[Retracted] microRNA‑574 inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting zinc finger E‑box‑binding homeobox 1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown in the cell invasion assays in Figs. 2C and 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal.

Safety risk management for low molecular weight process-related impurities in monoclonal antibody therapeutics: Categorization, risk assessment, testing strategy, and process development with leveraging clearance potential.

Process-related impurities (PRIs) derived from manufacturing process should be minimized in final drug product. ICH Q3A provides a regulatory road map for PRIs but excludes biologic drugs like monoclonal antibodies (mAbs) that contain biological PRIs (e.g.

microRNA‑574 inhibits cell proliferation and invasion in glioblastoma multiforme by directly targeting zinc finger E‑box‑binding homeobox 1.

Accumulated evidence has demonstrated that dysregulation of microRNAs (miRNAs) contributes to tumourigenesis and tumour development of glioblastoma multiforme (GBM). Therefore, miRNAs may be promising candidates in the development of prognosis biomarkers and effective therapeutic targets for patients with GBM. A number of studies have reported that miRNA‑574 (miR‑574) is aberrantly expressed in multiple types of human cancers.

Correlation of the expression of miR-146a in peripheral blood mononuclear cells of patients with ankylosing spondylitis and inflammatory factors.

We investigated the expression of miR-146a in peripheral blood mononuclear cell (PBMC) of patients with ankylosing spondylitis (AS) and its correlation with inflammatory factors to explore the clinical significance. In total 45 patients with AS were selected at the Weifang People's Hospital from June, 2014 to January, 2016. At the same time, 30 healthy volunteers were also selected to serve as control group.

Morphological features of IFN-γ-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity.

Human mesenchymal stromal cell (MSC) lines can vary significantly in their functional characteristics, and the effectiveness of MSC-based therapeutics may be realized by finding predictive features associated with MSC function. To identify features associated with immunosuppressive capacity in MSCs, we developed a robust in vitro assay that uses principal-component analysis to integrate multidimensional flow cytometry data into a single measurement of MSC-mediated inhibition of T-cell activation. We used this assay to correlate single-cell morphological data with overall immunosuppressive capacity in a cohort of MSC lines derived from different donors and manufacturing conditions.

Restoring immune tolerance in neuromyelitis optica: Part II.

Neuromyelitis optica spectrum disorder (NMO/SD) and its clinical variants have at their core the loss of immune tolerance to aquaporin-4 and perhaps other autoantigens. The characteristic phenotype is disruption of astrocyte function and demyelination of spinal cord, optic nerves, and particular brain regions. In this second of a 2-part article, we present further perspectives regarding the pathogenesis of NMO/SD and how this disease might be amenable to emerging technologies aimed at restoring immune tolerance to disease-implicated self-antigens.

Restoring immune tolerance in neuromyelitis optica: Part I.

Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials.

Combination Therapy Using IL-2/IL-2 Monoclonal Antibody Complexes, Rapamycin, and Islet Autoantigen Peptides Increases Regulatory T Cell Frequency and Protects against Spontaneous and Induced Type 1 Diabetes in Nonobese Diabetic Mice.

Regulatory T cells (Treg) play a crucial role in the maintenance of self-tolerance. In this study, we sought to expand Ag-specific Tregs in vivo and investigate whether the expanded Tregs can prevent or delay the development of type 1 diabetes (T1D) in the NOD mouse model. NOD mice were treated with a combination of IL-2/anti-IL-2 Ab complex, islet Ag peptide, and rapamycin.

Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models.

Multipotent mesenchymal stromal cells [also known as mesenchymal stem cells (MSCs)] are currently being studied as a cell-based treatment for inflammatory disorders. Experimental animal models of human immune-mediated diseases have been instrumental in establishing their immunosuppressive properties. In this review, we summarize recent studies examining the effectiveness of MSCs as immunotherapy in several widely-studied animal models, including type 1 diabetes, experimental autoimmune arthritis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, graft-vs-host disease, and systemic lupus erythematosus.

Assessment of immunosuppressive activity of human mesenchymal stem cells using murine antigen specific CD4 and CD8 T cells in vitro.

Introduction: Mesenchymal stem cells (MSCs) have immunosuppressive activity. They do not induce allospecific T cell responses, making them promising tools for reducing the severity of graft versus host disease (GVHD) as well as treating various immune diseases. Currently, there is a need in the MSC field to develop a robust in vitro bioassay which can characterize the immunosuppressive function of MSCs.

Evaluation of immunosuppressive function of regulatory T cells using a novel in vitro cytotoxicity assay.

Naturally occurring regulatory T cells (Tregs) play a pivotal role in the maintenance of self-tolerance due to their intrinsic immunosuppressive activity. Currently, a number of human clinical trials are being conducted to investigate the roles of Tregs in treating various immune-mediated disorders. Traditionally, the suppressive activity of Tregs is measured using either a thymidine incorporation assay, which is a radioactive assay; or CFSE based flow cytometry assay, which requires a relatively large number of cells.

Regulation of xenogeneic porcine pancreatic islets.

The use of xenogeneic porcine pancreatic islets has been shown to be a potentially promising alternative to using human allogeneic islets to treat insulin-dependent type 1 diabetes (T1D). This article provides an overview of the existing FDA regulatory framework that would be applied to the regulation of clinical trials utilizing xenogeneic porcine pancreatic islets to treat T1D.

The apoptotic pathway contributing to the deletion of naive CD8 T cells during the induction of peripheral tolerance to a cross-presented self-antigen.

The maintenance of T cell tolerance in the periphery proceeds through several mechanisms, including anergy, immuno-regulation, and deletion via apoptosis. We examined the mechanism underlying the induction of CD8 T cell peripheral tolerance to a self-Ag expressed on pancreatic islet beta-cells. Following adoptive transfer, Ag-specific clone 4 T cells underwent deletion independently of extrinsic death receptors, including Fas, TNFR1, or TNFR2.

N-terminal trimer extension of nominal CD8 T cell epitopes is sufficient to promote cross-presentation to cognate CD8 T cells in vivo.

Cross-priming is the process in which Ag-presenting dendritic cells (DCs) acquire, process, and present Ags scavenged from other cells, and use these cells to activate naive CD8 T cells. Cross-priming of cognate CD8 cells can result in either tolerance or immunity, depending upon the activation status of the Ag-presenting DC. Previous studies have shown that nominal peptide is inefficiently cross-presented and that proteins and large polypeptides that require proteasomal processing are the main source of naturally cross-presented Ags.

Tissue-resident memory CD8+ T cells can be deleted by soluble, but not cross-presented antigen.

Under noninflammatory conditions, both naive and central memory CD8 T cells can be eliminated in the periphery with either soluble peptide or cross-presented Ag. Here, we assess the tolerance susceptibility of tissue-resident memory CD8 T cells in mice to these two forms of tolerogen. Soluble peptide specifically eliminated the majority of memory CD8 cells present in both lymphoid and extralymphoid tissues including lung and liver, but was unable to reduce the number present in the CNS.

Regulation of expression of Bcl-2 protein family member Bim by T cell receptor triggering.

Bim, a proapoptotic BH3-only member of the Bcl-2 protein family, is required for central and peripheral deletion of T lymphocytes. Mechanisms regulating Bim activity in T cells remain poorly understood. We show that expression of Bim is up-regulated in human T cells after polyclonal or specific T cell receptor triggering.

Soluble factors released by virus specific activated cytotoxic T-lymphocytes induce apoptotic death of astroglioma cell lines.

Astrocytomas and astrogliomas represent the most common types of primary tumors in human central nervous system and are associated with high mortality due to the absence of efficient therapy. Here we demonstrate that, upon antigen-specific activation, cytotoxic T-lymphocytes (CTLs) secrete products that inhibit proliferation and induce apoptosis in a significant proportion of astroglioma cell lines. This effect is tumor specific in that normal cultured astrocytes do not develop apoptotic changes upon exposure to supernatant of activated CTLs.

Tetramer binding and secretion of interferon-gamma in response to antigenic stimulation are compatible with a range of affinities of MHC:TCR interaction and distinct programs of cytotoxic T-lymphocyte activation.

Tetramer staining and detection of IFN-gamma secretion in response to specific stimulation are widely used to quantify and isolate specific T-cells. However, it remains unclear how these assays reflect different functional outcomes of T-cell triggering with MHC:peptide ligands. An immunogenic EBV-derived A11-restricted CTL peptide epitope and its partially agonistic analogue trigger different programs of activation induced cell death (AICD) in specific CTLs.