Editorial comment
High-throughput technologies and bioinformatic tools to clarify the molecular mechanisms behind sepsis-induced cardiomyopathy
Tecnologias de alto rendimento e ferramentas bioinformáticas para clarificar os mecanismos moleculares por detrás da miocardiopatia induzida pela sepsis
a Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
b University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra, Portugal
c University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal
d Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
Lido
1320
Vezesque se leu este artigo
605
Total PDF
715
Total HTML
Compartilhar estatísticas
array:25 [ "pii" => "S087025512300063X" "issn" => "08702551" "doi" => "10.1016/j.repc.2023.01.014" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "2113" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2023" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2023;42:223-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S0870255123000446" "issn" => "08702551" "doi" => "10.1016/j.repc.2022.02.009" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "2094" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2023;42:225-34" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Frailty phenotype in heart failure: A condition that transcends age" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "225" "paginaFinal" => "234" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "O fenótipo de fragilidade na insuficiência cardíaca: uma condição que transcende idades" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rui Valdiviesso, Emília Moreira, Sónia Martins, Luís Filipe Azevedo, Rosário Ataíde, Lia Fernandes, José Silva-Cardoso, Nuno Borges" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Rui" "apellidos" => "Valdiviesso" ] 1 => array:2 [ "nombre" => "Emília" "apellidos" => "Moreira" ] 2 => array:2 [ "nombre" => "Sónia" "apellidos" => "Martins" ] 3 => array:2 [ "nombre" => "Luís Filipe" "apellidos" => "Azevedo" ] 4 => array:2 [ "nombre" => "Rosário" "apellidos" => "Ataíde" ] 5 => array:2 [ "nombre" => "Lia" "apellidos" => "Fernandes" ] 6 => array:2 [ "nombre" => "José" "apellidos" => "Silva-Cardoso" ] 7 => array:2 [ "nombre" => "Nuno" "apellidos" => "Borges" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255123000446?idApp=UINPBA00004E" "url" => "/08702551/0000004200000003/v1_202303051609/S0870255123000446/v1_202303051609/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0870255123000628" "issn" => "08702551" "doi" => "10.1016/j.repc.2023.01.013" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "2112" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2023;42:209-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Curcumin interferes with sepsis-induced cardiomyocyte apoptosis via TLR1 inhibition" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "209" "paginaFinal" => "221" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "A curcumina interfere com a apoptose cardiomiocitária induzida por sepsis através da inibição do gene TLR1" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 947 "Ancho" => 2925 "Tamanyo" => 193988 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Functional enrichment analysis on the up/down regulated differential expression genes and genes in weighted gene co-expression network analysis module. (A) Annotation of the entries of 601 genes in biological process (BP), molecular function, and cell composition, of which BP takes the top 15. (B) The top 15 of Kyoto Encyclopedia of Genes and Genomes enrichment analysis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Dandan Chen, Hongwu Wang, Xingjun Cai" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Dandan" "apellidos" => "Chen" ] 1 => array:2 [ "nombre" => "Hongwu" "apellidos" => "Wang" ] 2 => array:2 [ "nombre" => "Xingjun" "apellidos" => "Cai" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255123000628?idApp=UINPBA00004E" "url" => "/08702551/0000004200000003/v1_202303051609/S0870255123000628/v1_202303051609/en/main.assets" ] "asociados" => array:1 [ 0 => array:19 [ "pii" => "S0870255123000628" "issn" => "08702551" "doi" => "10.1016/j.repc.2023.01.013" "estado" => "S300" "fechaPublicacion" => "2023-03-01" "aid" => "2112" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2023;42:209-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Curcumin interferes with sepsis-induced cardiomyocyte apoptosis via TLR1 inhibition" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "209" "paginaFinal" => "221" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "A curcumina interfere com a apoptose cardiomiocitária induzida por sepsis através da inibição do gene TLR1" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 947 "Ancho" => 2925 "Tamanyo" => 193988 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Functional enrichment analysis on the up/down regulated differential expression genes and genes in weighted gene co-expression network analysis module. (A) Annotation of the entries of 601 genes in biological process (BP), molecular function, and cell composition, of which BP takes the top 15. (B) The top 15 of Kyoto Encyclopedia of Genes and Genomes enrichment analysis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Dandan Chen, Hongwu Wang, Xingjun Cai" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Dandan" "apellidos" => "Chen" ] 1 => array:2 [ "nombre" => "Hongwu" "apellidos" => "Wang" ] 2 => array:2 [ "nombre" => "Xingjun" "apellidos" => "Cai" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255123000628?idApp=UINPBA00004E" "url" => "/08702551/0000004200000003/v1_202303051609/S0870255123000628/v1_202303051609/en/main.assets" ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "High-throughput technologies and bioinformatic tools to clarify the molecular mechanisms behind sepsis-induced cardiomyopathy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "223" "paginaFinal" => "224" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Ilda Patrícia Ribeiro" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Ilda Patrícia" "apellidos" => "Ribeiro" "email" => array:1 [ 0 => "ildaribeiro.patricia@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Cytogenetics and Genomics Laboratory, Institute of Cellular and Molecular Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, Coimbra, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tecnologias de alto rendimento e ferramentas bioinformáticas para clarificar os mecanismos moleculares por detrás da miocardiopatia induzida pela sepsis" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The noteworthy progress over the last decade in molecular technologies and bioinformatic tools has led to the generation and integration of significant amounts of Big data, including DNA, RNA, protein and metabolite levels of a wide range of tissue samples and patients. These have improved our knowledge of health and disease and consequently enabled the leverage of precision medicine for several diseases.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Worldwide, sepsis is an ongoing challenge for physicians and health-care administrators due to its high incidence, mortality and its huge burden on public health resources in developed countries. It is the leading cause of intensive care unit related deaths.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Sepsis-induced cardiomyopathy (SICM) or sepsis-induced myocardial dysfunction (SIMD) is a form of transient cardiac dysfunction in sepsis patients and presents a challenging diagnosis. It is one of the major causes of death among sepsis patients.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> It is important to stress that in sepsis-induced cardiomyopathy, the myocardium is functionally and structurally injured by inflammatory cytokines and mitochondrial dysfunction. Nevertheless, knowledge of the pathophysiology of this condition remains elusive.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The analysis and integration of large volumes of data obtained using high-throughput technologies require bioinformatic and computational tools to reveal the complex biological processes and the molecular mechanisms behind diseases, increasing our understanding of the course of diseases and opening up new possibilities for drug development.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Considering this technological progress and the increasing in our knowledge of SICM, several potential therapies are under investigation in animal models of septic cardiomyopathy, such as statins, dexmedetomidine, hydrocortisone, alpha-2 blockers, yohimbine, Chinese yam, erythropoietin, vitamin c, and sulfur dioxide (see references in L’Heureux et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a>).</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the current issue of the Journal, Chen et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> conducted bioinformatic analysis on the myocardial transcription spectrum of sepsis chips from the GEO database, which revealed 601 genes significantly enriched in the following biological processes, cellular components and molecular functions: generation of ribosomal protein complexes, ribose RNA-related metabolism, myeloplast migration, phagocytic vesicles, membrane rafts, binding of Toll-like receptor and amide binding. These 601 genes are mostly involved in NF-κB signaling pathway, autophagy, mitochondrial autophagy, proteasome, RNA transport, TGF-beta signaling pathway and JAK-STAT signaling pathways.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After a detailed analysis of these results, the authors concluded that <span class="elsevierStyleItalic">TLR1</span> seems to influence the survival of cardiomyocytes by interacting with the NF-κB signaling pathway. So, the authors hypothesized that curcumin could have a therapeutic role through down regulating <span class="elsevierStyleItalic">TLR1</span> to mediate apoptosis of myocardial cells in septic myocardial injury.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Lipopolysaccharide (LPS) was used to construct a rat model of sepsis, where the results demonstrated that curcumin decreased the expression of pro-inflammatory factors TNF-α and IL-6, up-regulated the expression of anti-inflammatory factors IL-10, and down-regulated the expression levels of BNP, cTnI, CK and CK-MB.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Additionally, using a model of myocardial injury induced by LPS through <span class="elsevierStyleItalic">in vitro</span> cell experiments, the authors showed that curcumin can not only inhibit the expression levels of TLR1 mRNA and NF-κB mRNA, but also the protein expression of TLR1 and p-NF-κB was down-regulated. Curcumin seems to improve the survival rate of cells and inhibit apoptosis after LPS treatment in a dose-dependent manner.</p><p id="par0050" class="elsevierStylePara elsevierViewall">This work conducted biological function experiments after an <span class="elsevierStyleItalic">in silico</span> analysis of microarray gene expression from the Gene Expression Omnibus database to prove the effect of curcumin on LPS-induced cardiomyocytes and also explored the molecular mechanism of curcumin on <span class="elsevierStyleItalic">TLR1</span> through molecular docking experiments, which points to curcumin being a potential inhibitor of <span class="elsevierStyleItalic">TLR1</span>.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In 2022, Rattis et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> demonstrated that treatment with curcumin and nanocurcumin in a mice model promoted a cardioprotective response that could be linked to the modulation of the mTOR pathway.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Curcumin, extracted from the dried rhizomes of Curcuma longa (or turmeric), presents antioxidant, anti-apoptotic, and anti-inflammatory activities that seems to be related to its modulatory effects on AMPK, Nrf2, JAK/STAT, NF-κB, PI3k/Akt, MAPK, Notch, mTOR, PPARs, arachidonic signaling pathways and toll-like receptors, histone acetylation and deacetylation, and the renin angiotensin system.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Further studies are warranted to clarify the mechanisms of sepsis-induced myocardial injury and to validate the therapeutic potential of curcumin.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Most research on the mechanism of SICM is only based on a single omic technology.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> Therefore, considering technological progress together with the decreased costs and turnaround times a fast use of high-throughput techniques is expected and consequently an increase in the molecular omics-based data to unravel the complex biological networks underlying SICM, opening the pathway for new therapeutic target development.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of severe sepsis around the world" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.C. Angus" 1 => "C.A. Pereira" 2 => "E. Silva" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2174/187153006777442332" "Revista" => array:6 [ "tituloSerie" => "Endocr Metab Immune Disord Drug Targets" "fecha" => "2006" "volumen" => "6" "paginaInicial" => "207" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16787296" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sepsis-induced cardiomyopathy: a comprehensive review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. L’Heureux" 1 => "M. Sternberg" 2 => "L. Brath" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Curr Cardiol Rep" "fecha" => "2020" "volumen" => "22" "paginaInicial" => "35" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A review of sepsis-induced cardiomyopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Sato" 1 => "M. Nasu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40560-015-0112-5" "Revista" => array:5 [ "tituloSerie" => "J Intensive Care" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "48" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26566443" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Curcumin interferes with sepsis-induced cardiomyocite apoptosis via inhibiting TLR1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Chen" 1 => "H. Wang" 2 => "X. Cai" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2023" "volumen" => "42" "paginaInicial" => "209" "paginaFinal" => "221" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of the mTOR pathway by curcumin in the heart of septic mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B.A.C. Rattis" 1 => "H.L. Piva" 2 => "A. Duarte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/pharmaceutics14112277" "Revista" => array:5 [ "tituloSerie" => "Pharmaceutics" "fecha" => "2022" "volumen" => "14" "paginaInicial" => "2277" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36365096" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Curcumin and cardiovascular diseases: focus on cellular targets and cascades" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.M. Pourbagher-Shahri" 1 => "T. Farkhondeh" 2 => "M. Ashrafizadeh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.biopha.2020.111214" "Revista" => array:5 [ "tituloSerie" => "Biomed Pharmacother" "fecha" => "2021" "volumen" => "136" "paginaInicial" => "111214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33450488" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Research progress on the mechanism of sepsis induced myocardial injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.F. Bi" 1 => "J. Liu" 2 => "L.S. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/JIR.S374117" "Revista" => array:6 [ "tituloSerie" => "J Inflamm Res" "fecha" => "2022" "volumen" => "15" "paginaInicial" => "4275" "paginaFinal" => "4290" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35923903" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000004200000003/v1_202303051609/S087025512300063X/v1_202303051609/en/main.assets" "Apartado" => array:4 [ "identificador" => "93359" "tipo" => "SECCION" "pt" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "pt" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000004200000003/v1_202303051609/S087025512300063X/v1_202303051609/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S087025512300063X?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 7 | 5 | 12 |
| 2024 Outubro | 37 | 36 | 73 |
| 2024 Setembro | 49 | 27 | 76 |
| 2024 Agosto | 35 | 29 | 64 |
| 2024 Julho | 37 | 30 | 67 |
| 2024 Junho | 31 | 55 | 86 |
| 2024 Maio | 26 | 16 | 42 |
| 2024 Abril | 35 | 75 | 110 |
| 2024 Maro | 29 | 25 | 54 |
| 2024 Fevereiro | 30 | 17 | 47 |
| 2024 Janeiro | 25 | 19 | 44 |
| 2023 Dezembro | 35 | 27 | 62 |
| 2023 Novembro | 47 | 31 | 78 |
| 2023 Outubro | 19 | 19 | 38 |
| 2023 Setembro | 27 | 24 | 51 |
| 2023 Agosto | 23 | 8 | 31 |
| 2023 Julho | 35 | 5 | 40 |
| 2023 Junho | 25 | 13 | 38 |
| 2023 Maio | 30 | 29 | 59 |
| 2023 Abril | 21 | 12 | 33 |
| 2023 Maro | 80 | 72 | 152 |
| 2023 Fevereiro | 32 | 31 | 63 |
Mostrar tudo
