Search Results (322)

Jellyfish stings represent a significant global marine hazard, causing injuries from localized skin damage to fatal systemic complications. While skin reactions are the most common symptom, heart toxicity (cardiotoxicity) is the primary cause of death. A growing body of evidence shows that the immune system’s response worsens this venom-induced heart damage. However, current research remains disproportionately focused on cutaneous inflammatory responses, leaving systemic immunopathological processes—especially those potentiating cardiotoxicity—poorly understood. Moreover, few jellyfish toxins (like those from the Chironex fleckeri) have been thoroughly studied, and the molecular mechanisms of heart injury remain largely unknown. This review introduces a novel pathophysiological classification of jellyfish envenomation into three distinct categories—immunotoxicity-dominant, cardiotoxicity-dominant, and dual-mechanism synergistic—based on clinical and mechanistic profiles. By synthesizing current knowledge on venom components and their multi-system interaction, we aim to identify actionable therapeutic targets and propose mechanism-driven treatment strategies. This refined classification offers a foundation for future clinical decision-making and the development of targeted therapies, potentially improving patient outcomes through more personalized envenomation management. Full article

This study investigated the occurrence of fungi and mycotoxins throughout the rice processing chain, from paddy rice to final white rice, in two rice varieties (variety I and variety II). A total of 75 fungal isolates were identified, belonging to the genera Penicillium, Alternaria, Aspergillus, Fusarium, and Talaromyces. Variety I exhibited a higher prevalence of Penicillium and Alternaria, whereas Variety II was dominated mainly by Alternaria, accounting for 63% of all isolates. Multi-mycotoxin screening of 22 mycotoxins revealed contamination by tenuazonic acid (TeA), zearalenone (ZEN), and 15-acetyl-deoxynivalenol (15-AcDON), with TeA concentrations exceeding 4000 µg/kg in whitened rice of variety II. Cluster analysis showed paddy and brown rice grouping together due to higher fungal loads and toxin levels, whereas whitened and final white rice clustered separately, reflecting reduced fungal counts but persistence of TeA, 15-AcDON, ZEN, and citrinin (CIT). The co-clustering of Alternaria with TeA and ZEN indicates strong field-related contamination. Although processing significantly decreased fungal loads, residual toxins persisted, emphasizing that rice polishing does not fully mitigate mycotoxin risks. These findings underscore the need for comprehensive surveillance and integrated management practices across the rice supply chain to minimize potential health hazards associated with fungal contaminants and their toxic metabolites. Full article

Over the past 15 years, Nodularia spumigena blooms in the Gulf of Gdańsk (southern Baltic Sea) have reached exceptional intensity, accounting for up to 90% of phytoplankton biomass during peak summer periods. Our long-term observations revealed oscillations in blooms intensity, with peak nodularin concentrations (up to 45,000 μg/L) recorded in 2012, 2015, and 2018—the highest levels of this toxin documented to date in both the Baltic Sea and worldwide. An extreme cyanobacterial bloom in 2018, caused by unusually high air and water temperatures, covered almost the whole surface of the Gulf of Gdańsk, causing multi-day closures of bathing areas. During this bloom, high levels of microcystins (up to 6640 μg/L MC-LR) were also detected, as well as the presence of 42 cyanopeptides, mainly anabaenopeptides and spumigins, which were present at concentrations 5–10 times higher than hepatotoxins. Full article

Wild mushroom poisoning is an emerging global food safety issue, especially in subtropical regions like southwestern China, where incidents are geographically clustered. Current detection methods are often time-consuming and overlook region-specific toxins. We developed a rapid, sensitive, and accurate method for the simultaneous detection of ten characteristic mushroom toxins prevalent in Guizhou, China. The method combines graphite multi-walled carbon nanotubes (G-MWCNTs) for sample preparation with Orbitrap high-resolution mass spectrometry (HRMS). Wild mushroom samples were extracted via ultrasonic-assisted methanol–water extraction, purified using G-MWCNTs, and separated on a Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 μm). Gradient elution was performed with 0.1% formic acid + 0.01% ammonia and acetonitrile; quantification used the external standard method. The method achieved LODs of 0.005–0.2 mg/kg and LOQs of 0.015–0.6 mg/kg, with RSDs below 18.11% and excellent linearity (R² = 0.9936–0.9989). Among 45 wild mushroom samples, toxin levels ranged from 0.032 to 445.10 mg/kg, with a detection rate of 22.22%, suggesting notable poisoning risk. This method reduces pretreatment time while ensuring high analytical performance, offering a reliable tool for rapid toxin screening and supporting regional surveillance of wild mushroom poisoning. Full article

Bioactive peptides have significant potential for applications in pharmaceuticals, the food industry, and cosmetics due to their wide spectrum of biological activities. However, their pronounced structural and functional heterogeneity complicates the classification and prediction of biological activity. This study uses data from the PepLab platform, comprising 2748 experimentally confirmed bioactive peptides distributed across 15 functional classes, including ACE inhibitors, antimicrobial, anticancer, antioxidant, toxins, and others. For each peptide, the amino acid sequence and key physicochemical descriptors are provided, calculated via the integrated DMPep module, such as GRAVY index, aliphatic index, isoelectric point, molecular weight, Boman index, and sequence length. The dataset exhibits class imbalance, with class sizes ranging from 14 to 524 peptides. An innovative methodology is proposed, combining descriptive statistical analysis, structural modeling via DEMATEL, and structural equation modeling with neural networks (SEM-NN), where SEM-NN is used to capture complex nonlinear causal relationships between descriptors and functional classes. The results of these dependencies are integrated into a multi-class machine learning model to improve interpretability and predictive performance. Targeted data augmentation was applied to mitigate class imbalance. The developed classifier achieved predictive accuracy of up to 66%, a relatively high value given the complexity of the problem and the limited dataset size. These results confirm that integrating structured dependency modeling with artificial intelligence is an effective approach for functional peptide classification and supports the rational design of novel bioactive molecules. Full article

Background: Helicobacter pylori (H. pylori) is a major pathogen associated with a variety of gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. As a natural bioactive product, propolis exhibits multifaceted and multi-mechanistic effects. Due to its immunomodulatory, anti-inflammatory, and antioxidant properties, propolis has emerged as a promising therapeutic alternative, offering an innovative approach to managing H. pylori infections and providing new insights into addressing antibiotic resistance. Methods: This comprehensive review, synthesizing data from PubMed, ScienceDirect, and SciFinder, examines the mechanisms by which propolis combats H. pylori. Results: Propolis has demonstrated significant antibacterial efficacy against H. pylori in both in vitro and in vivo models. Its multitargeted mechanisms of action include direct inhibition of bacterial growth, interference with the expression of virulence factors, suppression of virulence-associated enzymes and toxin activity, immunomodulation, and anti-inflammatory effects. These combined actions alleviate gastric mucosal inflammation and damage, reduce bacterial colonization, and promote mucosal healing through antioxidant and repair-promoting effects. Furthermore, propolis disrupts oral biofilms, restores the balance of the oral microbiome, and exerts bactericidal effects in the oral cavity. Synergistic interactions between propolis and conventional medications or other natural agents highlight its potential as an adjunctive therapy. Conclusions: Propolis demonstrates dual functionality by inhibiting the release of inflammatory mediators and suppressing H. pylori growth, highlighting its potential as an adjuvant therapeutic agent. However, clinical translation requires standardized quality control and higher-level clinical evidence. Future research should focus on validating its clinical efficacy and determining optimal dosing regimens, and exploring its role in reducing H. pylori recurrence. Full article

The neurotoxin BoNT/B2 is the predominant Clostridium parabotulinum subtype in foodborne and infant botulism cases in Spain. This study characterizes a novel case of foodborne botulism in Spain caused by a dual-toxin A1(B5) strain. A 64-year-old male presented with acute, progressive flaccid paralysis including diplopia, dysphagia, and respiratory failure. Although botulism was not initially suspected, the patient recovered with supportive care and without antitoxin administration. Genomic characterization confirmed the presence of both bont/A1 and silent bont/B5 genes. The bont/A1 gene was associated with an orfX+ neurotoxin gene cluster, while the silent bont/B5 gene was in an ha+ cluster. Phylogenetic analysis of both bont/A1 and bont/B5 sequences showed 100% amino acid identity, respectively, to previously reported A1(B5) strains (e.g., CDC_69094, FE9504ACG). Multi-locus sequence typing (MLST) assigned the ST10, a genotype previously undetected in Spanish botulism cases, yet found in other European countries. This case highlights the importance of considering botulism in differential diagnosis due to its varied presentation and the significance of timely laboratory confirmation for effective management. The identification of this dual-toxin BoNT/A1(B5) orfX+/ha+ ST10 strain expands our understanding of C. botulinum epidemiology and genetic diversity in Spain. Full article

Background: Helcococcus kunzii, a facultative anaerobe and Gram-positive coccus, has been documented as a cunning pathogen, mainly in immunocompromised individuals, as evidenced by recent clinical and microbiological reports. It has been associated with a variety of polymicrobial infections, comprising diabetic foot ulcers, prosthetic joint infections, osteomyelitis, endocarditis, and bloodstream infections. Despite its emerging clinical relevance, no licensed vaccine or targeted immunotherapy currently exists for H. kunzii, and its rising resistance to conventional antibiotics presents a growing public health concern. Objectives: In this study, we employed an integrated subtractive proteomics and immunoinformatics pipeline to design a multi-epitope subunit vaccine (MEV) candidate against H. kunzii. Initially, pan-proteome analysis identified non-redundant, essential, non-homologous, and virulent proteins suitable for therapeutic targeting. Methods/Results: From these, two highly conserved and surface-accessible proteins, cell division protein FtsZ and peptidoglycan glycosyltransferase FtsW, were selected as promising vaccine targets. Comprehensive epitope prediction identified nine cytotoxic T-lymphocyte (CTL), five helper T-lymphocyte (HTL), and two linear B-cell (LBL) epitopes, which were rationally assembled into a 397-amino-acid-long chimeric construct. The construct was designed using appropriate linkers and adjuvanted with the cholera toxin B (CTB) subunit (NCBI accession: AND74811.1) to enhance immunogenicity. Molecular docking and dynamics simulations revealed persistent and high-affinity ties amongst the MEV and essential immune receptors, indicating a durable ability to elicit an immune reaction. In silico immune dynamic simulations predicted vigorous B- and T-cell-mediated immune responses. Codon optimization and computer-aided cloning into the E. coli K12 host employing the pET-28a(+) vector suggested high translational efficiency and suitability for bacterial expression. Conclusions: Overall, this computationally designed MEV demonstrates favorable immunological and physicochemical properties, and presents a durable candidate for subsequent in vitro and in vivo validation against H. kunzii-associated infections. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article

Aflatoxins are carcinogenic secondary metabolites produced by Aspergillus species and are common contaminants of many crops including maize. Atoxigenic Aspergillus flavus strains, formulated as biocontrol products such as Aflasafe^® TZ01, that comprises a mixture of four native atoxigenic strains, are used as pre-harvest agents to suppress toxigenic strains and reduce aflatoxin levels. This study assessed the intended and potential unintended impacts of Aflasafe^® TZ01 on mycotoxin contamination in maize. A total of 158 samples 79 from treated and 79 from untreated fields were collected from Chemba and Kiteto districts in Tanzania. Multi-mycotoxin analysis was conducted using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Detected toxins included aflatoxins (AFB1, AFB2, AFG1, AFG2), trichothecenes, and fumonisins (FB1, FB2, FB3). Non-parametric paired t-test analysis showed significant reductions in AFB1 (62%, p = 0.024) in treated samples. The mean concentrations of Fusarium mycotoxins such as NIV, T2, and ZEN were higher in treated maize. However, statistical analysis showed that these differences were only numerical trends, and were not significant (p > 0.05). These findings confirm the efficacy of Aflasafe^® TZ01 in reducing aflatoxins, while underscoring the importance of continued monitoring for other mycotoxins as part of integrated mycotoxin management strategies to mitigate both aflatoxins and co-occurring toxins. Full article

Chronic kidney disease (CKD) is associated with a significantly elevated mortality rate, primarily due to cardiovascular disease (CVD), highlighting a complex bidirectional relationship between the two conditions. Life-threatening cardiovascular events occur despite control of the traditional risk factors, emphasizing the underlying role of non-traditional risk factors. CKD, causing mineral imbalance and the accumulation of uremic toxins due to a compromised ability to excrete waste products, imposes extra pressure on the cardiovascular system. The retention of mineral and uremic toxins, in turn, aggravates the progression of CKD. This review aims to elucidate the pathophysiological connections between CKD and CVD, with a particular focus on the metabolic regulatory mechanisms influenced by minerals such as calcium and phosphate, as well as uremic toxins. We review how these factors contributed to accelerated multi-organ damage through mechanisms such as inflammation, endothelial dysfunction, oxidative stress, and vascular calcification. In addition, we discuss the therapeutic strategies for specific uremic toxins and proposed directions for future investigations. This review provides insights into the complex interplay between metabolic dysregulation and cardiovascular outcomes in CKD patients, promoting the development of innovative therapeutic interventions, ultimately improving the prognosis and quality of life for patients affected by these interconnected conditions. Full article

We report herein the development of a polyclonal antibody against ochratoxin A (OTA) using a specially designed synthetic OTA derivative as the immunizing hapten. This OTA derivative contains a tetrapeptide linker (glycyl-glycyl-glycyl-lysine, GGGK), through which it can be linked to a carrier protein and form an immunogenic conjugate. The OTA derivative (OTA-glycyl-glycyl-glycyl-lysine, OTA-GGGK) has been synthesized on a commercially available resin via the well-established Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS) strategy; overall, this approach has allowed us to avoid tedious liquid-phase synthesis protocols, which are often characterized by multiple steps, several intermediate products and low overall yield. Subsequently, OTA-GGGK was conjugated to bovine thyroglobulin through glutaraldehyde, and the conjugate was used in an immunization protocol. The antiserum obtained was evaluated with a simple-format ELISA in terms of its titer and capability of recognizing the natural free hapten; the anti-OTA antibody, as a whole IgG fragment, was successfully applied to three different immunoanalytical systems for determining OTA in various food materials and wine samples, i.e., a multi-mycotoxin microarray bio-platform, an optical immunosensor, and a biotin–streptavidin ELISA, which has proved the analytical effectiveness and versatility of the anti-OTA antibody developed. The same approach may be followed for developing antibodies against other low-molecular-weight toxins and hazardous substances. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

Aflatoxin contamination, primarily caused by Aspergillus flavus, poses a significant threat to peanut (Arachis hypogaea L.) production, food safety, and global trade. Despite extensive efforts, breeding for durable resistance remains difficult due to the polygenic and environmentally sensitive nature of resistance. Although germplasm such as J11 have shown partial resistance, none of the identified lines demonstrated stable or comprehensive protection across diverse environments. Resistance involves physical barriers, biochemical defenses, and suppression of toxin biosynthesis. However, these traits typically exhibit modest effects and are strongly influenced by genotype–environment interactions. A paradigm shift is underway with increasing focus on host susceptibility (S) genes, native peanut genes exploited by A. flavus to facilitate colonization or toxin production. Recent studies have identified promising S gene candidates such as AhS5H1/2, which suppress salicylic acid-mediated defense, and ABR1, a negative regulator of ABA signaling. Disrupting such genes through gene editing holds potential for broad-spectrum resistance. To advance resistance breeding, an integrated pipeline is essential. This includes phenotyping diverse germplasm under stress conditions, mapping resistance loci using QTL and GWAS, and applying multi-omics platforms to identify candidate genes. Functional validation using CRISPR/Cas9, Cas12a, base editors, and prime editing allows precise gene targeting. Validated genes can be introgressed into elite lines through breeding by marker-assisted and genomic selection, accelerating the breeding of aflatoxin-resistant peanut varieties. This review highlights recent advances in peanut aflatoxin resistance research, emphasizing susceptibility gene targeting and genome editing. Integrating conventional breeding with multi-omics and precision biotechnology offers a promising path toward developing aflatoxin-free peanut cultivars. Full article

The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article