Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

Background and Aims:The effect of ginsenoside Rb1 on D-galactosamine(D-GalN)/lipopolysaccharide(LPS)-induced acute liver injury(ALI)is unknown.The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.Methods:Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment,to induce ALI.The survival rate was monitored every hour for 24 h,and serum biochemical parameters,hepatic index and histopathological analysis were evaluated to measure the degree of liver injury.ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum.Immunohistochemistry staining,RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4(TLR4),nuclear factorkappa B(NF-κB),and NLR family,pyrin domain-containing 3 protein(NLRP3)in liver tissue and Kupffer cells(KCs).Results:Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%,significantly ameliorated the increased alanine and aspartate transaminase,restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS.Compared to the control group,the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment.D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin(IL)-1β,IL-18,NLRP3,apoptosis associated specklike protein containing CARD(ASC)and caspase-1 in isolated KCs.Furthermore,ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and NLRP3 inflammasome induced by D-GalN/LPS administration.Conclusions:Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and NLRP3 inflammasome activation.

Positive sputum culture of Candida spp.as a risk factor for 30-day mortality in patients with hospital-acquired pneumonia:A propensity-score matched retrospective clinical study

Background:Candida species(Candida spp.)are commonly isolated microorganisms from lower respiratory tract(LRT)specimens of patients with hospital-acquired pneumonia(HAP);however,the clinical significance remains controversial.This study aimed to investigate the correlation between Candida spp.in the LRT and the clinical features and prognosis of HAP.Methods:This retrospective analysis included eligible patients with HAP from the database of a prospective study carried out between 2018 and 2019 in nine Chinese hospitals.Data on demographics,clinical characteristics,and prognosis were collected and analyzed.Propensity score matching(PSM)was used to balance the baseline characteristics.Results:A total of 187 HAP patients were enrolled.After PSM of severity score,27 cases with positive sputum culture of Candida spp.were compared with the control group at a ratio of 1:1.The Candida-positive group had more bacterial isolates in blood culture than the Candida-negative group(39.1%[9/23]vs.7.7%[2/26],χ^(2)=6.928,effect size[ES]=0.38,95%CI:0.12-0.61,P=0.008).The proportion of patients with chronic lung diseases was significantly higher in the Candida-positive group(55.6%[15/27]vs.22.2%[6/27],χ^(2)=6.312,ES=0.34,95%CI:0.07-0.59,P=0.012).The 30-day prognosis of HAP was significantly different between the two groups(80.8%[21/26]vs.38.5%[10/26],χ^(2)=9.665,ES=0.43,95%CI:0.19-0.66,P=0.002).Univariable logistic regression analysis showed that LRT Candida spp.colonization was a risk factor for 30-day mortality of HAP(OR=6.720,95%CI:1.915-23.577,P=0.003).Conclusions:Candida spp.in the LRT was associated with 30-day mortality of HAP.Patients with chronic under-lying lung diseases tend to have Candida spp.colonization.