Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice.

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSC) distinctive from MDSCs obtained without TDCA treatment (MDSC) in the spleen of septic mice.

MBD6 is a direct target of Oct4 and controls the stemness and differentiation of adipose tissue-derived stem cells.

Argonaute 2 (Ago2) is a pivotal regulator of cell fate in adult stem cells. Its expression is significantly downregulated in late passages of cells, concomitant with a prominent increase in Ago2 cytosolic localization in single cells. Nuclear localization of Ago2 is crucial for the survival, proliferation, and differentiation of hATSCs (human adipose tissue-derived stem cells), mediated by the specific binding of the regulatory regions of functional genes, which positively or negatively altered gene expression.

MicroRNA 486 is a potentially novel target for the treatment of spinal cord injury.

MicroRNAs have been shown to effectively regulate gene expression at the translational level. Recently, we identified novel microRNAs that were upregulated in a mouse model of spinal cord injury. Among those, we have focused on microRNA 486, which directly represses NeuroD6 expression through a conserved sequence in its untranslated region.

Silencing of miR20a is crucial for Ngn1-mediated neuroprotection in injured spinal cord.

MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI).

miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4.

Aims: Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Until recently, researchers have been primarily focused on identifying the cellular or chemical sources of neuropathic pain or have approached neuropathic pain via the basis of biological study. We investigated whether mmu-mir-23b (miR23b) infusion can alleviate pain by compensating for the abnormally downregulated miR23b by reducing the expression of its target gene, NADPH oxidase 4 (NOX4), a reactive oxygen species (ROS) family member overexpressed in neuropathic pain.

Nuclear Ago2/HSP60 contributes to broad spectrum of hATSCs function via Oct4 regulation.

Aims: Argonaute2 (Ago2) plays a fundamental role in microRNA-mediated gene regulation through its intrinsic endonuclease activity. In this study we demonstrate the novel functions and molecular mechanisms by which nuclear Ago2 directly regulates HSP (heat shock protein) 60 expression and stem cell self-renewal. HSP60 is a crucial regulator of ROS (reactive oxygen species), senescence, and apoptotic cell death in several tissues and cell types.

Crucial role of nuclear Ago2 for hUCB-MSCs differentiation and self-renewal via stemness control.

Aims: Argonaute2 (Ago2) has intrinsic endonuclease activity in microRNA processing that plays a fundamental role in gene regulation. In this study, we demonstrate novel functions and molecular mechanisms of nuclear Ago2 in the self-renewal and plasticity of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs).

Results: Nuclear Ago2 binds to a set of regulatory genes, including Ago2 itself, Oct4, Sox2, Nanog, GATA, STAT3, and β-catenin, that potentially target fundamental functions of stem cells.

Knockdown of the potential cancer stem-like cell marker Rex-1 improves chemotherapeutic effects in gliomas.

In the present study, we show that Rex-1 mRNA and protein are found at high levels in both 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-resistant glioma cell subpopulations and malignant glioblastoma multiforme (GBM) tissue. We used a combination therapy of small interfering RNA (siRNA) against Rex-1 (siRex-1) and BCNU to target GBM cells. Rex-1 siRNA/BCNU treatment resulted in growth inhibition and a diminished S phase.

Nuclear Argonaute 2 regulates adipose tissue-derived stem cell survival through direct control of miR10b and selenoprotein N1 expression.

Argonaute 2 (Ago2) has a leading function in miRNA-induced RNA silencing, a conserved gene regulatory mechanism in cells and organisms. miRNAs are critical for stem cell self-renewal, development, and other functions. Here, we report that nuclear Ago2, by binding to a specific region of functional genes, directly controls adipose tissue-derived stem cell (ATSC) survival in response to a critical dose of reactive oxygen species (ROS)-mediated oxidative cell damage or senescence.