Predictors for unfavorable prognosis after stroke with perforator artery disease.

Background and purpose: Perforator artery disease (PAD) is an important subtype of ischemic stroke. The risk factors affecting the prognosis of patients with PAD are unclear. This study aimed to investigate the risk factors affecting the unfavorable prognosis of PAD. Methods: Patients with PAD were enrolled from Dushu Lake Hospital Affiliated to Soochow University and diagnosed as stroke with PAD during the period from September 2021 to July 2023 and followed up with a modified Rankin Scale (mRS) after 90 days, defining the mRS of 0-2 as a group with favorable prognosis, and 3-6 as a group with unfavorable functional outcome. Logistic regression was used to identify predictors for PAD. Multiple logistic regression analysis and receiver operating characteristics (ROC) were used to identify predictors of unfavorable prognosis. Results: Of the 181 enrolled patients, 48 (26.5%) were identified with unfavorable prognosis. On multivariate analysis, increased age (OR = 1.076, 95% CI: 1.012 ~ 1.144, p = 0.019), higher National Institutes of Health Stroke Scale (NIHSS) score at admission (OR = 2.930, 95% CI: 1. 905 ~ 4.508, p < 0.001), and increased neutrophil-to-lymphocyte ratio (NLR) (OR = 3.028, 95% CI: 1.615 ~ 5.675, p = 0.001) were independent risk factors for unfavorable prognosis in patients with PAD, and the area under the receiver operating characteristic curve was 0.590, 0.905, and 0.798, and the multi-factor diagnostic model (Model 2) showed reliable diagnostic specificity and sensitivity (area under the curve = 0.956, p < 0.001, specificity 0.805, sensitivity 0.958, accuracy 0.845). Conclusion: Increased baseline NLR and NIHSS score and aging may be independent risk factors for unfavorable prognosis of patients with PAD. NLR can be used as a potential biological indicator to predict the prognosis of stroke with PAD.

RAI2 acts as a tumor suppressor with functional significance in gastric cancer.

Metastasis of gastric cancer (GC) is one of the major causes of death among GC patients. GC metastasis involves numerous biological processes, yet the specific molecular biological mechanisms have not been elucidated. Here, we report a novel tumor suppressor, retinoic acid-induced 2 (RAI2), which is located in the Xp22 region of the chromosome and plays a role in inhibiting GC growth and invasion. In this study, integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and immunohistochemistry staining data suggested that RAI2 expression in GC samples was low. Moreover, the immune infiltration analysis indicated that low expression of RAI2 in GC was associated with a higher intensity of tumor-infiltrating lymphocytes (TILs) and an abundance of Programmed death ligand 1 (PD-L1) expression. Gene set enrichment analysis (GSEA) analysis further revealed that RAI2 regulated some pathways including the GAP junction, focal adhesion and ECM receptor interaction pathway, immune regulation, PI3K-Akt signaling, MAPK signaling, cell cycle, and DNA replication. Furthermore, the knockdown of RAI2 promoted GC cell proliferation, migration, and invasion in vitro. Taken together, these results suggest that the tumor suppressor RAI2 could be a potential target for the development of anti-cancer strategies in GC.

Macrophage-targeted Nanomedicine for Sepsis: Diagnosis and Therapy.

Sepsis is a syndrome involving complex pathophysiological and biochemical dysregulation. Nanotechnology can improve our understanding of the pathophysiology of sepsis and contribute to the development of novel diagnostic and therapeutic strategies to further reduce the risk of sepsis. Macrophages play a key role in the progression of sepsis, thus, macrophage-associated pathological processes are important targets for both diagnostic and treatment of sepsis. In this paper, we reviewed efforts in the past decade of nanotechnologybased solutions for manipulate macrophages in sepsis diagnosis and management according to the type of nanomaterial. We addressed the latest progress of nanoparticles targeting macrophages for early sepsis detection. Additionally, we summarized the unique advantages of macrophage-targeted nanoparticles in the treatment of sepsis. These nanoparticles can improve the dysregulation of inflammatory response in sepsis by inhibiting the release of inflammatory factors and regulating macrophage apoptosis, activity and polarization. Finally, we present future opportunities as well as challenges of novel diagnostic and therapeutic strategies with the aim of accelerating the clinical translation of nanomedicine for sepsis treatment.

Endoplasmic reticulum stress mediates the myeloid-derived immune suppression associated with cancer and infectious disease.

Myeloid-derived suppressor cells (MDSCs), which are immature heterogeneous bone marrow cells, have been described as potent immune regulators in human and murine cancer models. The distribution of MDSCs varies across organs and is divided into three subpopulations: granulocytic MDSCs or polymorphonuclear MDSCs (G-MDSCs or PMN-MDSCs), monocytic MDSCs (M-MDSCs), as well as a recently identified early precursor MDSC (eMDSCs) in humans. Activated MDSCs induce the inactivation of NK cells, CD4+, and CD8+ T cells through a variety of mechanisms, thus promoting the formation of tumor immunosuppressive microenvironment. ER stress plays an important protecting role in the survival of MDSC, which aggravates the immunosuppression in tumors. In addition, ferroptosis can promote an anti-tumor immune response by reversing the immunosuppressive microenvironment. This review summarizes immune suppression by MDSCs with a focus on the role of endoplasmic reticulum stress-mediated immune suppression in cancer and infectious disease, in particular leprosy and tuberculosis.

CCL8 as a promising prognostic factor in diffuse large B-cell lymphoma via M2 macrophage interactions: A bioinformatic analysis of the tumor microenvironment.

Backgrounds: Prior investigations of the tumor microenvironment (TME) of diffuse large B-cell lymphoma (DLBCL) have shown that immune and stromal cells are key contributing factors to patients' outcome. However, challenges remain in finding reliable prognostic biomarkers based on cell infiltration. In this study, we attempted to shed some light on chemokine C-C motif chemokine ligand 8 (CCL8) in DLBCL via interaction with M2 macrophages. Methods: The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to evaluate immune and stromal scores from transcriptomic profiles of 443 DLBCL samples from The Cancer Genome Atlas (TCGA) and GSE10846 datasets. Immune cell infiltration (ICI) clusters were obtained based on different immune cell infiltrations of each sample, and gene clusters were derived through differentially expressed genes (DEGs) between the distinct ICI clusters. Five immune-related hub genes related to overall survival (OS) and clinical stages were obtained by COX regression analysis and protein-protein interaction (PPI) network construction then verified by quantitative real-time PCR (qPCR) and immunofluorescence staining in the FFPE tissues. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and TIMER websites were employed to explore the biological functions of CCL8-related DEGs. Uni- and multivariable Cox regression analyses were performed to analyze CCL8 as an independent prognostic risk factor in GSE10846 and were verified in other independent GEO cohorts. Results: A higher stromal score was associated with favorable prognosis in DLBCL. Patients in the ICI B cluster and gene B clusters had a better follow-up status with a higher programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) expression. Most of ICI-related DEGs were enriched for immune-related signaling pathways. Five hub genes with a distinct prognosis association were identified, including CD163, which is a biomarker of M2 macrophages, and CCL8. Abundant M2 macrophages were discovered in the high-CCL8 expression group. The functional analysis indicated that CCL8 is a key component of immune-related processes and secretory granule groups. Cox regression analysis and data from other GSE datasets yielded additional evidence of the prognostic value of CCL8 in DLBCL. Conclusions: CCL8 has been implicated in macrophage recruitment in several solid tumors, and only a few reports have been published on the role of CCL8 in the pathogenesis of hematological malignancies. This article attempted to find out TME-related genes that associated with the survival in DLBCL patients. CCL8 was identified to be involved in immune activities. Importantly, a series of bioinformatics analysis indicated that CCL8 might become an effective target for DLBCL, which interacts with M2 macrophage and immune checkpoint. The potential related mechanisms need to be further elucidated.

Three-Dimensional Silk Fibroin/Chitosan Based Microscaffold for Anticancer Drug Screening.

Traditional monolayer cell cultures often fail to accurately predict the anticancer activity of drug candidates, as they do not recapitulate the natural microenvironment. Recently, three-dimensional (3D) culture systems have been increasingly applied to cancer research and drug screening. Materials with good biocompatibility are crucial to create a 3D tumor microenvironment involved in such systems. In this study, natural silk fibroin (SF) and chitosan (CS) were selected as the raw materials to fabricate 3D microscaffolds; Besides, sodium tripolyphosphate (TPP), and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) were used as cross-linking agents. The physicochemical properties of obtained scaffolds were characterized with kinds of testing methods, including emission scanning electron microscopy, x-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, water absorption, and swelling ratio analysis. Cancer cell lines (LoVo and MDA-MB-231) were then seeded on scaffolds for biocompatibility examination and drug sensitivity tests. SEM results showed that EDC cross-linked scaffolds had smaller and more uniform pores with great interconnection than the TPP cross-linked scaffolds, and the EDC cross-linked scaffold exhibited a water absorption ratio around 1000% and a swelling ratio of about 72%. These spatial structures and physical properties could provide more adhesion sites and sufficient nutrients for cell growth. Moreover, both LoVo and MDA-MB-231 cells cultured on the EDC cross-linked scaffold exhibited good adhesion and spreading. CCK8 results showed that increased chemotherapeutic drug sensitivity was observed in 3D culture compared with 2D culture, particularly in the condition of low drug dose (<1  µ M). The proposed SF/CS microscaffold can provide a promising in vitro platform for the efficacy prediction and sensitivity screening of anticancer drugs.

Reconstruction of the Defect at Temporal Hairline by a Scalp Keystone Island Flap: Clinical Experience on 14 Cases.

BACKGROUND: The reconstructions of defects at the temporal hairline always require more complicated designs and higher surgical skills to acquire better aesthetic results. By taking advantage of the unique anatomy of the temporal region, the authors designed a scalp keystone island flap pedicled by superficial temporal fascia to repair defects on the temporal hairline. METHODS: The authors retrospectively analyzed the clinical data of 14 patients who had lesions adjacent to the temporal hairline between April 2018 and June 2020. Patients were diagnosed with basal cell carcinoma, squamous-cell carcinoma, or seborrheic keratosis. These lesions were resected and reconstructed by scalp keystone island flaps. The defects ranged from 2.0 cm × 1.5 cm to 3.0 cm × 3.5 cm. RESULTS: All patients were satisfied with postoperative morphology and reported no recurrence at the 6 to 24 months follow-up. Flaps in two patients were partially necrosed but eventually healed by dressing changes. The rest had the first intention of healing. CONCLUSIONS: The scalp keystone island flap is a very useful method to repair small or medium defects at the temporal hairline. This flap can be flexibly designed and easily performed with a high survival rate and good aesthetic results. It provides another surgical option for complicated reconstruction.

Expression and prognostic value of E2F3 transcription factor in non-small cell lung cancer.

E2F transcription factor 3 (E2F3) plays a vital role in the development of various types of cancer. To verify whether E2F3 is a suitable biomarker for the prognosis of lung cancer, bioinformatics analysis was performed to determine the differential expression level of E2F3 in lung cancer and the surrounding non-tumor tissues, and the results were confirmed in a NSCLC cell line and a tissue microarray (TMA). The relevance of E2F3 in non-small cell lung cancer (NSCLC) was investigated in 19 studies from the Oncomine database and confirmed in The Cancer Genome Atlas database. In the lung cancer cell line A549, the inhibition of E2F3 mRNA expression level led to decreased tumor cell viability and cell migration, which was determined by a Cell Counting Kit-8 and wound healing assays, respectively. Immunohistochemistry analyses of E2F3, Bcl-2, Bax and caspase-3 were performed in the NSCLC TMA (n=50). The assessment of TMA detected the increase of E2F3 protein expression level in the tumor tissues, as compared with that in the non-tumor tissues, which was also correlated with the increase in expression of Bcl-2 in tumors. Analysis of the clinical data from patients with NSCLC revealed that the overexpression of E2F3 was associated with early lymphatic spreading, and poor patient survival time. The OncomiR website was used to predict the E2F3 upstream microRNAs and determine their prognostic value in patients with NSCLC. The results from the present study revealed that E2F3 was overexpressed at both the transcriptional and translational levels in NSCLC tissues, as compared with that in non-tumor tissues. The overexpression of E2F3 was associated with the upregulation of the anti-apoptotic factor, Bcl-2, which may contribute to uncontrolled tumor growth. Thus, E2F3 was shown to have important oncogenic properties in the development of NSCLC, and it may become a potential biomarker for patients with NSCLC.

A literature review on function and regulation mechanism of DKK4.

Dickkopf-related protein 4 (DKK4) is a member of the dickkopf family and an inhibitor of the Wnt/ß-catenin signalling pathway. This review surveyed the single nucleotide polymorphisms (SNPs), copy number variations (CNVs), hypermethylation, regulation mechanism, correlation with clinicopathological parameters and chemotherapeutic resistance of DKK4. The signal pathways involved in DKK4 mainly include Wnt/ß-catenin pathway and Wnt-JNK pathway independent ß-catenin. DKK4 expression was upregulated in Renal Cell Carcinoma (RCC), Colorectal Cancer, Gastric Cancer (GC), Non-small Cell Lung Cancer (NSCLC) and Epithelial Ovarian Cancer (EOC), while downregulated in Hepatocellular Carcinoma (HCC). DKK4 is not only involved in tumour growth, invasion, migration and chemotherapy resistance, but also in osteoblastogenesis and secondary hair or meibomian gland formation. DKK4 has also been linked to schizophrenia.

microRNA­196a­3p inhibits cell proliferation and promotes cell apoptosis by targeting ADP ribosylation factor 4 in diffuse large B­cell lymphoma.

Diffuse large B­cell lymphoma (DLBCL) is the most prevalent type of non­Hodgkin's lymphoma with a heterogeneous molecular pathogenesis and aggressive clinical manifestations. The aim of the present study was to investigate the role of miR­196a­3p and its target gene in the development and progression of DLBCL. RT­qPCR was used to detect the miR­196a­3p expression level in human DLBCL cell lines and DLBCL pathological tissues and compare them with the normal control. The clinical significance of the miR­196a­3p expression was also analyzed in DLBCL patients. Next, the effect of miR­196a­3p overexpression on the cell cycle, apoptosis, and proliferation of DLBCL cells was evaluated. To explore its underlying mechanism, the target gene of miR­196a­3p was predicted and validated using bioinformatics and molecular biological approaches. Finally, the expression of this target gene in clinical specimens and its correlation with clinicopathological characteristics were determined. The decreased expression of miR­196a­3p was validated in DLBCL, with further analysis proving that it was correlated with poor prognosis. It was shown that the overexpression of miR­196a­3p was associated with cell cycle arrest, enhanced apoptosis, and inhibited proliferation in DLBCL cells. Furthermore, ADP ribosylation factor 4 (ARF4) was verified as the downstream target gene of miR­196a­3p. Similar to miR­196a­3p restoration in vitro, endogenous ARF4­knockdown was proven to inhibit cell proliferation through cell cycle arrest and elevate apoptosis in DLBCL. The present results indicated that miR­196a­3p downregulation contributed to the tumorigenesis of DLBCL by targeting ARF4 expression, which may be used as a novel prognostic marker or potential molecular therapeutic target for DLBCL management in the future.

TGF-ß1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression.

Transforming growth factor-ß1 (TGF-ß1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-ß1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-ß1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-ß1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-ß1 contributes to the progression of PCa.

Hydrochloride fasudil attenuates brain injury in ICH rats.

AIM: The aim of this study was to investigate the neuroprotective effects of hydrochloride fasudil (HF) in rats following intracerebral hemorrhage (ICH). METHODS: Male Wistar rats were randomly divided into four groups: normal, sham-operated, ICH, and ICH/HF. ICH was induced by injection of non-anticoagulant autologous arterial blood into the right caudate nucleus. The levels of Rho-associated protein kinase 2 (ROCK2) mRNA and protein around the site of the hematoma were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The levels of interleukin-6 and tumor necrosis factor-α in serum were detected by ELISA. The inflammatory cells and changes in the neuronal morphology around the hematoma were visualized using hematoxylin and eosin and Nissl staining. Brain edema was measured by comparing wet and dry brain weights. RESULTS: Following ICH, the levels of ROCK2 were significantly increased from day 1 to day 7. The levels of ROCK2 were significantly lower in rats treated with HF than in controls. The levels of inflammatory cytokines and brain water content were significantly higher in rats treated with HF than in controls. Administration of HF significantly reduced the levels of inflammatory cytokines and brain water content from day 1 to day 7. In the acute phase of ICH, a large number of neutrophils infiltrated the perihematomal areas. In comparison with the ICH group, the ICH/HF group showed markedly fewer infiltrating neutrophils on day 1. Nissl staining showed that ICH caused neuronal death and loss of neurons in the perihematomal areas at all time points and that treatment with HF significantly attenuated neuronal loss. CONCLUSIONS: HF exerts neuroprotective effects in ICH rats by inhibiting the expression of ROCK2, reducing neutrophil infiltration and production of inflammatory cytokines, decreasing brain edema, and attenuating loss of neurons.

MiR-7e-5p downregulation promotes transformation of low-grade follicular lymphoma to aggressive lymphoma by modulating an immunosuppressive stroma through the upregulation of FasL in M1 macrophages.

BACKGROUND: In follicular lymphoma (FL), histologic transformation to high-grade FL and diffuse large B-cell lymphoma (DLBCL) is a critical adverse step in disease progression. Activation of the oncogene c-MYC and tumor microenvironment remodeling account for FL progression. A panel of microRNA (miRNA) was downregulated in transformed FL (tFL). METHODS: Differentially expressed miRNAs were systematically compared in 11 lymph nodes from patients at different stages of disease. Expression of miR-7e-5p was analyzed in 46 B-cell lymphomas, including 30 FL tissues and 16 DLBCL tissues. In FL cells, transcriptional regulation of the oncogene c-MYC on its target miR-7e-5p was revealed by Chromatin Immunoprecipitation (ChIP) assay. Exosome, carrying differentially expressed miR-7e-5p was isolated and visualized by transmission electron microscope and fluorescence tracing. The effect of miR-7e-5p on recipient macrophage was determined by target gene quantification, flow cytometry, and TUNEL method in a cocultured system with miR-7e-5p-mimics or inhibitors treatment. Expression of miR-7e-5p targets, macrophage proportions, and clinical parameters were included for correlation analysis. RESULTS: We determined that downregulation of miR-7e-5p, driven by c-MYC overexpression, was associated with poorer prognosis in FL patients. The decreased expression of miR-7e-5p in lymphoma cells led to a reduced exosomal transfer to surrounding macrophages. As a result, the target gene of miR-7e-5p, Fas ligand (FasL), was upregulated and activated the caspase signaling, which led to the apoptosis of M1 macrophages in tumor stroma. Finally, in transformed FL tissues, overexpression of FasL and activation of caspase proteins was detected in tumor stromal macrophages. Downregulation of miR-7e-5p was associated with poorer clinical outcomes. CONCLUSION: Downregulation of exosomal miR-7e-5p induces stromal M1 macrophage apoptosis, which leads to immunosurveillance and transformation of FL.

A Method to Reproduce Symmetry in Midfacial Reconstruction: A Report of 19 Cases.

BACKGROUND: Reconstruction of facial skin defects remains a clinical challenge. With aging, ptosis of tissue over fixed structures creates an important facial feature known as the tear trough. This study aimed to evaluate the efficacy and aesthetic outcome of a novel surgical technique that reproduced this facial feature while avoiding ectropion during midfacial skin defect repair. METHODS: Nineteen patients with midfacial skin defects received local flap reconstruction combined with an anchoring suture. The flap was designed in a unilateral pedicled V-Y pattern. When the flap was advanced to cover the defect, one or two sutures that connected the dermis of the flap with the infraorbital periosteum were made to reproduce the tear trough line. RESULTS: Midfacial defects were successfully repaired with the V-Y flap in all 19 patients. No lower eyelid ectropion or conspicuous scars were noted in any of the patients. Further, the tear trough was successfully reconstructed in each patient. Facial symmetry was maintained with static positioning and animation. CONCLUSIONS: The combination of local V-Y flap reconstruction with anchoring sutures to reproduce facial feature lines is an effective technique in midfacial skin defect repair.

Role of the autophagy-related marker LC3 expression in hepatocellular carcinoma: a meta-analysis.

BACKGROUND: Microtubule-associated protein 1 light chain 3 (LC3), an autophagic gene, has been reported as a vital marker for many diseases and cancers. However, the role of LC3 in hepatocellular carcinoma (HCC) was not still investigated. Therefore, we conducted a meta-analysis to examine the association of LC3 with its clinicopathological and prognostic in HCC. METHODS: We consulted the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure and Wan Fang databases for published studies on LC3 in HCC. Newcastle-Ottawa scale was used to screen the quality of the literature. The statistical analysis was calculated by STATA 14.2. RESULTS: Of the 1329 titles identified, 10 articles involving 949 patients in HCC were included in this meta-analysis. The results of our study show that increased LC3 expression is related to size of tumor, but not to gender, age, number of tumor, liver cirrhosis, HBsAg, TNM stage, alpha fetoprotein, vascular invasion and histological grade. Positive LC3 expression was associated with overall survival by pooled hazard ratio. CONCLUSIONS: This meta-analysis indicated that positive LC3 expression was related to size of tumor, and could predict prognosis in human hepatocellular carcinoma.

Oncolytic virotherapy armed with an engineered interfering lncRNA exhibits antitumor activity by blocking the epithelial mesenchymal transition in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has special characteristics of significant aggressiveness, and strong potential for metastasis and recurrence; currently there are no targeted drugs for TNBC. Abnormal activation of epithelial-mesenchymal transition (EMT) plays an important role in these malignant behaviors of TNBC. In the crosstalk among the multiple EMT-associated signaling pathways, many miRNAs participate in regulating pathway activity, where they act as "traffic lights" at the intersection of these pathways. In this study, we used miRNA microarray technology to detect differentially expressed miRNAs related to EMT in TNBC, and we identified and verified 9 highly expressed oncogenic miRNAs (OncomiRs). High expression of these OncomiRs in clinical breast cancer tissues affected the prognosis of patients, and inhibition of their expression blocked EMT in TNBC cell lines and suppressed cancer cell proliferation and migration. We constructed an oncolytic adenovirus (AdSVP-lncRNAi9) armed with an artificially-designed interfering lncRNA (lncRNAi9), which exhibited an activity to block EMT in TNBC cells by disrupting the functions of multiple OncomiRs; the efficacy of such a treatment for TNBC was demonstrated in cytology and animal experiments. This research provides a new candidate oncolytic virotherapy for treating highly malignant refractory TNBC.

Up-regulation of DcR3 in microbial toxins-stimulated HUVECs involves NF-κB signalling.

BACKGROUND: Sepsis is a severe condition characterised by the body's systemic inflammatory response to infection. The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc. RESULTS: In this study, we investigated the expression level of Decoy Receptor 3 (DcR3) and the mechanism of high expression in sepsis patients. Septic cell model experiments were performed by treating human umbilical vein endothelial cells (HUVECs) and Jurkat cells with lipopolysaccharide (LPS), lipoteichoic acid (LTA) and zymosan, respectively. SP600125, SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC) were used to inhibit JNK1/2, p38MAPK and NF-κB signalling pathways in septic cell model, respectively. These results showed that DcR3 levels were higher in sepsis group than control. DcR3 mRNA and protein levels in HUVECs were increased following treatment with LPS, LTA and zymosan, and also increased in Jurkat cells treated by LPS, but not by LTA or zymosan. When HUVECs were treated with the NF-κB inhibitor PDTC, DcR3 expression was decreased compared with controls. However, SP600125 and SB203580 had no effect on DcR3 mRNA or protein levels. CONCLUSIONS: The results indicated that DcR3 secretion proceeded through the NF-κB signalling pathway in HUVECs.

Clinical significance of decoy receptor 3 upregulation in patients with hepatitis B and liver fibrosis.

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.

Diagnostic value of decoy receptor 3 combined with procalcitonin and soluble urokinase-type plasminogen activator receptor for sepsis.

The levels of decoy receptor 3 (DcR3), soluble urokinase type plasminogen activator receptor (suPAR) and procalcitonin (PCT) are significantly increased in sepsis. We investigated the diagnostic value of DcR3 combined with suPAR and PCT in sepsis. Patients with sepsis, non-infectious systemic inflammatory response comprehensive syndrome (SIRS) and healthy controls were recruited according to the diagnostic standard. We measured DcR3, suPAR, PCT, interleukin-6 (IL-6) and C-reactive protein (CRP), and the diagnostic value was evaluated by receiver operating characteristics (ROC) curves. In our analysis, serum DcR3, suPAR and PCT levels of the sepsis group were significantly higher than those of the SIRS and control groups. However, IL-6, CRP and WBC showed no significant difference between the SIRS group and the sepsis group. The serum DcR3 level was positively correlated with the serum suPAR level (r = 0.37, p = 0.0022) and PCT level (r = 0.37, p = 0.0021). Using DcR3, suPAR and PCT to distinguish SIRS from sepsis, the area under the curve (AUC) values were 0.892, 0.778 and 0.692. When DcR3, suPAR and PCT combined were used for diagnosis of sepsis, the AUC was 0.933, at a cut-off point of 0.342. This combination improved the sensitivity and specificity of diagnosis of sepsis, suggesting that use of the combination of three indexes enhanced the efficiency of sepsis diagnosis.