Incidence of hepatocellular carcinoma (HCC) is dramatically increasing and is the third cause of cancer death worldwide. One key approach to control HCC is chemoprevention by naturally occurring agents. This study aims at investigating the antitumor effect of oleanolic acid (OA) and the molecular mechanisms. BALB/c mice were injected subcutaneously with HepG2 cells to establish transplanted tumors. Apoptosis and cell cycle arrest-related markers and signaling cascades were determined by western blot, immunofluorescence, reverse transcriptase-polymerase chain reaction and flow cytometric analysis. OA exhibited inhibitory effect on HCC through induction of apoptosis and cell cycle arrest both in transplanted tumors and in HepG2 cells. OA induced apoptosis through mitochondrial pathway, evidenced by inhibition of Akt/mammalian target of rapamycin pathway, mitochondrial dysfunction, transient increase of adenosine triphosphate, increase of Bax/Bcl-2 ratio, increased release of cytochrome c and activation of caspase/poly (ADP-ribose) polymerase. Activation of mitochondrial apoptotic pathway may be due to reactive oxygen species generated by mitochondrial fatty acid oxidation, resulted from enhancement of lipolysis regulated by cyclic adenosine 3',5'-monophosphate response element-binding protein-hormone-sensitive lipase/peroxisome proliferator-activated receptor γ signaling. OA induced G2/M cell cycle arrest through p21-mediated downregulation of cyclin B1/cdc2. Cyclooxygenase-2 (COX-2) and p53 were involved in OA-exerted effect, and extracellular signal-regulated kinase-p53 signaling played a central role in OA-activated cascades responsible for apoptosis and cell cycle arrest. OA demonstrated significant antitumor activities in HCC in vivo and in vitro models. These data provide new insights into the mechanisms underlying the antitumor effect of OA.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. Although the clear mechanisms of DM and insulin resistance are still to be cleared, it has been well documented that reactive oxygen species (ROS) play a pivotal role in DM and multiple types of insulin resistance. For the past few years, natural substances have been shown to have the potential to treatment DM. Attention has been especially focused on plants rich in triterpenoids, which generally show antioxidant and antiglycation effect. In our previous studies, it was shown that oleanolic acid (OA), a natural triterpenoid and an aglycone of many saponins, is a potent antioxidant acting as not only a free radical-scavenger through direct chemical reactions but also as a biological molecule, which may enhance the antioxidant defenses. The present study aimed to investigate the potential antidiabetic effect of OA. Oleanolic acid showed a significant blood glucose-lowering and weight-losing effect in diabetic animals induced by streptozotocin (STZ). In the insulin resistant model, it was also shown that OA may promote insulin signal transduction and inhibit oxidative stress-induced hepatic insulin resistance and gluconeogenesis, in which process the phosphorylation of ERK and the protective effect on mitochondrial function may be involved. These findings may significantly better the understanding of the pharmacological actions of OA and advance therapeutic approaches to DM.

Dental pulp stem cells (DPSCs) were the most widely used seed cells in the field of neural regeneration and bone tissue engineering, due to their easily isolation, lack of ethical controversy, low immunogenicity and low rates of transplantation rejection. The purpose of this study was to investigate the role of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on neural differentiation of DPSCs in vitro. DPSCs were cultured in neural differentiation medium containing NGF and bFGF alone or combination for 7 days. Then neural genes and protein markers were analyzed using western blot and RT-PCR. Our study revealed that bFGF and NGF increased neural differentiation of DPSCs synergistically, compared with bFGF and NGF alone. The levels of Nestin, MAP-2, βIII-tubulin and GFAP were the most highest in the DPSCs + bFGF + NGF group. Our results suggested that bFGF and NGF signifiantly up-regulated the levels of Sirt1. After treatment with Sirt1 inhibitor, western blot, RT-PCR and immunofluorescence staining showed that neural genes and protein markers had markedly decreased. Additionally, the ERK and AKT signaling pathway played a key role in the neural differentiation of DPSCs stimulated with bFGF + NGF. These results suggested that manipulation of the ERK and AKT signaling pathway may be associated with the differentiation of bFGF and NGF treated DPSCs. Our date provided theoretical basis for DPSCs to treat neurological diseases and repair neuronal damage.

Dual-template imprinted polymer coated silicon nanoparticles with epitope imprinting achieved specific fluorescence diagnosis and targeted therapy of breast cancer cells.

BackgroundChrysanthemum, a leading ornamental species, does not tolerate salinity stress, although some of its related species do. The current level of understanding regarding the mechanisms underlying salinity tolerance in this botanical group is still limited.ResultsA comparison of the physiological responses to salinity stress was made between Chrysanthemum morifolium ‘Jinba’ and its more tolerant relatives Crossostephium chinense, Artemisia japonica and Chrysanthemum crassum. The stress induced a higher accumulation of Na+ and more reduction of K+ in C. morifolium than in C. chinense, C. crassum and A. japonica, which also showed higher K+/Na+ ratio. Homologs of an Na+/H+ antiporter (SOS1) were isolated from each species. The gene carried by the tolerant plants were more strongly induced by salt stress than those carried by the non-tolerant ones. When expressed heterologously, they also conferred a greater degree of tolerance to a yeast mutant lacking Na+-pumping ATPase and plasma membrane Na+/H+ antiporter activity. The data suggested that the products of AjSOS1, CrcSOS1 and CcSOS1 functioned more effectively as Na+ excluders than those of CmSOS1. Over expression of four SOS1s improves the salinity tolerance of transgenic plants and the overexpressing plants of SOS1s from salt tolerant plants were more tolerant than that from salt sensitive plants. In addition, the importance of certain AjSOS1 residues for effective ion transport activity and salinity tolerance was established by site-directed mutagenesis and heterologous expression in yeast.ConclusionsAjSOS1, CrcSOS1 and CcSOS1 have potential as transgenes for enhancing salinity tolerance. Some of the mutations identified here may offer opportunities to better understand the mechanistic basis of salinity tolerance in the chrysanthemum complex.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-016-0781-9) contains supplementary material, which is available to authorized users.