Toxins最新文献

{"title":"Cholera Toxin-Mediated Targeting of Botulinum Neurotoxin Activity to Pain-Associated Sensory Neurons.","authors":"Eve Corrie, Rebecca Bresnahan, Ciara Doran, Charlotte Leese, Matthew R Balmforth, Anna Andreou, Aisha Zhantleuova, Elizabeth P Seward, Michael E Webb, W Bruce Turnbull, Bazbek Davletov","doi":"10.3390/toxins18040174","DOIUrl":"https://doi.org/10.3390/toxins18040174","url":null,"abstract":"<p><p>Botulinum neurotoxin injections are used off-label to treat chronic pain, but their efficacy is limited and paralytic effects restrict clinical utility in these applications. Here, we investigated whether combining the light chain and translocation domains of botulinum neurotoxin A (BoNT/A) with the GM1-binding B subunit of cholera toxin would be beneficial in silencing pain-associated sensory neurons. Chimeric ChoBot was assembled via a coiled-coil linking technology and was shown to retain the enzymatic activity of BoNT/A in vitro and in vivo. In cultured dorsal root ganglion neurons, ChoBot cleaved SNAP25 in a calcitonin gene-related peptide (CGRP)-rich subpopulation of sensory neurons, resulting in marked inhibition of CGRP release. ChoBot had a lesser effect on the compound muscle action potentials of the rat gastrocnemius muscle than BoNT/A following subcutaneous injections. In rat models of pain, including chemotherapy-induced peripheral neuropathy, intraplantar administration of ChoBot significantly attenuated mechanical allodynia. Immunohistochemical analysis confirmed SNAP25 cleavage in NF200- and CGRP-expressing sensory fibres in the epidermis following a single injection. ChoBot also mediated SNAP25 cleavage in human neuroblastoma cells in culture. Together, these findings indicate that ChoBot enables a silencing of pain-associated sensory pathways, providing a new strategy for the development of new long-lasting analgesics for chronic pain.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-Harvest Agronomic Reduction in <i>Fusarium</i> Mycotoxins in Winter Barley: Effects of Agrotechnical Intensity on Grain Mycobiome, DON/ZEN and Feed-Quality Traits.","authors":"Sylwia Barbara Okorska, Magdalena Serafin-Andrzejewska, Agnieszka Pszczółkowska, Agnieszka Falkiewicz, Marcin Włodarczyk, Mengcen Wang, Adam Okorski, Marcin Kozak","doi":"10.3390/toxins18040171","DOIUrl":"https://doi.org/10.3390/toxins18040171","url":null,"abstract":"<p><p>Winter barley (<i>Hordeum vulgare</i> L.) is an important crop used for feed, food, malting, and bioethanol production. Recent research indicates that the seed mycobiome significantly influences seed health and usability, affecting its potential applications. This study examined the fungal species present in seven barley cultivars grown under two agrotechnical regimes. Fungal species were classified according to their effects on seeds and plants, and biodiversity indices were calculated for each group. Enhanced agrotechnical practices increased yields and improved grain quality. Higher DON concentrations were observed in low-yield treatments. Mycological analysis revealed that field fungi, particularly <i>Fusarium</i>, dominated the grain mycobiome and were associated with infection and reduced seed quality. High Dominance (Y), Margalef, and Shannon-Wiener indices for quality-deteriorating fungi correlated with lower yields, while the Dominance index (λ) for these fungi was negatively correlated with grain protein content. The prevalence of specific fungi on seeds depends on storage conditions and fungal adaptations, which may result in complementary consortia. Understanding these interactions can support the development of effective seed storage strategies and inform material classification and future use decisions.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum Toxin Type A Injections in the Bladder Wall-An Effective Treatment for Urinary Incontinence with Low Long-Term Adherence.","authors":"Francisco Cruz, Martin C Michel, Yasuhiko Igawa","doi":"10.3390/toxins18040170","DOIUrl":"https://doi.org/10.3390/toxins18040170","url":null,"abstract":"<p><p>Botulinum toxin type A (BoNT/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique's reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Targeted Toxin Therapy for Malignant Gliomas: A Narrative Review.","authors":"Hanish Polavarapu, Walter A Hall","doi":"10.3390/toxins18040169","DOIUrl":"https://doi.org/10.3390/toxins18040169","url":null,"abstract":"<p><p>Malignant gliomas remain highly treatment-resistant brain tumors despite surgery and adjuvant therapies. Targeted toxin therapies represent a unique strategy that exploits receptor-mediated cellular internalization to deliver cytotoxic components that result in the irreversible inhibition of protein synthesis independent of DNA damage or cell-cycle status. Advances in molecular profiling, toxin engineering, and delivery development have refined components targeting IL4Rα, IL13Rα2, EGFR/EGFRvIII, uPAR, and the transferrin receptor. Early clinical studies demonstrated biological activity, acceptable safety, and durable responses in subsets of patients, validating the fundamental mechanism of this approach. However, late-phase trials failed to demonstrate a population-level survival benefit, largely due to variability in delivery, receptor heterogeneity, and limitations in trial design rather than insufficient cytotoxic potency. Recent progress has focused on multiple receptor-targeting and delivery systems capable of achieving reliable intratumoral distribution. MRI-guided convection-enhanced delivery, vector-mediated toxin expression, and blood-brain barrier penetrant nanocarriers now enable more precise tumor targeting. Emerging evidence also reveals that toxin-mediated cytotoxicity can enhance antitumor immune responses, supporting their integration with immunotherapy. These advances position targeted toxins as precision cytotoxic compounds whose success depends on coordinated molecular targeting, delivery optimization, and biologically stratified patient selection, establishing a translational pathway for future glioma therapy.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Tarihci Cakmak et al. Comment on \"Kang et al. The Effective Way of Botulinum Toxin Injection to Reduce Bite Force: Preliminary Study. <i>Toxins</i> 2025, <i>17</i>, 519\".","authors":"Kun-Hwa Kang, Jae-Kwang Jung, Jin-Seok Byun, Ji Rak Kim","doi":"10.3390/toxins18040166","DOIUrl":"https://doi.org/10.3390/toxins18040166","url":null,"abstract":"<p><p>We thank the authors for their thoughtful comments [...].</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Fungicide Protection on Mycotoxin Contamination and Microscopic Fungi in Spring Barley Grain Cultivated in Northeastern Poland.","authors":"Agnieszka Pszczółkowska, Elżbieta Suchowilska, Michael Sulyok, Wolfgang Kandler, Adam Okorski, Rudolf Krska, Marian Wiwart","doi":"10.3390/toxins18040164","DOIUrl":"https://doi.org/10.3390/toxins18040164","url":null,"abstract":"<p><p>A three-year experiment was conducted over the years 2020-2022 to determine the spectrum of microscopic fungi colonizing the grain of two fungicide-treated cultivars of spring barley and the profiles of mycotoxins identified in grain. In comparison with the unprotected control, fungicide treatment significantly increased grain yield by an average of approximately 10% in cv. Atrika and approximately 20% in cv. Vermont. The most abundantly isolated species were <i>Alternaria alternata</i> and <i>Bipolaris sorokiniana</i>. Fungi of the genus Fusarium were also widely represented, accounting for 7% to 27% of all isolates, depending on the year. Each year, 45 secondary fungal metabolites produced mainly by Fusarium and Alternaria species were identified. Fungicide protection did not reduce the overall concentration of Fusarium toxins and even caused a slight increase, while contributing to a decrease in the levels of nivalenol-3-glucoside, nivalenol, and deoxynivalenol. Concurrently, the concentrations of group A trichothecenes and moniliformin increased. The grain of spring barley cv. Vermont contained higher levels of the major Fusarium toxins than the grain of cv. Atrika. Non-parametric Friedman ANOVA revealed significant differences between years for eight mycotoxin concentrations. These results confirm the complex effects of chemical protection on the composition of grain microflora and mycotoxin profiles, indicating the need for further research into interactions between cultivars, environmental conditions, and integrated plant protection strategies in the production of food and feed cereals to improve food safety.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De Novo Assembly and Characterization of Venom Gland Transcriptome for <i>Rhabdophis lateralis</i>.","authors":"Jiahao Chen, Qin Liu, Songwen Tan, Peng Guo, Lianming Du","doi":"10.3390/toxins18040167","DOIUrl":"https://doi.org/10.3390/toxins18040167","url":null,"abstract":"<p><p><i>Rhabdophis lateralis</i> is a snake species within the family Natricidae, which is widely distributed across mainland China, Russia, and Korea. Although this species was once thought to be non-venomous, there are quite a few cases demonstrating its bite could be fatal. In this study, we performed de novo assembly and analysis of the transcriptome data from the Duvernoy's gland of <i>R. lateralis</i>, aiming to characterize its venom transcriptome and reveal the molecular basis of its toxicity. Among 6196 annotated transcripts, 77 were identified as potential toxin transcripts belonging to 26 toxin families. The most highly expressed toxin family was the SVMP family, accounting for 51.10% of the total toxin expression. The other notable toxins included cysteine-rich secretory proteins (CRISPs, 22.36%), c-type lectins (CTLs and snaclecs, 12.13%), and three-finger toxins (3Ftxs, 6.36%). Phylogenetic analyses indicated that SVMPs, CRISPs, and three-finger toxins (3FTxs) are evolutionarily conserved within Colubridae, whereas CTLs likely arose through convergent evolution. All identified SVMPs were classified as P-III type, with one sequence displaying a unique deletion distinct from conventional truncation patterns. The predominantly expressed CTLs are more likely to combine into dimers, exerting coagulation activity. This study provides an insight into the toxin gene expression in the Duvernoy's gland of <i>R. lateralis</i>, which will benefit future research into the ecological and pharmacological significance of toxins in the genus <i>Rhabdophis</i>.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Target-Immobilized and Library-Immobilized SELEX for Selecting High-Affinity α-Amanitin Aptamers.","authors":"Yang Li, Muling Shi, Wenyue Li, Yiqing Yang, Xiang Li, Chen Shen, Xiong Wang, Shuanglin Zhang, Jie Du","doi":"10.3390/toxins18040163","DOIUrl":"https://doi.org/10.3390/toxins18040163","url":null,"abstract":"<p><p>Deaths from the accidental ingestion of poisonous <i>Amanita</i> mushrooms occur every year due to the lack of a specific antidote against α-amanitin poisoning. Intervention and treatment can be promptly carried out to avoid serious consequences when the toxin can be effectively detected in whole blood before liver toxicity develops. Aptamers are molecular recognition units similar to antibodies, capable of specifically recognizing and detecting small molecules such as α-amanitin for which monoclonal antibodies are difficult to prepare. However, α-amanitin has a small molecular size and limited binding sites, which bring difficulties to aptamer selection. Moreover, achieving highly specific detection of α-amanitin in whole blood remains challenging due to the presence of potentially interfering components, such as human serum albumin (HSA). For these problems, we propose an aptamer selection method for small-molecule target α-amanitin, combining target-immobilized and library-immobilized SELEX to select high-affinity aptamers. To exclude HSA interference, counter-selection was introduced to remove HSA-bound sequences. Through these strategies, we successfully selected a highly specific α-amanitin aptamer with nanomolar affinity.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistence and Degradation of Bt Toxin in Two Soil Types Under Different Sterilization Regimes.","authors":"Yixuan Fan, Ziteng Liang, Lingli Zou, Luyao Wang, Lei Ge, Kai Zhao, Yu Sun, Peng Li","doi":"10.3390/toxins18040168","DOIUrl":"https://doi.org/10.3390/toxins18040168","url":null,"abstract":"<p><p>With the large-scale cultivation of transgenic <i>Bacillus thuringiensis</i> (<i>Bt</i>) crops, the Bt toxin released from Bt crops is continuously introduced into the soil. Its environmental fate represents a key indicator for assessing the ecological safety of transgenic crops. However, the persistence of Bt toxin in soil is influenced by both biotic and abiotic processes, and their respective contributions under natural conditions remain unclear. This study measured water-dissolved Bt toxin concentrations in paddy soil (PS) and red soil (RS) to compare the influence of biotic and abiotic factors on the dynamic retention of exogenous Bt toxin under different sterilization methods: no sterilization, heat sterilization (HT), and irradiation sterilization (IS). The water-dissolved Bt toxin exhibited a dynamic decrease-increase-decrease trend across all three treatments in both soil types during the 30 day experimental period. Bt toxin displayed rapid adsorption during the initial 2 h stage in RS, but subsequently showed a high desorption, whereas PS probably achieved more stable bonding through soil organic matter (SOM). Different sterilization methods significantly influenced the results by altering abiotic factors: Compared to CK, HT affected soil physicochemical properties and enhanced adsorption resilience, whereas IS caused minimal impact on the soil physicochemical properties, thereby providing a more accurate reflection of abiotic processes. And microbial, as biotic facters, also influence the reduction process of Bt toxin by participating in the adsorption-desorption-degradation equilibrium process. Therefore, we infer that over time, the concentration of water-soluble Bt proteins in the soil will tend toward zero. Additionally, the initial Bt toxin concentration influenced dynamic balance by adjusting adsorption site saturability, with more pronounced desorption reversibility at 500 ng/g concentrations. Overall, this study systematically reveals the effects of soil properties, microorganisms, and sterilization methods on Bt toxin persistence. The findings underscore the importance of selecting and justifying sterilization methods in related environmental behavior studies, while providing essential guidance for the scientific assessment of environmental risks posed by transgenic crops.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on Kang et al. The Effective Way of Botulinum Toxin Injection to Reduce Bite Force: Preliminary Study. <i>Toxins</i> 2025, <i>17</i>, 519.","authors":"Elif Tarihci Cakmak, Fatma Merih Akpinar, Ekin Ilke Sen, Nalan Capan","doi":"10.3390/toxins18040165","DOIUrl":"https://doi.org/10.3390/toxins18040165","url":null,"abstract":"<p><p>We read with great interest and some concerns the article by Kang and colleagues [...].</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}