No abstract

SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.

No abstract

Our findings suggest that MSC-like cells are components of the tumor microenvironment and provide proof for the origin of carcinoma-associated fibroblast, therefore may potentially be used as a target for gastric cancer diagnosis and therapy.

Background Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. Methods We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. Results After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. Conclusions The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

Reproductive and maturational nutritive needs are examples of situations in which alterations in circulating concentrations of estrogens are associated with changes in intestinal epithelial function. However, it is not clear that any of these effects is due to direct interaction of estrogen with intestinal epithelial estrogen receptors (ER). The experiments reported here were designed to determine whether the small intestinal epithelium contains functional ER and might, therefore, be an estrogen-responsive tissue. IEC-6 cells, a non-transformed line of cells isolated from rat small intestinal crypts, were used for many of the experiments, because they provide a pure preparation of crypt epithelial cells. IEC-6 cells were found to exhibit specific saturable binding of estradiol with a Kd of 5 x 10(-10) M and approximately 100 binding sites/cell. Reverse transcriptase-polymerase chain reaction demonstrated that IEC-6 cells as well as epithelial cells from each segment of the rat intestine (duodenum, jejunum, ileum, and colon) contained ER mRNA of the sequence determined from rat uterus. Estradiol was shown to stimulate IEC-6 cell c-fos mRNA content rapidly and transiently in a manner analogous to that which has been previously demonstrated for other estrogen-responsive tissues. These data demonstrate that intestinal epithelial cells contain ER capable of regulating gene transcription and provide the basis for future studies designed to elucidate the role of estrogens in the regulation of intestinal epithelial function and pathophysiology.

Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.

We sought to explore the treatment effects and the repair mechanisms of bone marrow derived mesenchymal stem cells (MSCs) during HCl-induced acute lung injury (ALI). MSCs were delivered through the tail veins of rats 24 h after intranasal instillation of HCl. The results showed that MSCs did not ameliorate the histopathologic changes of ALI and pulmonary fibrosis. We found that the activated Wnt/β-catenin signaling may regulate the differentiation of MSCs and is associated with lung fibroblasts activation, pulmonary fibrosis and tissue repair process in ALI rats. Immunofluorescence and histology analysis indicated that activated canonical Wnt/β-catenin signaling induced most MSCs to differentiate into myofibroblasts or fibroblasts in vivo. However, inhibition of Wnt/β-catenin signaling by Dickkopf-1 (DKK1) promotes epithelial differentiation of MSCs induced by native alveolar epithelial cells which are beneficial to repair the injured lung epithelium. Inhibition of Wnt/β-catenin signaling after MSCs transplantation ameliorated pulmonary fibrosis and improved pulmonary function which attenuated the lung injury. In vitro study, activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblasts markers, which was attenuated by DKK1. Furthermore, Wnt3α activated Wnt/β-catenin signaling in lung fibroblasts to enhance the expression of collagen I, vimentin and α-smooth muscle actin, but DKK1 attenuated these proteins expression. These findings demonstrated that canonical Wnt/β-catenin signaling plays a key role in regulating differentiation of MSCs in vivo or in vitro and the pathogenesis of fibrotic diseases. Our study suggested that inhibition of abnormal activated Wnt/β-catenin signaling would promote MSCs epithelial differentiation to repair lung injury and reduce pulmonary fibrosis.