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https://www.readbyqxmd.com/read/28222108/oxidative-stress-mediated-nf%C3%AE%C2%BAb-phosphorylation-upregulates-p62-sqstm1-and-promotes-retinal-pigmented-epithelial-cell-survival-through-increased-autophagy
#1
Chunjuan Song, Sayak K Mitter, Xiaoping Qi, Eleni Beli, Haripriya V Rao, Jindong Ding, Colin S Ip, Hongmei Gu, Debra Akin, William A Dunn, Catherine Bowes Rickman, Alfred S Lewin, Maria B Grant, Michael E Boulton
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress...
2017: PloS One
https://www.readbyqxmd.com/read/28219639/leishmania-l-amazonensis-induces-hyperalgesia-in-balb-c-mice-contribution-of-endogenous-spinal-cord-tnf%C3%AE-and-nf%C3%AE%C2%BAb-activation
#2
Sergio M Borghi, Victor Fattori, Kenji W Ruiz-Miyazawa, Milena M Miranda-Sapla, Rúbia Casagrande, Phileno Pinge-Filho, Wander R Pavanelli, Waldiceu A Verri
: Cutaneous leishmaniasis (CL) is the most common form of the leishmaniasis in humans. Ulcerative painless skin lesions are predominant clinical features of CL. Wider data indicate pain accompanies human leishmaniasis, out with areas of painless ulcerative lesions per se. In rodents, Leishmania (L.) major infection induces nociceptive behaviors that correlate with peripheral cytokine levels. However, the role of the spinal cord in pain processing after Leishmania infection has not been investigated...
February 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28219355/vaccaria-hypaphorine-alleviates-lipopolysaccharide-induced-inflammation-via-inactivation-of-nf%C3%AE%C2%BAb-and-erk-pathways-in-raw-264-7-cells
#3
Haijian Sun, Weiwei Cai, Xu Wang, Yanling Liu, Bao Hou, Xuexue Zhu, Liying Qiu
BACKGROUND: Activation of macrophage is involved in many inflammation diseases. Lipopolysaccharide (LPS) is a powerful inflammatory signal contributing to monocytes/macrophages activation associated with increased proinflammatory cytokines expressions. We recently identified that vaccarin was expected to protect endothelial cells from injury. Hypaphorine was abundantly found in vaccaria semen. However, the potential roles and underlying mechanisms of vaccaria hypaphorine on macrophage inflammation have been poorly defined...
February 20, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28217691/%C3%AE-1-antitrypsin-deficiency-a-misfolded-secretory-protein-variant-with-unique-effects-on-the-endoplasmic-reticulum
#4
David H Perlmutter
In the classical form of α1-antitrypsin deficiency (ATD) a point mutation leads to accumulation of a misfolded secretory glycoprotein in the endoplasmic reticulum (ER) of liver cells and so ATD has come to be considered a prototypical ER storage disease. It is associated with two major types of clinical disorders, chronic obstructive pulmonary disease (COPD) by loss-of-function mechanisms and hepatic cirrhosis and carcinogenesis by gain-of-function mechanisms. The lung disease predominantly results from proteolytic damage to the pulmonary connective tissue matrix because of reduced levels of protease inhibitor activity of α1-anitrypsin (AT) in the circulating blood and body fluids...
September 2016: Endoplasmic Reticulum Stress in Diseases
https://www.readbyqxmd.com/read/28216438/porphyromonas-gingivalis-lipopolysaccharide-induces-pro-inflammatory-adipokine-secretion-and-oxidative-stress-by-regulating-toll-like-receptor-mediated-signaling-pathways-and-redox-enzymes-in-adipocytes
#5
Fanny Le Sage, Olivier Meilhac, Marie-Paule Gonthier
Gut microbiota LPS contributes to obesity-related chronic inflammation and oxidative stress, promoting insulin resistance. Periodontal disease also represents a risk factor for type 2 diabetes and is associated with obesity. This study compared the effect of LPS from P. gingivalis periodontopathogen and E. coli enterobacteria on inflammatory adipokine secretion and redox status of 3T3-L1 adipocytes. We found that both LPS activated TLR2- and TLR4-mediated signaling pathways involving MyD88 adaptor and NFκB transcription factor, leading to an increased secretion of leptin, resistin, IL-6 and MCP-1...
February 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#6
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28214555/identification-of-a-fatty-acid-binding-protein4-ucp2-axis-regulating-microglial-mediated-neuroinflammation
#7
Cayla M Duffy, Hongliang Xu, Joshua P Nixon, David A Bernlohr, Tammy A Butterick
Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism...
February 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28212752/caspase-8-acts-in-a-non-enzymatic-role-as-a-scaffold-for-assembly-of-a-pro-inflammatory-faddosome-complex-upon-trail-stimulation
#8
Conor M Henry, Seamus J Martin
TRAIL is a potent inducer of apoptosis and has been studied almost exclusively in this context. However, TRAIL can also induce NFκB-dependent expression of multiple pro-inflammatory cytokines and chemokines. Surprisingly, whereas inhibition of caspase activity blocked TRAIL-induced apoptosis, but not cytokine production, knock down or deletion of caspase-8 suppressed both outcomes, suggesting that caspase-8 participates in TRAIL-induced inflammatory signaling in a scaffold role. Consistent with this, introduction of a catalytically inactive caspase-8 mutant into CASP-8 null cells restored TRAIL-induced cytokine production, but not cell death...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28210097/epac1-agonist-decreased-inflammatory-proteins-in-retinal-endothelial-cells-and-loss-of-epac1-increased-inflammatory-proteins-in-the-retinal-vasculature-of-mice
#9
Li Liu, Youde Jiang, Adam Chahine, Elizabeth Curtiss, Jena J Steinle
PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of β-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28203237/activation-of-the-wnt-pathway-by-mycobacterium-tuberculosis-a-wnt-wnt-situation
#10
REVIEW
Tomás Villaseñor, Edgardo Madrid-Paulino, Rafael Maldonado-Bravo, Antonio Urbán-Aragón, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28193872/nf%C3%AE%C2%BAb-pim-1-eomesodermin-axis-is-critical-for-maintaining-cd8-t-cell-memory-quality
#11
Karin M Knudson, Curtis J Pritzl, Vikas Saxena, Amnon Altman, Mark A Daniels, Emma Teixeiro
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28192862/long-term-dietary-quercetin-enrichment-as-a-cardioprotective-countermeasure-in-mdx-mice
#12
Christopher Ballmann, Thomas Denney, Ronald J Beyers, Tiffany Quindry, Matthew Romero, Joshua T Selsby, John C Quindry
Duchenne Muscular Dystrophy (DMD) causes declines in cardiac health resulting in premature mortality. As a potential countermeasure, quercetin is a polyphenol possessing inherent anti-inflammatory and antioxidant effects that activate proliferator-activated γ coactivator 1α (PGC-1α) increasing mitochondrial biogenesis protein abundance. We investigated the extent to which lifelong 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in mdx mice. Dystrophic animals were fed quercetin or control diet for 12 months while control C57 mice were fed a control diet...
February 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28187734/the-potential-neuroprotective-role-of-a-histone-deacetylase-inhibitor-sodium-butyrate-after-neonatal-hypoxia-ischemia
#13
Joanna Jaworska, Malgorzata Ziemka-Nalecz, Joanna Sypecka, Teresa Zalewska
BACKGROUND: Histone deacetylase inhibitor (HDACi), sodium butyrate (SB), has been shown to be neuroprotective in adult brain injury models. Potential explanation for the inhibitor action involves among others reduced inflammation. We therefore anticipated that SB will provide a suitable option for brain injury in immature animals. The aim of our study was to test the hypothesis that one of the mechanisms of protection afforded by SB after neonatal hypoxia-ischemia is associated with anti-inflammatory action...
February 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28186994/trim47-overexpression-is-a-poor-prognostic-factor-and-contributes-to-carcinogenesis-in-non-small-cell-lung-carcinoma
#14
Yudong Han, Haiying Tian, Pei Chen, Qiang Lin
Non-small cell lung carcinoma (NSCLC) is the most common malignancy with the highest morbidity and mortality. In this study, we found that tripartite motif containing 47 (TRIM47) expression level was higher in tumor tissues than in normal adjacent tissues. Overexpression of TRIM47 closely correlated with poor prognosis in patients with NSCLC. Multivariate Cox regression analyses showed that TRIM47 overexpression could be considered an independent prognostic factor for NSCLC. TRIM47 depletion significantly inhibited cell proliferation and induced G1phase arrest in A549 and H358 cell lines...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182729/rikkunshito-prevents-paclitaxel-induced-peripheral-neuropathy-through-the-suppression-of-the-nuclear-factor-kappa-b-nf%C3%AE%C2%BAb-phosphorylation-in-spinal-cord-of-mice
#15
Junzo Kamei, Shunsuke Hayashi, Akane Sakai, Yuki Nakanishi, Misa Kai, Megumi Ikegami, Hiroko Ikeda
Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn...
2017: PloS One
https://www.readbyqxmd.com/read/28181416/preventive-effects-of-ophiocordyceps-sinensis-mycelium-on-the-liver-fibrosis-induced-by-thioacetamide
#16
Yi-Hsieng Samuel Wu, Jung-Kai Tseng, Chung-Hsi Chou, Chih-Hsien Chiu, Yi-Ling Lin, Yi-Chen Chen
Thioacetamide (TAA), usually used as a fungicide to control the decay of citrus products, itself is not toxic to the liver, but its intermediates are able to increase oxidative stress in livers and further cause fibrosis. Ophiocordyceps sinensis mycelium (OSM) which contains 10% polysaccharides and 0.25% adenosine decreased (P < 0.05) the lipid accumulation and increased (P < 0.05) antioxidative capacity in livers of thioacetamide (TAA) injected rats. Meanwhile, the increased (P < 0.05) liver sizes, serum alanine transaminase (AST) and aspartate transaminase (ALT) values in thioacetamide (TAA)-injected rats were ameliorated (P < 0...
February 9, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28181347/biomechanical-forces-promote-immune-regulatory-function-of-bone-marrow-mesenchymal-stromal-cells
#17
Miguel F Diaz, Abishek B Vaidya, Siobahn M Evans, Hyun J Lee, Benjamin M Aertker, Alexander J Alexander, Katherine M Price, Joyce A Ozuna, George P Liao, Kevin R Aroom, Hasen Xue, Liang Gu, Rui Omichi, Supinder Bedi, Scott D Olson, Charles S Cox, Pamela L Wenzel
Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E2 (PGE2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells...
February 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28177892/pevonedistat-a-nedd8-activating-enzyme-inhibitor-sensitizes-neoplastic-b-cells-to-death-receptor-mediated-apoptosis
#18
Cody Paiva, J Claire Godbersen, Taylor Rowland, Olga V Danilova, Christopher Danes, Allison Berger, Alexey V Danilov
While death receptor ligands (Fas and TRAIL) kill chemoresistant tumor cell lines, related therapies have limited clinical efficacy as single agents. Death receptor signaling is modulated by nuclear factor-κB (NFκB), a family of transcription factors which are constitutively active in B-cell malignancies. We and others have shown that pevonedistat, an investigational inhibitor of the NEDD8-activating enzyme, abrogates NFκB activity in B-cell neoplasia. Here we demonstrate that diffuse large B-cell lymphoma, particularly activated B-cell type, and primary chronic lymphocytic leukemia cells are re-sensitized to extrinsic apoptosis by pevonedistat...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176624/vitamin-d-combined-with-resveratrol-prevents-cognitive-decline-in-samp8-mice
#19
Jinbo Cheng, Yehua Rui, Liqiang Qin, Jiaying Xu, Shufen Han, Linxi Yuan, Xuebin Yin, Zhongxiao Wan
Background Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. Objective We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms...
February 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28176622/the-tlr9-antagonist-icpg-odn-at-different-dosages-inhibits-cerebral-ischemia-reperfusion-injury-in-mice
#20
Ying Zhou, Jingrui Pan, Qingxia Peng, Zhaofei Dong Dong, Lingna Deng Deng, Yidong Wang
Inflammatory responses are important mechanisms that are involved in cerebral ischemia/reperfusion(I/R) injury. Whether toll-like receptor 9(TLR9), which belongs to the innate immune system, takes part in the inflammatory responses following cerebral I/R remains unclear. This study examined the effect of different dosages of the TLR9 antagonist inhibitory oligodeoxynucleotide (iCpG-ODN) on cerebral I/R injury by using a mouse model of transient middle cerebral artery occlusion. Neurological function, infarct size, splenocytes and the expression of TLR9 and the downstream products of the TLR9 pathways were determined after cerebral I/R for up to 72 hours...
February 6, 2017: CNS & Neurological Disorders Drug Targets
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