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Jing Shi, Pu Li, Lijin Zhou, Suwen Qi, Bo Wang, Dandan Li, Liang Duan, Wei Xian Chen, Jirong Xia, Lin Zou, Shuangshuang Yang
AIM: To investigate novel potential biomarkers for antidiastole of tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE). MATERIALS & METHODS: iTRAQTM-coupled LC-MS/MS were applied to analyze the proteome of TPE and MPE samples. The candidate proteins were verified by enzyme-linked immunosorbent assay. RESULTS: A total of 432 differential proteins were identified. Enzyme-linked immunosorbent assay revealed significantly higher levels of fibronectin (FN) and cathepsin G (CTSG) in MPE than in TPE, but lower levels of leukotriene-A4 hydrolase (LTA4H)...
February 2019: Biomarkers in Medicine
Yilan Li, Xueming Xu, Dandan Zhang, Wei Cheng, Yanan Zhang, Bo Yu, Yao Zhang
BACKGROUND: Genetic variation in the genes ALOX5 (arachidonate 5-lipoxygenase), ALOX5AP (arachidonate 5-lipoxygenase-activating protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to contribute to the risk of MI (myocardial infarction) in Caucasian and African American populations. All genes encode proteins playing a role in the synthesis of the pro-inflammatory leukotriene B mediators, possibly providing a link between MI and inflammation. The aim of the present study was to investigate whether these associations could be confirmed in the study of China MI patients...
January 24, 2019: Lipids in Health and Disease
John R Montford, Colin Bauer, Evgenia Dobrinskikh, Katharina Hopp, Moshe Levi, Mary Cm Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
In inflammatory diseases, the 5-lipoxygenase (5-LO) pathway contributes to epithelial damage and fibrosis by catalyzing the production of leukotrienes. Antagonists of the 5-LO pathway are currently approved for use in patients and are well tolerated. We found that expression of 5-LO is strongly induced in three models of chronic kidney disease, unilateral ureteral obstruction (UUO), folate nephropathy, and an orthologous mouse model of polycystic kidney disease. Immunohistochemistry showed that macrophages are the dominant source of 5-LO...
January 16, 2019: American Journal of Physiology. Renal Physiology
Nojan Nejatian, Ann-Kathrin Häfner, Firouzeh Shoghi, Klaus Badenhoop, Marissa Penna-Martinez
The arachidonate 5-lipoxygenase (ALOX5) pathway has been implicated in chronic inflammatory disease which may be influenced by vitamin D due to vitamin D response elements (VDRE). We investigated an ALOX5 polymorphism (rs4987105) in patients with type 2 diabetes (T2D) and the in vitro effects of calcitriol (1,25(OH)2 D3 ) on ALOX5 metabolism in monocytes of T2D patients and healthy controls (HC). 533 T2D and 473 HC were genotyped for the rs4987105 polymorphism. In addition, the 25(OH)D3 and 1,25(OH)2 D3 plasma levels were measured in both cohorts...
December 3, 2018: Journal of Steroid Biochemistry and Molecular Biology
JiaYing Wang, Xiaolong Yuan, Shaopan Ye, Shuwen Huang, Yingting He, Hao Zhang, Jiaqi Li, Xiquan Zhang, Zhe Zhang
Objective: Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genome-wide association study (GWAS) using sequence data imputed from SNP panel in a Chinese indigenous chicken population. Methods: A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K single nucleotide polymorphism (SNP) genotyping array...
October 26, 2018: Asian-Australasian Journal of Animal Sciences
Joseph Donovan, Nguyen Hoan Phu, Le Thi Phuong Thao, Nguyen Huu Lan, Nguyen Thi Hoang Mai, Nguyen Thi Mai Trang, Nguyen Thi Thu Hiep, Tran Bao Nhu, Bui Thi Bich Hanh, Vu Thi Phuong Mai, Nguyen Duc Bang, Do Chau Giang, Dang Thi Minh Ha, Jeremy Day, Nguyen Tt Thuong, Nguyen Nang Vien, Ronald B Geskus, Tran Tinh Hien, Evelyne Kestelyn, Marcel Wolbers, Nguyen Van Vinh Chau, Guy E Thwaites
Background:  Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy...
2018: Wellcome Open Research
Kavita Pal, Xin Feng, John W Steinke, Marie D Burdick, Yun M Shim, Sun-Sang Sung, W Gerald Teague, Larry Borish
RATIONALE: Asthma is associated with the over-production of leukotrienes (LT) including LTB4. Severe asthma patients can be highly responsive to 5-LO inhibition, which blocks production of both the cysteinyl LTs and LTB4. Production of LTB4 has traditionally been ascribed to neutrophils, mononuclear phagocytes and epithelial cells and acts as a chemoattractant for inflammatory cells associated with asthma. The source of LTB4 is unclear, especially in eosinophilic asthma. We speculated that the benefit of 5-LO inhibition could be mediated, in part, by inhibition of eosinophil-derived LTB4...
October 23, 2018: American Journal of Respiratory Cell and Molecular Biology
Joseph Donovan, Nguyen Hoan Phu, Nguyen Thi Hoang Mai, Le Tien Dung, Darma Imran, Erlina Burhan, Lam Hong Bao Ngoc, Nguyen Duc Bang, Do Chau Giang, Dang Thi Minh Ha, Jeremy Day, Le Thi Phuong Thao, Nguyen Tt Thuong, Nguyen Nang Vien, Ronald B Geskus, Marcel Wolbers, Raph L Hamers, Reinout van Crevel, Mugi Nursaya, Kartika Maharani, Tran Tinh Hien, Kevin Baird, Nguyen Huu Lan, Evelyne Kestelyn, Nguyen Van Vinh Chau, Guy E Thwaites
Background:  Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based...
2018: Wellcome Open Research
Joseph R Zunt
PURPOSE OF REVIEW: This article details the epidemiology and clinical manifestations of central nervous system (CNS) tuberculosis (TB), provides guidance for diagnostic imaging and CSF testing, and recommends treatment strategies for tuberculous meningitis and other forms of CNS TB, illustrating key aspects of diagnosis and management with case presentations. RECENT FINDINGS: Although improvements in our understanding of the pathogenesis and management of CNS TB have occurred over the past 50 years, the emergence of multidrug-resistant and extensively drug-resistant TB, the advent of acquired immunodeficiency syndrome (AIDS), and the subsequent availability of highly active antiretroviral therapy that can produce the immune reconstitution inflammatory syndrome have complicated the diagnosis and treatment of CNS TB...
October 2018: Continuum: Lifelong Learning in Neurology
Justin Beardsley, Nhat L T Hoang, Freddie M Kibengo, Nguyen L N Tung, Tran Q Binh, Le Q Hung, Wirongrong Chierakul, Guy E Thwaites, Nguyen V V Chau, Thuong T T Nguyen, Ronald B Geskus, Jeremy N Day
Background: The CryptoDex trial showed dexamethasone was associated with poorer clinical outcomes and slower fungal clearance in HIV-associated cryptococcal meningitis. We analysed CSF cytokine concentrations from CrytpoDex participants over the first week of treatment to investigate potential mechanisms of harm and test two hypotheses: dexamethasone reduced pro-inflammatory cytokine concentrations leading to poorer outcomes; and leukotriene A4 hydrolase (LTA4H) genotype (previously associated with dexamethasone responsiveness in tuberculous meningitis) influenced dexamethasone's clinical impact...
August 30, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jie-Ya Wang, Yan-Jiao Zhang, He Li, Xiao-Lei Hu, Mu-Peng Li, Pei-Yuan Song, Qi-Lin Ma, Li-Ming Peng, Xiao-Ping Chen
BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is a recommended treatment for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) to reduce the rate of ischemic events and stent thrombosis. However, high on-treatment platelet reactivity (HTPR) during clopidogrel therapy for some patients may lead to outcome failure and occurrence of cardiovascular events. Amounts of studies have proved that genetic factors may contribute to HTPR...
December 15, 2018: Gene
Robert P Jankov, Kathrine Louise Daniel, Shira Iny, Crystal Kantores, Julijana Ivanovska, Nadya Ben Fadel, Amish Jain
Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, while having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT...
August 9, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Tam Thuy Lu Vo, Won-Jun Jang, Chul-Ho Jeong
Cancer is the second leading cause of death worldwide and has become a global burden. It has long been known that inflammation is related to cancer, as inflammatory components have been identified in the tumor microenvironment and support tumor progression. Among the key inflammatory mediators, leukotrienes were found to be involved in cancer development. In particular, leukotriene B4, which is converted from leukotriene A4 by leukotriene A4 hydrolase (LTA4H), has been implicated in several types of cancer...
November 2018: Annals of the New York Academy of Sciences
Marco Tutone, Alessia Virzì, Anna Maria Almerico
Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydrolase (LTA4H), Phosphoserine phosphatase (HPSP), Phosphodiesterase 4D (PDE4D), AMPA receptor (GluA3 and GluA2 subunits) and Kainate receptor (GluK1 isoform) as potential targets for Indicaxanthin...
October 14, 2018: Journal of Theoretical Biology
Xia Mu, Dingguo Xu
LTA4H is a monozinc bifunctional enzyme which exhibits both aminopeptidase and epoxide hydrolase activities. Its dual functions in anti- and pro-inflammatory roles have attracted wide attention to the inhibitor design. In this work, we tried to construct Michaelis complexes of LTA4H with both a native peptide substrate and LTA4 molecule using combined quantum mechanics and molecular mechanics molecular dynamics simulations. First of all, the zinc ion is coordinated by H295, H299, and E318. For its aminopeptidase activity, similar to conventional peptidases, the fourth ligand to the zinc ion is suggested to be an active site water, which is further hydrogen bonded with a downstream glutamic acid, E296...
July 26, 2018: Journal of Physical Chemistry. B
Hui Wang, Ke Xue, Ping Li, Yuyun Yang, Zixu He, Wei Zhang, Wen Zhang, Bo Tang
Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA4 H through specific recognition and cleavage of amides containing the unnatural amino acid l-AspBzl...
May 15, 2018: Analytical Chemistry
Shelley A Deeke, Amanda E Starr, Zhibin Ning, Sara Ahmadi, Xu Zhang, Janice Mayne, Cheng-Kang Chiang, Ruth Singleton, Eric I Benchimol, David R Mack, Alain Stintzi, Daniel Figeys
OBJECTIVE: Improved biomarkers are an unmet clinical need for suspected inflammatory bowel disease (IBD). Need is greatest for children, since current biomarkers suffers from low specificity, particularly in this population; thus, invasive testing methods, with the accompanying risk of complications, are necessary. Additionally, current biomarkers do not delineate disease extent assessment for ulcerative colitis (UC), a factor involved in therapeutic decisions. METHODS: Intestinal mucosal-luminal interface (MLI) aspirates from the ascending colon (AC) and descending colon (DC) were collected during diagnostic colonoscopy from treatment-naïve children...
May 2018: American Journal of Gastroenterology
Claudia Calcagno, Olivier Lairez, Julie Hawkins, Steven W Kerr, Melanie S Dugas, Thomas Simpson, Jelle Epskamp, Philip M Robson, Mootaz Eldib, Ilda Bander, Purushothaman K-Raman, Sarayu Ramachandran, Alison Pruzan, Audrey Kaufman, Venkatesh Mani, Alexander Ehlgen, Heiko G Niessen, John Broadwater, Zahi A Fayad
OBJECTIVES: The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis. BACKGROUND: Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18 F-fluorodeoxyglucose (18 F-FDG) PET, DCE-MRI, and morphological MRI...
February 2018: JACC. Cardiovascular Imaging
Yu Gu, Xu Zhang, Yan-Kun Chen, Bo-Wen Zhao, Yan-Ling Zhang
5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H), as the major targets of 5-LOX branch in the arachidonic acid (AA) metabolic pathway, play an important role in the treatment of inflammation. Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix have clear anti-inflammation activities. In this paper, the targets of 5-LOX and LTA4H were used as the research carrier, and Hiphop module in DS4.0 (Discovery studio) was used to construct ingredients database for preliminary screening of three traditional Chinese medicines based on target inhibitor pharmacophore, so as to obtain 5-LOX and LTA4H potential active ingredients...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Philip J O'Reilly, Qiang Ding, Samia Akthar, Guoqiang Cai, Kristopher R Genschmer, Dhiren F Patel, Patricia L Jackson, Liliana Viera, Mojtaba Roda, Morgan L Locy, Ellen A Bernstein, Clare M Lloyd, Kenneth E Bernstein, Robert J Snelgrove, J Edwin Blalock
The neutrophil chemoattractant proline-glycine-proline (PGP) is generated from collagen by matrix metalloproteinase-8/9 (MMP-8/9) and prolyl endopeptidase (PE), and it is concomitantly degraded by extracellular leukotriene A4 hydrolase (LTA4H) to limit neutrophilia. Components of cigarette smoke can acetylate PGP, yielding a species (AcPGP) that is resistant to LTA4H-mediated degradation and can, thus, support a sustained neutrophilia. In this study, we sought to elucidate if an antiinflammatory system existed to degrade AcPGP that is analogous to the PGP-LTA4H axis...
November 16, 2017: JCI Insight
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