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Jianbo Li, Huixia Jia, Xiaojiao Han, Jin Zhang, Pei Sun, Mengzhu Lu, Jianjun Hu
Salix psammophila is a desert shrub willow that has extraordinary adaptation to abiotic stresses and plays an important role in maintaining local ecosystems. Moreover, S. psammophila is regarded as a promising biomass feedstock because of its high biomass yields and short rotation coppice cycle. However, few suitable reference genes (RGs) for quantitative real-time polymerase chain reaction (qRT-PCR) constrain the study on normalization of gene expression in S. psammophila until now. Here, we investigated the expression stabilities of 14 candidate RGs across tissue types and under four abiotic stress treatments, including heat, cold, salt, and drought treatments...
2016: Frontiers in Plant Science
Tomasz Szul, Peter Castaldi, Michael H Cho, J Edwin Blalock, Amit Gaggar
In chronic inflammatory lung disorders such as chronic obstructive pulmonary disease (COPD), the concurrent organ-specific and systemic inflammatory responses lead to airway remodelling and vascular dysfunction. Although a major common risk factor for COPD, cigarette smoke alone cannot explain the progression of this disease; there is increasing evidence that genetic predisposition also plays a role in COPD susceptibility and progression. A key enzyme in chronic lung inflammation is leukotriene A4 hydrolase (LTA4H)...
January 2016: ERJ Open Research
Sandra K Wittmann, Lena Kalinowsky, Jan S Kramer, René Bloecher, Stefan Knapp, Dieter Steinhilber, Denys Pogoryelov, Ewgenij Proschak, Jan Heering
The leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme, containing a peptidase and a hydrolase activity both activities having opposing functions regulating inflammatory response. The hydrolase activity is responsible for the conversion of leukotriene A4 to pro-inflammatory leukotriene B4, and hence, selective inhibitors of the hydrolase activity are of high pharmacological interest. Here we present the thermodynamic characterization of structurally distinct inhibitors of the LTA4H that occupy different regions of the binding site using different biophysical methods...
November 1, 2016: Bioorganic & Medicinal Chemistry
Gopalan Narendran, Dhanasekaran Kavitha, Ramesh Karunaianantham, Leonardo Gil-Santana, Jilson L Almeida-Junior, Sirasanambatti Devarajulu Reddy, Marimuthu Makesh Kumar, Haribabu Hemalatha, Nagesh Nalini Jayanthi, Narayanan Ravichandran, Raja Krishnaraja, Angamuthu Prabhakar, Tamizhselvan Manoharan, Lokeswaran Nithyananthan, Gunasundari Arjunan, Mohan Natrajan, Soumya Swaminathan, Bruno B Andrade
BACKGROUND: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory phenomenon complicating HIV management in coincidental tuberculosis (TB) infection, upon immune reconstitution driven by antiretroviral therapy (ART). Leukotriene A4 hydroxylase (LTA4H), an enzyme which converts LTA4 to LTB4, regulates the balance between the anti-inflammatory lipoxins and pro-inflammatory LTB4, with direct implications in TB-driven inflammation. In humans, a single nucleotide polymorphism (SNP) in the LTA4H promoter which regulates its transcriptional activity (rs17525495) has been identified and described to impact clinical severity of TB presentation and response to corticosteroid therapy...
2016: PloS One
Ricardo Wesley Alberca-Custódio, Flávia Regina Greiffo, BreAnne MacKenzie, Manoel Carneiro Oliveira-Junior, Adilson Santos Andrade-Sousa, Gustavo Silveira Graudenz, Angela Batista Gomes Santos, Nilsa Regina Damaceno-Rodrigues, Hugo Caire Castro-Faria-Neto, Fernanda Magalhaes Arantes-Costa, Milton De Arruda Martins, Asghar Abbasi, Chin Jia Lin, Marco Idzko, Ana Paula Ligeiro Oliveira, Hinnak Northoff, Rodolfo Paula Vieira
INTRODUCTION: Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma. METHODS: Sixty-four male, BALB/c mice were distributed into Control, Exercise (Exe), OVA, and OVA + Exe groups. Treadmill training was performed at moderate intensity, 5×/week, 1 h/session for 4 weeks...
2016: Frontiers in Immunology
Cláudia Regina Santos Silva, Joice Matos Biselli-Périco, Bruna Lancia Zampieri, Wilson Araujo Silva, Jorge Estefano Santana de Souza, Matheus Carvalho Bürger, Eny Maria Goloni-Bertollo, Érika Cristina Pavarino
OBJECTIVE: The aim of the study was to investigate the expression patterns of a specific set of genes involved in the inflammation process in children with Down Syndrome (DS) and children without the syndrome (control group) to identify differences that may be related to the immune abnormalities observed in DS individuals. METHOD: RNA samples were obtained from peripheral blood, and gene expression was quantified using the TaqMan® Array Plate Human Inflammation Kit, which facilitated the investigation into 92 inflammation-related genes and four reference genes using real-time polymerase chain reaction (qPCR)...
2016: Mediators of Inflammation
Nashid Farhan, Sean Fitzpatrick, Yun M Shim, Mikell Paige, Diana Shu-Lian Chow
4-Methoxydiphenylmethane (4-MDM), a selective augmenter of Leukotriene A4 Hydrolase (LTA4H), is a new anti-inflammatory compound for potential treatment of chronic obstructive pulmonary disease (COPD). Currently, there is no liquid chromatography tandem mass spectrometric (LC-MS/MS) method for the quantification of 4-MDM. A major barrier for developing the LC-MS/MS method is the inability of electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) to ionize 4-MDM due to its hydrophobicity and lack of any functional group for ionization...
September 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
Satu Kuokkanen, Alex J Polotsky, Justin Chosich, Andrew P Bradford, Anna Jasinska, Tzu Phang, Nanette Santoro, Susan E Appt
UNLABELLED: Obesity and malnutrition are associated with decreased fecundity in women. Impaired reproductive capacity in obese women is often attributed to anovulation. However, obese women with ovulatory cycles also have reduced fertility, but the etiology of their impaired reproduction is only partially understood. Accumulating evidence suggests that obesity directly impairs oocyte and embryo quality as well as endometrial receptivity. In obese women, urinary progesterone metabolite excretion is decreased, but in excess of what can be explained by suppressed gonadotropin secretion, suggesting that apart from its central effect obesity may directly affect progesterone (P4) production...
August 2016: Systems Biology in Reproductive Medicine
Qiang Xiao, Ningning Dong, Xue Yao, Dang Wu, Yanli Lu, Fei Mao, Jin Zhu, Jian Li, Jin Huang, Aifang Chen, Lu Huang, Xuehai Wang, Guangxiao Yang, Guangyuan He, Yong Xu, Weiqiang Lu
Neutrophils play an important role in the occurrence and development of acute lung injury (ALI). Leukotriene B4 (LTB4), a hydrolysis product of epoxide leukotriene A4 (LTA4) catalyzed by LTA4 hydrolase (LTA4H), is one of the most potent chemoattractants for neutrophil. Bufexamac is a drug widely used as an anti-inflammatory agent on the skin, however, the mechanism of action is still not fully understood. In this study, we found bufexamac was capable of specifically inhibiting LTA4H enzymatic activity and revealed the mode of interaction of bufexamac and LTA4H using X-ray crystallography...
2016: Scientific Reports
Kari Hemminki, Bowang Chen, Abhishek Kumar, Olle Melander, Jonas Manjer, Göran Hallmans, Ulrika Pettersson-Kymmer, Claes Ohlsson, Gunnar Folprecht, Harald Löffler, Alwin Krämer, Asta Försti
Cancer of unknown primary site (CUP) is a fatal cancer diagnosed through metastases at various organs. Little is known about germline genetics of CUP which appears worth of a search in view of reported familial associations in CUP. In the present study, samples from CUP patients were identified from 2 Swedish biobanks and a German clinical trial, totaling 578 CUP patients and 7628 regionally matched controls. Diagnostic data specified the organ where metastases were diagnosed. We carried out a genome-wide association study on CUP cases and controls...
April 19, 2016: Oncotarget
Yiqun Wu, Shuai Li, Kuo Liu, Xun Tang, Kai Fang, Na Li, Jin Li, Tao Wu, Dafang Chen, Yonghua Hu
OBJECTIVE: To investigate the association between polymorphism of leukotriene A4 hydrolase (LTA4H) gene among ischemic stroke patients and the related subtypes in the discordant sib pairs. METHODS: Families including ischemic stroke patients and their siblings were recruited. Four single nucleotide polymorphisms (SNPs) of LTA4H as rs2072512, rs2540489, rs2540500 and rs6538697 were selected. Generalized estimating equation (GEE) was used to adjust for in-family correlation in the analysis of discordant sib pairs...
August 2015: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
J L Blok, K Li, C Brodmerkel, P Horvátovich, M F Jonkman, B Horváth
BACKGROUND: Treatment of hidradenitis suppurativa (HS) is difficult and the search for effective therapies continues. OBJECTIVES: To evaluate the efficacy of ustekinumab and to discover a potential biomarker for HS. METHODS: Seventeen patients were included in this open-label study and treated with 45 or 90 mg ustekinumab at weeks 0, 4, 16 and 28. Proteomic technology and enzyme-linked assay analysis was applied to sera. RESULTS: Twelve patients completed the protocol...
April 2016: British Journal of Dermatology
Patrick Appiah-Kubi, Mahmoud E S Soliman
Human leukotriene A4 hydrolase/aminopeptidase (LTA4H) is a zinc metalloenzyme with a dual catalytic activity; conversion of LTA4 into LTB4 and degradation of chemotactic tripeptide Pro-Gly-Pro (PGP). Existing inhibitors, such as SC-57461A, block both catalytic activities of the enzyme, leading to drug failures. Recently, a novel compound, ARM1, was reported to selectively inhibit the hydrolase activity of LTA4H while sparing its aminopeptidase activity. However, the molecular understanding of such preferential inhibitory mechanism remains obscure...
November 2016: Journal of Biomolecular Structure & Dynamics
Sarah K Orr, Kathryn L Butler, Douglas Hayden, Ronald G Tompkins, Charles N Serhan, Daniel Irimia
OBJECTIVES: Specialized proresolving lipid mediators have emerged as powerful modulators of inflammation and activators of resolution. Animal models show significant benefits of specialized proresolving lipid mediators on survival and wound healing after major burn trauma. To date, no studies have investigated specialized proresolving lipid mediators and their relation to other lipid mediator pathways in humans after trauma. Here we determine if patients with poor outcomes after trauma have dysregulated lipid mediator pathways...
December 2015: Critical Care Medicine
Samia Akthar, Dhiren F Patel, Rebecca C Beale, Teresa Peiró, Xin Xu, Amit Gaggar, Patricia L Jackson, J Edwin Blalock, Clare M Lloyd, Robert J Snelgrove
Bioactive matrix fragments (matrikines) have been identified in a myriad of disorders, but their impact on the evolution of airway inflammation has not been demonstrated. We recently described a pathway where the matrikine and neutrophil chemoattractant proline-glycine-proline (PGP) could be degraded by the enzyme leukotriene A4 hydrolase (LTA4H). LTA4H classically functions in the generation of pro-inflammatory leukotriene B4, thus LTA4H exhibits opposing pro- and anti-inflammatory activities. The physiological significance of this secondary anti-inflammatory activity remains unknown...
2015: Nature Communications
Thea K Kleinschmidt, Martin Haraldsson, Devaraj Basavarajappa, Erik Lundeberg, Madhuranayaki Thulasingam, Maria Ekoff, Alexander Fauland, Christoph Lehmann, Astrid S Kahnt, Lennart Lindbom, Jesper Z Haeggström
Cysteinyl leukotrienes (cys-LTs) are lipid mediators of inflammation. The enzyme catalyzing synthesis of cys-LTs, leukotriene C4 synthase (LTC4S), is considered an important drug target. Here we report the synthesis and characterization of three tandem benzophenone amino pyridines as inhibitors of LTC4S in vitro and in vivo. The inhibitors were characterized in vitro using recombinant human LTC4S, MonoMac 6 cells, and a panel of peripheral human immune cells. In vivo, the compounds were tested in the Zymosan A-induced peritonitis mouse model...
October 2015: Journal of Pharmacology and Experimental Therapeutics
Brett D Noerager, Xin Xu, Virginia A Davis, Caleb W Jones, Svetlana Okafor, Alicia Whitehead, J Edwin Blalock, Patricia L Jackson
Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP...
December 2015: Inflammation
Yasufumi Kato, Haruhiko Nakamura, Hiromasa Tojo, Masaharu Nomura, Toshitaka Nagao, Takeshi Kawamura, Tatsuhiko Kodama, Tatsuo Ohira, Norihiko Ikeda, Thomas Fehniger, György Marko-Varga, Toshihide Nishimura, Harubumi Kato
BACKGROUND: In the new pathologic classification of lung adenocarcinoma proposed by IASLC/ATS/ERS in 2011, lepidic type adenocarcinomas are constituted by three subtypes; adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPIA). Although these subtypes are speculated to show sequential progression from preinvasive lesion to invasive lung cancer, changes of protein expressions during these processes have not been fully studied yet...
December 2015: Clinical and Translational Medicine
Rama K Mishra, Jasbir Singh
In this study, the role of highly structured water molecules present in the active site of the leukotriene A4 hydrolase (LTA4H) enzyme has been critically examined through the docking experiments. It was observed that different experiments were necessary to perform the docking studies. The ligands capable of displacing or interacting with bound-water(s) displayed different binding poses as well as the scores. The docking scores E (CvdW) from Glide and ChemScore (CS) from FlexX, with and without bound-waters, obtained through different docking experiments were used to construct two structure guided bi-parametric linear regression models using the IC50 enzyme activity data...
2015: Current Computer-aided Drug Design
Mahmoud Merhi, Sally Demirdjian, Essa Hariri, Nada Sabbah, Sonia Youhanna, Michella Ghassibe-Sabbagh, Joseph Naoum, Marc Haber, Raed Othman, Samer Kibbani, Elie Chammas, Roy Kanbar, Hamid El Bayeh, Youssef Chami, Antoine Abchee, Daniel E Platt, Pierre Zalloua, Georges Khazen
BACKGROUND: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis. AIM: The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD. METHODS: CAD was detected by cardiac catheterization...
June 2015: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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