Gastric cancer is currently the second leading cause of cancer-related death worldwide, especially in Japan, Korea and China, and the 5-year survival rate of gastric cancer is less than 30%. Thus, it is important to shed more lights on novel agents to prevent gastric cancer or to improve survival rate of the patients. Vitamin D not only maintains calcium and bone homeostasis, but also mostly inhibits tumor genesis, invasion, and metastasis through activation of vitamin D receptor. Although epidemiological results are not consistent, accumulating evidence from gastric cancer cells, animal models, and clinical trials suggest that vitamin D deficiency may increase the risk and mortality of gastric cancer, but vitamin D supplement might be a safe and economical way to prevent or treat gastric cancer. Here, we reviewed the current studies on vitamin D and its receptor and focused on the pathogenic roles of their alterations in gastric tumorigenesis.

Abstract. It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) alleviated liver fibrosis. We investigated whether BMSCs transfected with human matrix metalloproteinase 1 (BMSCs/MMP1) would improve their therapeutic effect in liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats. BMSCs were transfected with an adenovirus carrying enhanced green fluorescence protein (GFP) and human MMP1 gene. BMSCs or BMSCs/MMP1 were directly injected into fibrotic rats via the tail vein. GFP-labeled cells appeared in the fibrotic liver after BMSC transplantation. The expression of BMSCs/MMP1 elevated levels of MMP1 in vitro. Although BMSC administration reduced liver fibrosis, transplantation of BMSCs/MMP1 enhanced the reduction of liver fibrosis to a higher level. Treatment with BMSCs/MMP1 not only decreased collagen content but also suppressed activation of hepatic stellate cells (HSCs) in fibrotic liver, which led to subsequent improvement of both liver injury and fibrosis. Treatment with BMSCs/MMP1 resulted in an improved therapeutic effect compared with BMSCs alone, which is probably because of the sustainably expressed MMP1 level in the liver. BMSCs/MMP1 transplantation not only improved biochemical parameters but also attenuated progression of liver fibrosis, suggesting that BMSCs may be a potential cell source in preventing liver fibrosis and MMP1 gene may enhance the anti-fibrotic effect of BMSCs.

Although K + channels are important in mediating the driving force for colonic ion transport, their role in small intestinal transport is poorly understood. To investigate this, small intestinal short circuit currents ( I sc ) and HCO 3 − secretion were measured in mice, and intracellular pH (pH i ) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption. We found that K V 7.1 is not involved in duodenal ion transport, while K Ca 3.1 selectively regulates duodenal I sc and HCO 3 − secretion in a Ca 2+ -mediated but not cAMP-mediated manner. Blockade of K Ca 3.1 increased the rate of HCO 3 − fluxes via cystic fibrosis transmembrane conductance regulator (CFTR) channels in SCBN cells. Jejunal I sc was significantly stimulated by glucose, but markedly inhibited by 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice. This study not only examines the contribution of various K + channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K + channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus.