Toxins最新文献

This study investigated the systemic metabolic effects of feeding a Fusarium-contaminated diet to early-lactation Holstein cows, with or without a mycotoxin-deactivating product (MDP; Mycofix^® Plus, BIOMIN Holding GmbH, Tulln, Austria). Thirty cows were divided into three dietary groups: a mildly contaminated control (CTR), a moderately contaminated diet containing zearalenone and deoxynivalenol (MTX), and the same contaminated diet supplemented with MDP. Plasma collected at 56 days in milk was analyzed by untargeted ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS), and multivariate models identified discriminant metabolites and pathways. MTX-fed cows showed alterations in sphingolipid metabolism, including accumulation of ceramide (t18:0/16:0), lactosylceramide, and sphinganine 1-phosphate, consistent with ceramide synthase inhibition and lipid remodeling stress. Increases in estradiol, estrone, and cholesterol sulfate suggested endocrine disruption, while elevated 8-oxo-dGMP indicated oxidative DNA damage. MDP supplementation mitigated these alterations, reducing sphingolipid intermediates, modulating tryptophan and glycerophospholipid pathways, and lowering oxidative stress markers. Metabolites such as riboflavin, pipecolic acid, and N-acetylserotonin could be likely associated with an improved mitochondrial function and redox homeostasis, although future studies are required to confirm this hypothesis. Additionally, MDP-fed cows exhibited distinct shifts in pyrimidine and nucleotide metabolism. Overall, MDP effectively counteracted Fusarium-related metabolic disturbances, supporting its protective role in maintaining lipid balance, hormonal stability, oxidative control, and metabolic resilience.

This scoping review aimed to summarize the current literature on the etiological and pathophysiological mechanisms associated with the development of retrograde cricopharyngeus dysfunction (R-CPD) through a PRISMA literature search. According to the current literature, a family history of R-CPD was reported in 28.0% of patients across studies, with childhood onset in 55.5% of cases. Gastroesophageal reflux disease and laryngopharyngeal reflux disease prevalence in R-CPD patients ranged from 16.3 to 51.9%, with improvement of heartburn symptoms after treatment. High-resolution manometry revealed dysmotility disorders in 43.5-80.0% of patients, with absent peristalsis in 11-25%. Carbonated drink provocative testing provided diagnostic usefulness in patients with unclear diagnoses by demonstrating failure of cricopharyngeal sphincter relaxation for retrograde gas. Notably, 75.5-79.9% of patients maintained symptom relief beyond the expected pharmacologic duration of botulinum toxin (approximately 6 months), suggesting potential neuroplastic adaptation or learned compensatory mechanisms in overcoming retrograde cricopharyngeal sphincter dysfunction. The pathophysiology of R-CPD remains incompletely understood, with a lack of epidemiological and pediatric studies. The genetic and environmental factors may play a key role, but future studies are needed to clarify their roles in the development of R-CPD.

Mycotoxins are global contaminants of feedstuffs and feeds that are linked to animal health and performance challenges and subsequently lead to economic burden. Negative effects of mycotoxin consumption may increase as a result of multiple mycotoxin co-occurrences. To assess mycotoxin challenge in Europe, a seven-year survey (2018 to 2024) of 1867 samples of grains (barley, maize, and wheat) and 818 forages (maize silage and grass silage) was conducted to assess the simultaneous presence of 54 mycotoxins using ultra-pressure liquid chromatography-tandem mass spectrometry. Results were categorized by feedstuff, harvest year, and climatic region to gain insight on mycotoxin occurrence, concentration and co-occurrence. Grains contained a mean 3.6 to 6.7 mycotoxin types per sample, while silages contained 3.1 to 6.0. Barley in the Nordic climate region had some of the highest Fusarium mycotoxin concentrations, while maize silage had consistently higher mycotoxin concentrations across all climate regions. The B trichothecenes and emerging mycotoxins had the highest rates of co-occurrence (52.4% to 74.2% of samples) in grains and maize silage. Co-occurrence data can serve as an initial framework for identifying or reasserting known environmental conditions that favor mycotoxin biosynthesis in distinct fungal taxa and for refining risk assessment of animals simultaneously exposed to multiple mycotoxins. Collectively, this survey shows that mycotoxin contamination and co-occurrence in grains and silages from Europe is expected, with differences occurring by feedstuff type and climatic region.

Chronic kidney disease (CKD) is associated with gut microbiota alterations that contribute to increased inflammation and the generation of uremic toxins and may worsen the disease progression. While probiotics may improve the pro-inflammatory cytokine profile, their effects on mineral metabolism, vascular calcification (VC), and CKD progression remain unclear. We aimed to evaluate the impact of a commercial probiotic (Probimel) supplementation on kidney function, mineral metabolism, inflammation and VC in both an experimental rat model and patients with advanced CKD and VC. The experimental model of VC was performed through 5/6 nephrectomy (Nx), a high-phosphate diet, and calcitriol. Animals were divided into three groups: Sham, Nephrectomy, and Nephrectomy + Probiotic. In the exploratory clinical study, 23 patients with advanced stage 5 CKD and VC were randomized and either received or did not receive daily probiotics for 6 months. Kidney function, mineral metabolism, uremic toxins, inflammation, VC, and fecal microbiota were evaluated. Probiotic supplementation decreased interleukin-6 (IL-6) and interpheron-γ (IFN-γ) and levels of the uremic toxin, indoxyl sulfate (IS), in the experimental model. However, no clear evidence of improvement in kidney function or vascular calcification was observed in either rats or patients with this probiotic. Under our experimental and clinical conditions, the selected probiotic did not modify key parameters related to CKD progression or VC.

ST-elevation myocardial infarction (STEMI) remains a major health concern despite advances in care. Indoxyl sulfate (IS) and p-cresyl-sulfate (p-CS) are gut-derived uremic toxins linked to higher morbidity and mortality in patients with chronic kidney disease (CKD). IS has been identified as an independent predictor of major adverse cardiovascular events (MACE) after STEMI, but data on p-CS are lacking. This study assessed the predictive value of IS and p-CS in STEMI patients with preserved renal function (cohort # NCT03070496). Plasma IS and p-CS were measured in 260 patients with STEMI who underwent primary coronary angiography. Samples collected 4 h after inclusion were analyzed using ultra-performance liquid chromatography with fluorescence detection. Optimal cut-offs were determined by the Youden index, and associations with MACE were evaluated by log-rank tests and Cox regression. Among 234 analyzed patients, 11.5% experienced MACE within one year. IS and p-CS levels were higher in the MACE group (IS: 3.14 vs. 2.19 µmol/L, p < 0.05; p-CS: 6.76 vs. 2.70 µmol/L, p < 0.01). Elevated p-CS independently predicted MACE (HR 3.79, 95% CI 1.29-11.17, p < 0.05), whereas IS lost significance after adjusting for kidney function. In STEMI patients, plasma p-CS is a stronger independent predictor of MACE than IS, highlighting its potential role in the gut-heart axis.

Zearalenone (ZEN) poses serious risks to human and animal health. Compared with physical and chemical methods, microbial transformation offers a safer and more sustainable strategy for ZEN detoxification. The yeast Hannaella zeae, isolated from the Qinghai-Tibet Plateau, showed the highest ZEN removal efficiency among 11 strains, achieving an 85.87% transformation rate within 36 h. Optimal conditions for ZEN transformation were determined by varying culture time, temperature, and pH. The products were putatively identified as zearalenone-14-β-D-glucopyranoside (C₂₄H₃₂O₁₀) and zearalenone-16-β-D-glucopyranoside (C₂₄H₃₂O₁₀) by UHPLC-Q-Orbitrap-HRMS. The safety of the mixed culture medium extract was further evaluated using a Caenorhabditis elegans model, showing significantly lower toxicity than untreated ZEN. H. zeae maintained high transformation efficiency under low temperature (57.48%) and acidic stress (47.10%), supported by active antioxidant enzymes (SOD, CAT, APX, GPx) and stress metabolites (trehalose, proline). Overall, this study identifies H. zeae as a promising, stress-tolerant biocontrol agent and elucidates its glycosylation-based detoxification mechanism, providing a foundation for future application in real food and feed systems.

Patulin is a mycotoxin produced mainly by Penicillium expansum on apples. P. expansum is a fruit pathogen that can cause apple soft rot. However, much is unknown about the characteristics of P. expansum and influence of major environmental parameters on its patulin production and growth on apple puree agar media (APAM). In this study, we evaluated the influence of pH, temperature, and relative humidity (RH) on patulin production by P. expansum OM1 and its growth (colony diameter and mycelial dry weight) on APAM after isolation and identification of the patulin-producing fungal strain from an apple. The fungal isolate produced the largest quantity of patulin on APAM under 15 °C, pH 4.0, and RH 98%, while it had the highest growth rates on the same media under 25 °C, pH 4.0-6.0, and RH 98%. Our data demonstrated that three important physicochemical factors (pH, temperature, and RH) substantially influenced the patulin production by the fungal species and its growth on APAM. Moreover, our results revealed that patulin was not detected on APAM at 5 °C after 7 days of incubation and that a trace amount of patulin was produced by the fungal strain along with its slow growth on the same media at 5 °C after 14 days. It suggests that patulin contamination by P. expansum on apples could be controlled during postharvest storage below 5 °C. These findings could provide fundamental knowledge for development of efficient strategies to prevent the occurrence of apples contaminated with patulin produced by P. expansum on them during postharvest storage.

This study investigated the bioaccumulation of ciguatoxins (CTXs) in dusky grouper (Epinephelus marginatus) following dietary exposure to toxic fish flesh. Two feeding groups were established: group A (amberjack (Seriola spp.) and dusky grouper flesh) and group B (moray eel (Muraena spp. and Gymnothorax spp.) flesh). CTX-like toxicity was detected in muscle and liver of group A. Flesh toxicity progressively increased from the first sampling. In contrast, CTX activity was only detected in livers in group B. Liquid chromatography-mass spectrometry analysis revealed the presence of C-CTX1 in both groups, and the 17-OH-C-CTX1 analogue was exclusively observed in group A. Toxicity in the liver peaked at 10 weeks in experimental group A, but it showed a decline by the end of the experiment while increasing the storage of the toxin in muscle tissue. These findings demonstrate the differential bioaccumulation of CTXs in grouper flesh and liver, highlighting the potential role of the liver in metabolizing and/or detoxifying ciguatoxins. The efficacy of a combination of different techniques, including the cell-based assay (CBA) and liquid chromatography-low- and high-resolution mass spectrometry (LC-MS/MS and LC-HRMS), was demonstrated to confirm the presence of CTX analogues at very low levels. The results provide insights into CTX transfer and accumulation in marine food webs, underlining the need for further studies on toxin metabolism in predatory fish species.

Toxic Shock Syndrome Toxin-1 (TSST-1) is produced by Staphylococcus aureus strains encoded by the tst gene. Toxic shock syndrome (TSS) is a severe disease caused by TSST-1 toxin and associated with staphylococcal food poisoning (SFP). The aim of the present review was to present data on the occurrence of S. aureus TSST-1 in foods published in various countries. PCR-based assays are most frequently used for the detection of S. aureus TSST-1 in foods. S. aureus TSST-1 is predominantly detected in foods of animal origin. The highest occurrence has been observed in mastitic ruminants' milk, indicating that mastitis is a risk of milk contamination with the pathogen. High occurrence rates of S. aureus TSST-1 have also been identified in raw milk and artisanal cheeses. Various occurrence levels have also been reported in beef, pork, lamb, and chicken meat. Low occurrence levels have also been reported for fish or other seafood products. The tst gene was also found in combination with other toxigenic genes in S. aureus TSST-1 isolates (e.g., MRSA or Panton-Valentine Leukocidin, PVL). Monitoring S. aureus TSST-1 in food is important for public health because food can be a vehicle for transmitting the antibiotic-resistant pathogen to humans.

We present the case of a Vipera ammodytes ammodytes (Vaa, nose-horned viper)-bitten patient with recurrent thrombocytopenia. A 53-year-old patient envenomated by Vaa experienced three episodes of venom-dependent thrombocytopenia (4, 57 and 11 × 10⁹/L), all of which we managed with antivenom Fab fragments. Despite these three severe episodes of thrombocytopenia within 24 h, platelet function remained intact, as demonstrated by normal thromboelastometry and aggregometry (96, 126, and 150 U) results after antivenom was administered and the platelet count normalized. Furthermore, flow cytometry showed only 0.3-1.7% expression of P-selectin on platelets, indicating that platelets did not activate but remained functional during and after thrombocytopenia. We assessed platelet function using rotational thromboelastometry, which evaluates the overall kinetics of hemostasis, including clot formation and stability. We performed aggregometry, which also reflects platelet function, only when the platelet count was within the normal range. Flow cytometry quantified P-selectin expression as a key marker of platelet activation. This case demonstrates that a component of Vaa venom can repeatedly induce venom-dependent thrombocytopenia, which is reversible by intervention, while platelet function remains intact.