Renqing Changjue alleviates sepsis-induced acute lung injury by regulating renin-angiotensin system and inhibiting inflammatory response

Immunobiology, Journal Year: 2025, Volume and Issue: 230(3), P. 152883 - 152883

Published: Feb. 23, 2025

Sepsis, with high morbidity and mortality, represents a systemic inflammatory response syndrome. A common consequence of sepsis is acute lung injury (ALI). Renqing Changjue (RQCJ), renowned prescription in traditional Tibetan medicine, reported to have anti-inflammatory effects. The present study was aimed at exploring whether RQCJ could mitigate sepsis-induced ALI elucidating its underlying mechanism. rat model established by intraperitoneal injection lipopolysaccharide (LPS), high, medium, low doses were administered. results indicated that the intervention improved septic symptoms, mitigated murine score pulmonary edema LPS-induced rats, decreased cytokines tissue such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1). Furthermore, regulated balance renin-angiotensin system enhancing enzyme activity angiotensin converting 2 (ACE2) while inhibiting ACE, thereby promoting production 1-7 (Ang1-7). This highlights multiple protective effects on ALI, providing valuable reference for further development offering novel perspective treatment ALI.

Language: Английский

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The Role of HDAC3 in Pulmonary Diseases

Lung, Journal Year: 2025, Volume and Issue: 203(1)

Published: March 17, 2025

Language: Английский

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Roles of TLR4 in macrophage immunity and macrophage-pulmonary vascular/lymphatic endothelial cell interactions in sepsis

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

Published: March 21, 2025

In sepsis, acute lung injury (ALI) is a severe complication and leading cause of death, involving complex mechanisms that include cellular molecular interactions between immune parenchymal cells. recent decades, the role Toll-like receptor 4 (TLR4) in mediating infection-induced inflammation has been extensively studied. However, how TLR4 facilitates innate cells sepsis remains to be fully understood. This study aims explore regulating macrophage immunity metabolism greater depth. It also seeks reveal changes these processes affect interaction macrophages both pulmonary endothelial (ECs) lymphatic (LECs). Using knockout mice combined approaches single-cell RNA sequencing experimental validation, we demonstrate TLR4-deficient upregulate Abca1, enhance cholesterol efflux, reduce glycolysis, promoting M2 polarization attenuating inflammation. These metabolic phenotypic shifts significantly their with ECs LECs. Mechanistically, uncovered operates through multiple pathways dysfunction: mediates inflammatory damage ECs/LECs, while directly sensitizes lipopolysaccharide-induced determines susceptibility macrophage-derived signals. findings orchestrating immune-mediated direct responses during sepsis-induced ALI, supporting targeting on cell populations may present an effective therapeutic strategy. signaling contributes impairment vascular barriers, providing new insights into dysfunction ALI.

Language: Английский

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Activated Notch1 promotes macrophage polarization and exacerbates sepsis-induced acute lung injury via β-catenin/NF-κB signaling

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116892 - 116892

Published: March 1, 2025

Language: Английский

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Ethyl Caffeate Alleviates Inflammatory Response and Promotes Recovery in Septic-Acute Lung Injury via the TNF-α/NF-κB/MMP9 Axis

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156700 - 156700

Published: March 1, 2025

Language: Английский

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Melatonin-Mediated Protection against Sepsis-Induced Organ Dysfunction

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Sepsis-induced organ dysfunction represents a critical challenge in intensive care medicine, characterized by complex pathophysiological mechanisms that can lead to multiple failure and death. This review examines the fundamental underlying sepsis-induced explores therapeutic potential of melatonin, multifaceted molecule with potent antioxidant anti-inflammatory properties. We analyzed pathways involved damage during sepsis, including inflammatory cascades, oxidative stress, mitochondrial dysfunction, endothelial injury. Special attention is given melatonin’s protective effects on various systems, cardiac, pulmonary, renal, hepatic, central nervous system function sepsis. Recent evidence suggests ability modulate these pathways, combined its excellent safety profile, makes it promising agent sepsis management. Understanding applications may provide new strategies for improving outcomes septic patients.

Language: Английский

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Modulating the NLRP3 Inflammasome: Acitretin as a potential treatment for Sepsis-induced acute lung injury

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114504 - 114504

Published: April 1, 2025

Acitretin, a well-established dermatological drug primarily used for psoriasis treatment, has been clinically several decades. However, its potential role in modulating inflammation sepsis remains unexplored. This study seeks to explore the impact of acitretin on sepsis-induced acute lung injury (ALI) and elucidate underlying mechanisms involved. In mouse model induced by lipopolysaccharide (LPS), we assessed effects ALI. Transcriptome sequencing tissue was performed identify relevant signaling pathways. vitro, bone marrow-derived macrophages (BMDMs) were treated with (1 μM, 5 μM 10 μM) evaluate NOD-, LRR- pyrin domain-containing protein 3(NLRP3) inflammasome activation pyroptosis. vivo, wild-type, Nlrp3 knockout, Gsdmd knockout mice confirm NLRP3 mediating acitretin's effects. Acitretin significantly mitigated ALI, reducing mortality LPS-challenged mice. analysis revealed that suppressed pathway tissue. dose-dependently inhibited interleukin (IL)-1β release, caspase-1 p20 production, GSDMD cleavage BMDMs. Furthermore, preventing ASC oligomerization interaction NLRP3. reduced inflammation, IL-1β levels bronchoalveolar lavage fluid, ratio wet dry wide-type mice, but these abolished demonstrated significant anti-inflammatory properties through suppression inflammasome, suggesting as therapeutic strategy related complications.

Language: Английский

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USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 17, 2025

Abstract Disruption of the endothelial cell barrier and subsequent inflammatory response represent a central pathological feature acute lung injury (ALI). Ubiquitination plays pivotal role in regulating protein stability, intracellular transport, enzyme activity, which is typically reversed by deubiquitinating enzymes. Nevertheless, function enzymes biology ALI remains largely uninvestigated. The present study demonstrates that expression USP7 increased instances inflammation ALI. knockdown or inhibition using specific inhibitors was observed to significantly reduce TNF-α-induced cells their adhesion capacity monocytes. Conversely, overexpression promote cells. were found be effective mitigating induced LPS. From mechanistic perspective, our findings indicate binds deubiquitinates PDK1, thereby stabilizing PDK1 promoting activity pathway In conclusion, demonstrate novel USP7-PDK1 signaling axis vascular reveal deubiquitylating PDK1. These observations suggest targeting may offer promising therapeutic strategy for treatment injury.

Language: Английский

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Predicting mortality and risk factors of sepsis related ARDS using machine learning models

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 18, 2025

Sepsis related acute respiratory distress syndrome (ARDS) is a common and serious disease in clinic. Accurate prediction of in-hospital mortality patients crucial to optimize treatment improve prognosis under the new global definition ARDS. Our study aimed use machine learning models develop that can effectively predict with sepsis ARDS, calculate mortality, identify risk factors Based on MIMIC database, our included 3470 first-time admission records After excluding 4 age 18, 75 less than 24 h stay ICU, 5 cases missing indicators > 30%, finally 3386 were retained. The variance inflation factor (VIF) analysis was used test collinearity explanatory variables. data divided into training set according ratio 7:3. Six models, extreme gradient boosting (XGBoost), light (LightGBM), random forest (RF), classification regression tree (CART), naive bayes (NB) logistic (LR), designed for testing. In set, XGBoost (AUROC = 0.951, 95% CI 0.942-0.961), LR 0.835, 0.817-0.854), RF 1.0, 1.0-1.0), LightGBM CART 0.831, 0.811-0.852), NB 0.793, 0.772-0.814). 0.833, 0.804-0.861), 0.82695% 0.796-0.856), 0.846, 0.818-0.874), 0.827, 0.798-0.856), 0.753, 0.718-0.787), 0.799, 0.768-0.831). model has best performance set. Further analyze feature importance ranking partial dependence plots model. Acute physiology chronic health evaluation III (APACHE III), bicarbonate, anion gap non-invasive blood pressure systolic identified as four most important characteristics. this study, variety have been successfully constructed among which performs well. Key include APACHE III, systolic. identification these helps clinicians assess patients' conditions more accurately personalized plans, thereby improving survival rate quality

Language: Английский

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Decoding TMAO in the Gut-Organ Axis: From Biomarkers and Cell Death Mechanisms to Therapeutic Horizons

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 3363 - 3393

Published: April 1, 2025

The gut microbiota and its metabolites are bi-directionally associated with various human illnesses, which has received extensive attention. Trimethylamine N-oxide (TMAO) is a metabolite produced in the liver, may serve role of an "axis" connecting host organs. TMAO levels significantly higher blood individuals cardiovascular, renal, neurological, metabolic diseases. Endothelial cells crucial for regulating microcirculation maintaining tissue organ barriers widely recognized as target TMAO. not only induces endothelial dysfunction but also acts on cell types, such cells, epithelial vascular smooth muscle nerve pancreatic triggering multiple death mechanisms, including necrosis programmed death, thereby influencing health. This paper thoroughly covers origins, production, pathways TMAO, emphasizing importance early detection prognosis diseases "Gut-Organ" axis, well mechanisms influence diseases, particularly cross-talk death. Furthermore, we cover recent advances treating by structure enzyme activity to metabolism reduce levels, use probiotics, prebiotics, antibiotics, anti-inflammatory drugs, antiplatelet hypoglycemic lipid-lowering natural products.

Language: Английский

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