ABSTRACT
Diabetic nephropathy (DN) is one of the complex and severe complications of diabetes mellitus (DM). Icariin (ICA) is a flavonoid extracted from the leaves and stems of Herba epimedii with a wide range of pharmacological effects, such as anti-osteoporosis, anti-fibrosis, anti-aging, anti-inflammation and antioxidation. The purpose of our study was to explore the renal protective effect of ICA on DN in mice and its possible mechanisms. ICR mice were exposed to STZ-induced DN. The kidney organ coefficient of mice was computed. 24 h UP in urine was measured. Serum FBG, Cr and BUN were detected. The content of MDA and the activities of SOD, CAT and GSH-Px in renal tissues were tested. HE staining, PAS staining, PASM staining and transmission electron microscopy were used to observe renal pathological changes. Furthermore, TLR4, p-NF-κB p65, TNF-α and IL-6 of renal tissues were assayed by immunohistochemistry and western blotting. Our results indicated that ICA observably optimized the renal organ coefficient, reduced the level of 24 h UP in urine, decreased the content of Cr, BUN in serum and MDA in renal tissues, promoted the activities of SOD, CAT and GSH-Px in renal tissues, and ameliorated pathological lesions of kidneys noticeably. Besides, ICA inhibited the expressions of TLR4, p-NF-κB p65, TNF-α and IL-6 remarkably in renal tissues. ICA, which might lighten the renal inflammatory response by suppressing the TLR4/NF-κB signal pathway, played a protective role in kidneys of STZ-induced DN mice.
Subject(s)
Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/prevention & control , Flavonoids/pharmacology , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Animals , Flavonoids/chemistry , Gene Expression Regulation/drug effects , Inflammation/drug therapy , Inflammation/etiology , Kidney/drug effects , Kidney/pathology , Male , Mice , Mice, Inbred ICR , NF-kappa B/genetics , Signal Transduction/drug effects , Toll-Like Receptor 4/geneticsABSTRACT
Nicotinamide phosphoribosyltransferase (NAMPT) possesses various functions in human cells, and altered NAMPT expression is associated with human carcinogenesis. The present study detected the expression of NAMPT in normal and cancerous breast tissues from 83 patients using immunohistochemistry, and analyzed its association with the clinicopathological and survival data of the patients. NAMPT was significantly overexpressed in the breast invasive ductal carcinoma tissues compared with adjacent normal mammary gland tissues. Upregulated NAMPT expression was associated with a larger tumor size, lymph node metastasis, advanced clinical tumor-node-metastasis stages, and estrogen receptor and progesterone receptor expression. Furthermore, NAMPT expression was associated with poor overall and disease-free survival in patients with breast cancer. In conclusion, NAMPT increased protein expression in tumor cells may contribute to the development and progression of breast invasive ductal carcinoma. Thus, detection of NAMPT expression might be useful as a biomarker for the early detection and prognosis prediction of breast cancer.
ABSTRACT
BACKGROUND: The different expression level of Dickkopf-1 (DKK-1) in different cancers shows that the function of DKK-1 depends on the histological type of the cancer cells and the tissue microenvironment. To our knowledge, the serum expression level of DKK-1 in breast cancer is little known. METHODS: Blood samples from 125 consecutive patients diagnosed with breast cancer and 53 control subjects from March 2008 to August 2013 were investigated. Serum DKK-1 expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall survival (OS) and relapse-free survival (RFS) analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. RESULTS: The mean serum level of DKK-1 in patients with breast cancer was 4.99 ± 1.50 ng/mL, and was significantly higher than that in healthy individuals (1.88 ± 0.81 ng/mL, P < 0.001). DKK-1 level correlated significantly with TNM stage (P = 0.009), tumor grade (P = 0.02), lymph node metastasis (P = 0.001), and expression of HER2 (P = 0.002). The DKK-1 expression level was classified as high or low in relation to the median value, and patients with breast cancer (n = 125) were divided into a high expression group (n = 63) and a low expression group (n = 62). The Kaplan-Meier method for survival analysis showed that the patients with a high serum DKK-1 level had a poorer OS (48.7% vs. 81.3%, p = 0.01) and RFS (24.3% vs. 71.6%, p = 0.003) than those with a low expression level. The multivariate Cox regression analysis indicated that serum DKK-1 level was independent prognostic factors for OS and RFS. CONCLUSIONS: Serum DKK-1 level can be used as a noninvasive biomarker for the prognosis of breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_161.
