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Objective To investigate the clinical value of serum mast cell carboxypeptidase (MC-CP), C-C motif chemokine 26 (CCL26), and decoy receptor 3 (DcR3) in the diagnosis of obstructive sleep apnea syndrome (OSAS) in chronic obstructive pulmonary disease (COPD). Methods Ninety COPD patients who visited the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were collected. Among them, 48 patients with simple COPD were included in the COPD group, and 42 patients with COPD combined with OSAS were included in the COPD-OSAS group. During the same period, 48 healthy volunteers who underwent physical examination in that Hospital of Hebei North collected as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to detect serum level of MC-CP, CCL26, and DcR3. Receiver operating characteristic (ROC) curve was applied to analyze the clinical value of serum level of MC-CP, CCL26, and DcR3 in the diagnosis of COPD complicated with OSAS. Multivariate Logistic regression was applied to analyze the influencing factors of COPD complicated with OSAS. Results Compared with the control group, the smoking index, C-reactive protein (CRP)and white blood cell count (WBC) in the COPD and COPD-OSAS groups increased obviously in sequence, the ratio of forced expiratory volume in first second to forced vital capacity (FEV1/FVC) decreased obviously in sequence (P＜0.05); Compared with the control group, the level of MC-CP, CCL26, and DcR3 in patients with COPD and COPD-OSAS increased significantly in sequence (P＜0.05); The combination of serum MC-CP, CCL26 and DcR3 had a higher area under the curve(AUC) for the diagnosis of COPD complicated with OSAS compared to the individual diagnosis (Z=4.066, P＜0.001; Z=2.391, P＜0.05; Z=2.353, P＜0.05). Multivariate Logistic regression analysis showed that smoking index, serum level of MC-CP, CCL26 and DcR3 were influencing factors for COPD complicated with OSAS (P＜0.05). Conclusions The simultaneously increased expression of MC-CP, CCL26 and DcR3 in the serum of COPD may support clinical diagnostic of COPD patients with OSAS. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies.IMPORTANCESepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.

Introduction: The cardiovascular risk has been increased in chronic kidney disease associated with chronic inflammation and atherosclerosis. Decoy receptor 3, is a member of the TNF receptor superfamily and associated with inflammation and atherosclerosis. The aim of our study is to determine the relationship, between serum DcR3 levels and inflammatory markers in patients with renal transplantation, those receiving dialysis treatment and cases with chronic renal failure that did not receive replacement therapy, and to evaluate their correlation with USG findings. Material and methods: A total of 150 patients aged between 22–86 years, consisting of 4 groups, namely renal transplantation, dialysis, predialysis chronic kidney disease and control groups, were included in the study. Serum decoy receptor 3, VCAM-1, ICAM-1 and IL-8 measured with ELISA method. Carotid intima-media thickness and presence of carotis arter plaque performed by ultrasound probe, non-invasively. Results: All serum markers were higher in dialysis and pre-dialysis chronic kidney disease groups compared to renal transplant and control groups (p

Decoy receptor 3 (DcR3), a soluble glycosylated protein in the tumor necrosis factor receptor superfamily, plays a role in tumor and inflammatory diseases. Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the response to infection. Currently, no specific drug that can alleviate or even cure sepsis in a comprehensive and multi-level manner has been found. DcR3 is closely related to sepsis and considerably upregulated in the serum of those patients, and its upregulation is positively correlated with the severity of sepsis and can be a potential biomarker for diagnosis. DcR3 alone or in combination with other markers has shown promising results in the early diagnosis of sepsis. Furthermore, DcR3 is a multipotent immunomodulator that can bind FasL, LIGHT, and TL1A through decoy action, and block downstream apoptosis and inflammatory signaling. It also regulates T-cell and macrophage differentiation and modulates immune status through non-decoy action; therefore, DcR3 could be a potential drug for the treatment of sepsis. The application of DcR3 in the treatment of a mouse model of sepsis also achieved good efficacy. Here, we introduce and discuss the progress in, and suggest novel ideas for, research regarding DcR3 in the diagnosis and treatment of sepsis. [ABSTRACT FROM AUTHOR]

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Soluble Fas ligand (sFasL, sCD95L) and its specific soluble binders, soluble Fas receptor (sFas, sCD95) and decoy receptor 3 (DcR3), have been investigated as possible clinical biomarkers in many serious diseases. The present review aimed to provide an overview of the current state of this medically promising research by extensively examining the relevant literature. The summarized results of the survey are presented after classification into six categories according to the type of targeted disease. To date, the studies have been mainly devoted to the diagnosis of disease severity states and prognosis of treatments about various types of cancers and autoimmune diseases represented by autoimmune lymphoproliferative syndrome and systemic lupus erythematosus, because these important life-threatening or intractable diseases were suggested to be most relevant to the impairment of apoptotic cell death-inducing systems, including the Fas receptor-mediated signaling system, and the mechanisms responsible for their onset. However, various more general inflammation-related diseases, including, but not limited to, other autoimmune and allergic diseases (e.g., rheumatoid arthritis and atopic asthma), infectious diseases (e.g., sepsis and chronic hepatitis), cardiovascular system-specific disorders (e.g., acute coronary syndromes and heart failure) as well as other diseases specific to the renal, hepatic, and respiratory systems, etc., have also been targeted as important fields of research. The data obtained so far demonstrated that sFas, sFasL, and DcR3 possess significant potential in the assessment of various disease states, which can contribute to the development of therapeutic interventions. Although further studies in various relevant fields are essential, it is expected that clinical translation of sFas, sFasL, and DcR3 into practical biomarkers will contribute to effective treatments of a wide variety of diseases. [ABSTRACT FROM AUTHOR]

Gout is a common inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. This activates the macrophages into a proinflammatory state by inducing NLRP3-dependent interleukin-1β (IL-1β) secretion, resulting in neutrophil recruitment. Soluble decoy receptor 3 (DcR3) is an immune modulator and can exert biological functions via decoy and non-decoy actions. Previously, we showed that DcR3 suppresses lipopolysaccharides (LPS)- and virus-induced inflammatory responses in the macrophages and promotes the macrophages into the M2 phenotype. In this study, we clarified the actions of DcR3 and its non-decoy action motif heparin sulfate proteoglycan (HSPG) binding domain (HBD) in the MSU crystal-induced NLRP3 inflammasome activation in the macrophages and in mice. In bone marrow-derived macrophages, THP-1 and U937 cells, we found that the MSU crystal-induced secretion of IL-1β and activation of NLRP3 were suppressed by both DcR3.Fc and HBD.Fc. The suppression of the MSU-induced NLRP3 inflammasome activation is accompanied by the inhibition of lysosomal rupture, mitochondrial production of the reactive oxygen species (ROS), expression of cathepsins, and activity of cathepsin B, without affecting the crystal uptake and the expression of NLRP3 or pro-IL-1β. In the air pouch mice model of gout, MSU induced less amounts of IL-1β and chemokines secretion, an increased M2/M1 macrophage ratio, and a reduction of neutrophil recruitment in DcR3-transgenic mice, which expresses DcR3 in myeloid cells. Similarly, the mice intravenously treated with DcR3.Fc or HBD.Fc displayed less inflammation response. These findings indicate that HBD of DcR3 can reduce MSU crystal-induced NLRP3 inflammasome activation via modulation of mitochondrial and lysosomal functions. Therefore, we, for the first time, demonstrate a new therapeutic potential of DcR3 for the treatment of gout.

Gout is a common inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in the joints. This activates the macrophages into a proinflammatory state by inducing NLRP3-dependent interleukin-1β (IL-1β) secretion, resulting in neutrophil recruitment. Soluble decoy receptor 3 (DcR3) is an immune modulator and can exert biological functions via decoy and non-decoy actions. Previously, we showed that DcR3 suppresses lipopolysaccharides (LPS)- and virus-induced inflammatory responses in the macrophages and promotes the macrophages into the M2 phenotype. In this study, we clarified the actions of DcR3 and its non-decoy action motif h eparin sulfate proteoglycan (HSPG) b inding d omain (HBD) in the MSU crystal-induced NLRP3 inflammasome activation in the macrophages and in mice. In bone marrow-derived macrophages, THP-1 and U937 cells, we found that the MSU crystal-induced secretion of IL-1β and activation of NLRP3 were suppressed by both DcR3.Fc and HBD.Fc. The suppression of the MSU-induced NLRP3 inflammasome activation is accompanied by the inhibition of lysosomal rupture, mitochondrial production of the reactive oxygen species (ROS), expression of cathepsins, and activity of cathepsin B, without affecting the crystal uptake and the expression of NLRP3 or pro-IL-1β. In the air pouch mice model of gout, MSU induced less amounts of IL-1β and chemokines secretion, an increased M2/M1 macrophage ratio, and a reduction of neutrophil recruitment in DcR3-transgenic mice, which expresses DcR3 in myeloid cells. Similarly, the mice intravenously treated with DcR3.Fc or HBD.Fc displayed less inflammation response. These findings indicate that HBD of DcR3 can reduce MSU crystal-induced NLRP3 inflammasome activation via modulation of mitochondrial and lysosomal functions. Therefore, we, for the first time, demonstrate a new therapeutic potential of DcR3 for the treatment of gout. [ABSTRACT FROM AUTHOR]

Purpose: Serum decoy receptor 3 (DcR3) level increases in chronic inflammatory diseases. The present study aimed to examine serum DcR3 and IL-6 levels in male patients with stable chronic obstructive pulmonary disease (COPD) and acute exacerbation of the disease and correlations between these markers and airflow limitation. Methods: We measured serum DcR3 and IL-6 levels in 60 COPD patients [30 stable COPD (SCOPD), and 30 acute exacerbation of COPD (AECOPD)], and 30 control subjects and assessed their correlations with airflow limitation according to the COPD stage indicated by the global initiative for chronic obstructive pulmonary disease (GOLD) criteria, peripheral O2 saturation (SpO2), and COPD assessment test (CAT) score. We also tested associations between serum DcR3 levels and COPD patients' clinical parameters. Results: Both serum DcR3 and IL-6 levels increased with increasing severity of airflow limitation in SCOPD and AECOPD groups (P < 0.01 to 0.001). These markers also increased in patients with AECOPD compared with subjects in SCOPD group in GOLD stages III–IV (P < 0.05 to 0.001). In addition, there was a significant positive correlation between serum DcR3 level and IL-6, CAT score and smoking history (per year). Conclusion: The study revealed that serum DcR3 level elevated with increasing severity of airflow limitation in male COPD patients, particularly in acute exacerbation phase. This increase was associated with a reduced quality of life and increased severity of hypoxia. These results suggest that DcR3 may be associated with the underlying pathophysiology of COPD in male patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: To date, there is no report on the anti-hepatoma mechanism of Chinese herbal medicine targeting hepatocellular carcinoma stem cells; therefore, relevant research is necessary. OBJECTIVE: To observe the effect of baicalein on the expression of Decoy receptor 3 in hepatocellular carcinoma stem cells as well as the biological behavior of hepatocellular carcinoma stem cells after down-regulation of Decoy receptor 3. METHODS: Hepatocellular carcinoma stem cells were obtained from hepatocellular carcinoma cell lines (purchased from the Cell Bank, Chinese Academy of Sciences, Shanghai, China), cultured and passaged. The cells were cultured in the low-glucose DMEM containing nothing (control group), 200 (high-dose group), 100 (middle-dose group) or 50 μmol/L (low-dose group) baicalein. After treatment with baicalein, RT-PCR and western blot were used to detect the expression of decoy receptor 3 at mRNA and protein levels. Cell counting kit-8, flow cytometry, and Transwell assay were used to detect the proliferation, cell cycle distribution, apoptosis and migration of hepatocellular carcinoma stem cells. RESULTS AND CONCLUSION: Compared with the control group, high-dose baicalein could significantly down-regulated the expression of decoy receptor 3 mRNA and protein in hepatocellular carcinoma stem cells. High-dose baicalein was then confirmed to be the best concentration of action. Compared with the control group, in the high-dose baicalein group, the proliferation ability of hepatocellular carcinoma stem cells decreased significantly, the percentage of S-phase and G2-phase cells increased, while the percentage of G1-phase cells decreased (P < 0.05). Compared with the control group, in the high-dose baicalein group, the apoptotic rate of hepatocellular carcinoma stem cells increased significantly, while the migration ability decreased markedly. To conclude, high-dose baicalein can inhibit a series of biological behaviors of hepatocellular carcinoma stem cells by down-regulating the expression of Decoy receptor 3, which provides an experimental basis for clinical treatment of hepatocellular carcinoma with Decoy receptor 3 as the target and hepatocellular carcinoma stem cells as the object. [ABSTRACT FROM AUTHOR]

Background: Decoy receptor 3 (DcR3) is a protein with anti-apoptotic effect that belongs to the tumor necrosis factor receptor superfamily. DcR3 is highly expressed in a variety of malignant tumors including cholangiocarcinoma and its expression was found to be related to the clinical stage, the invasion, and the metastasis of the tumor. This in vitro study aimed to investigate the effect of downregulated expression of DcR3 on cell viability, cell apoptosis, and cell cycle in cholangiocarcinoma cell line TFK-1. Methods: Three different cell lines were cultured: human cholangiocarcinoma TFK-1, human biliary epithelial carcinoma HuCCT-1, and human cholangiocarcinoma RBE. The cholangiocarcinoma cell line with the highest expression of DcR3 was selected for further investigation. The expression of DcR3 was silenced/knocked down by transfection with DcR3-siRNA in the selected cell line. Various biological phenotype parameters such as cell viability, apoptosis, and cell cycle were observed. Results: The mRNA and protein levels of DcR3 were measured in the three cell lines, and TFK-1 was selected. After the treatment with DcR3-siRNA for 48 h, DcR3 mRNA and protein expression in the treatment group were 38.45% (P < 0.01) and 48.03% (P < 0.05) of that of the control, respectively. It was found that the cell viability decreased to 61.87% of the control group (P < 0.01) after the downregulation of DcR3 in cholangiocarcinoma cell line TFK-1 by transfection with DcR3-siRNA, while the percentage of apoptotic cells was 2.98 times as compared with the control group (P < 0.05). Compared with the control group the ratio of G0/G1increased, and the ratio of G2/M decreased in the treatment group. However, the differences were not statistically significant. Conclusions: The effect of DcR3 on the growth and apoptosis of cholangiocarcinoma has been demonstrated. DcR3 is not only a predictive marker for malignant tumor but it is also likely to be a potential target for cancer gene therapy. Further studies should focus on exploring the binding ligand of DcR3, the signaling pathway involved, and the molecular mechanism for the regulation of DcR3 expression in cholangiocarcinoma.

Abstract Background Microglia mediate amyloid-beta peptide (Aβ)-induced neuroinflammation, which is one of the key events in the pathogenesis of Alzheimer’s disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic immunomodulator that promotes macrophage differentiation toward the M2 anti-inflammatory phenotype. Based on its role as an immunosupressor, we examined whether DcR3 could alleviate neuroinflammation and AD-like deficits in the central nervous system. Method We crossed human APP transgenic mice (line J20) with human DcR3 transgenic mice to generate wild-type, APP, DcR3, and APP/DcR3 mice for pathological analysis. The Morris water maze, fear conditioning test, open-field, and elevated-plus maze were used to access their cognitive behavioral changes. Furthermore, the pathological and immune profiles were examined by immunostaining, ELISA, Q-PCR, and IP. In vitro assays were designed to examine DcR3-mediated innate cytokine profile alteration and the potential protective mechanism. Results We reported that DcR3 ameliorates hippocampus-dependent memory deficits and reduces amyloid plaque deposition in APP transgenic mouse. The protective mechanism of DcR3 mediates through interacting with heparan sulfate proteoglycans and activating IL-4+YM1+ M2a-like microglia that reduces Aβ-induced proinflammatory cytokines and promotes phagocytosis ability of microglia. Conclusion The neuroprotective effect of DcR3 is mediated via modulating microglia activation into anti-inflammatory M2a phenotype, and upregulating DcR3 expression in the brain may be a potential therapeutic approach for AD.

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissue leads to the formation of pannus, which invades joint cartilage and bone resulting in joint destruction. Tumor necrosis factor-like ligand 1A (TL1A), a member of the tumor necrosis factor superfamily (TNFSF15), contributes to the pathogenesis of autoimmune diseases, including RA. In the present study, a cDNA microarray was used to search for genes whose expression in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by TL1A. Four individual lines of primary cultured RA-FLS were incubated either with recombinant human TL1A protein or phosphate-buffered saline, as an unstimulated control, for 12 h. Gene expression was then detected through the microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by TL1A. The present study also demonstrated the functions of those genes whose expression in RA-FLS was regulated by TL1A. Among the genes in this profile, the present study focused on the following genes: Spectrin repeat-containing nuclear envelope 1, Fc receptor-like 2, PYD (pyrin domain)-containing 1, cell division cycle 45 homolog, signal transducer and activator of transcription 5B, and interferon regulatory factor 4. These genes may affect the pathogenesis of RA, including proliferation, regulation of B cells and T cells, inflammation, and cytokine processing. The present study revealed for the first time, to the best of our knowledge, the expression profile of genes in RA-FLS regulated by TL1A. The data indicate that TL1A may regulate the gene expression of various key molecules in RA-FLS, thus affecting the pathogenesis of RA. Further investigations of the genes detected in the current profiles may provide a deeper understanding of the pathogenesis and a novel target for the treatment of RA. [ABSTRACT FROM AUTHOR]

Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. Methods: The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. Results: The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = −0.399, p = 0.021; and r = −0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. Conclusion: High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma.

Background: Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2. Methods: HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant. Results:DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05). Conclusions: Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.

Introduction: Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. Material and Methods: The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. Results: The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). Conclusion: Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas.

Decoy receptor 3 (DcR3) is a tumor necrosis factor receptor, which may inhibit apoptosis. The aim of the present study was to investigate the clinical significance of DcR3 upregulation in patients with chronic hepatitis B (CHB) and hepatic fibrosis. A total of 128 patients with a clinical diagnosis of CHB who underwent liver biopsy were included in the present study. The expression levels of DcR3, hyaluronic acid (HA), type III procollagen, type IV collagen (IV-C) and laminin protein were assessed. The diagnostic value of DcR3 in patients with CHB with hepatic fibrosis was determined using receiver operating characteristic (ROC) curve analysis. DcR3 was significantly upregulated in patients with CHB, particularly in patients with active CHB. The expression of DcR3 was significantly increased in patients with CHB with liver fibrosis and liver cirrhosis, compared with patients with CHB without liver fibrosis. The area under the ROC curve for the diagnosis of CHB liver fibrosis based on DcR3 or DcR3 combined with IV-C/HA was 0.807 or 0.869, with a sensitivity and specificity of 76.9 and 77.8% or 84.6 and 81.2%, respectively. DcR3 is a marker for liver fibrosis in patients with hepatitis B infection. The use of DcR3 in combination with IV-C and HA may further increase its diagnostic value for liver fibrosis. [ABSTRACT FROM AUTHOR]

Background Decoy receptor 3 (DcR3) has been reported to be overexpressed in a wide range of solid tumors, suggesting that DcR3 plays a crucial role in the development and progression of cancer. The present meta-analysis assesses the association between DcR3 expression and prognosis in patients with solid tumors. Methods Eligible studies were identified by searching the PubMed, Web of Science, Cochrane Library, EMBASE, Chinese CNKI, and Wan Fang databases. The pooled hazard ratios (HRs) for overall survival (OS) and recurrence-free survival (RFS) were calculated using fixed effects models and random effects models, respectively. Results Data from the 16 included studies, with 2209 patients, were reviewed and analyzed. DcR3 overexpression was significantly associated with worse OS in patients with solid tumors, but its expression might not be related to RFS in malignancies. Conclusions Current evidence demonstrates that increased DcR3 expression correlates with a poor prognosis in cancer patients, which suggests that the expression status of DcR3 is a useful biomarker for the prediction of prognosis in patients with solid tumors. [ABSTRACT FROM AUTHOR]

Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL-mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL-mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid control HepG2 cells and wild-type HepG2 cells (WT) were treated with FasL (10 ng/ml). Flow cytometry was used to detect changes in the cell cycle and apoptosis. MTS, clonogenic, wound healing and Transwell assays were performed to examine changes in cell activity, proliferation, migration and invasiveness. Reverse transcription polymerase chain reaction and western blot analysis were performed to measure the expression of DcR3, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor (VEGF)-C and VEGF-D. The results demonstrated that, compared with WT cells, the proportion of KD cells in the G2/M phase decreased following treatment with FasL. KD cells were more sensitive to FasL-induced apoptosis. Following treatment with FasL, the activity and proliferation, migration and invasion of KD cells were reduced, and the expression of MMP9, VEGF-C and VEGF-D decreased. Furthermore, it was demonstrated that DcR3 is involved in the proliferation and invasion of HepG2 cells, and this mechanism may be associated with the regulatory effect of the expression of MMP9, VEGF-C and VEGF-D; however, the exact mechanism of action remains unclear. FollowingDcR3 silencing, FasL-mediated apoptosis increased in HepG2 cells. Therefore, DcR3 combined with FasL may be a potential target for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Background. Hepatic fibrosis is a reversible pathological process. Inflammatory responses are the prevailing reactions during hepatic fibrosis. Decoy receptor 3 (DcR3) has been reported to have an anti-inflammatory effect. Objectives. The aim of the study was to investigate the preventive effects of DcR3 on hepatic fibrosis. Material and methods. Hepatic fibrosis was induced in rats by administering intraperitoneally (ip.) 1% dimethylnitrosamine (DMN). DcR3 plasmid was delivered into rats by intravenous injection. After 4 weeks, the expression of DcR3, TNF-like molecule 1A (TL1A) and α-SMA of the liver tissue were checked. The levels of inflammatory cytokines such as TNF-α, IL-6 and IL-1β were detected using western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Masson's trichrome staining for histopathological changes of the liver tissue was observed. Finally, the activity of NF-κB in the liver was examined by enzyme-linked immunosorbent assay (ELISA). Results. A higher expression of DcR3 was observed in rats treated with DcR3 (p < 0.05). Histological results showed that DcR3 significantly attenuated pathology in hepatic fibrosis rats. Consistently, mRNA and protein levels of α-SMA, TL1A, TNF-α, IL-6, and IL-1β were repressed in the liver tissue after treatment with DcR3 (p < 0.05). Moreover, DcR3 also inhibited the activation of NF-κB in the liver tissue (p < 0.05). Conclusions. This study demonstrated that DcR3 attenuated liver injury and inflammatory responses in rats with hepatic fibrosis. We suggest DcR3 may be a prophylactic and promising therapeutic agent in the treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS. Methods: Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses. Results: CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. Conclusions: These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium. [ABSTRACT FROM AUTHOR]

Objective Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Methods Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥ 90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Results Plasma DcR3 level was significantly higher in good CCC group (328.00 ± 230.82 vs 194.84 ± 130.63 ng/l, p < 0.01) and positively correlated with Rentrope grade (p < 0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Conclusions Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. [ABSTRACT FROM AUTHOR]

Aims Treatment of non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, upregulated hepatic inflammation and oxidative stress, with the resultant M1 polarization of macrophages as well as imbalanced adipocytokines, all accelerate NASH progression. As a member of the tumor necrosis factor receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations. In this study, we aimed to investigate the possible non-decoy effects of DcR3 on diet-induced NASH mice. Methods Methionine- and choline-deficient (MCD) diet feeding for 9 weeks was applied to induce NASH in BALB/c mice. Decoy receptor 3 heterozygous transgenesis or pharmacological pretreatment with DcR3a for 1 month were designed as interventions. Intrahepatic inflammatory status as well as macrophage polarization, oxidative stress, and steatosis as well as lipogenic gene expression and fibrotic status were analyzed. Additionally, acute effects of DcR3a on HepG2 cells, Hep3B cells, and primary mouse hepatocytes in various MCD medium-stimulated changes were also evaluated. Results Both DcR3 genetic and pharmacologic supplement significantly reduced MCD diet-induced hepatic M1 polarization. In addition, DcR3 supplement attenuated MCD diet-increased hepatic inflammation, oxidative stress, adipocytokine imbalance, steatosis, and fibrogenesis. Moreover, acute DcR3a incubation in HepG2 cells, Hep3B cells, and mouse hepatocytes could normalize the expression of genes related to lipid oxidation along with inflammation and oxidative stress. Conclusion The ability of DcR3 to attenuate hepatic steatosis and inflammation through its non-decoy effects of immune modulation and oxidative stress attenuation makes it a potential treatment for NASH. [ABSTRACT FROM AUTHOR]

Small intestinal neuroendocrine tumors (SI-NETs) are amineand peptide-producing neoplasms. Most patients display metastases at the time of diagnosis; they have an unpredictable individual disease course and the tumors are often therapy resistant. Chromogranin A and 5-hydroxyindoleacetic acid are the biomarkers clinically used most often today, but there is a great need for novel diagnostic and prognostic biomarkers and new therapeutic targets. Sixty-nine biomarkers were screened in serum from 23 SI-NET patients and 23 healthy controls using the multiplex proximity ligation assay (PLA). A refined method, the proximity extension assay (PEA), was used to analyze 76 additional biomarkers. Statistical testing and multivariate classification were performed. Immunohistochemistry and ELISA were performed in an extended cohort. Using PLA, 19 biomarkers showed a significant difference in serum concentrations between patients and controls, and PEA revealed a difference in the concentrations of 17 proteins. Multivariate classification analysis revealed decoy receptor 3 (DcR3), trefoil factor 3 (TFF3), and midkine to be good biomarkers for the disease, which was confirmed by ELISA analysis. All 3 biomarkers were expressed in tumor tissue. DcR3 concentrations were elevated in patients with stage IV disease. High concentrations of DcR3 and TFF3 were correlated to poor survival. DcR3, TFF3, and midkine exhibited elevated serum concentrations in SI-NET patients compared to healthy controls, and DcR3 and TFF3 were associated with poor survival. DcR3 seems to be a marker for liver metastases, while TFF3 and midkine may be new diagnostic biomarkers for SI-NETs. [ABSTRACT FROM AUTHOR]

Background/purpose: Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients.Methods: The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed.Results: The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = -0.399, p = 0.021; and r = -0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients.Conclusion: High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma. [ABSTRACT FROM AUTHOR]

Type 17 T-helper (Th17) cells have been suggested to be involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. Decoy receptor 3 (DcR3) is known to block the TL1A-DR3 pathway by binding TL1A. To evaluate the Th17-TL1A systems as disease activity markers in AAV, we investigated the serum levels of TL1A and DcR3 in AAV patients. Serum IL-17, IL-23, TL1A, and DcR3 were measured by ELISA in 24 AAV patients with microscopic polyangiitis before the initial treatment, 24 AAV patients during remission, and 20 control subjects. There were no significant differences in serum IL-17, IL-23, and TL1A levels among the active-vasculitis patients, inactive-vasculitis patients, and controls. The mean serum DcR3 level was significantly higher in the active-vasculitis patients than in the inactive-vasculitis patients and controls ( P < 0.0001, respectively). There were significant positive correlations between the serum DcR3 levels and Birmingham Vasculitis Activity Score (BVAS), myeloperoxidase (MPO)-ANCA titers, white blood cell counts, serum creatinine levels, and serum C-reactive protein levels. In a multiple regression analysis, there was a significant positive correlation between the serum DcR3 level and BVAS ( β = 0.650, P = 0.0462). The mean BVAS level was significantly higher in the active-vasculitis patients with high serum DcR3 levels than in those with the low serum DcR3 levels ( P = 0.0202). The serum level of DcR3 may be a useful marker for disease activity in AAV. [ABSTRACT FROM AUTHOR]

Decoy receptor 3 (DcR3) competitively binds to three ligands, Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells and tumor necrosis factor-like ligand 1A (TL1A), to prevent their effects. Recent studies have suggested that DcR3 directly affects cells as a ligand. Using a microarray assay, our group newly identified interleukin (IL)-12B, which encodes the p40 subunit common to IL-12 and IL-23, as one of the genes for which expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is induced by DcR3. The present study demonstrated that IL-12B mRNA expression was upregulated by DcR3-Fc in RA-FLS in a dose-dependent manner, but not in OA-FLS. IL-12B p40 protein in RA-FLS was increased when stimulated with DcR3-Fc. Pre-treatment with anti-TL1A antibody suppressed the upregulation of IL-12B mRNA in RA-FLS stimulated with DcR3-Fc. DcR3 mRNA expression in RA-FLS was induced by IL-23, but not by IL-12. These results indicated that DcR3 may increase IL-12 or IL-23 by inducing IL-12B p40 expression via membrane-bound TL1A on RA-FLS and that IL-23 reciprocally induces DcR3 expression in RA-FLS. DcR3 and IL-23 may interact in a feedback loop that aggravates local inflammation in patients with RA. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC. [ABSTRACT FROM AUTHOR]

The suppression of immune responses in malignant gliomas is thought to be involved in glioma pathogenesis. The newly identified tumor-secreted soluble decoy receptor 3 (DcR3) can bind to the ligands CD95L and LIGHT, thereby neutralizing their pro-apoptotic actions. Little is known of the production of DcR3 by glioma cells. This study investigated the serum concentration of DcR3 in glioma patients before and after tumor removal. Blood samples were taken from 17 glioma patients and 10 control patients. The serum DcR3 concentration was measured using a DcR3 enzyme-linked immunosorbent assay. There was no statistically significant difference between preoperative (0.069 % 0.027 ng/mL) and postoperative DcR3 concentrations (0.068 % 0.022 ng/mL; p = 0.951). Similarly, there was no difference in preoperative DcR3 concentration between glioma patients (0.069 % 0.027 ng/mL) and controls (0.063 % 0.023 ng/mL; p = 0.106). Our study demonstrated no alteration in DcR3 concentration in glioma patients before and after tumor removal.

Influenza A virus (IAV) infects macrophages and stimulates innate immunity receptors and sensors to produce proinflammatory cytokines and chemokines, which are responsible for IAV-induced pulmonary inflammation and injury. Decoy receptor 3 (DcR3) is a soluble protein belonging to the tumor necrosis factor receptor superfamily (TNFRSF), and is able to skew macrophage differentiation into an M2 phenotype. We demonstrated that DcR3 attenuated IAV-induced secretion of proinflammatory cytokines and chemokine from macrophages, and mitigated pulmonary infiltration and reduce lethality. Proteome-wide phosphoproteomic mapping revealed that DcR3 not only activated STK10, a negative regulator of cell migration, but also inactivated PKC-α, which are crucial for the activation of ERK and JNK in human macrophages. Furthermore, less pulmonary infiltration with lower levels of proinflammatory cytokines and chemokine in bronchoalveolar lavage fluid (BALF) were observed in DcR3-transgenic mice. Moreover, recombinant DcR3.Fc and heparan sulfate proteoglycan binding domain of DcR3.Fc (HBD.Fc) fusion proteins attenuated weight loss and protected mice from IAV-induced lethality. Thus, DcR3-mediated protection is not only via suppression of proinflammatory cytokine and chemokine release, but also via activation of STK10 to inhibit cell infiltration. DcR3 fusion proteins may become therapeutic agents to protect host from IAV-induced lethality in the future. Key message • DcR3 suppresses IAV-induced cytokine secretion. • DcR3 inhibits IAV-induced JNK and ERK activation in human macrophages. • DcR3 downregulates TLR3 and 7 expressions in human macrophages. • DcR3 protects mice from IAV-induced lethality. [ABSTRACT FROM AUTHOR]

Decoy receptor 3 (DcR3) is expressed in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and downregulates the expression of tryptophan hydroxylase 1 (TPH1), which is the rate-limiting enzyme in serotonin synthesis. The aim of the present study was to determine the specificity of the effects of DcR3 on TPH1 in RA-FLS, and therefore determine whether DcR3 had the potential to modulate the pathogenesis of RA. The present study also aimed to compare the effects of DcR3 and inflammatory cytokines on the expression of TPH1 in RA-FLS and osteoarthritis (OA)-FLS. Primary cultured RAor OA-FLS were incubated with 1.0 µg/ml DcR3-Fc protein or 1.0 µg/ml control immunoglobulin G (IgG)1 for 12 h, or with 1.0 ng/ml tumor necrosis factor (TNF)α, 1.0 ng/ml interleukin (IL)-1β or serum-free Opti-MEM only, for 24 h. The relative mRNA expression levels of TPH1 were subsequently quantified using reverse transcription-polymerase chain reaction. The expression of serotonin in RA or OA synovial tissue was detected using immunohistochemistry. The mRNA expression of TPH1 was observed in both RA- and OA-FLS and was significantly decreased following treatment with DcR3 in the RA-FLS, however, not in the OA-FLS. The mRNA expression of TPH1 was significantly decreased following treatment with TNFα or IL-1β in both the RA- and OA-FLS. The expression of serotonin in the multi-layered lining synovial cells of RA and the outer layer lining synovial cells of OA was detected using immunohistochemistry. The present study is the first, to the best of our knowledge, to demonstrate that the expression of TPH1 in FLS is downregulated by inflammatory cytokines, and that DcR3 suppressed the expression of TPH1 in RA-FLS in a disease-specific manner. These results suggested that synovial serotonin may be involved in the pathogenesis of RA, and that TPH1 and DcR3 may be potential therapeutic targets for the treatment of RA. [ABSTRACT FROM AUTHOR]

Background and objective: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated. Methods: Lymphocyte-predominant exudative PE samples were assayed for inflammatory and anti- inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value for the predicted probability. Results: Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon-γ (IFN-γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo-attractant protein (MCP)-1, IFN-induced protein (IP)-10, granzyme A and perforinwere higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN-γ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF-sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specifcity under the cut-off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN-γ, MCP-1, IP-10 and perforin than those with positive sputum but negative PE culture. Conclusions: While pleural interferon-γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF-sR1 can improve the diagnostic effcacy. [ABSTRACT FROM AUTHOR]

Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p < 0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic >24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study. [ABSTRACT FROM AUTHOR]

Background: Protein-energy wasting (PEW) is common and associated with poor outcome in hemodialysis patients. In hemodialysis patients, geriatric nutritional risk index (GNRI) and decoy receptor 3 (DcR3) have been shown as the nutritional and inflammatory markers, respectively. The present study aimed to assess the predictive ability of GNRI and DcR3 for PEW status and long-term outcomes in chronic hemodialysis patients. Methods: A prospective cohort of 318 hemodialysis patients was conducted with a median follow-up of 54 months. Malnutrition-inflammation score (MIS) was used as the reference standard for the presence of PEW. Endpoints were cardiovascular and all-cause mortality. Results: Baseline GNRI had a strong negative correlation with DcR3 and MIS score. For patients with age < or ≥60, high DcR3 and low GNRI were independent predictors for the presence of PEW at baseline. At the end of the study, 81 patients died (27 cardiovascular deaths). The adjusted hazard ratios (95% confidence intervals) of low GNRI and high DcR3 were 1.93 (1.1-4.8) and 2.53 (1.2-5.5) for cardiovascular mortality and 1.85 (1.1-3.2) and 2.37 (1.5-3.7) for all-cause mortality, respectively. While integrated into a model of conventional risk factors, GNRI together with DcR3 further significantly improved the predictability for overall mortality (c statistic, 0.823). Conclusions: Low GNRI and high DcR3 were the alternatives for identifying hemodialysis patients at risk of PEW and overall mortality. Further studies are needed to verify whether timely recognition of hemodialysis patients with a high malnutrition-inflammation risk could reduce their mortality by appropriate interventional strategies. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer. Materials and methods: Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled–microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed. Results: DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3. Conclusions: The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3. [Copyright &y& Elsevier]

Background & Aims Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A ( TL1A), as a susceptibility gene for primary biliary cirrhosis ( PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC. Methods We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining. Results Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid ( UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients. Conclusions These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC. [ABSTRACT FROM AUTHOR]