Cheng X.,Huazhong University of Science and Technology |
He S.,Guilin Medical University |
He S.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair |
Yuan J.,Huazhong University of Science and Technology |
And 6 more authors.
Free Radical Biology and Medicine
A fundamental element of acute lung injury (ALI) is the inflammation that is part of the body's immune response to a variety of local or systemic stimuli. Lipoxins (LXs) are important endogenous lipids that mediate resolution of inflammation. Previously, we demonstrated that LXA4 reduced the LPS inhalation-induced pulmonary edema, neutrophil infiltration and TNF-α production in mice. With the same model, the current investigation focused on the role of the airway epithelium, a first-line barrier and a prime target of inhaled toxicants. We report that LXA4 strongly inhibited LPS-induced ALI in mice, in part by protecting the airway epithelium and preserving the E-cadherin expression and airway permeability. Using a cryo-imaging assay and fluorescence detection, LXA4 was shown to block LPS-induced ROS generation and preserve mitochondrial redox status both in vivo and in vitro. To further assess whether and how NF-E2-related factor 2 (Nrf2) was involved in the protective effect of LXA4, fluorescence resonance energy transfer (FRET) analysis was employed in human epithelial cell line (16HBE), to determine the relative distance between Nrf2 and its negative regulator or cytosolic inhibitor, Kelch-like ECH-associated protein 1 (Keap1). It provided us the evidence that LXA4 further promoted the dissociation of Nrf2 and Keap1 in LPS-treated 16HBE cells. The results also showed that LXA4 activates Nrf2 by phosphorylating it on Ser40 and triggering its nuclear translocation. Moreover, when the plasmid expression dominant negative mutation of Nrf2 was transfected as an inhibitor of wild-type Nrf2, the protective effect of LXA4 on E-cadherin expression was almost completely blocked. These results provide a new mechanism by which LXA4 inhibits LPS-induced ALI through Nrf2-mediated E-cadherin expression. © 2016 Elsevier Inc. All rights reserved. Source
Yang J.-J.,Guilin Medical University |
Hu Z.-G.,Guilin Medical University |
Shi W.-X.,Guilin Medical University |
Deng T.,Guilin Medical University |
And 3 more authors.
World Journal of Gastroenterology
AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer. METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters. RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009). CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients. © The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. Source
Zhu Q.,Nanjing Medical University |
Kang J.,Nanjing Medical University |
Miao H.,Nanjing Medical University |
Feng Y.,Nanjing Medical University |
And 8 more authors.
It has been reported that the effect of inflammatory cytokines on β-cell destruction in type 1 diabetes is concentration-dependent. However, the underlying mechanisms remain unclear. In the present study, we found that a high concentration of cytokines promoted apoptosis in the rat β-cell line INS-1, whereas a low concentration of cytokines had no effect. We also found that cytokines at a low concentration stimulated neutral ceramidase (NCDase) release via exosomes from INS-1 cells, whereas cytokines at a high concentration inhibited NCDase release. Furthermore, the results showed that the NCDase-containing exosomes isolated from the culture medium of INS-1 cells treated with cytokines at a low concentration inhibited apoptosis induced by a high concentration of cytokines. Finally, the results also showed that the protective action of NCDase in the exosomes on apoptosis was mediated by the generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 2. Taken together, these findings revealed a novel NCDase-S1P- phosphate-S1P receptor 2-dependent mechanism by which a low level of inflammatory cytokines protects pancreatic β-cells from apoptosis induced by a high level of inflammatory cytokines. © 2014 FEBS. Source
Liao W.,Guilin Medical University |
Liao W.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair |
Zhang J.,Medical University of South Carolina |
Zhu Q.,Nanjing Medical University |
And 12 more authors.
BACKGROUND: Preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cutoff value of NLR in several studies is not consistent. This study aims to investigate the correlation of preoperative NLR with clinicopathologic features and the prognosis in patients who have undergone resection for HCC. METHODS: Clinical data of 256 patients with HCC who underwent radical hepatectomy were retrospectively analyzed. The patients were divided into the low-NLR group (NLR ≤ 2.31) and the high-NLR group (NLR N 2.31). A univariate analysis was performed to assess clinicopathologic characteristics that influenced disease-free survival (DFS) and overall survival (OS) in patients. The significant variables were further analyzed by a multivariate analysis using Cox regression. The Kaplan-Meier method was used to assess the DFS and OS rate. RESULTS: The value of NLR was associated with tumor size, clinical tumor-node-metastasis (TNM) stage, portal vein tumor thrombus (PVTT), distant metastasis, and aspartate aminotransferase (AST) in HCC. NLR N 2.31, size of tumor N 5 cm, number of multiple tumors, III-IV of TNM stage, PVTT, distant metastasis, and AST N 40 U/l were predictors of poorer DFS and OS. NLR N 2.31, size of tumor N 5 cm, III-IV of TNM stage, and AST N 40 U/l were independent predictors of DFS and OS. CONCLUSION: Preoperative NLR N 2.31 was an adverse predictor of DFS and OS in HCC after hepatectomy. This study suggested that NLR might be a novel prognostic biomarker in HCC after curative resection. © 2014 Neoplasia Press. All rights reserved. Source
Yuan S.-G.,Guilin Medical University |
Yuan S.-G.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair |
Liao W.-J.,Guilin Medical University |
Liao W.-J.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair |
And 6 more authors.
Asian Pacific Journal of Cancer Prevention
Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (≥4cm), alpha-fetoprotein (≥100ng/ml), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041- 2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01- 2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients. Source