unsaturated fatty acids

Summary

Summary: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.

Top Publications

  1. Decher N, Streit A, Rapedius M, Netter M, Marzian S, Ehling P, et al. RNA editing modulates the binding of drugs and highly unsaturated fatty acids to the open pore of Kv potassium channels. EMBO J. 2010;29:2101-13 pubmed publisher
    ..x channels. Our findings provide a mechanistic understanding of lipid-induced inactivation and establish RNA editing as a mechanism to induce drug and lipid resistance in Kv channels. ..
  2. Yang Y, Jiang Y, Wang Y, An W. Suppression of ABCA1 by unsaturated fatty acids leads to lipid accumulation in HepG2 cells. Biochimie. 2010;92:958-63 pubmed publisher
    ..We previously reported that unsaturated fatty acids destabilise ABCA1 in murine macrophages and ABCA1-transfected baby hamster kidney cells by increasing its ..
  3. Morgan N, Dhayal S. Unsaturated fatty acids as cytoprotective agents in the pancreatic beta-cell. Prostaglandins Leukot Essent Fatty Acids. 2010;82:231-6 pubmed publisher
    ..to long chain fatty acids, such that saturated species are lipotoxic whereas long chain mono-unsaturated fatty acids can provide cytoprotection...
  4. Böttcher C, Pollmann S. Plant oxylipins: plant responses to 12-oxo-phytodienoic acid are governed by its specific structural and functional properties. FEBS J. 2009;276:4693-704 pubmed publisher
    ..In this context, aspects such as the differential recruitment of OPDA, either by de novo biosynthesis or by release from cyclo-oxylipin-galactolipids, and the conjugation of free OPDA are discussed. ..
  5. van Werven J, Schreuder T, Nederveen A, Lavini C, Jansen P, Stoker J. Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0T MR spectroscopy. Eur J Radiol. 2010;75:e102-7 pubmed publisher
    ..MRS) is a non-invasive technique to assess hepatic triglyceride content (HTGC) and allows assessment of unsaturated fatty acids (UFA). There is increasing evidence that hepatic UFA are associated with the development of NAFLD...
  6. Tianero M, Hanif N, de Voogd N, van Soest R, Tanaka J. A new antimicrobial fatty acid from the calcareous sponge Paragrantia cf. waguensis. Chem Biodivers. 2009;6:1374-7 pubmed publisher
  7. Hunter J, Zhang J, Kris Etherton P. Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am J Clin Nutr. 2010;91:46-63 pubmed publisher
    ..the cardiovascular health effects of dietary STA compared with those of trans, other saturated, and unsaturated fatty acids. We reviewed epidemiologic and clinical studies that evaluated the relation between STA and ..
  8. Liu Y, Hazzard C, Eustáquio A, Reynolds K, Moore B. Biosynthesis of salinosporamides from alpha,beta-unsaturated fatty acids: implications for extending polyketide synthase diversity. J Am Chem Soc. 2009;131:10376-7 pubmed publisher
    ..In vivo and in vitro experiments revealed that the crotonyl-CoA reductase/carboxylase SalG has broad substrate tolerance toward 2-alkenyl-CoAs that give rise to the salinosporamide C-2 substitution pattern. ..
  9. Collins J, Neville M, Hoppa M, Frayn K. De novo lipogenesis and stearoyl-CoA desaturase are coordinately regulated in the human adipocyte and protect against palmitate-induced cell injury. J Biol Chem. 2010;285:6044-52 pubmed publisher
    ..DNL may not act primarily to increase fat stores but may serve as a key regulator, in tandem with elongation and desaturation, to maintain cell membrane fluidity and insulin sensitivity within the human adipocyte. ..

More Information

Publications62

  1. Sepulveda J, Tanhehco Y, Frey M, Guo L, Cropcho L, Gibson K, et al. Variation in human erythrocyte membrane unsaturated Fatty acids: correlation with cardiovascular disease. Arch Pathol Lab Med. 2010;134:73-80 pubmed publisher
    ..Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease. ..
  2. Coyral Castel S, Rame C, Fatet A, Dupont J. Effects of unsaturated fatty acids on progesterone secretion and selected protein kinases in goat granulosa cells. Domest Anim Endocrinol. 2010;38:272-83 pubmed publisher
    ..Taken together, some fatty acids could improve ovarian steroidogenesis through the MAPK ERK1/2 signaling pathway and, consequently, have beneficial effects on goat fertility. ..
  3. García Rojas P, Antaramian A, González Dávalos L, Villarroya F, Shimada A, Varela Echavarria A, et al. Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal proliferator-activated receptor gamma coactivator 1 by unsaturated fatty acids, retinoic acid, and carotenoids in preadipocytes obtained from bovine white adipose tissue1,. J Anim Sci. 2010;88:1801-8 pubmed publisher
    ..differentiation after reaching confluence was induced by various treatments: rosiglitazone (20 microM); unsaturated fatty acids: phytanic acid (25, 50, 100 microM) and pristanic acid (25, 50, 100 microM); retinoids: 9-cis retinoic ..
  4. Maia M, Chaudhary L, Bestwick C, Richardson A, McKain N, Larson T, et al. Toxicity of unsaturated fatty acids to the biohydrogenating ruminal bacterium, Butyrivibrio fibrisolvens. BMC Microbiol. 2010;10:52 pubmed publisher
    ..The aim of this study was to investigate the mechanisms by which PUFA affect the growth of B. fibrisolvens, how PUFA are metabolized and the metabolic response to growth in the presence of PUFA...
  5. Gotoh N, Nagao K, Onoda S, Shirouchi B, Furuya K, Nagai T, et al. Effects of three different highly purified n-3 series highly unsaturated fatty acids on lipid metabolism in C57BL/KsJ-db/db mice. J Agric Food Chem. 2009;57:11047-54 pubmed publisher
    Triglycerides (TG) consisting of highly purified (>97%) n-3 series highly unsaturated fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were administered to C57BL/KsJ-db/db mice for ..
  6. Koppers A, Garg M, Aitken R. Stimulation of mitochondrial reactive oxygen species production by unesterified, unsaturated fatty acids in defective human spermatozoa. Free Radic Biol Med. 2010;48:112-9 pubmed publisher
    ..001). This relationship was causal and mediated by the range of unesterified, unsaturated fatty acids that are present in human spermatozoa...
  7. Hwang T, Su Y, Chang H, Leu Y, Chung P, Kuo L, et al. Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils. J Lipid Res. 2009;50:1395-408 pubmed publisher
    ..We also suggest that both the free carboxy group and the number of double bonds of the C(18) UFA structure are critical to providing the potent anti-inflammatory properties in human neutrophils. ..
  8. Lee J, Zhang X, Feramisco J, Gong Y, Ye J. Unsaturated fatty acids inhibit proteasomal degradation of Insig-1 at a postubiquitination step. J Biol Chem. 2008;283:33772-83 pubmed publisher
    ..Here we show that unsaturated fatty acids stabilize Insig-1 without affecting its ubiquitination...
  9. Xu D, Sillaots S, Davison J, Hu W, Jiang B, Kauffman S, et al. Chemical genetic profiling and characterization of small-molecule compounds that affect the biosynthesis of unsaturated fatty acids in Candida albicans. J Biol Chem. 2009;284:19754-64 pubmed publisher
    The balance between saturated and unsaturated fatty acids plays a crucial role in determining the membrane fluidity...
  10. Briard Bion V, Juaneda P, Richoux R, Guichard E, Lopez C. trans-C18:1 isomers in cheeses enriched in unsaturated fatty acids and manufactured with different milk fat globule sizes. J Agric Food Chem. 2008;56:9374-82 pubmed publisher
    ..this study, we examined the trans-octadecenoic acid (C18:1) composition of Emmental cheeses enriched in unsaturated fatty acids (FA) and manufactured with milks produced by cows selected to produce small and large fat globules...
  11. Koo A, Gao X, Jones A, Howe G. A rapid wound signal activates the systemic synthesis of bioactive jasmonates in Arabidopsis. Plant J. 2009;59:974-86 pubmed publisher
  12. Vinciguerra M, Carrozzino F, Peyrou M, Carlone S, Montesano R, Benelli R, et al. Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN. J Hepatol. 2009;50:1132-41 pubmed publisher
    ..We recently demonstrated that unsaturated fatty acids trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-kappaB-dependent mechanism in ..
  13. Russo G. Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol. 2009;77:937-46 pubmed publisher
  14. Matthan N, Dillard A, Lecker J, Ip B, Lichtenstein A. Effects of dietary palmitoleic acid on plasma lipoprotein profile and aortic cholesterol accumulation are similar to those of other unsaturated fatty acids in the F1B golden Syrian hamster. J Nutr. 2009;139:215-21 pubmed publisher
    ..These data suggest that an oil relatively high in palmitoleic acid does not adversely affect plasma lipoprotein profiles or aortic cholesterol accumulation and was similar to other unsaturated fatty acid-rich oils. ..
  15. Fukuda M, Kanou F, Shimada N, Sawabe M, Saito Y, Murayama S, et al. Elevated levels of 4-hydroxynonenal-histidine Michael adduct in the hippocampi of patients with Alzheimer's disease. Biomed Res. 2009;30:227-33 pubmed
    ..These results show that the hippocampi of patients with AD undergo lipid peroxidation and imply that this activity underlies the production of cytotoxic products such as HNE that are responsible for the pathogenesis of AD. ..
  16. Bokor S, Dumont J, Spinneker A, Gonzalez Gross M, Nova E, Widhalm K, et al. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. J Lipid Res. 2010;51:2325-33 pubmed publisher
    ..These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents. ..
  17. Sengupta A, Ghosh M. Modulation of platelet aggregation, haematological and histological parameters by structured lipids on hypercholesterolaemic rats. Lipids. 2010;45:393-400 pubmed publisher
    ..Organopathological examination showed that there was deposition of cholesterol in the liver in the hypercholesterolaemic condition, which was also reduced by treatment with the two experimental oils. ..
  18. Song B, Elbert A, Rahman T, Orr S, Chen C, Febbraio M, et al. Genetic ablation of CD36 does not alter mouse brain polyunsaturated fatty acid concentrations. Lipids. 2010;45:291-9 pubmed publisher
    ..These findings suggest that CD36 is not necessary for maintaining brain PUFA concentrations and that other mechanisms must exist. ..
  19. Shah M, Shah S. Nutrient deficiencies in the premature infant. Pediatr Clin North Am. 2009;56:1069-83 pubmed publisher
    ..This article reviews the normal accretion of nutrients in the fetus, discusses specific nutrient deficiencies that are exacerbated in the postnatal period, and identifies key areas for future research. ..
  20. Lands B. Planning primary prevention of coronary disease. Curr Atheroscler Rep. 2009;11:272-80 pubmed
  21. Fakas S, Makri A, Mavromati M, Tselepi M, Aggelis G. Fatty acid composition in lipid fractions lengthwise the mycelium of Mortierella isabellina and lipid production by solid state fermentation. Bioresour Technol. 2009;100:6118-20 pubmed publisher
    ..Pear pomace cultures yielded significant amounts of lipid, which reached 12% (w/w) in dry fermented mass. The produced lipid was rich in GLA and the maximum GLA content in dry fermented mass was 2.9 mg/g. ..
  22. Petrie J, Liu Q, Mackenzie A, Shrestha P, Mansour M, Robert S, et al. Isolation and characterisation of a high-efficiency desaturase and elongases from microalgae for transgenic LC-PUFA production. Mar Biotechnol (NY). 2010;12:430-8 pubmed publisher
    ..In addition, the Delta6-desaturase is homologous with acyl-CoA desaturases and shows a strong preference for the omega3 substrate ALA. ..
  23. McKain N, Shingfield K, Wallace R. Metabolism of conjugated linoleic acids and 18 : 1 fatty acids by ruminal bacteria: products and mechanisms. Microbiology. 2010;156:579-88 pubmed publisher
    Cultures of ruminal bacteria known to metabolize unsaturated fatty acids were grown in medium containing 50 microg ml(-1) of geometric and positional isomers of conjugated linoleic acid (CLA) or 18 : 1 fatty acids and 37...
  24. von Knethen A, Tzieply N, Jennewein C, Brüne B. Casein-kinase-II-dependent phosphorylation of PPARgamma provokes CRM1-mediated shuttling of PPARgamma from the nucleus to the cytosol. J Cell Sci. 2010;123:192-201 pubmed publisher
    ..We conclude that CK-II-dependent PPARgamma phosphorylation at Ser16 and Ser21 is necessary for CRM1/Ran/RanBP3-mediated nucleocytoplasmic translocation of PPARgamma. ..
  25. Kaur G, Begg D, Barr D, Garg M, Cameron Smith D, Sinclair A. Short-term docosapentaenoic acid (22:5 n-3) supplementation increases tissue docosapentaenoic acid, DHA and EPA concentrations in rats. Br J Nutr. 2010;103:32-7 pubmed publisher
    ..Future studies should examine the physiological effect of DPA in tissues such as liver and heart. ..
  26. Siems W, Crifo C, Capuozzo E, Uchida K, Grune T, Salerno C. Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes. Arch Biochem Biophys. 2010;503:248-52 pubmed publisher
    ..Cysteinyl-glycine-HNE adduct and mercapturic acids contribute to about 5%. ..
  27. Buaud B, Esterle L, Vaysse C, Alfos S, Combe N, Higueret P, et al. A high-fat diet induces lower expression of retinoid receptors and their target genes GAP-43/neuromodulin and RC3/neurogranin in the rat brain. Br J Nutr. 2010;103:1720-9 pubmed publisher
    ..These results suggest that dietary fat induces neurobiological alterations by modulating the brain RA signalling pathway and n-3 PUFA content, which have been previously correlated with cognitive impairment. ..
  28. Boss A, Lecoultre V, Ruffieux C, Tappy L, Schneiter P. Combined effects of endurance training and dietary unsaturated fatty acids on physical performance, fat oxidation and insulin sensitivity. Br J Nutr. 2010;103:1151-9 pubmed publisher
    ..Since n-3 and n-9 unsaturated fatty acids may also increase fat oxidation, we hypothesised that a diet enriched in these fatty acids may enhance ..
  29. Childs C, Romeu Nadal M, Burdge G, Calder P. The polyunsaturated fatty acid composition of hepatic and plasma lipids differ by both sex and dietary fat intake in rats. J Nutr. 2010;140:245-50 pubmed publisher
    ..Together, these findings show that sex is an important determinant of the effect of variations in fat and fatty acid intake on LCPUFA status, which may have implications for recommendations for fat and fatty acid intake in humans. ..
  30. Takenaka S, Sato T, Koshiya J, Murakami S, Aoki K. Gene cloning and characterization of a deaminase from the 4-amino-3-hydroxybenzoate-assimilating Bordetella sp. strain 10d. FEMS Microbiol Lett. 2009;298:93-8 pubmed publisher
  31. Hui J, Hayward A, Bendena W, Takahashi T, Tobe S. Evolution and functional divergence of enzymes involved in sesquiterpenoid hormone biosynthesis in crustaceans and insects. Peptides. 2010;31:451-5 pubmed publisher
  32. Sakuradani E. Advances in the production of various polyunsaturated fatty acids through Oleaginous Fungus Mortierella alpina breeding. Biosci Biotechnol Biochem. 2010;74:908-17 pubmed
    ..This review describes practical PUFA production through mutant breeding, functional analyses of the genes of the enzymes involved in PUFA biosynthesis, and recent advances in unique PUFA production through molecular breeding. ..
  33. Schopfer F, Cole M, Groeger A, Chen C, Khoo N, Woodcock S, et al. Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions. J Biol Chem. 2010;285:12321-33 pubmed publisher
    ..In contrast, nitro derivatives of unsaturated fatty acids (NO(2)-FA) are endogenous products of nitric oxide ((*)NO) and nitrite (NO(2)(-))-mediated redox ..
  34. Leng Y, Marinova Z, Reis Fernandes M, Nau H, Chuang D. Potent neuroprotective effects of novel structural derivatives of valproic acid: potential roles of HDAC inhibition and HSP70 induction. Neurosci Lett. 2010;476:127-32 pubmed publisher
    ..Our results suggest that these two VPA derivatives may ultimately be developed into potent neuroprotective drugs in preclinical and clinical studies. ..
  35. Rahman T, Taha A, Song B, Orr S, Liu Z, Chen C, et al. The very low density lipoprotein receptor is not necessary for maintaining brain polyunsaturated fatty acid concentrations. Prostaglandins Leukot Essent Fatty Acids. 2010;82:141-5 pubmed publisher
    ..These findings demonstrate that the VLDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFA into the brain must exist. ..
  36. Lee J, Panek J. Total synthesis of brevisamide. Org Lett. 2009;11:4390-3 pubmed publisher
    ..The side chain bearing a conjugated (E,E)-diene was efficiently constructed under modified Negishi cross-coupling conditions. ..
  37. Aratake S, Trianto A, Hanif N, de Voogd N, Tanaka J. A new polyunsaturated brominated fatty acid from a Haliclona sponge. Mar Drugs. 2009;7:523-7 pubmed publisher
    ..The structure of compound 1 was elucidated by analyzing its spectral data. It showed moderate cytotoxicity against cultured cells...
  38. Ntawubizi M, Colman E, Janssens S, Raes K, Buys N, De Smet S. Genetic parameters for intramuscular fatty acid composition and metabolism in pigs. J Anim Sci. 2010;88:1286-94 pubmed publisher
    ..It was concluded that there is meaningful genetic variation for long-chain PUFA metabolism that is only partly dependent on the carcass and muscle fat content. This may allow selection for improved FA composition of pork. ..
  39. Saw C, Huang Y, Kong A. Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol. 2010;79:421-30 pubmed publisher
    ..Taken together, the present study clearly shows the synergistic anti-inflammatory as well as anti-oxidative stress effects of CUR and PUFA. ..
  40. Fujii K, Luo Y, Sasahira T, Denda A, Ohmori H, Kuniyasu H. Co-treatment with deoxycholic acid and azoxymethane accelerates secretion of HMGB1 in IEC6 intestinal epithelial cells. Cell Prolif. 2009;42:701-9 pubmed publisher
    ..Leptomycin B inhibited extranuclear translocation and secretion of the HMGB1 protein. These findings suggest that DCA affects intracellular localization and secretion of HMGB1. ..
  41. Destaillats F, Cruz Hernandez C, Giuffrida F, Dionisi F. Identification of the botanical origin of pine nuts found in food products by gas-liquid chromatography analysis of fatty acid profile. J Agric Food Chem. 2010;58:2082-7 pubmed publisher
    ..The present study shows that the botanical origin of pine nuts can be identified in products based on the fatty acid profile. ..
  42. Selvaraj R, Shanmugasundaram R, Klasing K. Effects of dietary lutein and PUFA on PPAR and RXR isomer expression in chickens during an inflammatory response. Comp Biochem Physiol A Mol Integr Physiol. 2010;157:198-203 pubmed publisher
    ..It is concluded that dietary lutein and PUFA fat were anti-inflammatory due to modification of immune tissue lutein content, PPAR, RXR isomers and IL-1beta mRNA levels in liver and spleen. ..
  43. Juhlin J, Fikse F, Lundén A, Pickova J, Agenäs S. Relative impact of alpha-tocopherol, copper and fatty acid composition on the occurrence of oxidized milk flavour. J Dairy Res. 2010;77:302-9 pubmed publisher
    ..A clear association between concentrations of copper and poly-unsaturated fatty acids in milk and the risk for developing SOF was found...
  44. Malinska H, Oliyarnyk O, Hubová M, Zidek V, Landa V, Simakova M, et al. Increased liver oxidative stress and altered PUFA metabolism precede development of non-alcoholic steatohepatitis in SREBP-1a transgenic spontaneously hypertensive rats with genetic predisposition to hepatic steatosis. Mol Cell Biochem. 2010;335:119-25 pubmed publisher
    ..that excess fat accumulation in the liver in association with increased oxidative stress and disturbances in the metabolism of saturated and unsaturated fatty acids may precede and contribute to the primary pathogenesis of NASH.
  45. Barden A, Croft K, Durand T, Guy A, Mueller M, Mori T. Flaxseed oil supplementation increases plasma F1-phytoprostanes in healthy men. J Nutr. 2009;139:1890-5 pubmed publisher
    ..Future studies are needed to determine the physiological importance of increased plasma and urine F(1)-phytoprostanes and their relevance to heart disease prevention. ..
  46. Gnoni G, Priore P, Geelen M, Siculella L. The mitochondrial citrate carrier: metabolic role and regulation of its activity and expression. IUBMB Life. 2009;61:987-94 pubmed publisher
    ..Emphasis will be placed on the molecular basis of the regulation of CiC activity in coordination with fatty acid synthesis. ..
  47. Ganapathy S. Long chain polyunsaturated fatty acids and immunity in infants. Indian Pediatr. 2009;46:785-90 pubmed
    ..Clinicians should ensure that LC-PUFA are supplied to the term and preterm infant in the form of breastmilk or provided in right proportions in formula, if breast milk is unavailable. ..
  48. Spiteller G. Is lipid peroxidation of polyunsaturated acids the only source of free radicals that induce aging and age-related diseases?. Rejuvenation Res. 2010;13:91-103 pubmed publisher
    ..Since any cell preparation method causes membrane destruction, it is inevitable that protonated superoxide is generated, explaining why H(2)O(2) molecules are found as "byproducts" of many reactions. ..
  49. Busch A, Kiel T, Hübner S. Quantification of nuclear protein transport using induced heterodimerization. Traffic. 2009;10:1221-7 pubmed publisher
    ..Induced protein heterodimerization is thus a valuable tool to quantitatively study nucleocytoplasmic protein trafficking in cultured cells, in a non-invasive, time-saving manner. ..
  50. Banerjee A, Ghoshal A. Phenol degradation by Bacillus cereus: pathway and kinetic modeling. Bioresour Technol. 2010;101:5501-7 pubmed publisher
    ..Modeling of the biodegradation of phenol indicates that the Haldane inhibitory model predicts the experimental data fairly well for both the strains. ..
  51. Lorenc Kukuła K, Zuk M, Kulma A, Czemplik M, Kostyn K, Skala J, et al. Engineering Flax with the GT Family 1 Solanum sogarandinum Glycosyltransferase SsGT1 Confers Increased Resistance to Fusarium Infection. J Agric Food Chem. 2009;57:6698-705 pubmed publisher
    ..point of view and might suggest the involvement of polyphenol glycosides in the protection of unsaturated fatty acids against oxidation and thus improve oil storage...
  52. Degirolamo C, Kelley K, Wilson M, Rudel L. Dietary n-3 LCPUFA from fish oil but not alpha-linolenic acid-derived LCPUFA confers atheroprotection in mice. J Lipid Res. 2010;51:1897-905 pubmed publisher
    ..These outcomes indicate that dietary n-3 LCPUFA from fish oil and n-3 LCPUFA (mostly EPA) synthesized endogenously from ALA were not equally atheroprotective in these mice. ..
  53. Han H, Qiu F, Zhao H, Tang H, Li X, Shi D. Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice. Oxid Med Cell Longev. 2017;2017:3256241 pubmed publisher