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Thomas W Carion, Matthew Greenwood, Abdul Shukkur Ebrahim, Andrew Jerome, Susmit Suvas, Karsten Gronert, Elizabeth A Berger
Although autacoids primarily derived from the cyclooxygenase-2 and 5-lipoxygenase (LOX) pathways are essential mediators of inflammation, endogenous specialized proresolving mediators (SPMs) act as robust agonists of resolution. SPM biosynthesis is initiated by the conversion of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid primarily via the 12/15-LOX pathway. Although 12/15-LOX activity is prominent in the cornea, the role of SPM pathway activation during infection remains largely unknown and is the focus of the current study...
April 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Leona Matsumoto, Yasushi Hirota, Tomoko Saito-Fujita, Norihiko Takeda, Tomoki Tanaka, Takehiro Hiraoka, Shun Akaeda, Hidetoshi Fujita, Ryoko Shimizu-Hirota, Shota Igaue, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Tomoyuki Fujii, Yutaka Osuga
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure...
June 18, 2018: Journal of Clinical Investigation
Sofia Raniolo, Giulia Vindigni, Valeria Unida, Alessio Ottaviani, Elena Romano, Alessandro Desideri, Silvia Biocca
DNA has been used to build nanostructures with potential biomedical applications. However, their use is limited by the lack of information on the mechanism of entry, intracellular fate and degradation rate of nanostructures inside cells. We generated octahedral DNA nanocages functionalized with folic acid and investigated the cellular uptake mediated by two distinctive internalization pathways, using two cellular systems expressing the oxidized low-density lipoprotein receptor-1 (LOX-1) and the α isoform of the folate receptor (αFR), respectively...
June 18, 2018: Nanoscale
Alan R Brash
Catalase-related allene oxide synthase (cAOS) is a hemoprotein that converts a specific fatty acid hydroperoxide to an unstable allene oxide intermediate at turnover rates in the order of 1000 per second. Fatty acid allene oxides are intermediates in the formation of cyclopentenone or hydrolytic products in marine systems, most notably the prostanoid-related clavulones. Although the key catalytic amino acid residues around the active site of cAOS are the same as in true catalases, cAOS does not react with hydrogen peroxide...
2018: Methods in Enzymology
Fatih Demirci, Nursenem Karaca, Mehmet Tekin, Betül Demirci
Thymus sipyleus BOISS. subsp. sipyleus BOISS. var. sipyleus L. of the Lamiaceae, locally known as thyme scented lemon, which is an endemic taxon collected from Sivas in Anatolia, was investigated in this study due to its folk medicine use against rhinosinusitis. The aromatic characteristics of the plant material gave the idea for the detailed evaluation of the volatiles and essential oil thereof. Consequently, the oil was obtained by Clevenger type hydrodistillation followed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography/mass spectrometry (GC/MS) analyses for phytochemical characterization...
June 13, 2018: Microbial Pathogenesis
Derek J Erstad, Mozhdeh Sojoodi, Martin S Taylor, Sarani Ghoshal, Allen A Razavi, Katherine A Graham-O'Regan, Nabeel Bardeesy, Cristina R Ferrone, Michael Lanuti, Peter Caravan, Kenneth K Tanabe, Bryan C Fuchs
INTRODUCTION: Syngeneic, immunocompetent allograft tumor models recapitulate important aspects of the tumor microenvironment and have short tumor latency with predictable growth kinetics, making them useful for trialing novel therapeutics. We describe surgical techniques for orthotopic and heterotopic PDAC tumor implantation and characterize phenotypes based on implantation site. METHODS: Mice (n=8 per group) were implanted with 104 cells in the pancreas or flank...
June 14, 2018: Disease Models & Mechanisms
Sabrina M Peviani, Vinicius Guzzoni, Clara M Pinheiro-Dardis, Yara P da Silva, Alisson C R Fioravante, Adriana H Sagawa, Gabriel B Delfino, João L Q Durigan, Tania F Salvini
Stretching is a common method used to prevent muscle shortening and improve limited mobility. However, the effect of different time periods on stretching-induced adaptation of the extracellular matrix and its regulatory elements have yet to be investigated. We aimed to evaluate the expression of fibrillar collagens, sarcomerogenesis, metalloproteinase (MMP) activity and gene expression of the extracellular matrix (ECM) regulators in the soleus (SOL) muscle of rats submitted to different stretching periods. The soleus muscles were submitted to 10 sets of passive stretching over 10 (St 10d) or 15 days (St 15d) (1 min per set, with 30 seconds' rest between sets)...
June 13, 2018: Scientific Reports
Moussa Compaore, Sahabi Bakasso, Roland Nâg Tiero Meda, Odile Germaine Nacoulma
Background: According to recent studies, reactive oxygen is the leader of human metabolic disease development. The use of natural antioxidants is the best way to stop or prevent this problem. Therefore, the aim of this study was to evaluate the antioxidant and anti-inflammatory activities and to determine the polyphenolic contents of the Bidens engleri and Boerhavia erecta fractions. Methods: Plant fractions were obtained using Soxhlet procedures with hexane, dichloromethane, acetonitrile, ethyl acetate, methanol, and butanol solvent, successively...
June 12, 2018: Medicines (Basel, Switzerland)
Jeff Hirst, Harsh B Pathak, Stephen Hyter, Ziyan Y Pessetto, Thuc Ly, Stefan Graw, Devin C Koestler, Adam J Krieg, Katherine F Roby, Andrew K Godwin
Drug development for front-line treatment of epithelial ovarian cancer (EOC) has been stagnant for almost three decades. Traditional cell culture methods for primary drug screening do not always accurately reflect clinical disease. To overcome this barrier, we grew a panel of EOC cell lines in three-dimensional (3D) cell cultures to form multicellular tumor spheroids (MCTS). We characterized these MCTS for molecular and cellular features of EOC and performed a comparative screen with cells grown using two-dimensional (2D) cell culture to identify previously unappreciated anti-cancer drugs...
June 11, 2018: Cancer Research
Neha Merchant, Lakkakula V K S Bhaskar, Saimila Momin, Peela Sujatha, Aramati B M Reddy, Ganji Purnachandra Nagaraju
Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer...
July 2018: Critical Reviews in Oncology/hematology
Yi Zhao, Hai Gao, Jianhua He, Cuiping Jiang, Jing Lu, Wenli Zhang, Hu Yang, Jianping Liu
Aberrant lipid accumulation in both endothelial cells and macrophage foam cells as well as atherogenic inflammation in the atherosclerotic lesions, if left untreated, eventually lead to plaque rupture and arterial damage, causing devastating consequences. In this report, we explore a dual cell therapy modality by designing a dual-targeting core-shell nanoplatform to deliver LOX-1 siRNA and atorvastatin (AT) to control lipid trafficking to and from endothelial cells and macrophages in the atherosclerotic lesions selectively and sequentially...
June 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
P Jaismy Jacob, S L Manju, K R Ethiraj, Geetha Elias
Inflammatory mediators of the arachidonic acid cascade from cyclooxygenase (COX) and lipoxygenase (LOX) pathways are primarily responsible for many diseases in human beings. Chronic inflammation is associated with the pathogenesis and progression of cancer, arthritis, autoimmune, cardiovascular and neurological diseases. Traditional non-steroidal anti-inflammatory agents (tNSAIDs) inhibit cyclooxygenase pathway non-selectively and produce gastric mucosal damage due to COX-1 inhibition and allergic reactions and bronchospasm resulting from increased leukotriene levels...
June 5, 2018: European Journal of Pharmaceutical Sciences
Ala Orafaie, Maryam Moghaddam Matin, Hamid Sadeghian
Cancer-targeted therapy is an expanding and successful approach in treatment of many types of cancers. One of the main categories of targeted therapy is use of small molecule inhibitors. 15-Lipoxygenase (15-LOX) is an enzyme which reacts with polyunsaturated fatty acids and produces metabolites that are implicated in many important human diseases, such as cancer. Considering the role of 15-LOX (mainly 15-LOX-1) in the progression of some cancers, the discovery of 15-LOX inhibitors could potentially lead to development of novel cancer therapeutics and it can be claimed that 15-LOX inhibitors might be suitable as chemotherapy agents in the near future...
June 7, 2018: Cancer Metastasis Reviews
Sherif M Shoieb, Ayman O S El-Kadi
We have recently demonstrated that the racemic mixture of 19-hydroxyeicosatetraenoic acid (19-HETE) protects against angiotensin II (Ang II) induced cardiac hypertrophy. Therefore, the purpose of this study was to investigate whether R- or S-enantiomer of 19-HETE confers cardioprotection against Ang II-induced cellular hypertrophy in RL-14 and H9c2 cells. Both cell lines were treated with vehicle or 10 μM Ang II in the absence and presence of 20 &#[mu]M 19(R)-HETE or 19(S)-HETE for 24 h. Thereafter, the level of mid-chain HETEs was determined using liquid chromatography - mass spectrometry (LC/MS)...
June 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Kusum Dagar, C S Pundir
The data shown in this article are based on the original research article entitled "An improved amperometric L-lactate biosensor based on covalent immobilization of microbial lactate oxidase onto carboxylated multiwalled carbon nanotubes/copper nanoparticles/ polyaniline modified pencil graphite electrode" (Dagar and Pundir, 2017) [1]. This article explains the fabrication of an amperometric L-lactate biosensor based on microbial lactate oxidase (LOx) covalent immobilization onto nanomatrix [(carboxylated multiwalled carbon nanotubes (cMWCNT)/copper nanoparticles (CuNPs)/polyaniline (PANI) hybrid film/pencil graphite electrode (PGE)]...
April 2018: Data in Brief
David Hutin, Laura Tamblyn, Alvin Gomez, Giulia Grimaldi, Helen Soedling, Tiffany Cho, Shaimaa Ahmed, Christin Lucas, Chakravarthi Kanduri, Denis M Grant, Jason Matthews
The aryl hydrocarbon receptor (AHR) mediates the toxic effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD), which include thymic atrophy, steatohepatitis, and a lethal wasting syndrome in laboratory rodents. Although the mechanisms of dioxin toxicity remain unknown, AHR signaling in hepatocytes is necessary for dioxin-induced liver toxicity. We previously reported that loss of TCDD-inducible poly(ADP-ribose) polymerase (TIPARP/PARP7/ARTD14), an AHR target gene and mono-ADP-ribosyltransferase, increases the sensitivity of mice to dioxin-induced toxicities...
June 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jeremy D Eekhoff, Fei Fang, Spencer P Lake
The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding...
June 6, 2018: Connective Tissue Research
Rajshekhar A Kore, Jacob L Edmondson, Samir V Jenkins, Azemat Jamshidi-Parsian, Ruud P M Dings, Nathan S Reyna, Robert J Griffin
Hypoxia, a hallmark characteristic of glioblastoma (GBM) induces changes in the transcriptome and the proteome of tumor cells. We discovered that hypoxic stress produces significant qualitative and quantitative changes in the protein content of secreted exosomes from GBM cells. Among the proteins found to be selectively elevated in hypoxic exosomes were protein-lysine 6-oxidase (LOX), thrombospondin-1 (TSP1), vascular derived endothelial factor (VEGF) and a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), well studied contributors to tumor progression, metastasis and angiogenesis...
July 2018: Biochemistry and Biophysics Reports
Paula R Pinto, Karolline S da Silva, Rodrigo T Iborra, Ligia S Okuda, Diego Gomes-Kjerulf, Guilherme S Ferreira, Adriana Machado-Lima, Debora D F M Rocco, Edna R Nakandakare, Ubiratan F Machado, Maria L Correa-Giannella, Sergio Catanozi, Marisa Passarelli
Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session...
2018: Frontiers in Physiology
Patrina S P Poh, Verena Schmauss, Jacqui A McGovern, Daniel Schmauss, Mohit P Chhaya, Peter Foehr, Markus Seeger, Vasilis Ntziachristos, Dietmar W Hutmacher, Martijn van Griensven, Jan-Thorsten Schantz, Elizabeth R Balmayor
BACKGROUND: Capsular contracture is one of the most common complications in surgical interventions for aesthetic breast augmentation or post-mastectomy breast reconstruction involving the use of silicone prostheses. Although the precise cause of capsular contracture is yet unknown, the leading hypothesis is that it is caused by long-term unresolved foreign body reaction towards the silicone breast implant. To authors' best knowledge, this is the first study that elucidates the presence of lysyl oxidase (LOX)-an enzyme that is involved in collagen and elastin crosslinking within fibrous capsules harvested from patients with severe capsular contracture...
June 4, 2018: European Journal of Medical Research
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