Identification of a Novel Protein-Based Prognostic Model in Gastric Cancers.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. However, there are still no reliable biomarkers for the prognosis of this disease. This study aims to construct a robust protein-based prognostic prediction model for GC patients. The protein expression data and clinical information of GC patients were downloaded from the TCPA and TCGA databases, and the expressions of 218 proteins in 352 GC patients were analyzed using bioinformatics methods. Additionally, Kaplan-Meier (KM) survival analysis and univariate and multivariate Cox regression analysis were applied to screen the prognosis-related proteins for establishing the prognostic prediction risk model. Finally, five proteins, including NDRG1_pT346, SYK, P90RSK, TIGAR, and XBP1, were related to the risk prognosis of gastric cancer and were selected for model construction. Furthermore, a significant trend toward worse survival was found in the high-risk group (p = 1.495 × 10-7). The time-dependent ROC analysis indicated that the model had better specificity and sensitivity compared to the clinical features at 1, 2, and 3 years (AUC = 0.685, 0.673, and 0.665, respectively). Notably, the independent prognostic analysis results revealed that the model was an independent prognostic factor for GC patients. In conclusion, the robust protein-based model based on five proteins was established, and its potential benefits in the prognostic prediction of GC patients were demonstrated.

Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity.

INTRODUCTION: Berberrubine (BRB), an isoquinoline alkaloid, is a major constituent of medicinal plants Coptis chinensis Franch or Phellodendron chinense Schneid. BRB exhibits various pharmacological activities, whereas exposure to BRB may cause toxicity in experimental animals. METHODS: In this study, we thoroughly investigated the liver injury induced by BRB in mice and rats. To explore the underlying mechanism, a study of the metabolic activation of BRB was conducted. Furthermore, covalent modifications of cysteine residues of proteins were observed in liver homogenate samples of animals after exposure to BRB, by application of an exhaustive proteolytic digestion method. RESULTS: It was demonstrated that BRB-induced hepatotoxicities in a time- and dose-dependent manner, based on the biochemical parameters ALT and AST. H&E stained histopathological examination showed the occurrence of obvious edema in liver of mice after intraperitoneal (i.p.) administration of BRB at a single dose of 100 mg/kg. Slight hepatotoxicity was also observed in rats given the same doses of BRB after six weeks of gavage. As a result, four GSH adducts derived from reactive metabolites of BRB were detected in microsomal incubations with BRB fortified with GSH as a trapping agent. Moreover, four cys-based adducts derived from reaction of electrophilic metabolites of BBR with proteins were found in livers. CONCLUSION: These results suggested that the formation of protein adducts originating from metabolic activation of BRB could be a crucial factor of the mechanism of BRB-induced toxicities.

New withanolides from Physalis minima and their cytotoxicity against A375 human melanoma cells.

Seven previously undescribed withanolides, namely physaminilide A-G (1-7), and two artificial withanolides (8-9), along with 10 known analogues (10-19) were isolated from Physalis minima. The structures were established by spectroscopic analysis, including NMR and electronic circular dichroism (ECD) data. Cytotoxicity of all the isolates was evaluated against A375 human melanoma cells. Compounds 2, 5, 8, 10, 11 and 15 exhibited significant cytotoxic activities with IC50 values in the range of 1.2-9.4 µM.