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O gen prim&#225;rio de resolu&#231;&#227;o antig&#234;nica HLA&#8208;Cw6&#44; localizado no PSORS1 e que codifica um alelo do complexo principal de histocompatibilidade I &#40;MHCI&#41;&#44; foi significativamente associado &#224; psor&#237;ase&#46; Foram observadas altera&#231;&#245;es nos genes PSORS1 e PSORS2 no desenvolvimento da doen&#231;a&#44; afetando c&#233;lulas imunes e queratin&#243;citos&#46; Os fatores gen&#233;ticos afetam os sintomas cl&#237;nicos&#44; a idade de in&#237;cio da doen&#231;a&#44; seu tipo e gravidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Os microRNAs &#40;miRNAs&#41; s&#227;o membros da pequena fam&#237;lia de RNA&#44; cujo comprimento varia entre 19 a 25 nucleot&#237;deos&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">7</span></a> Mais de 2&#46;500 miRNAs que desempenham um papel fundamental na regula&#231;&#227;o de processos biol&#243;gicos b&#225;sicos foram identificados at&#233; o momento&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">8</span></a> Os miRNAs regulam a express&#227;o g&#234;nica durante a transcri&#231;&#227;o e podem atuar como um gene supressor de tumor e&#47;ou oncogene em doen&#231;as ou tecidos espec&#237;ficos&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">9</span></a> Estudos recentes mostraram que os miRNAs est&#227;o envolvidos na patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">10&#8211;13</span></a> Ap&#243;s o primeiro estudo que demonstrou a associa&#231;&#227;o entre miRNAs e psor&#237;ase&#44; mais de 250 miRNAs foram relatados como expressos de maneira aberrante na psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">14</span></a> V&#225;rios perfis de miRNA foram estudados em amostras de pele&#44; sangue e cabelo de pacientes com psor&#237;ase&#46; Polimorfismos gen&#233;ticos de miRNAs espec&#237;ficos &#40;como miR&#8208;146a&#41; t&#234;m sido associados &#224; patog&#234;nese da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">15&#44;16</span></a> No entanto&#44; na maioria dos estudos dispon&#237;veis&#44; as express&#245;es de miRNA foram demonstradas em les&#245;es cut&#226;neas psori&#225;sicas por meio de pain&#233;is de miRNA relativamente pequenos&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Este estudo teve como objetivo identificar e caracterizar express&#245;es de miRNA em amostras de sangue de pacientes com psor&#237;ase por meio de um grande painel de miRNA e investigar a rela&#231;&#227;o entre a express&#227;o de miRNA e a gravidade da psor&#237;ase com o &#205;ndice de &#193;rea e Gravidade da Psor&#237;ase &#40;PASI&#41; e o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Desenho do estudo</span><p id="par0020" class="elsevierStylePara elsevierViewall">Este foi um estudo de caso controle que incluiu 52 pacientes com psor&#237;ase e 54 controles saud&#225;veis recrutados nos Departamentos de Dermatologia e Gen&#233;tica M&#233;dica da Faculdade de Medicina da Universidade Mu&#287;la S&#305;tk&#305; Ko&#231;man&#46; O Comit&#234; de &#201;tica em Pesquisa Cl&#237;nica da Universidade Mu&#287;la S&#305;tk&#305; Ko&#231;man aprovou este estudo&#46; Os pacientes e controles assinaram um termo de consentimento livre e esclarecido&#46; O estudo incluiu 52 pacientes com psor&#237;ase vulgar e 54 volunt&#225;rios de mesma idade e sexo&#44; que foram admitidos no ambulat&#243;rio de dermatologia e atenderam aos crit&#233;rios de inclus&#227;o&#47;exclus&#227;o&#46; Foram inclu&#237;dos os pacientes com idade &#62; 18 anos que concordaram em participar do estudo&#46; Os seguintes crit&#233;rios de exclus&#227;o foram adotados&#58; idade &#60; 18 anos&#44; pacientes com psor&#237;ase que n&#227;o em placas &#40;psor&#237;ase pustulosa e psor&#237;ase eritrod&#233;rmica&#44; entre outras&#41;&#44; pacientes com doen&#231;as sist&#234;micas &#40;como doen&#231;a coronariana&#44; insufici&#234;ncia hep&#225;tica&#44; insufici&#234;ncia renal e neoplasia maligna&#41; e pacientes gr&#225;vidas ou lactantes&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">O hist&#243;rico m&#233;dico dos pacientes &#40;idade&#44; dura&#231;&#227;o da doen&#231;a&#44; presen&#231;a de artrite psori&#225;sica e comprometimento ungueal e tratamentos atuais&#41; foi registrado no prontu&#225;rio dos pacientes&#46; A gravidade da doen&#231;a foi calculada com o escore PASI&#46; Al&#233;m disso&#44; foram registrados o escore do DLQI dos pacientes&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Dois a tr&#234;s mL de sangue dos pacientes foram coletados em tubos de EDTA e enviados ao Laborat&#243;rio de Gen&#233;tica M&#233;dica&#46; Os RNAs dos pacientes foram armazenados a &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; a feitura do estudo&#46; Usando o <span class="elsevierStyleItalic">miRNeasy Mini Kit</span> &#40;QIAGEN Sample &#38; Assay Technologies Hilden&#44; Alemanha&#41;&#44; o miRNA foi isolado de acordo com o protocolo recomendado pelo fabricante&#46; O <span class="elsevierStyleItalic">kit miScript II RT</span> &#40;Qiagen&#41; foi usado para converter os RNAs obtidos em um DNA computacional &#40;cDNA&#41;&#46; Os n&#237;veis de express&#227;o do miRNA foram determinados pelo dispositivo <span class="elsevierStyleItalic">Biomark Real&#8208;Time PCR</span> &#40;Fluidigm&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Quarenta e dois primers de miRNA que podem estar relacionados &#224; psor&#237;ase &#40;hsa&#8208;miR&#8208;155&#8208;5p&#44; hsa&#8208;miR&#8208;31&#8208;5p&#44; hsa&#8208;miR&#8208;99a&#8208;5p&#44; hsa&#8208;miR&#8208;128&#8208;3p&#44; hsa&#8208;miR&#8208;146a&#8208;5p&#44; hsa&#8208;miR&#8208;210&#8208;3p&#44; hsa&#8208;miR&#8208;369&#8208;3p&#44; hsa&#8208;miR&#8208;378a&#8208;3p&#44; hsa&#8208;let&#8208;7i&#8208;5p&#44; hsa&#8208;miR&#8208;193b&#8208;3p&#44; hsa&#8208;miR&#8208;498&#44; hsa&#8208;miR&#8208;551a&#44; hsa&#8208;miR&#8208;1266&#8208;5p&#44; hsa&#8208;let&#8208;7d&#8208;5p&#44; hsa&#8208;miR&#8208;205&#8208;5p&#44; hsa&#8208;let&#8208;7c&#8208;3p&#44; hsa&#8208;let&#8208;7c&#8208;5p&#44; hsa&#8208;miR&#8208;30b&#8208;3p&#44; hsa&#8208;miR&#8208;130a&#8208;5p&#44; hsa&#8208;miR&#8208;515&#8208;3p&#44; hsa&#8208;miR&#8208;21&#8208;5p&#44; hsa&#8208;miR&#8208;125b&#8208;5p&#44; hsa&#8208;miR&#8208;142&#8208;3p&#44; hsa&#8208;miR&#8208;424&#8208;5p&#44; hsa&#8208;miR&#8208;223&#8208;3p&#44; hsa&#8208;miR&#8208;425&#8208;3p&#44; hsa&#8208;miR&#8208;26a&#8208;5p&#44; hsa&#8208;miR&#8208;26b&#8208;5p&#44; hsa&#8208;miR&#8208;106b&#8208;5p&#44; hsa&#8208;miR&#8208;126&#8208;5p&#44; hsa&#8208;miR&#8208;181a&#8208;5p&#44; hsa&#8208;miR&#8208;221&#8208;3p&#44; hsa&#8208;miR&#8208;222&#8208;3p&#44; hsa&#8208;miR&#8208;22&#8208;3p&#44; hsa&#8208;miR&#8208;24&#8208;3p&#44; hsa&#8208;miR&#8208;17&#8208;3p&#44; hsa&#8208;miR&#8208;17&#8208;5p&#44; hsa&#8208;miR&#8208;30b&#8208;5p&#44; and hsa&#8208;miR&#8208;130a&#8208;3p&#44; hsa&#8208;miR&#8208;30e&#8208;5p&#44; hsa&#8208;miR&#8208;16&#8208;5p&#44; and hsa&#8208;miR&#8208;30a&#8208;5p&#41; foram analisados&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">10&#8211;13</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">No grupo de pacientes&#44; foi avaliada a rela&#231;&#227;o entre express&#227;o de miRNA e escore do PASI&#44; escore do DLQI e comprometimento ungueal&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">An&#225;lise de dados</span><p id="par0050" class="elsevierStylePara elsevierViewall">A an&#225;lise estat&#237;stica do estudo foi feita com o SPSS&#174; for Windows&#44; v&#46; 15&#46;0&#46; Os resultados foram apresentados como m&#233;dia &#177; desvio&#8208;padr&#227;o&#46; A an&#225;lise foi feita no site <a href="http://www.qiagen.com/us/shop/genes-and-pathways/data-analysis-center-overview-page/">http&#58;&#47;&#47;www&#46;qiagen&#46;com&#47;us&#47;shop&#47;genes&#8208;and&#8208;pathways&#47;data&#8208;analysis&#8208;center&#8208;overview&#8208;page&#47;</a>&#46; Os resultados da RT&#8208;PCR &#40;valores de Ct&#41; foram calculados pelo m&#233;todo 2&#8208;&#916;&#916;CT&#46; Ap&#243;s o c&#225;lculo desses valores&#44; o teste <span class="elsevierStyleItalic">t</span> de Student foi empregado para fazer compara&#231;&#245;es entre os grupos &#40;c&#225;lculo dos valores&#8208;p&#41;&#59; valores&#8208;p &#60; 0&#44;05 foram considerados estatisticamente significativos&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Resultados</span><p id="par0055" class="elsevierStylePara elsevierViewall">O estudo incluiu 52 pacientes com psor&#237;ase &#40;32 mulheres&#44; 20 homens&#59; faixa et&#225;ria&#58; 18 a 68 anos&#41; e 54 controles &#40;33 mulheres&#44; 21 homens&#59; faixa et&#225;ria&#58; 18 a 69 anos&#41;&#46; A idade m&#233;dia foi de 46&#44;3 &#177; 17&#44;7 anos e 43&#44;5 &#177; 16&#44;5 anos nos grupos pacientes e controles&#44; respectivamente &#40;p &#62; 0&#44;05&#41;&#46; Enquanto 7&#44;6&#37; dos pacientes foram submetidos a tratamentos sist&#234;micos &#40;3&#44;8&#37;&#44; ciclosporina&#59; 3&#44;8&#37;&#44; acitretina&#41;&#44; 92&#44;4&#37; receberam apenas tratamentos t&#243;picos&#46; No grupo de pacientes&#44; 13&#44;4&#37; apresentaram comprometimento ungueal e 8&#44;2&#37; apresentaram artrite psori&#225;sica&#46; O escore m&#233;dio do PASI foi de 7&#44;90 &#177; 8&#44;83 e o escore m&#233;dio do DLQI foi de 8&#44;13 &#177; 5&#44;50 no grupo de pacientes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">As <a class="elsevierStyleCrossRefs" href="#tbl0010">tabelas 2 e 3</a> apresentam express&#245;es de miRNA reguladas dez para mais e para menos&#44; respectivamente&#44; nos grupos de pacientes e de controles&#46; Observou&#8208;se uma regula&#231;&#227;o para mais significativa na express&#227;o de hsa&#8208;miR&#8208;155&#8208;5p&#44; hsa&#8208;miR&#8208;369&#8208;3p&#44; hsa&#8208;miR&#8208;193b&#8208;3p&#44; hsa&#8208;miR&#8208;498&#44; hsa&#8208;miR&#8208;1266&#8208;5p&#44; hsa&#8208;let&#8208;7d&#8208;5p&#44; hsa&#8208;miR&#8208;205&#8208;5p&#44; hsa&#8208;let&#8208;7c&#8208;5p&#44; hsa&#8208;miR&#8208;30b&#8208;3p e hsa&#8208;miR&#8208;515&#8208;3p no grupo de pacientes em compara&#231;&#227;o com o grupo de controles &#40;p&#160;&#60;&#160;0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Verificou&#8208;se uma regula&#231;&#227;o para menos significativa na express&#227;o de hsa&#8208;miR&#8208;21&#8208;5p&#44; hsa&#8208;miR&#8208;142&#8208;3p&#44; hsa&#8208;miR&#8208;424&#8208;5p&#44; hsa&#8208;miR&#8208;223&#8208;3p&#44; hsa&#8208;miR&#8208;26a&#8208;5p&#44; hsa&#8208;miR&#8208;106b&#8208;5p&#44; hsa&#8208;miR&#8208;126&#8208;5p&#44; hsa&#8208;miR&#8208;181a&#8208;5p&#44; hsa&#8208;miR&#8208;222&#8208;3p&#44; hsa&#8208;miR&#8208;22&#8208;3p&#44; hsa&#8208;miR&#8208;24&#8208;3p&#44; hsa&#8208;miR&#8208;17&#8208;3p&#44; hsa&#8208;miR&#8208;30b&#8208;5p&#44; hsa&#8208;miR&#8208;130a&#8208;3p&#44; hsa&#8208;miR&#8208;30e&#8208;5p e hsa&#8208;miR&#8208;16&#8208;5p no grupo de pacientes em compara&#231;&#227;o com o grupo de controles &#40;p&#160;&#60;&#160;0&#44;05&#59; <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; As Tabelas 2 e 3 tamb&#233;m apresentam as <span class="elsevierStyleItalic">fold changes</span> no grupo de pacientes em compara&#231;&#227;o com o grupo controle&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">No grupo de pacientes&#44; n&#227;o foi observada rela&#231;&#227;o significativa entre as express&#245;es de miRNA e o escore PASI&#44; o escore DLQI e o comprometimento ungueal&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discuss&#227;o</span><p id="par0075" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a inflamat&#243;ria cr&#244;nica da pele em cuja patog&#234;nese est&#227;o envolvidos queratin&#243;citos epid&#233;rmicos&#44; c&#233;lulas imunes e mediadores inflamat&#243;rios&#46; Nos &#250;ltimos anos&#44; demonstrou&#8208;se que os miRNAs regulam a diferencia&#231;&#227;o&#44; a prolifera&#231;&#227;o e a resposta de citocinas dos queratin&#243;citos&#44; a sobreviv&#234;ncia e a ativa&#231;&#227;o das c&#233;lulas T&#44; bem como a associa&#231;&#227;o entre imun&#243;citos e queratin&#243;citos&#46; Embora diferentes perfis de express&#227;o de miRNAs tenham sido relatados em pacientes com psor&#237;ase&#44; os miRNAs n&#227;o foram identificados como um biomarcador para diagn&#243;stico&#44; atividade e gravidade da doen&#231;a na pr&#225;tica cl&#237;nica&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">17</span></a> Embora a maioria dos pacientes inclu&#237;dos no presente estudo apresentasse doen&#231;a mais leve&#44; foi observada regula&#231;&#227;o regula&#231;&#227;o para cima e para baixo na express&#227;o de miRNA em amostras de soro de pacientes com psor&#237;ase&#59; os presentes achados s&#227;o compat&#237;veis com os dados da literatura existente em amostras de soro e pele de pacientes com psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">18&#8211;20</span></a> No entanto&#44; no presente estudo&#44; essas express&#245;es de miRNA n&#227;o estavam significativamente associadas ao escore PASI&#44; DLQI e comprometimento ungueal&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Foi demonstrado que muitos miRNAs que envolvem miR&#8208;203 e miR&#8208;125b desempenham pap&#233;is&#8208;chave na resposta inflamat&#243;ria&#44; disfun&#231;&#227;o imunol&#243;gica e doen&#231;as hiperproliferativas&#44; inclusive psor&#237;ase&#46; Sugere&#8208;se que os miRNAs detectados em amostras de sangue podem ser biomarcadores no diagn&#243;stico&#44; progn&#243;stico e resposta ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">21</span></a> No presente estudo&#44; embora o miR&#8208;146a e o miR125b tenham sido regulados para cima e para baixo nos pacientes com psor&#237;ase&#44; respectivamente&#44; a associa&#231;&#227;o n&#227;o foi estatisticamente significativa&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A express&#227;o de diversos miRNAs foi relacionada &#224; atividade ou gravidade da psor&#237;ase em v&#225;rios estudos&#46; No estudo de Hou RX et al&#46;&#44; verificou&#8208;se maior express&#227;o do miR&#8208;155&#8208;5p nas c&#233;lulas&#8208;tronco mesenquimais d&#233;rmicas de pacientes com psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">18</span></a> Guo et al&#46; observaram que a express&#227;o do miR&#8208;369&#8208;3p estava aumentada no soro e na pele dos pacientes com psor&#237;ase e associada &#224; atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">19</span></a> Em outro estudo&#44; a express&#227;o de miR&#8208;1266&#8208;5p foi relatada como aumentada no soro de pacientes com psor&#237;ase e associada &#224; atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">20</span></a> De forma semelhante&#44; no presente estudo as express&#245;es de miR&#8208;155&#8208;5p&#44; miR&#8208;369&#8208;3p e miR&#8208;1266&#8208;5p estavam significativamente aumentadas em pacientes com psor&#237;ase quando comparadas aos controles&#46; No entanto&#44; nenhuma associa&#231;&#227;o estatisticamente significativa foi observada entre miRNAs e gravidade da doen&#231;a&#46; Esse resultado pode ser devido ao fato de a maioria dos pacientes apresentar psor&#237;ase leve ou moderada&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">O efeito de diversos tratamentos sist&#234;micos nas express&#245;es de miRNA e o papel dos miRNAs na patog&#234;nese da doen&#231;a foram investigados&#46; Raaby et al<span class="elsevierStyleItalic">&#46;</span> n&#227;o detectaram altera&#231;&#245;es na express&#227;o do miRNA quatro dias ap&#243;s o tratamento com adalimumabe&#44; sugeriram que o perfil de express&#227;o de citocinas n&#227;o &#233; facilitado por altera&#231;&#245;es precoces na express&#227;o do miRNA&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">22</span></a> Em contraste com o presente estudo&#44; os n&#237;veis de miR&#8208;142&#8208;3p estavam aumentados em pacientes com psor&#237;ase e diminu&#237;ram com o tratamento com etanercepte no estudo de Pivarcsi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">23</span></a> Ich&#305;hara et al<span class="elsevierStyleItalic">&#46;</span> encontraram uma express&#227;o diminu&#237;da de miR&#8208;424 nos tecidos de pacientes com psor&#237;ase e observaram que a diminui&#231;&#227;o da express&#227;o de miR&#8208;424 associada a n&#237;veis aumentados de MEK1 e ciclina E1 pode induzir a prolifera&#231;&#227;o de queratin&#243;citos na epiderme&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">24</span></a> Da mesma maneira&#44; no presente estudo&#44; a express&#227;o do miR&#8208;424 estava regulada para baixo em pacientes com psor&#237;ase quando comparada aos controles&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Estudos sobre miRNAs e outras doen&#231;as cr&#244;nicas tamb&#233;m podem ser &#250;teis para entender a patog&#234;nese e o efeito dos tratamentos sist&#234;micos na psor&#237;ase&#46; Em um estudo feito em pacientes com artrite reumatoide&#44; Xiang et al<span class="elsevierStyleItalic">&#46;</span> observaram que a express&#227;o aumentada de miR&#8208;498 suprimia a diferencia&#231;&#227;o de c&#233;lulas Th17&#44; ao focar em STAT3&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">25</span></a> Em outro estudo de Wang et al&#46;&#44; foi demonstrado que miR&#8208;223 causava doen&#231;a inflamat&#243;ria intestinal pela via IL23&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">26</span></a> Sabe&#8208;se que a via IL23&#47;17 desempenha um papel fundamental na patog&#234;nese da psor&#237;ase&#59; tratamentos contra essa via&#44; como o anti&#8208;IL17 &#40;secuquinumabe&#41;&#44; s&#227;o eficazes no tratamento da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">27&#44;28</span></a> Consequentemente&#44; a superexpress&#227;o do miR&#8208;498 pode ser eficaz no tratamento da psor&#237;ase pela via IL17&#46; Embora os autores n&#227;o tenham investigado as express&#245;es de miRNA antes e ap&#243;s os tratamentos&#44; observou&#8208;se uma express&#227;o significativamente aumentada de miR&#8208;498 em pacientes com psor&#237;ase&#46; Em outro estudo&#44; An et al<span class="elsevierStyleItalic">&#46;</span> demonstraram que a suprarregula&#231;&#227;o do miR&#8208;205 inibe o desenvolvimento de queloide&#44; suprime a produ&#231;&#227;o do fator de crescimento do endot&#233;lio vascular &#40;VEGF&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">29</span></a> Chamorro&#8208;Jorganes et al&#46; relataram que o VEGF estimula as c&#233;lulas endoteliais para a angiog&#234;nese por indu&#231;&#227;o do miR&#8208;17&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">30</span></a> Como &#233; sabido que o VEGF est&#225; envolvido na patog&#234;nese da psor&#237;ase&#44; esses relatos respaldam a hip&#243;tese de que a express&#227;o de miR&#8208;205 e miR&#8208;17 pode afetar o desenvolvimento da psor&#237;ase via VEGF&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">31</span></a> No presente estudo&#44; enquanto a express&#227;o de miR&#8208;205&#8208;5p estava significativamente regulada para cima&#44; a express&#227;o de mir&#8208;17&#8208;3p estava significativamente regulada para baixo em pacientes com psor&#237;ase quando comparada aos controles&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">V&#225;rios tipos de miRNA est&#227;o envolvidos na patog&#234;nese de diversos tipos de psor&#237;ase&#46; Enquanto a via IL23&#47;Th17 &#233; respons&#225;vel pelo desenvolvimento da psor&#237;ase vulgar&#44; IL&#8208;1&#44; IL&#8208;36 e IL&#8208;6 s&#227;o citocinas envolvidas no desenvolvimento da psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a> Chyi&#8208;Ying et al<span class="elsevierStyleItalic">&#46;</span> relataram que o miR&#8208;26 reduz a IL&#8208;6&#44; que &#233; ativada pelo TNF&#8208;&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">33</span></a> MiR&#8208;26 pode estar envolvido no desenvolvimento de psor&#237;ase mediada por IL&#8208;6&#46; Os medicamentos que suprimem a libera&#231;&#227;o de IL&#8208;6&#44; como o tocilizumabe&#44; s&#227;o usados no tratamento da artrite reumatoide e da artrite reumatoide juvenil e est&#227;o entre as poss&#237;veis op&#231;&#245;es de tratamento futuro da psor&#237;ase pustulosa&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">32</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">O transdutor de sinal e ativa&#231;&#227;o da transcri&#231;&#227;o &#40;STAT3&#41; foi apontado recentemente como um ator&#8208;chave na patog&#234;nese da psor&#237;ase e de condi&#231;&#245;es inflamat&#243;rias similares &#224; psor&#237;ase&#46; Relata&#8208;se que a hiperatividade do STAT3 &#233; uma mediadora da sinaliza&#231;&#227;o da maioria das citocinas&#44; inclusive a interleucina IL&#8208;23&#47;IL&#8208;17&#44; e &#233; observada em quase todos os tipos de c&#233;lulas envolvidas no surgimento da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">34</span></a> Maimaiti et al<span class="elsevierStyleItalic">&#46;</span> apontaram que o miR&#8208;106b modula a angiog&#234;nese em c&#233;lulas endoteliais e afeta a express&#227;o de STAT3&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">35</span></a> Em outro estudo&#44; foi demonstrado que o STAT3 inibe a express&#227;o de miR&#8208;22 em pacientes com linfoma cut&#226;neo de c&#233;lulas T&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">36</span></a> Assim&#44; o miR&#8208;22 pode ser inibido pela patog&#234;nese mediada por STAT3 na psor&#237;ase&#46; No presente estudo&#44; as express&#245;es de miR&#8208;106b&#8208;5p e miR&#8208;22 foram significativamente reguladas para cima e para baixo nos pacientes com psor&#237;ase&#44; respectivamente&#44; respaldando esses achados&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">O presente estudo tem algumas limita&#231;&#245;es&#58; apenas pacientes com psor&#237;ase leve a moderada foram inclu&#237;dos e a maioria estava em tratamento t&#243;pico&#59; portanto&#44; n&#227;o foi poss&#237;vel avaliar as altera&#231;&#245;es na express&#227;o de miRNA antes e ap&#243;s tratamentos sist&#234;micos&#46; Al&#233;m disso&#44; os pacientes atuais apresentavam psor&#237;ase do tipo placa e&#44; portanto&#44; a express&#227;o de miRNA n&#227;o foi avaliada em outros tipos de psor&#237;ase&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclus&#227;o</span><p id="par0115" class="elsevierStylePara elsevierViewall">O presente estudo incluiu pacientes com psor&#237;ase leve a moderada e avaliou miRNAs de amostras de sangue em vez de les&#245;es cut&#226;neas&#59; um determinado conjunto de miRNAs estava regulado para mais ou para menos nos pacientes com psor&#237;ase&#44; um achado compat&#237;vel com a literatura existente&#46; Portanto&#44; os presentes resultados confirmam mais uma vez o papel dos miRNAs na patog&#234;nese da psor&#237;ase&#46; No entanto&#44; n&#227;o foi observada associa&#231;&#227;o entre a express&#227;o de miRNA e o escore PASI&#44; o escore DLQI e o comprometimento ungueal nos pacientes&#46; Estudos adicionais devem ser feitos para entender melhor se os miRNAs podem ser usados como um marcador para o progn&#243;stico da psor&#237;ase&#44; qual miRNA &#233; mais espec&#237;fico para cada tipo de psor&#237;ase e se os miRNAs podem ser usados no tratamento da psor&#237;ase no futuro&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Suporte financeiro</span><p id="par0120" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Contribui&#231;&#227;o dos autores</span><p id="par0125" class="elsevierStylePara elsevierViewall">Emine Tugba Alatas&#58; Concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Murat Kara&#58; An&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Gursoy Dogan&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Asl&#305; Ak&#305;n Belli&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflitos de interesse</span><p id="par0145" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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            0 => "Biomarcadores farmacol&#243;gicos"
            1 => "MicroRNAs"
            2 => "Psor&#237;ase"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Em estudos recentes&#44; os microRNAs &#40;miRNAs&#41; demonstraram desempenhar um papel importante na patog&#234;nese da psor&#237;ase&#46; No entanto&#44; a literatura apresenta poucos estudos que avaliem miRNAs no sangue de pacientes com psor&#237;ase&#44; inclusive um grande n&#250;mero de pain&#233;is de miRNA&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar a express&#227;o de miRNA em amostras de sangue de pacientes com psor&#237;ase&#44; bem como avaliar a associa&#231;&#227;o entre a express&#227;o de miRNA e a gravidade da psor&#237;ase&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo de caso controle em 52 pacientes com psor&#237;ase vulgar e 54 controles&#46; O hist&#243;rico m&#233;dico dos pacientes&#44; os escores do &#205;ndice de Gravidade da Psor&#237;ase por &#193;rea &#40;PASI&#41; e do &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#44; do ingl&#234;s <span class="elsevierStyleItalic">Dermatology Life Quality Index</span>&#41; foram registrados&#46; Os 42 <span class="elsevierStyleItalic">primers</span> de miRNA relacionados &#224; doen&#231;a foram avaliados por PCR em tempo real&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">No grupo de pacientes&#44; 13&#44;4&#37; apresentaram comprometimento ungueal e 8&#44;2&#37; apresentaram artrite psori&#225;sica&#46; Os escores m&#233;dios do PASI e DLQI foram 7&#44;90 &#177; 8&#44;83 e 8&#44;13 &#177; 5&#44;50&#44; respectivamente&#46; Entre os 42 primers de miRNA&#44; as express&#245;es de hsa&#8208;miR&#8208;155&#8208;5p&#44; hsa&#8208;miR&#8208;369&#8208;3p&#44; hsa&#8208;miR&#8208;193b&#8208;3p&#44; hsa&#8208;miR&#8208;498&#44; hsa&#8208;miR&#8208;1266&#8208;5p&#44; hsa&#8208;let&#8208;7d&#8208;5p&#44; hsa&#8208;miR&#8208;205&#8208;5p&#44; hsa&#8208;let&#8208;7c&#8208;5p&#44; hsa&#8208;miR&#8208;30b&#8208;3p e hsa&#8208;miR&#8208;515&#8208;3p estavam significativamente reguladas para cima&#44; enquanto as express&#245;es de hsa&#8208;miR&#8208;21&#8208;5p&#44; hsa&#8208;miR&#8208;142&#8208;3p&#44; hsa&#8208;miR&#8208;424&#8208;5p&#44; hsa&#8208;miR&#8208;223&#8208;3p&#44; hsa&#8208;miR&#8208;26a&#8208;5p&#44; hsa&#8208;miR&#8208;106b&#8208;5p&#44; hsa&#8208;miR&#8208;126&#8208;5p&#44; hsa&#8208;miR&#8208;181a&#8208;5p&#44; hsa&#8208;miR&#8208;222&#8208;3p&#44; hsa&#8208;miR&#8208;22&#8208;3p&#44; hsa&#8208;miR&#8208;24&#8208;3p&#44; hsa&#8208;miR&#8208;17&#8208;3p&#44; hsa&#8208;miR&#8208;30b&#8208;5p&#44; hsa&#8208;miR&#8208;130a&#8208;3p&#44; hsa&#8208;miR&#8208;30e&#8208;5p e hsa&#8208;miR&#8208;16&#8208;5p estavam significativamente reguladas para baixo em pacientes com psor&#237;ase em compara&#231;&#227;o ao grupo controle &#40;p &#60; 0&#44;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Uma vez que o estudo incluiu pacientes com psor&#237;ase leve a moderada&#44; que na maioria das vezes s&#243; receberam tratamentos t&#243;picos&#44; as altera&#231;&#245;es nos miRNAs antes e depois dos tratamentos sist&#234;micos n&#227;o foram avaliadas&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A detec&#231;&#227;o de regula&#231;&#227;o para cima ou para baixo na express&#227;o de 24 miRNA em pacientes com psor&#237;ase&#44; mesmo naqueles com doen&#231;a mais leve&#44; respalda ainda mais o papel dos miRNAs na patog&#234;nese da psor&#237;ase&#46; Estudos futuros devem esclarecer se os miRNAs podem ser usados como um marcador para o progn&#243;stico da psor&#237;ase ou como um agente terap&#234;utico no tratamento da psor&#237;ase&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Alatas ET&#44; Kara M&#44; Dogan G&#44; Belli AA&#46; Blood microRNA expressions in patients with mild to moderate psoriasis and the relationship between microRNAs and psoriasis activity&#46; An Bras Dermatol&#46; 2020&#59;95&#58;702&#8211;7&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Departamento de Dermatologia&#44; University of Mu&#287;la S&#305;tk&#305; Ko&#231;man&#44; Mugla&#44; Turquia&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Psor&#237;ase &#40;n &#61; 52&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controle &#40;n &#61; 54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Idade &#40;anos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#44;30 &#177; 17&#44;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#44;53 &#177; 16&#44;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sexo &#40;feminino&#47;masculino&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#47;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#47;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tratamento t&#243;pico &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tratamento sist&#234;mico &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acitretina &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ciclosporina &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Artrite psori&#225;tica &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comprometimento ungueal &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">13&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">PASI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#44;90 &#177; 8&#44;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2467468.png"
              ]
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas sociodemogr&#225;ficas e par&#226;metros bioqu&#237;micos dos grupos pacientes e controles</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#916;&#44; Delta&#59; &#708;&#44; regula&#231;&#227;o para mais &#40;vermelho&#41;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Valores de <span class="elsevierStyleItalic">fold change</span> e <span class="elsevierStyleItalic">fold regulation</span> maiores que 2 est&#227;o apresentados em vermelho&#46;</p>"
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2467469.png"
              ]
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">miRNAs com express&#227;o regulada para mais nos grupos de pacientes e de controles</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
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            "detalle" => "Tabela "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">&#916;&#44; Delta&#59; &#709;&#44; regula&#231;&#227;o para menos &#40;azul&#41;&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Valores de <span class="elsevierStyleItalic">fold change</span> menores que 0&#44;5 s&#227;o indicados em azul&#46;</p>"
          "tablatextoimagen" => array:1 [
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