Toxins最新文献

A complex of Fusarium species frequently infects maize, causing root, ear, and stem rot, yield losses, reduced seed quality, and mycotoxin accumulation. To quantify Fusarium species composition and mycotoxin contamination, we conducted a first nationwide monitoring in Swiss commercial grain maize over three years (2008-2010), followed by grain maize hybrid experiments across five sites (2011-2013). Samples were analysed for species incidence, fungal DNA, and the mycotoxins deoxynivalenol, zearalenone, and fumonisins. For each field, crop management data were collected. Fusarium graminearum, F. verticillioides, F. subglutinans, and F. proliferatum were predominant, and deoxynivalenol was the most frequent toxin, with 55% of the samples exceeding the European pig feed guidance value (0.9 mg kg^-1). Overall, fumonisin contamination was low: only 11% of samples were above the limit of detection. The year, the length of the growing period, and the timing of the harvest were the principal determinants of F. graminearum infection and deoxynivalenol/zearalenone accumulation, whereas other agronomic factors, including crop rotation, soil management, and maturity class, showed only limited or inconsistent effects. Results from this study provide evidence that farmers should avoid long growing periods and late harvests to reduce the risk of high deoxynivalenol/zearalenone content. The maize hybrid experiments confirmed the overriding influence of weather conditions on Fusarium species incidence and mycotoxin content, leading to high inter-annual variability. These results highlight the need for standardised, long-term field experiments to disentangle agronomic effects and environmental drivers.

Limited data are available on gender differences in patients with post-stroke spasticity (PSS) treated with onabotulinumtoxinA (onabotA). This subgroup analysis of data from the BOTOX^® Economic Spasticity Trial (BEST) focused on onabotA-treated patients stratified by gender. BEST was a double-blind, placebo-controlled, randomized study with an open-label extension that allowed for up to five treatments. It evaluated the effectiveness of onabotA + Standard of Care (SC) vs. placebo + SC for the treatment of PSS. At baseline, out of 139 patients treated with onabotA, females (n = 54) had a slightly higher body mass index (BMI) compared to males (n = 85) (28.3 vs. 26.9 kg/m²), and a greater percentage of females (40.7%) took analgesic medications compared to males (31.8%). Scores from baseline assessments for pain, spasticity severity, and stroke recovery were comparable between groups. Despite these similarities at baseline, females received an average lower dose (range, 337-365 U) of onabotA compared to males (range, 343-421 U) across treatment sessions. Females also had lower changes from baseline compared to males on pain, spasticity severity, stroke recovery, and functional goal achievement assessments across most onabotA treatment sessions. There is a need for further investigation into treatment approaches to optimize outcomes for both males and females with PSS.

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia-reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential.

Bt Cry toxins remain the cornerstone of transgenic crop protection against Lepidopteran pests, yet field-evolved resistance, particularly in invasive species such as Spodoptera frugiperda and Helicoverpa armigera, can threaten their long-term efficacy. This review presents a comprehensive and unified mechanistic framework that synthesizes current understanding of Bt Cry toxin modes of action and the complex, multilayered regulatory mechanisms of field-evolved resistance. Beyond the classical pore-formation model, emerging evidence highlights signal transduction cascades, immune evasion via suppression of Toll/IMD pathways, and tripartite toxin-host-microbiota interactions that can dynamically modulate protoxin activation and receptor accessibility. Resistance arises from target-site alterations (e.g., ABCC2/ABCC3, Cadherin mutations), altered midgut protease profiles, enhanced immune regeneration, and microbiota-mediated detoxification, orchestrated by transcription factor networks (GATA, FoxA, FTZ-F1), constitutive MAPK hyperactivation (especially MAP4K4-driven cascades), along with preliminary emerging findings on non-coding RNA involvement. Countermeasures now integrate synergistic Cry/Vip pyramiding, CRISPR/Cas9-validated receptor knockouts revealing functional redundancy, Domain III chimerization (e.g., Cry1A.105), phage-assisted continuous evolution (PACE), and the emerging application of AlphaFold3 for structure-guided rational redesign of resistance-breaking variants. Future sustainability hinges on system-level integration of single-cell transcriptomics, midgut-specific CRISPR screens, microbiome engineering, and AI-accelerated protein design to preempt resistance trajectories and secure Bt biotechnology within integrated resistance and pest management frameworks.

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, people living with all three conditions often struggle with mood issues like depression and anxiety, which can originate from both the burden of illness and changes in brain biology. We studied 61 patients (CD, n = 30; BSP, n = 9; HFS, n = 22) and assessed depression and anxiety before and three weeks after botulinum neurotoxin type A (BoNT-A) therapy, considering injection site and dose. BoNT-A significantly reduced depressive and anxiety symptoms across all groups, regardless of disease type, dose, or glabellar injection. These psychiatric improvements were not associated with the degree of motor symptom reduction, suggesting a partially independent mechanism of mood modulation. Our findings indicate that BoNT-A's mood benefits may extend beyond local motor effects, possibly involving broader sensorimotor-limbic interactions. These results highlight the therapeutic potential of BoNT-A for addressing non-motor symptoms in both dystonic and non-dystonic hyperkinetic disorders. Future studies employing imaging and neurophysiological methods are necessary to explain the neural pathways underlying these effects.

Aflatoxins, particularly aflatoxin B₁ (AFB₁), are among the most potent naturally occurring carcinogens and remain a major food-borne hazard in parts of Asia and Africa. China has generated a uniquely cohesive body of evidence connecting aflatoxin contamination to hepatocellular carcinoma (HCC), especially in settings where chronic hepatitis B virus (HBV) infection is highly prevalent and acts synergistically with aflatoxin exposure. Over five decades, field investigations and laboratory innovations-exemplified by long-term work in Qidong-have assembled a multi-layered causal chain spanning the following: (i) contamination monitoring in staple foods; (ii) quantification of internal dose and biologically effective dose using validated biomarkers (e.g., urinary AFB₁-N⁷-guanine, AFM₁, and serum AFB₁-lysine albumin adducts); (iii) a characteristic molecular fingerprint in tumors and circulation (TP53 R249S); (iv) reversibility demonstrated through randomized intervention trials and policy-driven natural experiments. Chemoprevention and dietary interception studies (e.g., oltipraz, chlorophyllin, and broccoli sprout beverages) showed that enhancing detoxication pathways can lower biomarker burdens in exposed populations. At the population level, a sustained dietary transition from maize to rice, together with strengthened food governance, was accompanied by marked decreases in biomarker distributions and subsequent declines in HCC mortality in endemic regions. Nevertheless, regional heterogeneity, multi-mycotoxin co-exposure, and climate variability are expected to increase exposure volatility and complicate surveillance. Here, we translate and synthesize the Chinese evidence base, highlight biomarker-enabled monitoring and policy evaluation, and propose an integrated "5+1" prevention framework spanning source control, process detoxification, tiered governance, short-course interception, precision follow-up of high-risk individuals, and climate-sensitive early warning along the climate-agriculture-storage-processing-population (CAT-CSPP) chain.

Snakebite envenomation (SBE) is a major public health issue in sub-Saharan Africa (SSA), particularly in Cameroon. This Phase IV, multicenter, open-label study was conducted from June 2024 to December 2024 to evaluate the safety and efficacy of PANAF-Premium™, a World Health Organization (WHO)-approved polyvalent antivenom that was introduced in Cameroon in 2023, given that prospectively gathered data and studies on this antivenom's safety in SSA are limited. In total, 130 victims admitted to four district hospitals in North Cameroon with confirmed SBE were included. Data on envenomation syndromes, clinical outcomes, adverse events, and treatment response were recorded. Echis species were responsible for most bites, while clinical syndromes included hemotoxic (68.5%), cytotoxic (30.8%), and neurotoxic (0.8%) presentations. On average, victims required 3.34 vials and 5.55 days for clinical recovery. Early antivenom administration significantly reduced the number of antivenom vials required to manage the symptoms (p = 0.003) and hospital stay (p = 0.049). Seventeen patients experienced mild to moderate adverse events. Two deaths and a case of kidney injury were noted, all unrelated to antivenom use. These study findings indicate the safety and effectiveness of PANAF-Premium™ antivenom, meeting WHO performance targets. The results highlight the importance of timely antivenom administration in treating SBEs.

The removal of protein-bound uremic toxins (PBUTs) from the blood of kidney failure patients with conventional dialysis is limited. However, as their harmful effects and association with morbidity and mortality in dialysis patients are increasingly recognized, PBUTs have become important therapeutic targets. In this review, PBUT removal with current state-of-the-art dialysis technologies and future perspectives are discussed. Strategies to enhance PBUT clearance include methods that interfere with PBUT-albumin binding, such as chemical displacers, high ionic strength, pH changes, or electromagnetic fields, thereby increasing the free fraction available for dialysis. While these methods have shown promise in vitro, and some also in vivo, long-term safety data are lacking. PBUT removal can also be increased by adsorption, either directly via hemoperfusion, or indirectly, e.g., via sorbents incorporated in a mixed-matrix membrane or dissolved in the dialysate. In the kidney, PBUTs are secreted in the proximal tubules; hence, a cell-based bioartificial kidney (BAK) that secretes PBUTs is proposed as an add-on to current dialysis. Yet both PBUT adsorption strategies and, in particular, BAKs face considerable challenges in upscaling and mass production at acceptable costs. In conclusion, many novel technologies are under development, all requiring further (pre)clinical testing and upscaling before these strategies can be applied in the clinic.

Background: Spasticity, which occurs with certain neurological conditions, substantially affects quality of life, function, and social participation. Despite widespread botulinum toxin use, variability persists in patient information, access to specialized rehabilitation, and follow-up models.

Methods: This two-phase Delphi-Dialogue Patients-Professionals study (DDPP), promoted by SERMEF, integrated perspectives from 77 patients and 141 rehabilitation professionals. Phase 1 used parallel surveys to assess satisfaction, perceived effectiveness of botulinum toxin, communication preferences, and rehabilitation follow-up. Phase 2 applied Real-Time Delphi with 38 experts to generate consensus recommendations to improve spasticity management.

Results: Patients and professionals agreed on botulinum toxin benefits, the importance of ongoing rehabilitation, and the value of hybrid (in-person/remote) follow-up. Key gaps concerned access to Physical Medicine and Rehabilitation services, clarity and timing of information, and shared goal setting. Experts translated these misalignments into 10 prioritized recommendations, with highest feasibility for actions standardizing access pathways, optimizing botulinum toxin use, reinforcing structured education, and consolidating hybrid rehabilitation models.

Conclusions: The DDPP approach offers a reproducible framework to align stakeholder perspectives by converting quantified divergence into consensus-based innovation priorities. Implementing the recommendations-particularly those strengthening communication, education, and hybrid pathways regarding botulinum toxin treatment-may support more accessible, personalized, patient-centered spasticity care.

Aflatoxins, mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus, were discovered sixty-five years ago and remain a significant public health threat, particularly amid increasing instances of extreme weather events. Of the four principal forms of aflatoxins found in foods (B₁, B₂, G₁, and G₂), aflatoxin B₁ is the most potent carcinogen. Aflatoxins commonly contaminate a variety of foodstuffs, with maize being among the most susceptible. Chronic exposure to aflatoxins has been linked to liver cancer, childhood stunting, gallbladder cancer, and other adverse health effects. Due to public health concerns related to the consumption of aflatoxin-contaminated foods, most countries have established regulatory limits. Here, we present estimated aflatoxin exposure per day derived from human biomarker data across many studies around the world spanning more than forty years. We specifically focus on the impact of dietary aflatoxin in northern Latin America, where assessment of the total problem remains limited. These findings suggest a multipronged toolkit could mitigate aflatoxin exposure in the region, which would help to decrease the health burden.