WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4.

Pancreatic cancer (PC) is an aggressive malignant disease. Pancreatic ductal adenocarcinoma (PDAC) is a main type of PDAC. The inhibition of aerobic glycolysis in PC cells is one of the approaches to treat PDAC. WD repeat protein 79 (WDR79) acts as a scaffold protein and is involved in several physiological processes. Since WDR79 affects the progression of several types of cancers, whereas its role in PDAC remains unclear. This study was aimed to investigate the role of WDR79 in the progression of PDAC and clarify the mechanism. We found that WDR79 was highly expressed in PDAC cells. Knockdown of WDR79 inhibited the growth as well as the motility of PDAC cells, while overexpression of WDR79 contributed to the growth and motility. The ablation of WDR79 restrained aerobic glycolysis of PDAC cells. Mechanically, we found that WDR79 depletion increased SIRT4 expression by suppressing UHRF1 expression, which counteracted the function of WDR79 in PDAC. We thought that WDR79 could serve as a target for treating PDAC.

The effect of cadmium on the growth and antioxidant response for freshwater algae Chlorella vulgaris.

The objective of the present work was to evaluate the effect of exogenously applied cadmium on the physiological response of green algae Chlorella vulgaris. The study investigated the long-term effect (18 days) of cadmium on the levels of algae biomass, assimilation pigment composition, soluble protein, oxidative status (production of hydrogen peroxide and superoxide anion), antioxidant enzymes (such as superoxide dismutase, peroxidase, catalase and glutathione reductase enzyme) in C. vulgaris. The results showed that growth, the amount of chlorophyll a (Chl a), chlorophyll b (Chl b) and carotenoids gradually decreased with increasing cadmium over 18 days exposure. Cadmium at concentration of 7 mg L(-1) inhibited algal growth expressed as the number of cells. Our research found that C. vulgaris has a high tolerance to cadmium. Contents of chlorophylls (Chl a and Chl b) and carotenoids (Car) of C. vulgaris was significantly decline with rising concentration of cadmium (p < 0.05). The decrease of 54.04 and 93.37 % in Chl a, 60.65 and 74.32 % in Chl b, 50.00 and 71.88 % in total carotenoids was noticed following the treatment with 3 and 7 mg L(-1) cadmium doses compared with control treatment, respectively. Cadmium treatments caused a significant change in the physiological competence (calculated as chlorophyll a/b) which increased with increasing Cd(II) doses up to 1 mg L(-1) but decreased at 3 mg L(-1). While accumulation of soluble protein was enhanced by presence of cadmium, the treatment with cadmium at 3 and 7 mg L(-1) increased the concentration of soluble proteins by 88, 95.8 % in C. vulgaris, respectively. Moreover, low doses of cadmium stimulated enzymatic (superoxide dismutase, catalase and glutathione reductase) in C. vulgaris, The content of peroxidase increased with the increasing cadmium concentration, and had slightly decreased at the concentration of 7 mg L(-1), but was still higher than control group, which showed that cadmium stress at high concentration mainly peroxidase works in C. vulgaris. And therefore, suppressed reactive oxygen species (hydrogen peroxide and superoxide) accumulated. The present study also showed that cadmium increased oxidative stress and induced antioxidant defense systems against reactive oxygen species. The observation in here analyzed C. vulgaris after exposure to cadmium indicate that hydrogen peroxide, superoxide and peroxidase in the alga with exposure to Cd(II) seemed to be parameters as biomarkers for metal-induced oxidative stress.

Protective effects of curcumin in APPswe transfected SH-SY5Y cells.

The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to establish a cell model of Alzheimer's disease. Graded concentration and time course experiments demonstrate that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1 and ferritin expression, and that it significantly downregulates heme oxygenase 2, reactive oxygen species and amyloid-beta 40/42 expression. These effects of curcumin on PI3K, Akt and Nrf2 were blocked by LY294002 (PI3k inhibitor) and NF-E2-related factor-2 siRNA. The results indicate that the cytoprotection conferred by curcumin on APPswe transfected SH-SY5Y cells is mediated by its ability to regulate the balance between heme oxygenase 1 and 2 via the PI3K/Akt/Nrf2 intracellular signaling pathway.

Curcumin activates Wnt/ß-catenin signaling pathway through inhibiting the activity of GSK-3ß in APPswe transfected SY5Y cells.

Wnt/ß-catenin signaling pathway plays an important role in the genesis and development of Alzheimer's disease. The study aims to investigate the effect of Curcumin on the expression of GSK-3ß, ß-catenin and CyclinD1 in vitro, which are tightly correlated with Wnt/ß-catenin signaling pathway, and also to explore the mechanisms, which will provide a novel therapeutic intervention for treatment of Alzheimer's disease. Plasmid APPswe and BACE1-mychis were transiently co-transfected into SHSY5Y cells by Liposfectamin™2000. The cells were treated with Curcumin at 0, 1.25, 5.0, 20.0 µmol/L for 24 h, or with Curcumin at 5.0 µmol/L for 0, and 12, 24 and 48 h for time course assay. Cell lysates were collected for RT-PCR, Western blot assay and immunofluorescent staining were carried out for detecting the effect of Curcumin on the expression of GSK-3ß, ß-catenin and CyclinD1. RT-PCR and Western blot results showed that the expression of GSK-3ß mRNA and protein significantly decreased in the transfected cells treated with Curcumin, and that the changes were in a dose and time-dependent manner (P<0.05); however, the protein expression of GSK-3ß-Ser9 was increased (P<0.05). Meanwhile, the expressions of ß-catenin and transcriptional factors CyclinD1 mRNA and protein increased and the changes were also in a dose and time-dependent manner (P<0.05). Immunofluorescent staining results not only confirmed the above changes, but also showed that ß-catenin had translocated into the nucleus gradually with the increased dosage of Curcumin. Therefore, GSK-3ß is a potential target for treatment of AD. Curcumin could activate the Wnt/ß-catenin signaling pathway through inhibiting the expression of GSK-3ß and inducing the expression of ß-catenin and CyclinD1, which will provide a new theory for treatment of neurodegenerative diseases by Curcumin.