SYPL1 overexpression predicts poor prognosis of hepatocellular carcinoma and associates with epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide, which is mainly due to relapse and metastasis. Synaptophysin-like 1 (SYPL1), a member of SYP family proteins, exerts complicated functions, which prompted us to wonder whether SYPL1 contributed to HCC progress. Herein, we performed integrative experiments of quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis and immunohistochemistry (IHC), and found that SYPL1 overexpression in HCC tissues was closely correlated with several malignant clinicopathologic features of HCC. The results from IHC in serial sections of HCC tissues further indicated that SYPL1 expression was associated with epithelial-mesenchymal transition (EMT) biomarkers of HCC cells. Additionally, Kaplan-Meier survival analysis showed that SYPL1 overexpression was significantly associated with reduced overall survival (OS) (p<0.001) and disease-free survival (DFS) (p=0.002). Furthermore, univariate and multivariate Cox proportional hazards analysis identified SYPL1 as an independent prognostic factor for OS [hazard ratio (HR), 2.443, 95% confidence interval (CI), 1.429-4.177, p=0.001] and DFS (HR, 1.680, 95% CI=1.012-2.788, p=0.045) of HCC patients. Collectively, SYPL1 overexpression predicts poor prognosis of HCC and may associate with EMT of HCC cells. Therefore, SYPL1 could serve as a future novel biomarker and potential therapy target for HCC.

Sulodexide prevents diabetic nephropathy through inhibiting renal NF-κB activation and MCP-1 expression / 中华肾脏病杂志

Objective To study the effects of sulodexide on renal NF-κB activation and monocyte chemotactic protein 1 (MCP-1) expression in diabetic rats and elucidate the possible mechanism of sulodexide in preventing diabetic nephropathy (DN). Methods Wistar rats were fed with high-sucrose-high-fat diet and injected with a low dose of STZ (streptozotocin,35 mg/kg) into abdominal cavity to induce diabetes.DM rats were randomly divided into non-treated group of treatment,blood glucose (BG),triglyceride (TG),cholesterol,serum creatinine (Scr),urea nitrogen (BUN),24 h urinary albumin excretion (UAE) were measured.HE staining was performed in renal tissues for light microscopy examination of mean glomerular volume (MGV).MCP-1 expression was detected by immunohistochemical method.NF-κB activation was determined by Western blot. Results Compared with NC group,DM group and DMS group had significant elevated BG,TG and TC levels (all P＜0.01).There were no significant differences of BG,TG or TC levels between DM group and DMS group.Compared with NC group,DM group and DMS group had significant increased Scr,BUN,UAE levels (all P＜0.01).Scr,BUN,UAE levels were significantly lower in DMS group than those in DM group [(39.1±0.88) μmol/L vs (41.0±2.16) μmol/L,(9.12±1.06) mmol/L vs (9.87±0.19) mmol/L； (19.92±0.96) mg/24 h vs (25.99±0.52)mg/24 h,all P＜0.05].Compared with NC group,the MGV of DM group was significantly increased [(7.47±1.11)×105 μm3 vs (4.22±1.09)×105 μm3,P＜0.01].Compared with DM group,the MGA of DMS group was significantly reduced [(6.64±0.71)×105 μm3 vs (7.47±1.11)×105 μm3,P＜0.05],but was still increased compared with that of NC group (P＜0.01).Compared with NC group,the MCP-1 expression of DM group was significantly higher [(12.17±1.94)/HPF vs (1.19±0.70)/HPF,P＜0.01].MCP-1 expression in DSM group was significantly lower than that of DM group [(9.22± 1.61)/HPF vs (12.17±1.94)/HPF,P＜0.01],but still higher than that of control group (P＜0.01).Compared with NC group,the NF-κB activity was significantly higher in DM group [(0.89±0.07) vs (0.24±0.03),P＜0.01].Compared with DM group,NF-κB activity of DMS group was significantly lower [(0.27±0.01) vs (0.89±0.07),P＜0.01].There was no significant difference of NF-κB activity between DMS group and NC group. Conclusion Sulodexide has protective effects on diabetic nephropathy,and one of the mechanisms may involve the inhibition of NF-κB activation as well as the suppression of MCP-I expression.