{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:52:43Z","timestamp":1787003563081,"version":"build-2736575974"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T00:00:00Z","timestamp":1544054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T00:00:00Z","timestamp":1544054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials have been carried out but none have been effective due to its adverse effects. In present study, we discover that Guanosine 5\u2019-diphosphate (GDP) encapsulated in lipid vesicle (NH+) was found to inhibit NF-\u049dB activation by limiting phosphorylation and degradation of I\u049dB\u03b1, thus, attenuating IL-6 secretion from macrophage cells. Moreover, the suppressed IL-6 levels down regulated JAK2\/STAT3 pathway with decrease inflammation-mediated\n                    <jats:italic>Hamp<\/jats:italic>\n                    mRNA transcription (HepG2) and increase iron absorption (Caco2) in HepG2\/Caco2 co-culture model. Analogous results were obtained in acute and chronic AI mice model thus, correcting haemoglobin level. These results proved NH\u2009+\u2009GDP as novel therapeutic agent to overcome limitations and suggests it as potential drug to ameliorate AI.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-35992-2","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T03:12:37Z","timestamp":1543547557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation"],"prefix":"10.1038","volume":"8","author":[{"given":"Stanzin","family":"Angmo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Rana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamalendra","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat","family":"Sandhir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-4487","authenticated-orcid":false,"given":"Nitin Kumar","family":"Singhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,6]]},"reference":[{"key":"35992_CR1","first-page":"103","volume":"122","author":"N Agarwal","year":"2009","unstructured":"Agarwal, N. & Prchal, J. T. Anemia of chronic disease (Anemia of Inflammation). ActaHaematol. 122, 103\u2013108 (2009).","journal-title":"ActaHaematol."},{"key":"35992_CR2","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1172\/JCI21441","volume":"113","author":"NC Andrews","year":"2004","unstructured":"Andrews, N. C. Anemia of inflammation: The cytokine-hepcidin link. Journal of Clinical Investigation 113, 1251\u20131253 (2004).","journal-title":"Journal of Clinical Investigation"},{"key":"35992_CR3","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.hoc.2014.04.005","volume":"28","author":"E Nemeth","year":"2014","unstructured":"Nemeth, E. & Ganz, T. Anemia of inflammation. Hematol. Oncol. Clin. North Am. 28, 671\u2013681 (2014).","journal-title":"Hematol. Oncol. Clin. North Am."},{"key":"35992_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BSR20150014","volume":"35","author":"G Rishi","year":"2015","unstructured":"Rishi, G., Wallace, D. F. & Subramaniam, V. N. Hepcidin: regulation of the master iron regulator. Biosci. Rep. 35, 1\u201312 (2015).","journal-title":"Biosci. Rep."},{"key":"35992_CR5","doi-asserted-by":"publisher","first-page":"3204","DOI":"10.1182\/blood-2006-06-027631","volume":"108","author":"DM Wrighting","year":"2006","unstructured":"Wrighting, D. M. & Andrews, N. C. Interleukin-6 induces hepcidin expression through STAT3. Blood 108, 3204\u20133209 (2006).","journal-title":"Blood"},{"key":"35992_CR6","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1126\/science.1104742","volume":"306","author":"E Nemeth","year":"2004","unstructured":"Nemeth, E. Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization. Science (80-.) 306, 2090\u20132093 (2004).","journal-title":"Science (80-.)"},{"key":"35992_CR7","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1182\/blood-2006-07-033969","volume":"109","author":"MV Verga Falzacappa","year":"2007","unstructured":"Verga Falzacappa, M. V. et al. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 109, 353\u2013358 (2007).","journal-title":"Blood"},{"key":"35992_CR8","doi-asserted-by":"publisher","unstructured":"Parrow, N. L. & Fleming, R. E. Bone Morphogenic Proteins as Regulators of Iron Metabolism. Annu. Rev. Nutr. 1\u201318, https:\/\/doi.org\/10.1146\/annurev-nutr-071813-105646 (2014).","DOI":"10.1146\/annurev-nutr-071813-105646"},{"key":"35992_CR9","first-page":"2337","volume":"123","author":"N Zhao","year":"2013","unstructured":"Zhao, N., Zhang, aS. & Enns, C. A. Iron Regulatin By Hepcidin. Sci. Med. 123, 2337\u20132343 (2013).","journal-title":"Sci. Med."},{"key":"35992_CR10","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1084\/jem.20090560","volume":"206","author":"A Kimura","year":"2009","unstructured":"Kimura, A. et al. Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. J. Exp. Med. 206, 2027\u20132035 (2009).","journal-title":"J. Exp. Med."},{"key":"35992_CR11","doi-asserted-by":"crossref","first-page":"20042","DOI":"10.18632\/oncotarget.15373","volume":"8","author":"H Wu","year":"2017","unstructured":"Wu, H. et al. Thymol mitigates lipopolysaccharide-induced endometritis by regulating the TLR4- and ROS-mediated NF-\u03baB signaling pathways. Oncotarget 8, 20042\u201320055 (2017).","journal-title":"Oncotarget"},{"key":"35992_CR12","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1002\/hep.20663","volume":"41","author":"DQ Lou","year":"2005","unstructured":"Lou, D. Q. et al. Iron- and inflammation-induced hepcidin gene expression in mice is not mediated by Kupffer cells in vivo. Hepatology 41, 1056\u20131064 (2005).","journal-title":"Hepatology"},{"key":"35992_CR13","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s00109-008-0346-y","volume":"86","author":"M Theurl","year":"2008","unstructured":"Theurl, M. et al. Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression. J. Mol. Med. 86, 825\u2013835 (2008).","journal-title":"J. Mol. Med."},{"key":"35992_CR14","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/hep.20620","volume":"41","author":"G Montosi","year":"2005","unstructured":"Montosi, G. et al. Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload. Hepatology 41, 545\u2013552 (2005).","journal-title":"Hepatology"},{"key":"35992_CR15","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1124\/jpet.112.194613","volume":"342","author":"H-K Rim","year":"2012","unstructured":"Rim, H.-K., Cho, W., Sung, S. H. & Lee, K.-T. Nodakenin Suppresses Lipopolysaccharide-Induced Inflammatory Responses in Macrophage Cells by Inhibiting Tumor Necrosis Factor Receptor-Associated Factor 6 and Nuclear Factor- B Pathways and Protects Mice from Lethal Endotoxin Shock. J. Pharmacol. Exp. Ther. 342, 654\u2013664 (2012).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"35992_CR16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1089\/ars.2015.6315","volume":"24","author":"H Xin","year":"2016","unstructured":"Xin, H. et al. Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation. Antioxid. Redox Signal. 24, 70\u201383 (2016).","journal-title":"Antioxid. Redox Signal."},{"key":"35992_CR17","first-page":"1","volume":"11","author":"M Wang","year":"2016","unstructured":"Wang, M., Tang, W., Xin, H. & Zhu, Y. Z. S-Propargyl-cysteine, a novel hydrogen sulfide donor, inhibits inflammatory hepcidin and relieves anemia of inflammation by inhibiting IL-6\/STAT3 pathway. PLoS One 11, 1\u201315 (2016).","journal-title":"PLoS One"},{"key":"35992_CR18","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s00109-009-0588-3","volume":"88","author":"N Fatih","year":"2010","unstructured":"Fatih, N. et al. Natural and synthetic STAT3 inhibitors reduce hepcidin expression in differentiated mouse hepatocytes expressing the active phosphorylated STAT3 form. J. Mol. Med. 88, 477\u2013486 (2010).","journal-title":"J. Mol. Med."},{"key":"35992_CR19","doi-asserted-by":"publisher","first-page":"5032","DOI":"10.3748\/wjg.v17.i45.5032","volume":"17","author":"SP Zhang","year":"2011","unstructured":"Zhang, S. P., Wang, Z., Wang, L. X. & Liu, S. J. AG490: An inhibitor of hepcidin expression in vivo. World J. Gastroenterol. 17, 5032\u20135034 (2011).","journal-title":"World J. Gastroenterol."},{"key":"35992_CR20","unstructured":"Wang, M. et al. AMPK Serves as a Therapeutic Target Against Anemia of Inflammation. Antioxid. Redox Signal. 6, ars.2016 6846 (2017)."},{"key":"35992_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/srep40097","volume":"7","author":"S Angmo","year":"2017","unstructured":"Angmo, S. et al. Identification of Guanosine 5\u2032-diphosphate as Potential Iron Mobilizer: Preventing the Hepcidin-Ferroportin Interaction and Modulating the Interleukin-6\/Stat-3 Pathway. Sci. Rep. 7, 40097 (2017).","journal-title":"Sci. Rep."},{"key":"35992_CR22","doi-asserted-by":"publisher","first-page":"773","DOI":"10.3324\/haematol.2008.003400","volume":"94","author":"P Matak","year":"2009","unstructured":"Matak, P. et al. Activated macrophages induce hepcidin expression in HuH7 hepatoma cells. Haematologica 94, 773\u2013780 (2009).","journal-title":"Haematologica"},{"key":"35992_CR23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/S1074-7613(02)00446-6","volume":"17","author":"I Kinjyo","year":"2002","unstructured":"Kinjyo, I. et al. SOCS1\/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17, 583\u2013591 (2002).","journal-title":"Immunity"},{"key":"35992_CR24","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cmet.2005.02.006","volume":"1","author":"BM Forman","year":"2005","unstructured":"Forman, B. M. Are those phospholipids in your pocket? Cell Metab. 1, 153\u2013155 (2005).","journal-title":"Cell Metab."},{"key":"35992_CR25","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.4049\/jimmunol.170.6.3263","volume":"170","author":"C Niemand","year":"2003","unstructured":"Niemand, C. et al. Activation of STAT3 by IL-6 and IL-10 in Primary Human Macrophages Is Differentially Modulated by Suppressor of Cytokine Signaling 3. J. Immunol. 170, 3263\u20133272 (2003).","journal-title":"J. Immunol."},{"key":"35992_CR26","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1053\/j.gastro.2010.12.037","volume":"140","author":"C Brasselagnel","year":"2011","unstructured":"Brasselagnel, C. et al. Intestinal DMT1 co-transporter is down-regulated by hepcidin via proteasome internalization and degradation. Gastroenterology 140, 1261\u20131271 (2011).","journal-title":"Gastroenterology"},{"issue":"109","key":"35992_CR27","first-page":"905","volume":"2","author":"TD Pollard","year":"2008","unstructured":"Pollard, T. D., Thomas, D., Earnshaw, W. C., Lippincott-Schwartz, J. & Johnson, G. T. Cell biology. 2(109), 905 (2008).","journal-title":"Cell biology."},{"key":"35992_CR28","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1053\/gast.2002.35353","volume":"123","author":"DM Frazer","year":"2002","unstructured":"Frazer, D. M. et al. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 123, 835\u2013844 (2002).","journal-title":"Gastroenterology"},{"key":"35992_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0061050","volume":"8","author":"JC Deschemin","year":"2013","unstructured":"Deschemin, J. C. & Vaulont, S. Role of Hepcidin in the Setting of Hypoferremia during Acute Inflammation. PLoS One 8, 1\u20137 (2013).","journal-title":"PLoS One"},{"key":"35992_CR30","doi-asserted-by":"crossref","unstructured":"Cells, R. E. D. Regular Article Erythroferrone contributes to recovery from anemia of in fl ammation. 124, 2569\u20132575 (2015).","DOI":"10.1182\/blood-2014-06-584607"},{"key":"35992_CR31","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1053\/j.seminhematol.2009.06.001","volume":"46","author":"T Ganz","year":"2009","unstructured":"Ganz, T. & Nemeth, E. Iron Sequestration and Anemia of Inflammation. Semin. Hematol. 46, 387\u2013393 (2009).","journal-title":"Semin. Hematol."},{"key":"35992_CR32","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1172\/JCI31342","volume":"117","author":"JL Babitt","year":"2007","unstructured":"Babitt, J. L. et al. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J. Clin. Invest. 117, 1933\u20131939 (2007).","journal-title":"J. Clin. Invest."},{"key":"35992_CR33","doi-asserted-by":"crossref","unstructured":"Tonelli, M., Hemmelgarn, B. &Teiman, T. Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: A meta-analysis (Canadian Medical Association Journal (2009) 180, 11 (E62-E71)). Cmaj 181, 61 (2009).","DOI":"10.1503\/cmaj.090470"},{"key":"35992_CR34","doi-asserted-by":"crossref","unstructured":"Vincent, J. L. et al. Anemia and Blood Transfusion in Critically Ill Patients. 288, 1499\u20131507 (2002).","DOI":"10.1001\/jama.288.12.1499"},{"key":"35992_CR35","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1086\/382878","volume":"2111","author":"GS Teehan","year":"2004","unstructured":"Teehan, G. S. et al. Iron Storage Indices: Novel Predictors of Bacteremia in Hemodialysis Patients Initiating Intravenous Iron Therapy. Clin Infect Dis. 2111, 1090\u20131094 (2004).","journal-title":"Clin Infect Dis."},{"key":"35992_CR36","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1472-6882-14-21","volume":"14","author":"K-Y Su","year":"2014","unstructured":"Su, K.-Y., Yu, C. Y., Chen, Y.-P., Hua, K.-F. & Chen, Y.-L. S. 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-\u03baBsignaling. BMC Complement. Altern. Med. 14, 21 (2014).","journal-title":"BMC Complement. Altern. Med."},{"key":"35992_CR37","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.intimp.2016.05.010","volume":"38","author":"Q Yu","year":"2016","unstructured":"Yu, Q. et al. Resokaempferol-mediated anti-inflammatory effects on activated macrophages via the inhibition of JAK2\/STAT3, NF-\u049dB and JNK\/p38 MAPK signaling pathways. Int. Immunopharmacol. 38, 104\u2013114 (2016).","journal-title":"Int. Immunopharmacol."},{"key":"35992_CR38","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jep.2016.12.007","volume":"196","author":"DY Li","year":"2017","unstructured":"Li, D. Y. et al. Anti-inflammatory effect of the six compounds isolated from NaucleaofficinalisPierrc ex Pitard, and molecular mechanism of strictosamide via suppressing the NF-kB and MAPK signaling pathway in LPS-induced RAW 264.7 macrophages. J. Ethnopharmacol. 196, 66\u201374 (2017).","journal-title":"J. Ethnopharmacol."},{"key":"35992_CR39","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1093\/rheumatology\/kei282","volume":"45","author":"CH Jang","year":"2006","unstructured":"Jang, C. H., Choi, J. H., Byun, M. S. & Jue, D. M. Chloroquine inhibits production of TNF-\u03b1, IL-1\u03b2 and IL-6 from lipopolysaccharide-stimulated human monocytes\/macrophages by different modes. Rheumatology 45, 703\u2013710 (2006).","journal-title":"Rheumatology"},{"key":"35992_CR40","doi-asserted-by":"crossref","unstructured":"El-sunousi, R. Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration. Int J Nanomedicine 2163\u20132172 (2013).","DOI":"10.2147\/IJN.S44108"},{"key":"35992_CR41","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3844\/ajptsp.2008.219.224","volume":"3","author":"NA Sana","year":"2008","unstructured":"Sana, N. A., Abdullah, R. & Putra, U. Tamoxifen Drug Loading Solid Lipid Nanoparticles Prepared by Hot High Pressure Homogenization Techniques. American Journal of Pharmacology and Toxicology 3, 219\u2013224, https:\/\/doi.org\/10.3844\/ajptsp.2008.219.224 (2008).","journal-title":"American Journal of Pharmacology and Toxicology"},{"key":"35992_CR42","first-page":"10","volume":"3","author":"PR Kulkarni","year":"2011","unstructured":"Kulkarni, P. R., Yadav, J. D. & Vaidya, K. A. Liposomes: a Novel Drug Delivery System. Int. J. Curr. Pharm. Res. 3, 10\u201318 (2011).","journal-title":"Int. J. Curr. Pharm. Res."},{"key":"35992_CR43","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1023\/A:1015837321087","volume":"7","author":"X Guo-Xing","year":"1990","unstructured":"Guo-Xing, X. et al. Adenosine Triphosphate Liposomes: Encapsulation and Distribution Studies. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists 7, 553\u2013557 (1990).","journal-title":"Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists"},{"key":"35992_CR44","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1007\/s00535-009-0159-y","volume":"45","author":"R Sakamori","year":"2010","unstructured":"Sakamori, R. et al. STAT3 signaling within hepatocytes is required for anemia of inflammation in vivo. J. Gastroenterol. 45, 244\u2013248 (2010).","journal-title":"J. Gastroenterol."},{"key":"35992_CR45","doi-asserted-by":"publisher","first-page":"2502","DOI":"10.1016\/j.ejca.2005.08.016","volume":"41","author":"DR Hodge","year":"2005","unstructured":"Hodge, D. R., Hurt, E. M. & Farrar, W. L. The role of IL-6 and STAT3 in inflammation and cancer. Eur. J. Cancer 41, 2502\u20132512 (2005).","journal-title":"Eur. J. Cancer"},{"key":"35992_CR46","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.jnutbio.2014.02.013","volume":"25","author":"NM Scheers","year":"2014","unstructured":"Scheers, N. M., Almgren, A. B. & Sandberg, A. S. Proposing a Caco-2\/HepG2 cell model for in vitro iron absorption studies. J. Nutr. Biochem. 25, 710\u2013715 (2014).","journal-title":"J. Nutr. Biochem."},{"issue":"4","key":"35992_CR47","doi-asserted-by":"publisher","first-page":"G397","DOI":"10.1152\/ajpgi.00348.2013","volume":"307","author":"S Gulec","year":"2014","unstructured":"Gulec, S., Anderson, G. J. & Collins, J. F. Mechanistic and regulatory aspects of intestinal iron absorption. American Journal of Physiology - Gastrointestinal and Liver Physiology. 307(4), G397\u2013G409 (2014).","journal-title":"American Journal of Physiology - Gastrointestinal and Liver Physiology."},{"key":"35992_CR48","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/ajh.23670","volume":"89","author":"JM Langdon","year":"2014","unstructured":"Langdon, J. M. et al. Hepcidin-dependent and hepcidin-independent regulation of erythropoiesis in a mouse model of anemia of chronic inflammation. Am. J. Hematol. 89, 470\u2013479 (2014).","journal-title":"Am. J. Hematol."},{"key":"35992_CR49","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1053\/j.seminhematol.2009.06.003","volume":"46","author":"S Rivera","year":"2009","unstructured":"Rivera, S. & Ganz, T. Animal Models of Anemia of Inflammation. Semin. Hematol. 46, 351\u2013357 (2009).","journal-title":"Semin. Hematol."},{"key":"35992_CR50","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.1182\/blood-2011-03-345066","volume":"118","author":"I Theurl","year":"2012","unstructured":"Theurl, I. et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 118, 4977\u20134984 (2012).","journal-title":"Blood"},{"key":"35992_CR51","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1172\/JCI0215686","volume":"110","author":"G Nicolas","year":"2002","unstructured":"Nicolas, G. et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 110, 1037\u20131044 (2002).","journal-title":"J. Clin. Invest."},{"key":"35992_CR52","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.1097\/CCM.0b013e31818103b9","volume":"36","author":"S Lasocki","year":"2008","unstructured":"Lasocki, S. et al. Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia. Crit. Care Med. 36, 2388\u201394 (2008).","journal-title":"Crit. Care Med."},{"key":"35992_CR53","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1111\/j.1365-2141.2004.05044.x","volume":"126","author":"DM Frazer","year":"2004","unstructured":"Frazer, D. M. et al. Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE. Br. J. Haematol. 126, 434\u2013436 (2004).","journal-title":"Br. J. Haematol."},{"key":"35992_CR54","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1166\/jcsb.2012.1020","volume":"1","author":"A Laouini","year":"2012","unstructured":"Laouini, A. et al. Preparation, Characterization and Applications of Liposomes: State of the Art. J. Colloid Sci. Biotechnol. 1, 147\u2013168 (2012).","journal-title":"J. Colloid Sci. Biotechnol."},{"key":"35992_CR55","doi-asserted-by":"publisher","first-page":"185","DOI":"10.4314\/tjpr.v13i2.3","volume":"13","author":"B Sabeti","year":"2014","unstructured":"Sabeti, B., bin Noordine, M. I., Javar, H. A., Davoudi, E. T. & Kadivar, A. Characterization of diclofenac liposomes formulated with palm oil fractions. Trop. J. Pharm. Res. 13, 185\u2013190 (2014).","journal-title":"Trop. J. Pharm. Res."},{"key":"35992_CR56","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ijpharm.2013.06.078","volume":"454","author":"L Yuan","year":"2013","unstructured":"Yuan, L. et al. Effect of iron liposomes on anemia of inflammation. Int. J. Pharm. 454, 82\u201389 (2013).","journal-title":"Int. J. Pharm."},{"key":"35992_CR57","unstructured":"Studio2. Useful Numbers for Cell Culture. 1 (2005)."},{"key":"35992_CR58","doi-asserted-by":"crossref","unstructured":"Ruyra, A., Cano-Sarabia, M., MacKenzie, S. A., Maspoch, D. &Roher, N. A Novel Liposome-Based Nanocarrier Loaded with an LPS-dsRNA Cocktail for Fish Innate Immune System Stimulation. PLoS One 8, 1\u201313 (2013).","DOI":"10.1371\/journal.pone.0076338"},{"key":"35992_CR59","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1172\/JCI25683","volume":"115","author":"V Niederkofler","year":"2005","unstructured":"Niederkofler, V., Salie, R. & Arber, S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J. Clin. Invest. 115, 2180\u20132186 (2005).","journal-title":"J. Clin. Invest."},{"key":"35992_CR60","doi-asserted-by":"publisher","first-page":"G385","DOI":"10.1152\/ajpgi.00246.2003","volume":"286","author":"K Yeh","year":"2004","unstructured":"Yeh, K., Yeh, M. & Glass, J. Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G385\u2013G394 (2004).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"35992_CR61","doi-asserted-by":"publisher","first-page":"4308","DOI":"10.1182\/blood-2004-06-2422","volume":"104","author":"J Krijt","year":"2004","unstructured":"Krijt, J., Vokurka, M., Chang, K. T. & Ne\u010das, E. Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin. Blood 104, 4308\u20134310 (2004).","journal-title":"Blood"},{"key":"35992_CR62","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/hep.20620","volume":"41","author":"G Montosi","year":"2005","unstructured":"Montosi, G. et al. Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload. Hepatology 41, 545\u2013552 (2005).","journal-title":"Hepatology"},{"key":"35992_CR63","doi-asserted-by":"crossref","unstructured":"Mena, N. P., Tapia, V., Valde, P. & Nu, M. T. Hepcidin inhibits apical iron uptake in intestinal cells. 192\u2013198 (2008).","DOI":"10.1152\/ajpgi.00122.2007"},{"key":"35992_CR64","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.peptides.2007.01.016","volume":"28","author":"E Fein","year":"2007","unstructured":"Fein, E., Merle, U., Ehehalt, R., Herrmann, T. & Kulaksiz, H. Regulation of hepcidin in HepG2 and RINm5F cells. Peptides 28, 951\u2013957 (2007).","journal-title":"Peptides"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35992-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35992-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35992-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T07:16:18Z","timestamp":1671606978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-35992-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,6]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["35992"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-35992-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,6]]},"assertion":[{"value":"13 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"17684"}}