2,808 research outputs found
Hypoxia activates IKK-NF-κB and the immune response in <em>Drosophila melanogaster</em>
No full textHypoxia, or low oxygen availability, is an important physiological and pathological stimulus for multicellular organisms. Molecularly, hypoxia activates a transcriptional programme directed at restoration of oxygen homoeostasis and cellular survival. In mammalian cells, hypoxia not only activates the HIF (hypoxia-inducible factor) family, but also additional transcription factors such as NF-?B (nuclear factor ?B). Here we show that hypoxia activates the IKK–NF-?B [I?B (inhibitor of nuclear factor ?B)–NF-?B] pathway and the immune response in Drosophila melanogaster. We show that NF-?B activation is required for organism survival in hypoxia. Finally, we identify a role for the tumour suppressor Cyld, as a negative regulator of NF-?B in response to hypoxia in Drosophila. The results indicate that hypoxia activation of the IKK–NF-?B pathway and the immune response is an important and evolutionary conserved response.</p
The protective effects of betanin against experimental gastric ulcer by reduction of ROS and suppression of inflammatory genes via NF-κB, iNOS, COX-2 and TNF-α pathways
No full textBetanin, a prominent compound found in beetroot, however, the potential protective effects of this compound against gastric damage and ulceration have yet to be explored. This study aims to investigate the impact of purified beetroot betanin (Bet) on the activities of inflammatory enzymes and gene expressions associated with inflammation in gastric tissues. Gastric ulcer rats were induced by ethanol at dose 5ml/kg body weight. Ulcerated rats were treated by purified betanin or omeprazole; from which some inflammation-related genes and gastric-inflammation enzymes were investigated using RT-PCR and biochemical analysis, respectively. Bet effectively suppressed the activities of key enzymes involved in gastric mucosal inflammation, including 5-Lipoxygenase (5-LO), Hyaluronidase (HAase), and myeloperoxidase (MPO), by 58%, 50%, and 45%, respectively. Docking studies showed Bet binding to catalytic sites or key regions for enzymes’ activities, thus explaining the inhibitory capacity. Bet ingestion decreased the expression levels of inflammation-related genes, factor-kappa B (NF-ϰB) by 57%. This down-regulation subsequently led to a reduction in the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor-α (TNF-α). Bet ingestion supressed thiobarbituric acid reactive substance (TBARS) rates by 59%, augmented nitric oxide (NO) level by 107% and protected gastric tissues from damage and ulceration. Bet revealed gastro-protective effects as confirmed by a reduction in the ulceration surface area and the acidity by 75.9% and 40%, respectively, and a significant increase in the weight of mucus and the curative index by 117% and 74.5%, respectively. In conclusion, these outcomes of physiological and molecular-based investigations are indicative of potential use of Bet as a functional food additive for the prevention of gastric ulcer
NF-κB translocation assay ImageJ macro
No full textThis is ImageJ macro used to determine the degree of NF-κB translocation in cells stained for NF-κB and nuclear signal. It is a part of publication entitled "Plasma extracellular vesicles signal spleen fibroblasts facilitating Plasmodium vivax adherence". Please see the publication for full author details.</p
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
No full textDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease
No full textChronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD
Prevention of head and neck squamous cell carcinoma: removing the "chemo" from "chemoprevention"
No full textContains fulltext :
153725.pdf (Publisher’s version ) (Open Access)The concept of chemoprevention whereby the use of a systemic agent is intended to halt the carcinogenesis process has been an attractive topic in head and neck squamous cell carcinoma (HNSCC). Yet, despite the significant efforts over the past decades and the substantial gain in knowledge of the biology of pre-malignant lesions of the head and neck, no tangible indications for chemoprevention have emerged for this disease. The negative results observed in the earlier larger studies using retinoids did not encourage further trials with these agents. Attention has been more recently focused on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) as well as cyclo-oxygenase 2 (COX-2) inhibitors with early studies showing encouraging responses but rather poor tolerance to therapy. Natural compounds have gained more interest recently given preclinical evidence of activity as well as a low side effect profile. We herein offer a comprehensive overview of the field of chemoprevention in HNSCC with an in depth analysis of the challenges we face and discuss a road map for future directions
Environmental toxicity, redox signaling and lung inflammation:the role of glutathione
No full textGlutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox-sensitive transcription factors such as Nrf2, NF-kappaB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation of GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-l-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease
Vegetative growth and nutrient use efficiency of tissue-cultured ‛Saba’ banana (Musa) plantlets in response to fertigroe® N, P, and K nanofertilizers
No full textThe study determined the effect of using FertiGroe® Nano N (18-0-0), Nano P (0-18-0), and Nano K (0-0-38) nanofertilizers on the growth and nutrient use efficiency of tissue-cultured ‛Saba’ banana (Musa ABB) plantlets. For 7 wk, conventional fertilizers (CF) and FertiGroe® nanofertilizers (NF) were applied to the plantlets at graduated level of the recommended rate (RR). Vegetative growth was monitored weekly. At the end of the experiment, samples were collected for dry matter partitioning and leaf tissue analysis. Fertilizer treatment significantly improved pseudostem growth and dry matter production of ‛Saba’ banana plantlets. Plantlets applied with neither conventional fertilizer (CF) nor nanofertilizer NF (control) produced significantly shorter and thinner pseudostem, and less dry matter compared to plantlets that were applied with NF or CF, regardless of the recommended rate (RR) used. Despite having significantly shorter and thinner pseudostem, plantlets applied with NF at 50% RR and 75% RR produced dry matter comparable to plantlets applied with CF at 75% RR and 100% RR by allocating more dry matter to the leaves. Foliar P concentration was not limiting to the plants and its nutrient concentration in the leaves did not vary significantly across the treatments. N uptake was highest in plantlets applied with NF at 75% RR (0.187 g) and CF at 75% RR (0.158 g), 100% RR (0.167 g) and 125% RR (0.173 g). K uptake was highest in plantlets that received NF at 50% RR (0.355 g) and 75% RR (0.358 g) and CF at 75% RR (0.353 g). Nutrient use efficiency of the plantlets was measured using apparent nutrient recovery. Apparent potassium recovery of the plantlets applied with NF was higher compared to that of plantlets applied with CF. The computed optimum RR for FertiGroe® N nanofertilizer was 23.5% lower than the computed optimum RR for CF. FertiGroe® N nanofertilizer can also increase apparent nitrogen recovery by 36.87% compared to CF
Neutrophil-Derived IL-1β Impairs the Efficacy of NF-κB Inhibitors against Lung Cancer
No full textSummaryAlthough epithelial NF-κB signaling is important for lung carcinogenesis, NF-κB inhibitors are ineffective for cancer treatment. To explain this paradox, we studied mice with genetic deletion of IKKβ in myeloid cells and found enhanced tumorigenesis in KrasG12D and urethane models of lung cancer. Myeloid-specific inhibition of NF-κB augmented pro-IL-1β processing by cathepsin G in neutrophils, leading to increased IL-1β and enhanced epithelial cell proliferation. Combined treatment with bortezomib, a proteasome inhibitor that blocks NF-κB activation, and IL-1 receptor antagonist reduced tumor formation and growth in vivo. In lung cancer patients, plasma IL-1β levels correlated with poor prognosis, and IL-1β increased following bortezomib treatment. Together, our studies elucidate an important role for neutrophils and IL-1β in lung carcinogenesis and resistance to NF-κB inhibitors
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