(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Glutamate dehydrogenase inhibits tumor growth in gastric cancer through the Notch signaling pathway.

Glutamate dehydrogenase (GDH) is a key enzyme in glutaminolysis and can regulate allosteric functions. Immunohistochemical study found that GDH expressed in gastric cancer cell cytoplasm and membrane, and a few located in the nucleus, ranging from light yellow to tan to sepia. According to the analysis by Kaplan Meier survival curve and the Log-Rank test, the median survival of GDH high expression in patients was 51.7 months with 95% confidence intervals (CI) was 41.138-55.262. The expression level of GDH was significantly reduced after silencing GDH gene in gastric cancer cells and tissues. Further, after silencing GDH gene, gastric cancer cell migration and invasion ability were decreased significantly. Protein expression of. In addition, tumor growth was significantly reduced after silencing GDH gene. In vivo and in vitro experiments suggest that GDH can decrease gastric cancer cell migration and invasion, thus inhibiting tumor growth.

Serum Alkaline Phosphatase Predicts Poor Disease-Free Survival in Patients Receiving Radical Gastrectomy.

BACKGROUND Serum alkaline phosphatase (ALP) has been proved to be a negative prognostic factor for several malignancies, but its clinical significance in gastric cancer (GC) patients has not been sufficiently studied. In the present retrospective study, we investigated the effect of serum ALP on disease-free survival (DFS) after radical gastrectomy. MATERIAL AND METHODS We included 491 GC patients receiving radical gastrectomy at the Chinese People's Liberation Army 309th Hospital. Univariate and multivariate analyses were performed to determine factors influencing serum ALP and DFS. The changes in serum ALP and its clinical relevance were also analyzed using the log-rank test and Cox proportional hazards model. RESULTS There were 491 patients who met our inclusion and exclusion criteria. Pre-treatment serum ALP was elevated in 87 of these patients and was normal in the other 404 patients. Elevation of pre-treatment serum ALP was correlated with the tumor diameter (OR=2.642, P=0.017), TNM stage (OR=4.592, P=0.005), and T classification (OR=1.746, P=0.043). DFS was significantly different between patients with normal or elevated pre-treatment serum ALP (median 42.1 vs. 32.8 months, P=0.001) and multivariate analysis suggested pre-treatment serum ALP is an independent risk factor for poor DFS after radical gastrectomy (HR=2.035, P=0.021). In addition, removal of the primary tumor lesion led to an obvious decline in serum ALP activity (median 262 U/L vs. 152 U/L, P<0.001), and monitoring changes in serum ALP can help evaluate the risk of tumor relapse in GC patients (χ²=17.814, P<0.001). CONCLUSIONS Serum ALP is a good predictor of GC patient DFS after radical gastrectomy, and patients with elevated serum ALP have shorter relapse times.

Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis.

Nickel compounds have been found to be carcinogenic based upon epidemiological, animal and cell culture studies. Previous studies suggest that epigenetic mechanisms play a role in Nickel-induced carcinogenesis such as DNA methylation and histone modification. In this study, we investigated the role of microRNAs (miRNAs) in nickel-induced carcinogenesis. The expression of several miRNAs which may function as tumor suppressor genes revealed a strong downregulation of miR-203 in Ni3S2-transformed 16HBE cells (NSTCs). Meanwhile, we observed hypermethylation of CpGs in miR-203 promoter and first exon area, and proved that the hyper-methylated miR-203 was involved in the Nickel-induced tumorigenesis. Moreover, we identified that miR-203 may suppress the tumorigenesis at least in part through negatively regulating its target gene ABL1. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of Nickel-induced cancer.

Clinical observation of gastric bypass in treatment of type 2 diabetes.

BACKGROUND: Roux-en-Y gastric bypass (GBP) is the main surgical procedure used in type 2 diabetes. The objective of this study was to evaluate the different types of GBP in treatment of type 2 diabetes. METHODS: Patients with type 2 diabetes were randomly divided into two groups: those who underwent gastrojejunal loop anastomosis bypass and those who underwent gastrojejunal Roux-en-Y bypass. Blood glucose alterations, operation time, and operation complications were observed. RESULTS: Gastrojejunal loop anastomosis bypass and gastrojejunal Roux-en-Y bypass were both effective in the treatment of selected patients with type 2 diabetes. Compared with gastrojejunal Roux-en-Y bypass, gastrojejunal loop anastomosis bypass had the advantages of easier implementation, shorter operation time, and fewer operation complications. CONCLUSIONS: Gastrojejunal loop anastomosis is effective in treatment of type 2 diabetes. It is safe, easy to implement, and worthy of clinical popularization.

Effects of miR-541 on neurite outgrowth during neuronal differentiation.

MicroRNA (miRNAs) are short non-coding RNA molecules that downregulate gene expression at post-transcriptional level. miRNAs are post-transcriptional regulators of gene expression important for neuron development and function. This report demonstrated that a putative and chemically synthesized miRNA rno-mir-541 played an important role in the neuron development. Differentiation of PC12 cells with nerve growth factor (NGF) is associated with neurite outgrowth, a process that involves upregulation of Synapsin I. We predicted, detected and assessed the expression levels of a number of possible miRNAs for synapsin I in rats and our outcomes showed that rno-mir-541 was associated with rat synapsin I expression. miR-541, a brain specific miRNA, plays an important role in repressing neurite extension in cultured PC12 neurons. The neurites of PC12 cells was shortened drasticly as a result of the overexpression of rno-mir-541. In contrast, the neurites of PC12 cell developed well after the knockdown of rno-mir-541 by RNA interference. Our study showed that rno-mir-541 played an important role in neuron-cell proliferation and neurite outgrowth through suppressing the expression of its target gene synapsin I. Furthermore, the introduction of NGF causes downregulation of miR-541, de-repression of its target, Synapsin-I and allows for neuritogenesis. Thus, miR-541 functions in neuronal precursors as an endogenous conditional component between NGF and Synapsin-I.