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Ecotoxicology and Environmental Safety Jul 2024Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma...
Deoxynivalenol (DON) is one of the most common mycotoxins distributed in food and feed, which causes severe liver injury in humans and animals. Cold atmospheric plasma (CAP) has received much attention in mycotoxin degradation due to the advantages of easy operation, high efficiency, and low temperature. So far, the majority of studies have focused on the degradation efficiency and mechanism of CAP on DON, while there is still little information available on the hepatotoxicity of DON after CAP treatment. Herein, this study aimed to investigate the effect of CAP on DON-induced hepatotoxicity both in vitro and in vivo and its underlying mechanisms. The results showed that 120-s CAP treatment achieved 97 % degradation of DON. The vitro hepatotoxicity of DON in L02 cells was significantly reduced with CAP treatment time. Meanwhile, CAP markedly alleviated DON-induced liver injury in mice including the balloon-like degeneration of liver tissues and elevation of AST and ALP level. The underlying mechanism for CAP detoxification of DON-induced hepatotoxicity was further elucidated. The results showed that DON caused severe oxidative stress in cells by suppressing the antioxidant signaling pathway of Nrf2/HO-1/NQO-1, consequently leading to mitochondrial dysfunction and cell apoptosis, accompanied by cellular senescence and inflammation. CAP blocked DON inhibition on the Nrf2/HO-1/NQO-1 signaling pathway through the efficient degradation of DON, accordingly alleviating the oxidative stress and liver injury induced by DON. Therefore, CAP is an effective method to eliminate DON hepatotoxicity, which can be applied in the detoxification of mycotoxin-contaminated food and feed to ensure human and animal health.
Topics: Animals; Plasma Gases; Mice; Trichothecenes; Chemical and Drug Induced Liver Injury; Oxidative Stress; Liver; Apoptosis; Male; Humans; Inactivation, Metabolic; Cell Line
PubMed: 38843744
DOI: 10.1016/j.ecoenv.2024.116547 -
Food Chemistry May 2024Citrinin is a hepato-nephrotoxic mycotoxin produced by fungal species. The Monascus purpureus fungus plays a crucial role in the fermentation of red rice to produce red...
Development and validation of an analytical method for determination of citrinin in red rice and red yeast rice-based food supplements by ultra-high performance liquid chromatography tandem mass spectrometry.
Citrinin is a hepato-nephrotoxic mycotoxin produced by fungal species. The Monascus purpureus fungus plays a crucial role in the fermentation of red rice to produce red yeast rice-based food supplements, which represent the primary source of human exposure to citrinin. In this study, a simple and sensitive analytical method was successfully developed and validated for the citrinin determination in these products. The extraction process involved a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) step and citrinin determination by ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The proposed method provided satisfactory linearity, percentage of recovery from 82 to 104% with relative standard deviations (RSD) lower than 14%, and limits of detection and quantification of 0.07 μg/Kg and 0.24 μg/kg, respectively. Among the 14 samples analyzed, citrinin was found in two red rice samples (0.24 and 0.46 μg/kg) and in six food supplements (from 0.44 to 87 μg/kg).
PubMed: 38843711
DOI: 10.1016/j.foodchem.2024.139941 -
Food Microbiology Sep 2024Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for...
Penicillium spp. produce a great variety of secondary metabolites, including several mycotoxins, on food substrates. Chestnuts represent a favorable substrate for Penicillium spp. development. In this study, the genomes of ten Penicillium species, virulent on chestnuts, were sequenced and annotated: P. bialowiezense. P. pancosmium, P. manginii, P. discolor, P. crustosum, P. palitans, P. viridicatum, P. glandicola, P. taurinense and P. terrarumae. Assembly size ranges from 27.5 to 36.8 Mb and the number of encoded genes ranges from 9,867 to 12,520. The total number of predicted biosynthetic gene clusters (BGCs) in the ten species is 551. The most represented families of BGCs are non ribosomal peptide synthase (191) and polyketide synthase (175), followed by terpene synthases (87). Genome-wide collections of gene phylogenies (phylomes) were reconstructed for each of the newly sequenced Penicillium species allowing for the prediction of orthologous relationships among our species, as well as other 20 annotated Penicillium species available in the public domain. We investigated in silico the presence of BGCs for 10 secondary metabolites, including 5 mycotoxins, whose production was validated in vivo through chemical analyses. Among the clusters present in this set of species we found andrastin A and its related cluster atlantinone A, mycophenolic acid, patulin, penitrem A and the cluster responsible for the synthesis of roquefortine C/glandicoline A/glandicoline B/meleagrin. We confirmed the presence of these clusters in several of the Penicillium species conforming our dataset and verified their capacity to synthesize them in a chestnut-based medium with chemical analysis. Interestingly, we identified mycotoxin clusters in some species for the first time, such as the andrastin A cluster in P. flavigenum and P. taurinense, and the roquefortine C cluster in P. nalgiovense and P. taurinense. Chestnuts proved to be an optimal substrate for species of Penicillium with different mycotoxigenic potential, opening the door to risks related to the occurrence of multiple mycotoxins in the same food matrix.
Topics: Penicillium; Mycotoxins; Multigene Family; Secondary Metabolism; Genome, Fungal; Phylogeny; Food Contamination; Patulin; Fungal Proteins; Nuts; Polyketide Synthases; Food Microbiology; Corylus; Heterocyclic Compounds, 4 or More Rings; Indoles; Piperazines
PubMed: 38839238
DOI: 10.1016/j.fm.2024.104532 -
Frontiers in Plant Science 2024Fusarium crown rot (FCR) is an important and devastating disease of wheat () caused by the fungus and related pathogens. Using two distinct susceptible cultivars, we...
Fusarium crown rot (FCR) is an important and devastating disease of wheat () caused by the fungus and related pathogens. Using two distinct susceptible cultivars, we investigated the isolation frequencies of and quantified its biomass accumulation and the levels of the associated toxins deoxynivalenol (DON) and DON-3-glucoside (D3G) in inoculated field-grown wheat plants. We detected in stem, peduncle, rachis, and husk tissues, but not in grains, whereas DON and D3G accumulated in stem, rachis, husk, and grain tissues. Disease severity was positively correlated with the frequency of pathogen isolation, biomass, and mycotoxin levels. The amount of biomass and mycotoxin contents in asymptomatic tissue of diseased plants were associated with the distance of the tissue from the diseased internode and the disease severity of the plant. Thus, apparently healthy tissue may harbor and contain associated mycotoxins. This research helps clarify the relationship between occurrence, biomass, and mycotoxin accumulation in tissues of susceptible wheat cultivars with or without disease symptoms, providing information that can lead to more effective control measures.
PubMed: 38835863
DOI: 10.3389/fpls.2024.1356723 -
Neurotoxicology Jun 2024The rate of medical cannabis use has increased in parallel with the number of states legalizing its use. Parkinson's disease (PD) patients are of particular concern due...
The rate of medical cannabis use has increased in parallel with the number of states legalizing its use. Parkinson's disease (PD) patients are of particular concern due to their higher cannabis use rate than in the general US population (25-40% PD patient cannabis users vs. ~18% in the general population), as well as their susceptibility to environmental contaminants in cannabis, including pesticides, toxic elements, solvents, microbes, and mycotoxins. In order to address the complex nature of this industry, we examined the changes in PD-related qualifying conditions in the U.S. from 2019 to 2023. We also conducted an online survey to gain insight into the knowledge, risk perceptions, and opinions regarding medical cannabis and contamination issues from physicians who treated PD patients. The number of states including PD-related qualifying conditions increased over the past 5 years from 28 to 36 states. These conditions included PD (increasing from 14 to 16 states), muscle spasms (14 to 24), anxiety (1 to 5), and pain (17 to 35). State-by-state comparisons revealed high variability in the language used to describe the different qualifying conditions. Online surveys were sent out to 45 neurologists and movement disorder specialists who primarily treated PD patients. The response rate was 44% from nine states (AZ, CA, FL, MA, MN, WI, PA, IL, and NM). When asked if they were aware of any contaminants in cannabis products, we found that 65% of the physicians were unaware of any contaminants commonly found in cannabis and only 25%, 15%, and 15% of them were aware of pesticide, toxic element, and solvent contaminants, respectively. In their free-text opinion response on the health impact of cannabis-borne contaminants, "long-term effect" (35%) and "comorbidities and PD prognosis" (40%) were identified as the two most common themes. These results point to the need for further regulatory deliberation regarding risks and susceptibility to cannabis contaminants. Additionally, education is needed to inform physicians on cannabis safety issues. Further research will identify the implementation strategies to reduce contaminant exposure and protect patient health.
PubMed: 38834158
DOI: 10.1016/j.neuro.2024.05.008 -
Ecotoxicology and Environmental Safety Jul 2024Aflatoxin B (AFB) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious...
Aflatoxin B (AFB) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB on bovine hepatic cells and the protective role of allicin against AFB-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB for co-cultivation. Our findings indicate that AFB compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.
Topics: Animals; Sulfinic Acids; Aflatoxin B1; Cattle; Disulfides; NF-E2-Related Factor 2; Signal Transduction; Hepatocytes; Oxidative Stress; Apoptosis; Antioxidants; Female
PubMed: 38833978
DOI: 10.1016/j.ecoenv.2024.116527 -
Cell Biology and Toxicology Jun 2024Hippocampal neurons maintain the ability of proliferation throughout life to support neurogenesis. Deoxynivalenol (DON) is a mycotoxin that exhibits brain toxicity, yet...
Hippocampal neurons maintain the ability of proliferation throughout life to support neurogenesis. Deoxynivalenol (DON) is a mycotoxin that exhibits brain toxicity, yet whether and how DON affects hippocampal neurogenesis remains unknown. Here, we use mouse hippocampal neuron cells (HT-22) as a model to illustrate the effects of DON on neuron proliferation and to explore underlying mechanisms. DON exposure significantly inhibits the proliferation of HT-22 cells, which is associated with an up-regulation of cell cycle inhibitor p21 at both mRNA and protein levels. Global and site-specific mA methylation levels on the 3'UTR of p21 mRNA are significantly increased in response to DON treatment, whereas inhibition of mA hypermethylation significantly alleviates DON-induced cell cycle arrest. Further mechanistic studies indicate that the mA readers YTHDF1 and IGF2BP1 are responsible for mA-mediated increase in p21 mRNA stability. Meanwhile, 3'UTR of E3 ubiquitin ligase TRIM21 mRNA is also mA hypermethylated, and another mA reader YTHDF2 binds to the mA sites, leading to decreased TRIM21 mRNA stability. Consequently, TRIM21 suppression impairs ubiquitin-mediated p21 protein degradation. Taken together, mA-mediated upregulation of p21, at both post-transcriptional and post-translational levels, contributes to DON-induced inhibition of hippocampal neuron proliferation. These results may provide new insights for epigenetic therapy of neurodegenerative diseases.
Topics: Animals; Trichothecenes; Hippocampus; Mice; Neurons; Cyclin-Dependent Kinase Inhibitor p21; Up-Regulation; Cell Proliferation; RNA-Binding Proteins; Cell Line; 3' Untranslated Regions; Neurogenesis; RNA, Messenger; RNA Stability; Cell Cycle Checkpoints; Ribonucleoproteins; Methylation
PubMed: 38833095
DOI: 10.1007/s10565-024-09872-7 -
Mycology 2024Asexual spores, called conidia, are key reproductive fungal particles that enable survival in harsh environmental conditions or host systems. The conidia can infect...
Asexual spores, called conidia, are key reproductive fungal particles that enable survival in harsh environmental conditions or host systems. The conidia can infect humans, animals, and plants to cause various fungal diseases. Transcription factors, including VosA, WetA, and SscA, have key roles in conidia formation and long-term survival in . Herein, we report the pleiotropic functions of SscA in the conidia of the human pathogen . The deletion of increased conidia formation despite decreased fungal growth. Absence of impaired long-term survival and reduced spore resistance to various stresses, including heat, UV, and oxidation. Transcriptomic analyses showed that SscA involved the mRNA expression of cell wall organisation-related genes. Importantly, the deletion mutant conidia contained an increased amount of β-glucan and chitin compared to wild type conidia. In addition, conidial gliotoxin production was decreased in the deletion strain. Overall, SscA has pleiotropic roles in conidia formation, maturation and dormancy and mycotoxin production in .
PubMed: 38813476
DOI: 10.1080/21501203.2023.2294061 -
Food Chemistry Oct 2024In this study, we developed a hydrogel from cross-linked keratin and chitosan (KC) to remove patulin (PAT) from apple juice. We explored the potential of incorporating...
In this study, we developed a hydrogel from cross-linked keratin and chitosan (KC) to remove patulin (PAT) from apple juice. We explored the potential of incorporating Lactobacillus rhamnoses into the KC hydrogel (KC-LR) and tested its effectiveness in removing PAT from simulated juice solutions and real apple juice. The KC hydrogel was developed through a dynamic disulfide cross-linking reaction. This cross-linked hydrogel network provided excellent stability for the probiotic cells, achieving 99.9 % immobilization efficiency. In simulated juice with 25 mg/L PAT, the KC and KC-LR hydrogels showed removal efficiencies of 85.2 % and 97.68 %, respectively, using 15 mg mL of the prepared hydrogel at a temperature of 25 °C for 6 h. The KC and KC-LR hydrogels achieved 76.3 % and 83.6 % removal efficiencies in real apple juice systems, respectively. Notably, the encapsulated probiotics did not negatively impact the juice quality and demonstrated reusability for up to five cycles of the PAT removal process.
Topics: Chitosan; Malus; Fruit and Vegetable Juices; Lacticaseibacillus rhamnosus; Hydrogels; Patulin; Keratins; Probiotics; Food Contamination
PubMed: 38811285
DOI: 10.1016/j.foodchem.2024.139619 -
Journal of Pharmaceutical and... Sep 2024Consumption of misidentified foraged mushrooms containing bicyclic amanitin octapeptides is a worldwide public health and veterinary problem, being considered one of the...
Consumption of misidentified foraged mushrooms containing bicyclic amanitin octapeptides is a worldwide public health and veterinary problem, being considered one of the deadliest accidental human and canine food ingestion due to acute liver failure (ALF). Reversal of advanced ALF and complete clinical recovery can be achieved following definitive removal of accumulated amatoxin laden bile from the gallbladder. An accurate means of quantifying amanitin content in aspirated bile is, therefore, urgently needed. Building on our prior work validating a method to detect and quantify amanitin in hepatic autopsy tissue, the development of an accurate method of measuring α- and β-amanitin in aspirated gallbladder bile was performed to evaluate the efficiency of this emergency procedure applied as a clinical treatment for intoxicated patients. A solid-phase extraction (SPE) procedure was optimized followed by detection based on ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Low resolution mass spectrometry (LRMS) was compared with high resolution (HRMS) by the validation of UHPLC-MS/MS (triple quadrupole MS) and UHPLC-ToF-MS (time-of-flight MS). Both methods were able to detect amatoxins in bile with limits of detection and quantification ranging from 2.71 to 3.46 µg.kg, and 8.36-9.03 µg.kg for α-amanitin and, 0.32-1.69 µg.kg and 0.55-5.62 µg.kg for β-amanitin, respectively. Validation was completed with the evaluation of linearity, specificity, robustness, recovery, and precision following the ICH guidelines and CIR 808/2021. The validated methods were finally applied to bile samples obtained 48-96 hours + post-ingestion from 4 amatoxin poisoning patients who underwent gallbladder drainage procedures in Vietnam, Canada, and California. Gallbladder bile from patients with amatoxin mushroom poisoning contained significant amanitin content, even when aspirated several days post-ingestion, thus confirming the important role of enterohepatic circulation in amatoxin hepatotoxicity. This work represents a high and unique analytical throughput in amanitin poisoning allowing to efficiently respond to this fatal health problem.
Topics: Bile; Chromatography, High Pressure Liquid; Amanitins; Humans; Tandem Mass Spectrometry; Limit of Detection; Solid Phase Extraction; Reproducibility of Results; Alpha-Amanitin; Mushroom Poisoning
PubMed: 38810334
DOI: 10.1016/j.jpba.2024.116253