Prostaglandins, leukotrienes, and essential fatty acids最新文献

{"title":"Over-the-counter fish oil supplementation and pro-resolving and pro-inflammatory lipid mediators in rheumatoid arthritis","authors":"Nathalie E. Marchand ,&nbsp;May Y. Choi ,&nbsp;Emily G. Oakes ,&nbsp;Nancy R. Cook ,&nbsp;Emma Stevens ,&nbsp;Natalya Gomelskaya ,&nbsp;Gregory Kotler ,&nbsp;JoAnn E. Manson ,&nbsp;Jessica Lasky-Su ,&nbsp;Samia Mora ,&nbsp;I-Min Lee ,&nbsp;Raju Tatituri ,&nbsp;Karen H. Costenbader","doi":"10.1016/j.plefa.2023.102542","DOIUrl":"10.1016/j.plefa.2023.102542","url":null,"abstract":"<div><h3>Objective</h3><p>Little is known about the effects of over-the-counter fish oil (FO) supplements on circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving mediators (SPMs), nor about whether having a chronic inflammatory disease such as rheumatoid arthritis (RA) influences SPM levels. We investigated associations between over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with vs. without RA.</p></div><div><h3>Methods</h3><p>We studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid chromatography-tandem mass spectroscopy was performed on patient plasma to identify and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests and then multivariable linear regression analyses to assess whether having RA or taking FO supplements was associated with circulating lipid mediator concentrations, adjusting for age, race, sex, smoking, body mass index, and current medication use (statins, prednisone and immunomodulators among RA cases only). We tested for interactions between FO supplementation and RA status. We also conducted Spearman's correlations between EPA, DHA, and ARA and their downstream metabolites.</p></div><div><h3>Results</h3><p>Among patients who were taking FO compared to those who were not, in multivariable- adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14- and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series resolvins were present and identified, we did not find statistical elevations of other SPMs. Results were similar among patients with RA and patients without RA, taking vs. not taking FO supplementation (no formal statistical interaction observed). There was a strong positive correlation between EPA and DHA and their immediate downstream SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all patients.</p></div><div><h3>Conclusion</h3><p>Patients taking FO supplements, regardless of RA status, not only had higher blood levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor reserves, similarly to matched controls without RA, by taking oral FO supplements.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10027850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9774494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxylipin status, before and after LC n-3 PUFA supplementation, has little relationship with skeletal muscle biology in older adults at risk of sarcopenia","authors":"E. de Marco Castro ,&nbsp;N. Kampschulte ,&nbsp;C.H. Murphy ,&nbsp;N.H. Schebb ,&nbsp;H.M. Roche","doi":"10.1016/j.plefa.2022.102531","DOIUrl":"10.1016/j.plefa.2022.102531","url":null,"abstract":"<div><h3>Introduction</h3><p>Oxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC <em>n</em>-3 PUFA supplementation.</p></div><div><h3>Materials and methods</h3><p>This exploratory study investigated the baseline correlations between LC <em>n</em>-3, <em>n</em>-6 and <em>n</em>-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (<em>n</em> = 49). After examining the baseline relationship, the potential effect of supplementation (LC <em>n-</em>3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined.</p></div><div><h3>Results</h3><p>At baseline, the hydroxy product of mead acid (<em>n-</em>9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (<em>p</em> <em>=</em> 0.003, <em>r</em>=-0.41), skeletal muscle mass index (SMMI) (<em>p</em> <em>=</em> 0.001, <em>r</em>=-0.46), handgrip strength (HGS) (<em>p&lt;</em>0.001, <em>r</em> = 0.48) and isometric knee extension (<em>p&lt;</em>0.001, <em>r</em>=-0.48). Likewise, LC <em>n-</em>6 PUFA hydroxy‑PUFA were negatively correlated to HGS (i.e., 12-HETrE, <em>p</em> <em>=</em> 0.002, <em>r</em>=-0.42, and 5- and 11-HETE, <em>p</em> <em>=</em> 0.006, <em>r</em>=-0.47 and <em>p&lt;</em>0.001, <em>r</em>=-0.50 respectively), single leg stand time (i.e., 12-HETrE, <em>p</em> <em>=</em> 0.006, <em>r</em>=-0.39 and 16-HETE, <em>p</em> <em>=</em> 0.002, <em>r</em>=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, <em>p</em> <em>=</em> 0.006, <em>r</em> = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, <em>p</em> <em>=</em> 0.007, <em>r</em> = 0.38 and 16-HETE, <em>p</em> <em>=</em> 0.006, <em>r</em> = 0.39). LC <em>n-</em>3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced <em>n-</em>6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC <em>n</em>-3 PUFA or placebo groups. Changes in plasma oxylipin","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10842151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Placental F4-Neuroprostanes and F2-Isoprostanes are altered in gestational diabetes mellitus and maternal obesity","authors":"Carolina S. Ferreira ,&nbsp;Gabriela D.A. Pinto ,&nbsp;Desirée L. Reis ,&nbsp;Claire Vigor ,&nbsp;Vanessa A. Goes ,&nbsp;Deborah de A.B. Guimarães ,&nbsp;Daniela B. Mucci ,&nbsp;Livia Belcastro ,&nbsp;Marcelle A. Saraiva ,&nbsp;Camille Oger ,&nbsp;Jean-Marie Galano ,&nbsp;Fátima L.C. Sardinha ,&nbsp;Alexandre G. Torres ,&nbsp;Thierry Durand ,&nbsp;Graham J. Burton ,&nbsp;Tatiana El-Bacha","doi":"10.1016/j.plefa.2022.102529","DOIUrl":"https://doi.org/10.1016/j.plefa.2022.102529","url":null,"abstract":"<div><p>We investigated whether gestational diabetes mellitus (GDM) associated with maternal obesity modifies the placental profile of F₄-Neuroprostanes and F₂-Isoprostanes, metabolites of non-enzymatic oxidation of docosahexaenoic acid (DHA) and arachidonic acid (AA), respectively. Twenty-five placental samples were divided into lean (<em>n</em>=11), obesity (<em>n</em>=7) and overweight/obesity+GDM (<em>n</em>=7) groups. F₄-Neuroprostanes and F₂-Isoprostanes were higher in obesity compared to lean controls, but reduced to levels similar to lean women when obesity is further complicated with GDM. Lower content of F₂-Isoprostanes suggests adaptive placental responses in GDM attenuating oxidative stress. However, low levels of placental F₄-Neuroprostanes may indicate impaired DHA metabolism in GDM, affecting fetal development and offspring health. These results were not related to differences in placental content of DHA, AA and polyunsaturated fatty acids status nor to maternal diet or gestational weight gain. Placental DHA and AA metabolism differs in obesity and GDM, highlighting the importance of investigating the signalling roles of F₄-Neuroprostanes and F₂-Isoprostanes in the human term placenta.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49798598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between 19 dietary fatty acids intake and rheumatoid arthritis: Results of a nationwide survey","authors":"Ruijie Xie ,&nbsp;Ya Zhang","doi":"10.1016/j.plefa.2022.102530","DOIUrl":"10.1016/j.plefa.2022.102530","url":null,"abstract":"<div><h3>Background</h3><p>The relationship between dietary fatty acid intakes and rheumatoid arthritis (RA) is unclear and the available studies have focused on only a few fatty acids. This study investigated the association between the intake of 19 dietary fatty acids and RA in U.S. adults.</p></div><div><h3>Methods</h3><p>This cross-sectional study using nationally representative data from the 2010-2020 National Health and Nutrition Examination Survey (NHANES). Multivariate linear regression model, multivariate logic regression models, smoothing curve fitting, and two-segment linear regression model were used to explore the relationships between 19 dietary fatty acids intakes with high-sensitivity C-reactive protein (Hs-CRP) and RA risk.</p></div><div><h3>Results</h3><p>A total of 16,530 participants were included (1053 participants with RA). Intake of hexadecanoic acid<span> and octadecanoic acid were significantly associated with higher Hs-CRP levels, intake of hexadecenoic acid was significantly associated with higher RA risk, and intake of docosahexaenoic acid was significantly associated with lower RA risk. In addition, there was an inverted U-shaped relationship between total monounsaturated fatty acids (MUFAs) intake and RA risk, with the inflection point reached at 15.77% .</span></p></div><div><h3>Conclusions</h3><p>Among the 19 dietary fatty acids, only 4 subclasses were significantly associated with Hs-CRP or RA risk. The inverted U-shaped relationship between MUFAs and RA risk may provide insights to find potential prevention strategies for RA.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10789238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and behavioral effects of decreasing dietary linoleic acid and increasing eicosapentaenoic acid and docosahexaenoic acid in a rat chronic monoarthrits model","authors":"Anthony F. Domenichiello ,&nbsp;Breanne C. Wilhite ,&nbsp;Pranavi Nara ,&nbsp;Mark H. Pitcher ,&nbsp;Gregory S. Keyes ,&nbsp;Andrew J. Mannes ,&nbsp;M. Catherine Bushnell ,&nbsp;Christopher E. Ramsden","doi":"10.1016/j.plefa.2022.102512","DOIUrl":"10.1016/j.plefa.2022.102512","url":null,"abstract":"<div><p>Clinical studies have demonstrated that decreasing linoleic acid (LA) while increasing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in diets evokes an analgesic effect in headache sufferers. We utilized a rat chronic monoarthritis model to determine if these analgesic effects can be reproduced in rats and to and further probe potential analgesic mechanisms. We fed 8 rats a control diet (with fatty acid levels similar to standard US diets) and 8 rats a low LA diet with added EPA and DHA (H3L6 diet) and after 10 weeks, performed a unilateral intraarticular injection of Complete's Freund Adjuvant (CFA). We evaluated thermal and mechanical sensitivity as well as hind paw weight bearing prior to and at 4 and 20 days post CFA injection. At 28 days post CFA injection rats were euthanized and tissue collected. H3L6 diet fed rats had higher concentrations of EPA and DHA, as well as higher concentrations of oxidized lipids derived from these fatty acids, in hind paw and plasma, compared to control fed rats. LA and oxidized LA metabolites were lower in the plasma and hind paw of H3L6 compared to control fed rats. Diet did not affect thermal or mechanical sensitivity, nor did it affect hind paw weight bearing. In conclusion, the H3L6 diet evoked biochemical changes in rats but did not impact pain related behavioral measures in this chronic monoarthritis model.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10441096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specialized pro-resolvin mediators induce cell growth and improve wound repair in intestinal epithelial Caco-2 cell cultures","authors":"C.E. Storniolo ,&nbsp;M. Pequera ,&nbsp;A. Vilariño ,&nbsp;J.J. Moreno","doi":"10.1016/j.plefa.2022.102520","DOIUrl":"10.1016/j.plefa.2022.102520","url":null,"abstract":"<div><p>Specialized pro-resolvin mediators (SPMs) are a superfamily of bioactive molecules synthesized from polyunsaturated fatty acids (arachidonic, eicosapentaenoic and docosahexaenoic acids) that include resolvins, protectins and maresins. These metabolites are important to control the resolution phase of inflammation and the epithelial repair, which is essential in restoring the mucosal barriers. Unfortunately, the effects of SPMs on intestinal epithelial cell growth remain poorly understood. Caco-2 cell were used as intestinal epithelial cell model. Cell growth/DNA synthesis, cell signalling pathways, western blot and wound repair assay were performed. Our data demonstrated that SPMs such as lipoxin LxA₄, resolvin (Rv) E1, RvD1, protectin D 1 and maresin 1 were able to enhance intestinal epithelial Caco-2 cell growth and DNA synthesis. Furthermore, our results provide evidence that these effects of RvE1 and RvD1 were associated with a pertussis toxin-sensitive G protein-coupled receptor, and that leukotriene B₄ receptor 2 could be involved, at least in part, in these effects of RvE1/RvD1. Moreover, these mitogenic effects induced by SPMs were dependent on the ERK 1/2 and p38 MAPK pathways as well as phospholipase C and protein kinase C activation. Thus, these mitogenic effects of RvE1/RvD1 on intestinal epithelial cells could be involved in this signalling circuit involved in wounded epithelium and the catabasis process.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327822001314/pdfft?md5=391f06fa627b46ae9847abd3207b505d&pid=1-s2.0-S0952327822001314-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bimatoprost promotes satiety and attenuates body weight gain in rats fed standard or obesity-promoting diets.","authors":"Clayton Spada ,&nbsp;Chau Vu ,&nbsp;Iona Raymond ,&nbsp;Warren Tong ,&nbsp;Chia-Lin Chuang ,&nbsp;Christopher Walker ,&nbsp;Kerry Loomes ,&nbsp;David F. Woodward ,&nbsp;Neil J. Poloso","doi":"10.1016/j.plefa.2022.102511","DOIUrl":"10.1016/j.plefa.2022.102511","url":null,"abstract":"<div><p>Bimatoprost is a synthetic prostamide F_2α analog that down-regulates adipogenesis in vitro. This effect has been attributed to participation in a negative feedback loop that regulates anandamide-induced adipogenesis. A follow-on investigation has now been conducted into the broader metabolic effects of bimatoprost using rats under both normal state and obesity-inducing conditions. Chronic bimatoprost administration attenuated weight gain in a dose dependent-manner in rats fed either standard [max effect −7%] or obesity-promoting diets [max effect −23%] over a 9–10 week period. Consistent with these findings, bimatoprost promoted satiety as measured by decreased food intake [max effect, −7%], gastric emptying [max effect, −33–50%] and decreased circulating concentrations of the gut hormones, ghrelin and GLP-1 [max effect, −33–50%]. Additionally, subcutaneous, and visceral fat mass were distinctly affected by treatment [−30% diet independent]. Taken together, these results suggest that bimatoprost regulates energy homeostasis through promoting satiety and a decrease in food intake. These newly reported activities of bimatoprost reveal an additional method of metabolic disease intervention for potential therapeutic exploitation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327822001211/pdfft?md5=d0abb812458fb17f5a4a0935bf8b6a3e&pid=1-s2.0-S0952327822001211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISSFAL statement number 7 – Omega-3 fatty acids during pregnancy to reduce preterm birth","authors":"K P Best ,&nbsp;R A Gibson ,&nbsp;M Makrides","doi":"10.1016/j.plefa.2022.102495","DOIUrl":"10.1016/j.plefa.2022.102495","url":null,"abstract":"<div><p>Globally, preterm birth is the leading cause of death in children under the age of 5 years and survivors may suffer life-long consequences. Following many years of investigation, there is strong evidence that a proportion of preterm births can be prevented by increasing maternal dietary omega-3 long chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy. This Statement provides a synthesis of contemporary evidence on the role of omega-3 LCPUFA on prevention of preterm birth and is designed to provide fatty acid-specific knowledge and guidance for medical practitioners, midwives, health services, professional bodies and policy makers to consider for their contextual situations. The evidence synthesis, which underpins this statement, is based on the 2018 Cochrane systematic review with supplemental evidence from RCTs completed since that time as well as other systematic reviews. Heterogeneity between studies was explored to understand how the effect of omega-3 supplementation may vary in different population groups and by dose and type of omega-3 supplementation. Most trials were conducted in upper-middle or high-income countries and the evidence are most applicable in those settings. The evidence synthesis confirmed that omega-3 LCPUFA, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have an important role to play in determining gestational length in singleton pregnancies. Adequate intake of omega-3 LCPUFA in early pregnancy, consistent with existing nutritional guidelines, is associated with a lower risk of preterm and early preterm births for women with singleton pregnancies. Therefore, women with adequate omega-3 intakes in early pregnancy should maintain these intakes. Women who are low in omega-3 fatty acids will benefit most from omega-3 LCPUFA supplementation to reduce their risk of early birth. In such cases supplementation with a total of about 1000 mg of DHA plus EPA is effective at reducing risk of early birth, preferably with supplementation commencing before 20 weeks’ gestation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327822001077/pdfft?md5=4254f9177b1863777b94ae2d03347276&pid=1-s2.0-S0952327822001077-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiosynthesis of 20-[18F]fluoroarachidonic acid for PET-MR imaging: Biological evaluation in ApoE4-TR mice","authors":"Juno Van Valkenburgh ,&nbsp;Marlon Vincent V. Duro ,&nbsp;Erica Burnham ,&nbsp;Quan Chen ,&nbsp;Shaowei Wang ,&nbsp;Jenny Tran ,&nbsp;Bilal E. Kerman ,&nbsp;Sung Hee Hwang ,&nbsp;Xiaodan Liu ,&nbsp;Naomi S. Sta. Maria ,&nbsp;Francesca Zanderigo ,&nbsp;Etienne Croteau ,&nbsp;Stanley I. Rapoport ,&nbsp;Stephen C. Cunnane ,&nbsp;Russell E. Jacobs ,&nbsp;Hussein N. Yassine ,&nbsp;Kai Chen","doi":"10.1016/j.plefa.2022.102510","DOIUrl":"10.1016/j.plefa.2022.102510","url":null,"abstract":"<div><p>Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (<em>APOE4</em>) genotype, the strongest genetic risk factor of late-onset Alzheimer's disease (AD). Visualization of AA uptake and distribution in the brain can offer insight into neuroinflammation and AD pathogenesis. Here we present a novel synthesis and radiosynthesis of 20-[¹⁸F]fluoroarachidonic acid ([¹⁸F]-FAA) for PET imaging using a convergent route and a one-pot, single-purification radiolabeling procedure, and demonstrate its brain uptake in human ApoE4 targeted replacement (ApoE4-TR) mice. By examining p38 phosphorylation in astrocytes, we found that fluorination of AA at the ω-position did not significantly alter its biochemical role in cells. The brain incorporation coefficient (<em>K</em>*) of [¹⁸F]-FAA was estimated via multiple methods by using an image-derived input function from the right ventricle of the heart as a proxy of the arterial input function and brain tracer concentrations assessed by dynamic PET-MR imaging. This new synthetic approach should facilitate the practical [¹⁸F]-FAA production and allow its translation into clinical use, making investigations of dysregulation of lipid metabolism more feasible in the study of neurodegenerative diseases.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9140904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6 Iodo-delta lactone inhibits angiogenesis in human HT29 colon adenocarcinoma xenograft.","authors":"Romina Oglio ,&nbsp;Federico Buschittari ,&nbsp;Leonardo Salvarredi ,&nbsp;Jennifer Michaux ,&nbsp;Carla Rodriguez ,&nbsp;Marina Perona ,&nbsp;Alejandra Dagrosa ,&nbsp;Guillermo Juvenal ,&nbsp;Lisa Thomasz","doi":"10.1016/j.plefa.2022.102507","DOIUrl":"10.1016/j.plefa.2022.102507","url":null,"abstract":"<div><h3>Introduction</h3><p>Several studies have shown the antiproliferative effect of iodine and 5‑hydroxy-6 iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that molecular iodine (I₂) and IL-δ, but not iodide (<em>I</em>⁻), exerts anti-neoplastic actions in different cancers. The underlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of this study was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29 colorectal cancer xenografts.</p></div><div><h3>Methodology and Results</h3><p>HT29 cells were injected subcutaneously into the flanks of nude mice and IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenografts showed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression (<em>p</em> &lt; 0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (<em>p</em> &lt; 0.05). To assess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry was analyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively (<em>p</em> &lt; 0.05), as well as it decreased VEGF and VEGF-R2 expression (<em>p</em> &lt; 0.05). Additionally, our findings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (<em>p</em> &lt; 0.01).</p></div><div><h3>Conclusion</h3><p>The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as well as induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2 downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1 would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase would produce anti-proliferative effect on endothelial cells.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10440545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}