Toxins最新文献

Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from infertile patients for common mycotoxins, including deoxynivalenol (DON), zearalenone (ZEN), its main metabolite alpha-zearalenol (aZOL), and aflatoxin M1 (AfM1), and examined their relationship with oxidative stress markers (MDA, SOD, GPx, CAT, and TAOC) and hormones (cortisol, estradiol, and anti-Müllerian hormone). Higher mycotoxin levels were associated with increased oxidative stress, particularly elevated MDA levels, and disrupted antioxidant enzyme activity. Notably, DON showed a positive correlation with SOD and estradiol levels, indicating a compensatory antioxidant response, while AfM1 served as a negative predictor. The metabolite aZOL was strongly linked to cortisol, with effects influenced by estradiol levels, implying endocrine-disrupting activity. Importantly, the interaction between DON and AMH appeared to impact dominant follicle development, suggesting a potential mechanism by which environmental toxins impair fertility without directly reducing oocyte or embryo counts. These results highlight the complex, dose-dependent effects of mycotoxins on oxidative and hormonal balances within the follicular environment, with implications for oocyte quality and reproductive success. Better understanding these mechanisms could help develop early diagnostic markers and targeted interventions to improve fertility outcomes in women exposed to changing environmental conditions.

This study aimed to explore the potential role of artificial intelligence in optimizing botulinum toxin type A treatment for spasticity and to evaluate its alignment with expert clinical decisions. A comparative analysis was conducted using thirty hypothetical clinical cases involving individuals with spasticity resulting from various neurological conditions. Five rehabilitation physicians, each with more than five years of experience, participated in the study. An artificial intelligence model trained on scientific literature and clinical guidelines generated treatment recommendations, including target muscles and dosages, which were compared with those proposed independently by the physicians. The primary outcome was the level of agreement in muscle selection and dosage. The model demonstrated consistency and adherence to guidelines but showed limited adaptability in complex presentations, such as an adducted thigh and equinovarus foot. It generally recommended lower dosages and differed significantly from physicians in both muscle selection and treatment strategies. Artificial intelligence shows promise as a clinical support tool in spasticity management, offering standardized and reproducible recommendations. However, its limited capacity to interpret clinical subtleties currently restricts its practical application. Future models should integrate multimodal clinical data and real-time clinician feedback to better emulate expert decision-making processes.

Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary component of venoms, are mainly accountable for haemotoxic and myotoxic effects. Although predominantly found in viper venoms, these enzymes are also present in varying levels in elapid snake venoms. Marimastat and prinomastat are matrix metalloprotease inhibitors initially developed as cancer therapies. Recently, extensive research has focused on these inhibitors to neutralise venom metalloproteases. However, their effects on different viper and elapid snake venoms remain unclear. Here, we report the sensitivity of seven elapid venoms (specifically, cobras) and 12 viper venoms to marimastat and prinomastat, utilising selective in vitro experiments and molecular docking analyses performed using representative metalloprotease (VAP2, a viper metalloprotease from the venom of Crotalus atrox and an elapid metalloprotease from the venom of Naja atra) structures. Both compounds inhibited the metalloprotease, fibrinogenolytic, and caseinolytic activities of most viper venoms. While prinomastat displayed prominent inhibitory effects on cobra venoms in these assays, marimastat demonstrated limited inhibitory effects on these venoms. These findings illustrate the role of matrix metalloprotease inhibitors in modulating metalloprotease activities across a range of viper and cobra venoms. Collectively, this study establishes the differential effects of marimastat and prinomastat on various levels of metalloproteases present in viper and elapid venoms. This will enhance understanding of the abundance of metalloproteases in snake venoms and their sensitivity to different matrix metalloprotease inhibitors.

The plant-based protein industry has explored new material sources, such as agro-industrial by-products and extraction techniques based on chemical properties assisted by ultrasound, high pressure and other tools to improve the yield and functionality of protein concentrates. However, promising by-products from vegetable processing are susceptible to incidental and natural contaminants, mainly mycotoxins. Adopting sustainable strategies and understanding how they affect mycotoxin fate during processing remains a challenge to ensure food security. In this study, a systematic literature review and bibliometric analysis were conducted to identify reliable pre-treatments and treatments for producing protein concentrates and evaluate the efficiency of technologies to mitigate mycotoxin bioaccessibility. Searching for research in Scopus, Web of Science and ScienceDirect (2010-2024) identified 3688 scientific articles on techniques to improve the yield and functionality of recovered proteins, but only three studies addressed mycotoxin fate. Aflatoxin, the most prevalent mycotoxin in raw materials, was the only one considered, highlighting that chemical and enzymatic treatments may help mitigate mycotoxicological risks in protein concentrates. Results indicate a gap in plant-based food security regarding mycotoxin contamination, which must be addressed through mitigation strategies aligned with efficient processes to ensure sustainable and safe plant protein-based foods.

(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively. (3) Results: Seven trials (n = 229) were included. Across all studies, toxin treatment reduced spasticity within groups, whereas additional spasticity reduction with RAT versus conventional rehabilitation was inconsistent. In contrast, several lower-limb trials reported greater improvements in walking capacity and balance when RAT was added, while upper-limb trials showed comparable motor recovery across treatment arms with occasional advantages in strength and movement quality. A pilot four-arm study suggested that starting RAT around four weeks after injection may maximize upper-limb motor gains. (4) Conclusions: The combination of BoNT-A with RAT appears safe and is particularly promising for gait rehabilitation, but further research is needed to define optimal timing and protocols.

Amanita muscaria (L.) Lam., commonly known as fly agaric, remains an uncommon yet clinically important cause of acute mushroom intoxication. Although typically associated with mild to moderate neuropsychiatric disturbances, the mushroom's toxic profile is highly variable and continues to attract scientific, toxicological, and public health interest. This work provides an integrative review of the biochemical composition, toxicodynamics, and clinical manifestations associated with A. muscaria exposure, with particular emphasis on the pharmacological actions of its principal constituents, ibotenic acid and muscimol. The review is complemented by two contemporaneous cases of severe intoxication in elderly individuals, illustrating the real-world clinical expression of the toxidrome and the challenges in diagnosis and management. Both cases presented with rapid-onset gastrointestinal symptoms, profound central nervous system depression, and cholinergic features, requiring intensive supportive therapy, atropine infusion, and continuous monitoring. Full recovery was achieved in both patients. These clinical observations contextualize the broader toxicological framework discussed in the review and underscore the need for increased clinical vigilance, improved public education, and strengthened diagnostic and therapeutic preparedness regarding psychoactive wild mushroom exposures.

This study examined the effects of ochratoxin A (OTA) exposure and graded dietary selenium (Se) supplementation on fatty acid (FA) composition and oxidative stress markers in the liver of broiler chickens. OTA is known to generate oxidative stress, promote lipid peroxidation, and affect the antioxidant system. Se, an essential trace element with antioxidant properties, may help counteract OTA-induced toxicity. In this short-term (5-day) in vivo feeding experiment, 21-day-old broiler chickens were divided into six groups, each with six birds: Control (diet free from Se), 0.3 mg/kg Se, 0.5 mg/kg Se, 2 mg/kg OTA, 2 mg/kg OTA + 0.3 mg/kg Se, 2 mg/kg OTA + 0.5 mg/kg Se. Our findings show that supplementing 0.3 mg/kg (p < 0.01) or 0.5 mg/kg Se (p < 0.001) in OTA-exposed birds significantly reduced the early oxidative stress markers (conjugated dienes and trienes) and significantly increased (0.3 mg/kg p < 0.01; 0.5 mg/kg p < 0.001) glutathione levels, indicating enhanced glutathione-dependent antioxidant protection. The treatments also significantly altered the ratio of monounsaturated and n6/n3 polyunsaturated FAs. OTA with 0.3 mg/kg Se supplementation significantly (p ˂ 0.05) reduced total unsaturation and FA average chain length. At a dose of 0.3 mg/kg, the interaction of Se and OTA altered the PUFA composition, while 0.5 mg/kg Se supplementation enhanced antioxidant defense and reduced lipid peroxidation. These results highlight the dual but separate role of Se, where inadequate doses may enhance OTA toxicity, while optimal supplementation may have a protective effect on hepatic lipid homeostasis. These findings can be used in the future progress of the mitigation strategy against OTA exposure in poultry nutrition.

Experimental animal models of orofacial pain have been instrumental in elucidating biological pathways underlying the antinociceptive effect of botulinum neurotoxin type A (BoNT/A). Although several mechanisms have been proposed to explain how BoNT/A relieves pain, the precise modes of action, particularly in the oral and maxillofacial areas, remain elusive. The purpose of this review was to synthesize and assess the latest proposed mechanisms of action through which BoNT/A attenuates orofacial pain in established animal models. A comprehensive search was conducted using the terms "botulinum neurotoxin," "mechanism," and "orofacial pain" or "trigeminal neuralgia." Only animal studies involving the establishment of an orofacial pain model were selected. Additional relevant studies were identified through manual screening of cited references. Over the past five years, several animal pain models have been established to decipher the mechanisms underlying the BoNT/A-mediated antinociception in orofacial pain. The proposed mechanisms include retrograde transport, neuronal excitability regulation, neuropeptide inhibition, inflammatory modulation, and opioid system stimulation in both the peripheral and central nervous systems. Despite the insubstantial number of investigations and findings, BoNT/A exhibits multidimensional modulation of nociceptive responses and, therefore, remains a promising therapeutic agent for managing orofacial pain conditions, with animal studies consistently providing insights into the mechanism of its antinociceptive action.

Fumonisins are mycotoxins commonly found on corn and other grains, and have been linked to several health concerns. The aim of this study is to estimate the exposure of the Hungarian population to fumonisins from regular food consumption. Fumonisin B1 and B2 concentrations were determined in commercially available corn-, wheat- and rice-based foods. Daily intakes on an individual level were calculated deterministically based on recent individual food consumption data distributions, and the average contamination of the concerned food categories. The most significant sources of fumonisins were corn flour, cornmeal, cornflakes, other corn-based products, and wheat-based products (average total fumonisin contents in the middle bound scenario were 0.115, 0.074, 0.052, 0.091 and 0.077 mg/kg, respectively). In cases where the concentration values measured below the analytical determination limits, these were substituted by half of the corresponding limits (middle bound scenario). Mean and high (95th percentile) exposures to fumonisins B1 + B2 were 0.101 and 0.258 µg/bw kg/day for adults, and 0.313 and 0.744 µg/bw kg/day for children, respectively. Our results show that about 1.5% of children's exposure could exceed the tolerable daily intake limit (TDI) of fumonisins, established by EFSA in 2018, meaning that potential health risks cannot be ruled out for a low proportion of consumers. We found that besides corn-based products, wheat-based food products could also contribute to total intake, due to their high consumption levels. Constant monitoring of fumonisin levels in corn- and wheat-based products is recommended to safeguard consumer health.

Feed contaminated with the mycotoxin deoxynivalenol (DON) can negatively impact livestock health and performance. Bacteria capable of degrading DON present a method of mitigating its harmful effects. This study aimed to identify microbial consortia from soil samples that could degrade DON. Soil from central (Lacombe, LA) and southern (Lethbridge, LE) Alberta were used as microbial inoculant. The soils were mixed with DON-contaminated wheat (18 ppm/kg) on day 0, and each soil type was divided into triplicate pots (180 g) and placed in a controlled environment for 32 d. Control pots of each soil type were included, which contained no DON-contaminated wheat. On days 0, 7, 14, and 32, 1 g subsamples were collected from pots, serially diluted in a limited medium containing DON (10 µg/mL) as the only carbon source, and incubated for 2 weeks (30 °C). DNA was extracted from the pots across time, as well as the subsample consortia grown in DON-amended medium, and was analyzed for bacterial changes after 16S rRNA gene sequencing. The relative abundance of bacterial genera in soil samples after enrichment with DON-contaminated wheat increased across time compared to the baseline day 0 time point. DON-degrading activity (26%) was only detected in LA soil suspension on day 7, and was highest after 14 days of incubation. The most abundant bacteria in the LA DON-degrading consortia belonged to the Pseudomonas (8.8%), Delftia (7.4%), Acinetobacter (6.4%), Comamonas (5.7%), Stenotrophomonas (5.5%), Shinella (5.5%), Ensifer (5.1%), Agrobacterium (5.0%), Achromobacter (4.7%), and Rhizobium (3.7%) genera. Pseudomonas aeruginosa (n = 9) and Serratia liquefaciens (n = 3) strains isolated from the LA consortia did not degrade DON. Overall, this study shows that the soil contained bacteria capable of degrading DON; however, variation existed depending on the soil's source.