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https://www.readbyqxmd.com/read/28507800/formyl-peptide-receptor-1-suppresses-gastric-cancer-angiogenesis-and-growth-by-exploiting-inflammation-resolution-pathways
#1
Nella Prevete, Federica Liotti, Anna Illiano, Angela Amoresano, Piero Pucci, Amato de Paulis, Rosa Marina Melillo
Chronic inflammation can result from inadequate engagement of resolution mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs) arising from the metabolic activity of lipoxygenases (ALOX5/15) on ω-6 or ω-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by inhibiting its inflammatory/angiogenic potential. In this study, we asked whether FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and growth...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506553/inhibition-of-12-15-lo-ameliorates-cvb3-induced-myocarditis-by-activating-nrf2
#2
Feng Ai, Jiayong Zheng, Yanwei Zhang, Taibing Fan
Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated and involved in the development of heart failure. Nuclear factor E2-related factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and its underlying molecular mechanism have not yet been elucidated. Here, we demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes...
May 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28504669/nitric-oxide-prevents-a-pathogen-permissive-granulocytic-inflammation-during-tuberculosis
#3
Bibhuti B Mishra, Rustin R Lovewell, Andrew J Olive, Guoliang Zhang, Wenfei Wang, Eliseo Eugenin, Clare M Smith, Jia Yao Phuah, Jarukit E Long, Michelle L Dubuke, Samantha G Palace, Jon D Goguen, Richard E Baker, Subhalaxmi Nambi, Rabinarayan Mishra, Matthew G Booty, Christina E Baer, Scott A Shaffer, Veronique Dartois, Beth A McCormick, Xinchun Chen, Christopher M Sassetti
Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. Using M. tuberculosis mutants as indicators of the pathogen's environment, we inferred that granulocytic inflammation generates a nutrient-replete niche that supports M...
May 15, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28502039/possible-involvement-of-the-lipoxygenase-and-leukotriene-signaling-pathways-in-cisplatin-mediated-renal-toxicity
#4
Osama A Alkhamees, Abdulaziz S Alroujayee, Hatem M Abuohashish, Fatima S Alrojayee, Mohammed M Ahmed
PURPOSE: The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity. METHODS: Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively...
May 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28496472/synthesis-and-biological-evaluation-of-n-5-pyridin-2-yl-1-3-4-thiadiazol-2-yl-benzamide-derivatives-as-lipoxygenase-inhibitor-with-potential-anticancer-activity
#5
Alireza Aliabadi, Ahmad Mohammadi-Farani, Sahar Roodabeh, Farahnaz Ahmadi
In the recent years, the role of LOX enzymes in the origin of neoplastic diseases such as colorectal, skin, pancreatic and renal cancers has been confirmed. A new series of 1,3,4-thiadiazole derivatives bearing 2-pyridyl moiety was synthesized and the cytotoxicity of the members of this series was assessed using MTT protocol. Enzyme inhibitory activity of the prepared compounds was also tested against 15-lipoxygenase-1 as a novel target for the discovery of anticancer drugs. PC3, HT29 and SKNMC cell lines were utilized and the obtained results were compared with doxorubicin...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28492741/effect-of-alox-15-polymorphism-on-gcf-levels-of-lipoxin-a4-in-chronic-periodontitis-a-preliminary-study
#6
Fouzia Tarannum, Mohamed Faizuddin
Lipoxins play an important role in periodontal resolution, hence, investigation of genetic polymorphism of lipoxin gene may provide important information on the role of lipoxins in periodontal disease pathogenesis. The aim of this study was to investigate a polymorphism of C-to-T substitution at position c.-292 in ALOX15 (reticulocyte-type 15 lipoxygenase 1) gene in patients with chronic periodontitis and to associate the polymorphism with gingival crevicular fluid (GCF) lipoxin A4 (LXA4) levels. Forty-five chronic periodontitis and 45 periodontally healthy patients were included in this case-control study...
March 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/28477412/salvia-officinalis-l-essential-oil-from-spain-determination-of-composition-antioxidant-capacity-antienzymatic-and-antimicrobial-bioactivities
#7
Ana-Belen Cutillas, Alejandro Carrasco, Ramiro Martinez-Gutierrez, Virginia Tomas, José Tudela
Four essential oils (EOs) from Salvia officinalis L. cultivated in Spain (Murcia province) were analyzed by gas chromatography coupled with mass spectrometry (GC/MS) to determine their relative and absolute composition. The main components were α-thujone (22.8-41.7%), camphor (10.7-19.8%), 1,8-cineole (4.7-15.6%) and β-thujone (6.1-15.6%). Enantioselective gas chromatography identified (-)-α-thujone and (+)-camphor as the main enantiomers in all the analyzed EOs. Furthermore, when the EOs were tested to determine their antioxidant activity against free radicals and as ferric reducing and ferrous chelating agents, all were seen to have moderate activity due to the compounds they contained, such as linalool or terpinene...
May 6, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28465374/regulation-of-delta-opioid-receptor-mediated-signaling-and-antinociception-in-peripheral-sensory-neurons-by-arachidonic-acid-dependent-12-15-lipoxygenase-metabolites
#8
Laura C Sullivan, Teresa A Chavera, Xiaoli Gao, Miryam M Pando, Kelly A Berg
The function of delta opioid receptors (DOR) expressed by peripheral pain-sensing neurons (nociceptors) is regulated by both cyclooxygenase (COX)- and lipoxygenase (LOX)-dependent arachidonic acid (AA) metabolites (Sullivan et al., 2015). Whereas COX metabolites enhance responsiveness, LOX metabolites elicit a refractory, non-signaling state of the DOR receptor system for antinociceptive signaling. In this study, using high performance liquid chromatography tandem mass spectrometry analyses, we have found that the 12/15-LOX metabolites, 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE, were elevated following treatment of adult rat primary sensory neuron cultures with AA...
May 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28460604/the-15-lo-1-15-hete-system-promotes-angiogenesis-by-upregulating-vegf-in-ischemic-brains
#9
Li Chen, Yan-Mei Zhu, Yu-Nong Li, Peng-Yan Li, Di Wang, Yu Liu, You-Yang Qu, Da-Ling Zhu, Yu-Lan Zhu
OBJECTIVES: Angiogenesis promotes neurobehavioral recovery after cerebral ischemic stroke. 15(S)-hydroxyeicosatetraenoic acid (15-HETE) is one of the major metabolites of arachidonic acid by 15-lipoxygenase (15-LO) and stimulates the production of vascular endothelial growth factor (VEGF), thus, inducing autocrine-mediated angiogenesis. The present study aimed to investigate the role of 15-LO/15-HETE system on VEGF expression and angiogenesis in brain ischemia. METHODS: Rat cerebral arterial vascular endothelial cells were used to set up a cell injury model of oxygen-glucose deprivation and reoxygenation (OGD/R), mimicking a condition of brain ischemia...
May 1, 2017: Neurological Research
https://www.readbyqxmd.com/read/28436420/key-role-of-15-lo-15-hete-in-angiogenesis-and-functional-recovery-in-later-stages-of-post-stroke-mice
#10
Di Wang, Yu Liu, Li Chen, Pengyan Li, Youyang Qu, Yanmei Zhu, Yulan Zhu
This study sought to clarify the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests to determine functional recovery after stroke. Double immunofluorescence staining of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC proliferation and migration...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28411230/interaction-of-12-15-lipoxygenase-with-fatty-acids-alters-the-leukocyte-kinetics-leading-to-improved-post-myocardial-infarction-healing
#11
Ganesh V Halade, Vasundhara Kain, Kevin A Ingle, Sumanth D Prabhu
The metabolic transformation of fatty acids to form oxylipids using 12/15lipoxygenase (LOX) can promote either resolving or non-resolving inflammation. However, the mechanism of how 12/15LOX interacts with PUFA (polyunsaturated fatty acids) in post-myocardial infarction (MI) healing is unclear. Here, we reported the role of 12/15LOX in post-MI cardiac remodeling in a PUFA (10% w/w, 22 Kcal) enriched environment. Wild-type (WT; C57BL/6J) and 12/15LOX null (12/15LOX(-/-)) male mice of 8-12-weeks age were fed PUFA-enriched diet for 1 month and subjected to permanent coronary artery ligation...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28409415/%C3%AE-aminobutyric-acid-gaba-confers-chromium-stress-tolerance-in-brassica-juncea-l-by-modulating-the-antioxidant-defense-and-glyoxalase-systems
#12
Jubayer Al Mahmud, Mirza Hasanuzzaman, Kamrun Nahar, Anisur Rahman, Md Shahadat Hossain, Masayuki Fujita
Chromium (Cr) toxicity is hazardous to the seed germination, growth, and development of plants. γ-aminobutyric acid (GABA) is a non-protein amino acid and is involved in stress tolerance in plants. To investigate the effects of GABA in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.) seedlings with Cr (0.15 and 0.3 mM K2CrO4, 5 days) alone and in combination with GABA (125 µM) in a semi-hydroponic medium. The roots and shoots of the seedlings accumulated Cr in a dose-dependent manner, which led to an increase in oxidative damage [lipid peroxidation; hydrogen peroxide (H2O2) content; superoxide (O2(•-)) generation; lipoxygenase (LOX) activity], methylglyoxal (MG) content, and disrupted antioxidant defense and glyoxalase systems...
April 13, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28403941/obesity-is-positively-associated-with-arachidonic-acid-derived-5-and-11-hydroxyeicosatetraenoic-acid-hete
#13
Charles Austin Pickens, Lorraine M Sordillo, Chen Zhang, Jenifer I Fenton
BACKGROUND: Oxylipids are oxygenated polyunsaturated fatty acid (PUFA) metabolites that are responsible for the onset and resolution of the inflammatory response. Enzymatic oxygenation through the lipoxygenase (LOX) or cytochrome P450 (CYP) pathways can form oxylipids that have either proinflammatory or proresolving functions depending on the type of PUFA substrate and degree of metabolism. The objective of this study was to determine how PUFA substrates and their corresponding oxylipids are associated with obesity...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28393703/mir-106a-is-associated-with-diabetic-peripheral-neuropathy-through-the-regulation-of-12-15-lox-mediated-oxidative-nitrative-stress
#14
Yuanbo Wu, Dandan Xu, Xiang Zhu, Guangwei Yang, Mingshan Ren
BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that with a complex pathogenesis. Study has reported that oxidative stress and nitrative stress were all involved in the DPN, however, the mechanism between them was still unclear. In the present study, we investigated whether miR-106a signaling regulated 12/15-Lipoxygenase (12/15-LOX) on oxidative/nitrative stress in DPN. METHODS: Dorsal root ganglion (DRG) was isolated from 10 healthy mice and 10 DPN mice...
April 4, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28386601/on-the-mechanism-of-cytoprotection-by-ferrostatin-1-and-liproxstatin-1-and-the-role-of-lipid-peroxidation-in-ferroptotic-cell-death
#15
Omkar Zilka, Ron Shah, Bo Li, José Pedro Friedmann Angeli, Markus Griesser, Marcus Conrad, Derek A Pratt
Ferroptosis is a form of regulated necrosis associated with the iron-dependent accumulation of lipid hydroperoxides that may play a key role in the pathogenesis of degenerative diseases in which lipid peroxidation has been implicated. High-throughput screening efforts have identified ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent inhibitors of ferroptosis - an activity that has been ascribed to their ability to slow the accumulation of lipid hydroperoxides. Herein we demonstrate that this activity likely derives from their reactivity as radical-trapping antioxidants (RTAs) rather than their potency as inhibitors of lipoxygenases...
March 22, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28375641/a-pilot-study-to-examine-the-effects-of-an-anti-inflammatory-supplement-on-eicosanoid-derivatives-in-patients-with-chronic-kidney-disease
#16
Brian D Shelmadine, Rodney G Bowden, Jennifer J Moreillon, Matthew B Cooke, Peiying Yang, Erika Deike, Jackson O Griggs, Ron L Wilson
BACKGROUND: Chronic kidney disease (CKD) is a progressive disease with an inverse relationship between kidney function and levels of inflammation and oxidative stress. Curcumin and Boswellia serrata have been reported to exert anti-inflammatory effects on the cyclooxygenase and lipoxygenase pathways. Therefore, the purpose of this study was to study the effects of a supplement containing curcumin and B. serrata on eicosanoid derivatives in early stage CKD patients who had not initiated hemodialysis...
April 4, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28356517/protectin-d1n-3-dpa-and-resolvin-d5n-3-dpa-are-effectors-of-intestinal-protection
#17
Thomas Gobbetti, Jesmond Dalli, Romain A Colas, Donata Federici Canova, Marius Aursnes, Delphine Bonnet, Laurent Alric, Nathalie Vergnolle, Celine Deraison, Trond V Hansen, Charles N Serhan, Mauro Perretti
The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within the affected tissue; failure of effective resolution may lead to tissue injury. Because persistence of inflammatory signals is a main feature of chronic inflammatory conditions, including inflammatory bowel diseases (IBDs), herein we investigate expression and functions of SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human IBD colon biopsies, quantifying a significant up-regulation of the resolvin and protectin pathway compared with normal gut tissue...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28351645/targeting-of-12-15-lipoxygenase-in-retinal-endothelial-cells-but-not-in-monocytes-macrophages-attenuates-high-glucose-induced-retinal-leukostasis
#18
Ahmed S Ibrahim, Heba Saleh, Mohamed El-Shafey, Khaled A Hussein, Khaled El-Masry, Babak Baban, Nader Sheibani, Mong-Heng Wang, Amany Tawfik, Mohamed Al-Shabrawey
AIMS: Our previous studies have established a role for 12/15-lipoxygenase (LO) in mediating the inflammatory response in diabetic retinopathy (DR). However, the extent at which the local or systemic induction of 12/15-LO activity involved is unclear. Thus, the current study aimed to characterize the relative contribution of retinal endothelial versus monocytic/macrophagic 12/15-LO to inflammatory responses in DR. MATERIALS & METHODS: We first generated a clustered heat map for circulating bioactive lipid metabolites in the plasma of streptozotocin (STZ)-induced diabetic mice using liquid chromatography coupled with mass-spectrometry (LC-MS) to evaluate changes in circulating 12/15-LO activity...
March 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28347845/global-assessment-of-oxidized-free-fatty-acids-in-brain-reveals-an-enzymatic-predominance-to-oxidative-signaling-after-trauma
#19
Tamil S Anthonymuthu, Elizabeth M Kenny, Andrew A Amoscato, Jesse Lewis, Patrick M Kochanek, Valerian E Kagan, Hülya Bayır
Traumatic brain injury (TBI) is a major health problem associated with significant morbidity and mortality. The pathophysiology of TBI is complex involving signaling through multiple cascades, including lipid peroxidation. Oxidized free fatty acids, a prominent product of lipid peroxidation, are potent cellular mediators involved in induction and resolution of inflammation and modulation of vasomotor tone. While previous studies have assessed lipid peroxidation after TBI, to our knowledge no studies have used a systematic approach to quantify the global oxidative changes in free fatty acids...
March 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28344594/articular-inflammation-induced-by-an-enzymatically-inactive-lys49-phospholipase-a2-activation-of-endogenous-phospholipases-contributes-to-the-pronociceptive-effect
#20
Renata Gonçalves Dias, Sandra Coccuzzo Sampaio, Morena Brazil Sant'Anna, Fernando Queiroz Cunha, José María Gutiérrez, Bruno Lomonte, Yara Cury, Gisele Picolo
BACKGROUND: Arthritis is a set of inflammatory conditions that induce aching, stiffness, swelling, pain and may cause functional disability with severe consequences to the patient's lives. These are multi-mediated pathologies that cannot be effectively protected and/or treated. Therefore, the aim of this study was to establish a new model of acute arthritis, using a Lys49-PLA2 (Bothrops asper myotoxin II; MT-II) to induce articular inflammation. METHODS: The articular inflammation was induced by MT-II (10 μg/joint) injection into the left tibio-tarsal or femoral-tibial-patellar joints...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
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