore, the appropriateness of producing CIT reference materials is an important step towards food and feed quality control systems and the organization of proficiency tests. Full article

(This article belongs to the Special Issue Mycotoxins, Food Safety and Metrology)

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10 pages, 10209 KiB

Open AccessEditor’s ChoiceReview

Uremic Toxins and Blood Purification: A Review of Current Evidence and Future Perspectives

by Stefania Magnani and Mauro Atti

Toxins 2021, 13(4), 246; https://doi.org/10.3390/toxins13040246 - 30 Mar 2021

Cited by 44 | Viewed by 4526

Abstract

Accumulation of uremic toxins represents one of the major contributors to the rapid progression of chronic kidney disease (CKD), especially in patients with end-stage renal disease that are undergoing dialysis treatment. In particular, protein-bound uremic toxins (PBUTs) seem to have an important key [...] Read more.

Accumulation of uremic toxins represents one of the major contributors to the rapid progression of chronic kidney disease (CKD), especially in patients with end-stage renal disease that are undergoing dialysis treatment. In particular, protein-bound uremic toxins (PBUTs) seem to have an important key pathophysiologic role in CKD, inducing various cardiovascular complications. The removal of uremic toxins from the blood with dialytic techniques represents a proved approach to limit the CKD-related complications. However, conventional dialysis mainly focuses on the removal of water-soluble compounds of low and middle molecular weight, whereas PBTUs are strongly protein-bound, thus not efficiently eliminated. Therefore, over the years, dialysis techniques have been adapted by improving membranes structures or using combined strategies to maximize PBTUs removal and eventually prevent CKD-related complications. Recent findings showed that adsorption-based extracorporeal techniques, in addition to conventional dialysis treatment, may effectively adsorb a significant amount of PBTUs during the course of the sessions. This review is focused on the analysis of the current state of the art for blood purification strategies in order to highlight their potentialities and limits and identify the most feasible solution to improve toxins removal effectiveness, exploring possible future strategies and applications, such as the study of a synergic approach by reducing PBTUs production and increasing their blood clearance. Full article

(This article belongs to the Special Issue New Strategies for the Reduction of Uremic Toxins)

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25 pages, 3609 KiB

Open AccessEditor’s ChoiceArticle

Co-Occurrence of Regulated and Emerging Mycotoxins in Corn Silage: Relationships with Fermentation Quality and Bacterial Communities

by Antonio Gallo, Francesca Ghilardelli, Alberto Stanislao Atzori, Severino Zara, Barbara Novak, Johannes Faas and Francesco Fancello

Toxins 2021, 13(3), 232; https://doi.org/10.3390/toxins13030232 - 23 Mar 2021

Cited by 30 | Viewed by 5371

Abstract

Sixty-four corn silages were characterized for chemicals, bacterial community, and concentrations of several fungal metabolites. Silages were grouped in five clusters, based on detected mycotoxins, and they were characterized for being contaminated by (1) low levels of Aspergillus- and Penicillium-mycotoxins; (2) [...] Read more.

Sixty-four corn silages were characterized for chemicals, bacterial community, and concentrations of several fungal metabolites. Silages were grouped in five clusters, based on detected mycotoxins, and they were characterized for being contaminated by (1) low levels of Aspergillus- and Penicillium-mycotoxins; (2) low levels of fumonisins and other Fusarium-mycotoxins; (3) high levels of Aspergillus-mycotoxins; (4) high levels of non-regulated Fusarium-mycotoxins; (5) high levels of fumonisins and their metabolites. Altersetin was detected in clusters 1, 3, and 5. Rugulusovin or brevianamide F were detected in several samples, with the highest concentration in cluster 3. Emodin was detected in more than 50.0% of samples of clusters 1, 3 and 5, respectively. Kojic acid occurred mainly in clusters 1 and 2 at very low concentrations. Regarding Fusarium mycotoxins, high occurrences were observed for FB3, FB4, FA1, whereas the average concentrations of FB6 and FA2 were lower than 12.4 µg/kg dry matter. Emerging Fusarium-produced mycotoxins, such as siccanol, moniliformin, equisetin, epiequisetin and bikaverin were detected in the majority of analyzed corn silages. Pestalotin, oxaline, phenopirrozin and questiomycin A were detected at high incidences. Concluding, this work highlighted that corn silages could be contaminated by a high number of regulated and emerging mycotoxins. Full article

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

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13 pages, 890 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Applications of Botulinum Neurotoxin for Autonomic Symptoms in Parkinson’s Disease: An Updated Review

by Steven D. Mitchell and Christos Sidiropoulos

Toxins 2021, 13(3), 226; https://doi.org/10.3390/toxins13030226 - 19 Mar 2021

Cited by 11 | Viewed by 4176

Abstract

Parkinson’s disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms [...] Read more.

Parkinson’s disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms associated with Parkinson’s disease include sialorrhea, hyperhidrosis, gastrointestinal dysfunction, and urinary dysfunction. Botulinum neurotoxin has been shown to potentially improve these autonomic symptoms. In this review, the varied uses of botulinum neurotoxin for autonomic dysfunction in Parkinson’s disease are discussed. This review also includes discussion of some additional indications for the use of botulinum neurotoxin in Parkinson’s disease, including pain. Full article

(This article belongs to the Special Issue Botulinum Neurotoxin and Parkinson’s Disease)

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13 pages, 481 KiB

Open AccessEditor’s ChoiceReview

Botulinum Toxin A and Osteosarcopenia in Experimental Animals: A Scoping Review

by Min Jia Tang, H. Kerr Graham and Kelsey E. Davidson

Toxins 2021, 13(3), 213; https://doi.org/10.3390/toxins13030213 - 14 Mar 2021

Cited by 7 | Viewed by 3407

Abstract

We conducted a scoping review to investigate the effects of intramuscular injection of Botulinum Toxin A (BoNT-A) on bone morphology. We investigated if the muscle atrophy associated with Injection of BoNT-A had effects on the neighboring bone. We used the search terms: osteopenia, [...] Read more.

We conducted a scoping review to investigate the effects of intramuscular injection of Botulinum Toxin A (BoNT-A) on bone morphology. We investigated if the muscle atrophy associated with Injection of BoNT-A had effects on the neighboring bone. We used the search terms: osteopenia, bone atrophy, Botulinum Toxin A, Micro-CT, mice or rat. The following databases were searched: Medline, Embase, PubMed and the Cochrane Library, between 1990 and 2020. After removal of duplicates, 228 abstracts were identified of which 49 studies satisfied our inclusion and exclusion criteria. The majority of studies (41/49) reported a quantitative reduction in at least one measure of bone architecture based on Micro-CT. The reduction in the ratio of bone volume to tissue volume varied from 11% to 81% (mean 43%) according to the experimental set up and study time points. While longer term studies showed muscle recovery, no study showed complete recovery of all bone properties at the termination of the study. In experimental animals, intramuscular injection of BoNT-A resulted in acute muscle atrophy and acute degradation of the neighboring bone segment. These findings may have implications for clinical protocols in the use of Botulinum Toxin in children with cerebral palsy, with restraint recommended in injection protocols and consideration for monitoring bone density. Clinical studies in children with cerebral palsy receiving injections of Botulinum are indicated. Full article

(This article belongs to the Section Bacterial Toxins)

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20 pages, 2496 KiB

Open AccessEditor’s ChoiceArticle

Saccharomyces cerevisiae Cell Wall-Based Adsorbent Reduces Aflatoxin B1 Absorption in Rats

by Alexandros Yiannikouris, Juha Apajalahti, Osmo Siikanen, Gerald Patrick Dillon and Colm Anthony Moran

Toxins 2021, 13(3), 209; https://doi.org/10.3390/toxins13030209 - 13 Mar 2021

Cited by 24 | Viewed by 4420

Abstract

Mycotoxins are naturally occurring toxins that can affect livestock health and performance upon consumption of contaminated feedstuffs. To mitigate the negative effects of mycotoxins, sequestering agents, adsorbents, or binders can be included to feed to interact with toxins, aiding their passage through the [...] Read more.

Mycotoxins are naturally occurring toxins that can affect livestock health and performance upon consumption of contaminated feedstuffs. To mitigate the negative effects of mycotoxins, sequestering agents, adsorbents, or binders can be included to feed to interact with toxins, aiding their passage through the gastrointestinal tract (GI) and reducing their bioavailability. The parietal cell wall components of Saccharomyces cerevisiae have been found to interact in vitro with mycotoxins, such as, but not limited to, aflatoxin B1 (AFB1), and to improve animal performance when added to contaminated diets in vivo. The present study aimed to examine the pharmacokinetics of the absorption of radiolabeled AFB1 in rats in the presence of a yeast cell wall-based adsorbent (YCW) compared with that in the presence of the clay-based binder hydrated sodium calcium aluminosilicate (HSCAS). The results of the initial pharmacokinetic analysis showed that the absorption process across the GI tract was relatively slow, occurring over a matter of hours rather than minutes. The inclusion of mycotoxin binders increased the recovery of radiolabeled AFB1 in the small intestine, cecum, and colon at 5 and 10 h, revealing that they prevented AFB1 absorption compared with a control diet. Additionally, the accumulation of radiolabeled AFB1 was more significant in the blood plasma, kidney, and liver of animals fed the control diet, again showing the ability of the binders to reduce the assimilation of AFB1 into the body. The results showed the potential of YCW in reducing the absorption of AFB1 in vivo, and in protecting against the damaging effects of AFB1 contamination. Full article

(This article belongs to the Collection Aflatoxins)

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16 pages, 2583 KiB

Open AccessEditor’s ChoiceArticle

Natural Co-Occurrence of Multiple Mycotoxins in Unprocessed Oats Grown in Ireland with Various Production Systems

by Lorenzo De Colli, Karl De Ruyck, Mohamed F. Abdallah, John Finnan, Ewen Mullins, Steven Kildea, John Spink, Christopher Elliott and Martin Danaher

Toxins 2021, 13(3), 188; https://doi.org/10.3390/toxins13030188 - 4 Mar 2021

Cited by 26 | Viewed by 5367

Abstract

The natural co-occurrence of 42 mycotoxins was investigated in unprocessed oat grains grown in Ireland. The sample set included a total of 208 oat crops harvested during 2015–2016 and produced using conventional, organic, or gluten free farming systems. A range of different toxins [...] Read more.

The natural co-occurrence of 42 mycotoxins was investigated in unprocessed oat grains grown in Ireland. The sample set included a total of 208 oat crops harvested during 2015–2016 and produced using conventional, organic, or gluten free farming systems. A range of different toxins was identified, including the major type A (neosolaniol, HT-2 and T-2 toxins, T-2 triol, and T-2-glucoside, co-occurring in 21 samples) and B trichothecenes (deoxynivalenol, nivalenol, and deoxynivalenol-3-glucoside), enniatins (B1, B, and A1, co-occurring in 12 samples), as well as beauvericin, alternariol, mycophenolic acid, and sterigmatocystin. The influences of sowing season, year, and production system were investigated, eventually indicating that the latter factor may have a higher impact than others on the production of certain mycotoxins in oats. The most frequently quantified compounds were HT-2 (51%) and T-2 (41%) toxins, with gluten free oats containing significantly lower concentrations of HT-2 compared to conventionally produced oats. Although the prevalence and concentrations of mycotoxin found in oat samples in this study should be substantially reduced by processing. However, as mycotoxin occurrence is clearly influenced by multiple factors, controlled field trials should be carried out to define optimal agronomic practices and mitigate mycotoxin production. Furthermore, this work highlights the need for regularly testing cereal-based foods with multi-residue analytical methods with wider specificities than the traditionally screened and regulated toxins, to generate knowledge on the occurrence of several mycotoxins that are, to date, rarely investigated. Full article

(This article belongs to the Collection Understanding Mycotoxin Occurrence in Food and Feed Chains)

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16 pages, 1897 KiB

Open AccessEditor’s ChoiceArticle

Population Genetic Structure and Chemotype Diversity of Fusarium graminearum Populations from Wheat in Canada and North Eastern United States

by Abbot O. Oghenekaro, Maria A. Oviedo-Ludena, Mitra Serajazari, Xiben Wang, Maria A. Henriquez, Nancy G. Wenner, Gretchen A. Kuldau, Alireza Navabi, Hadley R. Kutcher and W. G. Dilantha Fernando

Toxins 2021, 13(3), 180; https://doi.org/10.3390/toxins13030180 - 1 Mar 2021

Cited by 17 | Viewed by 5476

Abstract

Fusarium head blight (FHB) is a major disease in wheat causing severe economic losses globally by reducing yield and contaminating grain with mycotoxins. In Canada, Fusarium graminearum is the principal etiological agent of FHB in wheat, producing mainly the trichothecene mycotoxin, deoxynivalenol (DON) [...] Read more.

Fusarium head blight (FHB) is a major disease in wheat causing severe economic losses globally by reducing yield and contaminating grain with mycotoxins. In Canada, Fusarium graminearum is the principal etiological agent of FHB in wheat, producing mainly the trichothecene mycotoxin, deoxynivalenol (DON) and its acetyl derivatives (15-acetyl deoxynivalenol (15ADON) and 3-acetyl deoxynivalenol (3ADON)). Understanding the population biology of F. graminearum such as the genetic variability, as well as mycotoxin chemotype diversity among isolates is important in developing sustainable disease management tools. In this study, 570 F. graminearum isolates collected from commercial wheat crops in five geographic regions in three provinces in Canada in 2018 and 2019 were analyzed for population diversity and structure using 10 variable number of tandem repeats (VNTR) markers. A subset of isolates collected from the north-eastern United States was also included for comparative analysis. About 75% of the isolates collected in the Canadian provinces of Saskatchewan and Manitoba were 3ADON indicating a 6-fold increase in Saskatchewan and a 2.5-fold increase in Manitoba within the past 15 years. All isolates from Ontario and those collected from the United States were 15ADON and isolates had a similar population structure. There was high gene diversity (H = 0.803–0.893) in the F. graminearum populations in all regions. Gene flow was high between Saskatchewan and Manitoba (Nm = 4.971–21.750), indicating no genetic differentiation between these regions. In contrast, less gene flow was observed among the western provinces and Ontario (Nm = 3.829–9.756) and USA isolates ((Nm = 2.803–6.150). However, Bayesian clustering model analyses of trichothecene chemotype subpopulations divided the populations into two clusters, which was correlated with trichothecene types. Additionally, population cluster analysis revealed there was more admixture of isolates among isolates of the 3ADON chemotypes than among the 15ADON chemotype, an observation that could play a role in the increased virulence of F. graminearum. Understanding the population genetic structure and mycotoxin chemotype variations of the pathogen will assist in developing FHB resistant wheat cultivars and in mycotoxin risk assessment in Canada. Full article

(This article belongs to the Special Issue New Insight into Fusarium Toxins and Aflatoxins)

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12 pages, 5230 KiB

Open AccessEditor’s ChoiceArticle

Primary Impacts of the Fungal Toxin Sporidesmin on HepG2 Cells: Altered Cell Adhesion without Oxidative Stress or Cell Death

by Magalie Boucher and T. William Jordan

Toxins 2021, 13(3), 179; https://doi.org/10.3390/toxins13030179 - 28 Feb 2021

Cited by 1 | Viewed by 2909

Abstract

The fungal metabolite sporidesmin is responsible for severe necrotizing inflammation of biliary tract and liver of livestock grazing on pasture containing spores of Pithomyces chartarum that synthesizes the toxin. The toxin is secreted into bile causing the erosion of the biliary epithelium accompanied [...] Read more.

The fungal metabolite sporidesmin is responsible for severe necrotizing inflammation of biliary tract and liver of livestock grazing on pasture containing spores of Pithomyces chartarum that synthesizes the toxin. The toxin is secreted into bile causing the erosion of the biliary epithelium accompanied by inflammation and damage to surrounding tissues. Toxicity has been suggested to be due to cycles of reduction and oxidation of sporidesmin leading to oxidative damage from the formation of reactive oxygen species. The current work is the first test of the oxidative stress hypothesis using cultured cells. Oxidative stress could not be detected in HepG2 cells incubated with sporidesmin using a dichlorodihydrofluorescein diacetate assay or by use of two-dimensional electrophoresis to search for oxidized peroxiredoxins. There was also no evidence for necrosis or apoptosis, although there was a loss of cell adhesion that was accompanied by the disruption of intracellular actin microfilaments that have known roles in cell adhesion. The results are consistent with a model in which altered contact between cells in situ leads to altered permeability and subsequent inflammation and necrosis, potentially from the leakage of toxic bile into surrounding tissues. There is now a need for the further characterization of the damage processes in vivo, including the investigation of altered permeability and mechanisms of cell death in the biliary tract and other affected organs. 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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38 pages, 2392 KiB

Open AccessEditor’s ChoiceReview

Non-Digestible Oligosaccharides and Short Chain Fatty Acids as Therapeutic Targets against Enterotoxin-Producing Bacteria and Their Toxins

by Mostafa Asadpoor, Georgia-Nefeli Ithakisiou, Paul A. J. Henricks, Roland Pieters, Gert Folkerts and Saskia Braber

Toxins 2021, 13(3), 175; https://doi.org/10.3390/toxins13030175 - 25 Feb 2021

Cited by 35 | Viewed by 5786

Abstract

Enterotoxin-producing bacteria (EPB) have developed multiple mechanisms to disrupt gut homeostasis, and provoke various pathologies. A major part of bacterial cytotoxicity is attributed to the secretion of virulence factors, including enterotoxins. Depending on their structure and mode of action, enterotoxins intrude the intestinal [...] Read more.

Enterotoxin-producing bacteria (EPB) have developed multiple mechanisms to disrupt gut homeostasis, and provoke various pathologies. A major part of bacterial cytotoxicity is attributed to the secretion of virulence factors, including enterotoxins. Depending on their structure and mode of action, enterotoxins intrude the intestinal epithelium causing long-term consequences such as hemorrhagic colitis. Multiple non-digestible oligosaccharides (NDOs), and short chain fatty acids (SCFA), as their metabolites produced by the gut microbiota, interact with enteropathogens and their toxins, which may result in the inhibition of the bacterial pathogenicity. NDOs characterized by diverse structural characteristics, block the pathogenicity of EPB either directly, by inhibiting bacterial adherence and growth, or biofilm formation or indirectly, by promoting gut microbiota. Apart from these abilities, NDOs and SCFA can interact with enterotoxins and reduce their cytotoxicity. These anti-virulent effects mostly rely on their ability to mimic the structure of toxin receptors and thus inhibiting toxin adherence to host cells. This review focuses on the strategies of EPB and related enterotoxins to impair host cell immunity, discusses the anti-pathogenic properties of NDOs and SCFA on EPB functions and provides insight into the potential use of NDOs and SCFA as effective agents to fight against enterotoxins. Full article

(This article belongs to the Section Bacterial Toxins)

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22 pages, 753 KiB

Open AccessEditor’s ChoiceReview

Mycotoxin Occurrence, Toxicity, and Detoxifying Agents in Pig Production with an Emphasis on Deoxynivalenol

by Debora Muratori Holanda and Sung Woo Kim

Toxins 2021, 13(2), 171; https://doi.org/10.3390/toxins13020171 - 23 Feb 2021

Cited by 103 | Viewed by 7609

Abstract

This review aimed to investigate the occurrence of mycotoxins, their toxic effects, and the detoxifying agents discussed in scientific publications that are related to pig production. Mycotoxins that are of major interest are aflatoxins and Fusarium toxins, such as deoxynivalenol and fumonisins, because [...] Read more.

This review aimed to investigate the occurrence of mycotoxins, their toxic effects, and the detoxifying agents discussed in scientific publications that are related to pig production. Mycotoxins that are of major interest are aflatoxins and Fusarium toxins, such as deoxynivalenol and fumonisins, because of their elevated frequency at a global scale and high occurrence in corn, which is the main feedstuff in pig diets. The toxic effects of aflatoxins, deoxynivalenol, and fumonisins include immune modulation, disruption of intestinal barrier function, and cytotoxicity leading to cell death, which all result in impaired pig performance. Feed additives, such as mycotoxin-detoxifying agents, that are currently available often combine organic and inorganic sources to enhance their adsorbability, immune stimulation, or ability to render mycotoxins less toxic. In summary, mycotoxins present challenges to pig production globally because of their increasing occurrences in recent years and their toxic effects impairing the health and growth of pigs. Effective mycotoxin-detoxifying agents must be used to boost pig health and performance and to improve the sustainable use of crops. Full article

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

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16 pages, 2766 KiB

Open AccessEditor’s ChoiceReview

The Buzz about ADP-Ribosylation Toxins from Paenibacillus larvae, the Causative Agent of American Foulbrood in Honey Bees

by Julia Ebeling, Anne Fünfhaus and Elke Genersch

Toxins 2021, 13(2), 151; https://doi.org/10.3390/toxins13020151 - 16 Feb 2021

Cited by 10 | Viewed by 3567

Abstract

The Gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood, a highly contagious and often fatal honey bee brood disease. The species P. larvae comprises five so-called ERIC-genotypes which differ in virulence and pathogenesis strategies. In the past two decades, [...] Read more.

The Gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood, a highly contagious and often fatal honey bee brood disease. The species P. larvae comprises five so-called ERIC-genotypes which differ in virulence and pathogenesis strategies. In the past two decades, the identification and characterization of several P. larvae virulence factors have led to considerable progress in understanding the molecular basis of pathogen-host-interactions during P. larvae infections. Among these virulence factors are three ADP-ribosylating AB-toxins, Plx1, Plx2, and C3larvin. Plx1 is a phage-born toxin highly homologous to the pierisin-like AB-toxins expressed by the whites-and-yellows family Pieridae (Lepidoptera, Insecta) and to scabin expressed by the plant pathogen Streptomyces scabiei. These toxins ADP-ribosylate DNA and thus induce apoptosis. While the presumed cellular target of Plx1 still awaits final experimental proof, the classification of the A subunits of the binary AB-toxins Plx2 and C3larvin as typical C3-like toxins, which ADP-ribosylate Rho-proteins, has been confirmed experimentally. Normally, C3-exoenzymes do not occur together with a B subunit partner, but as single domain toxins. Interestingly, the B subunits of the two P. larvae C3-like toxins are homologous to the B-subunits of C2-like toxins with striking structural similarity to the PA-63 protomer of Bacillus anthracis. Full article

(This article belongs to the Special Issue Structure and Function of Bacterial ADP-Ribosylation Toxins)

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16 pages, 1667 KiB

Open AccessEditor’s ChoiceArticle

Non-Transgenic CRISPR-Mediated Knockout of Entire Ergot Alkaloid Gene Clusters in Slow-Growing Asexual Polyploid Fungi

by Simona Florea, Jolanta Jaromczyk and Christopher L. Schardl

Toxins 2021, 13(2), 153; https://doi.org/10.3390/toxins13020153 - 16 Feb 2021

Cited by 16 | Viewed by 3568

Abstract

The Epichloë species of fungi include seed-borne symbionts (endophytes) of cool-season grasses that enhance plant fitness, although some also produce alkaloids that are toxic to livestock. Selected or mutated toxin-free endophytes can be introduced into forage cultivars for improved livestock performance. Long-read genome [...] Read more.

The Epichloë species of fungi include seed-borne symbionts (endophytes) of cool-season grasses that enhance plant fitness, although some also produce alkaloids that are toxic to livestock. Selected or mutated toxin-free endophytes can be introduced into forage cultivars for improved livestock performance. Long-read genome sequencing revealed clusters of ergot alkaloid biosynthesis (EAS) genes in Epichloë coenophiala strain e19 from tall fescue (Lolium arundinaceum) and Epichloë hybrida Lp1 from perennial ryegrass (Lolium perenne). The two homeologous clusters in E. coenophiala—a triploid hybrid species—were 196 kb (EAS1) and 75 kb (EAS2), and the E. hybrida EAS cluster was 83 kb. As a CRISPR-based approach to target these clusters, the fungi were transformed with ribonucleoprotein (RNP) complexes of modified Cas9 nuclease (Cas9-2NLS) and pairs of single guide RNAs (sgRNAs), plus a transiently selected plasmid. In E. coenophiala, the procedure generated deletions of EAS1 and EAS2 separately, as well as both clusters simultaneously. The technique also gave deletions of the EAS cluster in E. hybrida and of individual alkaloid biosynthesis genes (dmaW and lolC) that had previously proved difficult to delete in E. coenophiala. Thus, this facile CRISPR RNP approach readily generates non-transgenic endophytes without toxin genes for use in research and forage cultivar improvement. Full article

(This article belongs to the Special Issue Global Impact of Ergot Alkaloids)

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16 pages, 1184 KiB

Open AccessEditor’s ChoiceArticle

Toxic Effects of Fumonisins, Deoxynivalenol and Zearalenone Alone and in Combination in Ducks Fed the Maximum EUTolerated Level

by Céline Peillod, Marie Laborde, Angélique Travel, Amandine Mika, Jean Denis Bailly, Didier Cleva, Cyril Boissieu, Jean Le Guennec, Olivier Albaric, Sophie Labrut, Pascal Froment, Didier Tardieu and Philippe Guerre

Toxins 2021, 13(2), 152; https://doi.org/10.3390/toxins13020152 - 16 Feb 2021

Cited by 19 | Viewed by 3329

Abstract

Toxic effects among fumonisins B (FB), deoxynivalenol (DON) and zearalenone (ZEN) administered alone and combined were investigated in 84-day-old ducks during force-feeding. 75 male ducks, divided into five groups of 15 animals, received daily during the meal a capsule containing the desired among [...] Read more.

Toxic effects among fumonisins B (FB), deoxynivalenol (DON) and zearalenone (ZEN) administered alone and combined were investigated in 84-day-old ducks during force-feeding. 75 male ducks, divided into five groups of 15 animals, received daily during the meal a capsule containing the desired among of toxin. Treated animals received dietary levels of toxins equivalent to 20 mg FB1+FB2/kg (FB), 5 mg DON/kg (DON), 0.5 mg ZEN/kg (ZEN) and 20, 5 and 0.5 mg/kg of FB, DON and ZEN (FBDONZEN), respectively. Control birds received capsules with no toxin. After 12 days, a decrease in body weight gain accompanied by an increase in the feed conversion ratio was observed in ducks exposed to FBDONZEN, whereas there was no effect on performances in ducks exposed to FB, DON and ZEN separately. No difference among groups was observed in relative organ weight, biochemistry, histopathology and several variables used to measure oxidative damage and testicular function. A sphinganine to sphingosine ratio of 0.32, 1.19 and 1.04, was measured in liver in controls and in ducks exposed to FB and FBDONZEN, respectively. Concentrations of FB1 in liver were 13.34 and 15.4 ng/g in ducks exposed to FB and FBDONZEN, respectively. Together ZEN and its metabolites were measured after enzymatic hydrolysis of the conjugated forms. Mean concentrations of α-zearalenol in liver were 0.82 and 0.54 ng/g in ducks exposed to ZEN and FBDONZEN, respectively. β-zearalenol was 2.3-fold less abundant than α-zearalenol, whereas ZEN was only found in trace amounts. In conclusion, this study suggests that decreased performance may occur in ducks exposed to a combination of FB, DON and ZEN, but does not reveal any other interaction between mycotoxins in any of the other variables measured. Full article

(This article belongs to the Special Issue Effects of Mycotoxins on Health and Performance in Animals)

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26 pages, 2482 KiB

Open AccessEditor’s ChoiceArticle

Incentives to Stimulate European Wheat Farmers to Adapt Their Fusarium Species Mycotoxin Management

by Esmée M. Janssen, Monique C. M. Mourits, Alfons G. J. M. Oude Lansink and H. J. van der Fels-Klerx

Toxins 2021, 13(2), 144; https://doi.org/10.3390/toxins13020144 - 14 Feb 2021

Cited by 1 | Viewed by 2663

Abstract

Fusarium species infection in wheat can lead to Fusarium Head Blight (FHB) and contamination with mycotoxins. To fully exploit more recent insights into FHB and mycotoxin management, farmers might need to adapt their agronomic management, which can be stimulated through incentives. This study [...] Read more.

Fusarium species infection in wheat can lead to Fusarium Head Blight (FHB) and contamination with mycotoxins. To fully exploit more recent insights into FHB and mycotoxin management, farmers might need to adapt their agronomic management, which can be stimulated through incentives. This study aimed to identify incentives to stimulate European farmers to adapt their agronomic management to reduce FHB and related mycotoxins in wheat. A questionnaire was distributed among 224 wheat farmers from Italy, the Netherlands, Serbia, and the United Kingdom. Using the respondents’ data, Bayesian Network modelling was applied to estimate the probability that farmers would adapt their current agronomic management under eight different incentives given the conditions set by their farm and farmer characteristics. Results show that most farmers would adapt their current agronomic management under the incentives “paid extra when wheat contains low levels of mycotoxins” and “wheat is tested for the presence of mycotoxins for free”. The most effective incentive depended on farm and farmer characteristics, such as country, crop type, size of arable land, soil type, education, and mycotoxin knowledge. Insights into the farmer characteristics related to incentives can help stakeholders in the wheat supply chain, such as farmer cooperatives and the government, to design tailor-made incentive plans. Full article

(This article belongs to the Special Issue Occurrence and Integrated Management of Mycotoxins)

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15 pages, 4025 KiB

Open AccessEditor’s ChoiceArticle

Extracts Prepared from a Canadian Toxic Plant Induce Light-Dependent Perinuclear Vacuoles in Human Cells

by Jan M. Tuescher, Chad R. Beck, Locke Spencer, Benjamin Yeremy, Yutong Shi, Raymond J. Andersen and Roy M. Golsteyn

Toxins 2021, 13(2), 138; https://doi.org/10.3390/toxins13020138 - 12 Feb 2021

Cited by 1 | Viewed by 3323

Abstract

We are investigating plant species from the Canadian prairie ecological zone by phenotypic cell assays to discover toxins of biological interest. We provide the first report of the effects of extracts prepared from the shrub Symphoricarpos occidentalis in several human cell lines. S. [...] Read more.

We are investigating plant species from the Canadian prairie ecological zone by phenotypic cell assays to discover toxins of biological interest. We provide the first report of the effects of extracts prepared from the shrub Symphoricarpos occidentalis in several human cell lines. S. occidentalis (Caprifoliaceae) extracts are cytotoxic, and, strikingly, treated cells undergo light-dependent vacuolation near the nucleus. The range of irradiation is present in standard ambient light and lies in the visible range (400-700 nm). Vacuolization in treated cells can be induced with specific wavelengths of 408 or 660 nm at 1 J/cm² energies. Vacuolated cells show a striking phenotype of a large perinuclear vacuole (nuclear associated vacuole, NAV) that is distinct from vesicles observed by treatment with an autophagy-inducing agent. Treatment with S. occidentalis extracts and light induces an intense lamin A/C signal at the junction of a nuclear vacuole and the nucleus. Further study of S. occidentalis extracts and vacuolation provide chemical tools that may contribute to the understanding of nuclear envelope organization and human cell biology. Full article

(This article belongs to the Special Issue Basic Research for the Potential Use of Plant Toxins)

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9 pages, 3463 KiB

Open AccessEditor’s ChoiceArticle

Botulinum Neurotoxin Injections in Childhood Opisthotonus

by Mariam Hull, Mered Parnes and Joseph Jankovic

Toxins 2021, 13(2), 137; https://doi.org/10.3390/toxins13020137 - 12 Feb 2021

Cited by 7 | Viewed by 10249

Abstract

Opisthotonus refers to abnormal axial extension and arching of the trunk produced by excessive contractions of the paraspinal muscles. In childhood, the abnormal posture is most often related to dystonia in the setting of hypoxic injury or a number of other acquired and [...] Read more.

Opisthotonus refers to abnormal axial extension and arching of the trunk produced by excessive contractions of the paraspinal muscles. In childhood, the abnormal posture is most often related to dystonia in the setting of hypoxic injury or a number of other acquired and genetic etiologies. The condition is often painful, interferes with ambulation and quality of life, and is challenging to treat. Therapeutic options include oral benzodiazepines, oral and intrathecal baclofen, botulinum neurotoxin injections, and deep brain stimulation. Management of opisthotonus within the pediatric population has not been systematically reviewed. Here, we describe a series of seven children who presented to our institution with opisthotonus in whom symptom relief was achieved following administration of botulinum neurotoxin injections. Full article

(This article belongs to the Special Issue Botulinum Toxins: An Application in Humans and Animals)

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