Toxins最新文献

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.

Megalomyrmex ant species have a rich natural history that provides an interesting backdrop to understanding how venom has been shaped by evolution. However, like many other species in the tribe Solenopsidini, alkaloid investigations have dominated, limiting our understanding of the diversity of venom components. Here we use transcriptomics to qualify and quantify the proteins and peptides within Megalomyrmex milenae, a species of ant native to the Panamanian rainforest along the Panama Canal. RNA transcripts associated with and over-expressed in the venom gland allow the description of putative toxins and other significant protein components of the venom cocktail. Among other constituents, we find signatures for pore-forming toxins, neurotoxins, carbohydrate-digesting enzymes, proteins which potentially enhance trail pheromone efficacy, and peptides implicated in antimicrobial activity. This work greatly enhances our understanding of Megalomyrmex venoms, showing a multifaceted functional venom profile similar to other ant species. However, proteomic and functional assays are needed to clarify the venom functions hypothesized in this work.

The saw-scaled viper Echis carinatus, one of the "Big Four" causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in Echis carinatus sochureki (ECS) in northwestern India, we obtained 22 snakes from three locations in Rajasthan and identified 148-174 toxin isoforms belonging to 21-25 toxin families in their venom using a bottom-up proteomics approach. All samples showed a high abundance of snake venom metalloproteinases (SVMPs), particularly SVMP class III. Other major components were phospholipases A₂, L-amino-acid oxidases, snake venom serine proteases and snaclecs (C-type lectins). Variation in venom composition among locations in Rajasthan, compared to E. c. carinatus (ECC) from southern India, was primarily due to differences in the relative abundance of these toxin families. Recognition of all venom components by IPAV was poor at lower antivenom concentrations. Notably, SVMP classes II and III were poorly recognized at all venom-to-antivenom ratios in all ECS venoms, and a plasma clotting assay revealed poor neutralization of procoagulant activity. This collaborative study highlights the need for the development of regional antivenoms to effectively treat snakebites in northwestern India.

Ramaria flavobrunnescens is an ectomycorrhizal coral mushroom that is often found growing in eucalyptus forests. The mushroom has been linked to accidental ingestion-associated livestock poisonings in South America, though the toxicological agent has not yet been described. Mushroom samples identified as R. flavobrunnescens were analyzed by liquid chromatography high-resolution mass spectrometry (LC-MS/MS) to determine the potential source of the toxicity, and to provide a metabolomic profile of the species. Previously reported Ramaria secondary metabolites were detected, including ramarins, ramariolides, pistillarin and arsenic-containing compounds. A number of bacterial species were isolated from R. flavobrunnescens that produced iron-chelating cyclic peptides, which were detected in the mushroom samples. Interestingly, we detected a series of eucalyptus tree secondary metabolites in abundance from R. flavobrunnescens fruiting bodies, some of which have reported toxicities and bioactivities. To our knowledge, this is the first report of eucalyptus secondary metabolites in a mushroom. The diversity of secondary metabolites identified in the mushroom extracts provides insight into the potential complex ecological interactions between R. flavobrunnescens, its associated microbiota, and its mycorrhizal interaction with eucalyptus trees.

Improvement in passive function (i.e., ease of caring for a limb) is a common goal for treatment of spasticity in the arm with botulinum toxin. A large international, observational, 2-year longitudinal study (ULIS-III, N = 953) was conducted in real-life practice. This original secondary analysis examines whether improvement in passive function goals were met over repeated injection cycles. We report changes by cycle measured by the Passive Function sub-scale of the Arm Activity measure (ArmA-PF) and examine predictors of improvement and injection occurrence. Inclusion in this analysis was based on passive function being selected as a primary or secondary goal for one or more cycle of treatment (n = 542/953). Goals were assessed at the start and end of each cycle using the Goal Attainment Test score and the ArmA-PF. Over all cycles of treatment, goals were set for 1641/2187 injections (75.0%) and achieved in 1250 (76.2%). Significant improvements in ArmA-PF score were identified for at least six cycles (p < 0.001) with evidence of cumulative benefit over successive cycles. This occurred regardless of patient-related baseline characteristics, with the possible exception of some relationship with injection localization techniques. In conclusion, repeated botulinum toxin injections provide significant improvement in passive function, which was sustained over repeated cycles of treatment.

We thank Peigneur et al [...].

Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject.

Aflatoxin contamination of maize by Aspergillus section Flavi constitutes a major health and economic concern. While biological control using non-toxigenic strains has proven effective, the increasing global food demand underscores the need for alternative carrier materials to replace seeds and grains. The aims of the present study were (1) to develop an innovative macroporous starch polymer in which the biocontrol agent can grow and be transported to fields where the bioformulate is applied, and (2) to evaluate the effectiveness of this new formulate in reducing AF contamination in maize kernels in field trials, in comparison with the traditional formulate based on long-grain rice as a substrate. Several methods and different starch sources were tested, and the formulation consisting of 10% maize starch, 0.5% citric acid, 3% sucrose, 0.3% urea, and distilled water was the most effective. Furthermore, this bioformulate demonstrated a performance comparable to that of the traditional long-grain rice-based formulation, reducing AF accumulation by up to 81% in maize kernels under field conditions. The implementation of this macroporous starch polymer-based formulation, in combination with the biological control agent A. flavus AFCHG2, would not only reduce aflatoxin contamination in maize kernels but also minimise the use of food-grade seeds and grains for industrial purposes, thereby preserving their availability for human and animal nutrition. Consequently, this development could enhance the availability of these substrates for food and feed use, thereby contributing to improved safety and food security.