Search results for "NF-"
showing 10 items of 461 documents
Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach
2018
Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This netw…
Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation.
2020
[Significance]: Nuclear factor kappa B (NF-κB) is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. In addition, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.
The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19
2021
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 over…
Molecular evolution of antioxidant and hypoxia response in long-lived, cancer-resistant blind mole rats: The Nrf2-Keap1 pathway.
2015
The Nrf2-Keap1 pathway is crucial for the cellular antioxidant and hypoxia response in vertebrates. Deciphering its modifications in hypoxia-adapted animals will help understand its functionality under environmental stress and possibly allow for knowledge transfer into biomedical research. The blind mole rat Spalax, a long-lived cancer-resistant rodent, lives in burrows underground and is adapted to severely hypoxic conditions. Here we have conducted a bioinformatical survey of Spalax core genes from the Nrf2-Keap1 pathway on the coding sequence level in comparison to other hypoxia-tolerant and -sensitive rodents. We find strong sequence conservation across all genes, illustrating the pathw…
The angiotensin‐(1‐7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation
2019
Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. By activating the G protein-coupled receptor Mas, Ang-(1…
Balanced Bcl-3 expression in murine CD4+T cells is required for generation of encephalitogenic Th17 cells
2017
The function of NF-κB family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the IκB family. By using a murine model of conditional Bcl-3 overexpression specifically in T cells, we observed impairment in the development of Th2, Th1 and Th17 cells. High expression of Bcl-3 promoted CD4+ T-cell survival, but at the same time suppressed proliferation in response to TCR stimulation, resulting in reduced CD4+ T-cell expansion. As a consequence, T cell specific overexpression of Bcl-3 led to reduced inflammation in the small intestine of mice applied with anti-CD3 in a model of gut inflammation. Moreover, impaired Th17-cell develop…
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease
2018
Background: Aβ 1-42 peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Methods: A rat model of AD was obtained by intra-hippocampal injection of Aβ 1-42 peptide (23 μg/2 μl). After 6 days, 3.6 μg of IFNβ1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or …
NF-κB and Disease
2020
The role of NF-κB in all diseases characterized by an inflammatory process, from cancer to autoimmune diseases, is known, but—precisely because it is involved in many diseases—this transcriptional factor continues to attract scientific research and the new knowledge that emerges is fundamental in highlighting the therapeutic potential that this factor can have in the various diseases in which it is involved [...]
Inhibition of NF-κB pathway in LPS-stimulated THP-1 monocytes and COX-2 activity in vitro by berry pomace extracts from five Vaccinium species
2020
BACKGROUND: Berry processing residues called pomaces are rich in polyphenols, sugars, organic acids, and minerals. Polyphenols are reported to reduce the risk of non-communicable diseases, including cardiovascular diseases, cancer, and diabetes mellitus, owing to their anti-inflammatory activity. OBJECTIVE: We aimed to assess the anti-inflammatory properties of five Vaccinium spp. berry pomace extracts using LPS-stimulated THP-1 monocytes and a COX-2 inhibition assay. METHODS: THP-1 monocytes were pre-incubated with chemically characterized bilberry, blueberry, American cranberry, bog cranberry, and lingonberry pomace extracts following LPS stimulation. NF-κB nuclear translocation was asses…
Loss of MCL1 function sensitizes the MDA-MB-231 breast cancer cells to rh-TRAIL by increasing DR4 levels.
2019
Triple-negative breast cancer (TNBC) is a form of BC characterized by high aggressiveness and therapy resistance probably determined by cancer stem cells. MCL1 is an antiapoptotic Bcl-2 family member that could limit the efficacy of anticancer agents as recombinant human tumor necrosis factor related apoptosis-inducing ligand (rh-TRAIL). Here, we investigated MCL1 expression in TNBC tissues and cells. We found MCL1 differentially expressed (upregulated or downregulated) in TNBC tissues. Furthermore, in comparison to the human mammary epithelial cells, we found that MDA-MB-231 cells show similar messenger RNA levels but higher MCL1 protein levels, whereas it resulted downregulated in MDA-MB-…