Search Results (863)

Background/Objectives: The strategy of targeting endotoxins and circulating histones to alleviate excessive inflammation and tissue damage has been proposed as an important immunoregulatory strategy against sepsis. However, the development of a multifunctional hemoperfusion adsorber that simultaneously removes endotoxins and histones remains an unmet clinical need in sepsis management. Methods: We synthesized chitosan-cellulose composite (CSCE) microspheres utilizing phase inversion technology, while heparin-grafted chitosan-cellulose composite (CSCEHEP) microspheres were developed by grafting heparin onto CSCE microspheres through the carbodiimide coupling method. In our experimental design, we allocated healthy New Zealand rabbits to four distinct groups: a healthy control group, a lipopolysaccharides (LPS) group, a CSCE group, and a CSCEHEP group. Following the administration of LPS for 12 h, septic rabbits underwent extracorporeal hemoperfusion with either CSCE or CSCEHEP microspheres for a duration of 6 h, notably without the inclusion of heparin in the blood circuits. Post-hemoperfusion, we conducted an analysis of thrombus formation and total protein adsorption on the column. Concurrently, blood samples were collected from the venous side to evaluate inflammatory cytokine concentrations, liver and kidney function levels, LPS levels, the histone presence, and to perform histopathological assessments of liver and kidney injury. Results: Our in vivo experiments demonstrated that CSCEHEP microspheres for extracorporeal circulation could achieve a 6 h hemoperfusion session in septic rabbits without the need for continuous anticoagulation with heparin. A CSCEHEP column turns into a very light-red color (almost the original white) and light contamination or clotting was observed after the 6 h hemoperfusion. Moreover, CSCEHEP microspheres effectively reduced the concentration levels of leukocyte, serum IL-6 and TNF-α, mitigated pathological damage to the liver and kidneys, and removed over 56.7% of LPS and nearly 58.6% of histone H3 from the blood of septic rabbits during hemoperfusion. Conclusions: Hemoperfusion utilizing CSCEHEP microspheres exhibits excellent self-anticoagulation capabilities, remarkable anti-inflammatory performance, efficient endotoxin adsorption and histone antagonism properties, rendering it both effective and safe for use in septic rabbits. Full article

Similar to other municipal facilities, landfills are a substantial source of emissions of various biological pollutants. Numerous sustainability challenges result from the extremely high variability of emissions of harmful biological agents, which necessitates precise detection of microbiological emissions from these municipal facilities. This study aimed to assess whether a municipal waste landfill impacts indicator microorganisms and bacterial endotoxins occurring in soils within the landfill’s zone of influence. The research was conducted directly at the landfill site and in the surrounding area. Soil samples were collected monthly from eight sites over three years. Microbiological analyses included determination of total Salmonella counts and bacteria of the coliform group, Clostridium spp., Clostridium perfringens, and bacterial endotoxin concentrations. Results revealed a significant effect of the landfill on soil sanitary quality, indicating that adverse impacts depended mainly on the distance from the active waste sector of the landfill. The results also confirmed the usefulness of bacterial endotoxins as indicators of soil contamination with microorganisms within the municipal landfill and surroundings. Parametric statistical analyses effectively characterised contamination levels, and the Newman–Keuls multiple comparison test proved to be a rapid and reliable tool for assessing exceedances of established sanitary standards. Findings indicate that fresh waste is a critical source of microbiological contamination in soils, and they emphasise the value of combined microbial and endotoxin monitoring for sustainable landfill environmental assessment and management. While the current study focuses on soil contamination, future research should evaluate the impact of landfill on indicator microorganisms and bacterial endotoxins in air and water. Full article

Collagen is a major extracellular-matrix protein widely used in regenerative medicine, yet conventional terrestrial sources raise biosafety and acceptability concerns, motivating the search for marine alternatives. This study evaluates the jellyfish Rhizostoma pulmo (R. pulmo) from the Azov Sea as a sustainable collagen source and assesses its suitability for biomedical materials. Acid-soluble collagen was extracted using 0.5 M acetic acid and purified by salt precipitation and dialysis, followed by physicochemical/structural characterization (sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE), Limulus amebocyte lysate (LAL) endotoxin testing, transmission electron microscopy (TEM), and immunofluorescence with type I collagen antibodies) and biological evaluation in vitro (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity on MRC5 fibroblasts; adhesion and proliferation assays on HeLa cells). The extracted collagen showed a high yield (~26.2%), a type I-like electrophoretic profile with α-, β-, and γ-components, fibrillar ultrastructure by TEM, and positive type I collagen immunoreactivity; endotoxin levels were low (0.461 EU/µL), and no cytotoxicity was detected under the tested conditions. Porous collagen sponges/scaffolds were fabricated by lyophilization, displaying interconnected pores with an average size of ~80 µm and pH-dependent swelling, and they supported 3D cell growth and tumor-cell dissemination in an in vitro breast carcinoma scaffold model. Overall, Azov Sea R. pulmo collagen demonstrates promising structural quality, low endotoxin burden, and cytocompatibility, supporting its potential as a marine biomaterial for sponge/scaffold-based tissue engineering and wound-related applications. Full article

Porphyromonas gingivalis is described as a keystone pathogen associated with periodontal disease (PD), which exhibits enhanced representation upon microbial dysbiosis in such a chronic inflammatory disease. This oral pathogen drives and contributes to a dysregulated immune response, resulting in stages of aggressive destructive immune activation and inflammation punctuated by immune suppression, which underlies the relapsing–remitting nature of this disease. The understanding of key mechanisms and balance between protective innate, adaptive immune responses and dysregulated responses, linked to changes in the oral mucosal microbial environment, will afford researchers the potential to manipulate oral mucosal environments for clinical benefit. This review focuses on the dynamic interactions between the oral pathogen P. gingivalis and the immune system with an emphasis on immune evasion and how the potential correction of these mechanisms may benefit future therapeutic interventions, leading to the successful treatment of PD. Full article

Heat stress (HS) occurs when animals are unable to effectively dissipate excess body heat, leading to increased core temperature and physiological imbalance. In mammals, HS negatively affects female reproduction. Infertility associated with HS is well documented in swine and is increasingly recognized in other mammals, including humans. HS disrupts several systemic processes that are essential for normal reproductive function, including endocrine regulation, nutrient metabolism, immune activity, and intestinal barrier integrity. Reduced feed intake and changes in metabolic hormones such as insulin and prolactin can impair ovarian function. Increased intestinal permeability during HS may allow bacterial endotoxins to enter the bloodstream, triggering inflammation that further compromises reproductive physiology. At the ovarian level, HS alters key cellular pathways involved in cell survival and metabolism, including Janus Kinase/Signal Transducer and Activator of Transcription (JAK–STAT), Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT), oxidative stress responses, autophagy, apoptosis, and heat shock protein expression. These changes disrupt follicular development, hormone production, oocyte quality, and corpus luteum function, resulting in reduced conception rates and increased embryonic loss. This review summarizes current knowledge of systemic and ovarian mechanisms by which HS impairs female reproduction in pigs and identifies areas requiring further investigation to improve fertility under increasing environmental temperatures. Full article

Post-weaning piglets are vulnerable to intestinal barrier disruption and microbiota imbalance, which can be exacerbated by bacterial endotoxin; this study assessed whether a synbiotic diet based on grape seed and camelina meals plus Lactobacillus probiotics can attenuate an Escherichia coli lipopolysaccharide (LPS) challenge. Twenty weaned piglets were randomized (n = 5/group) to control, LPS, synbiotic (SYN), or SYN+LPS diets for 21 days. The control diet consisted of a complete standard corn–soybean-based feed. The SYN diet contained a basal diet with 5% prebiotic mix (grape seed meal–camelina meal) and 0.1% probiotic mix including Lactobacillus acidophilus, Lactobacillus paracasei, and Lactobacillus rhamnosus; on day 21, the LPS and SYN+LPS animals received an LPS challenge and were sampled 3 h later. The expression of colonic genes coding for proteins like tight junctions, mucus/epithelial function, Toll-like receptors and signaling molecules involved in innate response was quantified by quantitative PCR arrays, and the microbiota composition was profiled by 16S rRNA sequencing. The LPS challenge reduced the expression of barrier- and mucus-associated genes and increased that of Toll-like receptors and signaling pathway markers, accompanied by microbial shifts, with reduced beneficial taxa and increased Megasphaera elsdenii. The synbiotic diet counteracted these transcriptional and microbial changes. Overall, the synbiotic supported epithelial integrity and moderated innate immune activation during acute endotoxin stress after weaning. Full article

Hydroxyapatite-based ceramics are widely used in dental bioengineering, yet the reliable assessment of endotoxin activity in solid porous materials remains challenging. This study evaluated the applicability of a whole blood Monocyte Activation Test (MAT) to a hydroxyapatite ceramic relevant to dental applications. Two endotoxin association strategies (immersion and dropwise) were compared, followed by nonlinear modelling of cytokine dose–response curves using four-parameter logistic (4PL) regression and spike-recovery analysis to assess potential material interference. Immersion-based spiking produced reproducible, concentration-dependent cytokine responses, whereas dropwise application resulted in minimal functional recovery. IL-1β, IL-6, and TNF-α displayed sigmoidal dose–response profiles with high goodness-of-fit values (R² ≥ 0.93). Spike recovery remained within the 50–200% acceptance range for most concentrations, with IL-6 showing the most consistent analytical performance. TNF-α exhibited signal saturation at higher endotoxin levels, limiting its dynamic range. Multiplex cytokine profiling confirmed that classical MAT readouts were among the most strongly induced mediators and that hydroxyapatite did not trigger baseline inflammatory activation. These findings demonstrate that whole blood MAT can be reliably applied to hydroxyapatite-based dental ceramics when immersion-based endotoxin association and material-specific methodological optimization are employed. Full article

Marine lectins function as pattern recognition receptors in innate immunity through carbohydrate-binding mechanisms. However, mechanistic evidence detailing intracellular signaling cascades (e.g., MAPK/NF-κB/JAK-STAT activation linked to defined cytokine outputs) remains taxonomically uneven. Bivalve mollusks—particularly the Mytilectin family—represent the most extensively characterized group, whereas lectins from other marine phyla (echinoderms, cnidarians, fish, algae) have been studied primarily for structural and glycan-binding properties alongside phenotypic antimicrobial outcomes. Signaling-level resolution in native immune-cell contexts, while present in some cases, remains comparatively limited. This review synthesizes mechanistic insights dominated by bivalve-derived lectins, while integrating cross-taxa comparisons at evidence-supported levels. Specific bivalve lectins induce macrophage activation and pro-inflammatory cytokine production through reactive oxygen species-dependent activation of key signaling pathways including MAPK, NF-κB, and JAK-STAT cascades. These lectins exhibit context-dependent properties, promoting inflammatory responses in resting cells while inducing endotoxin tolerance in pre-activated macrophages through epigenetic reprogramming. Functional outcomes include broad-spectrum antiviral activity through viral envelope glycoprotein binding, anti-inflammatory effects in pain models, and cancer-associated immune responses through tumor glycan recognition and macrophage polarization. Critical gaps include uncharacterized effects on adaptive immunity, limited understanding of dendritic cell and natural killer cell interactions, and incomplete evaluation of cancer immunotherapy potential. Future research should prioritize mechanistic characterization of marine lectin-based immunotherapeutics. Full article

Introduction: Endotoxin-mediated septic shock is a life-threatening condition characterized by systemic inflammation and hemodynamic instability. While Polymyxin-B hemoadsorption (Toraymyxin^®) is well-studied in adults, its use in pediatric patients remains less explored and requires modified approaches to minimize invasiveness and complications. Case Presentation: We report a 9-year-old boy (25 kg) with endotoxin-mediated septic shock due to Klebsiella pneumoniae, who developed oliguric acute kidney injury requiring continuous renal replacement therapy (CRRT). On Day 4, worsening conditions prompted the initiation of Toraymyxin^® treatment, directly integrated into the ongoing CRRT circuit. This approach minimized extracorporeal volume expansion, avoided circuit replacement, and was complication-free. The patient improved rapidly, allowing CRRT discontinuation and transfer to the ward within 28 days. Conclusions: This case highlights the feasibility, safety, and potential benefits of integrating the Toraymyxin^® cartridge into an ongoing CRRT circuit in pediatric septic shock, minimizing extracorporeal volume, avoiding additional vascular access, and supporting hemodynamic stabilization. Full article

Lactococcus lactis, a safe food-grade lactic acid bacterium, has attracted increasing attention as a live biotherapeutic platform for mucosal vaccine development. Its genetic simplicity, absence of endotoxins, and availability of well-characterized inducible systems have enabled controlled expression and delivery of heterologous antigens and therapeutic molecules. This review highlights recent advances in the use of genetically modified L. lactis for mucosal immunization, focusing on expression technologies, routes of administration, and immune mechanisms relevant to protection or tolerance. Preclinical studies demonstrate its capacity to induce both mucosal and systemic immune responses against diverse pathogens, underscoring its potential as a safe and versatile vaccine chassis. Remaining challenges include regulatory harmonization, biosafety concerns, and the need for standardized manufacturing and evaluation frameworks. Together, these developments position L. lactis as a promising candidate for next-generation mucosal vaccines and live biotherapeutic products. Full article

Uncontrolled inflammation contributes to the development of neurodegenerative diseases (NDs) like Alzheimer’s disease (AD). N-(p-Coumaroyl) serotonin (CS) has demonstrated a significant capacity to modulate hyper-inflammation. We explored whether CS could mitigate inflammatory responses in endotoxin-challenged microglial cells and sought to elucidate the specific molecular mechanisms governing these effects. ELISA, nitric oxide (NO) assays, Western blotting and immunocytochemistry were performed to study inflammatory responses and related signal transduction mechanisms. CS pretreatment effectively attenuated the inflammatory output in endotoxin-primed microglial models. This was evidenced by a significant reduction in key cytokines (such as IL-6, TNF-α, and MCP-1) and a concomitant decrease in the protein levels of iNOS and COX-2. These effects were mediated through the disruption of MAPK/NF-κB signaling cascades and the sequestration of NF-κB within the cytoplasm. Beyond its anti-inflammatory role, CS promoted the HO-1/NQO1 signaling pathway and interfered with the LPS-mediated TLR4/MyD88 cascade. Our collective evidence indicates that the modulation of microglia-mediated inflammation by CS is underpinned by the suppression of MAPK/NF-κB and the induction of antioxidant systems, suggesting that CS may have the potential to improve NDs. Full article

In severe bacterial infections, endotoxin- and exotoxin-induced inflammation and tissue damage, combined with the consequent excessive production of inflammatory mediators by neutrophils, may result in sepsis, septic shock, organ failure, and possibly death. Evidence suggests that supplementation with polyvalent intravenous (IV) immunoglobulin (Ig) preparations, such as standard IVIg or IgM/IgA-enriched Ig preparations, could be an additional treatment option. However, their use in severe bacterial infections like sepsis and septic shock is still a matter of debate. This review summarizes the diverse beneficial mechanisms of (inter)actions of Igs with pathogens and the host. Support for these mechanisms comes from numerous nonclinical studies, complemented by clinical research in adult patients with sepsis, septic shock, and other severe infectious diseases. Depending on Ig type, timepoint of administration, patient population, and dose, the pathogen- and host-induced inflammatory responses are modulated by the combined (inter)actions of polyvalent IgM, IgA, and IgG, with pathogens, and particularly with the host’s neutrophil and complement pathways. However, while nonclinical and clinical studies suggest potential benefits of Ig therapy, clinical evidence remains heterogeneous, and trials with low risk of bias have not consistently demonstrated a definitive survival benefit. A deeper understanding of the conditions under which Ig treatment benefits patients with severe bacterial infections will help select patients most likely to profit from Ig treatment and achieve better outcomes. Full article

The oral cavity contains a complex and dynamic microbial ecosystem that plays a central role in maintaining both local and systemic homeostasis. Emerging evidence indicates that disturbances in oral microbial communities-including genetic and functional diversity within species-are associated not only with oral diseases but may also contribute to the development and progression of systemic diseases. This narrative review summarises the current state of knowledge on bidirectional interactions between oral microbial communities and major organ systems. A comprehensive search of PubMed/MEDLINE, Web of Science, Scopus, and Cochrane databases was conducted for studies published between 2019 and 2025, prioritising systematic reviews, meta-analyses, and high-quality mechanistic studies. Ultimately, 40 articles were included in the narrative synthesis. The results provide clear evidence of an association between oral dysbiosis and cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), chronic respiratory infections, and adverse pregnancy outcomes (APOs). Recent data also suggest links with neurodegenerative disorders, chronic kidney disease (CKD), autoimmune diseases, and cancer. Proposed mechanisms include transient or persistent bacteraemia, systemic inflammation caused by microbial metabolites and endotoxins, disruption of immune homeostasis, molecular mimicry, and modulation of host metabolic pathways. Despite growing evidence linking oral microbial communities to systemic health, most findings are based on observational studies, and causal relationships remain to be established through longitudinal and interventional research. Understanding the connection between the mouth and the body highlights the potential for targeting oral microbial activity, virulence factors, and host inflammatory responses in disease prevention and treatment. Full article

Poly(3-hydroxybutyrate) (P3HB) was used to produce biocompatible composites with hypromellose as an additive. The study aimed to assess their biological and mechanical properties, as well as specific thermal parameters and phase content. Differential scanning calorimetry was applied to analyze the phase transitions of both biocomposites and the polymer matrix. Furthermore, the thermal parameters—encompassing both non-equilibrium and equilibrium states—of the biocomposites and unfilled P3HB were evaluated according to their thermal history. Using equilibrium parameters such as the heat of fusion for fully crystalline materials and the heat capacity change at the glass transition for fully amorphous composites, we estimated the degrees of crystallinity as well as the mobile and rigid amorphous fractions. Adding hypromellose to the P3HB matrix reduced crystallinity compared to the unfilled material. At the same time, an increase in the amorphous phase was observed. It was also discovered that the rigid amorphous fraction exists solely in biocomposites containing 2% by mass of filler. Thermogravimetric analysis showed that the thermal stability of all biocomposites surpasses that of unfilled P3HB. Adding an extra 1% filler by mass raises the degradation temperature by about 37 °C compared to unfilled P3HB. The immunosafety of the tested biocomposites, with very low or no endotoxin contamination, was confirmed in accordance with Food and Drug Administration and European Medicines Agency guidelines. The study clearly demonstrates the influence of the filler in the P3HB matrix on various structural, thermal, mechanical, and biological properties of the prepared biocomposites. Full article

Metabolic Dysfunction-Associated Steato-Hepatitis (MASH) is a multiple-hit disease. Endotoxins, ethanol, and other metabolites of certain gut microbiota can reach the liver and accelerate inflammation and disease progression. Targeting ethanol-producing colonic bacteria with rifaximin could affect the progress of MASH. In the present study, thirty mice were assigned to three groups (n = 10 mice per group). Mice received either a normal diet, a Western diet, or a Western diet with oral rifaximin. After 12 weeks, liver function, serum levels of TNF-α, interleukin (IL)-1β, IL-6, and lipopolysaccharides (LPS) were measured. Liver specimens were assessed for pathological changes, lipid deposition, and fibrosis. Expression of p53, GFAP, CD68, and TLR-4 in the liver was also assessed. Faecal samples were evaluated for ethanol contents. Lactobacillus acidophilus, in addition to ethanol-producing Klebsiella pneumoniae and Escherichia coli, were isolated, quantified, and tested for sensitivity to rifaximin. Rifaximin was able to ameliorate Western diet-induced biochemical changes and elevated TNF-α, IL-1β, IL-6, and LPS levels. Changes in liver histology, fibrosis, and lipid content were attenuated. Expressions of p53, GFAP, CD68, and TLR-4 in the liver were all reduced. The Western diet-induced increases in faecal ethanol or ethanol-producing bacteria were not corrected by rifaximin. After 12 weeks, isolated bacteria from the rifaximin group were rifaximin-resistant. Our findings imply that the protective impact of rifaximin in the MASH model is unlikely to be mediated by alteration of ethanol-producing colonic bacteria because of acquired rifaximin resistance. Rifaximin-induced reduction in endotoxemia and inflammation in the liver appears to be a more relevant explanation. Full article