Toxins最新文献

Venom is a key evolutionary innovation of venomous organisms in the long-term process of survival adaptation. As one of the oldest arthropods, scorpions produce venom rich in bioactive peptides that also constitute a valuable pharmacological resource. Omics-driven discovery and structural biology have expanded the peptide catalog and clarified structure-function principles across disulfide-bridged (DBPs) and non-disulfide-bridged peptides (NDBPs). Within this arsenal, ion-channel targeting neurotoxins predominantly modulate Nav, Kv, Calcium, Chloride, and TRP channels to achieve predation, defense, and competition. Owing to their unique mechanisms of action and significant therapeutic potential, scorpion venom peptides have attracted sustained interest as leads and scaffolds for drug development. This review synthesizes current knowledge of scorpion venom composition, with an emphasis on the pivotal role of neurotoxins, covering their molecular diversity, structural features, and modes of ion-channel modulation, as well as emerging applications in disease treatment.

Cyanobacterial blooms are an escalating ecological concern driven by eutrophication and climate warming. Bloom-forming cyanobacteria can produce a broad spectrum of bioactive secondary metabolites. Among these, microcystins (MCs) are the most recognised hepatotoxins; however, natural populations of Planktothrix agardhii also synthesise numerous non-ribosomal peptides (NRPs) with poorly understood ecological roles and combined toxic effects. This review demonstrated the role of mixtures of P. agardhii cyanometabolites (oligopeptides and biogenic compounds) in cyanobacterial proliferation, emphasising the rapid evolution of chemotypes. The role of P. agardhii oligopeptides other than MCs in the cyanobacterial toxicity to duckweeds is also discussed. Laboratory experiments indicated that crude extracts containing complex peptide mixtures may inhibit Spirodela polyrhiza growth more strongly than pure MC-LR, suggesting synergistic effects within natural metabolite assemblages. Particular attention is given to variant-specific degradation pathways of MCs within duckweed-associated microbiota. By integrating biochemical, ecological, and microbiological perspectives, this synthesis outlines emerging directions in the study of mixtures of cyanobacterial peptides and other compounds, microbial degraders, and macrophyte-associated bioremediation strategies aimed at mitigating cyanotoxin risks in aquatic environments.

While distinguishing between collis and caput patterns in cervical dystonia (CD) has clear clinical and therapeutic relevance, the effects of botulinum toxin type A (BoNT-A) on segmental spinal excitability and inhibitory function in caput-pattern CD have not been previously investigated. This study aimed to advance understanding of the effects of BoNT-A and its broader neurophysiological impact in cervical dystonia, particularly in the caput subtype. The study utilised non-invasive neurophysiological methods to assess F-wave and cutaneous silent period (CSP or CuSP) parameters in 21 CD patients with caput motor patterns at waning and peak response phases of BoNT-A therapy. Significant prolongation of Fmin latency, increased F-M interlatency, reduced F-wave amplitude, and a marked increase in CSP duration and onset latencies were observed following BoNT-A administration, indicating that BoNT-A not only reduces spinal motoneuron excitability and strengthens spinal inhibitory processes, but also highlights its capacity to modulate central sensorimotor pathways beyond local chemodenervation. Together, the observed changes in CSP support its use as a potential biomarker for nervous system effects of BoNT-A in dystonia; however, further validation in controlled studies is warranted.

Aspergillus flavus colonizes oil-seed crops, contaminating them with aflatoxins; highly carcinogenic mycotoxins that cause severe health and economic losses. Genetic studies may reveal new targets for effective control strategies. Here, we characterized a putative WOPR transcription factor gene, osaA, in A. flavus. Our results revealed that osaA regulates conidiation and sclerotial formation. Importantly, deletion of osaA reduces aflatoxin B₁ production, while, unexpectedly, transcriptome analysis indicated upregulation of aflatoxin biosynthetic genes, suggesting post-transcriptional or cofactor-mediated regulation. Cyclopiazonic acid production also decreased in the absence of osaA. In addition, the osaA mutant exhibited upregulation of genes in the imizoquin and aspirochlorine clusters. Moreover, osaA is indispensable for normal seed colonization; deletion of osaA significantly reduced fungal burden in corn kernels. Aflatoxin content in seeds also decreased in the absence of osaA. Furthermore, deletion of osaA caused a reduction in cell-wall chitin content, as well as alterations in oxidative stress sensitivity, which could in part contribute to the observed reduction in pathogenicity. Additionally, promoter analysis of osaA-dependent genes indicated potential interactions with stress-responsive regulators, indicated by an enrichment in Sko1 and Cst6 binding motifs. Understanding the osaA regulatory scope provides insight into fungal biology and identifies potential targets for controlling aflatoxin contamination and pathogenicity.

This study evaluated 65 commercially available pet feed samples, including 33 cat feeds and 32 dog feeds (dry and wet formulations), for the presence of organic contaminants. These included mycotoxins, pesticides, pharmaceutical residues/veterinary drugs, and plant-based bioactive compounds. A suspect screening strategy was employed using QuEChERS extraction followed by LC-LTQ/Orbitrap HRMS analysis. A total of 29 compounds were tentatively identified within 186 detections. In total, 76.9% of the samples were contaminated with mycotoxins. Aflatoxins (B1, B2, G1, and G2), T2 toxins, and HT2 toxins were dominant, with Aflatoxin B1 occurring in 33.8% of the samples and exhibiting a higher prevalence in dry feeds than in wet feeds. Pesticides were present in 72.0% of the dry formulations, including aclonifen and pirimiphos-methyl, but were present in only 11% of the wet formulations. Plant-based bioactive compounds, including phytoestrogens, were identified in 51% of the samples, highlighting toxicologically relevant candidates that merit prioritization for targeted confirmation, particularly in cat feeds. Pharmaceuticals were found in 23.8% of dry feeds (sparfloxacin and fumagillin). Overall, the HRMS-based, standard-free suspect screening workflow provides an early-warning overview of multi-class co-occurrence patterns in complex pet feed matrices and supports the prioritization of candidates for subsequent confirmatory analysis.

Mycotoxins are toxic secondary metabolites produced mainly by filamentous fungi of the genera Aspergillus, Penicillium, and Fusarium and pose a significant food safety concern. This review summarizes current literature on the occurrence of major regulated and emerging mycotoxins, including aflatoxins, ochratoxin A, fumonisins, trichothecenes, zearalenone, and selected Fusarium and Alternaria metabolites, in herbs, spices, and plant-based dietary supplements. Available data indicate that spices-particularly chilli, paprika, ginger, and various types of pepper-represent high-risk commodities and are often more heavily contaminated than dried herbs. Although reported concentrations of individual mycotoxins are frequently low to moderate, numerous studies highlight the common co-occurrence of multiple toxins within a single product, raising concerns regarding cumulative and combined toxic effects. Dietary supplements, especially those containing concentrated plant extracts such as green tea or green coffee, are also identified as potential sources of multi-mycotoxin exposure. The review outlines key analytical approaches for mycotoxin determination, emphasizing the critical role of sample preparation for chromatographic analysis in complex plant matrices. Despite increasing evidence of contamination, important knowledge gaps persist regarding emerging mycotoxins, underrepresented botanical matrices, and long-term exposure assessment, while regulatory limits remain incomplete or inconsistent. Continued monitoring and harmonized analytical and risk assessment strategies are, therefore, essential to ensure consumer safety.

(1) Background: As an innovative drug derived from botulinum neurotoxin serotype E, TrenibotulinumtoxinE^® demonstrates a rapid onset and shorter effect. Due to concerns regarding specificity, test throughput, and animal welfare, a new cell-based potency assay (CBPA) method was developed for BoNT/E drug substance and drug product; independent evaluation of this new CBPA was required. (2) Methods: The CBPA for BoNT/E is a quantitative assay that measures the accumulated cleaved SNAP25₁₈₀ in human neuroblastoma cells. It involves sequential culturing, differentiation of cells, and then treatment with drug products. Data were analyzed using a quadratic parallel model via statistical software. Linearity was determined using five effective concentration levels. Key assay parameters including accuracy, linearity, repeatability, intermediate precision and range were evaluated. (3) Results: The overall assay's accuracy was 98%, and the intermediate precision was 6.3%. The coefficient of determination (R²) and slope were determined as 0.963 and 0.942, respectively. The root mean squared error (RMSE) was 0.057, and the intercept was 0.032 for the combined data. The repeatability was 2.4%, which is well within the acceptance criterion of ≤8%. (4) Conclusions: The evaluation was carried out within a single laboratory under controlled conditions; the new CBPA meets all acceptance criteria and can be used for BoNT/E potency determination.

Cephalothrix cf. simula is a highly toxic ribbon worm of the class Palaeonemertea, known for its high concentrations of tetrodotoxin. Recent transcriptomic and proteomic studies across Nemertea have revealed that species from all classes possess a diverse array of protein and peptide toxins, which are associated with unicellular glands of the proboscis and the integument epithelium. Previous studies have identified a large number of putative toxins in the transcriptome of C. cf. simula; however, corresponding proteomic data have so far been lacking. This study presents the first comprehensive analysis of the mucus and proboscis proteome of C. cf. simula using high-performance liquid chromatography-tandem mass spectrometry. We identified three putative toxins in the proboscis and three in the mucus. Additionally, four cysteine-rich peptides with putative toxic activity were identified in the mucus and one in the proboscis. The expression of the corresponding genes in both tissues was quantified using quantitative real-time PCR. The toxin compositions of the proboscis and mucus showed clear signs of functional specialization, with no overlapping toxins and tissue-specific patterns of gene expression. Feeding experiments combined with transmission electron microscopy confirmed the involvement of specialized proboscis structures, pseudocnidae, in delivering toxins into the prey.

Fireflies, which predominantly prey on various mollusks such as small snails and slugs, are renowned for their unique bioluminescence. Firefly toxins-particularly Lucibufagins (LBGs), which target the α-subunit of the sodium-potassium pump protein (ATPα)-play a crucial role in their survival strategies. However, the types and functions of venom proteins in fireflies remain to be elucidated. In this study, transcriptome sequencing was employed on the larval head of Pyrocoelia analis larvae, through which transcripts encoding several putative venom proteins were identified, including phospholipase A1/A2, 5'-nucleotidase, cysteine-rich secretory proteins (CRISPs), and insulin-like peptides. Structural comparison revealed that venom proteins in fireflies exhibited high sequence and structural similarity with venom proteins from various venomous animals (e.g., snakes, scorpions, spiders, and cone snails). These venom proteins may exert synergistic effects through multiple mechanisms, such as neurotoxicity, metabolic interference, and cytotoxicity, thereby playing an essential role in mollusk predation and defense against predators. Our study not only analyzes the complexity and uniqueness of Py. analis venom proteins but also provides a robust foundation for further exploration of the ecological adaptability and evolutionary mechanisms of these venom proteins.

Botulinum neurotoxin serotype A (BoNT/A) is the most potent known neurotoxin. While its light chain (LC) catalytic domain is a prime target for next-generation vaccines and therapeutics, the functional differences among BoNT/A subtype LCs (A1, A2, A3) remain to be definitively characterized, despite notable sequence variation. This work aimed to systematically compare the proteolytic activity and immunoprotective efficacy of recombinant BoNT/A1-LC, A2-LC, and A3-LC. Recombinant A1-LC-His, A2-LC-His, A3-LC-His, and A3-LC-Twin-Strep proteins were expressed in Escherichia coli (E. coli) and purified with affinity chromatography. Their proteolytic activity was assessed via in vitro SNAP-25 cleavage assays. The protective potency of these antigens was evaluated in a mouse model. In vitro cleavage assays revealed a substrate cleavage efficiency order of A2-LC > A1-LC > A3-LC. In vivo, both A1-LC and A2-LC immunization conferred robust, broad protection against high-dose challenges with all three toxin subtypes. In stark contrast, A3-LC provided only minimal protection against its homologous toxin and none against heterologous subtypes. Crucially, the functional deficit of A3-LC was confirmed to be an intrinsic property, as the A3-LC-TS variant, designed to exclude tag-specific interference, exhibited comparable low efficacy. According to structural research, A3-LC's compromised function may be caused by a four-amino-acid loss. The inferior performance of A3-LC is inherent to its primary structure. This work identified A1-LC or A2-LC as the potential proteolytic activity molecule and vaccine antigen by demonstrating functional differences among BoNT/A subtype LCs. These findings provide crucial insights for developing subtype-specific countermeasures against botulism.