EETs Attenuate Ox-LDL-Induced LTB4 Production and Activity by Inhibiting p38 MAPK Phosphorylation and 5-LO/BLT1 Receptor Expression in Rat Pulmonary Arterial Endothelial Cells
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{"title"=>"EETs Attenuate Ox-LDL-Induced LTB4 Production and Activity by Inhibiting p38 MAPK Phosphorylation and 5-LO/BLT1 Receptor Expression in Rat Pulmonary Arterial Endothelial Cells.", "type"=>"journal", "authors"=>[{"first_name"=>"Jun-xia", "last_name"=>"Jiang"}, {"first_name"=>"Shui-juan", "last_name"=>"Zhang"}, {"first_name"=>"Yao-kang", "last_name"=>"Xiong"}, {"first_name"=>"Yong-liang", "last_name"=>"Jia"}, {"first_name"=>"Yan-hong", "last_name"=>"Sun"}, {"first_name"=>"Xi-xi", "last_name"=>"Lin"}, {"first_name"=>"Hui-juan", "last_name"=>"Shen"}, {"first_name"=>"Qiang-min", "last_name"=>"Xie"}, {"first_name"=>"Xiao-feng", "last_name"=>"Yan"}], "year"=>2015, "source"=>"PloS one", "identifiers"=>{"issn"=>"1932-6203", "pmid"=>"26035589", "doi"=>"10.1371/journal.pone.0128278"}, "id"=>"4ab2db8f-baeb-33a2-a959-bee9ec787043", "abstract"=>"Cytochrome P-450 epoxygenase (EPOX)-derived epoxyeicosatrienoic acids (EETs), 5-lipoxygenase (5-LO), and leukotriene B4 (LTB4), the product of 5-LO, all play a pivotal role in the vascular inflammatory process. We have previously shown that EETs can alleviate oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation in primary rat pulmonary artery endothelial cells (RPAECs). Here, we investigated whether ox-LDL can promote LTB4 production through the 5-LO pathway. We further explored how exogenous EETs influence ox-LDL-induced LTB4 production and activity. We found that treatment with ox-LDL increased the production of LTB4 and further led to the expression and release of both monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 (ICAM-1). All of the above ox-LDL-induced changes were attenuated by the presence of 11,12-EET and 14,15-EET, as these molecules inhibited the 5-LO pathway. Furthermore, the LTB4 receptor 1 (BLT1 receptor) antagonist U75302 attenuated ox-LDL-induced ICAM-1 and MCP-1/CCL2 expression and production, whereas LY255283, a LTB4 receptor 2 (BLT2 receptor) antagonist, produced no such effects. Moreover, in RPAECs, we demonstrated that the increased expression of 5-LO and BLT1 following ox-LDL treatment resulted from the activation of nuclear factor-κB (NF-κB) via the p38 mitogen-activated protein kinase (MAPK) pathway. Our results indicated that EETs suppress ox-LDL-induced LTB4 production and subsequent inflammatory responses by downregulating the 5-LO/BLT1 receptor pathway, in which p38 MAPK phosphorylation activates NF-κB. These results suggest that the metabolism of arachidonic acid via the 5-LO and EPOX pathways may present a mutual constraint on the physiological regulation of vascular endothelial cells.", "link"=>"http://www.mendeley.com/research/eets-attenuate-oxldlinduced-ltb4-production-activity-inhibiting-p38-mapk-phosphorylation-5loblt1-rec", "reader_count"=>2, "reader_count_by_academic_status"=>{"Student > Ph. D. Student"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Student > Ph. D. Student"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2092785"], "description"=>"<p>Cells were pretreated with a BLT1 receptor antagonist (U75302) (10 μM) and a BLT2 receptor antagonist (LY255283) (10 μM) and then stimulated with ox-LDL (100 μg/mL) for 24 h. Expression levels of MCP-1/CCL2 (A) and ICAM-1 (B) mRNAs and proteins were determined by qRT-PCR and ELISA, respectively. The data represent means ± S.E.M. from five independent experiments. <i>* P</i> <0.05, <i>** P</i> <0.01, <i>*** P</i> <0.001 compared with the control group. <sup><i>#</i></sup><i>P</i> <0.05 and <sup><i>##</i></sup><i>P</i> <0.01 compared with the ox-LDL (100 μg/mL)-stimulated group.</p>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434385, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128278.g004", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Role_of_LTB_4_receptor_antagonists_on_ICAM_1_and_MCP_1_CCL2_expression_in_RPAECs_/1434385", "title"=>"Role of LTB<sub>4</sub> receptor antagonists on ICAM-1 and MCP-1/CCL2 expression in RPAECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-02 03:13:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2092787"], "description"=>"<p>RPAECs were pre-treated with a p38 inhibitor (10 μM SB203580) or an NF-κB inhibitor (20 μM PDTC) for 30 min and then incubated with ox-LDL (100 μg/mL) for another 24 h. The levels of 5-LO and BLT1 mRNAs and proteins were determined by qRT-PCR (A, C) and western blot (B, D), respectively. The data represent the means ± S.E.M. from four independent experiments. <i>* P</i> <0.05 and <i>** P</i> <0.01 compared with the untreated group. <sup><i>#</i></sup><i>P</i> <0.05 and <sup><i>##</i></sup><i>P</i> <0.01 compared with the ox-LDL (100 μg/mL)-stimulated group.</p>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434387, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128278.g005", "stats"=>{"downloads"=>3, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_p38_MAPK_and_NF_954_B_signaling_pathways_are_involved_in_ox_LDL_mediated_expression_of_5_LO_and_BLT1_/1434387", "title"=>"The p38 MAPK and NF-κB signaling pathways are involved in ox-LDL-mediated expression of 5-LO and BLT1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-02 03:13:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2092794", "https://ndownloader.figshare.com/files/2092795", "https://ndownloader.figshare.com/files/2092796", "https://ndownloader.figshare.com/files/2092797"], "description"=>"<div><p>Cytochrome P-450 epoxygenase (EPOX)-derived epoxyeicosatrienoic acids (EETs), 5-lipoxygenase (5-LO), and leukotriene B<sub>4</sub> (LTB<sub>4</sub>), the product of 5-LO, all play a pivotal role in the vascular inflammatory process. We have previously shown that EETs can alleviate oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation in primary rat pulmonary artery endothelial cells (RPAECs). Here, we investigated whether ox-LDL can promote LTB<sub>4</sub> production through the 5-LO pathway. We further explored how exogenous EETs influence ox-LDL-induced LTB<sub>4</sub> production and activity. We found that treatment with ox-LDL increased the production of LTB<sub>4</sub> and further led to the expression and release of both monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 (ICAM-1). All of the above ox-LDL-induced changes were attenuated by the presence of 11,12-EET and 14,15-EET, as these molecules inhibited the 5-LO pathway. Furthermore, the LTB<sub>4</sub> receptor 1 (BLT1 receptor) antagonist U75302 attenuated ox-LDL-induced ICAM-1 and MCP-1/CCL2 expression and production, whereas LY255283, a LTB<sub>4</sub> receptor 2 (BLT2 receptor) antagonist, produced no such effects. Moreover, in RPAECs, we demonstrated that the increased expression of 5-LO and BLT1 following ox-LDL treatment resulted from the activation of nuclear factor-κB (NF-κB) via the p38 mitogen-activated protein kinase (MAPK) pathway. Our results indicated that EETs suppress ox-LDL-induced LTB<sub>4</sub> production and subsequent inflammatory responses by downregulating the 5-LO/BLT1 receptor pathway, in which p38 MAPK phosphorylation activates NF-κB. These results suggest that the metabolism of arachidonic acid via the 5-LO and EPOX pathways may present a mutual constraint on the physiological regulation of vascular endothelial cells.</p></div>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434394, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0128278.s001", "https://dx.doi.org/10.1371/journal.pone.0128278.s002", "https://dx.doi.org/10.1371/journal.pone.0128278.s003", "https://dx.doi.org/10.1371/journal.pone.0128278.s004"], "stats"=>{"downloads"=>6, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/EETs_Attenuate_Ox_LDL_Induced_LTB_4_Production_and_Activity_by_Inhibiting_p38_MAPK_Phosphorylation_and_5_LO_BLT1_Receptor_Expression_in_Rat_Pulmonary_Arterial_Endothelial_Cells/1434394", "title"=>"EETs Attenuate Ox-LDL-Induced LTB<sub>4</sub> Production and Activity by Inhibiting p38 MAPK Phosphorylation and 5-LO/BLT1 Receptor Expression in Rat Pulmonary Arterial Endothelial Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-02 03:13:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2092779"], "description"=>"<p>(A) RPAECs were exposed to different concentration of ox-LDL (10–100 μg/mL) for 24 h. LTB<sub>4</sub> protein levels in cell culture supernatant was quantified by ELISA. (B, D) 5-LO and BLT1 mRNA and protein levels were respectively measured by qRT-PCR and western blot. (C, E) ICAM-1, MCP-1/CCL2 mRNA and protein levels in cell culture supernatant were quantified by qRT-PCR and ELISA. The data shown are means ± S.E.M. of results from at least four independent experiments. <i>*P</i><0.05, <i>**P</i><0.01, <i>***P</i><0.001 compared with the control group.</p>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434379, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128278.g001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ox_LDL_induces_the_expression_and_release_of_ICAM_1_and_MCP_1_CCL2_and_up_regulates_the_5_LO_pathway_/1434379", "title"=>"Ox-LDL induces the expression and release of ICAM-1 and MCP-1/CCL2 and up-regulates the 5-LO pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-02 03:13:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2092780"], "description"=>"<p>(A) RPAECs were incubated with the indicated concentrations of 11,12-EET or 14,15-EET (1 μM) for 30 min and then stimulated with ox-LDL (100 μg/mL) for 24 h. LTB<sub>4</sub> protein levels in cell culture supernatant were quantified by ELISA. (B, D) 5-LO and BLT1 mRNA and protein levels were respectively determined by qRT-PCR and western blot. (C, E) ICAM-1 and MCP-1/CCL2 mRNA expression and protein levels in cell culture supernatant were quantified by qRT-PCR and ELISA. The data represent means ± S.E.M. from six independent experiments. <i>*P</i><0.05, <i>**P</i><0.01, <i>***P</i><0.001 compared with the control group. <sup><i>#</i></sup><i>P</i><0.05 compared with the ox-LDL (100 μg/mL)-treated group.</p>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434380, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128278.g002", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EETs_inhibit_ox_LDL_induced_expression_and_production_of_ICAM_1_and_MCP_1_CCL2_by_down_regulating_the_5_LO_pathway_in_RPAECs_/1434380", "title"=>"EETs inhibit ox-LDL-induced expression and production of ICAM-1 and MCP-1/CCL2 by down-regulating the 5-LO pathway in RPAECs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-02 03:13:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/2092782"], "description"=>"<p>RPAECs were exposed to different concentrations of LTB<sub>4</sub> (30–300 ng/mL) for 24 h. ICAM-1 and MCP-1/CCL2 mRNA and protein levels were respectively measured by qRT-PCR (A) and ELISA (B). The data represent means ± S.E.M. from six independent experiments. <i>* P</i> <0.05, <i>** P</i> <0.01, <i>*** P</i> <0.001 compared with the control group.</p>", "links"=>[], "tags"=>["intercellular adhesion molecule", "leukotriene B 4", "Rat Pulmonary", "BLT 1 receptor", "eet", "LTB 4 receptor 1", "LTB 4", "arachidonic acid", "LTB 4 receptor 2", "expression", "monocyte chemoattractant protein", "BLT 2 receptor", "nf", "RPAEC", "LTB 4 production", "lo", "EPOX pathways", "Inhibiting p 38 MAPK Phosphorylation", "ly", "icam", "BLT 1", "mcp"], "article_id"=>1434382, "categories"=>["Biological Sciences"], "users"=>["Jun-xia Jiang", "Shui-juan Zhang", "Yao-kang Xiong", "Yong-liang Jia", "Yan-hong Sun", "Xi-xi Lin", "Hui-juan Shen", "Qiang-min Xie", "Xiao-Feng Yan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128278.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LTB_4_induces_ICAM_1_and_MCP_1_CCL2_expression_and_release_in_rat_pulmonary_arterial_endothelial_cells_/1434382", "title"=>"LTB<sub>4</sub> induces ICAM-1 and MCP-1/CCL2 expression and release in rat pulmonary arterial endothelial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-02 03:13:30"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
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  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
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  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
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  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
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  • {"unique-ip"=>"11", "full-text"=>"16", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"23", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"32", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"15", "full-text"=>"21", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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