A Cannabigerol Derivative Suppresses Immune Responses and Protects Mice from Experimental Autoimmune Encephalomyelitis
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{"title"=>"A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis", "type"=>"journal", "authors"=>[{"first_name"=>"Francisco J.", "last_name"=>"Carrillo-Salinas", "scopus_author_id"=>"55293355000"}, {"first_name"=>"Carmen", "last_name"=>"Navarrete", "scopus_author_id"=>"14631102400"}, {"first_name"=>"Miriam", "last_name"=>"Mecha", "scopus_author_id"=>"24344558900"}, {"first_name"=>"Ana", "last_name"=>"Feliú", "scopus_author_id"=>"6603717670"}, {"first_name"=>"Juan A.", "last_name"=>"Collado", "scopus_author_id"=>"12763079000"}, {"first_name"=>"Irene", "last_name"=>"Cantarero", "scopus_author_id"=>"56360769300"}, {"first_name"=>"María L.", "last_name"=>"Bellido", "scopus_author_id"=>"37046767800"}, {"first_name"=>"Eduardo", "last_name"=>"Muñoz", "scopus_author_id"=>"7202348306"}, {"first_name"=>"Carmen", "last_name"=>"Guaza", "scopus_author_id"=>"7006046907"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84899632221", "sgr"=>"84899632221", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24727978", "doi"=>"10.1371/journal.pone.0094733", "pui"=>"372981399"}, "id"=>"d075d859-e8f2-3a27-a5dc-e7c71bfef2e3", "abstract"=>"Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG35-55) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential of VCE-003 as an agent for the treatment of human immune diseases with both inflammatory and autoimmune components.", "link"=>"http://www.mendeley.com/research/cannabigerol-derivative-suppresses-immune-responses-protects-mice-experimental-autoimmune-encephalom-4", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>10, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Chemistry"=>1, "Psychology"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}}, "reader_count_by_country"=>{"Spain"=>2}, "group_count"=>4}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1462087"], "description"=>"<div><p>Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG<sub>35–55</sub>) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4<sup>+</sup> T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential of VCE-003 as an agent for the treatment of human immune diseases with both inflammatory and autoimmune components.</p></div>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "cannabigerol", "derivative", "suppresses", "responses", "protects", "mice", "autoimmune"], "article_id"=>997101, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733", "stats"=>{"downloads"=>3, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Cannabigerol_Derivative_Suppresses_Immune_Responses_and_Protects_Mice_from_Experimental_Autoimmune_Encephalomyelitis_/997101", "title"=>"A Cannabigerol Derivative Suppresses Immune Responses and Protects Mice from Experimental Autoimmune Encephalomyelitis", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462080"], "description"=>"<p>Representative images of axon morphology changes: (A) transversal thoracic spinal cord sections, neurofilament staining in red; (B) longitudinal thoracic spinal cord sections, neurofilament staining in green (please note axon swelling, arrows). (C) VCE-003 treatment helps to preserve the axon structure as showed in longitudinal thoracic spinal cord sections by SMI32 staining.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "axon"], "article_id"=>997095, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g006", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VCE_003_reduces_axon_damage_/997095", "title"=>"VCE-003 reduces axon damage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462071"], "description"=>"<p>Serum starved RAW264.7 cells were exposed to either JWH-133 (5 µM) or VCE-003 (1 and 2.5 µM) for 18 h and then maintained for 24 h in the presence or absence of recombinant mouse IL-17 (50 ng/ml). A) RT-PCR analysis of M1 gene expression in JWH-133-treated RAW264.7 cells. B) RT-PCR analysis of M1 gene expression in VCE-003-treated RAW264.7 cells. The results are expressed as the fold change with respect to untreated cells and they are the mean ± SEM of four independent experiments. C) CHO-CB2 cells were transiently transfected with the CRE-luc plasmid and then exposed to FSK (1 µM) for 6 h in the presence or absence of the indicated concentrations of WIN-55,212-2 (1 or 10 µM) and VCE-003 (5 µM) before luciferase activity was measured in the cell lysates. The results are expressed as the means ± SEM of three determinations and they are expressed as the percentage inhibition considering FSK stimulation as 100% activation: *p<0.05, **p<0.01 and ***p<0.005 in an unpaired two-tailed Student's <i>t</i> test.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "jwh-133", "il-17-induced", "m1", "polarization"], "article_id"=>997091, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g003", "stats"=>{"downloads"=>0, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VCE_003_and_JWH_133_reduces_IL_17_induced_M1_polarization_in_macrophages_/997091", "title"=>"VCE-003 and JWH-133 reduces IL-17-induced M1 polarization in macrophages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462070"], "description"=>"<p>(A) Human peripheral T cells were stimulated for 72 h with the OKT3 (1 µg/ml) and anti-CD28 (0.5 µg/ml) mAbs in the presence or absence of increasing concentrations of VCE-003, and the culture supernatants were collected and assayed using a R&D Systems Human Cytokine Array system (A, cytokines; B, chemokines and sICAM-1). (C) Human peripheral T cells were stimulated as indicated in 2A for 72 h, and the expression of CD25 and CD54 was detected by flow cytometry. The numbers represent the percentage of CD25<sup>+</sup> and CD54<sup>+</sup> cells and they are representative of three different experiments. (D) Jurkat T cells transfected with TNFα, IL-17 or IL-2 promoter luciferase reporter plasmids were treated for 30 min with increasing concentrations of VCE-003, and then stimulated with OKT3 (1 µg/ml) and anti-CD28 (0.5 µg/ml) mAbs for 6 h before measuring luciferase activity in the cell lysates. The results are the means ± SEM of three measurements and they are expressed as the percentage of inhibition, considering CD3/CD28 stimulation as 100% activation: **p≤0.01 indicates significant changes between CD3+CD28 and VCE-003 treatment.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "vce-003", "t-cell"], "article_id"=>997090, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_VCE_003_on_T_cell_activation_/997090", "title"=>"Effects of VCE-003 on T-cell activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462084"], "description"=>"<p>The mouse primer sequences used in quantitative Polymerase Chain Reactions.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "primer", "sequences", "quantitative", "polymerase"], "article_id"=>997099, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.t001", "stats"=>{"downloads"=>6, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_mouse_primer_sequences_used_in_quantitative_Polymerase_Chain_Reactions_/997099", "title"=>"The mouse primer sequences used in quantitative Polymerase Chain Reactions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462083"], "description"=>"<p>VCE-003 decreased the mRNA expression of TNFα, IFNγ, IL-1β and IL-17 (A), and the adhesion molecule ICAM-1 and iNOS (B). (C) Immunoblotting of iNOS. Proteins in lysates (30 µg) from BV2 cells stimulated with LPS (50 ng/ml) and IFNγ (100 u/ml), and pre-treated with VCE-003 (1 µM). Both CB2 and PPARγ antagonists (AM630 1 µM and GW9662 0.1 µM, respectively) were administered 10 min before than VCE-003 treatment. The results are presented as the relative ratio of proteins, where the iNOS signal obtained by densitometric analysis was normalized to the tubulin signal. VCE-003 treatment significantly reverses the LPS-IFNγ-induced effects to the control situation, and both CB2 and PPARγ antagonists blocked this effect of VCE-003. The results in (A, B) are shown as the means ± SEM: *p = 0,011 vs Intact (TNFα); *p = 0,003 vs Intact (ICAM-1); **p<0.01 vs Intact; #p = 0.05 vs EAE + VEH (ICAM-1); ##p<0.01 vs EAE + VEH; ###p<0.001 vs EAE + VEH). The results in (C) are shown as the means ± SEM from three independent experiments performed in triplicate: ***p<0.001 vs CTL; ##p<0.01 vs CTL + LPS- IFNγ; +p = 0.034 vs VCE-003 1 µM + LPS- IFNγ; ++p = 0.002 vs VCE-003 1 µM + LPS- IFNγ.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "inflammatory", "mrnas", "spinal", "inos", "bv2"], "article_id"=>997098, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g007", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VCE_003_reduces_the_expression_of_inflammatory_marker_mRNAs_in_the_spinal_cord_and_of_iNOS_protein_in_BV2_cells_/997098", "title"=>"VCE-003 reduces the expression of inflammatory marker mRNAs in the spinal cord and of iNOS protein in BV2 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462073"], "description"=>"<p>(A) VCE-003 notably reduces microglial activation (Iba1<sup>+</sup> cells). (B) Quantification of Iba1<sup>+</sup> cells are shown as means ± SEM (***p<0.001 vs Intact; #p = 0.021 vs EAE + VEH). Thoracic spinal cord sections from symptomatic animals show a clear disruption of myelin, whereas exposure to VCE-003 contributes to maintain the myelin structure (C, RIP immunofluorescence staining; D, LFB staining).</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "microglial", "activation", "preserves", "myelin"], "article_id"=>997093, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VCE_003_significantly_reduces_microglial_activation_and_preserves_myelin_structure_/997093", "title"=>"VCE-003 significantly reduces microglial activation and preserves myelin structure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462072"], "description"=>"<p>(A) VCE-003 significantly ameliorates the clinical signs and disease progression of EAE (squares), and these effects are partially blocked by a CB2 antagonist (AM630, triangles) or PPARγ antagonist (T0070907, circles). The results are shown as the means ± SD: *p = 0.015 EAE + VCE-003 vs EAE + VEH; **p = 0.005 EAE + VCE-003 vs EAE + VEH; ***p<0.001 EAE + VCE-003 vs EAE + VEH; #p = 0.016 EAE + VCE-003 + AM630 vs EAE + VCE-003; ##p = 0.008 EAE + VCE-003 + AM630 vs EAE + VCE-003; ###p<0.001 EAE + VCE-003 + AM630 vs EAE + VCE-003; +p = 0,009 EAE + VCE-003 + T0070907 vs EAE + VCE-003; ++p<0.01 EAE + VCE-003 + T0070907 vs EAE + VCE-003. (B) VCE-003 reduces the number of infiltrates and (C) it significantly reduces the number of CD4<sup>+</sup> T cells in thoracic spinal cord sections. The figure shows the representative staining of spinal cord sections: LFB (B) and CD4 immunohistochemistry (C). Arrows indicate CD4<sup>+</sup> T cells. The results (C) are shown as the means ± SEM: **p = 0,004 vs Intact; #p = 0,030 vs EAE + VEH.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "alleviates", "eae", "prevents", "cells"], "article_id"=>997092, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g004", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VCE_003_alleviates_EAE_and_prevents_CD4_cells_infiltration_/997092", "title"=>"VCE-003 alleviates EAE and prevents CD4<sup>+</sup> cells infiltration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/1462069"], "description"=>"<p>(A) Human peripheral T cells were stimulated with the OKT3 (1 µg/ml) and anti-CD28 (0.5 µg/ml) mAbs for 72 h in the presence or absence of increasing concentrations of VCE-003. Thymidine [<sup>3</sup>H] incorporation was measured by liquid scintillation and represented as the mean d.p.m ± SEM. Three independent experiments were performed. **p≤0.01 and ***p≤0.005 in an unpaired two-tailed Student's <i>t</i> test. (B) T cells were stained with CFSE, pre-treated with VCE-003 and stimulated with the CD3/CD28 mAbs for 6 days. Cell division was identified by flow cytometry. (C) T-cells were pre-treated with VCE-003 and stimulated with the CD3/CD28 mAbs for 72 h. The percentage of subdiploid cells (sub-G<sub>0</sub>), and cells entering the S and G<sub>2</sub>/M phases of the cell cycle are indicated. The results are representative of three independent experiments.</p>", "links"=>[], "tags"=>["immunology", "Clinical immunology", "immunomodulation", "autoimmunity", "Immune response", "neuroscience", "neurology", "Neurobiology of disease and regeneration", "vce-003", "t-cell"], "article_id"=>997089, "categories"=>["Biological Sciences"], "users"=>["Francisco J. Carrillo-Salinas", "Carmen Navarrete", "Miriam Mecha", "Ana Feliú", "Juan A. Collado", "Irene Cantarero", "María L. Bellido", "Eduardo Muñoz", "Carmen Guaza"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0094733.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_VCE_003_on_T_cell_proliferation_/997089", "title"=>"Effects of VCE-003 on T-cell proliferation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-11 03:51:25"}

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