TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway.

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) has been reported to regulate cell death pathways and is overexpressed in several types of cancers. In this study, we investigated whether high expression of TMBIM6 in breast cancer was significantly associated with cancer invasiveness. Knockdown of reduced proliferation and migration of invasive breast cancer cells through downregulation of the MAPK/ERK signaling pathway.

Efficient Neural Differentiation using Single-Cell Culture of Human Embryonic Stem Cells.

In vitro differentiation of human embryonic stem cells (hESCs) has transformed the ability to study human development on both biological and molecular levels and provided cells for use in regenerative applications. Standard approaches for hESC culture using colony type culture to maintain undifferentiated hESCs and embryoid body (EB) and rosette formation for differentiation into different germ layers are inefficient and time-consuming. Presented here is a single-cell culture method using hESCs instead of a colony-type culture.

GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells into Posterior Neural Progenitors.

Anterior-posterior (A-P) specification of the neural tube involves initial acquisition of anterior fate followed by the induction of posterior characteristics in the primitive anterior neuroectoderm. Several morphogens have been implicated in the regulation of A-P neural patterning; however, our understanding of the upstream regulators of these morphogens remains incomplete. Here, we show that the Krüppel-like zinc finger transcription factor GLI-Similar 3 (GLIS3) can direct differentiation of human embryonic stem cells (hESCs) into posterior neural progenitor cells in lieu of the default anterior pathway.

The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.

The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein.

Bax inhibitor-1 enhances survival and neuronal differentiation of embryonic stem cells via differential regulation of mitogen-activated protein kinases activities.

Bax inhibitor-1 (BI-1), a member of the BI-1 family of integral membrane proteins, was originally identified as an inhibitor of stress-induced cell death in mammalian cells. Previous studies have shown that the withdrawal of leukemia inhibitory factor (LIF) results in differentiation of the majority of mouse embryonic stem (mES) cells into various cell lineages, while some ES cells die within 3days. Thus, to investigate the function of BI-1 in ES cell survival and neuronal differentiation, we generated mES cell lines that overexpress BI-1 or a carboxy-terminal BI-1ΔC mutant.

Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model.

The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs).

Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice.

Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation.

Cytoprotective effect of eriodictyol in UV-irradiated keratinocytes via phosphatase-dependent modulation of both the p38 MAPK and Akt signaling pathways.

Although flavonoids exhibit a variety of beneficial biological activities, the exact molecular mechanism of the cellular effects is still not fully explained. In this study, we investigated the molecular mechanism of cytoprotective effect of eriodictyol in UV-irradiated keratinocytes. We found that treatment with eriodictyol effectively suppressed the UV-induced cell death of the keratinocytes, concomitant with the inhibition of pro-caspase-3 or pro-caspase-9 cleavage and the suppression of cytochrome C release.

The generation of iPS cells using non-viral magnetic nanoparticle based transfection.

Induced pluripotent stem (iPS) cells have been generated from various somatic cells; however, a major restriction of the technology is the use of potentially harmful genome-integrating viral DNAs. Here, without a viral vector, we generated iPS cells from fibroblasts using a non-viral magnetic nanoparticle-based transfection method that employs biodegradable cationic polymer PEI-coated super paramagnetic nanoparticles (NP). Our findings support the possible use of transient expression of iPS genes in somatic cells by magnet-based nanofection for efficient generation of iPS cells.

3,4-Dihydroxyflavone acts as an antioxidant and antiapoptotic agent to support bovine embryo development in vitro.

The effects of two antioxidants, superoxide dismutase (SOD) and the flavonoid 3,4-dihydroxyflavone (DHF), on bovine embryo development in vitro were examined. Blastocyst development, total cell and inner cell mass (ICM) numbers, intracellular levels of reactive oxygen species (ROS), apoptotic indices and gene expression levels were examined before and after treatment of day 2 bovine embryos (≥2-4 cells) with various concentrations of 3,4-DHF or SOD for 6 days. Statistical analysis was performed using analysis of variance, with significance defined at the P<0.

Differences between cellular and molecular profiles of induced pluripotent stem cells generated from mouse embryonic fibroblasts.

Induced pluripotent stem (iPS) cells are a new alternative for the development of patient-specific stem cells, and the aim of this study was to determine whether differences exist between the cellular and molecular profiles of iPS cells, generated using lentiviral vectors, compared to ES cells. The lentiviral infection efficiency differed according to the method of cell culture (adherent cells: 0.085%; suspended cells: 0.

Involvement of caspase-9 in autophagy-mediated cell survival pathway.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been considered for use in the prevention and treatment of cancer malignancy. FR122047 (FR) is known to have an anti-inflammatory effect, but the anticancer activity of the chemical has not yet been identified. In the present study, we could find that treatment of breast cancer MCF-7 cells with FR led to apoptosis accompanying with apparent activation of caspases.

A MAPK pathway is involved in the control of cortical granule reaction and mitosis during bovine fertilization.

In order to understand the mechanism by which mitogen-activated protein kinase (MAPK) regulates fertilization, we examined the effect of the MAPK pathway inhibitor U0126 on polyspermy, cortical granule reaction and mitosis in bovine oocytes during and after fertilization. Oocytes were treated with 30 microM U0126 for 30 min prior to insemination, or from 15 to 27 hr following insemination. Western blotting with antibodies that detect active, phosphorylated MAPK revealed that MAPK activity was decreased in U0126 treated oocytes.

Survivin protein expression in bovine follicular oocytes and their in vitro developmental competence.

This study examined the relationship between survivin expression and the stage of development of in vitro cultured bovine oocytes and embryos; and whether survivin expression is affected by the quality of cumulus-oocyte complexes (COCS) or the quality of pre-implantation embryos. A polyclonal antibody was prepared using recombinant bovine survivin protein. Expression of survivin mRNA and protein was analyzed by real-time quantitative RT-PCR and immunocytochemistry.

Survivin acts as anti-apoptotic factor during the development of bovine pre-implantation embryos.

Survivin, an inhibitor of apoptotic protein containing a single baculoviral inhibit apoptotic protein repeat domain, is a bifunctional protein that suppresses apoptosis and regulates cell division. Thus, we used double stranded RNA (dsRNA) interference to manipulate survivin expression in bovine embryos and analyze its role in blocking apoptosis and facilitating development of pre-implantation embryos. In vitro fertilized embryos (1-cell) were injected with survivin dsRNA, and expression of survivin mRNA was evaluated by real-time quantitative RT-PCR.