Search Results (3,907)

Endotoxins, lipopolysaccharides released from the outer membrane of Gram-negative bacteria, pose a significant risk in healthcare environments, particularly in Central Sterile Supply Departments (CSSDs), where the delivery of sterile pyrogen-free medical devices is critical for patient safety. Traditional methods for controlling endotoxins in water systems, such as ultraviolet (UV) disinfection, have proven ineffective at reducing endotoxin concentrations to comply with regulatory standards (<0.25 EU/mL). This limitation presents a significant challenge, especially in the context of reverse osmosis (RO) permeate used in CSSDs, where water typically has very low conductivity. Despite the established importance of endotoxin removal, a gap in the literature exists regarding effective chemical-free methods that can meet the stringent endotoxin limits in such low-conductivity environments. This study addresses this gap by evaluating the effectiveness of the eBooster™ electrochemical technology—featuring proprietary electrode materials and a reactor design optimized for potable water—for endotoxin removal from water, specifically under the low-conductivity conditions typical of RO permeate. Laboratory experiments using the B250 reactor achieved >90% endotoxin reduction (from 1.2 EU/mL to <0.1 EU/mL) at flow rates ≤5 L/min and current densities of 0.45–2.7 mA/cm². Additional real-world testing at three hospitals showed that the eBooster™ unit, when installed in the RO tank recirculation loop, consistently reduced endotoxin levels from 0.76 EU/mL (with UV) to <0.05 EU/mL over 24 months of operation, while heterotrophic plate counts dropped from 190 to <1 CFU/100 mL. Statistical analysis confirmed the reproducibility and flow-rate dependence of the removal efficiency. Limitations observed included reduced efficacy at higher flow rates, the need for sufficient residence time, and a temporary performance decline after two years due to a power fault, which was promptly corrected. Compared to earlier approaches, eBooster™ demonstrated superior performance in low-conductivity environments without added chemicals or significant maintenance. These findings highlight the strength and novelty of eBooster™ as a reliable, chemical-free, and maintenance-friendly alternative to traditional UV disinfection systems, offering a promising solution for critical water treatment applications in healthcare environments. Full article

This study aimed to assess whether dietary supplementation with probiotics could alleviate intestinal injury in lipopolysaccharide (LPS)-challenged piglets. Healthy weaned piglets were randomly allocated to four individual groups (n = 6): (1) a control group; (2) an LPS group; (3) an LPS + Lactobacillus group; and (4) an LPS + Bacillus group. The control and LPS groups received a basal diet, while the probiotic groups were provided with the same basal diet supplemented with 6 × 10⁶ cfu/g of Lactobacillus casei (L. casei) or a combination of Bacillus subtilis (B. subtilis) and Bacillus licheniformis (B. licheniformis) at a dosage of 3 × 10⁶ cfu/g, respectively. On day 31 of the trial, overnight-fasted piglets were killed following the administration of either LPS or 0.9% NaCl solution. Blood samples and intestinal tissues were obtained for further analysis several hours later. The results indicate that dietary supplementation with probiotics significantly exhibited health-promoting effects compared with the control group and effectively reduced LPS-induced histomorphological damage to the small intestine, impairments in barrier function, and dysregulated immune responses via modulation of enzyme activity and the expression of relevant genes, such as nuclear factor-kappa B (NF-κB), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), claudin-1, nuclear-associatedantigenki-67 (Ki-67), and β-defensins-1 (pBD-1). Collectively, these results suggest that dietary supplementation with probiotics could alleviate LPS-induced intestinal injury by enhancing the immunity and anti-inflammatory responses in piglets. Our research provides a theoretical basis for the rational application of probiotics in the future. Full article

Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GF_Red). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GF_Red-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids. Full article

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Backgrounds and aim: Protective effects of natural compounds have been suggested in the prevention and treatment of radiation-induced mucositis or bacterial infections. In this study, the protective effects of proanthocyanidin-rich grape seed extract (GSE) on bacterial Lipopolysaccharide (LPS) and radiation-induced epithelial barrier damage and Reactive Oxygen Species (ROS) production were investigated in an in vitro model. Methods: Human intestinal epithelial cells Caco-2, previously treated with LPS, GSE, or LPS + GSE, were irradiated with 10 Gy divided into five daily treatments. Epithelial barrier integrity and ROS production were measured before and after each treatment. Results: Irradiation, at different doses, significantly increased intestinal permeability and ROS production; pretreatment with GSE was able to significantly prevent the increased intestinal permeability (4.63 ± 0.76 vs. 15.04 ± 1.5; p < 0.05) and ROS production (12.9 ± 1.08 vs. 1048 ± 0.5; p < 0.0001) induced by irradiation treatment. When the cells were pretreated with LPS, the same results were observed: GSE cotreatment was responsible for preventing permeability alterations (5.36 ± 0.16 vs. 49.26 ± 0.82; p < 0.05) and ROS production (349 ± 1 vs. 7897.67 ± 1.53; p < 0.0001) induced by LPS exposure when added to the irradiation treatment. Conclusions: The results of the present investigation demonstrated, in an in vitro model, that GSE prevents the damage to intestinal permeability and the production of ROS that are induced by LPS and ionizing radiation, suggesting a potential protective effect of this extract on the intestinal mucosa during irradiation treatment. Full article

Disruption of the intestinal epithelial barrier is a key driver of gut-derived inflammation in various disorders, yet strategies to preserve or restore barrier integrity remain limited. To address this, we evaluated a four-strain Bifidobacterium mixture—selected for complementary anti-inflammatory potency and industrial scalability—in lipopolysaccharide (LPS)-challenged RAW 264.7 macrophages and a Caco-2/THP-1 transwell co-culture model. Pretreatment with the probiotic blend reduced nitric oxide (NO) release in a dose-dependent manner by 25.9–48.3% and significantly down-regulated the pro-inflammatory markers in macrophages. In the co-culture system, the formulation decreased these markers, increased transepithelial electrical resistance (TEER) by up to 31% at 10⁵ colony-forming unit (CFU)/mL after 48 h, and preserved the membrane localization of tight junction (TJ) proteins. Adhesion to Caco-2 cells (≈ 6%) matched that of the benchmark probiotic Lacticaseibacillus rhamnosus GG, suggesting direct epithelial engagement. These in vitro findings demonstrate that this probiotic mixture can attenuate LPS-driven inflammation and reinforce epithelial architecture, providing a mechanistic basis for its further evaluation in animal models and clinical studies of intestinal inflammatory disorders. Full article

Background: Obese women have a significantly higher risk of bearing breast tumors that are resistant to therapies and are associated with poorer prognoses/treatment outcomes. Breast cancer-promoting action of obesity is often attributed to elevated levels of insulin, glucose, inflammatory mediators, and misbalanced estrogen production in adipose tissue under obese conditions. Metabolic endotoxemia, characterized by chronic presence of extremely low levels of bacterial endotoxin (lipopolysaccharide [LPS]) in the circulation, is a less explored obesity-associated factor. Results: Here, utilizing in vitro and in vivo models of breast carcinoma (BC), we report that subclinical levels of LPS typical for metabolic endotoxemia enhance the malignant phenotype of breast cancer cells and accelerate breast tumor progression. Conclusions: Our study, while focusing primarily on the direct effects of metabolic endotoxemia on breast tumor progression, also suggests that metabolic endotoxemia can contribute to obesity–breast cancer link. Thus, our findings add novel mechanistic insights into how obesity-associated metabolic changes, particularly metabolic endotoxemia, modulate the biological and clinical behavior of breast carcinoma. In turn, understanding of the mechanistic aspects underlying the association between obesity and breast cancer could help inform better strategies to reduce BC risk in an increasingly obese population and to suppress the breast cancer-promoting consequences of excess adiposity. Full article

Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely unexplored. By leveraging Caenorhabditis elegans and its genetic and gnotobiotic advantages, we screened a panel of Escherichia coli LPS biosynthesis mutants. This screen revealed that the loss of outer core glycosylation in the ∆rfaG mutant causes significant developmental delay independent of bacterial metabolism. Animals exhibited developmental delay that was rescued by exogenous LPS or amino acid supplementation, implicating that LPS triggers nutrient-sensing signaling. Mechanistically, this developmental arrest was mediated by the host FOXO transcription factor DAF-16, which is the key effector of insulin/IGF-1 signaling (IIS). Our findings uncover an unprecedented role for microbial LPS as a critical regulator of host development, mediated through conserved host IIS pathways, fundamentally expanding our understanding of host–microbe crosstalk. Full article

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. Full article

Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) is an evergreen conifer native to temperate regions such as South Korea and Japan, traditionally used for its anti-inflammatory properties. However, the molecular mechanisms underlying the anti-inflammatory effects of C. obtusa bark extracts remain poorly understood. In this study, I compared the biological activities of C. obtusa bark extracts prepared using boiling water (COWB) and 70% ethanol (COEB), and investigated their anti-inflammatory mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. COEB significantly suppressed both mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), along with decreased production of their respective inflammatory mediators, nitric oxide (NO) and prostaglandin E₂ (PGE₂). Additionally, COEB selectively downregulated interleukin (IL)-1β expression, without affecting tumor necrosis factor-α (TNF-α), and unexpectedly upregulated IL-6. Notably, COEB did not inhibit the LPS-induced activation of major inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). These findings suggest that COEB exerts anti-inflammatory effects by modulating key inflammatory mediators independently of canonical signaling pathways and may offer a novel therapeutic strategy for controlling inflammation. Full article

This study investigated the effects of dietary capsaicinoid (CAP) supplementation on broiler chickens subjected to an inflammatory challenge induced by lipopolysaccharide (LPS). A total of 144 Cobb500™ male broilers (Rivelli Alimentos SA, Matheus Leme, Brazil), raised from 1 to 21 days, were randomly assigned to three treatments, with eight replicates of six birds. Treatments were a control diet (CON), a control diet with LPS administration (CON+LPS), and a control diet supplemented with 1 mg CAP/kg feed and LPS (CAP+LPS). LPS was administered intraperitoneally on days 14, 16, 18, and 20. Performance, intestinal morphometry, serum metabolites, and jejunal gene expression related to oxidative and inflammatory responses were evaluated. Slaughter was at 20 days. Data were subjected to ANOVA and means compared by Tukey’s test at 0.05 significance. CON broilers exhibited the highest feed intake and a better feed conversion ratio (p < 0.05) compared to CON+LPS. CAP+LPS broilers showed higher body weight gain than CON+LPS but lower than CON broilers (p < 0.001). CON+LPS broilers had the highest crypt depth (p = 0.002). Higher mRNA expression of superoxide dismutase and catalase (p > 0.05) was observed in CON broilers. In conclusion, supplementation with a 1 mg CAP/kg diet improves the growth performance and intestinal morphometry of LPS-challenged broiler chickens. Full article

High-altitude cognitive impairment (HACI) results from acute or chronic exposure to hypoxic conditions. Brain lipid homeostasis is crucial for cognitive function, and lipid droplet (LD) accumulation in glia cells is linked to cognitive decline in aging and stroke. However, whether high-altitude exposure affects brain lipid homeostasis is unclear. Microglia, key regulators of brain homeostasis and inflammation, play a significant role in pathological cognitive impairment and are implicated in LD formation. This study investigates whether lipid dysregulation contributes to HACI and explores microglia-driven mechanisms and potential interventions. Mice were exposed to a simulated 7000 m altitude for 48 h, followed by a week of recovery. Cognitive function and LD accumulation in brain cells were assessed. Microglia were depleted using PLX5622, and mice were exposed to hypoxia or lipopolysaccharide (LPS) to validate microglia’s role in driving astrocytic LD accumulation and cognitive decline. Minocycline was used to inhibit inflammation. In vitro, co-culture systems of microglia and astrocytes were employed to confirm microglia-derived pro-inflammatory factors’ role in astrocytic LD accumulation. Hypobaric hypoxia exposure induced persistent cognitive impairment and LD accumulation in hippocampal astrocytes and microglia. Microglia depletion alleviated cognitive deficits and reduced astrocytic LD accumulation. Hypoxia or LPS did not directly cause LD accumulation in astrocytes but activated microglia to release IL-1β, inducing astrocytic LD accumulation. Microglia depletion also mitigated LPS-induced cognitive impairment and astrocytic LD accumulation. Minocycline reduced hypoxia-induced LD accumulation in co-cultured astrocytes and improved cognitive function. Hypoxia triggers pro-inflammatory microglial activation, leading to LD accumulation and the release of IL-1β, which drives astrocytic LD accumulation and neuroinflammation, exacerbating HACI. Minocycline effectively restores brain lipid homeostasis and mitigates cognitive impairment. This study provides novel insights into HACI mechanisms and suggests potential therapeutic strategies. Full article

Kynurenic acid (KYNA), a tryptophan metabolite, possesses immunomodulatory properties, although the molecular mechanism of this action has not yet been resolved. In the present study, the effects of KYNA on the secretion of selected cytokines and chemokines by macrophages derived from the human THP-1 cell line are investigated. Furthermore, the involvement of the aryl hydrocarbon receptor (AhR) and the G protein-coupled receptor 35 (GPR35) in mediating the effects of KYNA was examined. In lipopolysaccharide (LPS)-stimulated THP-1-derived macrophages, KYNA significantly reduced IL-6 and CCL-2, but increased IL-10 and M-CSF levels. AhR antagonist CH-223191 reduced the KYNA influence on IL-6, CCL-2, and M-CSF production, while the GPR35 antagonist, ML-145, blocked KYNA-induced IL-10 production. Furthermore, it was shown that THP-1 derived macrophages were capable of synthesizing and releasing KYNA and that its production was increased in the presence of LPS. These findings suggest that THP-1-derived macrophages are a source of KYNA and that KYNA modulates inflammatory responses predominantly through AhR and GPR35 receptors. Our study provides further evidence for the involvement of macrophages in immunomodulatory processes that are dependent on AhR and GPR35 receptors, as well as the potential role of KYNA in these phenomena. Full article

Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C₁₈H₁₈O₂), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model’s translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders. Full article