Search results for "cellular"
showing 10 items of 6449 documents
The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis
2017
Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity …
Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma
2019
Background Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. Objective This study aims to analyze the presence of a regulation loop like that between MDA-9/Syntenin - NF-κB - RKIP in human liver carcinoma. Methods Transient transfection was performed with siRNA anti-MDA-9/Syntenin. Expression of different factors was evaluated by Real time-PCR and Western blotting, while NF-κB activation by TransAM assay. Invasion capacity was analyzed by Matrigel Invasion Assay and the effects…
MDA-MB-231 and 8701BC breast cancer lines promote the migration and invasiveness of ECV304 cells on 2D and 3D type-I collagen matrix
2017
Tumor angiogenesis is a multiphasic process, having the extracellular matrix remodeling as critical step. Different classes of proteolytic enzymes in matrix digestion/remodeling are involved. The role of lytic enzymes and their activation mode have not been completely elucidated. Herein, the crosstalk between endothelia and tumor cells, by realization of bi- and three-dimensional endothelial and breast cancer cells co-cultures, were studied in vitro. Particularly, the effects of two tumor conditioned media (TCM) were assessed about endothelial proliferation, migration, and invasiveness. An increase in expression of pro-MMP9 was detected when endothelial cells were cultured in the presence o…
3d collagen hydrogel promotes in vitro langerhans islets vascularization through ad-mvfs angiogenic activity
2021
Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33–955 μm that are able to maintain their original morphology. The isolated units of ad-MVFs that resulted were able to activate transcriptional switching toward angiogenesis, forming tubes, branches, and entire capillary networks when cultured in 3D collagen type-…
Negatively Charged Gangliosides Promote Membrane Association of Amphipathic Neurotransmitters
2018
Lipophilic neurotransmitters (NTs) such as dopamine are chemical messengers enabling neurotransmission by adhering onto the extracellular surface of the post-synaptic membrane in a synapse, followed by binding to their receptors. Previous studies have shown that the strength of the NT-membrane association is dependent on the lipid composition of the membrane. Negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, and phosphatidic acid have been indicated to promote NT-membrane binding, however these anionic lipids reside almost exclusively in the intracellular leaflet of the post-synaptic membrane instead of the extracellular leaflet facing the synaptic cleft. Meanwhile…
Effects of Ranolazine on Astrocytes and Neurons in Primary Culture.
2016
Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10-7, 10-6 and 10-5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The …
Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin.
2021
Abstract Background Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced…
p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.
2017
[Background]: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. [Methods]: Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. [Results]: We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M…
Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum
2019
Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3& #x202F;± 1.1 g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPARα-imm…
A role for TASK2 channels in the human immunological synapse.
2020
The immunological synapse is a transient junction that occurs when the plasma membrane of a T cell comes in close contact with an APC after recognizing a peptide from the antigen-MHC. The interaction starts when CRAC channels embedded in the T cell membrane open, flowing calcium ions into the cell. To counterbalance the ion influx and subsequent depolarization, Kv 1.3 and KCa3.1 channels are recruited to the immunological synapse, increasing the extracellular K+ concentration. These processes are crucial as they initiate gene expression that drives T cell activation and proliferation. The T cell-specific function of the K2P channel family member TASK2 channels and their role in autoimmune p…