Search Results (9,502)

The rapid evolution of ventilators and their circuits, coupled with varying maximum usage durations set by different hospitals globally, poses a significant risk for the proliferation and transmission of nosocomial infections in intensive care settings. This study investigated temporal changes in bacterial community structure and predicted metabolic functions in ventilator circuits over a three-week period, with a specific focus on ESKAPE pathogens. The results of full-length 16S rRNA sequencing revealed dynamic shifts in bacterial communities, with an increased bacterial diversity and unique species prevalence in week-2 compared to week-1 and week-3. However, a marked emergence of pathogenic bacteria, including Serratia marcescens and Chryseobacterium indologenes, was observed in week-3 compared to week-1 and week-2. Additionally, the abundance of ESKAPE pathogens, including Klebsiella pneumoniae and Acinetobacter baumannii, was higher in week-3 compared to week-1 and week-2. Furthermore, the PCR analysis revealed a higher detection rate of Pseudomonas aeruginosa and K. pneumoniae in week-3 than in the previous weeks. FAPROTAX analysis further revealed a high abundance of specific functions associated with the pathogens of pneumonia, nosocomial, and septicemia in week-3 compared to the other two weeks, suggesting a shift toward more virulent or opportunistic pathogens with increased utilization of ventilator circuits. These findings highlight the microbial risks associated with prolonged use of ventilator circuits, underscoring the need for continuous microbial surveillance throughout their usage, and provide a foundation for optimizing infection control strategies in intensive care settings. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. 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

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Sea anemone venoms contain diverse toxins that have significant pharmacological potential, including anticancer, ecticidal, and immunotherapeutic properties. However, critically, the extraction methodology influences venom composition and bioactivity. This study characterized venom from Stichodactyla haddoni obtained via homogenization, electrical stimulation, and milking. Extraction yields varied significantly between methods: the homogenization, electrical stimulation, and milking of healthy sea anemones yielded crude venoms at rates of 17.8%, 3.4%, and 1.5%, respectively. SDS-PAGE revealed distinct protein banding patterns and concentrations, while RP-HPLC demonstrated method-dependent compositional differences. Comprehensive proteomic profiling identified 2370 proteins, encompassing both unique and shared components across extraction techniques. Label-free quantitative analysis confirmed significant variations in protein abundance that was attributable to the extraction method. Cytotoxicity assays against cancer cell lines revealed concentration-dependent inhibition, with milking-derived venom exhibiting the highest potency. Insecticidal activity against Tenebrio molitor was also method-dependent, with milking venom inducing the highest mortality rate. These findings elucidate the profound impact of extraction methodology on the protein composition and functional activities of S. haddoni venom, providing crucial insights for its optimized exploitation in pharmacological development. Full article

Background: Enterotoxigenic Bacteroides fragilis (ETBF) carries the bft toxin gene, which influences the host immune response and inflammatory pathways and promotes colorectal cancer (CRC). This study investigated the potential role of ETBF in CRC liver metastasis. Methods: We reviewed the records of 226 consecutive patients who underwent curative-intent (R0) resection of CRC liver metastases. ETBF DNA in fresh-frozen metastasis specimens was quantified using droplet digital PCR (ddPCR). Patients were grouped into very-low (≤80%; N = 178), low (80–90%; N = 24), and high (>90%; N = 24) ETBF-DNA groups. Three tissue cores per specimen were stained for CD8, CD4, CD20, FOXP3, CD68, and CD163, and immune-cell densities were measured digitally (cells/mm²). Results: ETBF DNA was detected in 219 of 226 lesions (96.9%). The densities of cytotoxic CD8⁺ T-cells, effector CD4⁺ T-cells, CD20⁺ B-cells, and CD163⁺ macrophages did not differ significantly by ETBF-DNA group (P_trend all > 0.12). FOXP3⁺ regulatory T-cells (Tregs) decreased (P_trend = 0.010), and CD68⁺ macrophages increased (P_trend = 0.020) as ETBF-DNA levels increased. ETBF-DNA levels in CRC liver metastases were not associated with disease-free survival or overall survival or serum C-reactive protein levels. Conclusions: ETBF was present in almost all CRC liver metastases. Higher ETBF levels were associated with a tumor-immune microenvironment enriched in CD68⁺ macrophages and deficient in FOXP3⁺ Tregs, suggesting that ETBF facilitates immune evasion without loss of effector lymphocytes. Although ETBF-DNA levels did not predict survival in this single-center cohort, the potential role of ETBF in immune remodeling and as a candidate biomarker and therapeutic target in metastatic CRC warrants further study. Full article

The accumulation of blood toxins, including urea, uric acid, creatinine, bilirubin, p-cresyl sulfate, and indoxyl sulfate, poses severe health risks for patients with renal failure. Effective removal strategies are essential to mitigate complications associated with chronic kidney disease (CKD) and improve patient outcomes. Functional carbon-based materials, such as activated carbon (activated charcoal) and graphene oxide, have emerged as promising adsorbents due to their large surface area, adjustable porosity, and biocompatibility. This review comprehensively explores the latest advancements in carbon-based materials for blood purification across three key therapeutic modalities: (1) Hemoperfusion, where activated and modified carbonaceous materials enhance the adsorption of small-molecule and protein-bound toxins; (2) Hemodialysis, where functionalized carbon materials improve clearance rates and reduce treatment duration; and (3) Oral Therapeutics, where orally administered carbon adsorbents show potential in lowering systemic toxin levels in CKD patients. Furthermore, we present a comparative analysis of these approaches, highlighting their advantages, limitations, and future research directions for optimizing carbon-based detoxification strategies. The findings discussed in this review emphasize the significance of material engineering in advancing blood purification technologies. By enhancing the efficiency of toxin removal, carbon-based materials have the potential to revolutionize renal failure treatment, offering improved clinical outcomes and enhanced patient quality of life. Full article

Zearalenone (ZEN) is a widespread estrogenic mycotoxin that poses serious health risks to both humans and animals through the contamination of cereals and feeds. In this study, a novel Bacillus strain X13 was isolated from volcanic rock soil and demonstrated the unique ability to utilize ZEN as the sole carbon source for growth and metabolism. Under optimized conditions (37 °C, pH 8.0, and 5% inoculum in M9 minimal medium), strain X13 achieved a ZEN degradation efficiency of 98.57%. LC-MS analysis identified 1-(3,5-dihydroxyphenyl)-6′-hydroxy-1′-undecen-10′-one as the primary degradation product, indicating enzymatic hydrolysis of the lactone ring. Enzymatic assays revealed that the active components were extracellular, proteinaceous, and metal ion-dependent. Furthermore, the strain reduced ZEN content in mold-contaminated corn flour by 74.6%, effectively lowering toxin levels below regulatory limits. These findings suggest that Bacillus sp. X13 is a promising candidate for the bioremediation of ZEN-contaminated agricultural products, with significant potential for application in food and feed detoxification strategies. The robust degradation performance of strain X13 under simulated environmental conditions, combined with its adaptability to agricultural substrates, positions it as a viable solution for large-scale mycotoxin mitigation in the food industry chain, from pre-harvest field management to post-harvest storage processing. 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

Harmful algae are transported in various compartments of maritime vessels, making ports with heavy maritime traffic potential hotspots for their introduction and spread. In this study, we investigate the port of Papeete (Tahiti, French Polynesia), a key hub for numerous South Pacific shipping routes. Using metabarcoding on DNA extracted from water samples (environmental DNA, eDNA) we identified 21 species of harmful algae comprising to Bacillariophyceae (4), Dinophyceae (14), and Haptophyta (3 species). Three of those species are directly associated with fish mortality events without recognized toxigenic capacity. The remaining harmful algae species are known to produce a wide range of toxins, like the ciguatoxin produced by endemic Gambierdiscus sp., domoic acid, haemolysins, yessotoxins, and others. Health risks such as ciguatera and paralytic shellfish poisoning were identified. An increase in Gambierdiscus frequency in Papeete port waters was parallel to an increase in ciguatera fish poisoning events in Tahiti, which suggests the value of eDNA analysis for early warning of harmful algae presence. Management measures, including banning fishing near the ports, could prevent public health risks associated with harmful algae blooms. Full article

Electrochemical biosensors have emerged as a promising tool for the early detection of diseases in oilseed crops such as rapeseed, soybean, and peanut. These biosensors offer high sensitivity, portability, and cost-effectiveness. Timely diagnosis is critical, as many pathogens exhibit latent infection phases or produce invisible metabolic toxins, leading to substantial yield losses before visible symptoms occur. This review summarises recent advances in the field of nanomaterial-assisted electrochemical sensing for oilseed crop diseases, with a particular focus on sensor mechanisms, interface engineering, and biomolecular recognition strategies. The following innovations are highlighted: nanostructured electrodes, aptamer- and antibody-based probes, and signal amplification techniques. These innovations have enabled the detection of pathogen DNA, enzymes, and toxins at ultra-low concentrations. Notwithstanding these achievements, challenges persist, including signal interference from plant matrices, limitations in device miniaturization, and the absence of standardized detection protocols. Future research should explore the potential of AI-assisted data interpretation, the use of biodegradable sensor materials, and the integration of these technologies with agricultural IoT networks. The aim of this integration is to enable real-time, field-deployable disease surveillance. The integration of laboratory innovations with field applications has been demonstrated to have significant potential in supporting sustainable agriculture and strengthening food security through intelligent crop health monitoring. Full article

The southern pudu (Pudu puda) faces significant threats from anthropogenic activities and infectious diseases. Using whole-genome sequencing (WGS) and forensic microbiology research, we describe a triple bacterial co-infection in a southern pudu impacted by wildfire disasters. The deer presented infected burn wounds on the extremities and dog bite wounds in the lumbosacral region, from which a multidrug-resistant CTX-M-1-producing Escherichia coli sequence type (ST) ST224 and a Klebsiella oxytoca ST145 were isolated, respectively. The patient died 13 days after admission in a wildlife rehabilitation center. During the necropsy, a sample from intracardiac blood was collected, and WGS analyses confirmed systemic dissemination of an E. coli ST224 clone. The broad virulome (adhesins, invasins, toxins, and immune evasion genes) and resistome against beta-lactams (bla_CTX-M-1), aminoglycosides [aac(3)-IId, aph(3′)-Ia, aph(3″)-Ib, aph(6)-Id], macrolides [mph(A)], sulfonamides (sul2), trimethoprim (dfrA17), and fluoroquinolones (gyrA and parC mutations) of E. coli ST224 contributed to the treatment failure and death of the wild animal. Additionally, an oval nodule was identified in the abdominal cavity caused by Acinetobacter baumannii ST1365, the first WGS-confirmed report in wildlife. This study highlights the value of applying forensic microbiology and WGS to investigate and understand One Health pathogens threatening wildlife impacted by natural and anthropogenic disasters. Full article

In end-stage renal disease (ESRD), the accumulation of solutes normally excreted by the kidneys contributes to multiple complications, including vascular calcification (VC), a key factor in the heightened cardiovascular risk seen in these patients. Among VC drivers, hyperphosphatemia and the uremic milieu are major contributors. Kynurenine, a tryptophan metabolite classified as a uremic toxin, may further exacerbate this process. This study investigated whether kynurenine amplifies high phosphate (Pi)-induced calcification in human aortic endothelial cells (HAEC). Cells were treated with Pi and kynurenine for up to seven days. Kynurenine increased Pi-induced calcium deposition by 36%, accompanied by enhanced endothelial-to-mesenchymal transition (EndMT) and osteoblastic differentiation. Mechanistically, kynurenine activated the aryl hydrocarbon receptor (AhR) pathway, and pharmacological inhibition of AhR partially attenuated this effect. These findings suggest that kynurenine contributes to VC in ESRD by potentiating phosphate-induced endothelial dysfunction via AhR signaling. Full article

Deoxynivalenol (DON) is a prevalent mycotoxin in feed, raising concerns about its impact on animal health and feed safety. Insects such as yellow mealworm (Tenebrio molitor) may play a role in the biodegradation of DON-contaminated feed. This study presents the results of a two-week rearing experiment, where 19-week-old yellow mealworm larvae were fed diets with varying concentrations of DON. The larvae were divided into three groups (C, A, and B) that differed in the amount of mycotoxin added to the feed. Larval survival, body mass, and DON accumulation in larvae and their frass were evaluated. A statistical analysis revealed no significant differences in larval survival or body mass gain between the groups. The results point to the low accumulation of DON in larvae, reaching 13.13 ± 2.06 µg/kg (A) and 32.18 ± 4.20 µg/kg (B) after two weeks of feeding. Moreover, at the end of the experiment, DON was detected in larval frass at high concentrations of 507.65 ± 15.31 µg/kg (A) and 862.61 ± 18.53 µg/kg (B), suggesting that larvae are capable of effectively excreting this mycotoxin. The analyzed mycotoxin had no significant effect on larval survival or growth. Deoxynivalenol did not accumulate in the larval biomass and was excreted with frass. These findings enhance our understanding of the interactions between DON and yellow mealworm larvae and have potential implications for using insects in feed production and mycotoxin neutralization within ecosystems. Tenebrio molitor larvae tolerate DON-contaminated feed and effectively excrete the toxin, making them potential candidates for feed detoxification systems. 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