Toxins最新文献

{"title":"Against <i>Clostridioides difficile</i> Infection: An Update on Vaccine Development.","authors":"Jingyao Wang, Qianquan Ma, Songhai Tian","doi":"10.3390/toxins17050222","DOIUrl":"10.3390/toxins17050222","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> (<i>C. difficile</i>) is a major pathogen responsible for antibiotic-associated diarrhea, frequently observed in hospital settings. Due to the widespread use of antibiotics, the incidence and severity of <i>C. difficile</i> infection (CDI) are rising across the world. CDI is primarily driven by two homologous protein exotoxins, toxin A (TcdA) and toxin B (TcdB). Other putative virulence factors include binary toxin CDT, surface layer proteins, phosphorylated polysaccharides, and spore coat proteins. These <i>C. difficile</i> virulence factors are potential targets for vaccine development. Although several <i>C. difficile</i> vaccines have entered clinical trials, there is currently no approved vaccine on the market. This review outlines the intoxication mechanism during CDI, emphasizing the potential antigens that can be used for vaccine development. We aim to provide a comprehensive overview of the current status of research and development of <i>C. difficile</i> vaccines.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151902","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":"Is There a Correlation Between Masticatory Muscle Thickness and Pain After Botulinum Toxin Injections in Myogenic TMD Patients?: A Pilot Study.","authors":"Hye-Ji Park, Hee-Jin Kim, Sung Ok Hong","doi":"10.3390/toxins17050220","DOIUrl":"10.3390/toxins17050220","url":null,"abstract":"<p><p>Botulinum toxin type A (BoNT-A), a potent neurotoxin, is increasingly used to treat myogenic temporomandibular disorders (TMDs); however, the interplay between muscle atrophy and pain relief remains incompletely understood. This pilot study investigated how masseter and temporalis muscle thickness and pain intensity change over 12 weeks following BoNT-A injections in 15 patients (mean age 51.42 years) with myogenic TMD. Muscle thickness was measured via ultrasonography across multiple anatomical positions under both clenching and resting conditions at baseline and at 2, 4, 8, and 12 weeks post-injection. Significant thinning of both muscles occurred within 2 weeks, lasting until 12 weeks, but became less pronounced after the first month. Pain intensity showed parallel decreases, most notably early on, but these reductions were not consistently statistically significant. Correlation analyses revealed no strong persistent association between muscle thickness and pain except for a moderately positive correlation in the anterior temporalis at two weeks (r = 0.61, <i>p</i> = 0.04). BoNT-A induces rapid masticatory muscle atrophy and modest pain relief; however, these outcomes do not coincide. Pain relief was observed earlier than the full development of muscle atrophy and should be considered during TMD pain management.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151302","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":"Detection of Mycotoxins in Cereal Grains and Nuts Using Machine Learning Integrated Hyperspectral Imaging: A Review.","authors":"Md Ahasan Kabir, Ivan Lee, Chandra B Singh, Gayatri Mishra, Brajesh Kumar Panda, Sang-Heon Lee","doi":"10.3390/toxins17050219","DOIUrl":"10.3390/toxins17050219","url":null,"abstract":"<p><p>Cereal grains and nuts are the world's most produced food and the economic backbone of many countries. Food safety in these commodities is crucial, as they are highly susceptible to mold growth and mycotoxin contamination in warm, humid environments. This review explores hyperspectral imaging (HSI) integrated with machine learning (ML) algorithms as a promising approach for detecting and quantifying mycotoxins in cereal grains and nuts. This study aims to (1) critically evaluate current non-destructive techniques for processing these foods and the applications of ML in identifying mycotoxins through HSI, and (2) highlight challenges and potential future research directions to enhance the reliability and efficiency of these detection systems. The ML algorithms showed effectiveness in classifying and quantifying mycotoxins in grains and nuts, with HSI systems increasingly adopted in industrial settings. Mycotoxins exhibit heightened sensitivity to specific spectral bands within HSI, facilitating accurate detection. Additionally, selecting only relevant spectral features reduces ML model complexity and enhances reliability in the detection process. This review contributes to a deeper understanding of the integration of HSI and ML for food safety applications in cereal grains and nuts. By identifying current challenges and future research directions, it provides valuable insights for advancing non-destructive mycotoxin detection methods in the food industry using HSI.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151921","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":"TM9SF2 Maintains Golgi Integrity and Regulates Ricin-Induced Cytotoxicity.","authors":"Yue Meng, Hongzhi Wan, Xinyu Wang, Lina Zhang, Ruozheng Xin, Lingyu Li, Yuhui Wang, Chengwang Xu, Hui Peng, Lu Sun, Bo Wang, Xiaotao Duan","doi":"10.3390/toxins17050218","DOIUrl":"10.3390/toxins17050218","url":null,"abstract":"<p><p>TM9SF2 belongs to a family of highly conserved nonaspanin proteins, and has been frequently identified as one of the important host factors for a plethora of lethal pathogens and toxins in previous genome-wide screening studies. We reported herein a novel molecular mechanism of TM9SF2 in mediating the cytotoxicity of ricin, a type II ribosome-inactivating protein. We first showed that TM9SF2 displays a non-redundant requirement for ricin-induced cytotoxicity within the nonaspanin family. Then we found that genetic interference of TM9SF2 substantially affects/remodels intracellular cholesterol trafficking, which results in abnormal cholesterol accumulation in Golgi compartments and causes severe Golgi fragmentation. The disruption of Golgi integrity and network impedes the retrograde transport of ricin and thus attenuates ricin-induced cytotoxicity. We further verified this mechanism by pharmacological manipulation of cholesterol metabolism (e.g., by using A939572 and avasimibe, etc.), which well restores the integrity of the Golgi apparatus and reverses the ricin-resistant phenotype induced by TM9SF2 knockdown. Our finding provides new mechanistic insights into the pathology and toxicology of ricin and could potentially be applied to other ribosome-inactivating toxins.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151780","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 Uremic Toxins Inorganic Phosphate, Indoxylsulphate, p-Cresylsulphate, and TMAO Induce the Generation of Sulphated Glycosaminoglycans in Aortic Tissue and Vascular Cells via pAKT Signaling: A Missing Link in the \"Gut-Matrix Axis\".","authors":"Christian Freise, Susanne Metzkow, Andreas Zappe, Monika Ebert, Nicola Stolzenburg, Julia Hahndorf, Jörg Schnorr, Kevin Pagel, Matthias Taupitz","doi":"10.3390/toxins17050217","DOIUrl":"10.3390/toxins17050217","url":null,"abstract":"<p><p>Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently understood. Glycosaminoglycans (GAGs) as components of the extracellular matrix are known to interact with various ligands such as growth factors or receptors, thereby influencing (patho)physiological processes. We previously found that the UT inorganic phosphate (Pi) induces the synthesis and sulphation of the GAGs heparan sulphate and chondroitin sulphate in the rat vascular smooth muscle cell (VSMC) line A7r5 and in the human endothelial cell (EC) line EA.Hy926. The aim of this study was to investigate if other organic UTs modulate GAGs in vascular cells as well. We treated ex vivo cultures of rat aortic rings as well as primary rat VSMCs and human ECs with the UTs Pi, indoxylsulphate (IS), p-cresylsulphate (pCS), trimethylamine N-oxide (TMAO), and urea, and analyzed the samples by histological staining, qPCR, western blot, HPLC, and colorimetric assays. The UT treatment of aortic rings and cells increased contents of sulphated GAGs and hyaluronic acid. UT-treated cells contained higher amounts of 4S- and 6S-sulphated GAGs compared to controls. This was accompanied by altered expressions of genes and proteins relevant for GAG metabolism. Mechanistically, the effects of the UTs on GAGs involve the activation of the PI3K/Akt pathway and of the transcription factor NF-κB. In conclusion, the UT-induced remodeling of the cardiovascular matrix by upregulation of sulphated GAGs and hyaluronic acid in aortic tissue and vascular cells might be a missing link between gut-derived UT and pathophysiological alterations in the cardiovascular system in the sense of a gut-matrix axis.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151771","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":"Single-Dose <i>IncobotulinumtoxinA</i> in the Treatment of Early-Stage Knee Osteoarthritis: Results from a Preliminary Single-Arm Clinical Trial.","authors":"Sofia Durán-Hernández, Norma E Herrera-González, Nayar Durán-Hernández, Martha Carnalla, Manuel de Jesús Castillejos-López, Citlaltepetl Salinas-Lara","doi":"10.3390/toxins17050216","DOIUrl":"10.3390/toxins17050216","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most prevalent rheumatologic disease and a leading cause of years lived with disability worldwide. There are no disease-modifying drugs available to treat it. This study aimed to evaluate the effect of a single dose of 100U botulinum neurotoxin-A (BoNT-A) in patients with early knee OA. We designed a single-arm preliminary clinical trial in patients diagnosed with knee OA (KOA) grades I and II. 45 Patients received a single dose of 100U <i>IncobotulinumtoxinA</i> in the retro-patellar bursa and received nutritional and physical rehabilitation indications. Patients were evaluated at baseline and at days 5, 30, 60, and 90 after injection. The primary outcome was the reduction in pain using the visual analog scale (VAS). Knee function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We assessed secondary adverse effects and measured muscular strength in every consultation. Descriptive endpoint summaries and a generalized linear random-effect model were used to evaluate changes in each follow-up time compared to baseline. <i>IncobotulinumtoxinA</i> treatment significantly (<i>p</i> < 0.001) reduced pain in all treated patients at day 90 compared to day 0. Patients showed a significant reduction in total WOMAC score (<i>p</i> < 0.001), from a mean baseline of 44.6 (95% CI; 41.4, 47.8) to 4.4 at day 90 (95% CI; 0.2, 0.3). Our results show that <i>IncobotulinumtoxinA</i> applied in the retro-patellar bursa is a safe and effective treatment for pain in patients with early-stage KOA, offering a potential alternative for symptomatic control in KOA.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151722","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":"An Elastase Inhibitor ShSPI from Centipede Attenuates Bleomycin-Induced Pulmonary Fibrosis.","authors":"Xi Lian, Bin Liu, Dan Li, Xinyao Wang, Chengbo Long, Xing Feng, Qiong Liao, Mingqiang Rong","doi":"10.3390/toxins17050213","DOIUrl":"10.3390/toxins17050213","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the fibrotic thickening of the alveolar walls, resulting in compromised gas exchange, restricted ventilation, and respiratory failure. It has been indicated that elastase inhibitors reduced the severity of IPF by neutralizing excessive elastase levels in the lungs. ShSPI is an elastase inhibitor derived from centipede toxin. The present study evaluates the therapeutic effects of ShSPI in a bleomycin-induced idiopathic pulmonary fibrosis model. According to the results, ShSPI markedly reduced the weight loss, showing the improvement of health status in bleomycin-induced mice. Its robust antifibrotic effects were evidenced by the mitigation of alveolar structural damage, reduction in inflammatory cell infiltration, inhibition of collagen deposition, and suppression of fibrotic nodule formation. ShSPI effectively attenuated inflammatory responses by downregulating pro-inflammatory factors (IL-6, IL-1β, and MCP-1) and upregulating the anti-inflammatory factor interleukin-10 (IL-10). After delivered via inhalation, ShSPI exhibited favorable pharmacokinetic properties. It could be detected at 8 h at doses of 1 mg/kg and achieved maximum plasma concentrations (Cmax) of 188.00 ± 64.40 ng/mL in vivo. At high doses (160 mg/kg), ShSPI maintained a strong safety profile, with no detectable toxicity observed. This feature shows the therapeutic potential of ShSPI in the treatment of idiopathic pulmonary fibrosis and provides valuable evidence for its development as a novel peptide-based therapy.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151903","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":"Evaluation of Untargeted Metabolomic and Mycotoxin Profiles in Corn Silage and High-Moisture Corn.","authors":"Marco Lapris, Valentina Novara, Mattia Masseroni, Michela Errico, Gabriele Rocchetti, Antonio Gallo","doi":"10.3390/toxins17050214","DOIUrl":"10.3390/toxins17050214","url":null,"abstract":"<p><p>Corn silage (CS) and high-moisture corn (HMC) represent fundamental ingredients in ruminant diets; however, their chemical complexity and susceptibility to mycotoxin contamination pose challenges for feed safety and quality assessment. This study applied an innovative approach combining untargeted metabolomics and mycotoxin profiling through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to characterize the chemical profiles of CS (<i>n</i> = 19) and HMC (<i>n</i> = 13) samples collected from four farms in northern Italy over a period of two years. Fumonisin B1 (FB1) emerged as the most prevalent mycotoxin, with contamination levels significantly higher in HMC than CS, though all the detected levels complied with European Union (EU) guidance limits. Untargeted metabolomics distinguished CS and HMC based on their metabolic signatures: polyamines, amino acids, peptides, and phenolic acids typified CS, while HMC was primarily characterized by flavonoids and mycotoxins. Geographical origin significantly influenced both mycotoxin patterns and metabolite profiles, while the sampling season showed no significant impact. This study highlights the complementary value of metabolomics and mycotoxin screening to assess feed quality, identify biomarkers, and unravel the link between fungal contamination and biochemical composition, offering a robust strategy to support feed safety management in livestock production.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151934","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":"Decoding Mycoplasma Nucleases: Biological Functions and Pathogenesis.","authors":"Xinchao Yi, Ying Huang, Xinru Li, Hao Xu, Chang Liu, Chao Li, Qianrui Zeng, Haodang Luo, Zufeng Ye, Jun He, Xiaoxing You","doi":"10.3390/toxins17050215","DOIUrl":"10.3390/toxins17050215","url":null,"abstract":"<p><p>Nucleases are critical metabolic enzymes expressed by mycoplasmas to acquire nucleic acid precursors from the host for their parasitic existence. Certain nucleases, either membrane-bound or secreted, not only contribute to the growth of mycoplasmas but also serve as key virulence factors due to their unique spatial structures and physiological activity. The pathogenesis includes, but is not limited to, degradation of host DNA and RNA, leading to disruptions of nucleic acid metabolism and the induction of host cell apoptosis; degradation of neutrophil extracellular traps (NETs), allowing escape from neutrophil-mediated killing; and upregulation of inflammatory molecules to modulate the immune response of the host. Understanding the biological functions of nucleases is essential for gaining deeper insights into the virulence and immune evasion strategies of mycoplasmas, which can inform the development of novel approaches for the prevention, diagnosis, and treatment of mycoplasma infections.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151919","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 Efficacy of a Novel Water-Soluble Anti-Mycotoxin Solution in Improving Broiler Chicken Performance Under Mycotoxin Challenge.","authors":"Sayantani Sihi Arora, Anusuya Debnath, Amrita Kumar Dhara, Sudipto Haldar, Raquel Codina Moreno, Insaf Riahi","doi":"10.3390/toxins17050212","DOIUrl":"10.3390/toxins17050212","url":null,"abstract":"<p><p>Mycotoxins like aflatoxins (AFs), fumonisins (FBs), and ochratoxin A (OTA) pose serious health risks to humans and animals. Fruit pomace extracts, rich in natural nutrients and bioactive compounds, have the potential to enhance animal health and mitigate mycotoxin toxicity. This study evaluated a novel liquid anti-mycotoxin solution (LAS), a combination of grape and olive pomace extract administered to broiler chickens through drinking water (2 L:1000 L) for 1-42 days under a natural multi-mycotoxin challenge. The 42-day trial with 288 one-day-old male Ross 308AP95 chicks included four experimental groups: a negative control (NC); NC+LAS; a positive control (PC) group fed a diet containing 80 μg/kg AFs, 1600 μg/kg FBs, and 50 μg/kg OTA; and PC+LAS. The growth performance, oxidative defense genes (liver), and stress biomarkers (blood) were analyzed. Mycotoxin exposure negatively affected body weight (BW), the feed conversion ratio (FCR), and the oxidative defense mechanism. LAS supplementation improved BW and the FCR, reduced Nrf-2 expression, and enhanced mycotoxin detoxification via lower EPHX1 expression. Though the LAS did not fully restore performance to NC levels, it significantly mitigated mycotoxin-induced damage. This study concluded that the LAS is a promising solution to improve broiler resilience against moderate to high mycotoxin exposure.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151680","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}