Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Noncanonical pyroptosis pathway: a promising target of traditional Chinese medicine in the treatment of sepsis-related injury

Sepsis is a life-threatening disease of organ failure caused by dysregulated host responses to infection and other infectious factors.Multi-organ injury is the leading cause of high mortality and septic shock during sepsis.Recent studies suggest that noncanonical pyroptosis,characterized mainly by the direct activation of caspase-11-gasdermin D-mediated pyroptosis by cytoplastic lipopolysaccharide,is closely related to sepsis-related organ injury.Here,this review summarizes recent advances in the regulatory mechanisms and targeted natural products from traditional Chinese medicine of the noncanonical pyroptosis pathway in sepsis-related injury.

The role of quick Sepsis-related Organ Failure Assessment score as simple scoring system to predict Fournier gangrene mortality and the correlation with Fournier’s Gangrene Severity Index: Analysis of 69 patients

Objective:Fournier’s gangrene is a rare but life-threatening infection disease with high mortality rate.The quick Sepsis-related Organ Failure Assessment(qSOFA)is a new and simpler scoring system that may identify patients with suspected infection who are at greater risk for a poor outcome.The purpose of this study was to find out role of qSOFA in determining prognosis of Fournier’s gangrene patients.Methods:This study is a case control with retrospective review of Fournier’s gangrene patients treated at Hasan Sadikin Hospital from January 2013 to December 2017 who met inclusion criteria.Participants were divided into two groups according to qSOFA score as high qSOFA(2-3)and low qSOFA(0-1).Results:From 69 patients,the mortality rate was 24.6%.The sensitivity of qSOFA score to predict mortality was 88.2%;the specificity was 94.2%;positive predictive value was 83.3%;negative predictive value was 96.1%;positive likelihood ratio was 15.2;negative likelihood ratio was 0.12;and the area under the receiver operating characteristic curve of qSOFA was 94.2%.There was significant association between qSOFA scale and mortality with p-value of 0.0001.The qSOFA score has strong positive correlation with Fournier’s Gangrene Severity Index(p<0.0001,r=0.704).Conclusion:qSOFA scoring system has a high prognostic value and can be used to determine prognosis of Fournier’s gangrene patients.

Role of international normalized ratio in nonpulmonary sepsis screening:An observational study

Currently,there is a lack of sepsis screening tools that can be widely used worldwide.Pulmonary sepsis can be of sufficient concern to physicians due to their noticeable symptoms,which usually rely less on screening tools.AIM To investigate the efficiency of the international normalized ratio(INR)for the early rapid recognition of adult nonpulmonary infectious sepsis.METHODS This is a prospective observational study.A total of 108 sepsis patients and 106 nonsepsis patients were enrolled according to relevant inclusion and exclusion criteria.Commonly used clinical indicators,such as white blood cell,neutrophil count,lymphocyte count,neutrophil-lymphocyte count ratio(NLCR),platelets(PLT),prothrombin time,INR,activated partial thromboplastin time,and quick Sequential“Sepsis-related”Organ Failure Assessment(qSOFA)scores were recorded within 24 h after admission.The diagnostic performances of these clinical indicators were analyzed and compared through multivariate logistic regression analysis,Spearman correlation,and receiver operating characteristic curve analysis.The INR value of the sepsis group was significantly higher than that of the nonsepsis group.INR has superior diagnostic efficacy for sepsis,with an area under the curve value of 0.918,when those preexisting diseases which significantly affect coagulation function were excluded.The diagnostic efficacy of the INR was more significant than that of NLCR,PLT,and qSOFA(P<0.05).Moreover,INR levels of 1.17,1.20,and 1.22 could be used to categorize the relative risk of nonpulmonary infections sepsis into three categories:low,medium and high risk,respectively.CONCLUSION The INR is a promising and easily available biomarker for diagnosis,and it can be used as one of the indicators for early screening of adult nonpulmonary infectious sepsis.When its value is higher than the optimal cutoff value(1.22),high vigilance is required for adult nonpulmonary infectious sepsis.

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.