Alterations of Notch/Jagged mRNA and protein expression after partial hepatectomy in rats.

OBJECTIVE: To investigate alterations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, the Notch/Jagged signaling pathway, and hepatocyte proliferation, and their correlation in rats subjected to partial hepatectomy. MATERIAL AND METHODS: Blood and liver tissues were sampled immediately (0), 5, 15, 30, 60, 180, 360, and 720 min, and 1, 2, 4, and 7 days after partial (70%) hepatectomy to measure plasma levels of TNF-alpha and IL-6, the expression of proliferating cell nuclear antigen (PCNA), Notch-1 and Jagged-1 protein, and mRNA in liver tissue. RESULTS: Systemic levels of IL-6 significantly correlated with the expression of PCNA in hepatocytes (p<0.05) after partial (70%) hepatectomy. The increased expression of Notch-1 protein was located in the sinusoidal endothelium, while Jagged-1 protein was predominantly located in bile duct cells. Expression of both proteins was increased around the portal vein. mRNA expression of Notch-1 decreased between 6 h and 2 days after partial hepatectomy, while Jagged-1 increased between 3 and 6 h, decreased between 12 h and 2 days, and normalized on day 4 after hepatectomy. CONCLUSIONS: Partial hepatectomy-induced hepatocyte proliferation was accompanied by an increase in systemic levels of IL-6, a pro-inflammatory response that plays a part in the proliferative process. The Notch/Jagged signaling pathways are activated and probably represent important contributors to the regenerative process following hepatectomy including both hepatocyte proliferation and bile duct formation and growth.

BRAF, K-ras and BAT26 mutations in colorectal polyps and stool.

AIM: To assess the feasibility of using BRAF, K-ras and BAT26 genes as stool-based molecular markers for detection of colorectal adenomas and hyperplastic polyps (HPs). METHODS: We applied PCR-SSCP and direct sequencing to detect BRAF mutations of polyps and paired stool samples. Primer-mediated restriction fragment length polymorphism (RFLP) analysis and mutant-enriched PCR were used in detection of K-ras mutations of polyp tissues and paired stool samples respectively. BAT26, a microsatellite instability marker was examined by detection of small unstable alleles in a poly (A) repeat. RESULTS: No genetic alterations were detected in the 36 colonoscopically normal patients in either tissues or stools. BRAF, K-ras and BAT26 mutations were found in 4 (16%), 10 (40%) and 3 (12%) of 25 adenoma tissues and among them, 75%, 80% and 100% of patients were observed to contain the same mutations in their corresponding stool samples. In HPs, mutations of BRAF and K-ras were detected in the tumor DNA of 2 (11.1%) and 8 (33.3%) of 18 patients respectively, all of whom had identical alterations in their stools. Taken together, the three genetic markers detected 15 (60%) of 25 adenomas and 8 (44.4%) of 18 HPs. The sensitivity of stool detection was 80% for adenomas and 100% for HPs with an overall specificity of 92% for adenomas and 100% for HPs. CONCLUSION: BRAF, K-ras and BAT26 genes have the potential to be molecular markers for colorectal adenomas and HPs, and can be used as non-invasive screening markers for colorectal polyps.

[Source Apportionment and Ecological Risk Assessment of Polycyclic Aromatic Hydrocarbons in Surface Water from Yangtze River, China: Based on PMF Model].

To study the features and ecological risk of PAHs in surface water from Yangtze River, 19 water samples were collected from the main stream and branch of Yangtze River in August 2015. Solid phase extraction method was used to extract PAHs, and the concentrations of the 16 priority PAHs were determined using GC-MS. The results indicated that the concentration of total PAHs (∑PAHs) in the surface water ranged from 17.7-110 ng·L-1 with an average value of 42.6 ng·L-1. The predominant PAHs in the water were PAHs with 2-3 rings, accounting for 67.7% of ∑PAHs. The results of molecular diagnostic ratios indicated that the origin of PAHs was mostly combustion sources, including fossil fuel and biomass combustion. PMF model was used to quantitatively acquire the source contribution of PAHs, which indicated that four sources were identified and their contribution rates were respectively biomass and coal combustion (40.1%), petroleum source (19.6%), traffic source (17.5%) and coke oven source (22.8%). The results of ecological risk assessment indicated that PAHs with 2-3 rings had a relatively high risk level, and Wujiang station and lower reach had a relatively high risk level based on risk quotient. Overall, the ecological risk of PAHs in the Yangtze River was at a relatively low level.

TET1 exerts its tumor suppressor function by interacting with p53-EZH2 pathway in gastric cancer.

TET1 protein is reported to suppress cancer invasion and metastasis in prostate and breast cancer while EZH2, a polycomb group protein, has been identified as an oncogene in many types of cancers including gastric cancer. Here we report that there is an inverse relation of the expression pattern of TET1 and EZH2 in both normal gastric mucosa and gastric cancer. In gastric mucosa, EZH2 is selectively expressed in the proliferating neck cells while TET1 and 5-hydroxymethyl-cytosine (5-hmc) exhibit very low expression in the neck cells. In contrast, TET1 and 5-hmc expression is high in gastric glandular epithelium while EZH2 expression is absent in this cell population. On the other hand, in proliferating Ki67-positive gastric cancer cells, EZH2 is highly expressed while TET1 and 5-hmc expression is significantly down-regulated. When the mouse homologue of human TET1 protein Tet1 is overexpressed in a gastric cancer cell line MGC-803, we observed the dramatically down-regulation of EZH2 in one-third of the Tet1 overexpressed cells. In addition, Tet1 overexpressing cells also lost the H3K27 trimethylation mark and the cell proliferation protein Ki67. Furthermore, Tet1 overexpression induced p53 tumor suppressor protein. The increase of p53 protein level is accompanied by the phosphorylation of p53 by activated DNA-PK. Together, these results suggested a mechanism by which TET1 suppresses cancer formation by coupling DNA demethylation with DNA-PK activation of p53 and suppression of oncogenic protein EZH2. Conversely, loss of TET1 and 5-hmc expression might contribute to EZH2 up-regulation during gastric cancer development.