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19 pages, 13468 KB  
Article
Morphological Diversity of Epichloë sinensis from Festuca sinensis Germplasm on the Qinghai–Tibet Plateau
by Junying Liu, Jiawen Sun, Yanqun Zhao, Zhongxiang Li, Mei Zhang, Longxuan Cui, Jinhui Shen, Yang Luo, Yue Gao, Wei Zhou, Taixiang Chen, Tian Wang, Mingxiang Du, Wencong Liu, Chao Xia, Tao Hu and Pei Tian
J. Fungi 2026, 12(3), 166; https://doi.org/10.3390/jof12030166 - 25 Feb 2026
Viewed by 616
Abstract
Epichloë sinensis engages in mutualistic symbiosis with Festuca sinensis on the Qinghai–Tibet Plateau. The influence of variation within the Epichloë genus on morphology in this context is poorly understood, as is the influence of environmental factors (e.g., temperature, precipitation, and altitude). Accordingly, a [...] Read more.
Epichloë sinensis engages in mutualistic symbiosis with Festuca sinensis on the Qinghai–Tibet Plateau. The influence of variation within the Epichloë genus on morphology in this context is poorly understood, as is the influence of environmental factors (e.g., temperature, precipitation, and altitude). Accordingly, a total of 122 fungal endophyte strains were isolated from 270 F. sinensis seeds collected from different locations on the Qinghai–Tibet Plateau, and their morphological characteristics were observed. The colonies were white on the front, dark brown in the center on the back, and light brown or yellow around the PDA medium, exhibiting typical characteristics of E. sinensis. Morphological diversity was categorized into (1) colony features (six types based on texture, shape, and cracks), (2) growth rates (51 strains that produce spores: 0.23–0.78 mm/d; 71 strains that do not produce spores: 0.11–0.93 mm/d), and (3) hyphal width (51 strains that produce spores: 0.60–2.57 μm; 71 strains that do not produce spores: 0.95–2.10 μm). Correlation analyses revealed that temperature and altitude had significant effects on these traits. Phylogenetic relationships showed that 17 strains probably were E. sinensis, and only 4 strains probably were the endophyte E. poae. One strain was haploid and may have originated from E. festucae. All 22 tested strains lacked genes associated with toxic alkaloid biosynthesis (ergot alkaloid) but harbored regulatory genes for the insect-resistant alkaloid peramine, demonstrating potential for use in developing new germplasm in Festuca species. Full article
(This article belongs to the Special Issue Endophytic Fungi–Plant Interactions and Ecology)
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17 pages, 925 KB  
Review
The Dark Side of Grasslands: Endophyte Toxicosis in Horses—Exposure Risks, Health Consequences, and Management
by Qendrim Zebeli, Lena Lindner and Barbara U. Metzler-Zebeli
Toxins 2026, 18(3), 117; https://doi.org/10.3390/toxins18030117 - 24 Feb 2026
Viewed by 936
Abstract
Grasslands are the cornerstone of horse feeding, used for grazing and to produce roughages and their products. However, improper grassland management hides several threats for equine health. In this context, grasslands contaminated with toxin-producing endophytes are considered an increasing threat for horses in [...] Read more.
Grasslands are the cornerstone of horse feeding, used for grazing and to produce roughages and their products. However, improper grassland management hides several threats for equine health. In this context, grasslands contaminated with toxin-producing endophytes are considered an increasing threat for horses in many parts of the world. Endophytes are fungi that may grow in a mutualistic relationship in a range of grasses, including fescue grass and perennial ryegrass, two foliage species commonly found in European and American meadows and pastures. The endophytes produce alkaloids that are highly toxic to insects and animals, including horses. Among the four types of endophyte alkaloids, namely peramine, loline, indole diterpene, and ergot alkaloids, the latter two are known to be (neuro)toxic to horses. Recent research indicates that increasing concentrations and co-occurrence of ergot alkaloids and indole diterpene in horse pastures and meadows, especially during hot and arid summer months, increase the risk of endophyte toxicosis in horses. The main aim of this review article is to summarize the most recent knowledge on endophytic alkaloids of grasslands and products thereof, and the resulting endophyte toxicosis in horses, focusing mainly on the exposure risks, symptoms and management strategies. Full article
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15 pages, 4114 KB  
Article
Biochemical and Genetic Characterization of Ergot Alkaloid Biosynthesis in Aspergillus aspearensis
by Jessica L. Fuss and Daniel G. Panaccione
Toxins 2026, 18(1), 47; https://doi.org/10.3390/toxins18010047 - 16 Jan 2026
Viewed by 834
Abstract
Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized [...] Read more.
Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized the recently described fungus Aspergillus aspearensis (Aspergillaceae) would synthesize lysergic acid amides. Cultures of A. aspearensis produced abundant lysergic acid α-hydroxyethylamide (LAH) and lesser amounts of other lysergic acid derivatives. Conidia contained high concentrations of ergot alkaloids, whereas sclerotia contained significantly less. Approximately half of the ergot alkaloids produced were secreted into the culture medium. When spores of A. aspearensis were injected into larvae of the model insect Galleria mellonella, larvae died at a significantly faster rate than control larvae. The fungus produced ergot alkaloids during insect pathogenesis and later produced conidia and sclerotia on cadavers, indicating it can complete its life cycle in an insect. The genome of A. aspearensis contained two complete ergot alkaloid synthesis gene clusters, similar to those of A. leporis; however, unlike its sister species, none of the ergot cluster genes were pseudogenized. Aspergillus aspearensis is a newly discovered source of ergot alkaloids and may be useful for studying and producing these important chemicals. Full article
(This article belongs to the Section Mycotoxins)
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24 pages, 1672 KB  
Review
Innovative Detection and Mitigation of Ergot Alkaloids in Cereals: Advancing Food Safety
by Maria Balatsou, Aikaterini Koutsaviti, Yiannis Sarigiannis and Christos C. Petrou
Metabolites 2025, 15(12), 778; https://doi.org/10.3390/metabo15120778 - 3 Dec 2025
Cited by 1 | Viewed by 1281
Abstract
Background/Objectives: Ergot alkaloids are mycotoxins produced mainly by fungi of the genus Claviceps, infecting a wide variety of plants, especially cereals. These toxins usually manifest as black, hardened sclerotia (ergots), though they may also be invisible when dispersed in grain. They [...] Read more.
Background/Objectives: Ergot alkaloids are mycotoxins produced mainly by fungi of the genus Claviceps, infecting a wide variety of plants, especially cereals. These toxins usually manifest as black, hardened sclerotia (ergots), though they may also be invisible when dispersed in grain. They pose a significant risk to animals and humans when present in contaminated cereals. They can cause ergotism, with vasoconstriction, ischemia, hallucinations, and in severe cases gangrene. This study was carried out in response to the European legislative actions which determine the permissible levels of ergot alkaloids in cereals. Historically, consumers manually removed visible sclerotia from grain, and farmers applied fertilizers or timed harvests to specific periods to mitigate contamination. However, these traditional methods have proven insufficient. We therefore explored advanced techniques for detecting and quantifying ergot-contaminated cereals, as well as methods for reducing ergot alkaloid concentrations. Methods: Searches were conducted in scientific databases including Google Scholar, PubMed, and Scopus to identify research articles, reviews, and experimental studies published mainly between 2012 and August 2025, including accepted or in-press manuscripts, with special attention to works from 2021 onward to capture the most recent advancements. Results/Conclusions: Ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) is the reference method for confirmatory, epimer-aware quantification of ergot alkaloids, and is already standardized. Recent QuEChERS-UHPLC-MS/MS workflows in cereal matrices, including oat-based products, routinely achieve limits of quantification of about 0.5–1.0 µg/kg with single-run analysis times of about 5–15 min. Rapid screening options complement, rather than replace, confirmatory mass spectrometry: magnetic bead-based immunoassays that use magnetic separation and a smartphone-linked potentiostat provide sub-hour turnaround and field portability for trained quality-assurance staff, although external validation and calibration traceable to LC-MS/MS remain prerequisites for routine use. In practice, operators are adopting tiered, orthogonal workflows (e.g., immunoassay or electronic-nose triage at intake followed by DNA-based checks on grain washings and LC–MS/MS confirmation, or hydrazinolysis “sum parameter” screening followed by targeted MS speciation). Such combinations reduce turnaround time while preserving analytical rigor. Biotechnology also offers potential solutions for reducing ergot alkaloid concentrations at the source. Finally, to enhance consumer safety, artificial intelligence and blockchain-based food traceability appear highly effective. These systems can connect all stakeholders from producers to consumers, allowing for real-time updates on food safety and rapid responses to contamination issues. This review primarily synthesizes advances in analytical detection of ergot alkaloids, while mitigation strategies and supply chain traceability are covered concisely as supporting context for decision making. Full article
(This article belongs to the Special Issue Analysis of Specialized Metabolites in Natural Products)
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12 pages, 1119 KB  
Article
Effects of Clipping Heifer Hair Coats on Vaginal Temperatures and Performance of Fall-Born Heifers Stocked on Toxic Endophyte-Infected Tall Fescue During the Summer
by Christopher T. Beard, William S. Swecker, Ozzie Abaye and Gabriel J. Pent
Grasses 2025, 4(4), 47; https://doi.org/10.3390/grasses4040047 - 12 Nov 2025
Viewed by 645
Abstract
Achieving satisfactory levels of weight gain for developing replacement beef heifers is challenging when utilizing toxic endophyte-infected tall fescue (Schedonorus arundinaceus) as the primary forage. This is due to the intensifying impact of ergot alkaloids produced by the fungal endophyte on [...] Read more.
Achieving satisfactory levels of weight gain for developing replacement beef heifers is challenging when utilizing toxic endophyte-infected tall fescue (Schedonorus arundinaceus) as the primary forage. This is due to the intensifying impact of ergot alkaloids produced by the fungal endophyte on heifer heat stress in the summer. The purpose of this trial was to determine if clipping hair coats would reduce heat stress impacts experienced by fall-born heifers stocked on toxic endophyte-infected tall fescue. Heifers were randomly assigned to a control cohort and a clipped cohort. The heifers in the clipped treatment group were sheared along the body of the heifer. Vaginal temperature loggers were used to record core temperatures every ten minutes during several sampling periods. Hair coats on clipped heifers resembled hair coats of the control heifers by the conclusion of the 16-week trial. Average daily gains of the clipped heifers exceeded the average daily gains of the control heifers only in the first four-week period. There were no differences in seasonal average daily gain or pregnancy rates. Clipped heifers had cooler core temperatures by 0.2–0.3 °C in the morning compared to the control heifers. Clipping hair coats of heifers only provided short-term relief for cattle stocked on toxic endophyte-infected tall fescue. Full article
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16 pages, 2288 KB  
Article
Controlled Crystallization Enables Facile Fine-Tuning of Physical–Chemical Properties of Nicergoline Toward Easier Processability
by Barbora Blahová Prudilová, Roman Gabriel, Michal Otyepka and Eva Otyepková
Pharmaceuticals 2025, 18(10), 1465; https://doi.org/10.3390/ph18101465 - 29 Sep 2025
Cited by 1 | Viewed by 2897
Abstract
Background/Objectives: Crystallization is a key process in the manufacturing of active pharmaceutical ingredients (APIs), as it significantly affects the physical and chemical properties of the final product. Nicergoline, a clinically relevant ergot derivative, was chosen as a model compound to investigate how [...] Read more.
Background/Objectives: Crystallization is a key process in the manufacturing of active pharmaceutical ingredients (APIs), as it significantly affects the physical and chemical properties of the final product. Nicergoline, a clinically relevant ergot derivative, was chosen as a model compound to investigate how different crystallization strategies affect particle attributes. The objective of this study was to compare controlled and uncontrolled crystallization techniques and evaluate their impact on the physicochemical properties of nicergoline. Methods: Nicergoline was crystallized using controlled methods, including sonication-induced and seeding-induced crystallization, and uncontrolled methods, namely cubic and linear cooling, as well as acetone evaporation. The resulting powders were characterized by using a range of physicochemical techniques to assess particle morphology, size distribution, agglomeration behavior, and surface properties. Results: Uncontrolled crystallization methods produced particles prone to agglomeration, resulting in a broader particle size distribution ranging from 8 to 720 µm and heterogeneous surface characteristics. In contrast, controlled crystallization generated more uniform particles with reduced agglomeration and narrower particle size distributions. Among the evaluated methods, sonocrystallization provided the most effective control over particle size and morphology, demonstrated by a narrow size distribution ranging from 16 to 39 µm which correlated with improved flowability and surface energy. Conclusions: The study demonstrates that the choice of crystallization method significantly influences the structural and physicochemical properties of nicergoline. These findings highlight the importance of method selection for tailoring API properties to enhance downstream processing and product quality. Full article
(This article belongs to the Section Pharmaceutical Technology)
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21 pages, 3131 KB  
Article
Morphological, Molecular, and Alkaloid Gene Profiling of Epichloë Endophytes in Elymus cylindricus and Elymus tangutorum from China
by Taixiang Chen, Wencong Liu, Kai Huang, Gensheng Bao and Chunjie Li
Microorganisms 2025, 13(10), 2275; https://doi.org/10.3390/microorganisms13102275 - 28 Sep 2025
Viewed by 1054
Abstract
Epichloë endophytes are mutualistic associates with grasses, conferring host plants with enhanced competitiveness, improved stress tolerance, and increased ecological dominance. Epichloë can produce any of several classes of bioactive alkaloids, of which indole-diterpenes and ergot alkaloids are toxic to invertebrate and mammalian herbivores; [...] Read more.
Epichloë endophytes are mutualistic associates with grasses, conferring host plants with enhanced competitiveness, improved stress tolerance, and increased ecological dominance. Epichloë can produce any of several classes of bioactive alkaloids, of which indole-diterpenes and ergot alkaloids are toxic to invertebrate and mammalian herbivores; peramine acts as an insect-feeding deterrent; and loline alkaloids possess potent insecticidal activity. Here, it was characterized as Epichloë endophytes inhibiting the Elymus species, El. cylindricus, and El. tangutorum from the Qinghai–Tibet Plateau, China. Based on the results of four types of alkaloid synthesis genes, the 30 isolates were divided into five types; they exhibited distinct alkaloid synthesis capabilities, highlighting intraspecific diversity within E. bromicola regarding its alkaloid-producing potential. Considering the toxicity of these isolates to the safety of herbivorous livestock, the above five types of isolates can be divided into two categories. Category I includes five animal-safe strains of type V, which do not produce alkaloids. Category II includes the remaining 25 strains, which could produce indole-diterpene (paspaline) and/or ergot alkaloids (chanoclavine I, D-lysergic acid, ergovaline) that are toxic to herbivorous livestock. Morphology and phylogenetic analysis confirmed all 30 isolates were Epichloë bromicola; mating type gene detection shows that all belonged to mating type A. Overall, this study has laid a solid foundation for the scientific and rational utilization of Epichloë endophyte resources. Furthermore, the presence of ergovaline in El. cylindricus and El. tangutorum poses a potential concern for livestock managers who conduct grazing. Full article
(This article belongs to the Section Plant Microbe Interactions)
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12 pages, 457 KB  
Review
α1A-Adrenergic Receptor as a Target for Neurocognition: Cautionary Tale from Nicergoline and Quinazoline Non-Selective Blockers
by Dianne M. Perez
Pharmaceuticals 2025, 18(10), 1425; https://doi.org/10.3390/ph18101425 - 23 Sep 2025
Cited by 2 | Viewed by 3164
Abstract
Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further [...] Read more.
Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the α1A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective α1-AR antagonists of the quinazoline class, referred to as “osins”, as potential treatments for COVID-19/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not α1-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the α1A-adrenergic receptor as an “old target” to treat Alzheimer’s and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine’s actions, through α1A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases. Full article
(This article belongs to the Special Issue Pharmacotherapy for Alzheimer’s Disease)
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20 pages, 728 KB  
Communication
Effects of Dietary Inclusion of Tannin-Based Supplements on Performance and Health of Yearling Beef Heifers Grazing Toxic, Endophyte-Infected Tall Fescue
by Miriam A. Snider, Cody E. Gruber, Robin A. Cheek, Tom Hess, Elizabeth B. Kegley, Jeremy G. Powell, G. Doug Hufstedler, J. Daniel Rivera and M. Shane Gadberry
Vet. Sci. 2025, 12(8), 749; https://doi.org/10.3390/vetsci12080749 - 12 Aug 2025
Viewed by 1162
Abstract
This study evaluated dietary inclusion of tannin-based feed additives on heifer performance and physiological measures associated with fescue toxicosis and vaccine response. Forty-five yearling beef heifers (292.6 ± 29.0 kg) grazing toxic, endophyte-infected (E+) tall fescue pastures were assigned to 1 of 3 [...] Read more.
This study evaluated dietary inclusion of tannin-based feed additives on heifer performance and physiological measures associated with fescue toxicosis and vaccine response. Forty-five yearling beef heifers (292.6 ± 29.0 kg) grazing toxic, endophyte-infected (E+) tall fescue pastures were assigned to 1 of 3 treatment groups: (1) soybean hulls (SH; n = 3 pastures), (2) SH and BX tannin-saponin additive (BX; 10.0 g heifer−1 d−1; n = 3 pastures), and (3) SH and ATX tannin-polyphenol additive (ATX; 5.0 g heifer−1 d−1; n = 3 pastures). Treatments were administered over an 84 d period. Data were analyzed using R and SAS 9.4 with treatment as a fixed effect, block as a random effect, and pasture as the experimental unit. Treatment effects were assessed at the pasture level. Average daily gain (ADG) of heifers receiving ATX (0.53 kg/d) and BX (0.49 kg/d) were increased relative to heifers receiving SH only (0.23 kg/d) between D56 and D84 (p = 0.07). There was no impact of treatment on other performance measures (p > 0.15) or on serum metabolite responses including bovine herpesvirus type 1 (BHV-1) titers (p > 0.15), prolactin (p = 0.97), haptoglobin (p = 0.26), and blood urea nitrogen (BUN; p = 0.38). Preliminary results show the potential for improved weight gain, suggesting further investigation with more experimental units is warranted. Full article
(This article belongs to the Section Veterinary Physiology, Pharmacology, and Toxicology)
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20 pages, 1243 KB  
Article
Comparison of Capillary Electrophoresis and HPLC-Based Methods in the Monitoring of Moniliformin in Maize
by Sara Astolfi, Francesca Buiarelli, Francesca Debegnach, Barbara De Santis, Patrizia Di Filippo, Donatella Pomata, Carmela Riccardi and Giulia Simonetti
Foods 2025, 14(15), 2623; https://doi.org/10.3390/foods14152623 - 26 Jul 2025
Cited by 1 | Viewed by 1761
Abstract
Over the past few decades, scientific interest in mycotoxins—fungal metabolites that pose serious concern to food safety, crop health, and both human and animal health—has increased. While major mycotoxins such as aflatoxins, ochratoxins, deoxynivalenol, fumonisins, zearalenone, citrinin, patulin, and ergot alkaloids are well [...] Read more.
Over the past few decades, scientific interest in mycotoxins—fungal metabolites that pose serious concern to food safety, crop health, and both human and animal health—has increased. While major mycotoxins such as aflatoxins, ochratoxins, deoxynivalenol, fumonisins, zearalenone, citrinin, patulin, and ergot alkaloids are well studied, emerging mycotoxins remain underexplored and insufficiently investigated. Among these, moniliformin (MON) is frequently detected in maize-based food and feed; however, the absence of regulatory limits and standardized detection methods limits effective monitoring and comprehensive risk assessment. The European Food Safety Authority highlights insufficient occurrence and toxicological data as challenges to regulatory development. This study compares three analytical methods—CE-DAD, HPLC-DAD, and HPLC-MS/MS—for moniliformin detection and quantification in maize, evaluating linear range, correlation coefficients, detection and quantification limits, accuracy, and precision. Results show that CE-DAD and HPLC-MS/MS provide reliable and comparable sensitivity and selectivity, while HPLC-DAD is less sensitive. Application to real samples enabled deterministic dietary exposure estimation based on consumption, supporting preliminary risk characterization. This research provides a critical comparison that supports the advancement of improved monitoring and risk assessment frameworks, representing a key step toward innovating the detection of under-monitored mycotoxins and laying the groundwork for future regulatory and preventive measures targeting MON. Full article
(This article belongs to the Special Issue Recent Advances in the Detection of Food Contaminants and Pollutants)
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11 pages, 434 KB  
Article
The Effects of Endophyte-Infected Tall Fescue on the Production and Reproductive Performance Parameters of Beef Cattle and Calves
by Amber A. Taylor, John H. Fike, Vitor R. G. Mercadante and Gabriel J. Pent
Grasses 2025, 4(3), 29; https://doi.org/10.3390/grasses4030029 - 15 Jul 2025
Cited by 2 | Viewed by 1342
Abstract
Records from 2012 to 2019 for two herds were analyzed to determine how tall fescue (Schedonorus arundinaceus (Schreb.) Dumont) endophyte (Epichloë coenophialum) status affected the productivity of spring-calving cows and calves. Pastures either contained tall fescue with wildtype endophyte (high [...] Read more.
Records from 2012 to 2019 for two herds were analyzed to determine how tall fescue (Schedonorus arundinaceus (Schreb.) Dumont) endophyte (Epichloë coenophialum) status affected the productivity of spring-calving cows and calves. Pastures either contained tall fescue with wildtype endophyte (high levels of ergot alkaloids) or novel- or endophyte-free tall fescue (largely ergot alkaloid free). The experimental design was a randomized complete block with year as the replication unit. Forage samples from the farm with toxic endophyte-infected tall fescue contained 1136 ± 413 ppb total ergot alkaloids, while forage from the non-toxic pastures on the second farm contained 118 ± 83 ppb total ergot alkaloids. Artificial insemination pregnancy rates and calving rates were greater (p < 0.05) for cows that grazed non-toxic tall fescue (51.2 ± 2.8% and 93.5 ± 1.4%, respectively) than for cows on toxic endophyte-infected tall fescue (43.3 ± 2.8% and 88.8 ± 1.4%, respectively). Birth weights and weaning weights were greater (p < 0.05) for calves from the non-toxic tall fescue system (37 ± 1 kg and 278 ± 8 kg, respectively) than for calves from the toxic endophyte-infected tall fescue system (33 ± 1 kg and 254 ± 8 kg, respectively). Raising cattle on tall fescue without the toxic endophyte improved cow and calf productivity. Full article
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17 pages, 1906 KB  
Article
Effects of Psilocin and Psilocybin on Human 5-HT4 Serotonin and H2 Histamine Receptors in Perfused Hearts of Transgenic Mice
by Pauline Braekow, Joachim Neumann, Uwe Kirchhefer and Ulrich Gergs
Pharmaceuticals 2025, 18(7), 1009; https://doi.org/10.3390/ph18071009 - 6 Jul 2025
Viewed by 2814
Abstract
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or [...] Read more.
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or H2 histamine receptors. However, whether psilocybin or psilocin acts at isolated mammalian ventricular preparations and whether they increase protein phosphorylation in the mammalian ventricle remains to be elucidated. Methods: To this end, the FOC and phospholamban phosphorylation in isolated perfused hearts from transgenic mice with cardiomyocyte-specific overexpression of either human 5-HT4 receptors (5-HT4-TG) or human H2 receptors (H2-TG) and their wild-type littermates (WT) were examined. Furthermore, the ergot alkaloids ergometrine, ergotamine, and LSD were used as references. Results: Psilocybin and psilocin enhanced the FOC to 137% and to 152%, respectively, and elevated the phospholamban phosphorylation in isolated perfused hearts from 5-HT4-TG. In H2-TG hearts, psilocybin and psilocin increased the FOC to a much lesser extent but had no effect on the phospholamban phosphorylation. In contrast, LSD increased the FOC and phosphorylation state of phospholamban in isolated hearts of both 5-HT4-TG and H2-TG. On the other hand, ergometrine and ergotamine increased the FOC only in H2-TG. Ergometrine increased the phosphorylation state of phospholamban in perfused hearts from H2-TG, but not from 5-HT4-TG. Ergotamine failed to increase the phospholamban phosphorylation in both H2-TG and 5-HT4-TG. Psilocybin, psilocin, ergotamine, ergometrine, and LSD were unable to increase FOC and phospholamban phosphorylation in perfused hearts from WT. Conclusions: The increase in the phosphorylation state of phospholamban could provide a partial explanation for the positive inotropic effects and the relaxant effects of not only psilocybin and psilocin but also ergometrine and LSD in the isolated hearts of the animals used in this study. Full article
(This article belongs to the Special Issue Psychedelics: A New Drug Candidate for Treating Mental Illness)
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23 pages, 3679 KB  
Article
Impact of Low-Level Ergot Alkaloids and Endophyte Presence in Tall Fescue Grass on the Metabolome and Microbiome of Fall-Grazing Steers
by Ignacio M. Llada, Jeferson M. Lourenco, Madison M. Dycus, Jessica M. Carpenter, Zachery R. Jarrell, Dean P. Jones, Garret Suen, Nicholas S. Hill and Nikolay M. Filipov
Toxins 2025, 17(5), 251; https://doi.org/10.3390/toxins17050251 - 17 May 2025
Cited by 1 | Viewed by 1705
Abstract
Fescue toxicosis (FT) is a mycotoxin-related disease caused by the ingestion of tall fescue, naturally infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. Some grazing on endophyte-free (E−) or non-toxic (NT), commercial endophyte-infected pastures takes place in the US as well. [...] Read more.
Fescue toxicosis (FT) is a mycotoxin-related disease caused by the ingestion of tall fescue, naturally infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. Some grazing on endophyte-free (E−) or non-toxic (NT), commercial endophyte-infected pastures takes place in the US as well. Earlier, we found that grazing on toxic fescue with low levels of EAs during fall affects thermoregulation, behavior, and weight gain. Building on these findings, the current study aimed to investigate how the presence of low EA-producing E+ or NT endophytes can influence animal metabolome, microbiome, and, ultimately, overall animal health. Eighteen Angus steers were placed on NT, E+, and E− fescue pastures for 28 days. Urine, rumen fluid (RF), rumen solid (RS), and feces were collected pre-exposure, and on days 2, 7, 14, 21, and 28. An untargeted high-resolution metabolomics approach was used to analyze urine and RF, while 16S rRNA-based next-generation sequencing (NGS) was used to examine RF, RS, feces, and fescue plant microbiomes. While alpha- or beta-microbiota diversity across all analyzed matrices were unaffected, there were specific effects of E+ on the relative abundance of some taxa (i.e., Prevotellaceae). Additionally, E+ grazing impacted aromatic amino acid metabolism in the urine and the metabolism of lipids in both the RF and urine. In both matrices, trace amine-related metabolic features differed markedly between E+ and the other groups. Compared to the endophyte-free group, endophyte presence, whether novel or toxic, influenced amino acid and carbohydrate metabolism, as well as unsaturated fatty acid biosynthesis. These findings suggest that low-EA-producing and non-toxic endophytes in fescue have more prominent effects on the metabolome than the microbiome, and this metabolome perturbation might be associated with decreased performance and reported physiological signs of FT. Full article
(This article belongs to the Section Mycotoxins)
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13 pages, 1083 KB  
Article
Molasses-Based Block Supplements for Cattle Fed Endophyte-Infected Tall Fescue (Festuca arundinacea) Seed: Effects on Growth Performance, Circulating Biomarkers, Heat Stress, and Coccygeal Artery Diameter
by Luis F. B. B. Feitoza, Brad J. White and James S. Drouillard
Animals 2025, 15(5), 717; https://doi.org/10.3390/ani15050717 - 3 Mar 2025
Cited by 1 | Viewed by 1274
Abstract
Ergot alkaloids present in endophyte-infected tall fescue can cause a series of negative effects in exposed cattle. This study evaluated the effectiveness of molasses-based block supplements (MBSs) in alleviating vasoconstriction, which leads to reduced peripheral blood flow, heat stress, and impaired growth performance [...] Read more.
Ergot alkaloids present in endophyte-infected tall fescue can cause a series of negative effects in exposed cattle. This study evaluated the effectiveness of molasses-based block supplements (MBSs) in alleviating vasoconstriction, which leads to reduced peripheral blood flow, heat stress, and impaired growth performance in cattle. A total of 100 crossbred steers were assigned to five treatment groups: a negative control with no tall fescue seed; a positive control with ergot-infected tall fescue seeds; and three MBS treatments, including a control block, a block containing menthol, and a block containing capsaicin. Blood flow was assessed through ultrasound imaging of the coccygeal artery, while thermal imaging was used to monitor body temperature regulation. Growth performance, feed intake, and blood biomarkers were also measured. Cattle consuming MBS had improved weight gain, greater arterial diameters, and enhanced thermoregulation compared to those without supplements. No significant differences were observed between the different MBS formulations. These results suggest that molasses-based block supplementation can help mitigate heat stress and poor growth performance associated with ergot alkaloid consumption, potentially providing a practical nutritional strategy for cattle producers managing cattle exposed to ergot alkaloids. Full article
(This article belongs to the Section Animal Nutrition)
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Article
Optimization, Validation, and Application of Cleanup-Coupled Liquid Chromatography–Tandem Mass Spectrometry for the Simultaneous Analyses of 35 Mycotoxins and Their Derivatives in Cereals
by Dan-Bi Kim, Miso Nam, Yong-Suk Kim and Min-Sun Kim
Foods 2024, 13(22), 3617; https://doi.org/10.3390/foods13223617 - 13 Nov 2024
Cited by 1 | Viewed by 2741
Abstract
Mycotoxins occur singly or as co-contaminants and are primarily present in carbohydrate-rich foods such as cereals and cereal-based products. To effectively monitor mycotoxin co-contamination in cereals and cereal-based products, the simultaneous analysis of mycotoxins and their derivatives is required. Therefore, we coupled cleanup [...] Read more.
Mycotoxins occur singly or as co-contaminants and are primarily present in carbohydrate-rich foods such as cereals and cereal-based products. To effectively monitor mycotoxin co-contamination in cereals and cereal-based products, the simultaneous analysis of mycotoxins and their derivatives is required. Therefore, we coupled cleanup with LC-MS/MS for the rapid and robust quantitation of 35 analytes in wheat samples, including ergot alkaloids (EAs), which are rarely included in such analyses. To investigate the effects of different mycotoxin types on adsorbents, various dispersive solid-phase extraction sorbents were evaluated; a C18 end-capped sorbent exhibited the most effective cleanup performance. The method was validated by analyzing samples fortified with the mycotoxins at three concentration levels. The results exhibited high linearity, high recoveries, and repeatability. The methodology was applied for commercial cereal samples. The cereal samples were found to be 74% contaminated, and two samples measured levels of EAs at 609.63 μg/kg and 294.93 μg/kg, exceeding the limits defined by the EU for rye milling products. These findings highlight the validity of our novel method and the necessity of continuously monitoring mycotoxin levels in cereals to ensure food safety. Full article
(This article belongs to the Section Food Analytical Methods)
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