Search Results (624)

T-2 toxin and HT-2 toxin are commonly found in agricultural products and animal feed, posing serious effects to both humans and animals. This study employed combination index (CI) modeling and metabolomics to assess the combined cytotoxic effects of T-2 and HT-2 on four porcine cell types: intestinal porcine epithelial cells (IPEC-J2), porcine Leydig cells (PLCs), porcine ear fibroblasts (PEFs), and porcine hepatocytes (PHs). Cell viability assays revealed a dose-dependent reduction in viability across all cell lines, with relative sensitivities in the order: IPEC-J2 > PLCs > PEFs > PHs. Synergistic cytotoxicity was observed at low concentrations, while antagonistic interactions emerged at higher doses. Untargeted metabolomic profiling identified consistent and significant metabolic perturbations in four different porcine cell lines under co-exposure conditions. Notably, combined treatment with T-2 and HT-2 resulted in a uniform downregulation of LysoPC (22:6), LysoPC (20:5), and LysoPC (20:4), implicating disruption of membrane phospholipid integrity. Additionally, glycerophospholipid metabolism was the most significantly affected pathway across all cell lines. Ether lipid metabolism was markedly altered in PLCs and PEFs, whereas PHs displayed a unique metabolic response characterized by dysregulation of tryptophan metabolism. This study identified markers of synergistic toxicity and common alterations in metabolic pathways across four homologous porcine cell types under the combined exposure to T-2 and HT-2 toxins. These findings enhance the current understanding of the molecular mechanisms underlying mycotoxin-induced the synergistic toxicity. Full article

Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms. Full article

Background: Rapid loss of residual kidney function (RKF) is associated with unfavorable outcomes. We conducted an RCT to compare the effects on RKF preservation of incremental HD between once-weekly HD (1-WHD) and twice-weekly HD (2-WHD). Methods: ESKD patients with an eGFR of 5–10 mL/min/1.73 m² and urine output of ≥800 mL/day were randomly assigned to receive either once-weekly HD (1-WHD) or twice-weekly HD (2-WHD) for 12 months. Patients in the 1-WHD group were prescribed once-weekly HD combined with low-protein diet (0.6 g/kg/day) supplemented with keto-analogues (KAs) 0.12 g/kg/day. In the 2-WHD group, patients received twice-weekly HD with a regular-protein diet. Primary outcomes were changes in RKF by renal clearance and urine volume. Nutritional status, muscle parameters, and quality of life (QoL) were also assessed. Results: A total of 30 incident HD patients were randomized. Baseline RKF, urine volume, and demographic were not different between groups. After 3 months, urine volume was significantly higher in the 1-WHD group than in the 2-WHD group (1921 ± 767 mL/day vs. 1305 ± 599 mL/day, p = 0.02), and these significant findings persisted throughout the entire study period. For RKF, 1-WHD also had a lesser decline in urinary urea (CUrea) and creatinine clearance (CCr) than 2-WHD, with statistically significant differences observed from months 6–12. By month 6, the 1-WHD group exhibited significantly higher CUrea and CCr compared to the 2-WHD group, with CUrea at 3.2 ± 2.3 vs. 1.7 ± 1.0 mL/min (p = 0.03) and CCr at 5.9 ± 3.6 vs. 3.8 ± 1.4 mL/min (p = 0.04), respectively. Serum albumin levels, skeletal muscle mass, anemia status, metabolic parameters, protein-bound uremic toxins, and QoL scores were comparable between the two groups. Conclusions: Incremental HD, starting with once-weekly HD combined with protein restriction supplemented with KAs, appears to better preserve RKF among incident HD patients compared to twice-weekly HD with a regular-protein diet. This HD regimen was also associated with safety in metabolic and nutritional profiles. Full article

Infections caused by Acinetobacter baumannii are increasing worldwide. We evaluated the antibiotic resistance profile, biofilm production, and the frequency of 12 genes encoding carbapenemases and 13 virulence factors in 90 isolates from patients of three hospitals in various regions of Poland. Antibiotic resistance survey was performed using the disc-diffusion method, genes encoding resistance to carbapenems and virulence factors were detected with PCR, and biofilm formation was tested using microtiter plates. A total of 52.2% of isolates were resistant to all tested antibiotic groups (penicillins with β-lactamase inhibitors, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and trimethoprim plus sulfamethoxazole). Among the genes encoding carbapenem resistance, the bla_OXA-23 (68.9%), bla_OXA-40 (83.3%), and ISAba-bla_OXA-51 (18.9%) were detected. The ompA, ata, and recA genes responsible for biofilm formation, adhesion, and stress response, respectively, occurred in all isolates. Genes responsible for the production of other adhesins (bap—94.4%, espA—4.4%, chop—37.7%), biofilm formation (pbpG—90.0%), production of siderophore (basD—97.7%), toxins (lipA—92.2%, cpaA—1.1%), glycoconjugates (bfmR—84.4%), and inducing host cell death (fhaB—71.1%, abeD—93.3%) were also found. A total of 68.8% of isolates produced biofilm. The isolates from Masovia had more virulence genes than isolates from the other regions; moreover, all isolates from Masovia and West Pomerania were multidrug-resistant (MDR), including resistance to carbapenems. Full article

Autism spectrum disorder (ASD) is increasingly associated with microbial and metabolic disturbances, including the altered production of gut-derived uremic toxins. We investigated urinary concentrations of five representative uremic toxins—indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in 161 children with ASD and 71 healthy controls. Toxins were measured using LC-MS/MS and were normalized to creatinine. Subgroup analyses were performed by sex, age group (2–5.9 vs. 6–17 years), and autism severity based on the Childhood Autism Rating Scale (CARS). In addition to individual concentrations, we calculated the total toxin burden, proportional contributions, and functional ratios (IS/PCS, PCS/TMAO, and IS/ADMA). While individual toxin levels did not differ significantly between groups, stratified analyses revealed that PCS was higher in girls and in severe cases of ASD, whereas IS and TMAO were reduced in younger and more severely affected children. The functional ratios shifted consistently with severity—IS/PCS declined from 1.69 in controls to 0.99 in severe cases of ASD, while PCS/TMAO increased from 12.2 to 20.5. These patterns suggest a phenolic-dominant microbial signature and an altered host–microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone. Full article

Background/Objectives: Increasing levels of antimicrobial resistance (AMR) have recently been observed at the human–domestic animal–wildlife interface. Wild birds have been identified as carriers of antimicrobial-resistant bacteria and serve as excellent biomarkers for epidemiological studies. This study assessed the current AMR presence in Eastern Spain’s commensal Escherichia coli isolated from free-ranging Bonelli’s eagles (Aquila fasciata). Methods: Nestlings and their nests were intensively sampled between 2022 and 2024 to determine their AMR profile and characterize E. coli. AMR testing was conducted using the broth microdilution method, following the European Committee on Antimicrobial Susceptibility Testing guidelines. Additionally, the presence of eaeA (intimin gene) and stx-1 and stx-2 (shiga toxins) was analyzed by real-time PCR to classify E. coli strains into enteropathogenic (EPEC) and Shiga-toxigenic (STEC) pathotypes. Results: Of all E. coli isolates, 41.7% were resistant to at least one antimicrobial, and 30% were multidrug-resistant. Only two strains were classified as EPEC and none as STEC. The highest resistance rates were observed for amoxicillin and tetracycline (19.6% each). Alarmingly, resistance to colistin and meropenem, last-resort antibiotics in human medicine, was also detected. Conclusions: Although the mechanisms of resistance acquisition remain unclear, transmission is likely to occur through the food chain, with synanthropic prey acting as intermediary vectors. These results highlight the role of Bonelli’s eagles as essential sentinels of environmental AMR dissemination, even in remote ecosystems. Strengthening One Health-based surveillance is necessary to address AMR’s ecological and public health risks in wildlife. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD), a recently proposed term to replace non-alcoholic fatty liver disease (NAFLD), emphasizes the critical role of metabolic dysfunction and applies broader diagnostic criteria. Diagnosis of MAFLD requires evidence of hepatic steatosis combined with obesity, type 2 diabetes mellitus, or other metabolic dysregulation conditions, all of which significantly elevate the risk of chronic kidney disease (CKD). This review discusses the pathological mechanisms of lipid accumulation and insulin resistance in MAFLD and CKD, highlighting their mechanistic connections. Specifically, ectopic fat accumulation triggered by metabolic reprogramming, oxidative stress and inflammation induced by energy overload, modified lipids, uremic toxins, and senescence, as well as insulin resistance pathways activated by pro-inflammatory factors and lipotoxic products, collectively exacerbate simultaneous hepatic and renal injury. Moreover, interactions among hyperinsulinemia, the sympathetic nervous system, the renin–angiotensin system (RAS), and altered adipokine and hepatokine profiles further amplify insulin resistance, ectopic lipid deposition, and systemic damage. Finally, the review explores potential therapeutic strategies targeting lipid metabolism, insulin sensitivity, and RAS activity, which offer promise for dual-organ protection and improved outcomes in both hepatic and renal systems. Full article

Background/Objectives: European hedgehogs (Erinaceus europaeus) are present in areas where there is human activity; therefore, they can be a source of pathogens for other animals and humans. Methods: Eighteen hedgehog carcasses were collected and analyzed for Staphylococcus spp. Isolated strains were typed and analyzed for exfoliative toxins genes and the phenotypic and genotypic characteristics of antimicrobial resistance. Results: A total of 54 strains were isolated and typed as S. aureus, S. xylosus, S. sciuri, S. pseudintermedius, S. simulans, S. chromogenes, S. epidermidis, S. hyicus, and S. lentus. No strains had the eta and etb genes coding for exfoliative toxins. Overall, 39/54 (72.20%) isolates showed phenotypic resistance to at least one antimicrobial and 21/54 (38.80%) showed more than one resistance. The lowest efficacy was observed for erythromycin, with 40/54 (74.08%) strains classified as intermediate and 6/54 (11.11%) classified as resistant. Among the 29 isolates shown to be penicillin-resistant, 11 (37.93%) were oxacillin-resistant, with a minimum inhibitory concentration (MIC). Among the 54 staphylococcal strains, 2 (3.70%) were resistant to vancomycin, both with an MIC value equal to the maximum concentration of the antibiotic tested (256 μg/mL) and 2 (3.70%) had an intermediate resistance profile with an 8 μg/mL MIC value. No strains had the genes vanA and vanB. Two of the 29 (6.90%) penicillin-resistant strains had the blaZ gene; 8 (27.13%) strains had the mecA gene. Overall, 2/54 (3.70%) isolates were classified as extensively drug-resistant (XDR) and 9/54 (16.66%) were classified as multidrug-resistant (MDR). Conclusions: Hedgehogs can harbor antimicrobial-resistant staphylococci and can be sources of these bacteria for other animals and humans. They can also serve as bioindicators of the pathogens and antimicrobial-resistant bacteria circulating in a given habitat. Full article

Natural products have emerged as potential alternatives to antibiotics in the treatment of bacterial diarrhea, due to their multi-targeting effects, low potential for inducing resistance, and favorable safety profiles. Currently, the search for natural product-based therapies has become an emerging focus in medical research. This growing interest is driven by the increasing awareness that the widespread and irrational use of antibiotics has contributed to the alarming rise in antibiotic-resistant bacterial strains, which in turn diminishes the efficacy of conventional drugs. Among these concerns, the limitations of antibiotics in managing bacterial diarrhea and the potential mechanisms by which natural products exert therapeutic effects are the main focus of this paper. Natural products, containing a wide array of bioactive compounds, can not only directly inhibit the growth of pathogenic bacteria, disrupt bacterial membrane synthesis, and reduce toxin production, but also modulate inflammatory responses, enhance immune function, repair intestinal barriers, and restore gut microbial ecology—highlighting their systemic and multi-targeted therapeutic potential. Therefore, this paper will elaborate on how natural products combat bacterial diarrhea from three aspects: the pathogen and pathogenesis of bacterial diarrhea, natural product-based therapeutic studies, and the underlying mechanisms of action, thereby proposing natural products as viable alternatives to antibiotics. Full article

Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A₂s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom. Full article

Honeysuckle, derived from the dried flower buds or blossoms of Lonicera japonica Thunb, is a traditional Chinese medicine known for its properties in eliminating heat and toxins, reducing inflammation, and alleviating swelling. In this study, we investigated the potential therapeutic and preventive benefits of L. japonica extract on inflammatory diseases induced by lipopolysaccharide (LPS) using Misgurnus anguillicaudatus as a model organism. The fish were fed a diet supplemented with L. japonica extract, followed by LPS injection to induce inflammation. We then analyzed the transcriptional profile to identify differentially expressed genes (DEGs). A total of 6611 DEGs were identified through comprehensive analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Our results revealed significant enrichment of DEGs in pathways associated with proteasome function, immune system regulation, and infectious disease response. These findings suggest a strong correlation between L. japonica and immune defense mechanisms, providing valuable insights into the potential anti-inflammatory effects of this plant, particularly in the context of LPS-induced inflammation. This study highlights the potential use of L. japonica in treating inflammatory diseases and underscores its role in immune regulation. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

Declining kidney function contributes to the accumulation of uraemic toxins produced by gut microbiota, leading to the uraemic syndrome. This study aimed to identify associations between uraemic toxins, diet quality, symptoms and the gut microbiota in individuals initiating peritoneal dialysis. A cross-sectional analysis of baseline data from participants in a longitudinal study was conducted. Symptom scores using the Integrated Palliative Care Outcomes Scale-Renal were recorded. Plasma p-Cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide were measured using liquid chromatography-mass spectrometry. Gut microbiota was determined using 16S rRNA sequencing. Multivariate linear models examined associations across the cohort. Data from 43 participants (mean age 61 ± 13 years; 70% male; median eGFR 7 mL/min/1.73 m²) were analysed. Diabetes was the primary cause of kidney disease (51.2%). Patients were classified into ‘high’ (n = 18) and ‘low’ (n = 26) uraemic toxin groups using K-means clustering. The ‘high’ group had a lower eGFR (p < 0.05) but no differences in diet quality or symptom scores. Significant differences in alpha and beta diversity were observed between the groups (p = 0.01). The ‘high’ group had increased Catenibacterium, Prevotella, Clostridia, and decreased Ruminococcus gnavus abundances. Multivariate models identified 32 genera associated with uraemic toxins, including positive associations of Oscillospiraceae UCG-002 and UCG-005 with p-cresyl sulfate, and negative associations with Actinomyces and Enterococcus. Patients with kidney failure initiating peritoneal dialysis have distinct uraemic toxin profiles, associated with differences in microbial diversity. This phenotype was also associated with differences in residual kidney function but not with diet or symptom severity. Longitudinal studies are required to determine causality and guide therapeutic interventions. Full article

Introduction: Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global mortality, demands urgent action through diagnostics, vaccines, and therapeutics. In India, the Indian Council of Medical Research’s surveillance network identifies Escherichia coli as a major cause of urinary tract infections, with increasing prevalence in human gut microbiomes, highlighting its significance across One Health domains. Methods: Whole-genome sequencing of E. coli strain ECG015, isolated from a human gut sample, was performed using the Illumina NextSeq platform. Results: Genomic analysis revealed multiple antibiotic resistance genes, virulence factors, and efflux pump components. Phylogenomic comparisons showed close relatedness to pathovars from both human and animal origins. Notably the genome encoded protein tyrosine kinases (Etk/Ptk and Wzc) and displayed variations in the envelope stress-responsive CpxAR two-component system. Promoter analysis identified putative CpxR-binding sites upstream of genes involved in resistance, efflux, protein kinases, and the MazEF toxin–antitoxin module, suggesting a potential regulatory role of CpxAR in stress response and persistence. Conclusions: This study presents a comprehensive genomic profile of E. coli ECG015, a gut-derived isolate exhibiting clinically significant resistance traits. For the first time, it implicates the CpxAR two-component system as a potential central regulator coordinating antimicrobial resistance, stress kinase signaling, and programmed cell death. These findings lay the groundwork for future functional studies aimed at targeting stress-response pathways as novel intervention strategies against antimicrobial resistance. Full article

Yellow stunt and root rot causes premature degradation of Astragalus adsurgens grasslands in China. However, the etiological factors underlying livestock poisoning following the ingestion of diseased plants remain elusive. The present study aimed to comprehensively characterize the alterations in toxic substances such as swainsonine and trace element profiles in A. adsurgens after infection with Alternaria gansuense, thereby elucidating the underlying mechanisms of livestock toxicity. Using ELISA and regression analyses, we found that diseased plants had higher selenium levels than the healthy ones, with varietal differences. Selenium in the Zahua variety was higher in healthy plants, while diseased plants of the Henan variety had the highest levels. Moreover, the diseased plants demonstrated decreased levels of iron, zinc, sodium, and magnesium, while manganese and calcium concentrations remained unchanged. Swainsonine was detected in both the healthy and infected specimens of Zhongsha No.1 and Henan varieties, with a marked post-infection increase. In conclusion, swainsonine is the primary toxin causing livestock poisoning, and it is unlikely that soil-accumulated selenium poisons animals. However, potential correlations might exist among the contents of selenium, sodium, and swainsonine. We recommend the cautious use of diseased A. adsurgens as livestock feed. Full article