Search results for "Ligo"
showing 10 items of 1427 documents
Extracellular vesicles in the oligodendrocyte microenvironment
2019
Abstract Extracellular vesicles (EVs) recently took centre stage as mediators of cellular crosstalk modulating the tissue microenvironment. Released by all types of neural cells, EVs may execute a broad spectrum of functions ranging from maintenance of neuronal homeostasis and regulation of neural plasticity to the spread of neurodegenerative agents. Myelinating oligodendrocytes and axons form a highly specialized functional entity that depends on intimate interactions within the oligodendrocyte-neuron niche. EVs released by oligodendrocytes are internalized by neurons in response to neuronal signals and exhibit neuroprotective properties but also may influence other cells present in the mi…
Ultrastructural characterization of human oligodendrocytes and their progenitor cells by pre-embedding immunogold.
2021
Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white …
Flow cytometric analysis of T cell/monocyte ratio in clinically isolated syndrome identifies patients at risk of rapid disease progression.
2015
Background: Multiple sclerosis is a chronic inflammatory central nervous system disease diagnosed by clinical presentation and characteristic magnetic resonance imaging findings. The role of cerebrospinal fluid (CSF) analysis has been emphasized in particular in the context of differential diagnosis in patients with a first episode suggestive of multiple sclerosis. Objective: We investigated here the potential additional value of analysis of CSF cellularity by fluorescence activated cell sorting (FACS) in the setting of a routine diagnostic work-up in our inpatient clinic. Methods: CSF cells from back-up samples from patients with suspected chronic inflammatory central nervous system disord…
The iNOS Activity During an Immune Response Controls the CNS Pathology in Experimental Autoimmune Encephalomyelitis
2019
Inducible nitric oxide synthase (iNOS) plays a critical role in the regulation of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Previous studies have shown that iNOS plays pathogenic as well as regulatory roles in MS and EAE. However, how does iNOS alters the pathophysiology of the central nervous system (CNS) in neuronal autoimmunity is not clearly understood. In the present work, we show that treatment of mice with L-NAME, an iNOS inhibitor, during the antigen-priming phase primarily alters brain pathology, while in the subsequent effector phase of the immune response, the spinal cord is involved. Inhibition of iNOS during the priming phase of the immune res…
The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
2016
KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. M…
MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells.
2018
AbstractMir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific lo…
Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis
2016
Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. In particular, the drugs exerted a remarkable inhibitory effect on viability of stem-like cells. Such an effect was suppressed by N-acetylcysteine, suggesting a role of reactive oxygen species (ROS) generation in the cytotoxic effect. Instead z-VAD, a ge…
Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique
2016
Abstract Patients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of–function” mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in se…
Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives
2019
AbstractThe pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screen…
Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients
2017
In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary…