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sua digest&#227;o enzim&#225;tica e espectrometria de massa&#46; O projeto foi aprovado pelo Comit&#234; de &#201;tica institucional &#40;n&#176;&#160;1&#46;411&#46;931&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">As amostras foram analisadas em duplicata no sistema nanoACQUITY&#8208;UPLC acoplado a espectr&#244;metro de massa Xevo&#8208;Q&#8208;TOF&#8208;G2&#44; cujos resultados foram processados no <span class="elsevierStyleItalic">software</span> ProteinLynx GlobalServer 3&#46;03<span class="elsevierStyleHsp" style=""></span>v&#46; As prote&#237;nas foram indentificadas por meio do algoritmo de contagem de &#237;ons&#44; cujos padr&#245;es espectrais foram pesquisados no banco <span class="elsevierStyleItalic">Homo sapiens</span>&#44; no cat&#225;logo UniProt &#40;<a href="https://www.uniprot.org/">https&#58;&#47;&#47;www&#46;uniprot&#46;org&#47;</a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Todas as prote&#237;nas identificadas com&#160;&#62; 95&#37;&#160;de similaridade foram inclu&#237;das na an&#225;lise&#46; As intensidades dos picos de &#237;ons foram normalizadas&#44; escalonadas e comparadas entre as topografias por um algoritmo bayesiano &#40;m&#233;todo Monte Carlo&#41;&#44; que retorna um valor p &#8804; 0&#44;05 para prote&#237;nas sub&#8208;reguladas e&#160;&#8805; 0&#44;95&#160;para as super&#8208;reguladas&#44; corrigido pelo procedimento de Benjamini&#8208;Hochberg&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">O principal desfecho do estudo foi a diferen&#231;a entre as intensidades dos picos i&#244;nicos das prote&#237;nas &#40;melasma&#58;&#160;M&#59; perilesional&#58;&#160;P&#41;&#46; O tamanho do efeito foi estimado pela raz&#227;o dessas quantidades entre as topografias &#40;M&#47;P&#41;&#46; Prote&#237;nas com raz&#227;o M&#47;P&#160;&#8804; 0&#44;5 ou&#160;&#8805; 2&#44;0 foram consideradas neste estudo&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As prote&#237;nas identificadas e suas fun&#231;&#245;es biol&#243;gicas foram diagramadas em mapa t&#233;rmico e agrupadas por meio de procedimento de cluster &#40;m&#233;todo Ward&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A idade m&#233;dia &#40;desvio&#8208;padr&#227;o&#41; das pacientes foi de&#160;42&#44;8&#160;&#40;8&#44;9&#41;&#160;anos&#59; 70&#37;&#160;eram dos fototipos&#160;III&#8208;IV e 25&#37;&#160;exerciam profiss&#245;es expostas ao sol&#46; A idade de in&#237;cio do melasma foi&#160;de 29&#44;3&#160;&#40;7&#44;5&#41;&#160;anos&#59; 55&#37;&#160;das mulheres referiam hist&#243;rico familiar e 30&#37;&#160;usavam anticoncepcional&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Validaram&#8208;se&#160;256&#160;prote&#237;nas nas amostras de pele&#44; e as&#160;29&#160;prote&#237;nas diferencialmente quantificadas entre as topografias est&#227;o expostas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; As maiores discrep&#226;ncias ocorreram para as prote&#237;nas HBD&#44; EXPH5&#44; KRT1&#44; KRT9&#44; REV3L &#40;M&#47;S&#160;&#62; 4&#44;00&#41;&#59; e ACAP9&#44; ADGB&#44; CA1 &#40;M&#47;S&#160;&#60; 0&#44;33&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As principais fun&#231;&#245;es biol&#243;gicas dessas prote&#237;nas est&#227;o dispostas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; A <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a> representa a intera&#231;&#227;o entre as&#160;29&#160;prote&#237;nas e suas fun&#231;&#245;es biol&#243;gicas&#46; As prote&#237;nas ACTG1&#44; ALB&#44; SERPINA1&#44; HBD&#44; ALDOA e FGG mostraram&#8208;se coparticipantes em diferentes processos biol&#243;gicos&#44; como consumo de oxig&#234;nio&#44; glic&#243;lise&#44; gliconeog&#234;nese e transporte celular&#44; sugerindo aumento da atividade metab&#243;lica da pele com melasma&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Exofilina&#8208;5 &#40;EXPH5&#41; &#233; ligada ao transporte de ves&#237;culas intracelulares&#46; Foi super&#8208;regulada &#40;M&#47;S &#61; 8&#44;94&#41; no melasma&#44; o que pode decorrer da intensa transfer&#234;ncia epid&#233;rmica de melanossomas&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Treze das prote&#237;nas diferencialmente identificadas no melasma foram ligadas a fen&#244;menos de transporte intracelular&#44; que compreendem uma s&#233;rie de processos que v&#227;o da endocitose &#224; autofagia e diversas formas de exocitose&#46; Como autofagia e senesc&#234;ncia s&#227;o fen&#244;menos relacionados &#224; melanog&#234;nese&#44; a caracteriza&#231;&#227;o das ves&#237;culas de transporte no epit&#233;lio com melasma pode se revelar importante na fisiopatologia do melasma&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Citoqueratinas &#40;como KRT1&#41; s&#227;o constituintes estruturais dos queratin&#243;citos induzidas em resposta ao estresse oxidativo&#46; Foram identificadas em maior raz&#227;o no melasma &#40;M&#47;S&#160;&#62; 4&#44;10&#41;&#46; A hemoglobina&#8208;&#948; &#40;mas n&#227;o as demais subunidades&#41; apresentou elevada raz&#227;o &#40;M&#47;S &#61; 33&#44;12&#41; no melasma&#44; e&#44; al&#233;m do transporte de oxig&#234;nio&#44; sua express&#227;o n&#227;o eritroc&#237;tica ocorre em situa&#231;&#245;es de estresse celular&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Da mesma maneira&#44; o aumento da regula&#231;&#227;o de alfa&#160;1 antitripsina &#40;SERPINA1&#41; e actina gama&#8208;1 &#40;ACTG1&#41; tamb&#233;m &#233; verificado em condi&#231;&#245;es de estresse tecidual&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> As maiores express&#245;es de HBD&#44; ACTG1&#44; SERPINA1 e KRT1 no melasma podem decorrer do estresse oxidativo sustentado pela atividade das triptases mastocit&#225;rias e do fen&#243;tipo secret&#243;rio de fibroblastos da derme superior&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Anidrase carb&#244;nica &#40;CA1&#41; acidifica o meio extracelular da derme&#44; favorecendo o processo de reparo&#44; sendo sub&#8208;regulada &#40;M&#47;S&#160;&#60; 0&#44;33&#41; no melasma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Senesc&#234;ncia dos fibroblastos d&#233;rmicos&#44; associada &#224; atividade de MMP1 e MMP9&#44; promovem um microambiente proinflamat&#243;rio com degrada&#231;&#227;o da matriz extracelular e da zona de membrana basal&#44; cujo d&#233;ficit de reparo pode ser fator de manuten&#231;&#227;o da melanog&#234;nese&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Androglobina &#40;ADGB&#41; tem fun&#231;&#227;o regulat&#243;ria da ciste&#237;na&#8208;endopeptidase&#44; e &#233; identificada em raz&#227;o menor &#40;M&#47;S&#160;&#60; 0&#44;33&#41; no melasma&#46; As endopeptidases participam da degrada&#231;&#227;o dos melanossomas na epiderme&#44; notavelmente reduzidas no melasma&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">As prote&#237;nas de ancoragem alfa&#8208;quinase &#40;ANCHOR9&#44; ANCHOR13&#41; e a subunidade <span class="elsevierStyleItalic">z</span>&#8208;catal&#237;tica da DNA polimerase &#40;REV3L&#41; apresentaram um desbalan&#231;o na pele com melasma&#46; Elas s&#227;o importantes na regula&#231;&#227;o da prote&#237;na quinase&#8208;A e na via p38&#8208;MAP&#8208;quinase&#44; envolvidas na ativa&#231;&#227;o da prote&#237;na CREB&#44; que levam &#224; express&#227;o de MTIF&#44; promotora da melanog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Aldolase&#8208;A &#40;ALDOA&#41; tem fun&#231;&#227;o glicol&#237;tica e est&#225; associada &#224; atividade dos mast&#243;citos&#44; que&#44; na derme superficial promovem altera&#231;&#245;es na membrana basal&#44; elastose solar e dilata&#231;&#227;o endotelial&#44; refor&#231;ando a ideia de que est&#237;mulos origin&#225;rios na derme desempenhem um papel central na melanog&#234;nese do melasma&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">O fibrinog&#234;nio&#8208;&#947; &#40;FFG&#41; &#233; uma prote&#237;na que comp&#245;e a matriz extracelular e interage em v&#225;rias fun&#231;&#245;es biol&#243;gicas&#44; incluindo fibrin&#243;lise&#44; ativa&#231;&#227;o do fibrinog&#234;nio e ativa&#231;&#227;o da via ERK&#44; promotora da melanog&#234;nese&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">As principais limita&#231;&#245;es do estudo se referem &#224;s prote&#237;nas transmembranas&#44; s&#233;ricas e conjugadas com lip&#237;deos que n&#227;o s&#227;o identificadas pelo m&#233;todo&#46; Contudo&#44; aponta de maneira consistente uma s&#233;rie de prote&#237;nas cujo papel fisiopatol&#243;gico e potencial manipula&#231;&#227;o terap&#234;utica devem ser explorados em em ensaios espec&#237;ficos&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Concluindo&#44; identificamos&#160;29&#160;prote&#237;nas diferencialmente reguladas no melasma&#44; envolvidas com metabolismo energ&#233;tico&#44; fen&#244;menos de transporte celular&#44; regula&#231;&#227;o de vias da melanog&#234;nese&#44; hemostasia&#47;coagula&#231;&#227;o&#44; reparo&#47;cicatriza&#231;&#227;o e resposta ao estresse oxidativo&#46; Isso subsidia a pesquisa de estrat&#233;gias terap&#234;uticas voltadas &#224;s prote&#237;nas identificadas e suas fun&#231;&#245;es&#44; e evidencia que o melasma n&#227;o depende exclusivamente da hiperfun&#231;&#227;o dos melan&#243;citos&#44; mas de altera&#231;&#245;es funcionais envolvendo a unidade epidermo&#8208;mel&#226;nica&#44; zona da membrana basal e derme superior&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Suporte financeiro</span><p id="par0100" class="elsevierStylePara elsevierViewall">FUNADERSP &#40;048&#47;2016&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Contribui&#231;&#227;o dos autores</span><p id="par0105" class="elsevierStylePara elsevierViewall">Luiza Vasconcelos Schaefer&#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 intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; Revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Leticia Gomes de Pontes&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nayara Rodrigues Vieira Cavassan&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Lucilene Delazari dos Santos&#58; Revis&#227;o cr&#237;tica da literatura&#59; Revis&#227;o cr&#237;tica do manuscrito&#59; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Revis&#227;o cr&#237;tica da literatura&#59; Revis&#227;o cr&#237;tica do manuscrito&#59; An&#225;lise estat&#237;stica&#59; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; Concep&#231;&#227;o e planejamento do estudo&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflito de interesses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Departamento de Dermatologia e Radioterapia&#44; FMB&#8208;UNESP&#44; Botucatu&#44; SP&#44; Brasil e no Centro de Estudos de Venenos e Animais Pe&#231;onhentos &#40;CEVAP&#41;&#44; UNESP&#44; Botucatu&#44; SP&#44; Brasil&#46;</p>"
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          "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mapa t&#233;rmico e dendrogramas entre prote&#237;nas identificadas &#40;linhas&#41; e fun&#231;&#245;es biol&#243;gicas &#40;colunas&#41;&#46; Destaques em verde&#58; agrupamento de prote&#237;nas com padr&#227;o de ocorr&#234;ncia semelhante de acordo com as fun&#231;&#245;es que exercem&#59; e em vermelho&#58; as fun&#231;&#245;es com padr&#227;o de express&#227;o semelhante&#44; de acordo com as prote&#237;nas indicadas&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fructose&#8208;bisphosphate aldolase</span> ALDOA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Heat shock protein</span>&#160;75 kDa <span class="elsevierStyleItalic">mitochondrial</span> TRAP1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Keratin type</span>&#160;I <span class="elsevierStyleItalic">cytoskeletal</span>&#160;9 KRT9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Keratin type</span>&#160;I <span class="elsevierStyleItalic">cytoskeletal</span>&#160;9 KRT9&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">190&#44;36&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;60 &#40;0&#44;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;40 &#40;0&#44;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;06 &#40;0&#44;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#44;18&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">1&#44;00&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">P23&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"><span class="elsevierStyleItalic">Keratin type</span>&#160;II <span class="elsevierStyleItalic">cytoskeletal</span>&#160;1 KRT1&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">55&#44;74&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;62 &#40;0&#44;06&#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">0&#44;38 &#40;0&#44;06&#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">2&#44;08 &#40;0&#44;14&#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">4&#44;22&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">1&#44;00&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">P24&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">POTE <span class="elsevierStyleItalic">ankyrin domain family member</span> F POTEF&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">101&#44;00&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">1&#44;47 &#40;0&#44;07&#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">0&#44;53 &#40;0&#44;07&#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">1&#44;49 &#40;0&#44;14&#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">2&#44;80&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">1&#44;00&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">P25&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">Putative <span class="elsevierStyleItalic">beta&#8208;actin&#8208;like protein</span>&#160;3 POTEKP&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">101&#44;00&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">1&#44;47 &#40;0&#44;09&#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">0&#44;53 &#40;0&#44;09&#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">1&#44;47 &#40;0&#44;16&#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">2&#44;77&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">1&#44;00&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">P26&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">RNA&#8208;<span class="elsevierStyleItalic">binding protein</span>&#160;25 RBM25&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">29&#44;17&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">1&#44;57 &#40;0&#44;12&#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">0&#44;43 &#40;0&#44;12&#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">1&#44;86 &#40;0&#44;25&#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;63&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">1&#44;00&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">P27&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"><span class="elsevierStyleItalic">Splicing Regulatory glutamine&#47;Lysine&#8208;rich protein</span>&#160;1 SREK1&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">79&#44;89&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">1&#44;41 &#40;0&#44;26&#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">0&#44;59 &#40;0&#44;26&#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">1&#44;28 &#40;0&#44;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">2&#44;44&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;00&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">P28&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
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                  \t\t\t\t"><span class="elsevierStyleItalic">Tetratricopeptide repeat protein</span>&#160;37 TTC37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">443&#44;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;45 &#40;0&#44;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;55 &#40;0&#44;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;44 &#40;0&#44;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#44;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \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><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"><span class="elsevierStyleItalic">Tetratricopeptide repeat protein</span>&#160;37 TTC37&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">449&#44;05&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
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                  \t\t\t\t">1&#44;46 &#40;0&#44;18&#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
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                  \t\t\t\t">0&#44;54 &#40;0&#44;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;47 &#40;0&#44;36&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;77&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;00&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">P29&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"><span class="elsevierStyleItalic">Triosephosphate isomerase</span> TPI1&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">475&#44;34&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;39 &#40;0&#44;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;61 &#40;0&#44;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">&#60; 0&#44;0001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p8&#44; p15&#44; p23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">4&#46; Degranula&#231;&#227;o plaquet&#225;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p15&#44; p16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60; 0&#44;0001&nbsp;\t\t\t\t\t\t\n
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                  \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">5&#46; Regula&#231;&#227;o de flu&#237;dos corporais&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60; 0&#44;0001&nbsp;\t\t\t\t\t\t\n
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                  \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">6&#46; Transporte de oxig&#234;nio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p7&#44; p19&#44; p20&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60; 0&#44;0001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">7&#46; Transporte mediado por ves&#237;culas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">0&#44;0001&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
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                  \t\t\t\t">11&#46; Agrega&#231;&#227;o plaquet&#225;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46; Ativa&#231;&#227;o do plasminog&#234;nio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#46; Transporte de organismo &#250;nico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p7&#44; p8&#44; p10&#44; p11&#44; p12&#44; p14&#44; p15&#44; p16&#44; p19&#44; p20&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0004&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#46; Coagula&#231;&#227;o sangu&#237;nea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p15&#44; p16&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0008&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#46; S&#237;ntese de transles&#227;o propensa a erros&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0010&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#46; Cascata de ativa&#231;&#227;o de prote&#237;nas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p15&#44; p23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46; Homeostase da retina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p23&#44; p24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46; Regula&#231;&#227;o negativa de resposta a trauma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p8&#44; p10&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46; Regula&#231;&#227;o positiva da exocitose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">p14&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0016&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20&#46; Regula&#231;&#227;o da exocitose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p10&#44; p14&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0017&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21&#46; Regula&#231;&#227;o negativa do processo endotelial de apoptose celular&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0022&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46; Coagula&#231;&#227;o sangu&#237;nea&#44; forma&#231;&#227;o de co&#225;gulo de fibrina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0024&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#46; Regula&#231;&#227;o negativa da via de sinaliza&#231;&#227;o da apoptose extr&#237;nseca por meio da morte de receptores de dom&#237;nio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0024&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">24&#46; Transporte&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p4&#44; p5&#44; p6&#44; p7&#44; p10&#44; p11&#44; p12&#44; p15&#44; p16&#44; p19&#44; p20&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0029&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25&#46; Processo metab&#243;lico do &#225;cido monocarbox&#237;lico&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
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                  \t\t\t\t">p5&#44; p16&#44; p29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0030&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">26&#46; Regula&#231;&#227;o da dissemina&#231;&#227;o de c&#233;lulas dependentes da ades&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0033&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27&#46; Cicatriza&#231;&#227;o de feridas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p15&#44; p16&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;20&#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">0&#44;0035&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">28&#46; Transporte de bicarbonato&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">p11&#44; p19&#44; p20&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">3 &#40;10&#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">0&#44;0044&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
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                  \t\t\t\t">29&#46; Regula&#231;&#227;o positiva da vasoconstri&#231;&#227;o&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">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;0044&nbsp;\t\t\t\t\t\t\n
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                  \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">30&#46; Resposta ao &#237;on c&#225;lcio&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  " align="left" valign="\n
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                  \t\t\t\t">0&#44;0075&nbsp;\t\t\t\t\t\t\n
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                  \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">p8&#44; p10&#44; p14&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0083&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;0092&nbsp;\t\t\t\t\t\t\n
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                  \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">33&#46; Regula&#231;&#227;o negativa a est&#237;mulos externos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">p8&#44; p10&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3 &#40;10&#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">0&#44;0098&nbsp;\t\t\t\t\t\t\n
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                  \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">34&#46; Resposta ao estresse&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p13&#44; p16&#44; p19&#44; p20&#44; p21&#44; p23&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Principais vias funcionais envolvidas com as&#160;29&#160;prote&#237;nas identificadas como diferenciais entre melasma e pele perilesional</p>"
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                    0 => array:2 [
                      "titulo" => "Exploratory Study of Epidermis&#44; Basement Membrane Zone Upper Dermis Alterations and Wnt Pathway Activation in Melasma Compared to Adjacent and Retroauricular Skin"
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Carta ‐ Investigação
Estudo proteômico do melasma facial
Luiza Vasconcelos Schaefera,b,
Autor para correspondência
luizavasconcelos12@hotmail.com

Autor para correspondência.
, Leticia Gomes de Pontesc,d, Nayara Rodrigues Vieira Cavassanc,d, Lucilene Delazari dos Santosc,d, Hélio Amante Miote
a Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
b Departamento de Dermatologia, Universidade do Oeste Paulista, São Paulo, SP, Brasil
c Departamento de Pesquisa, Centro de Estudos de Venenos e Animais Peçonhentos, Universidade Estadual Paulista, Botucatu, SP, Brasil
d Programa de Pós‐Graduação em Doenças Tropicais, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
e Departamento de Dermatologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
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bFGF&#44; NGF&#44; HGF&#41; e mediadores inflamat&#243;rios &#40;p&#46; ex&#46;&#44; ET1&#44; IL1&#44; VEGF&#44; TGFb&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Este estudo objetivou explorar prote&#237;nas diferencialmente expostas na pele com melasma em rela&#231;&#227;o &#224; pele adjacente fotoexposta&#44; n&#227;o afetada&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Realizou&#8208;se estudo transversal envolvendo&#160;20&#160;mulheres com melasma facial&#44; sem tratamentos espec&#237;ficos por&#160;30&#160;dias&#46; Duas bi&#243;psias foram realizadas &#40;mesmo pesquisador&#41;&#44; uma no limite do melasma facial e outra na pele n&#227;o afetada&#44; a&#160;2&#160;cm de dist&#226;ncia da primeira&#44; conforme padronizado anteriormente&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;3</span></a> Realizou&#8208;se a extra&#231;&#227;o mec&#226;nica de prote&#237;nas&#44; sua digest&#227;o enzim&#225;tica e espectrometria de massa&#46; O projeto foi aprovado pelo Comit&#234; de &#201;tica institucional &#40;n&#176;&#160;1&#46;411&#46;931&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">As amostras foram analisadas em duplicata no sistema nanoACQUITY&#8208;UPLC acoplado a espectr&#244;metro de massa Xevo&#8208;Q&#8208;TOF&#8208;G2&#44; cujos resultados foram processados no <span class="elsevierStyleItalic">software</span> ProteinLynx GlobalServer 3&#46;03<span class="elsevierStyleHsp" style=""></span>v&#46; As prote&#237;nas foram indentificadas por meio do algoritmo de contagem de &#237;ons&#44; cujos padr&#245;es espectrais foram pesquisados no banco <span class="elsevierStyleItalic">Homo sapiens</span>&#44; no cat&#225;logo UniProt &#40;<a href="https://www.uniprot.org/">https&#58;&#47;&#47;www&#46;uniprot&#46;org&#47;</a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Todas as prote&#237;nas identificadas com&#160;&#62; 95&#37;&#160;de similaridade foram inclu&#237;das na an&#225;lise&#46; As intensidades dos picos de &#237;ons foram normalizadas&#44; escalonadas e comparadas entre as topografias por um algoritmo bayesiano &#40;m&#233;todo Monte Carlo&#41;&#44; que retorna um valor p &#8804; 0&#44;05 para prote&#237;nas sub&#8208;reguladas e&#160;&#8805; 0&#44;95&#160;para as super&#8208;reguladas&#44; corrigido pelo procedimento de Benjamini&#8208;Hochberg&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">O principal desfecho do estudo foi a diferen&#231;a entre as intensidades dos picos i&#244;nicos das prote&#237;nas &#40;melasma&#58;&#160;M&#59; perilesional&#58;&#160;P&#41;&#46; O tamanho do efeito foi estimado pela raz&#227;o dessas quantidades entre as topografias &#40;M&#47;P&#41;&#46; Prote&#237;nas com raz&#227;o M&#47;P&#160;&#8804; 0&#44;5 ou&#160;&#8805; 2&#44;0 foram consideradas neste estudo&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">As prote&#237;nas identificadas e suas fun&#231;&#245;es biol&#243;gicas foram diagramadas em mapa t&#233;rmico e agrupadas por meio de procedimento de cluster &#40;m&#233;todo Ward&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A idade m&#233;dia &#40;desvio&#8208;padr&#227;o&#41; das pacientes foi de&#160;42&#44;8&#160;&#40;8&#44;9&#41;&#160;anos&#59; 70&#37;&#160;eram dos fototipos&#160;III&#8208;IV e 25&#37;&#160;exerciam profiss&#245;es expostas ao sol&#46; A idade de in&#237;cio do melasma foi&#160;de 29&#44;3&#160;&#40;7&#44;5&#41;&#160;anos&#59; 55&#37;&#160;das mulheres referiam hist&#243;rico familiar e 30&#37;&#160;usavam anticoncepcional&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Validaram&#8208;se&#160;256&#160;prote&#237;nas nas amostras de pele&#44; e as&#160;29&#160;prote&#237;nas diferencialmente quantificadas entre as topografias est&#227;o expostas na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; As maiores discrep&#226;ncias ocorreram para as prote&#237;nas HBD&#44; EXPH5&#44; KRT1&#44; KRT9&#44; REV3L &#40;M&#47;S&#160;&#62; 4&#44;00&#41;&#59; e ACAP9&#44; ADGB&#44; CA1 &#40;M&#47;S&#160;&#60; 0&#44;33&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As principais fun&#231;&#245;es biol&#243;gicas dessas prote&#237;nas est&#227;o dispostas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; A <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a> representa a intera&#231;&#227;o entre as&#160;29&#160;prote&#237;nas e suas fun&#231;&#245;es biol&#243;gicas&#46; As prote&#237;nas ACTG1&#44; ALB&#44; SERPINA1&#44; HBD&#44; ALDOA e FGG mostraram&#8208;se coparticipantes em diferentes processos biol&#243;gicos&#44; como consumo de oxig&#234;nio&#44; glic&#243;lise&#44; gliconeog&#234;nese e transporte celular&#44; sugerindo aumento da atividade metab&#243;lica da pele com melasma&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Exofilina&#8208;5 &#40;EXPH5&#41; &#233; ligada ao transporte de ves&#237;culas intracelulares&#46; Foi super&#8208;regulada &#40;M&#47;S &#61; 8&#44;94&#41; no melasma&#44; o que pode decorrer da intensa transfer&#234;ncia epid&#233;rmica de melanossomas&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Treze das prote&#237;nas diferencialmente identificadas no melasma foram ligadas a fen&#244;menos de transporte intracelular&#44; que compreendem uma s&#233;rie de processos que v&#227;o da endocitose &#224; autofagia e diversas formas de exocitose&#46; Como autofagia e senesc&#234;ncia s&#227;o fen&#244;menos relacionados &#224; melanog&#234;nese&#44; a caracteriza&#231;&#227;o das ves&#237;culas de transporte no epit&#233;lio com melasma pode se revelar importante na fisiopatologia do melasma&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Citoqueratinas &#40;como KRT1&#41; s&#227;o constituintes estruturais dos queratin&#243;citos induzidas em resposta ao estresse oxidativo&#46; Foram identificadas em maior raz&#227;o no melasma &#40;M&#47;S&#160;&#62; 4&#44;10&#41;&#46; A hemoglobina&#8208;&#948; &#40;mas n&#227;o as demais subunidades&#41; apresentou elevada raz&#227;o &#40;M&#47;S &#61; 33&#44;12&#41; no melasma&#44; e&#44; al&#233;m do transporte de oxig&#234;nio&#44; sua express&#227;o n&#227;o eritroc&#237;tica ocorre em situa&#231;&#245;es de estresse celular&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Da mesma maneira&#44; o aumento da regula&#231;&#227;o de alfa&#160;1 antitripsina &#40;SERPINA1&#41; e actina gama&#8208;1 &#40;ACTG1&#41; tamb&#233;m &#233; verificado em condi&#231;&#245;es de estresse tecidual&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> As maiores express&#245;es de HBD&#44; ACTG1&#44; SERPINA1 e KRT1 no melasma podem decorrer do estresse oxidativo sustentado pela atividade das triptases mastocit&#225;rias e do fen&#243;tipo secret&#243;rio de fibroblastos da derme superior&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Anidrase carb&#244;nica &#40;CA1&#41; acidifica o meio extracelular da derme&#44; favorecendo o processo de reparo&#44; sendo sub&#8208;regulada &#40;M&#47;S&#160;&#60; 0&#44;33&#41; no melasma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Senesc&#234;ncia dos fibroblastos d&#233;rmicos&#44; associada &#224; atividade de MMP1 e MMP9&#44; promovem um microambiente proinflamat&#243;rio com degrada&#231;&#227;o da matriz extracelular e da zona de membrana basal&#44; cujo d&#233;ficit de reparo pode ser fator de manuten&#231;&#227;o da melanog&#234;nese&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Androglobina &#40;ADGB&#41; tem fun&#231;&#227;o regulat&#243;ria da ciste&#237;na&#8208;endopeptidase&#44; e &#233; identificada em raz&#227;o menor &#40;M&#47;S&#160;&#60; 0&#44;33&#41; no melasma&#46; As endopeptidases participam da degrada&#231;&#227;o dos melanossomas na epiderme&#44; notavelmente reduzidas no melasma&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">As prote&#237;nas de ancoragem alfa&#8208;quinase &#40;ANCHOR9&#44; ANCHOR13&#41; e a subunidade <span class="elsevierStyleItalic">z</span>&#8208;catal&#237;tica da DNA polimerase &#40;REV3L&#41; apresentaram um desbalan&#231;o na pele com melasma&#46; Elas s&#227;o importantes na regula&#231;&#227;o da prote&#237;na quinase&#8208;A e na via p38&#8208;MAP&#8208;quinase&#44; envolvidas na ativa&#231;&#227;o da prote&#237;na CREB&#44; que levam &#224; express&#227;o de MTIF&#44; promotora da melanog&#234;nese&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Aldolase&#8208;A &#40;ALDOA&#41; tem fun&#231;&#227;o glicol&#237;tica e est&#225; associada &#224; atividade dos mast&#243;citos&#44; que&#44; na derme superficial promovem altera&#231;&#245;es na membrana basal&#44; elastose solar e dilata&#231;&#227;o endotelial&#44; refor&#231;ando a ideia de que est&#237;mulos origin&#225;rios na derme desempenhem um papel central na melanog&#234;nese do melasma&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">O fibrinog&#234;nio&#8208;&#947; &#40;FFG&#41; &#233; uma prote&#237;na que comp&#245;e a matriz extracelular e interage em v&#225;rias fun&#231;&#245;es biol&#243;gicas&#44; incluindo fibrin&#243;lise&#44; ativa&#231;&#227;o do fibrinog&#234;nio e ativa&#231;&#227;o da via ERK&#44; promotora da melanog&#234;nese&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">As principais limita&#231;&#245;es do estudo se referem &#224;s prote&#237;nas transmembranas&#44; s&#233;ricas e conjugadas com lip&#237;deos que n&#227;o s&#227;o identificadas pelo m&#233;todo&#46; Contudo&#44; aponta de maneira consistente uma s&#233;rie de prote&#237;nas cujo papel fisiopatol&#243;gico e potencial manipula&#231;&#227;o terap&#234;utica devem ser explorados em em ensaios espec&#237;ficos&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Concluindo&#44; identificamos&#160;29&#160;prote&#237;nas diferencialmente reguladas no melasma&#44; envolvidas com metabolismo energ&#233;tico&#44; fen&#244;menos de transporte celular&#44; regula&#231;&#227;o de vias da melanog&#234;nese&#44; hemostasia&#47;coagula&#231;&#227;o&#44; reparo&#47;cicatriza&#231;&#227;o e resposta ao estresse oxidativo&#46; Isso subsidia a pesquisa de estrat&#233;gias terap&#234;uticas voltadas &#224;s prote&#237;nas identificadas e suas fun&#231;&#245;es&#44; e evidencia que o melasma n&#227;o depende exclusivamente da hiperfun&#231;&#227;o dos melan&#243;citos&#44; mas de altera&#231;&#245;es funcionais envolvendo a unidade epidermo&#8208;mel&#226;nica&#44; zona da membrana basal e derme superior&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Suporte financeiro</span><p id="par0100" class="elsevierStylePara elsevierViewall">FUNADERSP &#40;048&#47;2016&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Contribui&#231;&#227;o dos autores</span><p id="par0105" class="elsevierStylePara elsevierViewall">Luiza Vasconcelos Schaefer&#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 intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; Revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Leticia Gomes de Pontes&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nayara Rodrigues Vieira Cavassan&#58; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Lucilene Delazari dos Santos&#58; Revis&#227;o cr&#237;tica da literatura&#59; Revis&#227;o cr&#237;tica do manuscrito&#59; Obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#58; Revis&#227;o cr&#237;tica da literatura&#59; Revis&#227;o cr&#237;tica do manuscrito&#59; An&#225;lise estat&#237;stica&#59; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; Concep&#231;&#227;o e planejamento do estudo&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflito de interesses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Departamento de Dermatologia e Radioterapia&#44; FMB&#8208;UNESP&#44; Botucatu&#44; SP&#44; Brasil e no Centro de Estudos de Venenos e Animais Pe&#231;onhentos &#40;CEVAP&#41;&#44; UNESP&#44; Botucatu&#44; SP&#44; Brasil&#46;</p>"
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          "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mapa t&#233;rmico e dendrogramas entre prote&#237;nas identificadas &#40;linhas&#41; e fun&#231;&#245;es biol&#243;gicas &#40;colunas&#41;&#46; Destaques em verde&#58; agrupamento de prote&#237;nas com padr&#227;o de ocorr&#234;ncia semelhante de acordo com as fun&#231;&#245;es que exercem&#59; e em vermelho&#58; as fun&#231;&#245;es com padr&#227;o de express&#227;o semelhante&#44; de acordo com as prote&#237;nas indicadas&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Serum albumin</span> ALB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Androglobin</span> ADGB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fructose&#8208;bisphosphate Aldolase</span> A ALDOA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fructose&#8208;bisphosphate aldolase</span> ALDOA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Fructose&#8208;bisphosphate aldolase</span> ALDOA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">G <span class="elsevierStyleItalic">Patch domain&#8208;containing protein</span>&#160;1 GPATCH1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">G <span class="elsevierStyleItalic">patch domain&#8208;containing protein</span>&#160;1 GPATCH1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Heat shock protein</span>&#160;75 kDa <span class="elsevierStyleItalic">mitochondrial</span> TRAP1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Hemoglobin subunit delta</span> HBD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Keratin type</span>&#160;I <span class="elsevierStyleItalic">cytoskeletal</span>&#160;9 KRT9&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">340&#44;12&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">1&#44;61 &#40;0&#44;13&#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">0&#44;39 &#40;0&#44;13&#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">2&#44;05 &#40;0&#44;27&#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">4&#44;14&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">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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><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"><span class="elsevierStyleItalic">Keratin type</span>&#160;I <span class="elsevierStyleItalic">cytoskeletal</span>&#160;9 KRT9&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">190&#44;36&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">1&#44;60 &#40;0&#44;26&#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">0&#44;40 &#40;0&#44;26&#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">2&#44;06 &#40;0&#44;62&#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">4&#44;18&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">1&#44;00&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">P23&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"><span class="elsevierStyleItalic">Keratin type</span>&#160;II <span class="elsevierStyleItalic">cytoskeletal</span>&#160;1 KRT1&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">55&#44;74&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">1&#44;62 &#40;0&#44;06&#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">0&#44;38 &#40;0&#44;06&#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">2&#44;08 &#40;0&#44;14&#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">4&#44;22&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">1&#44;00&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">P24&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">POTE <span class="elsevierStyleItalic">ankyrin domain family member</span> F POTEF&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">101&#44;00&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">1&#44;47 &#40;0&#44;07&#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">0&#44;53 &#40;0&#44;07&#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">1&#44;49 &#40;0&#44;14&#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">2&#44;80&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">1&#44;00&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">P25&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">Putative <span class="elsevierStyleItalic">beta&#8208;actin&#8208;like protein</span>&#160;3 POTEKP&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">101&#44;00&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">1&#44;47 &#40;0&#44;09&#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">0&#44;53 &#40;0&#44;09&#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">1&#44;47 &#40;0&#44;16&#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">2&#44;77&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">1&#44;00&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">P26&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">RNA&#8208;<span class="elsevierStyleItalic">binding protein</span>&#160;25 RBM25&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">29&#44;17&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">1&#44;57 &#40;0&#44;12&#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">0&#44;43 &#40;0&#44;12&#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">1&#44;86 &#40;0&#44;25&#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;63&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">1&#44;00&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">P27&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"><span class="elsevierStyleItalic">Splicing Regulatory glutamine&#47;Lysine&#8208;rich protein</span>&#160;1 SREK1&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">79&#44;89&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">1&#44;41 &#40;0&#44;26&#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">0&#44;59 &#40;0&#44;26&#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">1&#44;28 &#40;0&#44;48&#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
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                  \t\t\t\t">2&#44;44&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">1&#44;00&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">P28&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"><span class="elsevierStyleItalic">Tetratricopeptide repeat protein</span>&#160;37 TTC37&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">443&#44;53&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">1&#44;45 &#40;0&#44;21&#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">0&#44;55 &#40;0&#44;21&#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">1&#44;44 &#40;0&#44;42&#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">2&#44;72&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">1&#44;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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><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"><span class="elsevierStyleItalic">Tetratricopeptide repeat protein</span>&#160;37 TTC37&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">449&#44;05&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">1&#44;46 &#40;0&#44;18&#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
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                  \t\t\t\t">0&#44;54 &#40;0&#44;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#44;47 &#40;0&#44;36&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46; Regula&#231;&#227;o positiva da ades&#227;o celular&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10&#46; Hemostasia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p15&#44; p16&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&#46; Agrega&#231;&#227;o plaquet&#225;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46; Ativa&#231;&#227;o do plasminog&#234;nio&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#46; Transporte de organismo &#250;nico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p7&#44; p8&#44; p10&#44; p11&#44; p12&#44; p14&#44; p15&#44; p16&#44; p19&#44; p20&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0004&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#46; Coagula&#231;&#227;o sangu&#237;nea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p15&#44; p16&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0008&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#46; S&#237;ntese de transles&#227;o propensa a erros&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#46; Cascata de ativa&#231;&#227;o de prote&#237;nas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p15&#44; p23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46; Homeostase da retina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p5&#44; p23&#44; p24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46; Regula&#231;&#227;o negativa de resposta a trauma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p8&#44; p10&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46; Regula&#231;&#227;o positiva da exocitose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">p14&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0016&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20&#46; Regula&#231;&#227;o da exocitose&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p10&#44; p14&#44; p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0017&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21&#46; Regula&#231;&#227;o negativa do processo endotelial de apoptose celular&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0022&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46; Coagula&#231;&#227;o sangu&#237;nea&#44; forma&#231;&#227;o de co&#225;gulo de fibrina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0024&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#46; Regula&#231;&#227;o negativa da via de sinaliza&#231;&#227;o da apoptose extr&#237;nseca por meio da morte de receptores de dom&#237;nio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0024&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24&#46; Transporte&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p2&#44; p4&#44; p5&#44; p6&#44; p7&#44; p10&#44; p11&#44; p12&#44; p15&#44; p16&#44; p19&#44; p20&#44; p21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0029&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">25&#46; Processo metab&#243;lico do &#225;cido monocarbox&#237;lico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">p5&#44; p16&#44; p29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;0030&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">26&#46; Regula&#231;&#227;o da dissemina&#231;&#227;o de c&#233;lulas dependentes da ades&#227;o&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">p15&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">1 &#40;3&#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">0&#44;0033&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">27&#46; Cicatriza&#231;&#227;o de feridas&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">p2&#44; p5&#44; p6&#44; p15&#44; p16&#44; p21&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">6 &#40;20&#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">0&#44;0035&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">28&#46; Transporte de bicarbonato&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">p11&#44; p19&#44; p20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;10&#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">0&#44;0044&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">29&#46; Regula&#231;&#227;o positiva da vasoconstri&#231;&#227;o&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">p15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;3&#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">0&#44;0044&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">30&#46; Resposta ao &#237;on c&#225;lcio&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">p2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;3&#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">0&#44;0075&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">31&#46; Regula&#231;&#227;o do transporte por ves&#237;culas&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">p8&#44; p10&#44; p14&#44; p15&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">4 &#40;14&#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">0&#44;0083&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">32&#46; Secre&#231;&#227;o&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">p5&#44; p6&#44; p8&#44; p15&#44; p16&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">5 &#40;17&#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">0&#44;0092&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">33&#46; Regula&#231;&#227;o negativa a est&#237;mulos externos&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">p8&#44; p10&#44; p15&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">3 &#40;10&#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">0&#44;0098&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">34&#46; Resposta ao estresse&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">p2&#44; p5&#44; p6&#44; p13&#44; p16&#44; p19&#44; p20&#44; p21&#44; p23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;31&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;0100&nbsp;\t\t\t\t\t\t\n
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          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Principais vias funcionais envolvidas com as&#160;29&#160;prote&#237;nas identificadas como diferenciais entre melasma e pele perilesional</p>"
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                    0 => array:2 [
                      "titulo" => "Exploratory Study of Epidermis&#44; Basement Membrane Zone Upper Dermis Alterations and Wnt Pathway Activation in Melasma Compared to Adjacent and Retroauricular Skin"
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                            4 => "T&#46; Bashir"
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ISSN: 26662752
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