ToxinsPub Date : 2025-06-07DOI: 10.3390/toxins17060290
Gihong Park, Christina Batoh, Hans G Dam
{"title":"The Ghost of Predator Past: Interaction of Past Predator Exposure and Resource Availability on Toxin Retention and Cell Growth in a Dinoflagellate.","authors":"Gihong Park, Christina Batoh, Hans G Dam","doi":"10.3390/toxins17060290","DOIUrl":"10.3390/toxins17060290","url":null,"abstract":"<p><p>The non-consumptive effects of past predator exposure on phytoplankton have gained recognition, but how these effects are modulated by resource availability requires further study. We examined the simultaneous effects of past predator exposure (direct, indirect, and no exposure) and nutrient regime (combinations of N- and P-repletion and limitation) on the paralytic shellfish toxin retention and cell growth rate of a toxic dinoflagellate, <i>Alexandrium catenella</i> (strain BF-5), under a laboratory-simulated bloom condition (exponential, stationary, and declining phases). Within a past predator exposure treatment, cell toxin retention was generally higher under N-replete than N-limited conditions. The cells of past direct predator exposure treatment retained or produced more toxin than those in the indirect-exposure or no-exposure treatments regardless of nutrient regime in the exponential and stationary phase. By contrast, cells directly exposed to predators showed lower growth rates than the other two treatments, and also showed a tradeoff between toxin retention rate and growth rate. Separate experiments also showed that the effect of past predator exposure on reducing cell growth is stronger under N repletion than N limitation. These results imply that the interactions of past predator exposure and resource availability impact bloom dynamics and toxin transfer in the food web.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485900","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}
ToxinsPub Date : 2025-06-07DOI: 10.3390/toxins17060291
Matija Ruparčič, Gašper Šolinc, Simon Caserman, Juan Carlos Garcia Galindo, Manuel Jimenez Tenorio, Gregor Anderluh
{"title":"The Biological Role of Conoporins, Actinoporin-like Pore-Forming Toxins from Cone Snails.","authors":"Matija Ruparčič, Gašper Šolinc, Simon Caserman, Juan Carlos Garcia Galindo, Manuel Jimenez Tenorio, Gregor Anderluh","doi":"10.3390/toxins17060291","DOIUrl":"10.3390/toxins17060291","url":null,"abstract":"<p><p>Cone snails are a large group of marine gastropods that produce a complex mixture of toxic compounds to hunt prey and defend against predators. The majority of the venom comprises small toxic peptides named conotoxins, which target membrane receptors. In contrast, a smaller part of the venom contains larger proteins and conoproteins, which are thought to be involved in conotoxin maturation and the envenomation process, respectively. Interestingly, many species of cone snails contain conoporins, which are similar to actinoporins-pore-forming toxins found in sea anemones. These actinoporin-like proteins (ALPs) have recently been detected in many molluscan species, and only a few have been experimentally characterized. Due to being highly expressed in the venom gland of many cone snail species, conoporins are thought to play an important part in the envenomation process. Despite this, the exact function of conoporins is currently unknown. We propose several hypotheses aiming to elucidate their biological role.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485897","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}
ToxinsPub Date : 2025-06-06DOI: 10.3390/toxins17060285
Wannes Hugo R Van Hassel, Benoît Guillaume, Julien Masquelier
{"title":"Hydroculture Cultivation of Strawberries as Potential Reference Material for Microcystin Analysis: Approaches and Pitfalls.","authors":"Wannes Hugo R Van Hassel, Benoît Guillaume, Julien Masquelier","doi":"10.3390/toxins17060285","DOIUrl":"10.3390/toxins17060285","url":null,"abstract":"<p><p>Toxic cyanobacterial blooms are prevalent in surface waters. Depending on several conditions, these blooms produce cyanotoxins. Human exposure to these toxins can occur through multiple routes, including contaminated crops through irrigation with contaminated water. Analytical methods have been developed for cyanotoxin quantification to investigate these exposures. Yet, proper comparisons between different labs via proficiency tests or interlaboratory comparison tests, as well as method quality assurance, are impossible. Developing reference materials for cyanotoxins in plants would help resolve these problems. Therefore, a novel liquid hydroculture setup was optimized to grow and contaminate strawberries. During fruit ripening, these plants were exposed to growth medium contaminated with pure microcystin-LR or freeze-dried cyanobacterial biomass containing different microcystin congeners. Afterwards, fruits, greens, and roots were harvested. Validated UHPLC-MS/MS methods were used to quantify the microcystin congeners in the growth medium and the plants. Furthermore, both contamination conditions resulted in the accumulation of toxin(s) in the roots and the greens. Yet in the contamination models, no toxin(s) accumulated in the fruits. Therefore, this contamination approach, combined with strawberries as a berry plant model, is only suitable for reference material production for limited matrices. Our cultivation model to produce reference material could be evaluated for other berry producers.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485813","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":"Clinical Efficacy of Bladder Neck Injection of Botulinum Toxin A in Treating Neurogenic and Non-Neurogenic Voiding Dysfunctions Due to Bladder Neck Dysfunction.","authors":"Yu-Shuang Lee, Yu-Khun Lee, Tien-Lin Chang, Cheng-Ling Lee, Sheng-Fu Chen, Jia-Fong Jhang, Yuan-Hong Jiang, Hann-Chorng Kuo","doi":"10.3390/toxins17060289","DOIUrl":"10.3390/toxins17060289","url":null,"abstract":"<p><p>Bladder neck dysfunction (BND) is a pathophysiology associated with voiding dysfunction in patients with neurogenic or non-neurogenic voiding dysfunction. Botulinum toxin A (BoNT-A) injection is a minimally invasive alternative for treating bladder outlet dysfunction; however, its efficacy for BND has not been well established. In this retrospective study, 41 patients with videourodynamic study-confirmed BND who failed medical therapy received a transurethral bladder neck injection of 100-U BoNT-A. Treatment outcomes were assessed using the Global Response Assessment. After BoNT-A injection, the patients were followed up and subsequent urological management was recorded. At 6 months, 65.9% of the patients reported satisfactory outcomes (26.8% successful and 39.0% improved). Patients with non-neurogenic BND had the highest satisfaction rate, higher than those with neurogenic BND (NBND) with and without detrusor sphincter dyssynergia (DSD). Among patients without detrusor acontractility (DA), a higher bladder outlet obstruction index predicted treatment failure. Patients with pure BND confirmed by urodynamics may benefit more from BoNT-A injections, whereas those with high baseline voiding detrusor pressure or spinal cord injury with detrusor sphincter dyssynergia may have less favorable results. Bladder neck BoNT-A injections for treating BND-associated voiding dysfunction did not achieve very successful outcomes. Only 26.8% of the patients had successful treatment outcomes, while 39.0% had improved outcomes and 34.1% failed the treatment.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485860","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}
ToxinsPub Date : 2025-06-06DOI: 10.3390/toxins17060288
Ákos Mesterhazy, Beata Tóth, Attila Berényi, Katalin Ács, Tamas Meszlényi
{"title":"Significance of the Stability of Fusarium Head Blight Resistance in the Variety Registration, Breeding, and Genetic Research of Winter Wheat Using Disease Index, Fusarium-Damaged Kernels, and Deoxynivalenol Contamination.","authors":"Ákos Mesterhazy, Beata Tóth, Attila Berényi, Katalin Ács, Tamas Meszlényi","doi":"10.3390/toxins17060288","DOIUrl":"10.3390/toxins17060288","url":null,"abstract":"<p><p>Fusarium head blight is one of the greatest threats to global wheat production. Despite the special attention paid by researchers to resistance genetics, the stability of resistance and the expression of its epidemiological relationships have not been tested in depth. As most studies only present data on visual symptoms, in this study, we present data from four experiments. Here, 15-40 genotypes were tested with four and eight isolates (inocula) in 3-4-year experiments, with 32, 24, 36, and 12 epidemic situations used to determine the disease index (DI), Fusarium-damaged kernels (FDKs), and DON. All genotypes were tested for stability by the variance across epidemics, and the b value of the linear function was considered. Both indices were suitable for measuring stability/instability, but the variance results were more closely correlated with the experimental data than the b value, known as the stability index (SI). The use of variance is recommended due to its simplicity and reliability. In the first test, the rate of maximum/minimum variance for DI, FDK, and DON differed 15-, 20-, and 120-fold, respectively. In the second test, the same rates were 200, 400, and over 4000, with the other tests exhibiting similar tendencies. The traits differ, the epidemics vary, and a dependence on resistance level can be proven. The genotype ranking varies strongly in different epidemics, with approximately 50% of the correlations between variety responses being insignificant. Therefore, many epidemics are needed to obtain a reliable picture of the adaptation ability of the resistance traits and their stability. Approximately 25% of the genotypes tested belong to the most stable group. About 35% were discarded, and in the 40% medium, we observed both highly unstable and moderately stable genotypes. Principal component analysis (PCA) of the three traits in the experiments showed a confirmatory, nearly uniform distribution of genotypes, with a different footprint or \"identity card\" present for each genotype. The genotypes for the traits belong to one or two groups, although sometimes individual genotypes seem to be independent. No strict rule was found. This underlines the necessity of considering the plant's traits (Di, FDK, and DON) in resistance testing. Highly resistant winter wheat lines could also be bred with very low variance and SI values and very high stability (SI values lower than 0.3). Of the traits, DON is the most important. With this methodology, variety registration also becomes possible. The epidemiological aspect has a decisive role in resistance studies, and without identifying stability in FHB resistance, no food safety estimates can be made.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485816","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}
ToxinsPub Date : 2025-06-06DOI: 10.3390/toxins17060287
John S Reif, Rebecca Koszalinski, Malcolm M McFarland, Michael L Parsons, Rachael Schinbeckler, Judyta Kociolek, Alex Rockenstyre, Adam M Schaefer
{"title":"Evaluating Bias in Self-Reported Symptoms During a Cyanobacterial Algal Bloom.","authors":"John S Reif, Rebecca Koszalinski, Malcolm M McFarland, Michael L Parsons, Rachael Schinbeckler, Judyta Kociolek, Alex Rockenstyre, Adam M Schaefer","doi":"10.3390/toxins17060287","DOIUrl":"10.3390/toxins17060287","url":null,"abstract":"<p><p>Algal blooms produced by cyanobacteria liberate microcystins and other toxins that create a public health hazard. During the 2018 bloom of <i>Microcystis aeruginosa</i> in Florida, USA, residential and recreational exposures were associated with an increased risk of self-reporting respiratory, gastrointestinal, or ocular symptoms for 125 participants. Subsequently, 207 persons were interviewed between 2019 and 2024 in the absence of large-scale algal blooms and were considered non-exposed. Analyses of cyanotoxins and brevetoxins in water and air showed only intermittent, background levels of toxins during the non-bloom period. The purpose of this report was to compare symptom reporting between active bloom and non-bloom periods. The assessment of information bias from self-reported symptoms is an important issue in epidemiologic studies of harmful algal blooms. During the non-bloom period, no statistically significant associations with residential, recreational, or occupational exposures were found for any symptom group. Estimated risks for respiratory, gastrointestinal, and ocular symptoms, headache, and skin rash were significantly higher for persons sampled during the bloom than the non-bloom period with odds ratios (ORs) of 2.3 to 8.3. ORs for specific respiratory symptoms were also significantly elevated. After adjustment for confounders and multiple exposures in multivariable analyses, the differences in symptom reporting between bloom and non-bloom periods remained statistically significant. In summary, the use of self-reported symptoms in this epidemiologic study of exposure to a cyanobacterial algal bloom did not appear to introduce substantial information bias.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485807","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":"Palytoxin Signal in LC-MS and UV: Preliminary Investigation on the Effect of Solvent and Temperature.","authors":"Chiara Melchiorre, Michela Varra, Valeria Tegola, Valentina Miele, Carmela Dell'Aversano","doi":"10.3390/toxins17060286","DOIUrl":"10.3390/toxins17060286","url":null,"abstract":"<p><p>Palytoxins (PLTXs) and ovatoxins (OVTXs) are a group of highly potent marine toxins that pose significant health risks through seafood contamination and environmental exposure. OVTX-producing algae have been linked to dermatitis and respiratory distress in Mediterranean beachgoers, while serious public health concerns are related to PLTX accumulation in seafood. In 2009, the European Food Safety Authority highlighted the need for analytical detection methods of the PLTX group of toxins and for the preparation of reference materials. This study investigates the stability of the palytoxin signal using liquid chromatography tandem mass spectrometry (LC-MRM-MS) and UV-Vis spectrophotometry under different experimental conditions: three concentrations (10, 1, and 0.5 µg/mL), three methanol-water mixtures (10%, 50%, and 90%), and two temperatures (6 °C and 25 °C). The results showed that the PLTX signal response is significantly influenced by the experimental conditions used. LC-MRM-MS analysis revealed the optimal response of PLTX in 50% and 90% MeOH at 25 °C, with minimal signal loss occurring over 16 h (9% and 6%). UV-Vis data indicated reduced absorbance in 10% MeOH, but a stable spectral intensity over 21 h in all the tested solvent mixtures. These results underscore the necessity of carefully controlled experimental conditions to ensure accurate and reproducible PLTX detection in environmental and food safety monitoring.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485876","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":"Serum Indoxyl Sulfate as a Potential Biomarker of Peripheral Arterial Stiffness in Patients with Non-Dialysis Chronic Kidney Disease Stages 3 to 5.","authors":"Yahn-Bor Chern, Jen-Pi Tsai, Chin-Hung Liu, Yu-Li Lin, Chih-Hsien Wang, Bang-Gee Hsu","doi":"10.3390/toxins17060283","DOIUrl":"10.3390/toxins17060283","url":null,"abstract":"<p><p>Indoxyl sulfate (IS), which is a protein-bound uremic toxin, is involved in vascular dysfunction and cardiovascular risk in subjects with chronic kidney disease (CKD). However, its role in peripheral arterial stiffness (PAS) remains unclear. This cross-sectional study evaluated the relationship between IS and PAS in patients diagnosed with CKD stages 3 through 5 who are not undergoing dialysis. Patients with CKD from a single center were enrolled. High-performance liquid chromatography analyzed the serum IS levels. PAS was evaluated using brachial-ankle pulse wave velocity (baPWV). IS was independently associated with PAS (odds ratio [OR]: 1.389 for 1 μg/mL increase in IS, 95% confidence interval [CI]: 1.086-1.775, <i>p</i> = 0.009) in a multivariable analysis after adjustment for age, hypertension, diabetes mellitus, blood pressure, lipid profiles, renal function, albumin, and proteinuria. Moreover, the mean baPWV (<i>p</i> = 0.010), left baPWV (<i>p</i> = 0.009), and right baPWV (<i>p</i> = 0.015) levels significantly correlated with the log-transformed IS (log-IS) levels. The area under the receiver operating characteristic curve for serum IS as a predictor of PAS was determined to be 0.667 (95% CI: 0.580-0.754; <i>p</i> = 0.0002). IS was associated with PAS in non-dialysis CKD stages 3-5, suggesting that IS may be a possible vascular risk marker. Future studies should address the nature of the relationship between IS and vascular dysfunction and assess therapeutic strategies to reduce IS.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485815","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}
ToxinsPub Date : 2025-06-05DOI: 10.3390/toxins17060284
Philip L Walker, Sean Walkowiak, Srinivas Sura, E RoTimi Ojo, Maria A Henriquez
{"title":"Genomics and Transcriptomics of 3ANX (NX-2) and NX (NX-3) Producing Isolates of <i>Fusarium graminearum</i>.","authors":"Philip L Walker, Sean Walkowiak, Srinivas Sura, E RoTimi Ojo, Maria A Henriquez","doi":"10.3390/toxins17060284","DOIUrl":"10.3390/toxins17060284","url":null,"abstract":"<p><p>Fusarium head blight (FHB) is an important fungal disease caused by <i>Fusarium graminearum</i> and other <i>Fusarium</i> spp., resulting in significant yield losses across cereal grains. Recently identified <i>F. graminearum</i> isolates in Canada, capable of producing type A trichothecene mycotoxins 3ANX (NX-2, 7-α hydroxy,15-deacetylcalonectrin) and NX (NX-3, 7-α hydroxy, 3,15-dideacetylcalonectrin), demonstrated high levels of genetic diversity. While recent studies have detected this genetic and chemical diversity, little is known of the underlying molecular mechanisms and processes influenced by these distinct chemotypes and regional populations. In the current study, we used an -omics approach coupled with high-resolution mass spectrometry to characterize twenty <i>F. graminearum</i> isolates collected from five distinct regions across Manitoba. These data identified regional <i>F. graminearum</i> populations within Manitoba that demonstrate distinct genomic variation and patterns of gene expression, particularly within pathogenicity-associated processes. Further, we identified genetic variation and differential expression between isolates showing high and low levels of pathogenicity, allowing for the identification of previously characterized and novel putative pathogenicity factors. Lastly, we detected the production of 3ANX and/or NX mycotoxins within the majority of our twenty characterized <i>F. graminearum</i> isolates, suggesting the 3ANX chemotype may be more prevalent than previously expected in Canada. Ultimately, these findings highlight the diversity of <i>F. graminearum</i> across Manitoba and, more importantly, uncover specific genomic regions and candidate pathogenicity factors influenced by this diversity.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485810","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}
ToxinsPub Date : 2025-06-05DOI: 10.3390/toxins17060282
Marta Rivas, Mariana Pichel, Vanesa Zylberman, Mariana Colonna, Marina Valerio, Carolina Massa, Romina Pardo, Andrés E Ciocchini, Santiago Sanguineti, Ian Roubicek, Linus Spatz, Fernando Alberto Goldbaum
{"title":"INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome.","authors":"Marta Rivas, Mariana Pichel, Vanesa Zylberman, Mariana Colonna, Marina Valerio, Carolina Massa, Romina Pardo, Andrés E Ciocchini, Santiago Sanguineti, Ian Roubicek, Linus Spatz, Fernando Alberto Goldbaum","doi":"10.3390/toxins17060282","DOIUrl":"10.3390/toxins17060282","url":null,"abstract":"<p><p>Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing <i>Escherichia coli</i>-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12197620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485814","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}