scholarly journals Serum developmental endothelial locus-1 is associated with severity of sepsis in animals and humans

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Won-Young Kim ◽  
Seung-Hwan Lee ◽  
Dong-Young Kim ◽  
Hyun Jin Ryu ◽  
Gyu Rak Chon ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
High Serum ◽  
Endothelial Glycocalyx ◽  
Inflammatory Factor ◽  
Healthy Controls ◽  
Cecal Ligation And Puncture ◽  
Diagnostic Biomarker ◽  
Median Serum ◽  
Severity Scores ◽  
Sepsis And Septic Shock

Abstract Disruption of the endothelial glycocalyx has a prominent role in the pathophysiology of sepsis. Developmental endothelial locus-1 (Del-1) is an endothelial-derived anti-inflammatory factor. We hypothesized that degradation of the endothelial glycocalyx during sepsis may increase serum Del-1. A mouse model of sepsis was created using cecal ligation and puncture. In septic mice, the endothelial glycocalyx was nearly completely degraded, with less formation of Del-1 in the endothelium and extracellular matrix than in control mice. Serum Del-1 levels were significantly increased in the septic mice with increasing severity of sepsis. Serum Del-1 levels were also measured in 84 patients with sepsis and septic shock and in 20 control subjects. The median serum Del-1 level in patients with sepsis was significantly higher than that in healthy controls. The high Del-1 group had higher illness severity scores and contained more patients with organ dysfunction than the low Del-1 group. The 90-day mortality rate was significantly higher in the high Del-1 group than in the low Del-1 group. Multivariate analysis indicated a tendency for a high serum Del-1 level to be associated with a higher mortality risk. Increased serum Del-1 may be a novel diagnostic biomarker of sepsis and an indicator of disease severity.

scholarly journals 5-HT Drives Mortality in Sepsis Induced by Cecal Ligation and Puncture in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jingyao Zhang ◽  
Jianbin Bi ◽  
Sushun Liu ◽  
Qing Pang ◽  
Ruiyao Zhang ◽  
...  
Keyword(s):  
Body Temperature ◽  
Organ Dysfunction ◽  
Tryptophan Hydroxylase ◽  
Cecal Ligation ◽  
Clinical Score ◽  
The Body ◽  
Sepsis Group ◽  
Cecal Ligation And Puncture ◽  
Lower Survival Rate ◽  
Sepsis And Septic Shock

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection with a high mortality. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation. The aim of this study is to investigate the role of 5-HT on cecal ligation and puncture- (CLP-) induced sepsis in the mouse model. CLP was performed on C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout (KO) mice. The results showed that the 5-HT-sufficient group mice had a significantly lower survival rate than the 5-HT-deficient group in CLP-induced sepsis and septic shock. The KO-CLP sepsis group received a lower clinical score than the WT-CLP sepsis group. Meanwhile, the body temperature of mice in the KO-CLP sepsis group was higher than that in the WT-CLP sepsis group and was much closer to the normal body temperature 24 hours after CLP. The tissue histopathology analysis revealed that 5-HT markedly exacerbated histological damages in the peritoneum, lung, liver, kidney, intestinal tissue, and heart in sepsis. Moreover, significant lower levels of TNF-α, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group. In conclusion, 5-HT drives mortality and exacerbates organ dysfunction by promoting serum cytokines and bacterial loads as well as facilitating oxidative stress in the process of sepsis.

scholarly journals The Prognostic Significance of Beta2 Microglobulin in Patients with Hemophagocytic Lymphohistiocytosis

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Tiantong Jiang ◽  
Xiurong Ding ◽  
Weixing Lu
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Roc Analysis ◽  
Hemophagocytic Syndrome ◽  
Prognostic Significance ◽  
Latex Agglutination ◽  
High Serum ◽  
Benign Disease ◽  
Healthy Controls ◽  
Median Serum ◽  
Study Population

Objective. To determine the prognostic significance of beta2 microglobulin (β2-m) concentrations in patients with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system.Patients and Methods. The study population consisted of 74 patients diagnosed with HLH and 35 healthy controls. Serumβ2-m levels were measured using a latex agglutination photometric immunoassay.Results. Median serumβ2-m levels were significantly higher in HLH patients than in healthy controls (4.05 versus 1.5 mg/L;P<0.001) and were significantly higher in patients with lymphoma associated hemophagocytic syndrome (LAHS) than in patients with benign disease-associated HLH (4.2 versus 3.3 mg/L;P<0.001). Higher serumβ2-m levels were positively correlated with LAHS (P=0.005), abnormal lactate dehydrogenase concentrations (P=0.009), and hypoalbuminemia (P=0.003). ROC analysis showed that overall survival (OS) was significantly shorter in LAHS patients with serumβ2-m levels ≥4.03 mg/L compared to <4.03 mg/L (P<0.001). Moreover, multivariate analysis showed that serumβ2-m level was an independent prognostic of OS (P=0.034) in patients with LAHS.Conclusion. High serumβ2-m levels and LAHS were associated with markedly poorer OS in patients with HLH. Serumβ2-m concentration was a powerful and independent prognostic factor for OS in patients with LAHS.

Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

2019 ◽  
Vol 18 (2) ◽  
pp. 176-182
Author(s):  
Chen Weiyan ◽  
Deng Wujian ◽  
Chen Songwei
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Light Chain ◽  
Cecal Ligation ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Cecal Ligation And Puncture ◽  
Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

P717Glucagon-like peptide 1 (GLP-1) improves endothelial dysfunction and vascular inflammation in polymicrobial sepsis induced by cecal ligation and puncture (CLP)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Steven ◽  
J Helmstaedter ◽  
F Pawelke ◽  
K Filippou ◽  
K Frenies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Knockout Mice ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Glucose Levels ◽  
Dpp4 Inhibitor ◽  
Cardioprotective Effects

Abstract Objective Sepsis causes severe hypotension, accompanied by high mortality in the setting of septic shock. LEADER, SUSTAIN-6 and other clinical trials revealed cardioprotective and anti-inflammatory properties of GLP-1 analogs like Liraglutide (Lira). We already demonstrated improved survival by amelioration of disseminated intravasal coagulation (DIC) in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of the GLP-1 degrading enzyme dipeptidylpeptidase-4 (DPP-4). With the present study we aim to investigate the mechanism of protective effects of the GLP-1 analog Lira and the DPP4 inhibitor Linagliptin (Lina) in the clinically relevant sepsis model cecal ligation and puncture (CLP). Methods C57/BL6j and endothelial cell-specific GLP-1 receptor knockout mice (Cdh5crexGLP-1rfl/flmice) were used and sepsis was induced by cecal ligation and puncture (CLP). DPP4 inhibitor (Lina, 5mg/kg/d; 3 days) and GLP-1 analog (Lira, 200μg/kg/d; 3 days) were applied subcutaneously. Aortic vascular function was tested by isometric tension recording. Aorta and heart tissue was used for Western blotting, dot blot and qRT-PCR. Endogenous GLP-1 (7–36 and 9–36) and insulin was determined by ELISA. Blood samples were collected for examination of cell count, oxidative stress and glucose levels. Results Body temperature was increased by CLP and normalized by Lina and Lira. Sham- and Lira- but not Lina-treated septic mice showed low blood glucose levels compared to healthy controls. Acetylcholine-induced (endothelium-dependent) vascular relaxation in aorta was impaired by CLP. This was accompanied by vascular inflammation and elevation of IL-6, iNOS, ICAM-1, and TNF-alpha mRNA levels in aortic tissue. Vascular, cardiac and whole blood oxidative stress were increased by CLP. Furthermore, we detected higher levels of IL-6, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-NHE) in plasma of CLP animals. Lina and Lira reduced oxidative stress and vascular inflammation, which was accompanied by improved endothelial function. In addition, CLP treatment in endothelial specific knockout mice of the GLP-1r strongly induced mortality compared to WT mice, with the effect being strongest in the Lira-treated group. Conclusion The present study demonstrates that Lina (DPP4 inhibitor) and the GLP-1 analog Lira ameliorate sepsis-induced endothelial dysfunction by reduction of vascular inflammation and oxidative stress. Clinical trials like LEADER and SUSTAIN-6 proved that GLP-1 analogs like Lira have cardioprotective effects in T2DM patients. The present study, performed in a clinically relevant model of polymicrobial sepsis, reveals that the known cardioprotective effects of GLP-1 might be translated to other diseases which affect the cardiovascular system like sepsis, underlining the potent anti-inflammatory effects of GLP-1 analogs.

scholarly journals Endothelial glycocalyx degradation is associated with early organ impairment in polytrauma patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Feng Qi ◽  
Hao Zhou ◽  
Peng Gu ◽  
Zhi-He Tang ◽  
Bao-Feng Zhu ◽  
...  
Keyword(s):  
Injury Severity ◽  
Early Stage ◽  
Endothelial Glycocalyx ◽  
Control Group ◽  
Metabolic System ◽  
Metabolic Systems ◽  
Organ Systems ◽  
Severity Scores ◽  
Polytrauma Patients ◽  
Trauma Group

Abstract Background Endothelial glycocalyx (EG) abnormal degradation were widely found in critical illness. However, data of EG degradation in multiple traumas is limited. We performed a study to assess the EG degradation and the correlation between the degradation and organ functions in polytrauma patients. Methods A prospective observational study was conducted to enroll health participants (control group) and polytrauma patients (trauma group) at a University affiliated hospital between Feb 2020 and Oct 2020. Syndecan1 (SDC1) and heparin sulfate (HS) were detected in serum sample of both groups. In trauma group, injury severity scores (ISS) and sequential organ failure assessments (SOFA) were calculated. Occurrences of acute kidney injury (AKI), trauma-induced coagulopathy (TIC) within 48 h and 28-day all-cause mortality in trauma group were recorded. Serum SDC1 and HS levels were compared between two groups. Correlations between SDC1/HS and the indicators of organ systems in the trauma group were analyzed. ROC analyses were performed to assess the predictive value of SDC1 and HS for AKI, TIC within 48 h, and 28-day mortality in trauma group. Results There were 45 polytrauma patients and 15 healthy participants were collected, totally. SDC1 and HS were significantly higher in trauma group than in control group (69.39 [54.18–130.80] vs. 24.15 [13.89–32.36], 38.92 [30.47–67.96] vs. 15.55 [11.89–23.24], P <  0.001, respectively). Trauma group was divided into high degradation group and low degradation group according to SDC1 median. High degradation group had more severe ISS, SOFA scores, worse organ functions (respiratory, kidney, coagulation and metabolic system), and higher incidence of hypothermia, acidosis and shock. The area under the receiver operator characteristic curves (AUC) of SDC1 to predict AKI, TIC occurrence within 48 h and 28-day mortality were 0.838 (95%CI: 0.720–0.957), 0.700 (95%CI: 0.514–0.885) and 0.764 (95%CI: 0.543–0.984), respectively. Conclusions EG degradation was elevated significantly in polytrauma patients, and the degradation was correlated with impaired respiratory, kidney, coagulation and metabolic systems in early stage. Serum SDC1 is a valuable predictive indicator of early onset of AKI, TIC, and 28-day mortality in polytrauma patients.

Short-term Effects of Metformin on Cardiac and Peripheral Blood Cells Following Cecal Ligation and Puncture-induced Sepsis

Drug Research ◽  
2020 ◽  
Author(s):  
Tina Didari ◽  
Shokoufeh Hassani ◽  
Maryam Baeeri ◽  
Mona Navaei-Nigjeh ◽  
Mahban Rahimifard ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Weight Loss ◽  
Blood Cells ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Cecal Ligation ◽  
Neutrophil Infiltration ◽  
Cardiac Cells ◽  
Cecal Ligation And Puncture ◽  
Blood Profile

Abstract Aim of the study Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis. Methods For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted. Results In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group. Conclusions Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.

scholarly journals Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats

2007 ◽  
Vol 97 (1) ◽  
pp. 118-137 ◽  
Author(s):  
Scott Banta ◽  
Murali Vemula ◽  
Tadaaki Yokoyama ◽  
Arul Jayaraman ◽  
François Berthiaume ◽  
...  
Keyword(s):  
Gene Expression ◽  
Burn Injury ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Metabolic Fluxes

HSP70.1 AND HSP70.3 MEDIATE SURVIVAL FOLLOWING CECAL LIGATION AND PUNCTURE IN AGED MALE MICE

Shock ◽  
2006 ◽  
Vol 25 (Supplement 1) ◽  
pp. 7-8
Author(s):  
AT Clark ◽  
KW McConnell ◽  
CR Hunt ◽  
TG Buchman ◽  
RS Hotchkiss ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Male Mice

scholarly journals SAT0290 HIGH SERUM MYOSTATIN LEVELS SUGGEST ACCELERATED MUSCLE SENESCENCE IN ACTIVE IDIOPATHIC INFLAMMATORY MYOSITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1089.2-1090
Author(s):  
A. Anuja ◽  
M. Singh ◽  
M. K. Rai ◽  
H. Singh ◽  
V. Agarwal ◽  
...  
Keyword(s):  
Young Adults ◽  
Elevated Serum ◽  
High Serum ◽  
Inactive Disease ◽  
Healthy Controls ◽  
Muscle Enzymes ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis ◽  
Healthy Control ◽  
Accelerated Senescence

Background:Inflammation is the forerunner to fibrosis and premature ageing in various systemic diseases. Hence it seems plausible that idiopathic inflammatory myopathies (IIM) may exhibit accelerated senescence too.Objectives:Hence we investigated the Myostatin: Follistatin system in the serum as a reflection of early senescence in myositis as compared with healthy and diseased controls.Methods:Patients with inflammatory myositis (ACR/EULAR criteria) presenting to the wards and outpatient clinic between December 2017 to August 2019 were recruited. Those with active infection, pregnancy, renal dysfunction or chronic kidney disease were excluded. Apart from patient and disease variables, activity and damage were assessed using standard IMACS score set measures. Patients in inception cohort were additionally followed up at 1 and 6 months. Myostatin and Follistatin were estimated in sera using ELISA (R&D systems, USA). Juvenile myositis and young adults (18-40 years) were subsequently analyzed separately. Non-parametric tests were used for paired and unpaired analysis. Results expressed as median.Results:95 myositis (8 Juvenile myositis, 26 DM, 10 PM, 29 Overlap, 2 NAM 1 CAM and 19 ASS) patients (23 Male and 72 Female) with median age 38 (24.5-46.0) years and disease duration 0.9 (2.3-5.1) years were included. Serum Myostatin was lower in IIM than in healthy control (HC) (153.5 vs. 243.6 p<0.0001, Fig 1A) but higher in IIM as compared with disease controls (153.5 vs 86.1 p=0.0174 Fig. 1B). Serum myostatin was comparable between juvenile and adult myositis and in the various subsets of adult myositis (Fig. 1 C and D). Myostatin levels were higher in active as compared with inactive myositis in young adults (211.7 vs. 158.9, p=0.0149, Figure 1E). Serum Myostatin correlated with height (r 0.3, p=0.003) and weight (r 0.2, p=0.047) but not MMT8 or muscle enzymes.Figure 1.Serum Myostatin levels in IIM as compared with healthy controls (A) and disease controls (B). Levels in juvenile myositis as compared with adult IIM (C) and in various subsets of IIM (D). Serum Myostatin levels in active and inactive disease (E).Although Follistatin was lower in IIM than HC (198.4 vs 243.6, p=<0.0001), the neither Follistatin nor Myostatin: Follistatin ratios differ between subsets, and in active versus inactive disease Figure 2 A-D). On follow-up, the serial Myostatin estimation paralleled change in disease activity.Figure 2.Serum Follistatin levels in IIM as compared with healthy controls (A) and disease controls (C). Levels in juvenile and adult IIM (D) and in various subsets of IIM (D).Conclusion:Elevated serum Myostatin levels in active myositis raise the possibility of accelerated senescence in the inflamed muscle tissues which need further investigation.Acknowledgments: :Partly funded by APLAR and IRA research grants awarded to LG.Disclosure of Interests:None declared

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