Serum N-glycan markers for diagnosing liver fibrosis induced by hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV) infection is the primary cause of hepatitis with chronic HBV infection, which may develop into liver fibrosis, cirrhosis and hepatocellular carcinoma. Detection of early-stage fibrosis related to HBV infection is of great clinical significance to block the progression of liver lesion. Direct liver biopsy is regarded as the gold standard to detect and assess fibrosis; however, this method is invasive and prone to clinical sampling error. In order to address these issues, we attempted to find more convenient and effective serum markers for detecting HBV-induced early-stage liver fibrosis. AIM: To investigate serum N-glycan profiling related to HBV-induced liver fibrosis and verify multiparameter diagnostic models related to serum N-glycan changes. METHODS: N-glycan profiles from the sera of 432 HBV-infected patients with liver fibrosis were analyzed. Significant changed N-glycan levels (peaks) (P < 0.05) in different fibrosis stages were selected in the modeling group, and multiparameter diagnostic models were established based on changed N-glycan levels by logistic regression analysis. The receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic efficacy of N-glycans models. These models were then compared with the aspartate aminotransferase to platelet ratio index (APRI) , fibrosis index based on the four factors (FIB-4), glutamyltranspeptidase platelet albumin index (S index), GlycoCirrho-test, and GlycoFibro-test. Furthermore, we combined multiparameter diagnostic models with alanine aminotransferase (ALT) and platelet (PLT) tests and compared their diagnostic power. In addition, the diagnostic accuracy of N-glycan models was also verified in the validation group of patients. RESULTS: Multiparameter diagnostic models constructed based on N-glycan peak 1, 3, 4 and 8 could distinguish between different stages of liver fibrosis. The area under ROC curves (AUROCs) of Model A and Model B were 0.890 and 0.752, respectively differentiating fibrosis F0-F1 from F2-F4, and F0-F2 from F3-F4, and surpassing other serum panels. However, AUROC (0.747) in Model C used for the diagnosis of F4 from F0-F3 was lower than AUROC (0.795) in FIB-4. In combination with ALT and PLT, the multiparameter models showed better diagnostic power (AUROC = 0.912, 0.829, 0.885, respectively) when compared with other models. In the validation group, the AUROCs of the three combined models (0.929, 0.858, and 0.867, respectively) were still satisfactory. We also applied the combined models to distinguish adjacent fibrosis stages of 432 patients (F0-F1/F2/F3/F4), and the AUROCs were 0.917, 0.720 and 0.785. CONCLUSION: Multiparameter models based on serum N-glycans are effective supplementary markers to distinguish between adjacent fibrosis stages of patients caused by HBV, especially in combination with ALT and PLT.

Higher expression of circulating miR-182 as a novel biomarker for breast cancer.

MicroRNAs (miRNAs), present in the serum in a stable and reproducible manner, may be used as biomarkers for various diseases. Few studies have previously investigated circulating miRNAs in the peripheral blood of breast cancer (BC) patients. To identify the role of serum miR-182 levels in BC, the present study detected miR-182 levels in the serum of 46 BC patients and 58 controls, by quantitative PCR. The results showed that the serum miR-182 levels in BC patients were significantly higher compared with the serum of healthy controls (P<0.01). The miR-182 was also overexpressed in the BC tissues compared with the para-carcinoma tissues. Furthermore, the serum levels of miR-182 in the estrogen receptor (ER)-positive patients were considerably lower compared with those in the ER-negative patients. The serum levels of miR-182 in the progesterone receptor (PR)-positive patients were also found to be lower compared with those in the PR-negative patients. The current study highlights results consistent with miR-182 as a novel and valuable biomarker for the diagnosis of BC.

Tanshinone IIA reverses the malignant phenotype of SGC7901 gastric cancer cells.

BACKGROUNDS: Tanshinone IIA (TIIA), a phenanthrenequinone derivative extracted from Salvia miltiorrhiza BUNGE, has been reported to be a natural anti-cancer agent in a variety of tumor cells. However, the effect of TIIA on gastric cancer cells remains unknown. In the present study, we investigated the influence of TIIA on the malignant phenotype of SGC7901 gastric cancer cells. METHODS: Cells cultured in vitro were treated with TIIA (0, 1, 5, 10 µg/ml) and after incubation for different periods, cell proliferation was measured by MTT method and cell apoptosis and cell cycling were assessed by flow cytometry (FCM). The sensitivity of SGC7901 gastric cancer cells to anticancer chemotherapy was investigated with the MTT method, while cell migration and invasion were examined by wound-healing and transwell assays, respectively. RESULTS: TIIA (1, 5, 10 µg/ml) exerted powerful inhibitory effects on cell proliferation (P < 0.05, and P < 0.01), and this effect was time- and dose-dependent. FCM results showed that TIIA induced apoptosis of SGC7901 cells, reduced the number of cells in S phase and increased those in G0/G1 phase. TIIA also significantly increased the sensitivity of SGC7901 gastric cancer cells to ADR and Fu. Moreover, wound-healing and transwell assays showed that TIIA markedly decreased migratory and invasive abilities of SGC7901 cells. CONCLUSIONS: TIIA can reverse the malignant phenotype of SGC7901 gastric cancer cells, indicating that it may be a promising therapeutic agent.

(4R*,5R*)-Diethyl 2-(4-nitro-phen-yl)-1,3-dioxolane-4,5-dicarboxyl-ate.

In the title compound, C(15)H(17)NO(8), the nitro group is essentially coplanar with the aromatic ring [dihedral angle = 6.4 (3) Å]. The five-membered ring has a twist conformation. In the crystal, C-H⋯O inter-actions link the mol-ecules into a helical chain propagating along [010].

(4R*,5R*)-2-(4-Meth-oxy-phen-yl)-1,3-dioxolane-4,5-dicarboxamide.

In the title compound, C(12)H(14)N(2)O(5), the five-membered 1,3-dioxolane ring has a twisted conformation. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a two-dimensional network lying parallel to the ab plane. There are also C-H⋯π inter-actions present in the crystal structure.