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https://www.readbyqxmd.com/read/29135572/long-term-observational-studies-of-chronic-granulomatous-disease
#1
Maria Kanariou, Kleopatra Spanou, Sofia Tantou
PURPOSE OF REVIEW: Chronic granulomatous disease (CGD) is a primary immunodeficiency, with a defect of phagocytes in killing specific pathogens. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response. Since its first description as fatal disease about 60 years ago, a significant improvement in outcome has been achieved in the last 20 years. The purpose of this review is to framework recent advances in CGD immunopathogenesis, management of disease manifestation and cure of CGD patients...
November 10, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29081748/coq10-augments-rosuvastatin-neuroprotective-effect-in-a-model-of-global-ischemia-via-inhibition-of-nf-%C3%AE%C2%BAb-jnk3-bax-and-activation-of-akt-foxo3a-bim-cues
#2
Sarah A Abd El-Aal, Mai A Abd El-Fattah, Hanan S El-Abhar
Statins were reported to lower the Coenzyme Q10 (CoQ10) content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg), CoQ10 (10 mg/kg) and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29079525/conversion-of-nox2-into-a-constitutive-enzyme-in-vitro-and-in-living-cells-after-its-binding-with-a-chimera-of-the-regulatory-subunits
#3
Rawand Masoud, Xavier Serfaty, Marie Erard, Paul Machillot, Gilda Karimi, Elodie Hudik, Frank Wien, Laura Baciou, Chantal Houée-Levin, Tania Bizouarn
During the phagocytosis of pathogens by phagocyte cells, the NADPH oxidase complex is activated to produce superoxide anion, a precursor of microbial oxidants. The activated NADPH oxidase complex from phagocytes consists in two transmembrane proteins (Nox2 and p22(phox)) and four cytosolic proteins (p40(phox), p47(phox), p67(phox) and Rac1-2). In the resting state of the cells, these proteins are dispersed in the cytosol, the membrane of granules and the plasma membrane. In order to synchronize the assembly of the cytosolic subunits on the membrane components of the oxidase, a fusion of the cytosolic proteins p47(phox), p67(phox) and Rac1 named trimera was constructed...
October 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29069584/dendritic-cell-amiloride-sensitive-channels-mediate-sodium-induced-inflammation-and-hypertension
#4
Natalia R Barbaro, Jason D Foss, Dmytro O Kryshtal, Nikita Tsyba, Shivani Kumaresan, Liang Xiao, Raymond L Mernaugh, Hana A Itani, Roxana Loperena, Wei Chen, Sergey Dikalov, Jens M Titze, Bjorn C Knollmann, David G Harrison, Annet Kirabo
Sodium accumulates in the interstitium and promotes inflammation through poorly defined mechanisms. We describe a pathway by which sodium enters dendritic cells (DCs) through amiloride-sensitive channels including the alpha and gamma subunits of the epithelial sodium channel and the sodium hydrogen exchanger 1. This leads to calcium influx via the sodium calcium exchanger, activation of protein kinase C (PKC), phosphorylation of p47(phox), and association of p47(phox) with gp91(phox). The assembled NADPH oxidase produces superoxide with subsequent formation of immunogenic isolevuglandin (IsoLG)-protein adducts...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29043330/procyanidins-extracted-from-the-litchi-pericarp-ameliorate-atherosclerosis-in-apoe-knockout-mice-their-effects-on-nitric-oxide-bioavailability-and-oxidative-stress
#5
Shuang Rong, Xueting Hu, Siqi Zhao, Yanting Zhao, Xiao Xiao, Wei Bao, Liegang Liu
Epidemiological studies strongly support the role of procyanidin-rich beverages and fruit in the prevention of cardiovascular diseases. Procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins, were isolated and identified in our laboratory and have been proven to possess strong antioxidant activity in vitro. In the present study, we investigated the anti-atherosclerotic effects of LPPC in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet for 24 weeks. LPPC (100 mg kg(-1) body mass daily) significantly reduced the atherosclerotic lesion size (P < 0...
October 18, 2017: Food & Function
https://www.readbyqxmd.com/read/29042313/the-hypothetical-protein-p47-of-clostridium-botulinum-e1-strain-beluga-has-a-structural-topology-similar-to-bactericidal-permeability-increasing-protein
#6
Kwok-Ho Lam, Ruifeng Qi, Shun Liu, Amelie Kroh, Guorui Yao, Kay Perry, Andreas Rummel, Rongsheng Jin
Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening disease botulism. They are naturally produced by species of the bacteria Clostridium botulinum as stable and non-covalent complexes, in which the BoNT molecule is assembled with several auxiliary non-toxic proteins. Some BoNT serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced by Clostridium strains that carry the ha gene cluster, which encodes four neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an important role to deliver and protect BoNTs in the gastrointestinal tract during oral intoxication...
October 16, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29024866/diclofenac-but-not-celecoxib-improves-endothelial-function-in-rheumatoid-arthritis-a-study-in-adjuvant-induced-arthritis
#7
Frank Verhoeven, Perle Totoson, Christine Marie, Anne Prigent-Tessier, Daniel Wendling, Maude Tournier-Nappey, Clément Prati, Céline Demougeot
BACKGROUND AND AIMS: We aimed at investigating the effect of celecoxib (COX-2 selective inhibitor) and diclofenac (non-selective COX inhibitor) on endothelial function, and at identifying the underlying mechanisms in adjuvant-induced arthritis (AIA). METHODS: At the first signs of AIA, diclofenac (5 mg/kg twice a day, i.p), celecoxib (3 mg/kg/day, i.p) or saline (Vehicle) was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of NOS, arginase, EDHF and superoxide anions (O2(-°)) production...
November 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28978491/complement-receptor-3-mediates-nadph-oxidase-activation-and-dopaminergic-neurodegeneration-through-a-src-erk-dependent-pathway
#8
Liyan Hou, Ke Wang, Cong Zhang, Fuqiang Sun, Yuning Che, Xiulan Zhao, Dan Zhang, Huihua Li, Qingshan Wang
Microglial NADPH oxidase (Nox2) plays a key role in chronic neuroinflammation and related dopaminergic neurodegeneration in Parkinson's disease (PD). However, the mechanisms behind Nox2 activation remain unclear. Here, we revealed the critical role of complement receptor 3 (CR3), a microglia-specific pattern recognition receptor, in Nox2 activation and subsequent dopaminergic neurodegeneration by using paraquat and maneb-induced PD model. Suppression or genetic deletion of CR3 impeded paraquat and maneb-induced activation of microglial Nox2, which was associated with attenuation of dopaminergic neurodegeneration...
September 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28949377/structure-activity-relationship-of-three-synthesized-benzimidazole-based-oligosaccharides-in-human-platelet-activation
#9
Yi Chang, Wen-Hsien Hsu, Wen-Bin Yang, Thanasekaran Jayakumar, Tzu-Yin Lee, Joen-Rong Sheu, Wan-Jung Lu, Jiun-Yi Li
Antiplatelet agents have considerable benefits in the treatment of thromboembolic diseases; however, these agents still have substantial limitations due to their severe side-effects. In this study, the antiplatelet activity of three newly synthesized saccharide based benzimidazole derivatives, M3BIM, Malto-BIM and Melibio-BIM, in collagen and thrombin-stimulated human platelets in vitro was examined. Among the compounds tested, only compound M3BIM exerted concentration (20-60 µM)-dependent inhibitory effects against collagen (1 µg/ml) and thrombin (0...
September 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28941186/three-novel-mutations-in-cyba-among-22-iranians-with-chronic-granulomatous-disease
#10
M Badalzadeh, S Tajik, M R Fazlollahi, M Houshmand, F Fattahi, Z Alizadeh, M Movahedi, Z Adab, G T Khotaei, A A Hamidieh, H Heidarnazhad, Z Pourpak
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. The enzyme is at least composed of membrane-bound subunits gp91-phox and p22-phox (also named cytochrome b558 ), and cytosolic ones p40-phox, p47-phox and p67-phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22-phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive-CGD (AR-CGD) were identified...
September 20, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28939422/suppressed-ubiquitination-of-nrf2-by-p47-phox-contributes-to-nrf2-activation
#11
Kyun Ha Kim, Ruxana T Sadikot, Ji Yeon Lee, Han-Sol Jeong, Yu-Kyoung Oh, Timothy S Blackwell, Myungsoo Joo
Although critical in phagocytosis in innate immunity, reactive oxygen species (ROS) collaterally inflict damage to host phagocytes because they indiscriminate targets. Since Nrf2 increases the expression of anti-oxidant enzymes that nullifies ROS, ROS activating Nrf2 is a critical negative regulatory step for countering the deleterious effects of ROS. Here, we postulate whether, along with ROS activating Nrf2, NADPH oxidase components also participate in direct activation of Nrf2, contributing to protection from ROS...
September 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28939294/the-novel-compound-mp407-inhibits-platelet-aggregation-through-cyclic-amp-dependent-processes
#12
Chung-Shuen Lin, Tso-Hsiao Chen, I-Hsin Lin, An-Rong Lee, Tz-Chong Chou
Platelet hyperactivity plays a critical role for initiating several vascular diseases such as atherothrombosis. Therefore, development of effective antiplatelet agents is necessary for ameliorating platelet-related diseases. In this study, we investigated the effects of the new synthesized compound, MP407 on platelet aggregation and further elucidated the underlying mechanisms. Our results demonstrated that MP407 dose-dependently inhibited collagen-induced platelet aggregation, thromboxane B2 (TXB2) production, intracellular Ca(2+) mobilization, platelet membrane GPIIb/IIIa expression, and the phosphorylation of Akt, GSK3β, p38MAPK, and phospho (Ser) PKC substrate (p47)...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28916473/down-regulation-of-nox2-activity-in-phagocytes-mediated-by-atm-kinase-dependent-phosphorylation
#13
Sylvain Beaumel, Antoine Picciocchi, Franck Debeurme, Corinne Vivès, Anne-Marie Hesse, Myriam Ferro, Didier Grunwald, Heather Stieglitz, Pahk Thepchatri, Susan M E Smith, Franck Fieschi, Marie José Stasia
NADPH oxidases (NOX) have many biological roles, but their regulation to control production of potentially toxic ROS molecules remains unclear. A previously identified insertion sequence of 21 residues (called NIS) influences NOX activity, and its predicted flexibility makes it a good candidate for providing a dynamic switch controlling the NOX active site. We constructed NOX2 chimeras in which NIS had been deleted or exchanged with those from other NOXs (NIS1, 3 and 4). All contained functional heme and were expressed normally at the plasma membrane of differentiated PLB-985 cells...
September 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28878675/inhibition-of-collagen-induced-platelet-aggregation-by-the-secobutanolide-secolincomolide-a-from-lindera-obtusiloba-blume
#14
Sang-Hyuk Jung, Joo-Hui Han, Hyun-Soo Park, Jung-Jin Lee, Seo Young Yang, Young Ho Kim, Kyung-Sun Heo, Chang-Seon Myung
Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28878301/epa-dha-6-1-prevents-angiotensin-ii-induced-hypertension-and-endothelial-dysfunction-in-rats-role-of-nadph-oxidase-and-cox-derived-oxidative-stress
#15
Zahid Rasul Niazi, Grazielle C Silva, Thais Porto Ribeiro, Antonio J León-González, Mohamad Kassem, Abdur Mirajkar, Azhar Alvi, Malak Abbas, Faraj Zgheel, Valérie B Schini-Kerth, Cyril Auger
Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg(-1) per day) before chronic infusion of Ang II (0...
September 7, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28855537/activation-of-nadph-oxidases-leads-to-dna-damage-in-esophageal-cells
#16
Vikas Bhardwaj, Ravindran Caspa Gokulan, Andela Horvat, Liudmila Yermalitskaya, Olga Korolkova, Kay M Washington, Wael El-Rifai, Sergey I Dikalov, Alexander I Zaika
Gastroesophageal reflux disease (GERD) is the strongest known risk factor for esophageal adenocarcinoma. In the center of tumorigenic events caused by GERD is repeated damage of esophageal tissues by the refluxate. In this study, we focused on a genotoxic aspect of exposure of esophageal cells to acidic bile reflux (BA/A). Analyzing cells generated from patients with Barrett's esophagus and human esophageal specimens, we found that BA/A cause significant DNA damage that is mediated by reactive-oxygen species...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835433/integration-of-trpc6-and-nadph-oxidase-activation-in-lysophosphatidylcholine-induced-trpc5-externalization
#17
Pinaki Chaudhuri, Michael A Rosenbaum, Lutz Birnbaumer, Linda M Graham
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate TRPC6, and the subsequent increase in intracellular Ca(2+) leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47(phox) and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca(2+) as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6(-/-) endothelial cells...
August 23, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28827764/traf4-promotes-lung-cancer-aggressiveness-by-modulating-tumor-microenvironment-in-normal-fibroblasts
#18
EunGi Kim, Wanyeon Kim, Sungmin Lee, Jahyun Chun, JiHoon Kang, Gaeul Park, IkJoon Han, Hee Jung Yang, HyeSook Youn, BuHyun Youn
Normal fibroblasts surrounding tumor cells play a crucial role in cancer progression through formation of the tumor microenvironment. Because factors secreted from normal fibroblasts can modulate the tumor microenvironment, it is necessary to identify key factors associated with regulation of secreted factors and to investigate the molecular mechanisms contributing to the tumor microenvironment formation process. In this study, we found that radiation induced the expression and K63-linkage poly-ubiquitination of TRAF4 in normal lung fibroblasts...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821269/age-exacerbates-microglial-activation-oxidative-stress-inflammatory-and-nox2-gene-expression-and-delays-functional-recovery-in-a-middle-aged-rodent-model-of-spinal-cord-injury
#19
Ramona E von Leden, Guzal Khayrullina, Kasey E Moritz, Kimberly R Byrnes
BACKGROUND: Spinal cord injury (SCI) among people over age 40 has been steadily increasing since the 1980s and is associated with worsened outcome than injuries in young people. Age-related increases in reactive oxygen species (ROS) are suggested to lead to chronic inflammation. The NADPH oxidase 2 (NOX2) enzyme is expressed by microglia and is a primary source of ROS. This study aimed to determine the effect of age on inflammation, oxidative damage, NOX2 gene expression, and functional performance with and without SCI in young adult (3 months) and middle-aged (12 months) male rats...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28793292/huangqi-decoction-ameliorates-streptozotocin-induced-rat-diabetic-nephropathy-through-antioxidant-and-regulation-of-the-tgf-%C3%AE-mapk-ppar-%C3%AE-signaling
#20
Haiyan Han, Aili Cao, Li Wang, Hengjiang Guo, Yingjun Zang, Zezheng Li, Xuemei Zhang, Wen Peng
BACKGROUND/AIMS: Huangqi Decoction (HQD) has been traditionally used to treat diabetes mellitus in China. The present study was carried out to assess the protective effect of HQD on diabetic nephropathy (DN) using the streptozotocin-induced (STZ) diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Wistar rats. 40 diabetic rats were divided into 5 groups: vehicle-treated (DN group), 0.45, 0.15, 0.05 g/kg HQD-treated diabetic group (HQD group) and 1 mg/kg rosiglitazone-treated diabetic group (RGZ group)...
2017: Cellular Physiology and Biochemistry
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