Toxins

24 pages, 400 KiB

Open AccessReview

by Harriet L. Hammond and Chad J. Roy

Toxins 2024, 16(10), 417; https://doi.org/10.3390/toxins16100417 - 26 Sep 2024

Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and [...] Read more.

Palytoxins are a group of highly potent and structurally complex marine toxins that rank among some of the most toxic substances known to science. Palytoxins are naturally synthesized by a variety of marine organisms, including Palythoa zoanthids, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria, and are widely distributed in tropical and temperate regions where they can bioaccumulate in marine life. The evolution of research on palytoxins has been an intricate exchange between interdisciplinary fields, drawing insights from chemistry, biology, medicine, and environmental science in efforts to better understand and mitigate the health risks associated with this family of toxins. In this review, we begin with a brief history covering the discovery of this group of toxins and the events that led to its isolation. We then focus on the chemical structure of these compounds and their proposed mechanism of action. Finally, we review in vitro, ex vivo, and in vivo studies related to their toxicity, with the aim to provide a broad overview of the current knowledge on palytoxin toxinology. Full article

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

15 pages, 3079 KiB

Open AccessArticle

Effects of Propolis Supplementation on Gut Microbiota and Uremic Toxin Profiles of Patients Undergoing Hemodialysis

by Larissa Fonseca, Marcia Ribeiro, Júnia Schultz, Natália A. Borges, Ludmila Cardozo, Viviane O. Leal, Marcelo Ribeiro-Alves, Bruna R. Paiva, Paulo E. C. Leite, Carmen L. Sanz, Fernanda Kussi, Lia S. Nakao, Alexandre Rosado, Peter Stenvinkel and Denise Mafra

Toxins 2024, 16(10), 416; https://doi.org/10.3390/toxins16100416 - 25 Sep 2024

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Abstract

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota [...] Read more.

Background: Propolis possesses many bioactive compounds that could modulate the gut microbiota and reduce the production of uremic toxins in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This clinical trial aimed to evaluate the effects of propolis on the gut microbiota profile and uremic toxin plasma levels in HD patients. These are secondary analyses from a previous double-blind, randomized clinical study, with 42 patients divided into two groups: the placebo and propolis group received 400 mg of green propolis extract/day for eight weeks. Indole-3 acetic acid (IAA), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) plasma levels were evaluated by reversed-phase liquid chromatography, and cytokines were investigated using the multiplex assay (Bio-Plex Magpix^®). The fecal microbiota composition was analyzed in a subgroup of patients (n = 6) using a commercial kit for fecal DNA extraction. The V4 region of the 16S rRNA gene was then amplified by the polymerase chain reaction (PCR) using short-read sequencing on the Illumina NovaSeq PE250 platform in a subgroup. Forty-one patients completed the study, 20 in the placebo group and 21 in the propolis group. There was a positive correlation between IAA and TNF-α (r = 0.53, p = 0.01), IL-2 (r = 0.66, p = 0.002), and between pCS and IL-7 (r = 0.46, p = 0.04) at the baseline. No significant changes were observed in the values of uremic toxins after the intervention. Despite not being significant, microbial evenness and observed richness increased following the propolis intervention. Counts of the Fusobacteria species showed a positive correlation with IS, while counts of Firmicutes, Lentisphaerae, and Proteobacteria phyla were negatively correlated with IS. Two months of propolis supplementation did not reduce the plasma levels of uremic toxins (IAA, IS, and p-CS) or change the fecal microbiota. Full article

(This article belongs to the Section Uremic Toxins)

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16 pages, 6101 KiB

Open AccessArticle

Enhancing the Cytotoxicity and Apoptotic Efficacy of Parasporin-2-Derived Variants (Mpp46Aa1) on Cancer Cell Lines

by Juan S. Alarcón-Aldana, Lydia Visser, Nohora J. Rueda-Forero, Efraín H. Pinzón-Reyes, Paola Rondón-Villarreal and Miguel O. Suárez-Barrera

Toxins 2024, 16(10), 415; https://doi.org/10.3390/toxins16100415 - 25 Sep 2024

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Abstract

Parasporin PS2Aa1, recently renamed Mpp46Aa1, is an anti-cancer protein known for its selectivity against various human cancer cell lines. We genetically modified native PS2Aa1 to create a library of approximately 100 mutants. From this library, we selected promising mutants based on their half-maximal [...] Read more.

Parasporin PS2Aa1, recently renamed Mpp46Aa1, is an anti-cancer protein known for its selectivity against various human cancer cell lines. We genetically modified native PS2Aa1 to create a library of approximately 100 mutants. From this library, we selected promising mutants based on their half-maximal inhibitory concentration (IC₅₀) and sequence variations. In this study, Variant 3–35, with the G257V substitution, demonstrated increased cytotoxicity and selectivity against the colon cancer cell line SW480. Conversely, Variant N65, featuring substitutions N92D, K175R, and S218G, yielded the most favorable results against the cancer cell lines SW-620, MOLT-4, and Jurkat. The caspase 3/7 and 9, Annexin V-Cy3 and 6-GFDA activities, and, most notably, mitochondrial membrane permeabilization assays confirmed the apoptotic marker elevation. These findings indicate that residues 92, 175, 218, and 257 may play a critical role in the cytotoxic activity and selectivity. We successfully obtained genetically improved variants with substitutions at these key amino acid positions. Additionally, we conducted molecular dynamic simulations to explore the potential interactions between PS2Aa1 and the CD59 GPI-anchored protein. The simulation results revealed that residues 57, 92, and 101 were consistently present, suggesting their possible significance in the interactions between parasporin and the CD59 protein. Full article

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15 pages, 1341 KiB

Open AccessArticle

Effect of Temperature, Relative Humidity, and Incubation Time on the Mycotoxin Production by Fusarium spp. Responsible for Dry Rot in Potato Tubers

by Maria Gutiérrez-Pozo, Carol Verheecke-Vaessen, Sofia Kourmpetli, Leon A. Terry and Angel Medina

Toxins 2024, 16(10), 414; https://doi.org/10.3390/toxins16100414 - 24 Sep 2024

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Abstract

Potato is the fourth most consumed crop in the world. More than half of the crop is stored for three to nine months at cold temperatures (3–10 °C) for the fresh and seed market. One of the main causes of fresh potato waste [...] Read more.

Potato is the fourth most consumed crop in the world. More than half of the crop is stored for three to nine months at cold temperatures (3–10 °C) for the fresh and seed market. One of the main causes of fresh potato waste in the retail supply chain is the processing of fungal and bacterial rots during storage. Dry rot is a fungal disease that mainly affects the potato crop during storage and is responsible for 1% of tuber losses in the UK. It is produced by Fusarium spp., such as Fusarium sambucinum and F. oxysporum, which can lead to the accumulation of mycotoxins in the potato tuber. Little is known about the impact of environmental factors on the accumulation of mycotoxins in potato tubers. Understanding the ecophysiology of these fungi is key to mitigating their occurrence under commercial storage conditions. Therefore, this work aimed to elucidate the effect of three different temperatures (5, 10, and 15 °C) and two different water activities (a_w; 0.97, 0.99) on the ecophysiology and mycotoxin accumulation of F. sambucinum and F. oxysporum in a potato-based semi-synthetic medium. The mycotoxin accumulation was then studied in vivo, in potato tubers cultivated under organic farming conditions, stored for 40 days at 8.5 °C. Results showed that higher temperatures and a_w enhanced fungal growth, lag time, and mycotoxin accumulation in vitro. Growth rate was 2 and 3.6 times higher when the temperature increased from 5 to 10 and 15 °C, respectively. Six different mycotoxins (T-2, HT-2, diacetoxyscirpenol, 15-acetoxyscirpenol, neosolaniol, and beauvericin) were detected in vitro and in vivo. T-2 was the most abundant mycotoxin detected in vitro, observing 10⁶ ng of T-2/g media after 21 days of incubation at 10 °C and 0.99 a_w. Due to the long period of time that potato tubers spend in storage, the fluctuations of environmental factors, such as temperature and relative humidity, could promote the development of fungal rot, as well as mycotoxin accumulation. This could result in important food and economic losses for the potato market and a threat to food safety. Full article

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

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15 pages, 2730 KiB

Open AccessReview

Ultrasound-Guided Botulinum Toxin-A Injections into the Masseter Muscle for Both Medical and Aesthetic Purposes

by Marius Nicolae Popescu, Cristina Beiu, Carmen Andrada Iliescu, Andreea Racoviță, Mihai Berteanu, Mădălina Gabriela Iliescu, Ana Maria Alexandra Stănescu, Diana Sabina Radaschin and Liliana Gabriela Popa

Toxins 2024, 16(10), 413; https://doi.org/10.3390/toxins16100413 - 24 Sep 2024

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Abstract

With the increasing use of Botulinum toxin type A (BoNT-A) injections in the masseter muscles for both medical and aesthetic purposes, there is a constant need to continually enhance the efficacy of these treatments and reduce the risk of potential adverse events. This [...] Read more.

With the increasing use of Botulinum toxin type A (BoNT-A) injections in the masseter muscles for both medical and aesthetic purposes, there is a constant need to continually enhance the efficacy of these treatments and reduce the risk of potential adverse events. This review provides an in-depth analysis of the masseter muscle’s anatomical structure and essential landmarks and emphasizes the advantages of ultrasound (US) guidance in improving the precision of BoNT-A injections compared to conventional blind methods. The review is supplemented with comprehensive figures, including graphics, clinical images, and ultrasound visuals, to support the discussion. Potential complications such as paradoxical bulging, inadvertent injections into the risorius muscle or parotid gland, facial paralysis, and the risk of bone resorption are examined. Future research should aim at refining injection techniques and assessing the long-term effects of repeated treatments to ensure optimal patient care and safety. Full article

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

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28 pages, 4713 KiB

Open AccessArticle

A Monoclonal Antibody with a High Affinity for Ricin Isoforms D and E Provides Strong Protection against Ricin Poisoning

by Loïs Lequesne, Julie Dano, Audrey Rouaix, Camille Kropp, Marc Plaisance, Stéphanie Gelhaye, Marie-Lou Lequesne, Paloma Piquet, Arnaud Avril, François Becher, Maria Lucia Orsini Delgado and Stéphanie Simon

Toxins 2024, 16(10), 412; https://doi.org/10.3390/toxins16100412 - 24 Sep 2024

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Abstract

Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have [...] Read more.

Ricin is a highly potent toxin that has been used in various attempts at bioterrorism worldwide. Although a vaccine for preventing ricin poisoning (RiVax™) is in clinical development, there are currently no commercially available prophylaxis or treatments for ricin intoxication. Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. In this article, we describe the neutralizing and protective efficacy of a new generation of high-affinity anti-ricin mAbs, which bind and neutralize very efficiently both ricin isoforms D and E in vitro through cytotoxicity cell assays. In vivo, protection assay revealed that one of these mAbs (RicE5) conferred over 90% survival in a murine model challenged intranasally with a 5 LD₅₀ of ricin and treated by intravenous administration of the mAbs 6 h post-intoxication. Notably, a 35% survival rate was observed even when treatment was administered 24 h post-exposure. Moreover, all surviving mice exhibited long-term immunity to high ricin doses. These findings offer promising results for the clinical development of a therapeutic candidate against ricin intoxication and may also pave the way for novel vaccination strategies against ricin or other toxins. Full article

(This article belongs to the Section Plant Toxins)

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13 pages, 3203 KiB

Open AccessArticle

Brevetoxin Aptamer Selection and Biolayer Interferometry Biosensor Application

by Bo Hu, Sheng-Qun Ouyang, Yu-Ping Zhu, Xiao-Ling Lu, Zhe Ning, Bing-Hua Jiao, Liang-Hua Wang, Hao-Bing Yu and Xiao-Yu Liu

Toxins 2024, 16(10), 411; https://doi.org/10.3390/toxins16100411 - 24 Sep 2024

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Abstract

Brevetoxins (PbTxs) are very potent marine neurotoxins that can cause an illness clinically described as neurologic shellfish poisoning (NSP). These toxins are cyclic polyether in chemistry and have increased their geographical distribution in the past 2 decades. However, the ethical problems as well [...] Read more.

Brevetoxins (PbTxs) are very potent marine neurotoxins that can cause an illness clinically described as neurologic shellfish poisoning (NSP). These toxins are cyclic polyether in chemistry and have increased their geographical distribution in the past 2 decades. However, the ethical problems as well as technical difficulties associated with currently employed analysis methods for marine toxins have spurred the quest for suitable alternatives to be applied in a regulatory monitoring regime. In this work, we reported the first instance of concurrent aptamer selection of Brevetoxin-1 (PbTx-1) and Brevetoxin-2 (PbTx-2) and constructed a biolayer interferometry (BLI) biosensor utilizing PbTx-1 aptamer as a specific recognition element. Through an in vitro selection process, we have, for the first time, successfully selected DNA aptamers with high affinity and specificity to PbTx-1 and PbTx-2 from a vast pool of random sequences. Among the selected aptamers, aptamer A5 exhibited the strongest binding affinity to PbTx-1, with an equilibrium dissociation constant (K_D) of 2.56 μM. Subsequently, we optimized aptamer A5 by truncation to obtain the core sequence (A5-S3). Further refinement was achieved through mutations based on the predictions of a QGRS mapper, resulting in aptamer A5-S3G, which showed a significant increase in the K_D value by approximately 100-fold. Utilizing aptamer A5-S3G, we fabricated a label-free, real-time optical BLI aptasensor for the detection of PbTx-1. This aptasensor displayed a broad detection range from 100 nM to 4000 nM PbTx-1, with a linear range between 100 nM and 2000 nM, and a limit of detection (LOD) as low as 4.5 nM. Importantly, the aptasensor showed no cross-reactivity to PbTx-2 or other marine toxins, indicating a high level of specificity for PbTx-1. Moreover, the aptasensor exhibited excellent reproducibility and stability when applied for the detection of PbTx-1 in spiked shellfish samples. We strongly believe that this innovative aptasensor offers a promising alternative to traditional immunological methods for the specific and reliable detection of PbTx-1. Full article

(This article belongs to the Special Issue Unraveling the Environmental Threat of Harmful Algae Blooms (HABs): Causes and Impacts)

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Toxins, Volume 16, Issue 10 (October 2024) – 7 articles

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