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Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
NF-κB transcriptionally regulates expression of genes which are involved in cell survival, apoptosis, differentiation and immune responses [42, 43]. As discussed above, NF-κB family consists of five members. Both the precursors (NF-κB1/p105 and NF-κB2/ p100) contain IκB-homologous regions at the C-terminal that function as NF-κB inhibitors. Proteolytic processing removes inhibitory domains, allowing the processed proteins (NF-κB1/ p50 and NF-κB2/p52) to enter into the nucleus. Inside the nucleus, p50 and p52 form homodimers or heterodimers with Rel family proteins [42]. All these NF-κB associated proteins have Rel homology domain (RHD) at the N-terminal region. Some of the NF-κB proteins (p65, c-Rel and RelB) contain transcriptional activation domain (TAD) at C-terminal, and these TAD containing proteins positively regulate transcriptional activity. On the other hand, two TAD lacking proteins, p52 and p100, negatively regulate gene expression when bound as homodimer, but can activate gene expression when recruited with other TAD containing proteins like p65. RelB and cRel [44]. Activation of NF-κB pathway is either by classical/canonical or the alternate/non-canonical signaling pathways.
Nutraceutical’s Role in Proliferation and Prevention of Gynecological Cancers
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Aaishwarya B. Deshmukh, Jayvadan K. Patel, Bharat Mishra
NF-κB as a nuclear factor was found to bind to the enhancer element of the immunoglobulin kappa light chain of activated B cells (hence abbreviated NF-κB) [41]. The five members of NF-κB group of proteins identified are RelB, p65 (RelA), NF-κB1 (p105/p50), NF-κB2 (p100/p52), and c-Rel [42–45]. The expression of genes involved in the various processes of transformation and development of tumor cells is regulated by the transcription factor NF-κB by various proinflammatory stimuli such as TNF-α, lipopolysaccharide, IL-1b, and oxidative stress, which induce expression of multiple genes encoding proinflammatory cytokines, growth and angiogenic factors, chemokines adhesion molecules, such as ICAM-1 and e-selectin VCAM-1, and inducible enzymes like iNOS and COX-2 [46]. The apprehension that the c-rel, which is a cellular homologue of the oncogene v-rel, encodes for a NF-κB subunit and binds to the same DNA binding domain has given the first proof of link between NF-κB and cancer [47]. In addition, the detection of active NF-κB in cancer tissues of the patients, including those with lymphoma and leukemia and cancers of breast, prostate, pancreas, oral cavity, colon, liver, and ovary support the link between NF-κB and cancer [48]. All these point to the relevance or importance of NF-κB pathway in cancer, and so this pathway has been manifested as a favored target for therapeutic development.
Antipsoriatic Medicinal Plants
Published in José L. Martinez, Amner Muñoz-Acevedo, Mahendra Rai, Ethnobotany, 2019
José Luis Ríos, Guillermo R. Schinella, Isabel Andújar
Other studies were focused on the suppression of NF-κB signaling and its consequences. In this sense, Saelee et al. (2011) studied the effects of Alpinia galanga (Thai ginger), Curcuma longa (turmeric) and Annona squamosa (sweetsop) extracts on ten different genes of the NF-κB signaling network in HaCaT cells, and observed that Thai ginger extract reduced the expression of NF-κB2, turmeric extract significantly decreased the expression of both NF-κB2 and NF-κB1, while Annona squamosa extract significantly lowered the expression of NF-κB1. So, this in vitro study suggested that these medicinal plants might exert their antipsoriatic activity by controlling the expression of NF-κB signaling biomarkers.
Depleting microRNA-146a-3p attenuates lipopolysaccharide-induced acute lung injury via up-regulating SIRT1 and mediating NF-κB pathway
Published in Journal of Drug Targeting, 2021
MicroRNAs (miRs), small non-coding RNAs with a length of 21–22 nucleotides, can result in translational suppression and silence the target mRNAs [6]. It was displayed that serum miR-146a is a potential biomarker for the prognosis and diagnosis of ALI after hip fracture [7]. It was revealed that miR-146a is a new biomarker for predicting the treatment outcome and mortality of sever sepsis and sepsis-induced ALI [8]. Sirtuin-1 (SIRT1) is a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, and is considered to be an anti-aging gene [9]. A study has demonstrated that hydrogen lightens hyperoxic ALI correlated endoplasmic reticulum stress in rats by overexpression of SIRT1 [10]. Also, a study presented that acute depletion of miR-199a decreases sepsis-induced ALI through targeting SIRT1 [11]. It was revealed that resolvin D1 accelerates the expression of SIRT1 to counteract the activation of NF-κB in septic-related lung injury mice [12]. Nuclear factor-kappa B (NF-κB) transcription factor family includes NFKB1 (p50/p105), NFKB2 (p52/p100), c-Rel, RelB and RelA (p65), which construct various homo- and heterodimers [13]. A study has presented a protective effect of down-regulated NF-κB pathway on oxidative stress of lung tissue in ALI rat [14]. According to Wu et al. [15], miR-326 increases ALI in septic shock through mediating the NF-κB signalling pathway. Therefore, it is hypothesised in this study that miR-146a-3p might act as a novel biomarker in ALI. For verifying this, we aim to clarify the effects of miR-146a-3p/SIRT1/NF-κB axis on ALI.
Mechanical strain mimicking breathing amplifies alterations in gene expression induced by SiO2 NPs in lung epithelial cells
Published in Nanotoxicology, 2019
Carmen Schmitz, Jennifer Welck, Isabella Tavernaro, Marianna Grinberg, Jörg Rahnenführer, Alexandra K. Kiemer, Christoph van Thriel, Jan G. Hengstler, Annette Kraegeloh
Furthermore, TNF-α treatment of A549 cells not only caused induction of NFKB1 (p105/p50) and NFKBIA, coding for its cytoplasmic inhibitor Iκβα, but also induction of TNFAIP3/A20 and BIRC3/IAP2, involved in the inhibition of TNF-α induced NF-κB signaling by an auto-feedback loop (Dos Santos et al. 2004). Of these, only TNFAIP3/A20 and BIRC3/IAP2 were upregulated after treatment of A549 with Si25 plus stretch. Deviating from the above described pattern, under the conditions applied in this study, the genes coding for NF-κB p105/p50 and the corresponding inhibitor IκBα were not induced, supporting the finding that induced response deviates from the TNF-α induced pathway. Instead, the NFKB2 gene, coding for the NF-κB p100/p52 subunits, was induced. These two subunits are involved in the alternative or noncanonical NF-κB pathway, leading to translocation of a p52/RelB complex into the nucleus (Gilmore 2006). In order to test for translocation of NF-κB p100/p52, nuclear accumulation of NF-κB p100/p52 was analyzed by confocal microscopy. However, a significant translocation of NF-κB p100/p52 was not supported by qualitative data (Supplementary material Figure S11).
Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability
Published in Expert Opinion on Drug Delivery, 2019
Dallan McMahon, Charissa Poon, Kullervo Hynynen
At the level of transcription, evidence of an acute inflammatory response has been demonstrated in isolated microvessels 6 h following sonication, with an upregulation of Ccl2, Ccl3, Ccl7, C3, Il1b, Il6, Sele, etc. By 24 h, expression levels of these genes largely return to baseline or are reduced relative to the 6 h time point [122]. In whole brain tissue, transcription of Nfkb2 pathway-related genes has been investigated following FUS+MBs in two independent studies. The Nfkb2 pathway is involved in a wide range of biological processes, including innate and adaptive immunity, inflammation, and stress responses. The first study demonstrated a significant upregulation of several genes involved in acute inflammation, including Il1a, Il1b, Selp, Tnf, and Icam1, at 0.5, 6, and 12 h following FUS+MBs. A number of other genes displayed increased expression only at the two later time points, including Mmp9, Ccl5, Sele, and Birc3. These changes in gene expression were largely mirrored at the protein level with elevated levels of Mcp1, Icam1, Tnfa, and Mmp9, persisting to the latest time point investigated, 24 h post-FUS+MBs [61]. A subsequent study replicated the magnitude of this response at 6 h following sonication and, notably, showed that the expression level of several key genes involved in acute inflammation, including Tnf, Icam1, Ccl5, Birc3, Il1a, and Il1b, were strongly correlated to the degree of BBB permeability. Additionally, MB dose appeared to significantly influence BBB permeability [62].