Search results for "Gli"

Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.

2018

Abstract Background: Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients. Aim: To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS. Methods: We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways a…

Dual role of the RNA helicase DDX5 in post-transcriptional regulation of Myelin Basic Protein in oligodendrocytes

2017

In the central nervous system, oligodendroglial expression of Myelin Basic Protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly on the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (alias p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes. Manipulation of DDX5 protein amounts inversely affects levels of MBP protein. We present evid…

First report on the presence of Alloxan in bleached flour by LC-MS/MS method

2017

Abstract In this work the presence of Alloxan in bread, pastry and cake bleached flour was investigate in order to verify possible risk for consumers related to the use of chemicals for flour bleaching. A selective UHPLC–MS/MS method has been developed and validated for the purpose. Alloxan is one of the possible minor side products of oxidation after chemical bleaching of wheat flours, when several chemical agents are used. One hundred and seventy-five flour samples were analyzed for Alloxan determination. The validation of the method was performed in accordance with the ISO/IEC/EN 17025 for linearity, detection limit, quantification limit, accuracy, precision and ruggedness determination.…

Novel Microglia Depletion Systems: A Genetic Approach Utilizing Conditional Diphtheria Toxin Receptor Expression and a Pharmacological Model Based on…

2019

Microglia are the main population of macrophage residing in the central nervous system (CNS). Depletion experiments gave important insights into the physiology and function of microglia in healthy and diseased CNS. Ablation of microglia can be achieved by application of pharmacological or genetic tools. Here, we describe two approaches to ablate microglia: an efficient genetic model that utilizes DTRMG mouse line that has diphtheria toxin receptor (DTR) expression regulated by the promoter activity of the fractalkine receptor (CX3CR1) gene, and a pharmacological model that utilizes the blocking of macrophage colony-stimulating factor 1 receptor (CSF-1R) with a blocking antibody. Both the ad…

Identification of novel drug resistance mechanisms by genomic and transcriptomic profiling of glioblastoma cells with mutation-activated EGFR.

2021

Abstract Aims Epidermal growth factor receptor (EGFR) is not only involved in carcinogenesis, but also in chemoresistance. We characterized U87.MGΔEGFR glioblastoma cells with constitutively active EGFR due to deletion at the ligand binding domain in terms of gene expression profiling and chromosomal aberrations. Wild-type U87.MG cells served as control. Materials and methods RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed to identify novel drug resistance mechanisms related to expression of mutation activated EGFR. Chromosomal aberrations were characterized by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (…

2018

There is a growing evidence that antimalarial chloroquine could be re-purposed for cancer treatment. A dozen of clinical trials have been initiated within the past 10 years to test the potential of chloroquine as an adjuvant treatment for therapy-refractory cancers including glioblastoma, one of the most aggressive human cancers. While there is considerable evidence for the efficacy and safety of chloroquine the mechanisms underlying the tumor suppressive actions of this drug remain elusive. Up until recently, inhibition of the late stage of autophagy was thought to be the major mechanism of chloroquine-mediated cancer cells death. However, recent research provided compelling evidence that …

Retinal homeobox promotes cell growth, proliferation and survival of mushroom body neuroblasts in the Drosophila brain.

2016

Abstract The Drosophila mushroom bodies, centers of olfactory learning and memory in the fly ‘forebrain’, develop from a set of neural stem cells (neuroblasts) that generate a large number of Kenyon cells (KCs) during sustained cell divisions from embryonic to late pupal stage. We show that retinal homeobox ( rx ), encoding for an evolutionarily conserved transcription factor, is required for proper development of the mushroom bodies. Throughout development rx is expressed in mushroom body neuroblasts (MBNBs), their ganglion mother cells (MB-GMCs) and young KCs. In the absence of rx function, MBNBs form correctly but exhibit a reduction in cell size and mitotic activity, whereas overexpress…

Targeting CD52 does not affect murine neuron and microglia function.

2020

The humanized anti-CD52 antibody alemtuzumab is successfully used in the treatment of multiple sclerosis (MS) and is thought to exert most of its therapeutic action by depletion and repopulation of mainly B and T lymphocytes. Although neuroprotective effects of alemtuzumab have been suggested, direct effects of anti-CD52 treatment on glial cells and neurons within the CNS itself have not been investigated so far. Here, we show CD52 expression in murine neurons, astrocytes and microglia, both in vitro and in vivo. As expected, anti CD52-treatment caused profound lymphopenia and improved disease symptoms in mice subjected to experimental autoimmune encephalomyelitis (EAE). CD52 blockade also …

Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarc…

2019

Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. Methods and results The mechanisms underlying Shh pathway func…

Genome-wide association study between CNVs and milk production traits in Valle del Belice sheep.

2019

Copy number variation (CNV) is a major source of genomic structural variation. The aim of this study was to detect genomic CNV regions (CNVR) in Valle del Belice dairy sheep population and to identify those affecting milk production traits. The GO analysis identified possible candidate genes and pathways related to the selected traits. We identified CNVs in 416 individuals genotyped using the Illumina OvineSNP50 BeadChip array. The CNV association using a correlation-trend test model was examined with the Golden Helix SVS 8.7.0 tool. Significant CNVs were detected when their adjusted p-value was <0.01 after false discovery rate (FDR) correction. We identified 7,208 CNVs, which gave 365 C…