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Naveen K V Gundala, Vegi G M Naidu, Undurti N Das
OBJECTIVE: We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. MATERIAL AND METHODS: In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied...
November 15, 2016: BioFactors
Patricia L Mitchell, Renato Nachbar, Dominic Lachance, Philippe St-Pierre, Jocelyn Trottier, Olivier Barbier, André Marette
AIMS: To compare the therapeutic potential of TP-113, a unique molecular entity linking DHA with metformin, for alleviating insulin resistance in obese diabetic mice through the PDX/IL-6 pathway. MATERIAL AND METHODS: We utilized the generically obese diabetic db/db mouse model for all experiments. Initial studies investigated both a dose and time course response. These results were then utilized to design a long term (5wk) treatment protocol. Mice were gavaged twice a day with one of three treatments: 200 mg/kg BW TP113, and equivqlent dose of metformin alone (70 mg/kg BW) or water...
November 1, 2016: Diabetes, Obesity & Metabolism
Ganesh V Halade, Vasundhara Kain, Laurence M Black, Sumanth D Prabhu, Kevin A Ingle
Post-myocardial infarction (MI), overactive inflammation is the hallmark of aging, however, the mechanism is unclear. We hypothesized that excess influx of omega 6 fatty acids may impair resolution, thus impacting the cardiosplenic and cardiorenal network post-MI. Young and aging mice were fed on standard lab chow (LC) and excess fatty acid (safflower oil; SO)-enriched diet for 2 months and were then subjected to MI surgery. Despite similar infarct areas and left ventricle (LV) dysfunction post-MI, splenic mass spectrometry data revealed higher levels of arachidonic acid (AA) derived pro-inflammatory metabolites in young-SO, but minimal formation of docosanoids, D- and E- series resolvins in SO-fed aged mice...
October 18, 2016: Aging
Esther Titos, Bibiana Rius, Cristina López-Vicario, José Alcaraz-Quiles, Verónica García-Alonso, Aritz Lopategi, Jesmond Dalli, Juan José Lozano, Vicente Arroyo, Salvadora Delgado, Charles N Serhan, Joan Clària
Persistent activation of the innate immune system greatly influences the risk for developing metabolic complications associated with obesity. In this study, we explored the therapeutic potential of the specialized proresolving mediator (SPM) resolvin D1 (RvD1) to actively promote the resolution of inflammation in human visceral adipose tissue from obese (Ob) patients. Using liquid chromatography-tandem mass spectrometry-based metabololipidomic analysis, we identified unbalanced production of SPMs (i.e., D- and E-series resolvins, protectin D1, maresin 1, and lipoxins) with respect to inflammatory lipid mediators (i...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jesmond Dalli, Romain A Colas, Carolina Quintana, Diana Barragan-Bradford, Shelley Hurwitz, Bruce D Levy, Augustine M Choi, Charles N Serhan, Rebecca M Baron
OBJECTIVE: To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. DESIGN: Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. SETTING: Brigham and Women's Hospital Medical Intensive Care Unit...
September 14, 2016: Critical Care Medicine
Anna Polus, Barbara Zapala, Urszula Razny, Anna Gielicz, Beata Kiec-Wilk, Malgorzata Malczewska-Malec, Marek Sanak, Caroline E Childs, Philip C Calder, Aldona Dembinska-Kiec
The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured...
November 2016: Biochimica et Biophysica Acta
Trond V Hansen, Jesmond Dalli, Charles N Serhan
The n-3 polyunsaturated fatty acids are substrates for lipoxygenases and cyclooxygenases. During inflammatory processes, these enzymes form several distinct families of oxygenated polyunsaturated fatty acids coined specialized pro-resolving lipid mediators. Structural elucidation of these natural products using LC-MS/MS based metabololipidomics with the pico- to nanogram amounts of biosynthetic material available have been performed. The specialized pro-resolving lipid mediators display stereospecific and potent anti-inflammatory and pro-resolving actions...
2016: RSC Advances
Olivier Friedli, Stefan Freigang
Inflammation represents a powerful innate immune response that defends tissue homeostasis. However, the appropriate termination of inflammatory processes is essential to prevent the development of chronic inflammatory disorders. The resolution of inflammation is actively induced by specialized pro-resolving lipid mediators, which include eicosanoids, resolvins, protectins and maresins. The responsible pro-resolution pathways have emerged as promising targets for anti-inflammatory therapies since they mitigate excessive inflammation without compromising the anti-microbial defenses of the host...
July 12, 2016: Biochimica et Biophysica Acta
Ondrej Kuda, Marie Brezinova, Martina Rombaldova, Barbora Slavikova, Martin Posta, Petr Beier, Petra Janovska, Jiri Veleba, Jan Kopecky, Eva Kudova, Terezie Pelikanova, Jan Kopecky
White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation...
September 2016: Diabetes
Christopher Beermann, Sandy Neumann, Daniela Fußbroich, Stefan Zielen, Ralf Schubert
Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies...
November 2016: Nutrition
Michael Bauer, Evangelos J Giamarellos-Bourboulis, Andreas Kortgen, Eva Möller, Karen Felsmann, Jean Marc Cavaillon, Orlando Guntinas-Lichius, Olivier Rutschmann, Andriy Ruryk, Matthias Kohl, Britta Wlotzka, Stefan Rußwurm, John C Marshall, Konrad Reinhart
Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions...
April 2016: EBioMedicine
Tarec K Elajami, Romain A Colas, Jesmond Dalli, Nan Chiang, Charles N Serhan, Francine K Welty
Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipid mediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animal models, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients...
August 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Anne E Barden, Mahin Moghaddami, Emilie Mas, Michael Phillips, Leslie G Cleland, Trevor A Mori
INTRODUCTION: Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA. METHODS: Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2...
April 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Jérôme Tourret, Erick Denamur
The emergence of genomics over the last 10 years has provided new insights into the evolution and virulence of extraintestinal Escherichia coli. By combining population genetics and phylogenetic approaches to analyze whole-genome sequences, it became possible to link genomic features to specific phenotypes, such as the ability to cause urinary tract infections. An E. coli chromosome can vary extensively in length, ranging from 4.3 to 6.2 Mb, encoding 4,084 to 6,453 proteins. This huge diversity is structured as a set of less than 2,000 genes (core genome) that are conserved between all the strains and a set of variable genes...
February 2016: Microbiology Spectrum
Jun Ren, Shanshan Meng, Bingdi Yan, Jinyan Yu, Jing Liu
Protectin D1 (PD1) is a bioactive product generated from docosahexaenoic acid, which may exert anti-inflammatory effects in various inflammatory diseases. However, the underlying molecular mechanism of its anti‑inflammatory activity on concanavalin A (Con A)-induced hepatitis remains unknown. The aim of the present study was to investigate the protective effects of PD1 against Con A‑induced liver injury and the underlying mechanisms via intravenous injection of PD1 prior to Con A administration. C57BL/6 mice were randomly divided into four experimental groups as follows: Control group, Con A group (30 mg/kg), 20 µg/kg PD1 + Con A (30 mg/kg) group and 10 µg/kg PD1 + Con A (30 mg/kg) group...
April 2016: Molecular Medicine Reports
Sesquile Ramon, Jesmond Dalli, Julia M Sanger, Jeremy W Winkler, Marius Aursnes, Jørn E Tungen, Trond V Hansen, Charles N Serhan
Inflammation and its natural resolution are host-protective responses triggered by infection or injury. The resolution phase of inflammation is regulated by enzymatically produced specialized pro-resolving mediators. We recently identified a new class of peptide-conjugated specialized pro-resolving mediators that carry potent tissue regenerative actions that belong to the protectin family and are coined protectin conjugates in tissue regeneration (PCTR). Herein, with the use of microbial-induced peritonitis in mice and liquid chromatography-tandem mass spectrometry-based lipid mediator metabololipidomics, we found that PCTR1 is temporally regulated during self-resolving infection...
April 2016: American Journal of Pathology
Mancy Tong, Torsten Kleffmann, Shantanu Pradhan, Caroline L Johansson, Joana DeSousa, Peter R Stone, Joanna L James, Qi Chen, Larry W Chamley
STUDY QUESTION: What proteins are carried by extracellular vesicles (EVs) released from normal first trimester placentae? SUMMARY ANSWER: One thousand five hundred and eighty-five, 1656 and 1476 proteins were characterized in macro-, micro- and nano-vesicles, respectively, from first trimester placentae, with all EV fractions being enriched for proteins involved in vesicle transport and inflammation. WHAT IS KNOWN ALREADY: Placental EVs are being increasingly recognized as important mediators of both healthy and pathological pregnancies...
April 2016: Human Reproduction
Robert G Martindale, Malissa M Warren, Stephen A McClave
PURPOSE OF REVIEW: The literature regarding the use of fish oils in the critically ill to limit the inflammatory and catabolic response have been inconsistent. The objective of this manuscript is to review a newly discovered class of specialized proresolving molecules (SPMs), which could help elucidate the discrepancies reported in the critical care literature regarding the anti-inflammatory benefits of fish oil/ω-3 fatty acids. RECENT FINDINGS: Although use of fish oil has traditionally been thought to reduce or limit the inflammatory process in the critical ill, a new class of endogenously produced highly active lipid mediators derived from arachidonic acid and ω-3 fatty acids (lipoxins, resolvins, protectins, and maresins) have been shown to actively enhance resolution of inflammation...
March 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Undurti N Das
The inflammatory process seen in inflammatory bowel disease (IBD) is due to excess production of pro-inflammatory cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α), interferons (IFNs), macrophage migration inhibitory factor (MIF), HMGB1 (high mobility group B1) and possibly, a reduction in anti-inflammatory cytokines IL-10, IL-4, and transforming growth factor-β (TGF-β). These pro-inflammatory molecules lead to increased production of reactive oxygen species (ROS) including nitric oxide resulting in target tissue damage...
2016: Lipids in Health and Disease
Ondrej Kuda, Martina Rombaldova, Petra Janovska, Pavel Flachs, Jan Kopecky
Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4...
January 15, 2016: Biochemical and Biophysical Research Communications
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