Toxins最新文献

Hazelnut (Corylus avellana L.) is a major crop in the Caucasus region, but its safety is often threatened by Aspergillus flavus colonization and aflatoxin contamination. Although aflatoxins (AFs) are strictly regulated in the EU, the influence of post-harvest practices on fungal persistence and AF accumulation remains poorly defined. A three-year study was conducted to evaluate the effects of drying protocols, storage temperature, and conservation practices on fungal growth and AF occurrence in hazelnuts from three producing regions of Azerbaijan. Freshly harvested nuts were subjected to two drying regimes: good drying (sun-exposed, mixed, protected from rewetting) and bad drying (shaded, piled, rewetted). After drying, samples were stored at cold (8-10 °C) or room temperature (18-22 °C). Fungal prevalence was determined by CFU counts with morphological and qPCR identification of Aspergillus section Flavi. AFs were quantified by HPLC, and water activity (a_w) was monitored during storage. Drying emerged as the decisive factor: bad drying consistently resulted in markedly higher fungal loads for A. section Flavi, with mean counts up to 1.3 log10 (CFU/g), compared with 0.8 log10 (CFU/g) under good drying, representing a 7-fold increase. In contrast, storage temperature and shell condition had negligible effects when nuts were properly dried. Aflatoxins were consistently below the 5 µg/kg EU limit for AFB₁ in traced and well-dried samples, whereas market samples occasionally exhibited AFB₁ concentrations >450 µg/kg. These findings highlight drying efficiency as the key determinant of fungal persistence and AF risk in hazelnut post-harvest management.

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1-3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice.

Clostridial neurotoxins, botulinum neurotoxins (BoNTs), and tetanus neurotoxin (TeNT) are potent toxins responsible for severe diseases, botulism and tetanus, respectively. BoNTs associate with non-toxic proteins (non-toxic non-hemagglutinin, hemagglutinins, and OrfXs), which protect BoNTs against acidic pH and protease degradation and facilitate BoNT passage through the intestinal barrier. TeNT enters motor neurons and undergoes a retrograde axonal transport until the target inhibitory interneurons in the central nervous system. BoNTs and TeNT recognize specific cell surface receptors which consist of complex sets of protein(s)-glycan-gangliosides and determine specific cell entry pathways. Recent data on structural and functional investigations of BoNT and TeNT receptors bring a better understanding of toxin trafficking in the host and entry into target neuronal cells, which is useful for the development of updated strategies of prevention and treatment of the corresponding diseases. Since clostridial neurotoxins, notably BoNTs, are important therapeutic tools, detailed knowledge of their activity opens the way of the development of engineered molecules for specific clinical applications.

Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (Ca_V) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A₂ subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on Ca_V heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba²⁺ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type Ca_V2.2 and Ca_V1.2 L-type calcium channels, in a dose-dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications.

The objective of this study was to evaluate the protective effect of curcumin (Cur) on reproductive toxicity induced by fumonisin B₁ (FB₁) in laying ducks during the peak egg-laying period. A total of seventy-two 50-week-old Cherry Valley ducks were randomly assigned to four groups: control, FB₁ (30 mg/kg), Cur (200 mg/kg), and Cur + FB₁ (200 mg/kg + 30 mg/kg). The experiment lasted for 35 days. Our results showed that cur supplementation effectively restored the reductions in final body weight (p = 0.005) and oviduct length (p = 0.020) induced by FB₁ exposure. Residual FB₁ concentrations in serum, liver, and ovaries were markedly increased in the FB₁-treated group, while Cur significantly decreased the FB₁ residual in duck liver (p < 0.05). Meanwhile, Cur supplementation markedly counteracted the FB₁-induced reductions in serum total protein, albumin, triglycerides, and high-density lipoprotein induced by FB₁ exposure. Cur supplementation effectively regulated FB₁-induced oxidative stress, inflammation, and endocrine disruption. Specifically, Cur lowered FB₁-induced malondialdehyde levels (p < 0.010), attenuated interleukin-1β increase (p = 0.083), and reversed the reduction in immunoglobulin G levels. FB increased the levels of hormones associated with duck reproduction, including estradiol, follicle-stimulating hormone, and luteinizing hormone; in contrast, curcumin supplementation decreased the levels of these hormones (p < 0.010). Histopathological analysis revealed that Cur significantly alleviated the inflammation and necrosis in the liver, kidneys, ovaries, and oviducts induced by FB₁. In conclusion, dietary Cur supplementation effectively alleviated FB₁-induced reproductive toxicity in laying ducks by enhancing antioxidant capacity, improving lipid metabolism, and restoring hormonal homeostasis.

Aflatoxins are highly toxic secondary metabolites that contaminate dietary staples in many developing world regions, with hundreds of millions of people estimated to be chronically exposed. In this review, we summarize the evidence about AF exposure assessment and its relationship to stunting. Despite multiple attempts, this question has eluded a strong scientific conclusion due to the nature of the toxin and exposure, the disparate methods used for assessment, and the ethical difficulties of studying a toxin in low-resource settings. We highlight current challenges in defining these relationships, how this has reduced the ability to draw conclusions in this area, and approaches to overcome these to advance the field. Current reviews tend to report mixed associations, but typically lack critique of the study designs, and a limited understanding of patterns of aflatoxin exposure coupled with a probable variable threshold for effect. We highlight the potential diverse patterns of AF exposure over time and how that may influence study design to address this critical public health issue.

Bacillus anthracis has three main virulence factors: an extracellular capsule and two binary toxins (lethal toxin-consists of a lethal factor and a protective antigen, and edema toxin-consists of an edema factor and a protective antigen). In the Russian Federation, the epidemiological situation regarding anthrax infection remains unfavorable. In the late stages of an anthrax infection, antibiotic therapy becomes ineffective and the patient dies within 24 h as a large amount of lethal toxin accumulates in the patient's blood. Antibodies capable of neutralising lethal toxin (LT) can be an effective treatment for these patients. The objective of the study was to construct a chimeric monoclonal antibody targeting the protective antigen of the LT and to elucidate its mechanism of toxin neutralization. In this work, a chimeric monoclonal antibody (xi1E10) directed against the protective antigen was successfully produced. Both in vitro and in vivo experiments demonstrated the capacity of xi1E10 to neutralize lethal toxin. Confocal microscopy revealed that xi1E10 effectively suppresses the formation of a functional pore, thereby blocking the translocation of the lethal factor into the cytosol. These findings indicate that the monoclonal antibody xi1E10 represents a promising candidate for the development of a therapeutic drug.

Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments.

Animal venoms, complex mixtures of molecules refined over thousands of years of evolution, represent far more than a simple defense or predatory system in venomous animals. [...].

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. One-third of patients with DN develop primary glomerulonephritis, and membranous nephropathy (MN) is the most common concurrent glomerulonephritis. Nephrotic syndrome (NS) due to DN and MN is often refractory to immunosuppressants because increased levels of low-density lipoprotein (LDL) not only accelerates kidney injury but also reduce the bioavailability of cyclosporine, a first-line immunosuppressant for MN. Given the pathological role of LDL, especially oxidized LDL, reducing LDL cholesterol levels can help achieve remission of NS and halt the progression of kidney injury. Although some lipoproteins are not excreted by the kidneys, excessive LDL, including oxidized LDL, can be considered uremic toxic-like factors that contribute to the development of NS or DN. We encountered a 74-year-old patient with concomitant DN and MN who achieved complete remission following additional LDL apheresis (LDL-A) with immunosuppressant therapy. Here, we provide a narrative review summarizing the role of LDL, especially ox-LDL, in the progression of DN and glomerulonephritis, including MN, and discuss the therapeutic rationale for LDL-A. We also present a representative case of concomitant MN and DN refractory to conventional immunosuppression who achieved clinical improvement following LDL-A.