NLRP3 promotes inflammatory signaling and IL-1β cleavage in acute lung injury caused by cell wall extract of Lactobacillus casei

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 7, 2025

Gram-positive bacterial pneumonia is a significant cause of hospitalization and death. Shortage good experimental model therapeutic targets hinders the cure acute lung injury (ALI). This study has established mouse ALI using bacteria Lactobacillus casie cell wall extracts (LCWE) identified key regulator NLRP3. We show that LCWE induces TNF, NF-κB signaling, so on pathways. Similar to lipopolysaccharide (LPS), infiltration CD11b-positive cells inflammation in lungs. also triggers inflammatory signaling through TLR2, different from LPS TLR4. It suggests cytokines amplify relying NLRP3 LCWE-induced ALI. deletion disrupts inflammation, IL-1β cleavage, neutrophils macrophages injured lung. Our highlights an animal for target prevent damage drives cleaved induced by casei extracts, highlighting its role as pneumonia.

Language: Английский

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Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15805 - 15805

Published: Oct. 31, 2023

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release mesh-like structure called neutrophil extracellular traps (NETs) as part their defensive strategy against microbial pathogen attack. This web-like architecture includes DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), elastase (NE), histones deploys in entrapment clearance encountered pathogens. Thus NETs play an inevitable beneficial role host's protection. However, recent accumulated evidence shows that dysregulated enhanced NET formation has various pathological aspects including promotion sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases, list is increasing gradually. In this review, we summarize NET-mediated pathophysiology different diseases focus on some updated potential therapeutic approaches NETs.

Language: Английский

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Health position paper and redox perspectives – Bench to Bedside Transition for Pharmacological Regulation of NRF2 in Noncommunicable Diseases

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103569 - 103569

Published: March 1, 2025

Nuclear factor erythroid 2-related 2 (NRF2) is a redox-activated transcription regulating cellular defense against oxidative stress, thereby playing pivotal role in maintaining homeostasis. Its dysregulation implicated the progression of wide array human diseases, making NRF2 compelling target for therapeutic interventions. However, challenges persist drug discovery and safe targeting NRF2, as unresolved questions remain especially regarding its context-specific diseases off-target effects. This comprehensive review discusses dualistic disease pathophysiology, covering protective and/or destructive roles autoimmune, respiratory, cardiovascular, metabolic well digestive system cancer. Additionally, we also development drugs that either activate or inhibit discuss main barriers translating NRF2-based therapies from bench to bedside, consider ways monitor activation vivo.

Language: Английский

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Post-operative sepsis-induced acute respiratory distress syndrome: risk factors for a life-threatening complication

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: March 5, 2024

Introduction Prevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis major surgery conditions associated with ARDS. We aimed to examine impact 60-day mortality. Methods performed a secondary analysis prospective observational study 454 patients who underwent admitted into single ICU. Patients were stratified two groups depending whether they met criteria for Primary outcome was Secondary measures potential risk factors ARDS, Results Higher SOFA score (OR 1.1, 95% CI 1.0–1.3, p = 0.020) higher lactate 1.9, 1.2–2.7, 0.004) at inclusion independently ( n 45) had ICU stay [14 (18) vs. 5 (11) days, < 0.001] longer need mechanical ventilation [6 (14) 1 (5) than non-ARDS 409). Sixty-day 2.7, 1.1–6.3, 0.024). Chronic renal failure 4.0, 1.2–13.7, 0.026), elevated dehydrogenase 1.7, 1.1–2.7, 0.015) APACHE II 1.3–5.4, 0.006) Conclusion Post-operative compared septic patients. severity illness have greater worse outcomes. Further investigation needed prevent

Language: Английский

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By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 5, 2025

This study investigated pathogenic role and mechanism of extracellular histone H4 during oleic acid (OA)-induced acute respiratory distress syndrome (ARDS). Methods: ARDS was induced by intravenous injection OA in mice, evaluated blood gas, pathological analysis, lung edema, survival rate. Heparan sulfate (HS) degradation using immunofluorescence flow cytometry. The released von Willebrand factor (vWF) measured ELISA. P-selectin translocation neutrophil infiltration were via immunohistochemical analysis. Changes VE-cadherin western blot. Blocking antibodies against TLRs used to investigate the signaling pathway. Results: Histone plasma BALF increased significantly after injection. closely correlated with dose, which determined severity. Pretreatment further aggravated pulmonary edema death rate, while anti-H4 antibody exerted obvious protective effects. directly activated endothelia. Endothelial activation evidently manifested as HS degradation, release vWF, translocation, VE-Cadherin reduction. synergistic stimulus endothelia required for effective H4. Both calcium mediated H4-induced endothelial activation. Conclusions: is a pro-inflammatory pro-thrombotic molecule OA-induced mice. As main risk (ARDS), fat embolism (PFE) common complication following long bone fractures, cardiopulmonary resuscitation, infusion through an intraosseous catheter. showed that essential ARDS. induces indispensable are intimately involved endothelium

Language: Английский

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Targeting alveolar epithelial cells with lipid micelle-encapsulated necroptosis inhibitors to alleviate acute lung injury

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: April 6, 2025

Abstract Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS), represents a critical condition characterized by extensive inflammation within the airways. Necroptosis, form of cell death, has been implicated in pathogenesis various inflammatory diseases. However, precise characteristics and mechanisms necroptosis ARDS remain unclear. Thus, our study seeks to elucidate specific alterations regulatory factors associated with identify potential therapeutic targets for disease. We discovered that mediates progression ALI through activation formation RIPK1/RIPK3/MLKL complex. Moreover, we substantiated involvement both MYD88 TRIF TLR4 signaling pathway ALI. Furthermore, have developed lipid micelle-encapsulated drug targeting MLKL alveolar type II epithelial cells successfully applied it treat mice. This targeted nanoparticle selectively inhibited necroptosis, thereby mitigating damage reducing injury. Our delves into proposes novel agents, presenting innovative strategies management ARDS.

Language: Английский

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Sparstolonin B nano-formulation attenuates LPS-induced lung injury

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Nanomedicines can improve drug delivery and efficacy while reducing side effects. Our study examines the impact of a nano-formulation Sparstolonin B (nSsnB), TLR-4 antagonist, on LPS-induced inflammation in RAW264.7 cells lung injury mice. were treated with LPS (1 μg/mL) ± nSsnB (2-64 for 24 h. Cell viability was assessed, cytokine levels media measured, cell lysates used to quantify NF-κB activation. C57BL/6 mice prophylactic intratracheal (IT) (0.625 mg/kg) IT (2.5 mg/kg). Blood BALF collected cytokine, protein cytological analysis. Lung histology scored evaluate injury. The relative abundance MyD88 phosphorylated measured HLL measure activation vivo. demonstrated reduced toxicity vs. free SsnB. ameliorated increase TNF-α, IL-6 P65 phosphorylation cells. LPS-treated revealed histologic ALI, elevated neutrophils/macrophages/total protein, increased TNF-α/IL-6 both plasma. Prophylactic attenuated all these parameters LPS/nSsnB group. P-NF-κB from group induced by demonstrates less than SsnB attenuates effects ALI via MyD88/NF-κB signaling pathways. Collectively findings support therapeutic potential nano-formulated treatment.

Language: Английский

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Inhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 77 - 77

Published: Dec. 20, 2023

Acute Respiratory Distress Syndrome (ARDS) is a major health concern with urgent unmet need for treatment options. There are three million new ARDS cases annually, and the disease’s mortality rate high (35–46%). Cluster of differentiation 24 (CD24), long-known protein multifaceted functions, small, heavily glycosylated, membrane-anchored which functions as an immune checkpoint control. CD24 allows discrimination between Damage-Associated Molecular Patterns Pathogen-Associated derived from pathogens. Exosomes intraluminal vesicles play important role in intercellular communication. offer advantage targeted delivery, improves safety efficacy. The efficacy EXO-CD24 promising, was shown >180 patients phase 1b/2a, 2b, compassionate use. binds Damage-associated molecular patterns (DAMPs) inhibits activation NF-ĸB pathway, pivotal mediator inflammatory responses. In contrast to anti-inflammatory therapies that cytokine-specific or steroids shut down entire system, acts upstream, reverting system back normal activity. Herein, mEXO-CD24 murine models several pulmonary diseases (sepsis, allergic asthma, Chronic Obstructive Pulmonary Disease(COPD), fibrosis). EXO can suppress hyperinflammatory response lungs significant

Language: Английский

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Lung ultrasound score and in-hospital mortality of adults with acute respiratory distress syndrome: a meta-analysis

BMC Pulmonary Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 29, 2024

Abstract Background Lung ultrasound (LUS) score could quantitatively reflect the lung aeration, which has been well applied in critically ill patients. The aim of systematic review and meta-analysis was to evaluate association between LUS at admission risk in-hospital mortality adults with acute respiratory distress syndrome (ARDS). Methods Toachieve objective this meta-analysis, we conducted a thorough search PubMed, Embase, Cochrane Library, Web Science identify relevant observational studies longitudinal follow-up. We employed random-effects models combine outcomes, considering potential influence heterogeneity. Results Thirteen cohort 1,022 hospitalized patients ARDS were included. Among them, 343 (33.6%) died during hospitalization. pooled results suggested that higher non-survivors as compared survivors (standardized mean difference = 0.73, 95% confidence interval [CI]: 0.55 0.91, p < 0.001; I 2 25%). Moreover, high associated (risk ratio: 1.44, CI: 1.14 1.81, 0.002; 46%). Subgroup analyses showed consistent analyzed 12 or 16 regions, reporting ICU within 1-month Conclusion Our findings suggest may be ARDS.

Language: Английский

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Advanced Respiratory Monitoring during Extracorporeal Membrane Oxygenation

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(9), P. 2541 - 2541

Published: April 26, 2024

Advanced respiratory monitoring encompasses a diverse range of mini- or noninvasive tools used to evaluate various aspects function in patients experiencing acute failure, including those requiring extracorporeal membrane oxygenation (ECMO) support. Among these techniques, key modalities include esophageal pressure measurement (including derived pressures), lung and muscle ultrasounds, electrical impedance tomography, the diaphragm activity, assessment flow index. These play critical role assessing essential parameters such as recruitment overdistention, aeration morphology, ventilation/perfusion distribution, inspiratory effort, drive, contraction, patient–ventilator synchrony. In contrast conventional methods, advanced offers deeper understanding pathological changes caused by underlying diseases. Moreover, it allows for meticulous tracking responses therapeutic interventions, aiding development personalized support strategies aimed at preserving integrity. The integration represents significant advancement clinical management failure. It serves cornerstone scenarios where treatment rely on tailored approaches, empowering clinicians make informed decisions about intervention selection adjustment. By enabling real-time modification support, not only optimizes care with distress syndrome but also contributes improved outcomes enhanced patient safety.

Language: Английский

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