Toxins最新文献

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.

Bacteria use cholesterol-dependent cytolysins (CDCs) to damage eukaryotes. While well-studied in mammals, the mechanisms by which CDCs bind to and kill protozoans remain unclear. CDCs bind to the human pathogen Leishmania major but only kill in the absence of sphingolipids. The contribution of other leishmanial membrane components to CDC binding and cytotoxicity remains unknown. Here, we used genetic knockouts and inhibitors to determine the contribution of key membrane components to CDC binding and killing in L. major. We analyzed toxin binding and killing using flow cytometry and Western blotting. Loss of the virulence factor GP63 enhanced toxicity of perfringolysin O but not streptolysin O. Plasmenylethanolamine and lipophosphoglycan had minimal contributions to CDC binding and cytotoxicity. Removal of sterols protected cells from CDCs yet failed to reduce binding. We used CDCs defective in engaging glycans or cholesterol to confirm that CDCs deficient in sterol binding, but not glycan binding, could bind to L. major. Thus, in non-mammalian systems, CDCs may rely on glycans for binding, while using sterols for pore formation. This suggests that CDCs may not be sterol-specific probes in some non-mammalian systems. We conclude that early-branching eukaryotes use distinct mechanisms from mammals to limit CDC pore formation and killing.

Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized the recently described fungus Aspergillus aspearensis (Aspergillaceae) would synthesize lysergic acid amides. Cultures of A. aspearensis produced abundant lysergic acid α-hydroxyethylamide (LAH) and lesser amounts of other lysergic acid derivatives. Conidia contained high concentrations of ergot alkaloids, whereas sclerotia contained significantly less. Approximately half of the ergot alkaloids produced were secreted into the culture medium. When spores of A. aspearensis were injected into larvae of the model insect Galleria mellonella, larvae died at a significantly faster rate than control larvae. The fungus produced ergot alkaloids during insect pathogenesis and later produced conidia and sclerotia on cadavers, indicating it can complete its life cycle in an insect. The genome of A. aspearensis contained two complete ergot alkaloid synthesis gene clusters, similar to those of A. leporis; however, unlike its sister species, none of the ergot cluster genes were pseudogenized. Aspergillus aspearensis is a newly discovered source of ergot alkaloids and may be useful for studying and producing these important chemicals.

Patulin (PAT) is a fatal mycotoxin that exerts serious threats to human and animal health. Biodegradation of PAT is considered to be one of the promising ways for controlling its contamination. In this study, Lactiplantibacillus plantarum 6076 (LP 6076) with reliable removal efficiency on PAT was screened out from three lactic acid bacteria (LAB) strains. It was found that the PAT was eliminated through degradation by LP 6076, and the intracellular proteins played a crucial role in PAT degradation with the induction of PAT. The proteomic analysis showed that the response of LP 6076 to PAT was by a concerted effort to repair DNA damage, in parallel to adaptive changes in cell wall biosynthesis and central metabolism. Eleven differentially expressed proteins with high fold changes were picked out and identified as PAT degradation candidate enzymes. The 3D structures of the candidate enzymes were predicted, and molecular docking between the enzymes and PAT was performed. Five enzymes, including Acetoin utilization AcuB protein (AU), GHKL domain-containing protein (GHLK), Dihydroneopterin aldolase (DA), YdeI/OmpD-associated family protein (YDEL), and Transcription regulator protein (TR), could dock with PAT with lower affinity and shorter distance. Through molecular docking analysis, DA was ultimately identified as a potential key degrading enzyme. The choice of DA was substantiated by its superior combination of strong binding affinity and a productive binding pose with PAT. VAL84 and GLN51 residues of DA were likely the active sites, forming four hydrogen bonds with PAT. Our study could accelerate the commercial application of biodegradation toward PAT decontamination.